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Phosphorylated Mechanistic Target of Rapamycin (p-mTOR) and Noncoding RNA Expression in Follicular and Hürthle Cell Thyroid Neoplasm.

Oncocytic (Hürthle cell) and follicular neoplasms are related thyroid tumors with distinct molecular profiles. Diagnostic criteria separating adenomas and carcinomas for these two types of neoplasms are similar, but there may be some differences in the biological behavior of Hürthle cell and follicular carcinomas. Recent studies have shown that noncoding RNAs may have diagnostic and prognostic utility in separating benign and malignant Hürthle cell and follicular neoplasms. In this study, we examined expression of various noncoding RNAs including metastasis associated lung adenocarcinoma transcript 1 (MALAT1) and miR-RNA-885-5p (miR-885) in distinguishing between benign and malignant neoplasms. In addition, the expression of phosphorylated mechanistic receptor of rapamycin (p-mTOR) was also analyzed in these two groups of tumors. Tissue microarrays (TMAs) with archived tissue samples were analyzed using in situ hybridization (ISH) for MALAT1 and miR-885 and immunohistochemistry (IHC) for p-mTOR. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was also performed on a subset of the cases.MALAT1 and miR-885 were increased in all neoplastic groups compared to the normal thyroid tissues (p < 0.05). MALAT1 was more highly expressed in HCCs compared to FTCs, although the differences were not statistically significant (p = 0.06). MiR-885 was expressed at similar levels in FTCs and HCCs. P-mTOR protein was more highly expressed in FTCs than in HCCs (p<0.001). qRT-PCR analysis of noncoding RNAs supported the ISH findings. These results indicate that the noncoding RNAs MALAT1 and miR-885 show increased expression in neoplastic follicular and Hürthle cell thyroid neoplasms compared to normal thyroid tissues. P-mTOR was most highly expressed in FTC but was also increased in HCC, suggesting that drugs targeting this pathway may be useful for treatment of tumors unresponsive to conventional therapies.

Carcinoma Hürthle cell carcinoma;Follicular carcinoma;Long noncoding RNA;MALAT1;Oncocytic;P-mTOR;Thyroid;miR885-5p

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Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway.

The polysaccharide extract of Momordica charantia has various biological activities; however, its effect on endothelial dysfunction in myocardial infarction remains unclear. To elucidate this, myocardial infarction was induced in rats using isoproterenol (ISP). Pretreatment with M. charantia polysaccharides (MCP; 150 or 300mg/kg) for 25days significantly inhibited increases in heart weight, the heart-weight-to-body-weight ratio, and infarction size, and ameliorated the increased serum levels of aspartate transaminase, creatine kinase, lactate dehydrogenase, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In addition, MCP enhanced the activity of superoxide dismutase, catalase, and non-protein sulfhydryls, and decreased the level of lipid peroxidation. Moreover, MCP pretreatment downregulated the expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin (IL)-6, and IL-10), inflammatory markers (nitric oxide, myeloperoxidase, and inducible nitric oxide synthase), and apoptotic markers (caspase-3 and BAX), and upregulated Bcl-2 expression. Pretreatment with MCP reduced myonecrosis, edema, and inflammatory cell infiltration, and restored cardiomyocytes architecture. This myocardial protective effect could be related to the enhancement of the antioxidant defense system through the nuclear factor kappa B (NF-kB) pathways, and to anti-apoptosis through regulation of Bax, caspase-3, and Bcl-2.

Apoptosis;Inflammation;Isoproterenol;Momordica charantia polysaccharides;Myocardial infarction;Oxidative stress

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The mRNA expression of insulin-like growth factor-1 (Igf1) is decreased in the rat frontal cortex following gamma-hydroxybutyrate (GHB) administration.

In recent years, growth hormone (GH), together with its secondary mediators insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have been highlighted for their beneficial effects in the central nervous system (CNS), in particular as cognitive enhancers. Cognitive processes, such as learning and memory, are known to be impaired in individuals suffering from substance abuse. In the present study, we investigated the effect of gamma-hydroxybuturate (GHB), an illicit drug used for its sedating and euphoric properties, on genes associated with the somatotrophic axis in regions of the brain important for cognitive function. Sprague Dawley rats (n=36) were divided into three groups and administered either saline, GHB 50mg/kg or GHB 300mg/kg orally for seven days. The levels of Ghr, Igf1 and Igf2 gene transcripts were analyzed using qPCR in brain regions involved in cognition and dependence. The levels of IGF-1 in blood plasma were also determined using ELISA. The results demonstrated a significant down-regulation of Igf1 mRNA expression in the frontal cortex in high-dose treated rats. Moreover, a significant correlation between Igf1 and Ghr mRNA expression was found in the hippocampus, the frontal cortex, and the caudate putamen, indicating local regulation of the GH/IGF-1 axis. To summarize, the current study concludes that chronic GHB treatment influences gene expression of Ghr and Igf1 in brain regions involved in cognitive function.

Central nervous system (CNS);Cognition;Frontal cortex (FC);Gamma-hydroxybutyrate (GHB);Growth hormone (GH);Insulin-like growth factor-1 (IGF-1)

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Delving within: the new science of the unconscious.

What exactly is the relationship between conscious awareness and the unconscious mind? How, for example, does the brain classify and sort its different functions into conscious or unconscious processes? How has the history of human conceptualizations about the unconscious influenced current theories? Steve Paulson, executive producer of To the Best of Our Knowledge, moderated a discussion among neuroscientist Heather Berlin, psychologist Efrat Ginot, and psychiatrist George Makari to shed light on the history of the mind and the latest insights into the still emerging science of the unconscious.

Freud;Jung;brain;consciousness;mind;mindfulness;neuroscience;psychoanalysis;the self;therapeutic techniques;transference;unconscious

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Beat gestures and postural control in youth at ultrahigh risk for psychosis.

Beat gestures, rhythmic hand movements that co-occur with speech, appear to be uniquely associated with the cerebellum in healthy individuals. This behavior may also have relevance for psychosis-risk youth, a group characterized by cerebellar dysfunction. This study examined beat gesture frequency and postural sway (a sensitive index of cerebellar functioning) in youth at ultrahigh risk (UHR) for psychosis. Results indicated that decreased beat gesture frequency, but not self-regulatory movement, is associated with elevated postural sway, suggesting that beat gestures may be an important biomarker in this critical population.

Cerebellum;Gesture;Postural sway;Prodrome;Psychosis

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Symptom severity classification with gradient tree boosting.

In this paper, we present our system as submitted in the CEGS N-GRID 2016 task 2 RDoC classification competition. The task was to determine symptom severity (0-3) in a domain for a patient based on the text provided in his/her initial psychiatric evaluation. We first preprocessed the psychiatry notes into a semi-structured questionnaire and transformed the short answers into either numerical, binary, or categorical features. We further trained weak Support Vector Regressors (SVR) for each verbose answer and combined regressors' output with other features to feed into the final gradient tree boosting classifier with resampling of individual notes. Our best submission achieved a macro-averaged Mean Absolute Error of 0.439, which translates to a normalized score of 81.75%.

Bootstrap;Gradient tree boosting;NLP;Psychiatric evaluation;Severity prediction;Text classification

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Noninvasive Microsurgery Using Aptamer-Functionalized Magnetic Microdisks for Tumor Cell Eradication.

Magnetomechanical cell disruption using nano- and microsized structures is a promising biomedical technology used for noninvasive elimination of diseased cells. It applies alternating magnetic field (AMF) for ferromagnetic microdisks making them oscillate and causing cell membrane disruption with cell death followed by apoptosis. In this study, we functionalized the magnetic microdisks with cell-binding DNA aptamers and guided the microdisks to recognize cancerous cells in a mouse tumor in vivo. Only 10 min of the treatment with a 100 Hz AMF was enough to eliminate cancer cells from a malignant tumor. Our results demonstrate a good perspective of using aptamer-modified magnetic microdisks for noninvasive microsurgery for tumors.

aptamer;magnetic microdisks;magnetodynamic therapy;tumor eradication

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Primary angioplasty: Effect of deferred stenting on stent size.

Primary angioplasty with immediate stenting (IS) is the gold standard for ST-segment elevation myocardial infarction (STEMI). Deferred stenting (DS) has been proposed to limit periprocedural complications, and may influence stent size because of thrombus and spasm alleviation. We sought to study the effect of DS on stent size. Over the study period, 258 patients underwent primary angioplasty for STEMI (DS, n=84; IS, n=174). An informative coronary angiogram run - i.e. allowing for proper lesion analysis - was selected and anonymized by an independent operator. Two experienced operators randomly analysed these runs, and proposed stent dimensions after having measured vessel diameter and lesion length by quantitative coronary analysis. The primary objective was the variation in stent size between the two coronary angiograms. The median delay between the two coronary angiograms was 2 days. Overall, the stent length was shorter (-1.64mm; P=0.030) and its diameter was larger (+0.13mm; P<0.001) during the second coronary angiogram, especially in the right coronary arteries. DS led to the implantation of a larger and shorter stent; this is probably because DS allows for more accurate assessment of the residual lesion after relief of spasm and thrombus, and may have clinical consequences in terms of stent thrombosis and restenosis.

Angioplastie primaire;Infarctus du myocarde;Myocardial infarction;Primary angioplasty;ST-segment elevation myocardial infarction;Stent;Syndrome coronarien aigu avec sus-décalage du segment ST;Thrombus

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Downregulated miRNA-1269a variant (rs73239138) decreases the susceptibility to gastric cancer via targeting ZNF70.

Although emerging evidence has indicated that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are associated with susceptibility to gastric cancer, a limited number of studies have revealed the underlying molecular mechanisms. In the present study, the results suggested that miR-1269a rs73239138 has a role in decreasing the risk of gastric cancer. The level of miR-1269a variant expression was significantly downregulated compared with the wild-type miR-1269a in the gastric cells (Fig. 1). Furthermore, overexpression of miR-1269a inhibited apoptosis of gastric cancer cells. Expression of the miR-1269a variant inhibited the function of miR-1269a by increasing the apoptotic rate and the expression of Bik, Bim and Bak was upregulated consistently. In addition, zinc-finger protein 70 (ZNF70) was identified to be a target gene of miR-1269a, which was downregulated by miR-1269a and upregulated by miR-1269a variant. ZNF70 was indicated to exert a role as a tumor suppressor in gastric cancer. To the best our knowledge, the present study for the first time highlights a critical role of miR-1269a variant rs73239138 in decreasing the susceptibility to gastric cancer by downregulating its expression and targeting ZNF70, which promotes apoptosis of gastric cancer cells. This SNP is indicated to serve as a potential biomarker and therapeutic target for gastric cancer.

apoptosis;gastric cancer;miR-1269a;rs73239138;zinc-finger protein 70

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Understanding of Electrochemical Mechanisms for CO₂ Capture and Conversion into Hydrocarbon Fuels in Transition-Metal Carbides (MXenes).

Two-dimensional (2D) transition-metal (groups IV, V, VI) carbides (MXenes) with formulas M₃C₂ have been investigated as CO₂ conversion catalysts with well-resolved density functional theory calculations. While MXenes from the group IV to VI series have demonstrated an active behavior for the capture of CO₂, the Cr₃C₂ and Mo₃C₂ MXenes exhibit the most promising CO₂ to CH₄ selective conversion capabilities. Our results predicted the formation of OCHO^• and HOCO^• radical species in the early hydrogenation steps through spontaneous reactions. This provides atomic level insights into the computer-aided screening for high-performance catalysts and the understanding of electrochemical mechanisms for CO₂ reduction to energy-rich hydrocarbon fuels, which is of fundamental significance to elucidate the elementary steps for CO₂ fixation.

CO2 capture and conversion;MXene;density functional theory;electrochemical mechanisms;transition-metal carbides

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Qualitative analysis of Parkinson's disease information on social media: the case of YouTube™.

There is a paucity of data pertaining to the usefulness of information presented on social media platforms on chronic neuropsychiatric conditions such as Parkinson's disease (PD). The aim of this study was to examine the quality of YouTube™ videos that deliver general information on PD and the availability and design of instructional videos addressing the caregiving role in PD. YouTube™ was searched using the keyword "Parkinson's disease" for relevant videos. Videos were assessed for usefulness and accuracy based on pre-defined criteria. Data on video characteristics including total viewership, duration, ratings, and source of videos were collated. Instructional PD videos that addressed the role of caregivers were examined closely for the design and scope of instructional content. A total of 100 videos met the inclusion criteria. Just under a third of videos (28%) was uploaded by trusted academic organisations. Overall, 15% of PD videos were found to be somewhat useful and only 4% were assessed as providing very useful PD information; 3% of surveyed videos were misleading. The mean number of video views (regardless of video source) was not significantly different between the different video ratings (<i>p</i> = 0.86). Although personal videos trended towards being less useful than videos from academic organisations, this association was not statistically significant (<i>p</i> = 0.13). To our knowledge, this is the first study to assess the usefulness of PD information on the largest video-sharing website, YouTube™. In general, the overall quality of information presented in the videos screened was mediocre. Viewership of accurate vs. misleading information was, however, very similar. Therefore, healthcare providers should direct PD patients and their families to the resources that provide reliable and accurate information.

Caregiver;Parkinson’s disease;Personalised medicine;Social media;Video;YouTube™

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First Detection of a Fosfomycin Resistance Gene, <i>fosA7</i>, in Salmonella enterica Serovar Heidelberg Isolated from Broiler Chickens.

We previously described <i>Salmonella enterica</i> serovar Heidelberg isolates harboring a chromosomal gene cluster similar to the glutathione <i>S</i>-transferase gene, a putative <i>fosA</i> gene conferring resistance to fosfomycin. Here, we show that this new gene, named <i>fosA7</i>, confers resistance to fosfomycin. The introduction of <i>fosA7</i> into the fosfomycin-susceptible <i>Salmonella enterica</i> serovar Enteritidis resulted in a substantial increase in the fosfomycin MIC. This finding increases the awareness of antibiotic resistance in <i>Salmonella</i> Heidelberg from broilers as related to the food safety and public health.

Salmonella Heidelberg;broiler chicken;fosA7 gene;fosfomycin resistance

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Corneal, Scleral, Choroidal, and Foveal Thickness in Patients with Rheumatoid Arthritis.

To investigate corneal, scleral, choroidal, and foveal thicknesses in female patients with rheumatoid arthritis (RA) and compare them with healthy subjects. This prospective study included consecutive female patients diagnosed with RA and healthy subjects. Corneal, scleral, choroidal, and retinal (foveal) thicknesses were obtained by using optical coherence tomography and a comparison was performed between groups for all outcome measures. Thirty-six eyes of 36 female patients diagnosed with RA (group 1) and 36 eyes of 36 healthy female volunteers (group 2) were included. Mean corneal, scleral, choroidal thicknesses and retinal thickness at the fovea of group 1 were 543.3±33.7 µm, 343.7±42.2 µm, 214.6±50, and 213.5±18.9 µm, respectively; in group 2, these values were 549.9±29.6 μm, 420.9±42.4 μm, 206.4±41.9 μm, and 222±15.5 μm, respectively. The comparison between group 1 and 2 with respect to corneal, choroidal, and foveal thicknesses did not reveal statistical significant differences (p>0.05). On the contrary, there was a statistically significant difference with respect to scleral thickness between the groups, with the RA patients demonstrating a thinner scleral layer (p<0.001). Female patients with RA seem to demonstrate statistically significant scleral thinning when compared with healthy subjects, while there was no difference concerning corneal, choroidal, and foveal thickness.

Rheumatoid arthritis;choroidal-retinal thickness;corneal thickness;optical coherence tomography;scleral thickness

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N-terminal pro-B-type natriuretic peptide diagnostic algorithm versus American Heart Association algorithm for Kawasaki disease.

Diagnosis of Kawasaki disease (KD) can be challenging in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete. We recently proposed serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunctive diagnostic test. We retrospectively tested a new algorithm to help KD diagnosis based on NT-proBNP, coronary artery dilation (CAD) at onset, and abnormal serum albumin or C-reactive protein (CRP). The goal was to assess the performance of the algorithm and compare its performance with that of the 2004 American Heart Association (AHA)/American Academy of Pediatrics (AAP) algorithm. The algorithm was tested on 124 KD patients with NT-proBNP measured on admission at the present institutions between 2007 and 2013. Age at diagnosis was 3.4 ± 3.0 years, with a median of five diagnostic criteria; and 55 of the 124 patients (44%) had incomplete KD. CA complications occurred in 64 (52%), with aneurysm in 14 (11%). Using this algorithm, 120/124 (97%) were to be treated, based on high NT-proBNP alone for 79 (64%); on onset CAD for 14 (11%); and on high CRP or low albumin for 27 (22%). Using the AHA/AAP algorithm, 22/47 (47%) of the eligible patients with incomplete KD would not have been referred for treatment, compared with 3/55 (5%) with the NT-proBNP algorithm (P < 0.001). This NT-proBNP-based algorithm is efficient to identify and treat patients with KD, including those with incomplete KD. This study paves the way for a prospective validation trial of the algorithm.

Kawasaki disease;aminoterminal pro-B-type natriuretic peptide;coronary aneurysm;heart disease;pediatrics

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Comprehensive Proteomic Profiling of Wheat Gluten Using a Combination of Data-Independent and Data-Dependent Acquisition.

Wheat is the most important food crop in the world, the unique physiochemical properties of wheat gluten enabling a diverse range of food products to be manufactured. However, genetic and environmental factors affect the technological properties of gluten in unpredictable ways. Although newer proteomic methods have the potential to offer much greater levels of information, it is the older gel-based methods that remain most commonly used to identify compositional differences responsible for the variation in gluten functionality, in part due to the nature of their primary sequences. A combination of platforms were investigated for comprehensive gluten profiling: a QTOF with a data independent schema, which incorporated ion mobility (DIA-IM-MS) and a data dependent acquisition (DDA) workflow using a linear ion trap quadrupole (LTQ) instrument. In conjunction with a manually curated gluten sequence database a total of 2736 gluten peptides were identified with only 157 peptides identified by both platforms. These data showed 127 and 63 gluten protein accessions to be inferred with a minimum of one and three unique peptides respectively. Of the 63 rigorously identified proteins, 26 were gliadin species (4 ω-, 14 α-, and 8 γ-gliadins) and 37 glutenins (including 29 LMW glutenin and 8 HMW glutenins). Of the HMW glutenins, three were 1Dx type and five were 1Bx type illustrating the challenge of unambiguous identification of highly polymorphic proteins without cultivar specific gene sequences. The capacity of the platforms to sequence longer peptides was crucial to achieving the number of identifications, the combination of QTOF-LTQ technology being more important than extraction method to obtain a comprehensive profile. Widespread glutamine deamidation, a post-translational modification, was observed adding complexity to an already highly polymorphic mixture of proteins, with numerous insertions, deletions and substitutions. The data shown is the most comprehensive and detailed proteomic profile of gluten to date.

LTQ-Orbitrap;QTOF-MS/MS;chymotrypsin;coeliac disease;gluten;mass spectrometry;plant proteomics;proteomics

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Clinical and Hemodynamic Correlates and Prognostic Value of VE/VCO₂ Slope in Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Hypertension.

Impaired exercise capacity is one of the hallmarks of heart failure with preserved ejection fraction (HFpEF), but the clinical and hemodynamic correlates and prognostic value of exercise testing in patients with HFpEF is unknown. Patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) and pulmonary hypertension underwent cardiopulmonary exercise test (CPX) to measure maximal (peak VO₂) and submaximal (ventilatory equivalent for carbon dioxide [VE/VCO₂] slope) exercise capacity. In addition, right heart catheterization was performed. Patients were grouped in tertiles based on the VE/VCO₂ slope. Univariate and multivariate regression analyses were performed. A Cox regression analysis was performed to determine the mortality during follow-up. We studied 88 patients: mean age 73 ± 9 years, 67% female, mean LVEF 58%, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 840 (interquartile range 411-1938) ng/L. Patients in the highest VE/VCO₂ tertile had the most severe HF, as reflected in higher New York Heart Association functional class and higher NT-proBNP plasma levels (all P < .05 for trend), whereas LVEF was similar between the groups. Multivariable regression analysis with backward elimination on invasive hemodynamic measurements showed that VE/VCO₂ slope was independently associated with pulmonary vascular resistance (PVR). Cox regression analysis showed that increased VE/VCO₂ slope (but not peak VO₂) was independently associated with increased mortality. Increased VE/VCO₂ slope was associated with more severe disease and higher PVR and was independently associated with increased mortality in patients with HFpEF.

VE/VCO(2) slope;cardiopulmonary exercise test;heart failure with preserved ejection fraction

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Incorrect ventricular lead placement into the systemic right ventricle of a patient with D-transposition of the great vessels after Mustard procedure.

Incorrect pacemaker lead placement into the systemic ventricle is a complication that has rarely been described in patients with D-transposition status after atrial baffle palliation. We present a case of ventricular lead misplacement in the systemic right ventricle of a patient with D-transposition of the great arteries after Mustard procedure. This case demonstrates the challenges with proper imaging of lead placement in patients with atrial baffles and long-term management of a lead in the systemic ventricle.

Atrial switch;mustard procedure;ventricular lead misplacement

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T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection.

T follicular helper (Tfh) cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART), excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh-B cell interactions.

HIV and aging;T follicular helper cells and HIV;T follicular helper cells and immunity;T follicular helper cells and influenza vaccine;T follicular helper cells in aging and HIV

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<i>Drosophila</i> TG-A transglutaminase is secreted via an unconventional Golgi-independent mechanism involving exosomes and two types of fatty acylations.

Transglutaminases (TGs) play essential intracellular and extracellular roles by covalently cross-linking many proteins. <i>Drosophila</i> TG is encoded by one gene and has two alternative splicing-derived isoforms, TG-A and TG-B, which contain distinct N-terminal 46- and 38-amino acid sequences, respectively. The TGs identified to date do not have a typical endoplasmic reticulum (ER)-signal peptide, and the molecular mechanisms of their secretion under physiologic conditions are unclear. Immunocytochemistry revealed that TG-A localizes to multivesicular-like structures, whereas TG-B localizes to the cytosol. We also found that TG-A, but not TG-B, was modified concomitantly by <i>N-</i>myristoylation and <i>S</i>-palmitoylation, and <i>N-</i>myristoylation was a pre-requisite for <i>S-</i>palmitoylation. Moreover, TG-A, but not TG-B, was secreted in response to calcium signaling induced by Ca²⁺ ionophores and uracil, a pathogenic bacteria-derived substance. Brefeldin A and monensin, inhibitors of the ER/Golgi-mediated conventional pathway, did not suppress TG-A secretion, whereas inhibition of <i>S</i>-palmitoylation by 2-bromopalmitate blocked TG-A secretion. Ultracentrifugation, electron microscopy analyses, and treatments with inhibitors of multivesicular body formation revealed that TG-A was secreted via exosomes together with co-transfected mammalian CD63, an exosomal marker, and the secreted TG-A was taken up by other cells. The 8-residue N-terminal fragment of TG-A containing the fatty acylation sites was both necessary and sufficient for the exosome-dependent secretion of TG-A. In conclusion, TG-A is secreted through an unconventional ER/Golgi-independent pathway involving two types of fatty acylations and exosomes.

Drosophila;exosome (vesicle);protein myristoylation;protein palmitoylation;protein secretion;transglutaminase

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Thrombotic risk stratification by platelet count in patients with antiphospholipid antibodies: a longitudinal study.

Essentials Thrombotic risk stratification is an unmet need in antiphospholipid antibody carriers. Platelet count and antiphospholipid score (aPL-S) were combined to predict thrombotic events. Patients with high aPL-S are at high thrombotic risk regardless of platelet count. If platelet count is low, patients with low aPL-S are also on high thrombotic risk. Background Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome. However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. Objectives To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carriers, and to stratify the thrombotic risk by combining platelet count and antiphospholipid score (aPL-S), which represents a quantification of aPL varieties and titers. Patients/methods A single-center, retrospective, longitudinal study comprising 953 consecutive patients who were suspected of having autoimmune disease between January 2002 and December 2006 was performed. Low platelet count was defined as a count of < 150 × 10³ μL^-1 at the time of aPL testing. Results A negative correlation was observed between aPL-S and platelet count (r = - 0.2477). Among aPL-positive patients, those with a low platelet count developed thrombosis more frequently than those without (hazard ratio [HR] 2.95, 95% confidence interval [CI] 1.11-7.88). Among aPL-negative patients, no difference was found in the predictive value of thrombosis regardless of platelet count. Patients with aPLs were further divided into two subgroups according to aPL-S. Among low-aPL-S patients, those with low platelet counts developed thrombosis more frequently than those without (HR 3.44, 95% CI 1.05-11.2). In contrast, high-aPL-S patients developed thrombosis frequently regardless of platelet count. Conclusions aPL carriers with low platelet counts are at high risk of developing thrombosis. In particular, 'low-aPL-S carriers' may be stratified by platelet count in terms of predicting future thrombotic events.

antiphospholipid antibodies;antiphospholipid syndrome;platelet count;thrombocytopenia;thrombosis

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Treatment of periodontal intrabony defects using autologous platelet-rich fibrin and titanium platelet-rich fibrin: a randomized, clinical, comparative study.

The aim of the present study was to compare the effectiveness of open flap debridement (OFD) alone and OFD with either autologous platelet-rich fibrin (PRF) or titanium PRF (TPRF) in the treatment of intrabony defects (IBD). The study was conducted on patients reporting to the Department of Periodontics, The Oxford Dental College and Hospital, Bangalore, India. Thirty-eight patients with 90 periodontal IBD of moderate-severe periodontitis were selected and assigned to the OFD alone group (group I), the OFD with autologous PRF group (group II), or the OFD with TPRF group (group III). In each patient, a minimum number of two sextants were present, with probing pocket depths (PPD) ≥5 mm in at least three teeth. At 9 months' postoperatively, upon comparing the PPD reduction, defect depth reduction, and clinical attachment level gains, it was noted that groups II and III showed statistically-significant improvements compared with group I, but no statistically-significant difference was noted between groups II and III. The present study demonstrated that marked improvements in the clinical parameters and radiographic outcomes were noted with both autologous PRF and TPRF in the treatment of IBD.

growth factor;periodontal regeneration;periodontitis

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Early Developmental Disruption of Type 2 Deiodinase Pathway in Mouse Skeletal Muscle Does Not Impair Muscle Function.

Myogenesis is positively regulated by thyroid hormone (triiodothyronine [T3]), which is amplified by the type 2 deiodinase (D2) activation of thyroxine to T3. Global inactivation of the Dio2 gene impairs skeletal muscle (SKM) differentiation and regeneration in response to muscle injury. Given that newborn and adult mice with late developmental SKM Dio2 disruption do not develop a significant phenotype, it was hypothesized that D2 plays an early role in this process. This was tested in mice with SKM disruption of Dio2 driven by two early developmental promoters: MYF5 and MYOD. MYF5 myoblasts in culture differentiate normally into myotubes, despite loss of almost all D2 activity. Dio2 mRNA levels in developing SKM obtained from MYF5-D2KO embryos (E18.5) were about 54% of control littermates, but the expression of the T3-responsive genes Myh1 and 7 and Atp2a1 and 2 were not affected. In MYF5-D2KO and MYOD-D2KO neonatal hind-limb muscle, the expression of Myh1 and 7 and Atp2a2 remained unaffected, despite 60-70% loss in D2 activity and/or mRNA. Only in MYOD-D2KO neonatal muscle was there a 40% reduction in Atp2a1 mRNA. Postnatal growth of both mouse models and SKM function as assessed by exercise capacity and measurement of muscle strength were normal. Furthermore, an analysis of the adult soleus revealed no changes in the expression of T3-responsive genes, except for an about 18% increase in MYOD-D2KO SOL Myh7 mRNA. Two mouse models of early developmental disruption of Dio2 in myocyte precursor exhibit no significant SKM phenotype.

deiodinases;myogenesis;skeletal muscle function;thyroid hormone signaling

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Diabetes Distress or Major Depressive Disorder? A Practical Approach to Diagnosing and Treating Psychological Comorbidities of Diabetes.

The presence of major depressive disorder (MDD) in people with diabetes may be up to three times more common than in the general population. People with diabetes and major depressive disorder have worse health outcomes and higher mortality rates. Diabetes distress refers to an emotional state where people experience feelings such as stress, guilt, or denial that arise from living with diabetes and the burden of self-management. Diabetes distress has also been linked to worse health outcomes. There are multiple treatment options for MDD including pharmacotherapy and cognitive behavioral approaches. Providers treating patients with diabetes must be aware of the frequent comorbidity of diabetes, diabetes distress, and depression and manage patients using a multidisciplinary team approach. This article discusses the epidemiology, pathophysiology, and bi-directional relationship of diabetes and depression and provides a practical, patient-centered approach to diagnosis and management.

Chronic care management;Depression;Diabetes distress;Major depressive disorder

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Novel Metabolic Pathway for <i>N</i>-Methylpyrrolidone Degradation in Alicycliphilus sp. Strain BQ1.

The molecular mechanisms underlying the biodegradation of <i>N</i>-methylpyrrolidone (NMP), a widely used industrial solvent that produces skin irritation in humans and is teratogenic in rats, are unknown. <i>Alicycliphilus</i> sp. strain BQ1 degrades NMP. By studying a transposon-tagged mutant unable to degrade NMP, we identified a six-gene cluster (<i>nmpABCDEF</i>) that is transcribed as a polycistronic mRNA and encodes enzymes involved in NMP biodegradation. <i>nmpA</i> and the transposon-affected gene <i>nmpB</i> encode an <i>N</i>-methylhydantoin amidohydrolase that transforms NMP to γ-<i>N</i>-methylaminobutyric acid; this is metabolized by an amino acid oxidase (NMPC), either by demethylation to produce γ-aminobutyric acid (GABA) or by deamination to produce succinate semialdehyde (SSA). If GABA is produced, the activity of a GABA aminotransferase (GABA-AT), not encoded in the <i>nmp</i> gene cluster, is needed to generate SSA. SSA is transformed by a succinate semialdehyde dehydrogenase (SSDH) (NMPF) to succinate, which enters the Krebs cycle. The abilities to consume NMP and to utilize it for growth were complemented in the transposon-tagged mutant by use of the <i>nmpABCD</i> genes. Similarly, <i>Escherichia coli</i> MG1655, which has two SSDHs but is unable to grow in NMP, acquired these abilities after functional complementation with these genes. In wild-type (wt) BQ1 cells growing in NMP, GABA was not detected, but SSA was present at double the amount found in cells growing in Luria-Bertani medium (LB), suggesting that GABA is not an intermediate in this pathway. Moreover, <i>E. coli</i> GABA-AT deletion mutants complemented with <i>nmpABCD</i> genes retained the ability to grow in NMP, supporting the possibility that γ-<i>N</i>-methylaminobutyric acid is deaminated to SSA instead of being demethylated to GABA.<b>IMPORTANCE</b><i>N</i>-Methylpyrrolidone is a cyclic amide reported to be biodegradable. However, the metabolic pathway and enzymatic activities for degrading NMP are unknown. By developing molecular biology techniques for <i>Alicycliphilus</i> sp. strain BQ1, an environmental bacterium able to grow in NMP, we identified a six-gene cluster encoding enzymatic activities involved in NMP degradation. These findings set the basis for the study of new enzymatic activities and for the development of biotechnological processes with potential applications in bioremediation.

Alicycliphilus;N-methylpyrrolidone;biodegradation

pubmed

Takotsubo Cardiomyopathy: Another Form of Cardiorenal Syndrome.

Takotsubo cardiomyopathy (TC) is a life-threatening syndrome with ambiguous pathophysiology. The interdependency between heart failure and kidney failure (KF) is well established, but the influence of KF on TC outcome is not known. This single-center cohort from January 2003 to September 2015 consisted of 114 consecutive patients with TC. They were divided into 2 groups according to the presence (n = 32, 29.6%) or absence (n = 76, 70.3%) of KF. The end point of this retrospective study was a composite of in-hospital events, all-cause mortality, rehospitalization due to heart failure, stroke, and recurrence of TC (mean follow-up: 5 years). Although there were no differences in baseline characteristics between patients with/without KF, we found a significantly higher mortality rate in those with KF, 1 (7.9% vs 21.8%, P < .05), 2 (11.8% vs 31.5%, P < .05), and 5 years (22.3% vs 43.7%, P < .05) after the index event. There were no differences in life-threatening arrhythmias, cardiogenic shock, cardiopulmonary resuscitation, and thromboembolic events in both groups at the index event. Patients with TC and KF have a much worse long-term prognosis. This is clinically relevant, but the mechanisms responsible remain to be determined.

Takotsubo cardiomyopathy;Takotsubo predisposing factors;acute left ventricular dysfunction;kidney failure;mortality

pubmed

The prognostic value of high sensitivity cardiac troponin T in patients with congenital heart disease.

Cardiac troponin T (cTnT) is a specific marker of myocardial injury that is elevated in patients with coronary artery disease or heart failure; it has been investigated as a prognostic marker. A highly sensitive, commercially available assay has been developed to detect cardiac troponin T (hs-cTnT). This study aimed to evaluate the clinical implications and prognostic value of hs-cTnT in patients with congenital heart disease (CHD). We evaluated 122 consecutive patients hospitalized at our institution because of heart failure or scheduled cardiac catheterization. We measured the serum concentration of hs-cTnT at the time of hospitalization, and we prospectively followed-up all patients for 3 years and monitored rates of cardiovascular events (e.g. cardiac death, readmission owing to worsening of heart failure or arrhythmia, and reintervention) as endpoints. We classified the patients according to their hs-cTnT level into non-detectable (ND group, hs-cTnT <0.003ng/mL), detectable normal (DN group, 0.003ng/mL ≤hs-cTnT <0.014ng/mL), or elevated (EL group, 0.014ng/mL ≤hs-cTnT) group; 20 of 122 (16.4%) patients were in the EL group, in which 17 cardiovascular events occurred during follow-up. In the multivariate Cox proportional hazard analyses, the EL group [p=0.024, hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.1-5.8] was an independent significant predictor of cardiovascular events. A Kaplan-Meier curve revealed a high incidence of cardiovascular events in the EL group (EL vs ND log rank p<0.0001, HR 7.6, 95% CI 3.2-20.0, EL vs DN log rank p<0.0001, HR 4.1, 95% CI 2.1-7.8). Because the EL group is more likely to have an adverse outcome, elevated hs-cTnT level can be a prognostic marker in patients with CHD.

Congenital heart disease;Heart failure;High sensitivity cardiac troponin T;Prognostic value

pubmed

Genus-Wide Screening Reveals Four Distinct Types of Structural Plastid Genome Organization in Pelargonium (Geraniaceae).

Geraniaceae are known for their unusual plastid genomes (plastomes), with the genus Pelargonium being most conspicuous with regard to plastome size and gene organization as judged by the sequenced plastomes of P. x hortorum and P. alternans. However, the hybrid origin of P. x hortorum and the uncertain phylogenetic position of P. alternans obscure the events that led to these extraordinary plastomes. Here, we examine all plastid reconfiguration hotspots for 60 Pelargonium species across all subgenera using a PCR and sequencing approach. Our reconstruction of the rearrangement history revealed four distinct plastome types. The ancestral plastome configuration in the two subgenera Magnipetala and Pelargonium is consistent with that of the P. alternans plastome, whereas that of the subgenus Parvulipetala deviates from this organization by one synapomorphic inversion in the trnNGUU–ndhF region. The plastome of P. x hortorum resembles those of one group of the subgenus Paucisignata, but differs from a second group by another inversion in the psaI–psaJ region. The number of microstructural changes and amount of repetitive DNA are generally elevated in all inverted regions. Nucleotide substitution rates correlate positively with the number of indels in all regions across the different subgenera. We also observed lineage- and species-specific changes in the gene content, including gene duplications and fragmentations. For example, the plastid rbcL–psaI region of Pelargonium contains a highly variable accD-like region. Our results suggest alternative evolutionary paths under possibly changing modes of plastid transmission and indicate the non-functionalization of the plastid accD gene in Pelargonium.

plastid genome;Geraniaceae;molecular evolution;Pelargonium

pubmed

Factors Influencing the Eating Practices of Hospital Nurses During Their Shifts.

The purpose of this study was to identify factors influencing hospital nurses' dietary practices during their shifts. Semistructured interviews grounded in the Social Ecological Model focused on individual, interpersonal, organizational, and public policy factors affecting intake. Responses from 20 female nurses were qualitatively coded and categorized based on common themes. Four major themes emerged: occupational characteristics, hesitation to take breaks, influence of unhealthy food, and organizational and industry policies. Of note, nurses' perceived inability to take breaks was due to patient load, unpredictability of patient needs, reluctance to burden other nurses, a tendency to prioritize patient care over self-care, and the repercussions of working longer hours to complete work. Other influential factors included the presence of unhealthy food options, regulations restricting nurses' ability to eat and drink in the workplace, and the need for more staff. Multilevel interventions are necessary to ensure nurses take appropriate meal breaks and maintain satisfactory dietary habits.

best practices;health coaching/motivational interviewing;health education;health promotion;leadership;management;mental health;occupational health and safety programs;organizational culture/climate;program planning and evaluation;work and family balance

pubmed

Solid-State Carbon Dots with Red Fluorescence and Efficient Construction of Dual-Fluorescence Morphologies.

Stable solid-state red fluorescence from organosilane-functionalized carbon dots (CDs) with sizes around 3 nm is reported for the first time. Meanwhile, a novel method is also first reported for the efficient construction of dual-fluorescence morphologies. The quantum yield of these solid-state CDs and their aqueous solution is 9.60 and 50.7%, respectively. The fluorescence lifetime is 4.82 ns for solid-state CDs, and 15.57 ns for their aqueous solution. These CDs are detailedly studied how they can exhibit obvious photoluminescence overcoming the self-quenching in solid state. Luminescent materials are constructed with dual fluorescence based on as-prepared single emissive CDs (red emission) and nonfluorescence media (starch, Al₂ O₃ , and RnOCH₃ COONa), with the characteristic peaks located at nearly 440 and 600 nm. Tunable photoluminescence can be successfully achieved by tuning the mass ratio of CDs to solid matrix (such as starch). These constructed dual-fluorescence CDs/starch composites can also be applied in white light-emitting diodes with UV chips (395 nm), and oxygen sensing.

carbon dots;dual emission;red fluorescence;solid state

pubmed

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study.

Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Observational study. 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFR_cr) and serum cystatin C level (eGFR_cys) and urine albumin-creatinine ratio. Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). 341 (7%) participants were classified as frail, 1,475 (30%) had eGFR_cr<60mL/min/1.73m², 2,480 (50%) had eGFR_cys<60mL/min/1.73m², and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFR_cr and eGFR_cys<60mL/min/1.73m² were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFR_cr and a strong association with eGFR_cys and albumin-creatinine ratio. Frail individuals with eGFR_cr of 60 to <75mL/min/1.73m² were frequently reclassified to lower eGFR categories using eGFR_cys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m²). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Cross-sectional study design. Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFR_cys versus eGFR_cr. Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.

Frailty;albuminuria;biomarker;chronic kidney disease (CKD);estimated glomerular filtration rate (eGFR);frail;geriatric;older adults;polypharmacy;prefrail;reduced kidney function;serum creatinine;serum cystatin C;urine albumin

pubmed

LC-MS/MS analysis of permethylated N-glycans facilitating isomeric characterization.

The biosynthesis of glycans is a template-free process; hence compositionally identical glycans may contain highly heterogeneous structures. Meanwhile, the functions of glycans in biological processes are significantly influenced by the glycan structure. Structural elucidation of glycans is an essential component of glycobiology. Although NMR is considered the most powerful approach for structural glycan studies, it suffers from low sensitivity and requires highly purified glycans. Although mass spectrometry (MS)-based methods have been applied in numerous glycan structure studies, there are challenges in preserving glycan structure during ionization. Permethylation is an efficient derivatization method that improves glycan structural stability. In this report, permethylated glycans are isomerically separated; thus facilitating structural analysis of a mixture of glycans by LC-MS/MS. Separation by porous graphitic carbon liquid chromatography at high temperatures in conjunction with tandem mass spectrometry (PGC-LC-MS/MS) was utilized for unequivocal characterization of glycan isomers. Glycan fucosylation sites were confidently determined by eliminating fucose rearrangement and assignment of diagnostic ions, achieved by permethylation and PGC-LC at high temperatures, respectively. Assigning monosaccharide residues to specific glycan antennae was also achieved. Galactose linkages were also distinguished from each other by CID/HCD tandem MS. This was attainable because of the different bond energies associated with monosaccharide linkages. Graphical Abstract LC-MS and tandem MS of terminal galactose isomers.

LC-MS/MS;N-Glycan isomers;Permethylation;Porous graphitic carbon column;Tandem mass spectrometry

pubmed

Distributive Shock in a Neonate with Diffuse Infantile Hepatic Hemangioma.

Hemangiomas are common cutaneous findings on healthy infants. These vascular malformations are generally benign, though in rare circumstances they can potentially be fatal. This is particularly true when the hemangiomas are large or numerous and occurring in visceral organs. Previously unrecognized visceral hemangiomas are part of the differential for any neonate presenting unexpectedly in shock. A 10-day-old neonate presented to the pediatric emergency department with difficulty breathing. On examination, he appeared to be in respiratory distress and in shock. Echocardiography showed cardiomegaly, and an abdominal ultrasound showed a massive and heterogeneous liver. Magnetic resonance imagine performed after stabilization in the pediatric intensive care unit verified the presence of diffuse infantile hepatic hemangiomas. This case demonstrates how numerous visceral hemangiomas can generate high-volume vascular steal, distributive shock, and cardiac failure. Our patient was subsequently noted to have bruits over his liver. WHY AN EMERGENCY PHYSICIAN SHOULD BE AWARE OF THIS?: Diffuse hemangiomas and arteriovenous malformations are rare causes of extrinsic cardiogenic shock in the neonate. Targeted palpation of an enlarged liver or auscultation of a right upper quadrant bruit can raise suspicion of this diagnosis.

DIHH;cardiac failure;distributive shock;hepatic hemangioma;neonatal shock;vascular shunt

pubmed

Employing Microbial Electrochemical Technology-driven electro-Fenton oxidation for the removal of recalcitrant organics from sanitary landfill leachate.

The feasibility of employing Microbial Electrochemical Technology (MET)-driven electro-Fenton oxidation was evaluated as a post-treatment of an anammox system treating sanitary landfill leachate. Two different MET configuration systems were operated using effluent from partial nitrification-anammox reactor treating mature leachate. In spite of the low organic matter biodegradability of the anammox's effluent (2401±562mgCODL^-1; 237±57mgBOD₅L^-1), the technology was capable to reach COD removal rates of 1077-1244mgL^-1d^-1 with concomitant renewable electricity production (43.5±2.1Am^-3N_CC). The operation in continuous mode versus batch mode reinforced the removal capacity of the technology. The recirculation of acidic catholyte into anode chamber hindered the anodic efficiency due to pH stress on anodic electricigens. The obtained results demonstrated that the integrated system is a potentially applicable process to deal with bio-recalcitrant compounds present in mature landfill leachate.

Advanced oxidation processes;Anammox;Electricity production;Hydroxyl radicals;Recalcitrant organics

pubmed

An Intelligent Remote Monitoring System for Total Knee Arthroplasty Patients.

For the first six weeks following total knee arthroplasty (TKA), a patient will attend an outpatient clinic typically seen twice weekly. Here, an exercise regime is performed and improvement assessed using a hand held goniometer that measures the maximum angle of knee flexion, an important metric of progress. Additionally a series of daily exercises is performed at home, recorded in a diary. This protocol has problems. Patients must attend the hospital with assistance since they are not permitted to drive for six weeks following the procedure; appointments are sometimes missed; there are occasionally not enough physiotherapy appointment available; furthermore, it is difficult to be sure that patients are compliant with their exercises at home. The economic and social costs are therefore significant both to the patient and the health service. We describe here an automatic system that performs the monitoring of knee flexion within a domestic environment rather than in a hospital setting. It comprises a master and slave sensor unit that attach using Velcro straps to the thigh and shin above and below the operation wound. The patient performs the prescribed knee exercises whilst wearing the device, during which time it measures and records the angles of knee flexion. The device utilises the Global System for Mobile Communications (GSM) infrastructure to transmit data through the Internet to a secure hospital-based server using an on-board GSM modem. The clinician is then able to view and interpret the information from any computer with internet access and the software. The system does not require the patient to possess a mobile telephone, a computer, or have internet access; the necessary communications technology is completely integrated into the device.

Flexion;Remote monitoring;Telemonitoring;Total knee arthroplasty;mHealth

pubmed

Psychometric evaluation of a multi-dimensional measure of satisfaction with behavioral interventions.

Treatment satisfaction is recognized as an essential aspect in the evaluation of an intervention's effectiveness, but there is no measure that provides for its comprehensive assessment with regard to behavioral interventions. Informed by a conceptualization generated from a literature review, we developed a measure that covers several domains of satisfaction with behavioral interventions. In this paper, we briefly review its conceptualization and describe the Multi-Dimensional Treatment Satisfaction Measure (MDTSM) subscales. Satisfaction refers to the appraisal of the treatment's process and outcome attributes. The MDTSM has 11 subscales assessing treatment process and outcome attributes: treatment components' suitability and utility, attitude toward treatment, desire for continued treatment use, therapist competence and interpersonal style, format and dose, perceived benefits of the health problem and everyday functioning, discomfort, and attribution of outcomes to treatment. The MDTSM was completed by persons (N = 213) in the intervention group in a large trial of a multi-component behavioral intervention for insomnia within 1 week following treatment completion. The MDTSM's subscales demonstrated internal consistency reliability (α: .65 - .93) and validity (correlated with self-reported adherence and perceived insomnia severity at post-test). The MDTSM subscales can be used to assess satisfaction with behavioral interventions and point to aspects of treatments that are viewed favorably or unfavorably.

behavioral intervention;insomnia;instrument validation;outcome;process;satisfaction

pubmed

Hobnail Variant of Papillary Thyroid Carcinoma: a Literature Review.

Papillary thyroid carcinoma is the most common thyroid malignancy and it is usually associated with a good prognosis. However, recurrence, metastases, and cancer death may occur in 10 to 15% of patients with more aggressive types of papillary thyroid carcinoma, such as tall cell, columnar cell, solid variant, or the more recently described hobnail variant of papillary thyroid carcinoma. Papillary thyroid carcinoma with a prominent hobnail pattern is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. The hobnail variant of papillary thyroid carcinoma shows prominent hobnail features, which have also been referred to as micropapillary. The typical hobnail/micropapillary morphological features show loss of cellular polarity/cohesiveness and support an epithelial-mesenchymal transition as a possible mechanism of metastasis. BRAF p.V600E is the most common mutation in papillary thyroid carcinoma, including the hobnail variant; recent and continuing studies are focused on defining other molecular anomalies that may be useful for prognostic stratification and may provide therapeutic targets.

Aggressive variant;BRAF mutation;Epithelial-mesenchymal transition;Hobnail;Papillary thyroid carcinoma

pubmed

Colchicine triggered severe rhabdomyolysis after long-term low-dose simvastatin therapy: a case report.

Rhabdomyolysis is a widely recognized yet rare complication in statin use. Rhabdomyolysis might be triggered by the prescription of high doses of statins or by statin accumulation due to interactions with concomitant medication. Muscle cell destruction as evidenced by myoglobin elevation can induce potentially life-threatening acute renal failure. We report a case of a 70-year-old obese white man with sudden onset of severe rhabdomyolysis with consecutive renal failure. His medication included low-dose simvastatin, which he had taken for 6 years up until the event. The statin was withdrawn immediately. After 3 days of veno-venous hemofiltration his renal function was completely restored. Clinicians in both primary and special care might be unaware that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years.

Anti-HMGCR-antibody;Case report;Colchicine;Rhabdomyolysis;Statin therapy;Statin-associated myopathies (SAM)

pubmed

Frontline Science: <i>Leishmania mexicana</i> amastigotes can replicate within neutrophils.

Cutaneous leishmaniasis is a neglected tropical disease, causing a spectrum of clinical manifestations varying from self-healing to unhealing lesions that may be very difficult to treat. Emerging evidence points to a detrimental role for neutrophils during the first hours following infection with many distinct <i>Leishmania</i> species (spp.) at a time when the parasite is in its nonreplicative promastigote form. Neutrophils have also been detected at later stages of infection in unhealing chronic cutaneous lesions. However, the interactions between these cells and the replicative intracellular amastigote form of the parasite have been poorly studied. Here, we show that <i>Leishmania</i><i>mexicana</i> amastigotes are efficiently internalized by neutrophils and that this process has only a low impact on neutrophil activation and apoptosis. In neutrophils, the amastigotes were found in acidified vesicles. Furthermore, within cutaneous unhealing lesions, heavily infected neutrophils were found with up to 6 parasites per cell. To investigate if the amastigotes could replicate within neutrophils, we generated photoconvertible fluorescent parasites. With the use of flow cytometry imaging and time-lapse microscopy, we could demonstrate that a subset of parasites replicated within neutrophils. Overall, our data reveal a novel role for neutrophils that can act as a niche for parasite replication during the chronic phase of infection, thereby contributing to disease pathology.

granulocytes;photoconvertible parasite;promastigotes;replication

pubmed

A comparison of the proximate, fibre, mineral content, amino acid and the fatty acid profile of Marula (Sclerocarya birrea caffra) nut and soyabean (Glycine max) meals.

As a result of shortages and the cost of the currently utilized conventional dietary protein sources in the Sub-Saharan Africa feed industry, the chemical evaluation of available non-conventional sources for feed is imperative. One such source is Marula nut meal (a by-product of Marula oil extraction). The present study chemically characterized the nutritional composition of two differently processed Marula nut meals (MNMs) and compared them with that of solvent extracted soyabean meal (SBM). The MNMs had higher dry matter, ether extract and gross energy but lower crude protein and ash contents compared to SBM. The cold press produced Marula nut meal (MNM2) had higher arginine than the hydraulic filter press produced Marula nut meal (MNM1) and SBM. The meals had similar neutral and acid detergent fibre contents. The MNMs had higher phosphorus, magnesium and copper concentrations than SBM. Although the total saturated fatty acid proportion was similar across the meals, total monounsaturated and polyunsaturated fatty acid proportions were higher in MNMs and SBM, respectively. Oleic acid was higher in MNMs than in SBM. The low crude protein content in MNMs compared to SBM is comparable with other conventional dietary protein sources. Thus, the MNMs could be used as protein and energy feed ingredients. © 2017 Society of Chemical Industry.

energy;non-conventional feeds;nutrient content;protein

pubmed

Bcl-2 inhibitors reduce steroid-insensitive airway inflammation.

Asthmatic inflammation is dominated by accumulation of either eosinophils, neutrophils, or both in the airways. Disposal of these inflammatory cells is the key to disease control. Eosinophilic airway inflammation is responsive to corticosteroid treatment, whereas neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid-resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies. We sought to explore the underlying mechanisms of airway inflammation persistence, as well as corticosteroid resistance, and to investigate a new strategy of effective treatment against corticosteroid-insensitive neutrophilic asthma. Mouse models of either eosinophil-dominated or neutrophil-dominated airway inflammation were used in this study to test corticosteroid sensitivity in vivo and in vitro. We also used vav-Bcl-2 transgenic mice to confirm the importance of granulocytes apoptosis in the clearance of airway inflammation. Finally, the Bcl-2 inhibitors ABT-737 or ABT-199 were tested for their therapeutic effects against eosinophilic or neutrophilic airway inflammation and airway hyperresponsiveness. Overexpression of Bcl-2 protein was found to be responsible for persistence of granulocytes in bronchoalveolar lavage fluid after allergic challenge. This was important because allergen-induced airway inflammation aggravated and persisted in vav-Bcl-2 transgenic mice, in which nucleated hematopoietic cells were overexpressed with Bcl-2 and resistant to apoptosis. The Bcl-2 inhibitors ABT-737 or ABT-199 play efficient roles in alleviation of either eosinophilic or corticosteroid-resistant neutrophilic airway inflammation by inducing apoptosis of immune cells, such as eosinophils, neutrophils, T_H2 cells, T_H17 cells, and dendritic cells. Moreover, these inhibitors were found to be more efficient than steroids to induce granulocyte apoptosis ex vivo from patients with severe asthma. Apoptosis of inflammatory cells is essential for clearance of allergen-induced airway inflammation. The Bcl-2 inhibitors ABT-737 or ABT-199 might be promising drugs for the treatment of airway inflammation, especially for corticosteroid-insensitive neutrophilic airway inflammation.

Airway inflammation;Bcl-2;apoptosis;eosinophil;neutrophil;steroid insensitive

pubmed

Cinnamaldehyde induces cell apoptosis mediated by a novel circular RNA hsa_circ_0043256 in non-small cell lung cancer.

Cinnamaldehyde (CA), the primary chemical component of the Chinese traditional herb Cinnamomum cassia, is an effective cytotoxic agent against various human cancers. Our previous study indicated that CA could trigger apoptosis in three kinds of non-small cell lung cancer (NSCLC) cells. However, CA mechanism of action in NSCLC has not been unveiled completely. Herein, we showed that a novel circular RNA hsa_circ_0043256 was upregulated in NSCLC cells in response to CA treatment, as detected by microarray and real-time PCR. Hsa_circ_0043256 could inhibit cell proliferation and induce apoptosis, while hsa_circ_0043256 knock-down could promote cell proliferation and restrain apoptosis induced by CA. Bioinformatics analysis predicted that hsa_circ_0043256 could work as a miR-1252 sponge, which could in turn directly target a vital negative regulator of Canonical Wnt signaling, Itchy E3 ubiquitin protein ligase (ITCH), as validated by dual-luciferase assay. Western blot results further confirmed that hsa_circ_0043256 could upregulate ITCH expression, whereas miR-1252 could partially abolish this effect. Interestingly, hsa_circ_0043256 knock-down could weaken Wnt/β-catenin pathway inhibition induced by CA. Finally, we discovered that CA induced apoptosis and meanwhile upregulated hsa_circ_0043256 expression in vivo. Immunohistochemical analysis revealed that ITCH expression was positively association with hsa_circ_0043256 levels. Above all, we characterized a new mechanism mediated by hsa_circ_0043256/miR-1252/ITCH axis in CA function against NSCLC, providing a novel insight into lung cancer therapy.

Apoptosis;Cinnamaldehyde;ITCH;NSCLC;hsa_circ_0043256

pubmed

<i>In-Vitro</i> Assessment of Magnetic Dextran-Spermine Nanoparticles for Capecitabine Delivery to Cancerous Cells.

Cationic polymeric nanoparticles have great potential for developing drug delivery systems with limited side effects for tumor medication. The goal of this research is investigation of cationic dextran-spermine polymer (DS) efficacy for improvement of hydrophilic drug delivery to negatively charged cancerous cells. Capecitabine (as a hydrophilic antineoplastic drug) was loaded into the magnetic dextran-spermine nanoparticles (DS-NPs) via ionic gelation. Design of experiments was applied to specify how the significant factors affect size, surface charge and capecitabine entrapment efficiency of the DS-NPs. Physicochemical properties, <i>in-vitro</i> release profile and cellular studies of the optimized DS-NPs were evaluated. The experimental results indicated that DS-NPs with favorable properties can be achieved at an optimized condition of 2 mg/mL DS and 0.75 mg/mL tri-polyphosphate (TPP) concentrations, TPP addition rate of 35 mL/min, pH 3 of DS solution and super paramagnetic iron oxide nanoparticles (SPION)/DS mass ratio of 0.5. The entrapment efficiency of capecitabine was 26.1% at optimum condition and drug release at neutral pH after 24 h and acidic pH within 3 h was 56 and 98%, respectively. The cytotoxicity assessment exhibited that capecitabine loaded DS-NPs was more toxic than corresponding free drug as control. Significant cellular uptake of capecitabine loaded DS-NPs by U87MG glioblastoma cells were proved by Prussian blue staining and TEM, qualitatively. DS-NPs are suitable candidates for delivery of the hydrophilic drugs in cancer treatment and due to positive charge of the dextran-spermine, the uptake of the hydrophilic drugs by the cancerous cells was improved.

Cancer;Controlled release;Drug delivery systems;Factorial design;U87MG

pubmed

Examination of neighborhood disadvantage and sleep in a multi-ethnic cohort of adolescents.

Neighborhood-level socioeconomic disadvantage and lower individual-level socioeconomic status are associated with poorer sleep health in adults. However, few studies have examined the association between neighborhood-level disadvantage and sleep in adolescents, a population at high-risk for sleep disturbances. The current study is the first to examine how objective (i.e. via census tract-level data) and subjective measures of neighborhood disadvantage are associated with sleep in a racially/ ethnically and socioeconomically diverse sample of 2493 youth [Non-Hispanic White (20%), Hispanic (46%), Asian (21%), and Multiracial/ Other (13%)]. Findings indicated that greater perceived neighborhood-level social cohesion and lower neighborhood-level poverty were associated with better sleep outcomes in adolescents. However, there was some evidence that the magnitude of the associations differed according to family-level socioeconomic status and race/ ethnicity. Findings suggest that subjective and objective neighborhood characteristics may affect the sleep health of older adolescents, with certain demographic subgroups being particularly vulnerable.

Adolescents;Neighborhoods, socioeconomic status, poverty;Sleep;Social environments

pubmed

Celebrity-endorsed e-cigarette brand Instagram advertisements: Effects on young adults' attitudes towards e-cigarettes and smoking intentions.

Celebrities endorsing e-cigarette brands on social media may exert a strong influence on e-cigarette uptake. Using a between-subject experiment, this study examines the effects of endorser type (celebrities, non-celebrities and products only) in e-cigarette brand Instagram advertisements on e-cigarette attitudes and smoking intentions. Results showed that celebrity endorsers significantly increased positive attitudes towards e-cigarettes and smoking intentions, compared to non-celebrities or products only. Celebrity endorsers also rated significantly higher on trustworthiness, expertise, goodwill and attractiveness, compared to non-celebrities. Additionally, identification, social comparison, health consciousness and social networking site use moderated between endorser type and key dependent measures. Implications for e-cigarette marketing regulation are discussed.

advertising;celebrity endorsers;electronic cigarettes;smoking;social media

pubmed

Antibacterial Toxins: Gram-Positive Bacteria Strike Back!

Bacteria live in communities where strains compete with each other by deploying an arsenal of antibacterial toxins. While the past decade revealed the vast array of antibacterial toxins secreted by Gram-negative bacteria, several recent studies have begun to uncover the ability of Gram-positive bacteria to battle with their own weapons.

competition;firmicutes;secretion;toxin

pubmed

Single-centre experience of granulomatous interstitial nephritis-time for a new approach?

<b>Background:</b> Differentiating between renal-limited sarcoidosis and tuberculosis (TB) infection as a cause of granulomatous interstitial nephritis (GIN) can be difficult. This series compares clinical features and response to treatment between the different underlying aetiologies in order to propose a management algorithm for GIN to assist with diagnosis and treatment. <b>Methods:</b> This retrospective study reports on all patients presenting with a histological diagnosis of GIN between 2000 and 2012 at our unit. <b>Results:</b> Twenty-one patients were identified, 57% were male and the mean age was 53 years. Eight cases were associated with sarcoidosis with evidence of extra-renal disease and five with renal-limited sarcoidosis. Five patients had GIN that may have been related to TB infection or to renal-limited sarcoidosis, and three were idiopathic or drug related. All those with sarcoidosis were treated with steroids and renal function, as measured by estimated glomerular filtration rate (eGFR), improved from a mean of 24 mL/min at baseline to 37 mL/min at 1 year. Baseline eGFR was 19 mL/min in those with possible TB infection. Four received steroids as well as anti-TB drugs. Anti-TB therapy was delayed in four patients by a mean of 22 months due to difficulties in diagnosis. Two patients with TB developed end-stage kidney disease and the remaining three patients had a mean eGFR of 28 mL/min at 1 year. <b>Conclusions:</b> This series represents the largest cohort of patients with GIN in the UK and supports previous findings that patients with sarcoid have a favourable outcome with steroid treatment. Those with TB have an inferior prognosis, perhaps due to delayed diagnosis. We suggest an algorithm when investigating a diagnosis of GIN with the aim of expediting diagnosis and considering a trial of anti-TB therapy in order to prevent deterioration of renal function.

chronic kidney disease;granulomatous;interstitial nephritis;sarcoidosis;tuberculosis

pubmed

Distributed Simulation as a modelling tool for the development of a simulation-based training programme for cardiovascular specialties.

<i>Distributed Simulation</i> is the concept of portable, high-fidelity immersive simulation. Here, it is used for the development of a simulation-based training programme for cardiovascular specialities. We present an evidence base for how accessible, portable and self-contained simulated environments can be effectively utilised for the modelling, development and testing of a complex training framework and assessment methodology. Iterative user feedback through mixed-methods evaluation techniques resulted in the implementation of the training programme. Four phases were involved in the development of our immersive simulation-based training programme: <b>(</b>1) initial conceptual stage for mapping structural criteria and parameters of the simulation training framework and scenario development (<i>n</i> = 16), (2) training facility design using <i>Distributed Simulation</i>, (3) test cases with clinicians (<i>n</i> = 8) and collaborative design, where evaluation and user feedback involved a mixed-methods approach featuring (a) quantitative surveys to evaluate the realism and perceived educational relevance of the simulation format and framework for training and (b) qualitative semi-structured interviews to capture detailed feedback including changes and scope for development. Refinements were made iteratively to the simulation framework based on user feedback, resulting in (4) transition towards implementation of the simulation training framework, involving consistent quantitative evaluation techniques for clinicians (<i>n</i> = 62). For comparative purposes, clinicians' initial quantitative mean evaluation scores for realism of the simulation training framework, realism of the training facility and relevance for training (<i>n</i> = 8) are presented longitudinally, alongside feedback throughout the development stages from concept to delivery, including the implementation stage (<i>n</i> = 62). Initially, mean evaluation scores fluctuated from low to average, rising incrementally. This corresponded with the qualitative component, which augmented the quantitative findings; trainees' user feedback was used to perform iterative refinements to the simulation design and components (collaborative design), resulting in higher mean evaluation scores leading up to the implementation phase. Through application of innovative Distributed Simulation techniques, collaborative design, and consistent evaluation techniques from conceptual, development, and implementation stages, fully immersive simulation techniques for cardiovascular specialities are achievable and have the potential to be implemented more broadly.

Collaborative design;Distributed Simulation;Evaluation;Immersive simulation;Implementation;Mixed-methods;Training

pubmed

Cross-linked beads of activated oil palm ash zeolite/chitosan composite as a bio-adsorbent for the removal of methylene blue and acid blue 29 dyes.

Cross-linked beads of activated oil palm ash zeolite/chitosan (Z-AC/C) composite were prepared through the hydrothermal treatment of NaOH activated oil palm ash followed by beading with chitosan. The effects of initial dye concentration (50-400mg/L), temperature (30°C-50°C) and pH (3-13) on batch adsorption of methylene blue (MB) and acid blue 29 (AB29) were studied. Adsorption of both dyes was better described by Pseudo-second-order kinetics and Freundlich isotherm model. The maximum adsorption capacities of Z-AC/C were 151.51, 169.49, and 199.20mg/g for MB and 212.76, 238.09, and 270.27mg/g for AB29 at 30°C, 40°C, and 50°C, respectively.

Chitosan;Methylene blue;Zeolite

pubmed

On mixed electron-photon radiation therapy optimization using the column generation approach.

Despite considerable increase in the number of degrees of freedom handled by recent radiotherapy optimisation algorithms, treatments are still typically delivered using a single modality. Column generation is an iterative method for solving large optimisation problems. It is well suited for mixed-modality (e.g., photon-electron) optimisation as the aperture shaping and modality selection problem can be solved rapidly, and the performance of the algorithm scales favourably with increasing degrees of freedom. We demonstrate that the column generation method applied to mixed photon-electron planning can efficiently generate treatment plans and investigate its behaviour under different aperture addition schemes. Column generation was applied to the problem of mixed-modality treatment planning for a chest wall case and a leg sarcoma case. 6 MV beamlets (100 cm SAD) were generated for the photon components along with 5 energies for electron beamlets (6, 9, 12, 16 and 20 MeV), simulated as shortened-SAD (80 cm) beams collimated with a photon MLC. For the chest wall case, IMRT-only, modulated electron radiation therapy (MERT)-only, and mixed electron-photon (MBRT) treatment plans were created using the same planning criteria. For the sarcoma case, MBRT and MERT plans were created to study the behaviour of the algorithm under two different sets of planning criteria designed to favour specific modalities. Finally, the efficiency and plan quality of four different aperture addition schemes was analysed by creating chest wall MBRT treatment plans which incorporate more than a single aperture per iteration of the column generation loop based on a heuristic aperture ranking scheme. MBRT plans produced superior target coverage and homogeneity relative to IMRT and MERT plans created using the same optimisation criteria, all the while preserving the normal tissue-sparing advantages of electron therapy. Adjusting the planning criteria to favour a specific modality in the sarcoma case resulted in the algorithm correctly emphasizing the appropriate modality. As expected, adding a single aperture per iteration yielded the lowest (best) cost function value per aperture included in the treatment plan. However, a greedier scheme was able to converge to approximately the same cost function after 125 apertures in one third of the running time. Electron apertures were on average 50-100% larger than photon apertures for all aperture addition schemes. The distribution of intensities among the available modalities followed a similar trend for all schemes, with the dominant modalities being 6 MV photons along with 6, 9 and 20 MeV electrons. The column generation method applied to mixed modality treatment planning was able to produce clinically realistic treatment plans and combined the advantages of photon and electron radiotherapy. The running time of the algorithm depended heavily on the choice of mixing scheme. Adding the highest ranked aperture for each modality provided the best trade-off between running time and plan quality for a fixed number of apertures. This work contributes an efficient methodology for the planning of mixed electron-photon treatments.

Direct aperture optimization;Mixed beam radiation therapy;Monte Carlo;column generation;intensity modulated radiation therapy;modulated electron radiation therapy

pubmed

Subchondral bone in osteoarthritis: association between MRI texture analysis and histomorphometry.

Magnetic resonance imaging (MRI) texture analysis is a method of analyzing subchondral bone alterations in osteoarthritis (OA). The objective of this study was to evaluate the association between MR texture analysis and ground-truth subchondral bone histomorphometry at the tibial plateau. The local research ethics committee approved the study. All subjects provided written, informed consent. This was a cross-sectional study carried out at our institution between February and August 2014. Ten participants aged 57-84 with knee OA scheduled for total knee arthroplasty (TKA) underwent pre-operative MRI of the symptomatic knee at 3T using a high spatial-resolution coronal T1 weighted sequence. Tibial plateau explants obtained at the time of TKA underwent histological preparation to allow calculation of bone volume fraction (BV.TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N). Texture analysis was performed on the tibial subchondral bone of MRI images matched to the histological sections. Regression models were created to assess the association of texture analysis features with BV.TV, Tb.Th, Tb.Sp and Tb.N. MRI texture features were significantly associated with BV.TV (R² = 0.76), Tb.Th (R² = 0.47), Tb.Sp (R² = 0.75) and Tb.N (R² = 0.60, all P < 0.001). Simple gray-value histogram based texture features demonstrated the highest standardized regression coefficients for each model. MRI texture analysis features were significantly associated with ground-truth subchondral bone histomorphometry at the tibial plateau.

Histomorphometry;Magnetic resonance imaging;Osteoarthritis;Subchondral bone;Texture analysis

pubmed

Comparison of FFPE histological versus LBP cytological samples for HPV detection and typing in cervical cancer.

Human papillomavirus (HPV) infection is closely associated with cervical cancer. This study analyzed HPV genotype prevalence in 75 cases of formalin-fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with cervical cancer. Genotype prevalence was assessed using Reverse Blot Assay (REBA) and quantitative polymerase chain reaction (qPCR), which target the HPV L1 and HPV E6/E7 genes, respectively. HPV DNA chip tests were also performed using liquid based preparation (LBP) cytological samples from the same patients who provided the FFPE histological samples. We observed a slight difference in HPV genotype distribution as assessed by DNA chip versus REBA. One possible explanation for this difference is that normal regions could be mixed with lesion regions when cytological samples are extracted from each patient with cancer. For the detection of moderate dysplasia, the main target of diagnosis, this difference is anticipated to be greater. We also made several unexpected observations. For example, HPV multi-infection was not detected. Moreover, the rate of HPV positivity varied radically depending on the cancer origin, e.g. squamous cell carcinoma versus adenocarcinoma. Our results imply that it is important to determine whether cytological specimens are suitable for HPV genotyping analysis and cervical cancer diagnosis. Future research on the mechanisms underlying cervical cancer pathogenesis is also necessary.

Cervical cancer;FFPE;HPV;qPCR

pubmed

Determinants and Duration of Impact of Early Gut Bacterial Colonization.

An increasing number of studies show low diversity of the gut microbiome in those with chronic diseases such as obesity, inflammatory bowel disease, and allergy. Manipulation of the microbiota may promote health. However, the adult microbiota is stable and may be difficult to change. Understanding the fixed and modifiable factors, which determine colonization in early life, may provide strategies for acquisition of a health-promoting microbiome. Not enough is known about the long-term effects of established determinants of gut colonization, including delivery mode, perinatal antibiotics, and infant diet. It has been suggested that weaning onto solid diet containing non-digestible carbohydrates and cessation of breastfeeding are key stages in the colonization process. In addition, the microbiome of the placenta, amniotic fluid, and breast milk, alongside vaginal and fecal bacteria, may aid the transfer of maternal bacteria to the infant. However, methodological issues such as contamination during collection and/or analysis should be considered. Key Messages: The factors determining early colonization are becoming more evident. However, longitudinal studies of microbiome maturation into late childhood and adulthood are required. The nutrition and health status of the mother before, during, and after birth may be major factors in the early colonization of the infant.

Bacteria;Gut;Infant colonization;Microbiota

pubmed

Optimization of Manufacturing Conditions for Improving Storage Stability of Coffee-Supplemented Milk Beverage Using Response Surface Methodology.

This study aimed at optimizing the manufacturing conditions of a milk beverage supplemented with coffee, and monitoring its physicochemical and sensory properties during storage. Raw milk, skim milk powder, coffee extract, and emulsifiers were used to manufacture the beverage. Two sucrose fatty acid esters, F110 and F160, were identified as suitable emulsifiers. The optimum conditions for the beverage manufacture, which can satisfy two conditions at the same time, determined by response surface methodology (RSM), were 5,000 rpm primary homogenization speed and 0.207% sucrose fatty acid emulsifier addition. The particle size and zeta-potential of the beverage under the optimum condition were 190.1 nm and - 25.94±0.06 mV, respectively. In comparison study between F110 added group (GF110) and F160 added group (GF160) during storage, all samples maintained its pH around 6.6 to 6.7, and there was no significant difference (<i>p</i><0.05). In addition, GF110 showed significantly higher zeta-potential than GF160 (<i>p</i><0.05). The particle size of GF110 and GF160 were approximately 190.1 and 223.1 nm, respectively at initial. However, size distribution of the GF160 tended to increase during storage. Moreover, increase of the particle size in GF160 was observed in microphotographs of it during storage. The L* values gradually decreased within all groups, whereas the a* and b* values did not show significant variations (<i>p</i><0.05). Compared with GF160, bitterness, floating cream, and rancid flavor were more pronounced in the GF110. Based on the result obtained from the present study, it appears that the sucrose fatty acid ester F110 is more suitable emulsifier when it comes to manufacturing this beverage than the F160, and also contributes to extending product shelf-life.

RSM;coffee;emulsification;shelf-life

pubmed

Sustained-release study on Exenatide loaded into mesoporous silica nanoparticles: in vitro characterization and in vivo evaluation.

Exenatide (EXT), the first glucagon-like peptide-1 receptor agonist, has been approved as an adjunctive therapy for patients with type 2 diabetes. Due to EXT's short half-life, EXT must be administrated by continuous subcutaneous (s.c.) injection twice daily. In previous studies, many studies on EXT loaded into polymer materials carriers for sustained release had been reported. However, these carriers have some defects, such as hydrophobicity, low surface energy, low mechanical strength, and poor chemical stability. Therefore, this study aims to develop a novel drug delivery system, which is EXT loaded into well-ordered hexagonal mesoporous silica structures (EXT-SBA-15), to control the sustainability of EXT. SBA-15 was prepared by hydrothermal method with uniform size. Morphology of SBA-15 was employed by transmission electron microscopy. The pore size of SBA-15 was characterized by N₂ adsorption-desorption isotherms. The in vitro drug release behavior and pharmacokinetics of EXT-SBA-15 were investigated. Furthermore, the blood glucose levels of diabetic mice were monitored after subcutaneous injection of EXT-Sol and EXT-SBA-15 to evaluate further the stable hypoglycemic effect of EXT-SBA-15. EXT-SBA-15 showed a higher drug loading efficiency (15.2 ± 2.0%) and sustained-release features in vitro. In addition, pharmacokinetic studies revealed that the EXT-SBA-15 treatment group extended the half-life t _1/2(β) to 14.53 ± 0.70 h compared with that of the EXT solution (EXT-Sol) treatment group (0.60 ± 0.08 h) in vivo. Results of the pharmacodynamics study show that the EXT-SBA-15 treatment group had inhibited blood glucose levels below 20 mmol/L for 25 days, and the lowest blood glucose level was 13 mmol/L on the 10th day. This study demonstrates that the EXT-SBA-15 delivery system can control the sustainability of EXT and contribute to improve EXT clinical use.

Exenatide;Mesoporous silica nanoparticles;Pharmacokinetics/Pharmacodynamics;Sustained release;Type 2 diabetic

pubmed

GryphSens: A Smartphone-Based Portable Diagnostic Reader for the Rapid Detection of Progesterone in Milk.

Enzyme-linked immunosorbent assay (ELISA) is a popular assay technique for the detection and quantification of various biological substances due its high sensitivity and specificity. More often, it requires large and expensive laboratory instruments, which makes it difficult to conduct when the tests must be performed quickly at the point-of-care (POC). To increase portability and ease of use, we propose a portable diagnostic system based on a Raspberry Pi imaging sensor for the rapid detection of progesterone in milk samples. We designed, assembled, and tested a standalone portable diagnostic reader and validated it for progesterone detection against a standard ELISA assay using a commercial plate reader. The portable POC device yielded consistent results, regardless of differences in the cameras and flashlights between various smartphone devices. An Android application was built to provide front-end access to users, control the diagnostic reader, and display and store the progesterone measurement on the smartphone. The diagnostic reader takes images of the samples, reads the pixel values, processes the results, and presents the results on the handheld device. The proposed POC reader can perform to superior levels of performance as a plate reader, while adding the desirable qualities of portability and ease of use.

android application;image analysis;immunoassay;point-of-care reader;progesterone detection

pubmed

Morphology and force probing of primary murine liver sinusoidal endothelial cells.

Liver sinusoidal endothelial cells (LSECs) represent unique type of endothelial cells featured by their characteristic morphology, ie, lack of a basement membrane and presence of fenestrations-transmembrane pores acting as a dynamic filter between the vascular space and the liver parenchyma. Delicate structure of LSECs membrane combined with a submicron size of fenestrations hinders their visualization in live cells. In this work, we apply atomic force microscopy contact mode to characterize fenestrations in LSECs. We reveal the structure of fenestrations in live LSECs. Moreover, we show that the high-resolution imaging of fenestrations is possible for the glutaraldehyde-fixed LSECs. Finally, thorough information about the morphology of LSECs including great contrast in visualization of sieve plates and fenestrations is provided using Force Modulation mode. We show also the ability to precisely localize the cell nuclei in fixed LSECs. It can be helpful for more precise description of nanomechanical properties of cell nuclei using atomic force microscopy. Presented methodology combining high-quality imaging of fixed cells with an additional nanomechanical information of both live and fixed LSECs provides a unique approach to study LSECs morphology and nanomechanics that could foster understanding of the role of LSECs in maintaining liver homeostasis.

AFM imaging;LSEC;LSEC nanomechanics;fenestrations;fixed cells;force mapping;live cells

pubmed

Evaluation of serum level of Osteocalcin hormone in male infertility.

The suggested concept of "bone as an endocrine organ" had shed the light on the role of osteocalcin, an osteoblast secreted hormone, in regulation of testosterone production. This study aimed to assess the association between the active undercarboxylated form of osteocalcin (ucOC) and semen parameters and hormonal levels in infertile male patients. The study was carried on 34 infertile male patients and 20 fertile healthy control males. Semen analysis and serum level of testosterone, LH and FSH were performed in addition to serum level of ucOC in cases and controls. The results revealed significant differences between cases and controls in all measured semen and hormonal parameters. In addition, significant higher level of ucOC in cases than control group (p = .019). On the other hand, ucOC was not related significantly to any of the measured hormones or semen parameters. There was no significant correlation between ucOC and sperm concentration, total motility, morphology (p = .594, .640, .940 respectively) and similarly between ucOC and testosterone level or LH level (p = .275, .954 respectively). The significant higher level of ucOC in infertile cases cannot be used as a predictor of male reproductive parameters.

infertility;male infertility;osteocalcin;osteocalcin hormone

pubmed

Dysregulated Glycine Signaling Contributes to Increased Impulsivity during Protracted Alcohol Abstinence.

Persons with alcoholism who are abstinent exhibit persistent impairments in the capacity for response inhibition, and this form of impulsivity is significantly associated with heightened relapse risk. Brain-imaging studies implicate aberrant prefrontal cortical function in this behavioral pathology, although the underlying mechanisms are not understood. Here we present evidence that deficient activation of glycine and serine release in the ventral medial prefrontal cortex (vmPFC) contributes to increased motor impulsivity during protracted abstinence from long-term alcohol exposure. Levels of 12 neurotransmitters were monitored in the rat vmPFC during the performance of a challenging variant of the five-choice serial reaction time task (5-CSRTT) in which alcohol-exposed rats exhibit excessive premature responding. Following long-term ethanol exposure, rats showed blunted task-related recruitment of vmPFC glycine and serine release, and the loss of an inverse relationship between levels of these neurotransmitters and premature responding normally evident in alcohol-naive subjects. Intra-vmPFC administration of the glycine transport inhibitor ALX5407 prevented excessive premature responding by alcohol-exposed rats, and this was reliant on NMDA glycine site availability. Alcohol-exposed rats and controls did not differ in their premature responding and glycine and serine levels in vmPFC during the performance of the standard 5-CSRTT. Collectively, these findings provide novel insight into cortical neurochemical mechanisms contributing to increased impulsivity following long-term alcohol exposure and highlight the NMDA receptor coagonist site as a potential therapeutic target for increased impulsivity that may contribute to relapse risk.<b>SIGNIFICANCE STATEMENT</b> Persons with alcoholism demonstrate increased motor impulsivity during abstinence; however, the neuronal mechanisms underlying these behavioral effects remain unknown. Here, we took advantage of an animal model that shows deficiencies in inhibitory control following prolonged alcohol exposure to investigate the neurotransmitters that are potentially responsible for dysregulated motor impulsivity following long-term alcohol exposure. We found that increased motor impulsivity is associated with reduced recruitment of glycine and serine neurotransmitters in the ventromedial prefrontal cortex (vmPFC) cortex in rats following long-term alcohol exposure. Administration of glycine transport inhibitor ALX5407 in the vmPFC alleviated deficits in impulse control.

alcohol dependence;five-choice serial reaction time task;glycine;motor impulsivity

pubmed

Conjugated Polymer Nanoparticles for Bioimaging.

During the last decade, conjugated polymers have emerged as an interesting class of fluorescence imaging probes since they generally show high fluorescence brightness, high photostability, fast emission rates, non-blinking behavior and low cytotoxicity. The main concern related to most conjugated polymers is their lack of hydrophilicity and thereby poor bio-availability. This can, however, be overcome by the formulation of conjugated polymer nanoparticles in aqueous medium. This review provides an overview of the different techniques employed for the preparation of conjugated polymer nanoparticles, together with methods to improve their photoluminescence quantum yields. For selective targeting of specific cells, dedicated surface functionalization protocols have been developed, using different functional groups for ligand immobilization. Finally, conjugated polymer nanoparticles have recently also been employed for theranostic applications, wherein the particles are simultaneously used as fluorescent probes and carriers for anti-tumor drugs.

bioimaging;conjugated polymers;fluorescence;nanoparticles

pubmed

Evidence of accessibility and utility of point-of-care diagnostics as an integral part of prevention of mother-to-child transmission services: systematic scoping review protocol.

Point-of-care (POC) testing has been shown to help improve healthcare access in resource-limited settings. However, there is paucity of evidence on accessibility of POC testing for prevention of mother-to-child transmission (PMTCT) in resource-limited settings. We propose to conduct a systematic scoping review to map the evidence on POC testing services for PMTCT. A scoping review framework, proposed by Arksey and O'Malley, will guide the study. A comprehensive literature search will be performed in the following electronic databases: PubMed, Science Direct, Cochrane Central, Google Scholar and databases within EBSCOhost (Medline and CINAHL). The primary research articles published in peer-reviewed journals and grey articles addressing our question will be included. One reviewer will conduct title screening and the results will be exported to endnote library. Two independent reviewers will perform abstract, then full article screening in parallel. The same process shall be employed to extract data from eligible studies. Data analysis will involve a narrative summary of included studies and thematic content analysis aided by NVIVO software V.11. The mixed methods assessment tool will be used to assess the quality of studies that will be included. Ethical approval is not applicable to this study. The study findings will be disseminated through publication in a peer-reviewed journal and presentations at conferences related to syphilis, HIV, PMTCT, bacterial infections and POC diagnostics. CRD42017056267.

point of care testing;prevention of mother to child transmission;women

pubmed

Monoclonal B lymphocytosis and minimal change disease: a new monoclonal B-cell disorder of renal significance?

Chronic lymphocytic leukemia (CLL) may induce renal complications, which are becoming increasingly common, but in this context the occurrence of minimal change disease (MCD) remains rare. Monoclonal B lymphocytosis (MBL) is a precursor state of CLL and is currently under recognized. Since MBL is seen as a benign disorder that rarely evolves into CLL, screening for MBL is not standardized and does not require any treatment. When reviewing renal disease associated with MBL, there is very scant data in the literature and to date there is no case describing the association between MBL and MCD. Here, we describe the case of a 71-year old woman admitted for nephrotic syndrome (NS). We diagnosed a MBL. Kidney biopsy revealed MCD. Treatment with corticosteroids was introduced but no improvement was observed. Chemotherapy with rituximab and chlorambucil was thus started, leading to complete remission of both MBL and MCD. To our knowledge, this is the first description of the association of MBL and MCD. This case suggests that screening for MBL may have unexpected diagnostic and therapeutic implications in patients presenting with seemingly idiopathic NS.

B lymphocytosis;Chrnic lynmphocytic leukemia;Hematology;Minimal change disease;Nephrotic syndrome

pubmed

Long-term oncologic and functional outcome in pleomorphic adenomas of the submandibular gland.

The aim of the study was to evaluate the oncologic and functional long-term outcome after surgical therapy of pleomorphic adenomas of the submandibular gland. The medical charts of all patients treated for pleomorphic adenomas of the submandibular gland by means of submandibulectomy between 2000 and 2016 were studied retrospectively. Patients who had had revision after external primary surgery, as well as patients with insufficient data were excluded from our study sample. A total of 75 patients formed our study sample (28 men, 47 women, male:female ratio 0.59:1). Their mean age was 48 years (14-78 years). Mean follow-up was 82 months (12-170 months). No recurrences of a pleomorphic adenoma could be detected in our study cases. Normal facial nerve function (House-Brackmann grade I) in the direct postoperative phase was shown in 54/75 cases (72%). In the remaining 21/75 cases (28%), mild paresis of the marginal mandibular branch of the facial nerve (House-Brackmann II) could be detected in the direct postoperative phase. All cases with facial palsy had recovered with normal facial nerve function (House-Brackmann I) in 3-6 months. Our study was able to show oncologic and consistently acceptable oncologic and functional outcomes after submandibulectomy for pleomorphic adenomas of the submandibular gland. 4.

Pleomorphic adenoma;facial nerve;recurrence;submandibular gland;submandibulectomy

pubmed

Fluazifop-P-butyl induced ROS generation with IAA (indole-3-acetic acid) oxidation in Acanthospermum hispidum D.C.

Acanthospermum hispidum D.C. was particularly susceptible to fluazifop-P-butyl, an aryloxyphenoxypropionate herbicide, and the primary action site for the herbicide was shoot apical meristem, which is also the main site of indole-3-acetic acid (IAA) biosynthesis and action. Membrane lipid peroxidation caused by increasing levels of reactive oxygen species (ROS) was considered as an action mechanism of fluazifop-P-butyl in A. hispidum. To further clarify the ROS inducing mechanism of fluazifop-P-butyl in the plant, the interactions between fluazifop-P-butyl and auxin compounds IAA or 2,4-dichlorophenoxyacetic acid (2,4-D) were studied. Haloxyfop-P-methyl, an AOPP herbicide which is inactive on A. hispidum, was used for comparison. The results showed that the growth inhibition and malondialdehyde or H₂O₂ increases induced by fluazifop-P-butyl on A. hispidum were reversed by IAA or 2,4-D. The IAA content was decreased but the contents of three IAA oxidation metabolites, indole-3-methanol, indole-3-aldehyde and indole-3-carboxylic acid were increased by fluazifop-P-butyl in A. hispidum, but not by haloxyfop-P-methyl. The growth of A. hispidum was not inhibited by three IAA oxidative compounds. Moreover, the activities of IAA oxidase and peroxidase were increased by fluazifop-P-butyl but not by haloxyfop-P-methyl, and the increase was reversed by IAA or 2,4-D. We suggest that there is an antagonistic effect between fluazifop-P-butyl and IAA or 2,4-D, and the IAA oxidation may be involved in the action mechanism of fluazifop-P-butyl in A. hispidum.

Acanthospermum hispidum;Antagonistic effect;Fluazifop-P-butyl;IAA oxidase;IAA oxidation;Peroxidase

pubmed

Resilience and the rehabilitation of adult spinal cord injury survivors: A qualitative systematic review.

To synthesize the qualitative research evidence that explored how survivors of adult spinal cord injury experience and make sense of resilience. Spinal cord injury is often a sudden and unexpected life-changing event requiring complex and long-term rehabilitation. The development of resilience is essential in determining how spinal cord injury survivors negotiate this injury and rehabilitation. A qualitative systematic review and thematic synthesis of the research evidence. CINAHL, PubMed, Embase, Scopus and PsycINFO were searched, no restriction dates were used. Methodological quality was assessed using the Critical Appraisal Skills Programme checklist. Thematic synthesis focused on how survivors of adult spinal cord injury experience and make sense of resilience. Six qualitative research articles reported the experiences of 84 spinal cord injury survivors. Themes identified were: uncertainty and regaining independence; prior experiences of resilience; adopting resilient thinking; and strengthening resilience through supports. Recovery and rehabilitation following spinal cord survivors is influenced by the individual's capacity for resilience. Resilience may be influenced by previous life experiences and enhanced by supportive nursing staff encouraging self-efficacy. Survivors identified the need for active involvement in decision-making about their care to enable a sense of regaining control of their lives. This has the potential to have a significant impact on their self-efficacy and in turn health outcomes.

nursing;qualitative;rehabilitation;resilience;social support;spinal cord injuries;systematic review

pubmed

Uncovering the pathogenesis of microtia using bioinformatics approach.

Bioinformatics is widely used in the field of cancer research, but in the research of pathogenesis of congenital malformations the situation is different. The aim of this study was to explore the underlying mechanism using bioinformatics approach. The data were available from Mouse Genome Informatics and Pubmed. Protein-protein interaction (PPI) network of pathogenic genes was conducted using STRING. Gene ontology and pathway enrichment analyses were also performed to pathogenic genes. Total 63 genes were identified as pathogenic genes in the study. The PPI networks for pathogenic genes were constructed, which contained 62 nodes and 228 edges with PAX6, FGFR1 and CTNNB1 as the hub genes. All the genes were linked to 921 pathways in biological processes, 31 pathways in cell component, 41 pathways in molecular function, and 76 pathways in the KEGG. These genes were discovered significantly enriched in embryonic organ development, ear morphogenesis, ear development, and regulation of RNA synthesis and processing. bioinformatics methods were utilized to analysis pathogenic genes involved in microtia development, including pathogenic genes identifying, PPI network construction and functional analysis. And we also predicted that several potential mechanisms might contribute to occurrence of microtia by disturbing GO terms and pathways. This approach could be useful for the study of the etiology and pathogenesis of microtia.

Bioinformatics;Gene ontology (GO);Kyoto encyclopedia of genes and genomes;Microtia;Protein-protein interaction

pubmed

Pneumonia with pleural empyema caused by Salmonella Typhi in an immunocompetent child living in a non-endemic country.

Extra-intestinal complications of Salmonella Typhi (S. Typhi) infections usually occur in endemic countries and in patients with underlying risk conditions. A 14-year-old immunocompetent girl was admitted with respiratory distress owing to S. Typhi pneumonia and pleural empyema. She was a native of Ivory Coast but had lived in France for 4 years and had not travelled abroad for several years. There were no gastro-intestinal symptoms and no S. Typhi carriage was detected in her family. She recovered completely with ceftriaxone and ciprofloxacin and pleural drainage was not required. An atypical presentation of S. Typhi should be considered even in settings where there are no risk factors.

Salmonella Typhi;ceftriaxone;child;ciprofloxacin;immunocompetent;pleural empyema;pneumonia

pubmed

Laparoscopic choledochoduodenostomy as a reliable rescue procedure for complicated bile duct stones.

Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction is generally accepted as first line management for common bile duct (CBD) stones. CBD exploration, either by open or laparoscopic approach nowadays, is usually reserved for ERCP failures, complicated stone locations, along with altered anatomical situations. The aim of this study was to highlight the increasing role of laparoscopic choledochoduodenostomy which is not only a reliable but also as a rescue procedure for those failed ERCP cases due to complicated bile duct stones. It is a retrospective review of the database, from a tertiary care teaching institution from India, from Jan 2012 up to December 2016. Out of total 30 patients who underwent laparoscopic choledochoduodenostomy, 28 had failed ERC stone clearance while two patients were directly offered drainage in view of unfavorable anatomy. The major reasons for failed ERC stone clearance were as follows-multiple large calculi (42.8%), recurrent stones (21.4%), and associated stricture (21.4%). Mean operating time was 130 (± 27) minutes with mean blood loss of 60 (± 19) ml. Stone extraction was successful, primarily by milking in 13 (43.33%) patients, rest required augmentation by Dormia basket/balloon. Two patients (6.66%) developed controlled bile leak which resolved with conservative treatment. The median length of hospital stay was 5 days (IQR 3-9). Mean duration of follow-up was 17 (± 3.2) months. Laparoscopic common bile duct exploration with choledochoduodenostomy has been shown to be a safe, reliable, and efficient method for treating complex CBDS, especially after failed ERCP procedures.

Biliary calculi;Biliary drainage;Choledochoduodenostomy;ERCP;Laparoscopy

pubmed

Luminomagnetic Eu³⁺- and Dy³⁺-doped hydroxyapatite for multimodal imaging.

Multimodal imaging has recently attracted much attention due to the advantageous combination of different imaging modalities, like photoluminescence (PL) and magnetic resonance imaging (MRI). In the present study, luminescent and magnetic hydroxyapatites (HAp) were prepared via doping with europium (Eu³⁺) and dysprosium (Dy³⁺), respectively. Co-doping of Eu³⁺ and Dy³⁺ was used to combine the desired physical properties. Both lanthanide ions were successfully incorporated in the HAp crystal lattice, where they preferentially occupied calcium(I) sites. While Eu-doped HAp (Eu:HAp) exhibits dopant concentration dependent persistent PL properties, Dy-doped HAp (Dy:HAp) shows paramagnetic behavior due to the high magnetic moment of Dy³⁺. Co-doped HAp (Eu:Dy:HAp) nanoparticles combine both properties in one single crystal. Remarkably, multimodal co-doped HAp features enhanced PL properties due to an energy transfer from Dy³⁺ sensitizer to Eu³⁺ activator ions. Eu:Dy:HAp exhibits strong transverse relaxation effects with a maximum transverse relaxivity of 83.3L/(mmol·s). Due to their tunable PL, magnetic properties and cytocompatibility Eu:-, Dy:- and Eu:Dy:HAp represent promising biocompatible ceramic materials for luminescence imaging that simultaneously may serve as a contrast agent for MRI in permanent implants or functional coatings.

Contrast agent;Europium;Hydroxyapatite;Luminescence;MRI

pubmed

Ivabradine vs metoprolol in patients with acute inferior wall myocardial infarction-"Expanding arena for ivabradine".

Atrioventricular (AV) blocks are of concern with the use of beta blockers in inferior wall myocardial infarction (MI). Ivabradine lowers heart rate with a lesser risk of AV blocks. To compare ivabradine with metoprolol in acute inferior wall MI in terms of feasibility, tolerability, and efficacy. It was a prospective double-blind single-center randomized controlled study. Of 1032 patients with acute inferior wall MI, 468 eligible patients were randomized in 1:1 manner to ivabradine (group A) and metoprolol (group B). Intention to treat analysis of 426 patients (group A-232 and group B-232) was performed. The primary endpoint was 30-day incidence of major adverse cardiovascular events including death, reinfarction, complete heart block (CHB), and heart failure. Secondary endpoints included 30 days incidence of recurrent angina, readmission, first- or second-degree AV block, and tachyarrhythmias. Both the drugs decreased the mean heart rate to 62.22±2.95 (group A) vs 62.53±3.59 (group B) beats per minute (P=0.33). Ejection fraction improved in both the groups (5.15±1.93% in group A vs 5.52±2.18% in group B, P=0.065). The two groups did not differ significantly in their primary endpoints in terms of death (group A=1.72% vs group B=1.72%, OR=1.00, 95% CI=0.25-4.05, P=1.00), reinfarction (group A=0.86% vs group B=0.86%, OR=1.00, 95% CI=0.14-7.16, P=1.00), heart failure (group A=4.31% vs group B=2.59%, OR=1.70, 95% CI=0.61-4.75, P=0.31), or CHB (0% vs 2.59%, OR=0.07, 95% CI=0.00-1.34, P=0.08). There were no significant differences in the secondary endpoints of recurrent angina, readmission, and tachyarrhythmias except for more first- and second-degree AV blocks with metoprolol (12.93% vs 2.59%, OR=5.59, 95% CI=2.28-13.72, P=0.0002). Ivabradine is well tolerated and equally effective as metoprolol in acute inferior wall ST elevation myocardial infarction patients for lowering the heart rate with lesser risk of AV blocks.

Atrioventicular blocks;Inferior wall myocardial infarction;Ivabradine;Metoprolol

pubmed

High prevalence of cardiovascular risk factors in Peruvian adolescents living in a peri-urban shantytown: a cross-sectional study.

Adults of the peri-urban Peruvian shantytown of Lomas de Zapallal have a high prevalence of risk factors for developing cardiovascular disease (CVD)-likely due to behavioral choices established during childhood and adolescence. To guide the development of community-based risk reduction programs, we assessed the prevalence of risk factors for developing CVD among adolescents. We collected cross sectional data from adolescents of Peruvian peri-urban shantytown to evaluate four domains of CVD risk factors: (1) clinical (blood pressure, fasting blood glucose, and blood lipids), (2) anthropometric (height, weight, and waist circumference), (3) behavioral (physical activity, diet, and substance abuse), and (4) psychosocial (mental health and violence). We enrolled 275 adolescents (56.4% female, mean age 14 years). Prevalence of overweight or obese status was 27.8%. High blood pressure was more common in males (37.4%) than females (20.5%) (p = 0.002). Total cholesterol was elevated (>170 mg/dL) in nearly half (45.5%) of the adolescents, and 71% had impaired fasting blood glucose (>100 mg/dL). Females were less likely to exercise daily (95.4%) than males (84.2%) (p = 0.002) but reported higher rates of depression (66.4%), anhedonia (67.6%), and self-harm behavior (37.9%) (all p < 0.01). Adolescents living in the peri-urban population of Puente Piedra had high prevalence of risk factors for future development of CVD; preventative efforts focused on improving nutrition, increasing physical inactivity, and addressing mental health conditions could reduce such risk factors.

Adolescent health;Cardiovascular disease;Peru;Primary prevention;Risk factors

pubmed

Evaluation of the Level of Knowledge of Oral Cancer Among High School Students.

The present study aims to determine the knowledge level of high school students regarding oral cancer. The present study included students from 20 high schools located in the city center of Kahramanmaras between 1 and 28 April 2015. The students were informed prior to the study and 2759 students who gave written consent were included in the study. The participants were administered a questionnaire that was prepared by the investigators. The questionnaire included 25 questions that were prepared using literature in order to establish the knowledge level of the students about oral cancer, and it was evaluated scoring one point to each question. There were 1711 (62.0 %) female students and 1048 (38.0 %) male students; the mean age was 16.01 ± 1.09 years. The knowledge score of the male students was 7.48 ± 5.15 and the knowledge score of the female students was 7.58 ± 4.96. The knowledge score of the female and male participants was similar (p = 0.605). Of the students, 2107 (76.4 %) stated that they heard the expression of oral cancer before compared to 652 (23.6 %) students stating they did not. The study found that high school students had insufficient levels of knowledge about oral cancer. There was a general lack of knowledge about oral cancer and the risks among these students.

High school students;Knowledge;Oral cancer

pubmed

The Incomplete Glutathione Puzzle: Just Guessing at Numbers and Figures?

Glutathione metabolism is comparable to a jigsaw puzzle with too many pieces. It is supposed to comprise (i) the reduction of disulfides, hydroperoxides, sulfenic acids, and nitrosothiols, (ii) the detoxification of aldehydes, xenobiotics, and heavy metals, and (iii) the synthesis of eicosanoids, steroids, and iron-sulfur clusters. In addition, glutathione affects oxidative protein folding and redox signaling. Here, I try to provide an overview on the relevance of glutathione-dependent pathways with an emphasis on quantitative data. Recent Advances: Intracellular redox measurements reveal that the cytosol, the nucleus, and mitochondria contain very little glutathione disulfide and that oxidative challenges are rapidly counterbalanced. Genetic approaches suggest that iron metabolism is the centerpiece of the glutathione puzzle in yeast. Furthermore, recent biochemical studies provide novel insights on glutathione transport processes and uncoupling mechanisms. Which parts of the glutathione puzzle are most relevant? Does this explain the high intracellular concentrations of reduced glutathione? How can iron-sulfur cluster biogenesis, oxidative protein folding, or redox signaling occur at high glutathione concentrations? Answers to these questions not only seem to depend on the organism, cell type, and subcellular compartment but also on different ideologies among researchers. A rational approach to compare the relevance of glutathione-dependent pathways is to combine genetic and quantitative kinetic data. However, there are still many missing pieces and too little is known about the compartment-specific repertoire and concentration of numerous metabolites, substrates, enzymes, and transporters as well as rate constants and enzyme kinetic patterns. Gathering this information might require the development of novel tools but is crucial to address potential kinetic competitions and to decipher uncoupling mechanisms to solve the glutathione puzzle. Antioxid. Redox Signal. 27, 1130-1161.

compartmentalization;concentration;function;glutathione;kinetics;rate constant

pubmed

Particle size distribution: A key factor in estimating powder dustiness.

A wide variety of raw materials, involving more than 20 samples of quartzes, feldspars, nephelines, carbonates, dolomites, sands, zircons, and alumina, were selected and characterised. Dustiness, i.e., a materials' tendency to generate dust on handling, was determined using the continuous drop method. These raw materials were selected to encompass a wide range of particle sizes (1.6-294 µm) and true densities (2650-4680 kg/m³). The dustiness of the raw materials, i.e., their tendency to generate dust on handling, was determined using the continuous drop method. The influence of some key material parameters (particle size distribution, flowability, and specific surface area) on dustiness was assessed. In this regard, dustiness was found to be significantly affected by particle size distribution. Data analysis enabled development of a model for predicting the dustiness of the studied materials, assuming that dustiness depended on the particle fraction susceptible to emission and on the bulk material's susceptibility to release these particles. On the one hand, the developed model allows the dustiness mechanisms to be better understood. In this regard, it may be noted that relative emission increased with mean particle size. However, this did not necessarily imply that dustiness did, because dustiness also depended on the fraction of particles susceptible to be emitted. On the other hand, the developed model enables dustiness to be estimated using just the particle size distribution data. The quality of the fits was quite good and the fact that only particle size distribution data are needed facilitates industrial application, since these data are usually known by raw materials managers, thus making additional tests unnecessary. This model may therefore be deemed a key tool in drawing up efficient preventive and/or corrective measures to reduce dust emissions during bulk powder processing, both inside and outside industrial facilities. It is recommended, however, to use the developed model only if particle size, true density, moisture content, and shape lie within the studied ranges.

Dust physics;dustiness measurement;minerals;particulate matter;prediction model

pubmed

Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study.

Colorectal cancer (CRC) is the second most common cancer in women and the third in men in Poland. The role of chemotherapy (CTX) depends on the stage of CRC: adjuvant CTX is a standard treatment in stage III and should also be considered in stage II with risk factors. The aim of the paper was to assess the cardiovascular consequences of CTX in CRC enrolled to the ONCOECHO multicentre study (2012-2014). To identify potential cardiotoxicity, we focused on myocardial function, heart rhythm and conduction disorders, and adverse cardiovascular events. Twenty-five CRC patients (12 women, mean age 61.3 [35-76] years), all receiving six-month adjuvant CTX were included. Thirteen patients received 5-fluorouracil (5FU)-based CTX, and 12 patients received a capecitabine-based scheme. Subjects were assessed at baseline and followed-up three, six, and 12 months after the onset of treatment. In this analysis we focused on conduction abnormalities, systolic and diastolic function of the left ventricle (LV), and cardiovascular events. In 12-month follow-up a decrease of selected tissue Doppler parameters (e.g. S'IVS, S'lat, and E'sept) was observed, and it was significant. LV structural parameters and ejection fraction (EF) remained unaffected. Changes in myocardial performance were not influenced by CTX regimen or treatment with beta-blockers or angiotensin-converting enzyme inhibitors. CTX did not affect LV structural parameters, EF, or conduction system, nor was it associated with cardiovascular events during the 12-month follow-up. CTX in CRC patients does not affect LV structural parameters and EF. It may, however, trigger subtle changes in myocardial performance detectable by tissue Doppler echocardiography after 12 months. Moreover, it causes a transient increase of QT, which resolves after CTX cessation.

cardiotoxicity;chemotherapy;colon cancer;echocardiography

pubmed

Successful treatment of three severe MDR or XDR Pseudomonas aeruginosa infections with ceftolozane/tazobactam.

Ceftolozane/tazobactam is a novel fifth-generation cephalosporin β-lactamase combination with activity against extended-spectrum β-lactamases-producing enterobacteriaceae, and multidrug resistant Pseudomonas aeruginosa. However, clinical experience in real cases caused by these microorganisms is scarce. In this study, we describe three patients with severe infections caused by multidrug resistant and extensively drug-resistant (XDR) P. aeruginosa that were successfully treated with ceftolozane/tazobactam.

Pseudomonas aeruginosa;ceftolozane/tazobactam;clinical experience;multidrug-resistant organisms;severe infections

pubmed

What Does "the RNA World" Mean to "the Origin of Life"?

Corresponding to life's two distinct aspects: Darwinian evolution and self-sustainment, the origin of life should also split into two issues: the origin of Darwinian evolution and the arising of self-sustainment. Because the "self-sustainment" we concern about life should be the self-sustainment of a relevant system that is "defined" by its genetic information, the self-sustainment could not have arisen before the origin of Darwinian evolution, which was just marked by the emergence of genetic information. The logic behind the idea of the RNA world is not as tenable as it has been believed. That is, genetic molecules and functional molecules, even though not being the same material, could have emerged together in the beginning and launched the evolution-provided that the genetic molecules can "simply" code the functional molecules. However, due to these or those reasons, alternative scenarios are generally much less convincing than the RNA world. In particular, when considering the accumulating experimental evidence that is supporting a de novo origin of the RNA world, it seems now quite reasonable to believe that such a world may have just stood at the very beginning of life on the Earth. Therewith, we acquire a concrete scenario for our attempts to appreciate those fundamental issues that are involved in the origin of life. In the light of those possible scenes included in this scenario, Darwinian evolution may have originated at the molecular level, realized upon a functional RNA. When two or more functional RNAs emerged, for their efficient cooperation, there should have been a selective pressure for the emergence of protocells. But it was not until the appearance of the "unitary-protocell", which had all of its RNA genes linked into a chromosome, that Darwinian evolution made its full step towards the cellular level-no longer severely constrained by the low-grade evolution at the molecular level. Self-sustainment did not make sense before protocells emerged. The selection pressure that was favoring the exploration of more and more fundamental raw materials resulted in an evolutionary tendency of life to become more and more self-sustained. New functions for the entities to adapt to environments, including those that are involved in the self-sustainment per se, would bring new burdens to the self-sustainment-the advantage of these functions must overweigh the corresponding disadvantage.

Darwinian evolution;protocell;self-sustaining;the essence of life;the origin of evolution

pubmed

Structural dependence on the property of chiral stationary phases derived from chitosan bis(arylcarbamate)-(amide)s.

The goal of present study was to investigate the structural dependence of chitosan derivatives on enantioseparation and mobile phase tolerance of the corresponding chiral packing materials for liquid chromatography. Hence, a series of chitosan bis(arylcarbamate)-(n-pentyl amide)s and the related chiral stationary phases (CSPs) were prepared from chitosans with different molecular weights. Because of the H-bond formed via CH₃-π interaction, the CSP bearing methyl substituent exhibited high tolerance than the ones bearing dichloro substituents. The CSP derived from the chitosan bis(3,5-dichlorophenylcarbamate)-(n-pentyl amide) with a higher molecular weight possessed high tolerance to mobile phases, whereas the enantioseparation capability of this CSP was not as good as that of the one prepared from the chitosan derivative with a lower molecular weight. Therefore, enantioseparation capability and mobile phase tolerance have to be counterbalanced in designing chiral selectors for the CSPs derived from chitosan bis(arylcarbamate)-(amide)s.

Chiral stationary phase;Chitin;Chitosan;Enantioseparation;High-performance liquid chromatography;Packing material

pubmed

Photocatalysis of S-metolachlor in aqueous suspension of magnetic cerium-doped mTiO₂ core-shell under simulated solar light.

Magnetic cerium-doped mesoporous titanium dioxide was synthesized by combining sol-gel method and calcination using tetrabutanate and ammonium cerium nitrate as precursors and Pluronic P123 as a template coating on iron oxide covered with carbon in ethanol. The magnetic Ce-doped catalyst showed only anatase structure with a slight increase in lattice parameters compared to the undoped catalyst. The Ce L_III-edge X-ray absorption near-edge spectroscopy (XANES) spectra showed Ce³⁺, and the cerium substitution doping into titanium dioxide was proposed. Degradation of S-metolachlor in aqueous magnetic photocatalyst suspension followed (pseudo) first-order kinetics in the presence of 0.5 g L^-1 of γ-Fe₂O₃@[email protected] mol% Ce-mTiO₂ with a half-life of 55.18 ± 1.63 min. Fifteen degradation products were identified, and their transformation routes of the photocatalytic degradation were then proposed. Complementary toxicity assessment of the treated S-metolachlor solution was undertaken with Environment Canada's algal microplate assay measuring growth inhibition (72-h IC₅₀) in the freshwater chlorophyte Pseudokirchneriella subcapitata. This test method revealed a significant decrease in toxicity (1.7-fold reduction after 180 min of irradiation treatment), thereby confirming that the by-products formed following photocatalysis would be less harmful from an environmental point of view. Photocatalytic degradation of S-metolachlor thus appears to hold promise as a cost-effective treatment technology to diminish the presence of this herbicide in aquatic systems.

Algal toxicity;Magnetic cerium-doped mesoporous titanium dioxide;Photocatalysis;Pseudokirchneriella subcapitata;S-metolachlor

pubmed

IL-17 Activates the IL-6/STAT3 Signal Pathway in the Proliferation of Hepatitis B Virus-Related Hepatocellular Carcinoma.

We performed this study to determine the role of IL-17 in the immune microenvironment of hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). HepG2 cells were treated with IL-17, STAT3 inhibitor S31-201 or IL-6 neutralizing monoclonal antibody (IL-6 mAb). Cell proliferation and migration were compared using the Cell Counting kit-8 (CCK-8) and Transwell assays, respectively. Real-time quantitative PCR (RT-qPCR), Western Blot, ELISA, immunofluorescence and histological staining were used for determining the expression levels of IL-17, IL-6, MCP-1, CCL5, VEGF, STAT3 and p-STAT3. HCC xenograft models were constructed in wild type and IL-17 knockout mice to clarify the effects of IL-17 on HCC in vivo. Exogenous IL-17 enhanced the proliferation and migration of HepG2 cells, and it activated the phosphorylation of STAT3. RT-qPCR and ELISA showed that IL-17 promoted the expression of IL-6. The CCK-8 and Transwell assays showed that S31-201 or IL-6 mAb remarkably reversed the promotion effects of proliferation and migration by exogenous IL-17 in HepG2 cells. Additionally, IL-6 could promote the phosphorylation of STAT3, while IL-6 mAb acted as an inhibitor, and exogenous IL-17 could neutralize the inhibitory effects of IL-6 mAb. In vivo, compared to the wild type mice, the tumor volume, weight, density and size were decreased in IL-17 knockout mice. Additionally, the expression levels of p-STAT3, IL-6, MCP-1, CCL5 and VEGF decreased in IL-17 knockout mice. IL-17 can enhance the proliferation of HepG2 cells in vitro and in vivo via activating the IL-6/STAT3 pathway. Therefore, the IL-17/IL-6/STAT3 signaling pathway is a potential therapeutic target for HBV-related HCC.

HBV;HCC;IL-17;IL-6;pSTAT3

pubmed

How different is a 3D-printed replica from a conspecific in the eyes of a zebrafish?

Robotics is emerging as a promising tool for aiding research on animal behavior. The possibility of generating customizable, controllable, and standardized robotic stimuli has been demonstrated through a number of behavioral assays, involving vertebrates and invertebrates. However, the specific appraisal of the nature of robotic stimuli is currently lacking. Here, we attempt to evaluate this aspect in zebrafish, through a within-subject design in which experimental subjects are faced with three experimental conditions. In the first test, we investigated sociability by measuring zebrafish response to a conspecific separated by a one-way glass. In the second test, we studied zebrafish behavior in response to a 3D-printed zebrafish replica actuated along realistic trajectories through a novel four-degree-of-freedom robotic platform. Last, we investigated fear responses in a shelter-seeking test. In agreement with our expectations, zebrafish exhibited an equivalent preference for live and robotic stimuli, and the degree of preference for the robotic replica correlated negatively with the individual propensity to seek shelter. The equivalent preference for the replica and conspecific suggests that the appraisal of the target stimuli is analogous. The preliminary evidence of a correlation between behavioral responses across tests points to the readability of robotics-based approaches to investigate interindividual differences.

Danio rerio;binary choice;robotics;shelter-seeking;social behavior

pubmed

Subjectivity of the Anomalous Sense of Self Is Represented in Gray Matter Volume in the Brain.

The self includes complicated and heterogeneous functions. Researchers have divided the self into three distinct functions called "agency," "ownership," and "narrative self". These correspond to psychiatric symptoms, behavioral characteristics and neural responses, but their relationship with brain structure is unclear. This study examined the relationship between the subjectivity of self-related malfunctions and brain structure in terms of gray matter (GM) volume in 96 healthy people. They completed a recently developed self-reported questionnaire called the Embodied Sense of Self Scale (ESSS) that measures self-related malfunctions. The ESSS has three subscales reflecting the three distinct functions of the self. We also determined the participants' brain structures using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM). Multiple regression analysis revealed a significant negative correlation between ownership malfunction and the insular cortex GM volume. A relationship with brain structure could thus only be confirmed for the ESSS "ownership" subscale. This finding suggests that distinct brain structures feel ownership and that the ESSS could partly screen for distinct brain structures.

agency;minimal self;narrative self;ownership;voxel-based morphometry

pubmed

A first-in-human, randomized, controlled, subject- and reviewer-blinded multicenter study of Actamax™ Adhesion Barrier.

Post-surgical adhesions remain a significant concern following abdominopelvic surgery. This study was to assess safety, manageability and explore preliminary efficacy of applying a degradable hydrogel adhesion barrier to areas of surgical trauma following gynecologic laparoscopic abdominopelvic surgery. This first-in-human, prospective, randomized, multicenter, subject- and reviewer-blinded clinical study was conducted in 78 premenopausal women (18-46 years) wishing to maintain fertility and undergoing gynecologic laparoscopic abdominopelvic surgery with planned clinically indicated second-look laparoscopy (SLL) at 4-12 weeks. The first two patients of each surgeon received hydrogel, up to 30 mL sprayed over all sites of surgical trauma, and were assessed for safety and application only (n = 12). Subsequent subjects (n = 66) were randomized 1:1 to receive either hydrogel (Treatment, n = 35) or not (Control, n = 31); 63 completed the SLL. No adverse event was assessed as serious, or possibly device related. None was severe or fatal. Adverse events were reported for 17 treated subjects (17/47, 36.2%) and 13 Controls (13/31, 41.9%). For 95.7% of treated subjects, surgeons found the device "easy" or "very easy" to use; in 54.5%, some residual material was evident at SLL. For 63 randomized subjects who completed the SLL, adjusted between-group difference in the change from baseline adhesion score demonstrated a 41.4% reduction for Treatment compared with Controls (p = 0.017), with a 49.5% reduction (p = 0.008) among myomectomy subjects (n = 34). Spray application of a degradable hydrogel adhesion barrier during gynecologic laparoscopic abdominopelvic surgery was performed easily and safely, without evidence of clinically significant adverse outcomes. Data suggest the hydrogel was effective in reducing postoperative adhesion development, particularly following myomectomy.

Adhesion barrier study;Gynecological laparoscopic surgery;Hydrogel adhesion barrier;Post-surgical adhesions;Second-look laparoscopy

pubmed

Cardiovascular Hypertensive Crisis: Recent Evidence and Review of the Literature.

Despite the high prevalence of hypertension (HTN), only a small proportion of the hypertensive patients will ultimately develop hypertensive crisis. In fact, some patients with hypertensive crisis do not report a history of HTN or previous use of antihypertensive medication. The majority of the patients with hypertensive crisis often report non-specific symptoms, whereas heart-related symptoms (dyspnea, chest pain, arrhythmias, and syncope) are less common. Hypertensive crises can be divided into hypertensive emergencies or hypertensive urgencies according to the presence or absence of acute target organ damage, respectively. This differentiation is an extremely useful classification in clinical practice since a different management is needed, which in turn has a significant effect on the morbidity and mortality of these patients. Therefore, it is very crucial for the physician in the emergency department to identify the hypertensive emergencies and to manage them through blood pressure lowering medications in order to avoid further target organ damage or deterioration. The aim of this narrative review is to summarize the recent evidence in an effort to improve the awareness, recognition, risk stratification, and treatment of hypertensive crisis in patients referred to the emergency department.

hypertension;hypertensive crisis;hypertensive emergencies;hypertensive urgencies;management

pubmed

Prostatic abscess of Klebsiella pneumonia complicating septic pulmonary emboli and meningitis: A case report and brief review.

Prostatic abscess is a rare entity with an incidence of 0.5%-2.5% in all prostate diseases and usually occurs in the 5th and 6th decades of life with immunocompromised status. Prostatic abscess might be a process of evolution from acute prostatitis. Klebsiella pneumoniae is the leading microorganism in the diabetic patients of prostatic abscess in Taiwan. A 60-year-old diabetic man, with a one-week history of acute bacterial prostatitis was reported in this study, presenting to the emergency department with sudden altered mental status. The abdominal computed tomographic scan demonstrated lobulated prostatic abscess and multiple septic pulmonary emboli with lung abscesses. Analysis of cerebrospinal fluid showed white blood cells of 10771 counts/mm³ with segmented neutrophils of 99%. Cultures of blood, cerebrospinal fluid and sputum yielded Klebsiella pneumoniae. We concluded that computed tomographic scan can make a definite diagnosis of prostatic abscess associated with complications and management with empiric antibiotics and adequate drainage is suggested.

Klebsiella pneumoniae;Lung abscess;Meningitis;Prostatic abscess;Septic emboli

pubmed

Intraoperative acceleration measurements to quantify improvement in tremor during deep brain stimulation surgery.

Deep brain stimulation (DBS) surgery is extensively used in the treatment of movement disorders. Nevertheless, methods to evaluate the clinical response during intraoperative stimulation tests to identify the optimal position for the implantation of the chronic DBS lead remain subjective. In this paper, we describe a new, versatile method for quantitative intraoperative evaluation of improvement in tremor with an acceleration sensor that is mounted on the patient's wrist during surgery. At each anatomical test position, the improvement in tremor compared to the initial tremor is estimated on the basis of extracted outcome measures. This method was tested on 15 tremor patients undergoing DBS surgery in two centers. Data from 359 stimulation tests were acquired. Our results suggest that accelerometric evaluation detects tremor changes more sensitively than subjective visual ratings. The effective stimulation current amplitudes identified from the quantitative data (1.1 ± 0.8 mA) are lower than those identified by visual evaluation (1.7 ± 0.8 mA) for similar improvement in tremor. Additionally, if these data had been used to choose the chronic implant position of the DBS lead, 15 of the 26 choices would have been different. These results show that our method of accelerometric evaluation can potentially improve DBS targeting.

Acceleration;Deep brain stimulation;Essential tremor;Intraoperative monitoring;Parkinson’s disease;Tremor

pubmed

Using Real-Time Social Media Technologies to Monitor Levels of Perceived Stress and Emotional State in College Students: A Web-Based Questionnaire Study.

College can be stressful for many freshmen as they cope with a variety of stressors. Excess stress can negatively affect both psychological and physical health. Thus, there is a need to find innovative and cost-effective strategies to help identify students experiencing high levels of stress to receive appropriate treatment. Social media use has been rapidly growing, and recent studies have reported that data from these technologies can be used for public health surveillance. Currently, no studies have examined whether Twitter data can be used to monitor stress level and emotional state among college students. The primary objective of our study was to investigate whether students' perceived levels of stress were associated with the sentiment and emotions of their tweets. The secondary objective was to explore whether students' emotional state was associated with the sentiment and emotions of their tweets. We recruited 181 first-year freshman students aged 18-20 years at University of California, Los Angeles. All participants were asked to complete a questionnaire that assessed their demographic characteristics, levels of stress, and emotional state for the last 7 days. All questionnaires were completed within a 48-hour period. All tweets posted by the participants from that week (November 2 to 8, 2015) were mined and manually categorized based on their sentiment (positive, negative, neutral) and emotion (anger, fear, love, happiness) expressed. Ordinal regressions were used to assess whether weekly levels of stress and emotional states were associated with the percentage of positive, neutral, negative, anger, fear, love, or happiness tweets. A total of 121 participants completed the survey and were included in our analysis. A total of 1879 tweets were analyzed. A higher level of weekly stress was significantly associated with a greater percentage of negative sentiment tweets (beta=1.7, SE 0.7; P=.02) and tweets containing emotions of fear (beta=2.4, SE 0.9; P=.01) and love (beta=3.6, SE 1.4; P=.01). A greater level of anger was negatively associated with the percentage of positive sentiment (beta=-1.6, SE 0.8; P=.05) and tweets related to the emotions of happiness (beta=-2.2, SE 0.9; P=.02). A greater level of fear was positively associated with the percentage of negative sentiment (beta=1.67, SE 0.7; P=.01), particularly a greater proportion of tweets related to the emotion of fear (beta=2.4, SE 0.8; P=.01). Participants who reported a greater level of love showed a smaller percentage of negative sentiment tweets (beta=-1.3, SE 0.7; P=0.05). Emotions of happiness were positively associated with the percentage of tweets related to the emotion of happiness (beta=-1.8, SE 0.8; P=.02) and negatively associated with percentage of negative sentiment tweets (beta=-1.7, SE 0.7; P=.02) and tweets related to the emotion of fear (beta=-2.8, SE 0.8; P=.01). Sentiment and emotions expressed in the tweets have the potential to provide real-time monitoring of stress level and emotional well-being in college students.

monitoring;social media;twitter messaging, stress

pubmed

Cotton functional genomics reveals global insight into genome evolution and fiber development.

Due to the economic value of natural textile fiber, cotton has attracted much research attention, which has led to the publication of two diploid genomes and two tetraploid genomes. These big data facilitate functional genomic study in cotton, and allow researchers to investigate cotton genome structure, gene expression, and protein function on the global scale using high-throughput methods. In this review, we summarized recent studies of cotton genomes. Population genomic analyses revealed the domestication history of cultivated upland cotton and the roles of transposable elements in cotton genome evolution. Alternative splicing of cotton transcriptomes was evaluated genome-widely. Several important gene families like MYC, NAC, Sus and GhPLDα1 were systematically identified and classified based on genetic structure and biological function. High-throughput proteomics also unraveled the key functional proteins correlated with fiber development. Functional genomic studies have provided unprecedented insights into global-scale methods for cotton research.

Cotton;Fiber development;Functional genomics;Genome evolution

pubmed

Ruptured de novo Aneurysm following Gamma Knife Surgery for Arteriovenous Malformation: Case Report.

Stereotactic radiosurgery is a well-known treatment tool for arteriovenous malformations (AVMs). The method has high validity and minimal invasiveness, but late-onset problems involving tumor formation and vasculopathy induced by radiation have been reported. We present a rare case of a radiation-induced ruptured de novo aneurysm following Gamma Knife surgery (GKS) for an AVM. A 17-year-old, right-handed male underwent GKS for AVM at the left parietal lobe. After 3 years, a follow-up angiogram showed a residual AVM at the angular gyrus. Then, a 2nd GKS was performed for the residual lesion. Six years after the 1st GKS, the AVM disappeared on the angiogram. Seven years later, he suffered a sudden onset of headache. A left carotid angiogram revealed a ruptured aneurysm at the M2-M3 junction of the middle cerebral artery parietal branch. Coil embolization was performed, and the aneurysm was occluded. The patient was discharged without any neurologic deficits.

Arteriovenous malformation;Gamma Knife surgery;Radiation-induced aneurysm;Rupture;Stereotactic radiosurgery

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Adipocytes properties and crosstalk with immune system in obesity-related inflammation.

Obesity is a condition likely associated with several dysmetabolic conditions or worsening of cardiovascular and other chronic disturbances. A key role in this mechanism seem to be played by the onset of low-grade systemic inflammation, highlighting the importance of the interplay between adipocytes and immune system cells. Adipocytes express a complex and highly adaptive biological profile being capable to selectively activate different metabolic pathways in order to respond to environmental stimuli. It has been demonstrated how adipocytes, under appropriate stimulation, can easily differentiate and de-differentiate thereby converting themselves into different phenotypes according to metabolic necessities. Although underlying mechanisms are not fully understood, growing in adipocyte size and the inability of storing triglycerides under overfeeding conditions seem to be crucial for the switching to a dysfunctional metabolic profile, which is characterized by inflammatory and apoptotic pathways activation, and by the shifting to pro-inflammatory adipokines secretion. In obesity, changes in adipokines secretion along with adipocyte deregulation and fatty acids release into circulation contribute to maintain immune cells activation as well as their infiltration into regulatory organs. Over the well-established role of macrophages, recent findings suggest the involvement of new classes of immune cells such as T regulatory lymphocytes and neutrophils in the development inflammation and multi systemic worsening. Deeply understanding the pathways of adipocyte regulation and the de-differentiation process could be extremely useful for developing novel strategies aimed at curbing obesity-related inflammation and related metabolic disorders.

adipocytes;adipokines;inflammation;liposecretion;obesity

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Stem cell mobilization in patients with dialysis-dependent multiple myeloma: Report of the Polish Myeloma Study Group.

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Myeloma Study Group. Twenty-eight dialysis-dependent MM-patients were enrolled into this retrospective analysis. The study population comprised patients diagnosed between 2004 and 2015 in whom an attempt to collect auto-HSC was made (68%: women, median age: 56). Patients received granulocyte-colony stimulating factor (G-CSF) alone or in combination with chemotherapy and autologous peripheral blood stem cells (auto-PBSCs) were collected by leukapheresis. The success rate in terms of obtaining sufficient number of CD34(+) cells/kg for an auto-HSCT (≥2 × 10⁶ cells/kg body weight) during the first mobilization attempt was 92% (26/28 patients), and for 2 auto-HSCTs (≥4 × 10⁶ cells/kg) - was 75% (21/28 patients). After the second mobilization attempt (undertaken in 8 patients), a sufficient number of CD34(+)/kg cells for an auto-HSCT was obtained for all patients and the number of CD34(+)/kg collected cells was sufficient for 2 auto-HSCT in 6 additional patients. Hematologic toxicity and infections were the most frequent complications. Higher doses of cytarabine (>1.6 g/m² ) and cyclophosphamide (> 2 g/m² ) should be avoided in MMDD patients due to toxicity. Further studies are needed to establish mobilization regimens, confirm their safety, and dosing in MMDD patients.

autologous peripheral stem cell mobilization;dialysis dependence;multiple myeloma

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Administration of cloprostenol and oxytocin before electroejaculation in goat bucks reduces the needed amount of electrical stimulation without affecting seminal quality.

Electroejaculation (EE) is a widely used semen collection technique; but, it is stressful and painful for the animals. Considering these concerns, it may be important to develop practices to decrease the negative implications of EE on animals. Oxytocin and prostaglandin-F2alpha (PGF2α) stimulate the contractions of the muscles of the male genital tract. Therefore, the aim of this study was to analyze the effectiveness of the administration of oxytocin and/or a PGF2α analogue (cloprostenol) to bucks in relation to their stress response and sperm parameters before semen collection by EE was performed. Semen was collected with EE from 12 Gabon bucks in a 2 × 2 factorial arrangement (factors: with or without oxytocin, with or without cloprostenol). Each treatment was applied to different animals every 3 to 6 days, allowing all the animals to receive all the four treatments. The treatments applied to bucks before EE were as follows: 1) control (ConT), bucks received no hormonal treatment; 2) oxytocin (OxyT), bucks received 10 IU of oxytocin intramuscularly (IM) 30 s before beginning the EE; 3) PGF2α (PgT), bucks received 250 μg of cloprostenol IM 5 min before beginning the EE; and 4) oxytocin plus PGF2α (OxPgT), animals received treatment with both OxT and PgT. The number of electrical pulses, time length needed to achieve ejaculation, number of vocalizations, creatine kinase (CK) concentration and sperm parameters in goat bucks were recorded. The administration of cloprostenol and oxytocin before EE shortened the procedure and decreased the number of pulses and the pulse/voltage applied (P = 0.02 for all). This treatment also tended to decrease the number of vocalizations (P = 0.067). There were no treatment effects in the initial values; neither were there increases in heart rate and rectal temperature, or CK concentration. Seminal variables were not affected by the treatments. In conclusion, it would be important to consider the combined application of cloprostenol and oxytocin before EE, as it can shorten the process, reducing the electrical stimulus with positive effects on animal welfare and without affecting seminal quality in goat bucks.

Pain;Semen;Sperm;Stress;Welfare

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Disparities in access to anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration.

Late neovascular age-related macular degeneration (nvAMD) is very common and causes irreversible severe visual loss unless treated swiftly with vascular endothelial growth factor (VEGF) inhibitors. Although publicly subsidized access to treatment may be inequitable, which is why we assessed treatment provision across Australia. Secondary analysis of Australian data. All Pharmaceutical Benefits Scheme (including Repatriation PBS) beneficiaries. Treatment and incidence data were obtained from Medicare Australia, the Royal Australian and New Zealand College of Ophthalmologists, Optometry Australia, the Blue Mountains Eye Study and the Australian Bureau of Statistics. Data were mapped using geographical information software, and factors associated with treatment provision were assessed using multiple linear regression models. Unmet need (%) for anti-VEGF treatment for nvAMD. On average, we estimated 7316 incident cases of nvAMD not to be treated per year from 2010 to 2014 (50.1% of total). Number of ophthalmologists and optometrists (per 1000, β = -0.024; 95% confidence interval [CI] -0.041, -0.007) and being located in remote regions (β = 0.186; 95% CI 0.110, 0.262) were associated with percentage of untreated cases. A higher proportion of the population speaking a language other than English at home was associated in univariate analyses only (β = 0.0015; 95% CI -0.0004, 0.0027; P = 0.007). A large proportion of incident nvAMD is not treated with anti-VEGF. Not receiving treatment is more likely in regional or remote areas and areas with fewer service providers. Not speaking English at home may further limit access. Service delivery models for more equitable service provision are needed.

Australia;access;anti-VEGF;neovascular age-related macular degeneration

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Acute heart failure presentations and outcomes during the fasting month of Ramadan: an observational report from seven Middle Eastern countries.

Fasting during the month of Ramadan is practiced by over 1.5 billion Muslims worldwide. It remains unclear, however, how this change in lifestyle affects heart failure, a condition that has reached epidemic dimensions. This study examined the effects of fasting in patients with acute heart failure (AHF) using data from a large multi-center heart failure registry. Data were derived from Gulf CARE (Gulf aCute heArt failuRe rEgistry), a prospective multi-center study of consecutive patients hospitalized with AHF during February-November 2012. The study included 4,157 patients, of which 306 (7.4%) were hospitalized with AHF in the fasting month of Ramadan, while 3,851 patients (92.6%) were hospitalized in other days. Clinical characteristics, precipitating factors, management, and outcome were compared among the two groups. Patients admitted during Ramadan had significantly lower prevalence of symptoms and signs of volume overload compared to patients hospitalized in other months. Atrial arrhythmias were significantly less frequent and cholesterol levels were significantly lower in Ramadan. Hospitalization in Ramadan was not independently associated with increased immediate or 1-year mortality. The current study represents the largest evaluation of the effects of fasting on AHF. It reports an improved volume status in fasting patients. There were also favorable effects on atrial arrhythmia and total cholesterol and no effects on immediate or long-term outcomes.

Heart failure;fasting;middle east;morbidity;mortality

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"What I Did for My Loved One Is More Important than Whether We Talked About Death": A Nationwide Survey of Bereaved Family Members.

Actions in preparation for death and talks about death between advanced cancer patients and their families are considered essential to achieve a good death. However, little is known about the prevalence of such actions compared with talks and their association with bereaved families' psychological morbidity. To clarify the prevalence of bereaved families having acted in preparation for death and talked about death with their loved one, and to explore their associations with bereaved families' depression and complicated grief (CG). A nationwide survey. Setting/Subject: A total of 999 bereaved families of cancer patients admitted to 133 inpatient hospices in Japan. The prevalence of families' actions in preparation for and talks about death, Patient Health Questionnaire (PHQ)-9, and Brief Grief Questionnaire (BGQ). Among 678 bereaved families (response rate = 68%), 513 (76%) acted in preparation for death, and 315 (46%) talked about death with their loved one. Those who acted and talked were significantly less likely to suffer depression (PHQ-9 ≥ 10) than those who neither acted nor talked (odds ratio [OR], 0.405; 95% confidence interval [CI], 0.195-0.845; adjusted p = 0.016). Families who acted were significantly less likely to suffer complicated grief (CG; BGQ ≥8), whether they talked (OR, 0.394; 95% CI, 0.185-0.84; adjusted p = 0.016) or not (OR, 0.421; 95% CI, 0.191-0.925; adjusted p = 0.031). Most families acted in preparation for death, and those who acted were less likely to suffer depression and CG. Clinicians may minimize families' later psychological morbidity by helping patients and families act in preparation for death.

actions in preparation for death;cancer;depression;end-of-life discussions;family;grief

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Improvement of start-up and nitrogen removal of the anammox process in reactors inoculated with conventional activated sludge using biofilm carrier materials.

The start-up of the anaerobic ammonium oxidation (anammox) process in three up-flow column reactors seeded with common mixed activated sludge and added with three materials, sponge (R1), sponge + volcanic rock (R2) and sponge + charcoal (R3), as carriers for biofilm formation were comparatively investigated in this study. The supplement of volcanic rock and charcoal could significantly shorten the start-up time of the anammox process, which primarily occurred in the activity-enhanced phase, with ammonium and nitrite removal efficiencies stabilized above 92.5% and 93.4% after an operation period of 145, 105 and 121 d for R1, R2 and R3, respectively. After the successful anammox start-up, R2 performed significantly better in TN removal (p < .05), achieving an average rate of 91.0% and 191.5 g N m^-3 d^-1 compared to R1 of 88.4% and 172.1 g N m^-3 d^-1, and R3 of 89.9% and 180.1 g N m^-3 d^-1 in the steady running phase. The ratios of consumed [Formula: see text] and generated [Formula: see text]/consumed [Formula: see text] after anammox start-up were lower than the theoretical values, probably suggesting the simultaneous existences of anammox, denitrification as well as nitrification processes in the reactors. A reddish brown biofilm was wrapped on the carriers and morphological detection of biofilm displayed the presentations of thick and compact floc aggregates and some filamentous bacteria on the sponge, and spherical-, ovoid- and shortrod-shaped microorganisms on the volcanic rock and charcoal. Using porous material as carrier for biofilm development is an effective strategy for practical application of the anammox reactor.

Anammox;biofilm carrier;biofilm morphology;charcoal;nitrogen removal;sponge;start-up;volcanic rock

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2-Methoxylated FA Display Unusual Antibacterial Activity Towards Clinical Isolates of Methicillin-Resistant Staphylococcus aureus (CIMRSA) and Escherichia coli.

The naturally occurring (6Z)-(±)-2-methoxy-6-hexadecenoic acid (1) and (6Z)-(±)-2-methoxy-6-octadecenoic acid (2) were synthesized in 7-8 steps with 38 and 13% overall yields, respectively, by using an acetylide coupling approach, which made it possible to obtain a 100% cis-stereochemistry for the double bonds. In a similar fashion, the acetylenic analogs (±)-2-methoxy-6-hexadecynoic acid (3) and (±)-2-methoxy-6-octadecynoic acid (4) were also synthesized in 6-7 steps with 48 and 16% overall yields, respectively. The antibacterial activity of acids 1-4 was determined against clinical isolates of methicillin-resistant Staphylococcus aureus (ClMRSA) and Escherichia coli. Among the series of compounds, acid 4 was the most active bactericide towards CIMRSA displaying IC_50s (half maximal inhibitory concentrations) between 17 and 37 μg/mL, in sharp contrast to the 6-octadecynoic acid, which was not bactericidal at all. On the other hand, acids 1 and 3 were the only acids that displayed antibacterial activity towards E. coli, but 1 stood out as the best candidate with an IC₅₀ of 21 μg/mL. The critical micelle concentrations (CMCs) of acids 1-4 were also determined. The C18 acids 2 and 4 displayed a five-fold lower CMC (15-20 μg/mL) than the C16 analogs 1 and 3 (70-100 μg/mL), indicating that 4 exerts its antibacterial activity in a micellar state. None of the studied acids were inhibitory towards S. aureus DNA gyrase discounting this type of enzyme inhibition as a possible antibacterial mechanism. It was concluded that the combination of α-methoxylation and C-6 unsaturation increases the bactericidal activity of the C16 and C18 FA towards the studied bacterial strains. Acids 1 and 4 stand out as viable candidates to be used against E. coli and CIMRSA, respectively.

Antibacterial;Escherichia coli;Methicillin-resistant;Methoxylated fatty acids;Staphylococcus aureus;Synthesis

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Cardiac Tamponade Provoked by a Subphrenic Abscess.

pericardial effusion;subphrenic abscess

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The influence of closure technique in total laryngectomy on the development of a pseudo-diverticulum and dysphagia.

In total laryngectomy, the neopharynx can be closed in several ways. It is suggested that a pseudo-diverticulum is seen more frequently in patients closed with vertical closure than with "T"-shaped closure, causing postoperative dysphagia. We report the results of patients treated with vertical closure and "T"-shaped closure with regard to the formation of a pseudo-diverticulum and postoperative dysphagia. In our retrospective cohort study, we identified 117 consecutive laryngectomized patients treated in the VU University Medical Center of Amsterdam between March 2009 and December 2013. Evaluations with statistical analysis of postoperative outcome measures (the formation of a pseudo-diverticulum and dysphagia), qualitative and quantitative variables were conducted. Patient demographics were similar between the vertical-shaped closure and the "T"-shaped closure groups. In 84.6% of patients with vertical closure, a pseudo-diverticulum was seen compared to 18.5% with "T"-shaped closure (p < 0.001). Dysphagia was increasingly seen in patients with a pseudo-diverticulum (60.5%) compared to patients without a pseudo-diverticulum (39.5%) (p = 0.090). Formation of a pseudo-diverticulum is more frequently seen in laryngectomy patients closed with vertical closure than in patients closed with "T"-shaped closure of the neopharynx. It is favorable to implement "T"-shaped closure in laryngectomy.

Dysphagia;Head and neck surgery;Laryngectomy;Oncology;Pseudo-diverticulum;Suture methods

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The complete mitochondrial genome of <i>Euplatypus parallelus</i> (Coleoptera: Curculionidae).

Beetles in the weevil subfamily Platypodinae are among the dominant groups of insects in wet tropical forests, which together with bark and ambrosia beetles in the subfamily Scolytinae. Easily recognised by the circle-shaped entrance holes in fallen logs and a very elongated body shape, they have earned the common name, "pinhole borers". All except two Platypodinae species are ambrosia beetles that cultivate fungi in wood tunnels as the sole food for their larvae. Platypodinae is a peculiar weevil subfamily of species that cultivate fungi in tunnels excavated in dead wood. The Platypodinae is likely the oldest known lineage of fungus-cultivating insects, with an origin of the ambrosial habit more than 80 Ma. Here, we sequenced and characterized the complete mitochondrial genome of E. parallelus, which was collected from logs imported from SierraLeone. The complete circular mitochondrial genome (mitogenome) of <i>Euplatypus parallelus</i> is 16,095 bp in size, containing 37 typical genes and one non-coding AT-rich region. The AT content of the AT-rich region is 87.5%. All protein-coding genes (PCGs) start with standard ATN initiation codons except for <i>nad1</i>and end with complete termination codons TAA except for <i>cox1</i>genes using an incomplete stop codon T. <i>tRNA</i> genes are predicted with a characteristic cloverleaf secondary structure except for <i>trnS1^(AGN)</i> , whose dihydrouridine (DHU) arm is replaced by a simple loop. The size of the large and small ribosomal RNA genes are 1386 and 741 bp, respectively.

Coleoptera;Euplatypus parallelus;mitochondrial genome

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High-sensitive CRP as a predictive marker of long-term outcome in juvenile idiopathic arthritis.

To evaluate whether C-reactive protein (CRP), including variation within the normal range, is predictive of long-term disease outcome in Juvenile Idiopathic Arthritis (JIA). Consecutive patients with newly diagnosed JIA were included prospectively from defined geographic areas of the Nordic countries from 1997 to 2000. Inclusion criteria were availability of a baseline serum sample within 12 months after disease onset and 8-year clinical assessment data. Systemic onset JIA was not included. CRP was measured by high-sensitive ELISA (detection limit of 0.2 mg/l). One hundred and thirty participants with a median follow-up time of 97 months (range 95-100) were included. At follow-up, 38% of the patients were in remission off medication. Absence of remission was associated with elevated level of CRP at baseline (odds ratio (OR) 1.33, confidence interval (CI) 1.08-1.63, p = 0.007). By applying a cutoff at the normal upper limit (>10 mg/l), the risk of not achieving remission was increased to an OR of 8.60 (CI 2.98-24.81, p < 0.001). Variations of CRP within the normal range had no predictive impact on disease activity at follow-up. Baseline levels of ESR were available in 80 patients (61%) and elevated ESR was associated with absence of remission in a multivariable logistic regression analysis (OR 2.32, CI 1.35-4.00, p = 0.002). This results of this study indicate that baseline CRP concentrations above 10 mg/l are predictive of a poor outcome at 8-year follow-up. We could not demonstrate any predictive value of CRP variations within the normal range.

Arthritis;Erythrocyte sedimentation rate;Follow-up;High-sensitive CRP;Juvenile idiopathic

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