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Cognitive impairment is present in approximately 30% of patients with amyotrophic lateral sclerosis (ALS) and, especially when severe, has a negative impact on survival and caregiver burden. Our 2010 meta-analysis of the cognitive profile of ALS showed impairment of fluency, executive function, language and memory. However, the limited number of studies resulted in large confidence intervals. To obtain a more valid assessment, we updated the meta-analysis and included methodological improvements (controlled data extraction, risk of bias analysis and effect size calculation of individual neuropsychological tests). Embase, Medline and PsycInfo were searched for neuropsychological studies of non-demented patients with ALS and age-matched and education-matched healthy controls. Neuropsychological tests were categorised in 13 cognitive domains and effect sizes (Hedges' g) were calculated for each domain and for individual tests administered in >/=5 studies. Subgroup analyses were performed to assess the influence of clinical and demographic variables. Forty-four studies were included comprising 1287 patients and 1130 healthy controls. All cognitive domains, except visuoperceptive functions, showed significant effect sizes compared to controls. Cognitive domains without bias due to motor impairment showed medium effect sizes (95% CI): fluency (0.56 (0.43 to 0.70)), language (0.56 (0.40 to 0.72)), social cognition (0.55 (0.34 to 0.76)), or small effect sizes: delayed verbal memory 0.47 (0.27 to 0.68)) and executive functions (0.41 (0.27 to 0.55)). Individual neuropsychological tests showed diverging effect sizes, which could be explained by bias due to motor impairment. Subgroup analyses showed no influence of bulbar disease onset and depression and anxiety on the cognitive outcomes. The cognitive profile of ALS consists of deficits in fluency, language, social cognition, executive functions and verbal memory. Social cognition is a new cognitive domain with a relatively large effect size, highlighting the overlap between ALS and frontotemporal dementia. The diverging effect sizes for individual neuropsychological tests show the importance of correction for motor impairment in patients with ALS. These findings have implications for bedside testing, the design of cognitive screening measures and full neuropsychological examinations. | Mental Status Schedule |
Regular national surveys of all public and private radiation oncology facilities in Australia have been carried out between 1986 and 1999. Workforce data recorded were numbers of radiation oncologists and trainees, radiation therapists, medical physicists and physics technicians, nursing staff, data managers, social workers and clerical staff. Workloads included treatments with megavoltage beams (linear accelerators, cobalt-60), orthovoltage/superficial X-rays, brachytherapy, total body irradiation and stereotactic radiosurgery. Major equipment recorded included numbers of megavoltage and orthovoltage/superficial X-ray machines, planning simulators, computerized dosimetry systems and brachytherapy equipment. The use of radiotherapy beds and the public-private mix of treatments were also documented. Data were assembled for Australia based on each individual state. Within Australia the number of public and private treatment facilities has increased by 44% from 18 in 1986 to 26 in 1999. The population has increased by 16.4%, cancer incidence by 51.8% and megavoltage workloads (fields) by 102%. The number of radiation therapists and physicists and the number of linear accelerators have, in general, increased with the growth in workloads. The number of radiation oncologists has increased by 60% from 4.5 full-time equivalent (FTE) radiation oncologists per million population in 1986 to 7.2 per million in 1999. There is currently a deficit of at least 40 radiation oncologists to be able to treat the 50% of newly diagnosed cancer patients requiring radiotherapy. In addition, a significant deficiency exists in numbers of radiation therapists, nursing staff, data managers, social workers and clerical staff. Clearly the demands for medical physicists has increased but the data are insufficient to comment on deficiencies. Despite the increases in workloads the proportion of patients with cancer receiving radiotherapy remains below 40%. A positive correlation has been shown between the proportion of newly diagnosed cancer patients treated and the number of FTE radiation oncologists, the number of megavoltage machines and number of radiation therapists. This was shown for Australia as a whole, for each state and for the years 1986 to 1999. This was also the case when total megavoltage fields was used as the dependent variable. Multiple regression analysis using the same independent variables confirmed these positive correlations. It is concluded that the low treatment rate with radiation oncology for cancer patients in Australia is due mainly to the lack of resource allocation. The stated commitment of governments and health departments to a 50% treatment rate can only become a reality if there is a concerted effort to increase the numbers of radiation oncologists, radiation therapists, megavoltage machines and support staff. Otherwise at least one in every 10 newly diagnosed cancer patients will continue to be denied adequate and equitable access to radiotherapy - in 1999 that total figure was 9400 persons. | Radiation Oncology |
PURPOSE: Dynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma. METHODS: In total, 21 patients with liver metastases were recruited within a prospective trial and underwent daily sorafenib therapy. DCE-US of a target lesion was performed before initiation of treatment, on day 15 and 56. Two independent blinded investigators performed software analysis for DCE-US parameters and inter-observer-correlation was calculated. Response to treatment was evaluated on day 56. DCE-US parameters were correlated with clinical response and RECIST1.1 criteria. RESULTS: Inter-observer-correlation (r) of DCE-US parameters [time-to-peak (TTP), mean-transit-time (MTT), peak intensity (PI), regional blood volume (RBV), regional blood flow (RBF)] at baseline, day 15, and day 56 was highly significant (r-range 0.73-0.97, all p < 0.001). Out of 17 evaluable patients, 12 patients survived day 56 (clinical responders, cRE), whereas, five patients died before day 56 and were classified as non-responders (cNR). TTP values significantly increased in the cRE group 15 days after initiation of treatment for investigator 1 (p = 0.034) and at day 56 for both investigators (p = 0.028/0.028). MTT had increased significantly in the cRE group on day 56 (p = 0.037/0.022). In the cNR group changes for TTP and MTT remained insignificant. Thus, increase of the DCE-US parameters TTP and MTT are associated with response to treatment and prognosis. CONCLUSION: An increase of TTP and MTT at frequent intervals could serve as a surrogate marker for early response evaluation to anti-angiogenic treatment of metastatic uveal melanoma. | Uveal Neoplasms |
Effective phytoremediation of Mn contaminated soil requires the selection of a species with good manganese tolerance. Broussonetia papyrifera is an important economic plant and pioneer species, it could be well adapted to drought and saline-alkali environment. In order to understand the effect of Mn stress on B. papyrifera, the effects of different concentrations of Mn (0-50â¯mmol/L) stress on the growth, morphology, Mn tolerance and physiological indexes of the plant were explored. The results showed that the biomass, surface area, length, root volume, tips, forks, and crossings of B. papyrifera reached the maximum at the Mn concentration of 1â¯mmol/L. Mn content in the tissue and TF in plants increased with the increase of concentration, while the BCF increased first and then decreased, and the maximum BCF was 0.154â¯at 10â¯mmol/L. The accumulation of Mn lead to cell membrane lipid peroxidation, which increased toxic substances in plants, resulting in the increase of MDA and PRO, and affected the synthesis of chlorophyll. However, B. papyrifera could effectively alleviate oxidative stress by increasing the activities of antioxidant enzymes (SOD, POD, CAT), protein and soluble sugar. The results suggested that B. papyrifera had a good oxidative stress mechanism to Mn stress and could be used as candidates for remediation of pollution in mining areas. | Broussonetia |
We describe new myxosporean species from Malaysian fishes cultured in pond farms and net-cages. Myxobolus omari sp. nov. and M. leptobarbi sp. nov. were found in the muscles of Pangasianodon hypophthalmus and Leptobarbus hoevenii, respectively, while plasmodia and spores of Thelohanellus zahrahae sp. nov. and Henneguya daoudi sp. nov. were detected in the gills of Barbonymus gonionotus and Trichogaster trichopterus, respectively. Plasmodia and spores found in these fishes differed from the known myxosporean species in respect of their morphology, tissue tropism and 18S rDNA structure. No major pathological changes were found, but in the future these species might pose a potential threat to more intensified fish culture. | Myxozoa |
Traumatic brain injury (TBI) has both high morbidity and mortality rates and can negatively influence physical and mental health, while also causing extreme burden to both individual and society. Hitherto, there is no effective treatment for TBI because of the complexity of the brain anatomy and physiology. Currently, management strategies mainly focus on controlling inflammation after TBI. Tumor necrotizing factor alpha (TNF-alpha) plays a crucial role in neuroinflammation post-TBI. TNF-alpha acts as the initiator of downstream inflammatory signaling pathways, and its activation can trigger a series of inflammatory reactions. Infliximab is a monoclonal anti-TNF-alpha antibody that reduces inflammation. Herein, we review the latest findings pertaining to the role of TNF-alpha and infliximab in TBI. We seek to present a comprehensive clinical application prospect of infliximab in TBI and, thus, discuss potential strategies of infliximab in treating TBI. | Infliximab |
BACKGROUND: The term 'Responsibility Sharing', albeit poorly defined, has emerged from the diabetes literature, to describe a distinct mechanism for comprehensively managing the characteristic shift in responsibility that underpins the transition to self-management for adolescents. METHODS: A scoping review, following the PRISMA-ScR guidelines, distilled the literature from seven databases to answer the questions: What is responsibility sharing? Who are the key stakeholders? What factors affect responsibility transaction? What are its recognized outcomes? How is responsibility shared? RESULTS: Responsibility sharing is a transactional arrangement between youth and their caregiver/s that functions to repeatedly and flexibly apply ownership to the management of diabetes care tasks, across the course of adolescence. In the main, responsibility sharing was associated with better metabolic and/or psychosocial outcomes. Effective responsibility sharing was seen as being responsive to adolescent capacity and driven by autonomy supportive, sustained communication patterns that enable mutually agreeable responsibility assumption by all stakeholders. CONCLUSION: Different perspectives on responsibility sharing for adolescents with Type 1 diabetes, and the lack of a universal definition, have led to discordance within the literature about its operationalization and measurement. This paper proposes a definition of responsibility sharing for future researchers to apply. | Diabetes Mellitus, Type 1 |
Yak (Bos grunniens) inhabit an oxygen-deficient environment at the altitude of 3000 m on the Tibetan Plateau, with a distinctive gut micro-ecosystem. This study evaluated the probiotic potential and physiological property of Bacillus licheniformis and Bacillus pumilus isolated from the gut of yaks. Four strains, two Bacillus licheniformis (named D1 and D2) and two Bacillus pumilus (named X1 and X2), were isolated and identified by 16S rRNA sequencing. All strains had potential antibacterial ability against three indicator pathogens: Escherichia coli C83902, Staphylococcus aureus BNCC186335, and Salmonella enteritidis NTNC13349. The antioxidant activity test showed that D2 sample showed the highest antioxidant activity. Furthermore, all four strains had a higher hydrophobicity, auto-aggregation, acid tolerance, bile tolerance, and antibiotic sensitivity, which all contribute to their survival in the gastrointestinal tract and clinical utility. The animal experimentation (40 KM mice, equally divided into five groups of eight mice each) showed that the strain supplementation not only increased daily weight gain and reduced feed conversion ratio, but also increased the length of the jejunum villi and the value of the V/C (Villi/Crypt). In conclusion, this is the first study demonstrated the probiotic potential of Bacillus licheniformis and Bacillus pumilus isolated from yaks, providing a theoretical basis for the clinical application and development of new feed additives. | Bacillus pumilus |
The CD45 glycoprotein isoforms exhibit a receptor-like composition and display intracellular protein tyrosine phosphatase (PTPase) activity. The present study links CD45 to the regulation of L-selectin (CD62L), a leucocyte glycoprotein important for extravasation and homotypic aggregation. Monoclonal antibodies (MoAbs) IOL1b and AICD45.2, but not GAP8.3, all of which are directed against common CD45 epitopes, were found to elicit lymphocyte L-selectin down-regulation. Lymphocyte L-selectin down-regulation in response to anti-CD45 MoAbs was enhanced by high cell density and partially antagonized by the protein tyrosine kinase (PTK) inhibitor, herbimycin A. The MoAbs IOL1b, AICD45.2 and GAP8.3 recognized granulocyte-expressed CD45 but did not induce loss of L-selectin expression of granulocytes. In contrast, the CD45 PTPase inhibitor, vanadate, induced L-selectin down-regulation both in lymphocytes and granulocytes. The PTPase activation by nitric oxide (NO) or the NO-generating compound, sodium nitroprusside, did not affect L-selectin surface expression. Increased concentrations of soluble L-selectin were detected after anti-CD45 or vanadate-induced down-regulation of L-selectin surface expression. While activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) induces rapid L-selectin down-regulation of L-selectin surface expression in both lymphocytes and granulocytes, the PKC inhibitor, H 7, was also found to down-regulate lymphocyte and granulocyte L-selectin surface expression. The inhibitor H 7 synergized with vanadate in down-regulating lymphocyte L-selectin surface expression, but partially inhibited vanadate-induced granulocyte L-selectin down-regulation. The results suggest that in a cell type-specific fashion the PKC system and tyrosine phosphorylation and dephosphorylation cascades are involved in the regulation of L-selectin surface expression. | Leukocyte Common Antigens |
The hypothesis that cross-reactivity between microbial and self determinants recognized by the adaptive immune system could induce autoimmune diseases is very intriguing. However, definite proof in humans is very difficult to achieve and evidence is frequently circumstantial. Therefore, animal models are instrumental for understanding, how and when mimicry could be involved in the pathogenesis of autoimmunity. In this article, we will discuss experimental scenarios, where mimicry between foreign and self determinants does not cause disease per se, but rather aggravates a pre-existing yet sub-clinical autoimmune condition. We would like to propose that molecular mimicry is more likely to impact on an already existing autoimmune process rather than precipitate novel disease by breaking of tolerance from the beginning. Already activated autoreactive cells might be easier re-activated and primed for effector functions by cross-reactive ligands than naive lymphocytes. | Molecular Mimicry |
Public-private partnerships (PPPs) can be an effective and advantageous way to accomplish extension and outreach objectives in plant pathology. The greatest opportunities for extension-focused PPPs may be in response to large-scale or emerging disease management concerns or in addressing complex issues that impact agriculture, such as climate change, digital technology, and public perception of science. The most fertile ground for forming PPPs is where the needs and strengths of the public and private sectors are complementary. Developing PPPs depends as much on professional relationships as on technical skills or contracts. Defining and making room for the success of all partners, identifying and addressing barriers to success, and earning and maintaining trust are components that contribute to the effectiveness of PPPs. Case studies in plant pathology demonstrate the positive impact PPPs can have on partners and stakeholders and provide guidance on the formation of PPPs in the future. | Plant Pathology |
Neisseria meningitidis is the causative microorganism of many human diseases, including bacterial meningitis; together with Streptococcus pneumoniae, it accounts for approximately 80% of bacterial meningitis infections. The emergence of antibiotic-resistant strains of N. meningitidis has created a strong urgency for the development of new therapeutics, and the high-resolution structural elucidation of enzymes involved in cell metabolism represents a platform for drug development. Acetyl-CoA hydrolase is involved in multiple functions in the bacterial cell, including membrane synthesis, fatty-acid and lipid metabolism, gene regulation and signal transduction. Here, the first recombinant protein expression, purification and crystallization of a hexameric acetyl-CoA hydrolase from N. meningitidis are reported. This protein was crystallized using the hanging-drop vapour-diffusion technique at pH 8.5 and 290 K using ammonium phosphate as a precipitant. Optimized crystals diffracted to 2.0 A resolution at the Australian Synchrotron and belonged to space group P2(1)3 (unit-cell parameters a = b = c = 152.2 A), with four molecules in the asymmetric unit. | Acetyl-CoA Hydrolase |
The PSD-95 family of PSD-95/Discs large/ZO-1 (PDZ) domain-containing proteins plays a role in the clustering and localization of specific ion channels and receptors at synapses. Previous studies have shown that PSD-95 forms multimers through an N-terminal region (termed the N-segment) and that the multimerization of PSD-95 is critical for its ability to cluster Shaker-type potassium channel Kv1.4 in heterologous cells. We show here that the PSD-95 N-segment functions as a multimerization domain only when located at the N-terminal end of a heterologous protein. A pair of N-terminal cysteines, Cys3 and Cys5, is essential for the ability of PSD-95 to self-associate and to form cell surface clusters with Kv1.4. However, PSD-95 mutants lacking these cysteine residues retain their ability to associate with membranes and to bind to Kv1.4. Unlike wild type PSD-95, the cysteine mutant of PSD-95 cannot form a ternary complex with Kv1.4 and the cell adhesion molecule Fasciclin II. These results suggest that the N-terminal cysteines are essential for PSD-95 multimerization and that multimerization is required for simultaneous binding of multiple membrane protein ligands by PSD-95. | Kv1.4 Potassium Channel |
Adolescence is an important period of nutritional vulnerability due to increased dietary requirements for growth and development and special dietary habits. Calcium needs are elevated as a result of the intensive bone and muscular development and thus adequate calcium intake during growth is extremely important to reach the optimum peak bone mass and to protect against osteoporosis in the adult age, a major public health threat whose incidence is increasing in Western countries. However, most children and adolescents worldwide fail to achieve the recommended calcium intake. The hormonal changes associated with the pubertal period promote greater mineral utilization, which needs to be satisfied with suitable calcium consumption. Diet, therefore, must contribute nutrients in sufficient quality and quantity to allow maximum bone mass development. Consequently, adolescents should be educated and encouraged to consume adjusted and balanced diets that, together with healthy lifestyles, enable optimal calcium utilization." | Adolescent Nutritional Physiological Phenomena |
OBJECTIVE: Frontotemporal lobar degeneration (FTLD) is the most common cause of early-onset dementia. Pathological ubiquitinated inclusion bodies observed in FTLD and motor neuron disease (MND) comprise trans-activating response element (TAR) DNA binding protein (TDP-43) and/or fused in sarcoma (FUS) protein. Our objective was to identify the causative gene in an FTLD-MND pedigree with no mutations in known dementia genes. METHODS: A mutation screen of candidate genes, luciferase assays, and quantitative polymerase chain reaction (PCR) was performed to identify the biological role of the putative mutation. Neuropathological characterization of affected individuals and western blot studies of cell lines were performed to identify the pathological mechanism of the mutation. RESULTS: We identified a nonpolymorphic mutation (c.672*51G>T) in the 3'-untranslated region (UTR) of the Sigma nonopioid intracellular receptor 1 (SIGMAR1) gene in affected individuals from the FTLD-MND pedigree. The c.672*51G>T mutation increased gene expression by 1.4-fold, corresponding with a significant 1.5-fold to 2-fold change in the SIGMAR1 transcript or Sigma-1 protein in lymphocyte or brain tissue. Brains of SIGMAR1 mutation carriers displayed a unique pathology with cytoplasmic inclusions immunopositive for either TDP-43 or FUS but not Sigma-1. Overexpression of SIGMAR1 shunted TDP-43 and FUS from the nucleus to the cytoplasm by 2.3-fold and 5.2-fold, respectively. Treatment of cells with Sigma-1 ligands significantly altered translocation of TDP-43 by up to 2-fold. INTERPRETATION: SIGMAR1 is a causative gene for familial FTLD-MND with a unique neuropathology that differs from other FTLD and MND cases. Our findings also suggest Sigma-1 drugs as potential treatments for the TDP-43/FUS proteinopathies. | Opipramol |
This article reports on the journey of a child with an inoperable hypothalamic-origin pilocytic astrocytoma causing hydrocephalus, which was refractory to treatment with shunts, and required a new approach. With multidisciplinary support, excellent nursing care and parental education, the child's hydrocephalus was managed long term in the community with bilateral long-tunnelled external ventricular drains (LTEVDs). This article describes the patient's journey and highlights the treatment protocols that were created to achieve this feat. Despite the difficulties in initially setting up these protocols, they proved successful and thus the team managing the patient proposed that LTEVDs are a viable treatment option for children with hydrocephalus in the context of inoperable tumours to help maximise quality of life. | Drainage |
OBJECTIVE: To define molecular mechanisms underlying the clinical spectrum of epilepsy and movement disorder in individuals with de novo mutations in the GNAO1 gene. METHODS: We identified all GNAO1 mutations reported in individuals with epilepsy (early infantile epileptiform encephalopathy 17) or movement disorders through April 2016; 15 de novo mutant alleles from 25 individuals were introduced into the Galpha(o) subunit by site-directed mutagenesis in a mammalian expression plasmid. We assessed protein expression and function in vitro in HEK-293T cells by Western blot and determined functional Galpha(o)-dependent cyclic adenosine monophosphate (cAMP) inhibition with a coexpressed alpha(2A) adrenergic receptor. RESULTS: Of the 15 clinical GNAO1 mutations studied, 9 show reduced expression and loss of function (LOF; <90% maximal inhibition). Six other mutations show variable levels of expression but exhibit normal or even gain-of-function (GOF) behavior, as demonstrated by significantly lower EC(50) values for alpha(2A) adrenergic receptor-mediated inhibition of cAMP. The GNAO1 LOF mutations are associated with epileptic encephalopathy while GOF mutants (such as G42R, G203R, and E246K) or normally functioning mutants (R209) were found in patients with movement disorders with or without seizures. CONCLUSIONS: Both LOF and GOF mutations in Galpha(o) (encoded by GNAO1) are associated with neurologic pathophysiology. There appears to be a strong predictive correlation between the in vitro biochemical phenotype and the clinical pattern of epilepsy vs movement disorder. | Blotting, Far-Western |
BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes and obesity. They elicit robust improvements in glycemic control and weight loss, combined with cardioprotection in individuals at risk of or with pre-existing cardiovascular disease. These attributes make GLP-1 a preferred partner for next-generation therapies exhibiting improved efficacy yet retaining safety to treat diabetes, obesity, non-alcoholic steatohepatitis, and related cardiometabolic disorders. The available clinical data demonstrate that the best GLP-1R agonists are not yet competitive with bariatric surgery, emphasizing the need to further improve the efficacy of current medical therapy. SCOPE OF REVIEW: In this article, we discuss data highlighting the physiological and pharmacological attributes of potential peptide and non-peptide partners, exemplified by amylin, glucose-dependent insulinotropic polypeptide (GIP), and steroid hormones. We review the progress, limitations, and future considerations for translating findings from preclinical experiments to competitive efficacy and safety in humans with type 2 diabetes and obesity. MAJOR CONCLUSIONS: Multiple co-agonist combinations exhibit promising clinical efficacy, notably tirzepatide and investigational amylin combinations. Simultaneously, increasing doses of GLP-1R agonists such as semaglutide produces substantial weight loss, raising the bar for the development of new unimolecular co-agonists. Collectively, the available data suggest that new co-agonists with robust efficacy should prove superior to GLP-1R agonists alone to treat metabolic disorders." | Glucagon-Like Peptide-1 Receptor |
X-ray inactivation studies on the type strain of Torulaspora hansenii carried out to determine ploidy, provided proof that the species has a haplontic life cycle, a fact which hitherto has only been presumed. Observations on the genesis of the ascus by light microscopy and transmission electron microscopy provide no evidence for, what some earlier workers in this field have presumed to be, heterogamous conjugation between a mother cell and its bud. They do, however, show that asci, bearing obliquely-attached, vestigal, bud-like appendages, arise from some cells to form single, non-abstricting, and frequently, recurving protuberances which enlarge. These could, conceivably, be responsible for the impression that abstricted buds are connected to the mother-cells by bent copulatory tubes. The formation during sporulation of elongated protuberances and the presence of a medial, electron-dense line within the electron-translucent layer of the walls of ascospores fixed with OsO4 preclude the possibility of using these features to differentiate between the genera Torulaspora and Debaryomyces. Furthermore, recombinant studies, which involved the use of auxotrophic mutants, indicated that during sporulation the fusion of independent cells accounted for only 0.03-0.6% of the asci formed. The conclusion was reached that somatogamous autogamy must be the main agency of diploidization and that the species is largely inbreeding. | Yeasts |
Although painless transient obscurations of vision are usually attributed to conditions affecting the posterior segment, careful slit-lamp, gonioscopic, and angiographic evaluations may establish an anterior segment origin for these symptoms. Recurrent hyphema, an uncommon late complication following routine cataract extraction, can be caused by spontaneous rupture of incisional vessels. In pseudophakic eyes, the uveitis-glaucoma-hyphema (UGH) syndrome and intermittent visual white out" are late complications that may necessitate removal of the implant. The authors report five patients with uncomplicated extracapsular cataract extraction and implantation of a Binkhorst biplane, two-loop, capsule-fixated lens who presented with episodes of visual white out on the basis of iris bleeding. Argon laser photocoagulation to sites of iris leakage, at points of lens iris contact, resulted in prompt cessation of bleeding. Laser treatment appears to be a safe and effective alternative to removal of an otherwise satisfactory intraocular lens." | Iris |
At its very early phase, septic shock is characterized by severe hypovolemia related to abundant fluid losses, increased venous compliance and maldistribution of extracellular fluid (interstitial edema, splanchnic pooling). It results in a drop in venous return and cardiac output. Volume expansion, with crystalloids or colloids produces a hyperdynamic state with high cardiac output and low peripheral resistances. The quantity of liquid administered rather than its composition is the main determinant. Clinical examination and hemodynamic monitoring (Swan-Ganz catheter) appear to provide the most useful criteria to assess the limits of liquid administration. Better understanding in the mechanisms of circulatory dysfunction due to the inflammation cascades might soon lead to a new approach in fluid therapy. | Hypovolemia |
Never go to sleep on an argument: an old wives' tale or a scientifically proven technique for controlling the memories you store? Recent findings show that sleep selectively enhances emotional memories, creating a long-lasting and potentially traumatic representation of distressing experiences. | Retention, Psychology |
PURPOSE: To compare the effectiveness of the Foley balloon with vaginal misoprostol for cervical ripening and labor induction. METHODS: Randomized clinical trial, not blind, conducted from January 2006 to January 2008. A total of 160 pregnant women with indication for induction of labor were included and divided into two groups, 80 for Foley and 80 for vaginal misoprostol. Inclusion criteria were: gestational age of 37 weeks or more, a live single fetus with cephalic presentation and a Bishop score of four or less. We excluded patients with a uterine scar, ruptured membranes, estimated fetal weight greater than 4000 g, placenta previa, chorioamnionitis and conditions that imposed the immediate termination of pregnancy. Statistical tests employed were Mann-Whitney, chi(2) test or Fisher's exact test, and p value was significant if less than 0.005. RESULTS: Misoprostol triggered more frequently spontaneous delivery (50.0 versus 15.0% for Foley, p<0.001) and required less use of oxytocin (41.2 versus 76.2%), and this group presented more tachysystole (21.2 versus 5.0%). The Foley catheter caused more discomfort to the patient (28.7 versus 1.2%). There were no differences in the time required for development of the Bishop score (20.69 versus 21.36 hours), for triggering delivery (36.42 versus 29.57 hours) or in rates of cesarean delivery (51.2 versus 42.5%). There were no significant differences in perinatal performance, with similar rates of abnormal cardiotocography (20.0 versus 21.2%), presence of meconium (13.7 versus 17.5%) and need for neonatal intensive care unit (3.7 versus 6.2%). CONCLUSIONS: The use of the Foley catheter was as effective as misoprostol for cervical ripening, but less effective in triggering spontaneous labor. Our results support the recommendation of its use for cervical ripening, especially in patients with cesarean scar. | Cervical Ripening |
BACKGROUND: The Kell blood group system consists of 25 antigens that result from single-nucleotide polymorphisms. Most polymorphic Kell antigens reside on the N-terminal domain of Kell before the zinc-binding catalytic motif, which is the major site for endothelin-3-converting enzyme activity. Kell antigens are important in transfusion medicine owing to their strong immunogenicity, and the corresponding antibodies are clinically significant. Two probands were studied whose serum samples contained antibodies to different high-prevalence Kell antigens. STUDY DESIGN AND METHODS: Standard hemagglutination methods were used for serologic testing of Proband 1 and Proband 2. DNA was prepared from both probands and family members. The 19 exons and the intron-exon regions of KEL from both probands were amplified by polymerase chain reaction, and the sequences were compared with that of common KEL. The identified substitutions were located on a three-dimensional model of Kell generated based on the crystal structure of neutral endopeptidase, a homolog of Kell. RESULTS: In Proband 1, a homozygous 1988G>A mutation (Arg623Lys) in Exon 17 was present. One sibling of Proband 1 was homozygous for 1988G>A. In Proband 2, a homozygous 1033G>A mutation (Asp305Asn) in Exon 8 was present. Three siblings of Proband 2 were heterozygous for 1033G>A. CONCLUSION: The identified KEL mutations of the two probands are novel and inherited. The antigen absent from the red blood cells (RBCs) of Probands 1 and 2 are named KALT and KTIM, respectively. KALT is unique in that it is the only Kell antigen sensitive to treatment of RBCs by trypsin. | Kell Blood-Group System |
Five cases of dentin dysplasia type I within one family are described. Clinically and radiologically, such patients are characterized by a delayed eruption pattern, opacity of the incisional margins, hypermobility of the teeth, short and defective roots, and obliterated pulp chambers. A conservative attitude toward the treatment of common conditions in dentin dysplasia type I favors the preservation of a vulnerable dentition. | Dentin Dysplasia |
With the increasing number of traumatic injuries being seen in emergency departments, physicians must be aware of the less common and less obvious types of serious injury. Portal vein injury is serious (death rate 50%) and may be diagnosed only at laparotomy. Fortunately this injury is rare. Its management can be difficult, but an awareness of the possible methods of treatment could be life-saving. The authors report their experience with this injury and survey the literature on the subject. | Portal Vein |
Caveolae are flask-like invaginations of the cell surface that have been identified as signaling epicenters. Within these microdomains, caveolins are structural proteins of caveolae, which are able to interact with numerous signaling molecules affecting temporal and spatial dimensions required in cardiac protection. This complex moiety is essential to the mechanisms involved in volatile anesthetics. In this review we will outline a general overview of caveolae and caveolins and their role in protective signaling with a focus on the effects of volatile anesthetics. These recent developments have allowed us to better understand the mechanistic effect of volatile anesthetics and their potential in cardiac protection. | Caveolae |
AIM: This study was to evaluate the association between peri-implant bleeding on probing in peri-implant diseases and its association with multilevel factors (site specific factors, implant factors, and patient level factors). METHODOLOGY: A cross-sectional study involved consented adult patients with >/= 1 dental implant. Two calibrated operators examined the patients. BoP was outcome variable and peri-implant gingival biotype was principal predictor variable. The effects of site, implant, and patient level factors on BoP were assessed using a multilevel logistic regression model. RESULTS: Eighty patients for a total of 119 implants and 714 sites were included in the study. Bleeding on probing was observed in 42 implants (35.29%) with a significant higher risk observed in presence of gingival recession, thin peri-implant gingival biotype, duration of implant placement, smokers, and male patients. CONCLUSION: Peri-implant bleeding on probing was associated with site specific, implant, and patient level factors. | Multilevel Analysis |
Concerns about body image may affect athletes, mainly because of specific sports models to achieve successful performance. This systematic review reports on body image dissatisfaction (BID) in athletes following the guidelines for systematic reviews and meta-analyses. From a total of 887 articles identified through a systematic search of electronic databases, 15 articles conducted on 2412 athletes were included in this review. To be eligible for inclusion, the studies must have been published in the last ten years up until September 2022 and analyze body image perception using body figure drawings and anthropometric profiles. The quality of the included studies was evaluated using the adapted Newcastle-Ottawa Scale for observational studies. These studies were compared through thematic analysis of BID to develop four general issues, including gender, sport type and level, and weight status. According to the meta-analyses, the significant medium and small effect sizes found for gender and weight status, respectively, indicated that male athletes had lower BID than females and that, among the latter, normal-weight athletes had a higher BID than underweight ones. The implications and limitations of the included studies are discussed extensively in this review, highlighting the need for further research on BID examined both in the social and the sports contexts. Sports activity should be carried out following healthy lifestyles, and promoting positive BI. | Body Image |
Major syndromes of psychoneurologic disorders in cardial achalasia are described. Their major pathogenic mechanisms were revealed in a combined clinico-electrophysiological study involving psychological testing. Differentiated methods treatment of psychoneurologic complications of cardial achalasia are described (sedative, neuroleptic drugs, general enforcing and supporting therapies) that proved effective in catamnestic observations. | Neurotic Disorders |
Night eating syndrome (NES) is characterized by excessive evening and/or nocturnal eating episodes. Studies indicate an attentional bias towards food in other eating disorders. For NES, however, evidence of attentional food processing is lacking. Attention towards food and non-food stimuli was compared using eye-tracking in 19 participants with NES and 19 matched controls without eating disorders during a free exploration paradigm and a visual search task. In the free exploration paradigm, groups did not differ in initial fixation position or gaze duration. However, a significant orienting bias to food compared to non-food was found within the NES group, but not in controls. A significant attentional maintenance bias to non-food compared to food was found in both groups. Detection times did not differ between groups in the search task. Only in NES, attention to and faster detection of non-food stimuli were related to higher BMI and more evening eating episodes. The results might indicate an attentional approach-avoidance pattern towards food in NES. However, further studies should clarify the implications of attentional mechanisms for the etiology and maintenance of NES. | Night Eating Syndrome |
PURPOSE: The current study attempts to clarify the mediating role of cognitive function on the relationship between environmental pressure (pressure caused by negative parenting styles and dysfunctional school environments) and Internet Use Disorder (IUD); this study explores the effects of sex and left-behind children (LBC). METHODS: A cross-sectional sample of adolescents aged 12-15â¯years was recruited in 2018. A total of 3048 junior high school adolescents in rural areas of the Sichuan province in western China completed a series of psychological inventories, including the Adolescent Pathological Internet Use Scale (APIUS), the Junior High School Students' Perceived School Climate Inventory (PSCI-M), the Egna Minnen av. Barndoms Uppfostran (EMBU), and the Mental Health Screening Inventory for Children and Adolescents (MHS-C), for an analysis of IUD, school climate, parenting styles and cognition, respectively. RESULTS: Among the participants, 18.5% (Nâ¯=â¯565) exhibited significant symptoms of IUD. The correlation analysis showed that IUD was positively correlated with parents' punishment, rejection and over-interference and academic pressure, whereas IUD was negatively associated with good teacher-student relationships, good schoolmate relationships and cognitive function scores. Structural equation modelling (SEM) showed that cognitive function partially contributed to the association between family and school pressures and IUD. DISCUSSION: Cognitive function is one of the mediating pathways through which environmental pressures may predict IUD among junior high school students. Interventions may target the mediating pathway of cognitive function to alleviate the negative impact of environmental pressure on IUD. | Family Separation |
Lymphatic metastasis (LM) is a significant mechanism for the spread of esophageal cancer (EC) and predicts the poor prognosis of EC patients. This research aimed to assess the survival of patients with LM from EC by developing a nomogram. In this retrospective study, EC patients with LM from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were divided by year of diagnosis into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were employed to determine the prognostic factors of LM, and a nomogram was constructed. The discrimination and calibration of the nomogram were compared by the C-index, area under the curve value, and calibration plots. The survival time difference was compared using Kaplan-Meier curves. A total of 11,695 patients with EC were included in this analysis. LM occurred in 56.5% (n = 6614) of EC patients. In the post-propensity score matching (PSM) cohort, patients with LM had significantly lower median overall survival (OS) than those without LM. Multivariate Cox regression was used to identify the eleven independent prognostic factors. The C-index was 0.709 in both the training and test sets, revealing the good predictive performance of the nomogram. Based on the results of calibration plots and the receiver operating characteristic (ROC) curve, we demonstrate the great performance of the prognostic model. The survival time of EC patients with LM was remarkably lower than that of EC patients without LM. The nomogram model established in this study can precisely predict the survival of EC patients with LM. | SEER Program |
In the framework of the European project aimed at the sequencing of the Bacillus subtilis genome, a DNA fragment of 12315 bp was cloned and sequenced. The DNA fragment is located between rrnB (275 degrees) and pai (284 degrees). Twelve ORFs were predicted to encode putative proteins. Two of these (ald and yukl) coincided with known B. subtilis genes. The products of two other genes (yukK and yukL) showed significant similarity to known proteins present in databases, e.g. pyoverdin synthase of Pseudomonas aeruginosa and pristinamycin synthase D of Streptomyces pristinaespiralis. | Alanine Dehydrogenase |
INTRODUCTION: Surgical intervention for duodenal atresia most commonly entails duodenoduodenostomy in the neonatal period. Occasionally, type I duodenal atresia with incomplete obstruction may go undiagnosed until later in life. Endoscopic approach to dividing intestinal webs has been reported as successful in patients as young as 7 days of age, and can be a useful modality particularly in patients with comorbidities who may not tolerate open or laparoscopic surgery. METHODS: A 2-year-old female with a history of trisomy 21 and tetralogy of Fallot underwent laparoscopic and endoscopic exploration of intestinal obstruction as seen on upper gastrointestinal series for symptoms of recurrent emesis and weight loss. After laparoscopy confirmed a duodenal web as the cause of intestinal obstruction, endoscopic division of the membrane was carried out with a triangle tip electrocautery knife and 15 mm radially dilating balloon. RESULTS: The patient tolerated the procedure well, and also tolerated full age-appropriate diet by time of discharge on postoperative day 2. She remains asymptomatic as of 6 months postoperatively. CONCLUSIONS: This report describes a successful endoscopic approach for definitive treatment of a duodenal web in a 2-year-old girl with trisomy 21, and laparoscopy confirmed no intraabdominal obstructive process or complication from endoscopy. Endoscopy enables minimal recovery time and suggests an improved method of duodenal web division over pure surgical intervention. | Duodenal Obstruction |
Epithelia can be defined morphologically as tissues that line surfaces, and ultrastructurally with reference to their cells' apico-basal polarity and possession of specific cell-cell junctions. Defining the epithelial phenotype at a molecular level is more problematic--while it is easy to name proteins (e.g. keratins) expressed by a 'typical' epithelium, no known molecules are expressed by every epithelium but by no other tissues. Cells can differentiate to and from the epithelial state as part of normal development, as a response to disease or when manipulated in culture. Many factors (matrix components, adhesion molecules, growth factors, transcription factors) have been identified that can trigger these transitions of phenotype in specific cases, but to date no general master regulators of the epithelial state have been found. The epithelial state may therefore be controlled by multiple regulatory genes so that there is no single molecule responsible for all of the diverse types of epithelium that exist in higher animals. | Basement Membrane |
The HLA (human leukocyte antigens) system, or human major histocompatibility complex, is the most polymorphic functional genetic entity known at present. It consists of HLA class I genes and molecules (A, B and C) which control CD8+ cell-mediated antiviral responses, and class II genes and molecules (DR, DQ and DP) which control CD4+ cell responses (anti-bacterial and anti-toxin). HLA molecules function by presenting antigenic peptides to CD8+ cells (class I) and CD4+ cells (class II). Antigen presentation depends on the intracellular location of the antigen. Antigens present in the exocytosis pathway are presented by class I molecules, while class II molecules present antigens associated with the endocytosis pathway. More than 200 alleles have been detected by means of serological testing (microlymphocytotoxicity) and biochemical methods (IEF) in the HLA class I system, and now by means of molecular biology techniques for class II molecules (PCR-SSO and PCR-RFLP). This molecular typing has revealed the amino acids in HLA molecules that confer genetic susceptibility or resistance to numerous HLA-associated diseases. This is the case for example of ankylosing spondylitis (region 45-46 of HLA-B27 molecules), juvenile diabetes (aa 57 of D beta Q) and rheumatoid arthritis (aa 65-71 of DR beta). Thus, the HLA system is a genetic tool for diagnostic and therapeutic decision-making. | HLA Antigens |
BACKGROUND: Minimally invasive surgery (MIS) for diagnostic or even ablative purposes in pediatric oncology is gradually evolving, but little is known about its biological consequences and surgical complications. Especially for hepatoblastoma (HB), no study on the influence of laparoscopy is available yet. A special tumor model could facilitate a variety of investigations. The present study introduces a laparoscopic technique to create subperitoneal metastases of human HB. METHODS: 7 immuno-incompetent (rnu/rnu) rats (mean weight 198 g) received a stab incision in the lower abdomen to insert a 4 mm scope. Under laparoscopic guidance (CO2 pressure of 1 mmHg, flow of 0.2 l/min) an 18 G needle was introduced, to inject several subperitoneal deposits of the tumor cell suspension (HuH6, 3 x 10 (6) in 1 ml of RPMI-1640 medium). Tumor growth was allowed for 6 - 7 weeks and finally the animals were laparoscopically evaluated for peritoneal metastases. Each suspicious lesion was harvested for histology. RESULTS: One animal was investigated after 6 weeks without evidence of tumor growth. After 7 weeks, in 4 out of 6 animals at least one lesion could be detected. Histology revealed HB in all specimens. CONCLUSION: Subperitoneal inoculation of human HB cells in nude rats achieves intraabdominal tumor growth. The present model allows a variety of laparoscopic strategies and their oncological impact to be studied. Thus it may contribute to the development of distinct oncological concepts for MIS in children with HB. | Rats, Nude |
IMPORTANCE: The National Cancer Database (NCDB), a joint quality improvement initiative of the American College of Surgeons Commission on Cancer and the American Cancer Society, has created a shared research file that has changed the study of cancer care in the United States. A thorough understanding of the nuances, strengths, and limitations of the database by both readers and investigators is of critical importance. This review describes the use of the NCDB to study cancer care, with a focus on the advantages of using the database and important considerations that affect the interpretation of NCDB studies. OBSERVATIONS: The NCDB is one of the largest cancer registries in the world and has rapidly become one of the most commonly used data resources to study the care of cancer in the United States. The NCDB paints a comprehensive picture of cancer care, including a number of less commonly available details that enable subtle nuances of treatment to be studied. On the other hand, several potentially important patient and treatment attributes are not collected in the NCDB, which may affect the extent to which comparisons can be adjusted. Finally, the NCDB has undergone several significant changes during the past decade that may affect its completeness and the types of available data. CONCLUSIONS AND RELEVANCE: The NCDB offers a critically important perspective on cancer care in the United States. To capitalize on its strengths and adjust for its limitations, investigators and their audiences should familiarize themselves with the advantages and shortcomings of the NCDB, as well as its evolution over time. | American Cancer Society |
Batroxobin is a snake venom that is a thrombinlike enzyme used for clinical treatment. We analyzed hepatic mRNA levels for fibrinogen subunit polypeptides and prothrombin by reverse transcription-polymerase chain reaction as well as coagulation and fibrinolysis factors in plasma 1, 3, 5 and 24 hours after Batroxobin treatment (3 BU/100 g) in rats. The mRNA levels of alpha- and beta-chains of fibrinogen were significantly increased with decreases in plasma fibrinogen, alpha2-plasmin inhibitor, and plasminogen levels, while the mRNA levels for prothrombin remained unchanged. These results suggest that fibrinogen mRNA synthesis is regulated by plasma fibrinogen levels in Batroxobin-induced defibrinogenated rats. | Batroxobin |
PURPOSE: To evaluate the relationship between serum beta-human chorionic gonadotropin (HCG) levels and early pregnancy outcomes in women who became pregnant using assisted reproductive technologies (ARTs). METHODS: In this study, we retrospectively analyzed 523 pregnancies after ART use, with respect to the early clinical outcomes based on the serum beta-HCG levels. The significance of using serum beta-HCG levels to predict outcomes in early pregnancy was evaluated by the receiver operating characteristic (ROC) curve and cutoff values of serum beta-HCG. RESULTS: We found that elevated serum beta-HCG levels resulted in decreased biochemical pregnancy rates, increased multiple rates, and decreased ongoing and ectopic pregnancy rates. The cutoff values of serum beta-HCG levels for the prediction of biochemical pregnancy were 213.15 IU/L, 986.65 IU/L, and 2206.5 IU/L for singletons, multiples, and twins or triplets, respectively. CONCLUSION: The serum beta-HCG level 14 or 12 days after D3 or D5 embryo transfer (conducted 3 or 5 days after oocyte retrieval), respectively, predicts biochemical/clinical pregnancy and singleton/multiple pregnancy with robust sensitivity and specificity." | Chorionic Gonadotropin, beta Subunit, Human |
In this article periapical disease is discussed. A differentiation is made in infections, abscesses, granuloma and cysts. | Periapical Diseases |
Giardia lamblia is a widespread parasitic protist with a complex MT cytoskeleton that is critical for motility, attachment, mitosis and cell division, and transitions between its two life cycle stages-the infectious cyst and flagellated trophozoite. Giardia trophozoites have both highly dynamic and highly stable MT organelles, including the ventral disc, eight flagella, the median body and the funis. The ventral disc, an elaborate MT organelle, is essential for the parasite's attachment to the intestinal villi to avoid peristalsis. Giardia's four flagellar pairs enable swimming motility and may also promote attachment. They are maintained at different equilibrium lengths and are distinguished by their long cytoplasmic regions and novel extra-axonemal structures. The functions of the median body and funis, MT organelles unique to Giardia, remain less understood. In addition to conserved MT-associated proteins, the genome is enriched in ankyrins, NEKs, and novel hypothetical proteins that also associate with the MT cytoskeleton. High-resolution ultrastructural imaging and a current inventory of more than 300 proteins associated with Giardia's MT cytoskeleton lay the groundwork for future mechanistic analyses of parasite attachment to the host, motility, cell division, and encystation/excystation. Giardia's unique MT organelles exemplify the capacity of MT polymers to generate intricate structures that are diverse in both form and function. Thus, beyond its relevance to pathogenesis, the study of Giardia's MT cytoskeleton informs basic cytoskeletal biology and cellular evolution. With the availability of new molecular genetic tools to disrupt gene function, we anticipate a new era of cytoskeletal discovery in Giardia. | Microtubules |
A seven-year-old, entire female boxer presented with a history of restless behaviour and inappetence. Physical examination revealed that the dog was listless and had a hunched gait. Neurological examination was normal. Abdominal ultrasonography revealed a 4 cm x 4 cm mass in the cranial pelvic canal. Neurological abnormalities were detected three days after presentation, and progressed from proprioceptive deficits to loss of deep pain sensation in the pelvic limbs over a two-day period. The dog was euthanased and postmortem examination revealed that the pelvic mass was a urethral haemangiosarcoma with metastasis to the second lumbar vertebra. This case is unusual as urethral tumours are usually transitional cell carcinomas and frequently present with signs of dysuria. | Urethral Neoplasms |
BACKGROUND: Juvenile idiopathic arthritis is the most common chronic rheumatic disease of childhood. The term JIA encompasses a heterogenous group of diseases. The variability in phenotype of patients affected by the disease means it is not uncommon for mimics of JIA to be misdiagnosed. CASE PRESENTATION: We present four cases who were treated in single tertiary rheumatology centre for JIA who were subsequently diagnosed with a rare monogenic disease. All four patients shared the unifying features of presenting in early childhood and subsequently suffered with refractory disease, not amenable to usual standards of treatment. Multicentric Carpotarsal Osteolysis Syndrome and Camptodactyly-arthropathy-coxa vara-pericarditis syndrome are non-inflammatory conditions and patients typically present with arthropathy, normal inflammatory markers and atypical radiological features. Blau syndrome is an autosomal dominant condition and patients will typically have symmetrical joint involvement with a strong family history of arthritis, signifying the genetic aetiology. CONCLUSIONS: We share our learning from these cases to add to the growing portfolio of JIA mimics and to highlight when to consider an alternative diagnosis. In cases of refractory disease and diagnostic uncertainty further imaging and genetic testing can play a crucial role in establishing the aetiology. In all of these cases the correct diagnosis was made due to careful, longitudinal clinical phenotyping and a close working relationship between rheumatology, radiology and clinical genetics; highlighting the importance of the multidisciplinary team in managing complex patients. | Bone Anteversion |
DNA methylation is the best studied epigenetic factor, playing a key role in producing stable changes in gene expression, thus defining cell identity and function and adapting cells to environmental changes. DNA methylation has also been recently shown to mediate cell responses to physiological endocrine signals. Moreover, alterations of the normal DNA methylation pattern can also contribute to the development of endocrine and metabolic diseases and can explain the relationship between an individual's genetic background, the environment, and disease. It should be remarked that although DNA methylation and demethylation are active processes, epigenetic changes produced during development can impact adult processes, establishing the idea that endocrine function can be persistently affected by events occurring in early life. Given the complexity of the endocrine system, both genetic and epigenetic processes, including DNA methylation, must be involved in its proper development and functioning. In this study, we summarize the recent knowledge in the field of DNA methylation and endocrinology. Given that DNA methylation can be involved in a number of endocrine and metabolic disorders, understanding and manipulating this modification opens a new door for preventing and treating endocrine diseases." | Site-Specific DNA-Methyltransferase (Adenine-Specific) |
The pathogenicity for mice of nine strains of mouse hepatitis virus was studied in mice free from the virus by the intracerebral, intraperitoneal, intravenous and intranasal routes of inoculation. | Drug Administration Routes |
Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is alpha-galactosidase A (alpha-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers. | alpha-Galactosidase |
Meta-analyses provide researchers with an overview of the body of evidence in a topic, with quantified estimates of effect sizes and the role of moderators, and weighting studies according to their precision. We provide a guide for conducting a transparent and reproducible meta-analysis in the field of developmental psychology within the framework of the MetaLab platform, in 10 steps: (1) Choose a topic for your meta-analysis, (2) Formulate your research question and specify inclusion criteria, (3) Preregister and document all stages of your meta-analysis, (4) Conduct the literature search, (5) Collect and screen records, (6) Extract data from eligible studies, (7) Read the data into analysis software and compute effect sizes, (8) Visualize your data, (9) Create meta-analytic models to assess the strength of the effect and investigate possible moderators, (10) Write up and promote your meta-analysis. Meta-analyses can inform future studies, through power calculations, by identifying robust methods and exposing research gaps. By adding a new meta-analysis to MetaLab, datasets across multiple topics of developmental psychology can be synthesized, and the dataset can be maintained as a living, community-augmented meta-analysis to which researchers add new data, allowing for a cumulative approach to evidence synthesis. | Meta-Analysis as Topic |
OBJECTIVE: The aim of this study was to compare the mandibular position when speaking with the intercuspal position and to check the stability of phonetics when determining the horizontal jaw relation in healthy adults. METHODS: A total of 19 healthy volunteers were recruited. Seven Chinese letters, namely, /xi/, /er/, /yi/, /ci/, /mi/, /ni/, and /ri/, were chosen in the test. O-bite was used to record the mandibular position when speaking these letters. A full-adjusted articulator was used to find the mandibular position during speech, and the mandibular position was measured using a vernier caliper. The mandibular position during speech with intercuspal position was compared in both anterior-posterior and left-right directions of the horizontal plane. Multi-factor analysis of variance was conducted for the statistical analysis of the effect of objects and letters on the mandibular position. RESULTS: 1) The mandibular position was in front of the intercuspal occlusion position when speaking all seven letters, and almost no deviation was observed in the left and right directions (the mandibular position value of 82% was in the range of 0.5 mm). 2) Different objects had different mandibular positions during speech, whereas different letters did not. The distance between the centric relation position and the intercuspal position had a positive correlation with the range of the mandibular position during speech. CONCLUSION: The mandibular position was in front of the intercuspal position when speaking all seven words in the test. In the same object, the mandibular position was stable during speech. | Jaw Relation Record |
In summary, the extent of toxicity studies which can be carried out with bound residues of nitroimidazole drugs will be dictated by the availability and the amount of residues that can be produced. For evaluating their toxicity the use of the Salmonella assay, which has been proven to be sensitive for the parent drugs, is proposed. Furthermore, it is suggested that the toxicity of bound residues for in vivo effects should be investigated in cells of target tissues, such as the epithelial cells of the gastrointestinal tract. Nuclear aberration and sister chromatid exchange assays in this tissue would be good candidates for evaluation. It should be pointed out also that an examination of the literature for genotoxic effects of nitroimidazole drugs reveals an apparent contradiction, especially in the context of genotoxicity testing strategy discussed above. It appears first that these drugs are potent mutagens in vitro in microbial systems (Salmonella and yeast). However, they are not active in mammalian cells in vitro, in both mutation and chromosomal aberration assays, as well as in vivo, in assays such as the dominant lethal test and the micronucleus assay. Thus, it may be of interest to speculate that, although these drugs are in vitro mutagens, they may not be in vivo mutagens in mammals. Their tumorigenic effects, which have been detected at high doses in rodents, may, therefore, be due to other than genotoxic activity. To resolve this conflict, reassessment of genotoxicity of these drugs in vivo would be a worthwhile pursuit. In addition, such seeming discrepancies would also argue strongly for toxicity screening to be conducted in a battery of complementary short-term in vitro and in vivo tests. This would help insure the likelihood of detection of at least some meaningful biological activity, which would serve to flag chemicals warranting further testing. | Drug Residues |
Chagas disease is an inflammatory, infectious disease caused by the parasite Trypanosoma cruzi found in the feces of the triatomine bug, which can cause a sudden, brief acute illness, or it may become a long-lasting chronic condition. Chagas disease is common in South America and Central America, however, the constantly expanding global community has brought Chagas disease to the forefront of non-endemic areas, particularly the United States and Europe. The authors present a case of a 47-year-old healthy farmer diagnosed with a right orbital cellulitis refractory to systemic antibiotics. Based on clinical symptoms, the patient's medical/demographical history and a proper differential diagnosis, an acute phase of Chagas disease was diagnosed. After antiparasitic treatment, the patient had a proper recovery and continued with a regular follow-up to monitor the possible development of a chronic phase. | Chagas Disease |
PURPOSE OF REVIEW: To identify important home care (HC) aide occupational safety and health (OSH) hazards and examine how addressing these can improve aide health and the delivery of HC services overall. Specifically, this review seeks to answer: Why is HC aide OSH important? What are the most significant OSH challenges? How can improving HC aide OSH also improve the safety and health of their clients? What implications do the findings have for future research? RECENT FINDINGS: HC is one of the fastest growing US industries. Aides comprise its largest workforce and are increasingly needed to care for the rapidly aging population. There is an aide shortage due in part to instabilities in HC work organization and to serious job-specific hazards, resulting in aides losing work time. Recent social, economic, and technological factors are rapidly changing the nature of HC work, creating OSH hazards similar to those found in nursing homes. At the same time, aides are experiencing social and economic inequities that increase their vulnerability to OSH hazards. These hazards are also a burden on employers who are challenged to recruit, retain, and train aides. OSH injuries and illness interrupt the continuity of care delivery to clients. Many OSH hazards also put HC clients and families at risk. A new framework and methodologies are needed to assess aide and client safety together in order to guide future HC research, policies, and practices. Government, industry, and labor commitment is needed to fund and coordinate a comprehensive, multidisciplinary research program. | Home Health Aides |
The suppressor of cytokine signaling (SOCS) family of negative regulatory proteins is up-regulated in response to several cytokines and pathogen-associated molecular patterns (PAMP) and suppresses cellular signaling responses by binding receptor phosphotyrosine residues. Exposure of bone marrow-derived dendritic cells (BMDC) to 1D8 cells, a murine model of ovarian carcinoma, suppresses their ability to express CD40 and stimulate antigen-specific responses in response to PAMPs and, in particular, to polyinosinic acid:poly-CMP (polyI:C) with the up-regulated SOCS3 transcript and protein levels. The ectopic expression of SOCS3 in both the macrophage cell line RAW264.7 and BMDCs decreased signaling in response to both polyI:C and IFNalpha. Further, knockdown of SOCS3 transcripts significantly enhanced the responses of RAW264.7 and BMDCs to both polyI:C and IFNalpha. Immunoprecipitation and pull-down studies show that SOCS3 binds to the IFNalpha receptor tyrosine kinase 2 (TYK2). Because polyI:C triggers autocrine IFNalpha signaling, binding of SOCS3 to TYK2 may thereby suppress the activation of BMDCs by polyI:C and IFNalpha. Thus, elevated levels of SOCS3 in tumor-associated DCs may potentially resist the signals induced by Toll-like receptor 3 ligands and type I IFN to decrease DC activation via binding with IFNalpha receptor TYK2." | Suppressor of Cytokine Signaling Proteins |
Replacing trifluoroacetic acid with a catalytic amount of Lewis acid in the osmium mediated oxidative cyclization results in higher yielding reactions that can proceed nearly an order of magnitude faster. The osmium loading can also be reduced to as little as 0.2 mol %. Furthermore, these mildly acidic conditions are capable of tolerating a wide range of acid sensitive protecting groups that are incompatible with previous cyclization conditions. | Osmium |
BACKGROUND: Guidelines for obstetric anesthesia recommend neuraxial anesthesia (i.e., spinal or epidural block) for cesarean delivery in most patients. Little is known about the association of anesthesiologist specialization in obstetric anesthesia with a patient's likelihood of receiving general anesthesia. The authors conducted a retrospective cohort study to compare utilization of general anesthesia for cesarean delivery among patients treated by generalist versus obstetric-specialized anesthesiologists. METHODS: The authors studied patients undergoing cesarean delivery for live singleton pregnancies from 2013 through 2017 at one academic medical center. Data were extracted from the electronic medical record. The authors estimated the association of anesthesiologist specialization in obstetric anesthesia with the odds of receiving general anesthesia for cesarean delivery. RESULTS: Of the cesarean deliveries in our sample, 2,649 of 4,052 (65.4%) were performed by obstetric-specialized anesthesiologists, and 1,403 of 4,052 (34.6%) by generalists. Use of general anesthesia differed for patients treated by specialists and generalists (7.3% vs. 12.1%; P < 0.001). After adjustment, the odds of receiving general anesthesia were lower among patients treated by obstetric-specialized anesthesiologists among all patients (adjusted odds ratio, 0.71; 95% CI, 0.55 to 0.92; P = 0.011), and in a subgroup analysis restricted to urgent or emergent cesarean deliveries (adjusted odds ratio, 0.75; 95% CI, 0.56 to 0.99; P = 0.049). There was no association between provider specialization and the odds of receiving general anesthesia in a subgroup analysis restricted to evening or weekend deliveries (adjusted odds ratio, 0.76; 95% CI, 0.56 to 1.03; P = 0.085). CONCLUSIONS: Treatment by an obstetric anesthesiologist was associated with lower odds of receiving general anesthesia for cesarean delivery; however, this finding did not persist in a subgroup analysis restricted to evening and weekend deliveries. | Anesthesiologists |
In an attempt to identify chromosomal abnormalities that may be associated with a metastatic phenotype, we investigated the pattern of chromosomal gains and losses in 66 node-positive and 63 node-negative primary breast carcinomas. For both subgroups of tumours, losses were more common than gains and the losses were most often the result of structural aberrations. The exceptions were the long arm of chromosome 1, and chromosomes 7, 8, 12, 18 and 20, which were more often gained than lost. Node-negative tumours were preferentially characterised by loss of 6q10-21 and loss of 16q, whereas loss of chromosome 18 was significant for node-positive tumours. Other aberrations that tended to be associated with one of the phenotypes, though not statistically significant, were gain of chromosome 18 and loss of chromosome 10 in node-negative tumours, and gain of chromosome 14 and loss of 12p in node-positive tumours. Our data show that there are differences among the genetic lesions present in node-negative and node-positive breast tumours. Int. J. Cancer (Pred. Oncol.) 84:370-375, 1999. | Chromosomes, Human, 16-18 |
Since angiogenesis is essential for the growth of any solid tumor, emerging efforts are being made to develop antiangiogenic therapy. To date, however, no antiangiogenic agent has become widely available for the clinical setting. Angiotensin I-converting enzyme (ACE) inhibitors are commonly used as antihypertensive agents and it has recently been suggested that they decrease the risk of cancer. Studies have found that an ACE inhibitor, perindopril, is a potent inhibitor of experimental tumor development and angiogenesis at a clinically comparable dose. The potent angiogenic factor, vascular endothelial growth factor (VEGF), is significantly suppressed by perindopril and also inhibits VEGF-induced tumor growth. In vitro studies showed that perindopril is not cytotoxic to either tumor cells or endothelial cells. Since perindopril is already in widespread clinical use without serious side effects, it may represent a potential new strategy for anticancer therapy. | Perindopril |
Glycerophospholipids (GPLs), one of the main components of bacterial cell membranes, exhibit high levels of structural complexity that are directly correlated with biophysical membrane properties such as permeability and fluidity. This structural complexity arises from the substantial variability in the individual GPL structural components such as the acyl chain length and headgroup type and is further amplified by the presence of modifications such as double bonds and cyclopropane rings. Here we use liquid chromatography coupled to high-resolution and high-mass-accuracy ultraviolet photodissociation mass spectrometry for the most in-depth study of bacterial GPL modifications to date. In doing so, we unravel a diverse array of unexplored GPL modifications, ranging from acyl chain hydroxyl groups to novel headgroup structures. Along with characterizing these modifications, we elucidate general trends in bacterial GPL unsaturation elements and thus aim to decipher some of the biochemical pathways of unsaturation incorporation in bacterial GPLs. Finally, we discover aminoacyl-PGs not only in Gram-positive bacteria but also in Gram-negative C. jejuni, advancing our knowledge of the methods of surface charge modulation that Gram-negative organisms may adopt for antibiotic resistance. | Photolysis |
BACKGROUND: Autoimmune gastritis (AIG) and Primary Sjogren's syndrome (pSS) are both autoimmune diseases with low prevalence in China. Subacute combined degeneration (SCD) of the spinal cord is the most common neurological manifestation of vitamin B12 deficiency. Until now, a patient with pSS and complications of AIG including SCD has not been reported. CASE PRESENTATION: A 69-year-old woman presented with palpitations and symmetrical and progressive numbness in her hands and feet. The patient had a sense of stepping on cotton and could not write or walk without help. We reviewed the patient's history and analyzed her blood tests, imaging, gastroscopic findings, and pathological results. The patient fulfilled the criteria of AIG, pSS, spinal cord SCD and early pernicious anemia (PA) simultaneously. Although pSS can lead to reduction of vitamin B12, this is the first overlapping case of pSS with spinal cord SCD. After symptomatic treatment, the patient returned to a normal life. CONCLUSIONS: This first report about the coexistence of pSS and complications of AIG including SCD and PA will promote a better understanding of the relationship between these diseases." | Subacute Combined Degeneration |
BACKGROUND: Animal and neuroimaging studies suggest that the volume of the motor-circuit region decreases in tardive dyskinesia (TD). This study examined the differences in functional connectivity within the motor circuit of patients with schizophrenia with and without TD to further clarify how the dysfunction is related to the pathogenesis of TD. METHODS: Functional magnetic resonance images were taken of 56 schizophrenic patients with TD (TD group), 64 without TD (non-TD group), and 68 healthy controls (HC group). The motor-circuit area was selected as the seed region for a whole brain resting-state functional connectivity (rsFC) analysis. Psychopathological symptoms and TD severity were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Group differences and correlations among 18 brain regions of interest (e.g., the global strength of connectivity between two regions) were analyzed. RESULTS: The analysis of variance results were as follows: The three groups exhibited rsFC losses in the left primary motor cortex, bilateral parietal cortices, right postcentral gyrus, right putamen, right superior parietal lobule, right supplementary motor area and bilateral thalami (false discovery rate,p < 0.05). The TD group showed a significant rsFC loss between the right postcentral gyrus and the inferior frontal gyrus of the left triangular part when compared with the non-TD group (AlphaSim, p < 0.001), which was negatively correlated with the AIMS total score (r=-0.259, p = 0.03). CONCLUSIONS: These findings may suggest dysfunction of the postcentral and inferior frontal gyri of the triangular part in patients with schizophrenia and TD. | Tardive Dyskinesia |
The n-octanol/buffer solution distribution coefficient (or n-octanol/water partition coefficient) is of critical importance for measuring lipophilicity of drug candidates. After 4885 molecular descriptor generation, 15 molecular descriptors were selected to develop quantitative structure-property relationship (QSPR) models for distribution coefficients at pH 7.4 (log D (7.4)) of a large data set consisting of 1043 organic compounds, which was divided into a training set (600 compounds) and a test set (443 compounds). Support vector machine (SVM) based on genetic algorithm was used to develop a model for log D (7.4) that has coefficient of determination r (2) of 0.919 for the training set and 0.893 for the test set. The results suggest that the SVM model is accurate in predicting log D (7.4)." | Quantitative Structure-Activity Relationship |
A systems approach to regulation of neuronal excitation in the mollusc Pleurobranchaea has described novel interactions of cyclic AMP-gated cation current (I(Na,cAMP)), Ca(2+), pH(i), and NO. I(Na,cAMP) appears in many neurons of feeding and locomotor neuronal networks. It is likely one of the family of hyperpolarization-activated, cyclic-nucleotide-gated currents (h-current) of vertebrate and invertebrate pacemaker networks. There are two isoforms. Ca(2+) regulates both voltage dependence and depolarization-sensitive inactivation in both isoforms. The Type 1 I(Na,cAMP) of the feeding network is enhanced by intracellular acidification. A direct dependence of I(Na,cAMP) on cAMP allows the current to be used as a reporter on cAMP concentrations in the cell, and from there to the intrinsic activities of the synthetic adenyl cyclase and the degradative phosphodiesterase. Type 2 I(Na,cAMP) of the locomotor system is activated by serotonergic inputs, while Type 1 of the feeding network is thought to be regulated peptidergically. NO synthase activity is high in the CNS, where it differs from standard neuronal NO synthase in not being Ca(2+) sensitive. NO acidifies pH(i), potentiating Type 1, and may act to open proton channels. A cGMP pathway does not mediate NO effects as in other systems. Rather, nitrosylation likely mediates its actions. An integrated model of the action of cAMP, Ca(2+), pH(i), and NO in the feeding network postulates that NO regulates proton conductance to cause neuronal excitation in the cell body on the one hand, and relief of activity-induced hyperacidification in fine dendritic processes on the other. | Pleurobranchaea |
Yersinia spp. (741 strains) were recovered from 81% of 48 surface water samples collected over a 12-month period from four rivers in Matsue, Japan. The precipitation methods with FeCl3 or Kaolin and the cold enrichment method with Peptone-Mannitol-Phosphate buffer solution were used for recovery. Isolates belonged to Yersinia enterocolitica (Ye) (133 strains), Yersinia intermedia (511 strains), Yersinia frederiksenii (57 strains), Yersinia kristensenii (10 strains) and X2-like organisms (30 strains). Thirty colonies of Ye O3 biotype 3 per ml surface water may relate to the drainage containing 2 X 10(4) Ye O3 biotype 3 per ml, from the piggery that raised Ye O3 biotype 3-positive pigs. There was the negative interrelation between the incidence of isolation of Yersinia spp. and the environmental- and water temperatures. This may be the first documentation of isolation of Ye O3 from surface water. | Yersinia |
Maternal diabetes significantly increases the risk for birth defects. Studies using animal models indicate that oxidative stress may play a causative role. Oxidative stress can result from exposure to certain drugs, ionizing radiation and folic acid deficiency. Therefore, study of the mechanisms by which maternal diabetes affects embryogenesis may provide insight into general processes by which birth defects occur. Study of embryonic gene expression has demonstrated that maternal diabetes causes birth defects by disturbing expression of genes that control essential developmental processes, and that oxidative stress is involved. A model in which oxidative stress-induced deficient gene expression leads to congenital defects involving p53-dependent apoptosis is discussed. | PAX3 Transcription Factor |
Zika virus is a re-emerging flavivirus transmitted primarily by arthropod vectors. The recent devastating outbreak of Zika virus in Brazil was preceded by the slow global encroachment of this virus over many decades. To date, significant research efforts are underway to understand the spread and the unique pathogenesis of this virus; with the intent to rapidly develop vaccines and therapeutics. Several model systems have emerged to study Zika. This review will focus on the use of nonhuman primates to model Zika infection. | Zika Virus |
Three new aaptamine-type alkaloids, 2,3-dihydro-2,3-dioxoaaptamine (1), 6-(N-morpholinyl)-4,5-dihydro-5-oxo-demethyl(oxy)aaptamine (2) and 3-(methylamino)demethyl(oxy)aaptamine (3), along with known aaptamines were isolated from the sponge Aaptos sp. Their structures were determined on the basis of detailed analysis of their 1D and 2D NMR spectroscopic and mass spectral data. The isolated compounds induced apoptosis in human leukemia THP-1 cells. | Naphthyridines |
Within the literature, there is overlap in the histopathological features described in eosinophilic folliculitis associated with chronic lymphocytic leukemia (CLL), eosinophilic dermatosis of hematologic malignancy, and acneiform follicular mucinosis. These disorders are described with varying degrees of superficial and deep lymphocytic and eosinophilic inflammation demonstrating perivascular, perifollicular, and folliculocentric involvement with or without follicular mucin deposition. Given significant histopathological overlap, these diagnoses may represent a continuum on a spectrum of dermatoses. Here, we present two cases with histopathological elements that reflect components of this clinicopathological spectrum and compare our findings with previously reported cases to compare and contrast reported features. Our first case is a 71-year-old African American man with long-standing CLL who developed a pruritic erythematous papular eruption on the face and chest with biopsy revealing a dense folliculotropic lymphocytic infiltrate with conspicuous eosinophils and follicular mucinosis. Our second case is a 70-year-old Caucasian man recently diagnosed with CLL/small lymphocytic lymphoma who developed an erythematous papular rash on the neck and face with biopsy revealing superficial and deep perivascular and periadnexal lymphocytic inflammation with scattered eosinophils. Characterization of our two cases and comparison with available literature suggest that these disorders may represent a continuum of dermatoses. | Mucinosis, Follicular |
AIMS: Hypertriglyceridemic waist (HTgW) is predictive of cardiovascular disease. The HTgW relationship with diabetes is little studied. METHODS: This study analysed data from diabetes and cardiovascular risk factor screening programmes in remote Indigenous Australian settlements. Elevated waist girth (EW) was defined as >/=90 cm for men (n = 1134) or >/=80 cm for women (n = 1313). Hypertriglyceridemia (ETg) was defined as >/=1.7 mmol/L. Diabetes was defined as fasting plasma glucose >/=7.0 mmol/L. Body mass index (BMI) was categorised as <22, 22-24.9 and >25.0 kg/m(2). Logistic regression was used to analyse the odds of newly-diagnosed diabetes for individuals with either HTgW, ETg or EW, relative to individuals with values below cut-offs. RESULTS: The prevalence of HTgW was 33.2% for men and 34.8% for women. Accounting for age-group and gender, newly-diagnosed diabetes was associated (odds ratio (OR) (95% confidence interval)) with HTgW: 9.6 (6.6, 13.8). The relationship remained strong after accounting for the covariates BMI and smoking (OR = 4.9 (2.7, 8.8)). In BMI-stratified analyses the strongest odds were observed for the lowest category (<22 kg/m(2): OR = 12.9 (4.0, 41.7)). CONCLUSIONS: HTgW has a high prevalence and is associated with newly-diagnosed diabetes in Indigenous people, particularly those with BMI <22 kg/m(2), whom clinicians might not normally consider for screening. | Hypertriglyceridemic Waist |
Oxytocin (OT) is a neuropeptide hormone that modulates several social behaviors and can affect the anxiety and stress response. The aim of this study was to determine if administration of intranasal OT affects the stress response to social isolation in sheep. Twenty adult Merino ewes were assigned to two groups; 1) Control group (CG, n = 10), which received an intranasal administration of isotonic saline and 2) Oxytocin-treated group (OTG, n = 10), which received an intranasal administration of OT (24 IU) 40 min before the animals were placed in the social isolation test. During the social isolation test (10 min), the behavior of the sheep was recorded, and blood samples were obtained before and after the test for the determination of cortisol, glucose and serum proteins, and heart rate and surface temperature were recorded. The OTG ewes had a higher cortisol concentration (P = 0.04) after social isolation, tended to vocalize more (P = 0.06) during isolation, and tended to have lower globulin concentrations (P = 0.10) than the CG ewes. Contrary to what we expected, the administration of intranasal OT increased the stress response to social isolation in ewes, which was evidenced by endocrine (greater increase in cortisol concentration), physiological (a tendency to present lower concentration of globulins in blood) and behavioral (a tendency to vocalize more) indicators. This study suggests that the administration of intranasal OT increased the stress response to isolation possibly by strengthening the social bond among ewes. | Administration, Intranasal |
Purpose Clinical supervision for counseling skill development can be variable and can undermine student ability to learn patient-centered care communication. The current study aimed to evaluate the effectiveness of consultation and feedback sessions on counseling behavior, in actual clinical practice, among clinical audiology supervisors. We also collected qualitative data on participants' experiences and suggestions for improving the counseling intervention to increase counseling communication in audiology graduate training programs. Method We used a noncurrent multiple baseline design and staggered the counseling intervention to control for effects of concurrent events and passage of time. Results Two participants showed small but reliable increases in counseling behavior, whereas the 3rd participant showed bigger but less stable increases in counseling. Participants reported that brief feedback sessions were helpful; however, they also mentioned barriers to counseling, such as worries with how much time counseling could take when they have back-to-back appointments. Conclusion Clinical audiology supervisors were able to improve their counseling skills in real-life sessions with regular feedback. More structure may be needed to strengthen future counseling skills. | Audiology |
The Tocantins-Araguaia Basin is one of the largest river systems in South America, located entirely within Brazilian territory. In the last decades, capital-concentrating activities such as agribusiness, mining, and hydropower promoted extensive changes in land cover, hydrology, and environmental conditions. These changes are jeopardizing the basin's biodiversity and ecosystem services. Threats are escalating as poor environmental policies continue to be formulated, such as environmentally unsustainable hydropower plants, large-scale agriculture for commodity production, and aquaculture with non-native fish. If the current model persists, it will deepen the environmental crisis in the basin, compromising broad conservation goals and social development in the long term. Better policies will require thought and planning to minimize growing threats and ensure the basin's sustainability for future generations. | Environment |
Scientific enquiry must be the driving force of research. This sentiment is manifested as the profound impact gene editing technologies are having in our current world. There exist three main gene editing technologies today: Zinc Finger Nucleases, TALENs and the CRISPR-Cas system. When these systems were being uncovered, none of the scientists set out to design tools to engineer genomes. They were simply trying to understand the mechanisms existing in nature. If it was not for this simple sense of wonder, we probably would not have these breakthrough technologies. In this chapter, we will discuss the history, applications and ethical issues surrounding these technologies, focusing on the now predominant CRISPR-Cas technology. Gene editing technologies, as we know them now, are poised to have an overwhelming impact on our world. However, it is impossible to predict the route they will take in the future or to comprehend the full impact of its repercussions. | Zinc Finger Nucleases |
Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4'-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3'-dihydroxy-3,6,7,4',5'-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3',4',5'-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-alpha-L-rhamnopyranoside (4), isorhamnetin-3-O-beta-D-glucopyranoside (5), quercetin 7-O-alpha-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-alpha-L-rhamnopyranoside (7) along with benzyl-O-beta-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1-3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3',4',5'-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC(50) values at 2.17 microM, 0.53 microM, and 2.16 microM, respectively, and was 2-9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G(1) cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC(50) values at 2.19 microM and 3.18 microM, respectively, and was 6-8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells. | Rhamnus |
The federal Medicare Diagnosis Related Group payment mechanism is undergoing constant change. Significant interest has been generated at the health policy level regarding reimbursement for patients with complications and comorbidities. The purpose of this study was to analyze hospital resource consumption for patients in the seventeen urology non-complicating condition (CC) stratified Diagnostic Related Groups (DRGs), currently 45 percent of urology DRGs. We analyzed 185 Medicare patients in these non-CC stratified urology DRGs and found that patients with more CCs per patient had higher total hospital costs per patient, financial risk under DRGs, a greater percentage of outliers, and a higher mortality, than patients in these same DRGs with fewer CCs per patient. These findings suggest that the current DRG system is inequitable to some patients and certain hospitals vis-a-vis non-CC stratified urology DRGs. The Health Care Financing Administration has not significantly changed the complicating condition urology DRG classification, as of its recent May, 1988 legislation. Financial disincentives to treat these patients may affect both their access and quality of care in the future." | Prospective Payment Assessment Commission |
BACKGROUND: The U.S. health care system faces increasing pressures for reform. The importance of nurses in addressing health care delivery challenges cannot be overstated. PURPOSE: To present a Nursing Health Services Research (NHSR) agenda for the 2020s. METHOD: A meeting of an interdisciplinary group of 38 health services researchers to discuss five key challenges facing health care delivery (behavioral health, primary care, maternal/neonatal outcomes, the aging population, health care spending) and identify the most pressing and feasible research questions for NHSR in the coming decade. FINDINGS: Guided by a list of inputs affecting health care delivery (health information technology, workforce, delivery systems, payment, social determinants of health), meeting participants identified 5 to 6 research questions for each challenge. Also, eight cross-cutting themes illuminating the opportunities and barriers facing NHSR emerged. DISCUSSION: The Agenda can act as a foundation for new NHSR - which is more important than ever - in the 2020s. | Health Priorities |
OBJECTIVE: To compare the retention and the caries preventive effect of a glass-ionomer developed for fissure sealing (Fuji III) and a chemically polymerized resin-based fissure sealant (Delton). DESIGN: A split mouth randomized design using contralateral teeth. SETTING: WHO Regional Demonstration, Training and Research Center for Oral Health, Damascus, Syrian Arab Republic. SAMPLE AND METHODS: 179 children, 7 years old at the start of the study, were recruited from schools close to the Center. Only children with at least one pair of permanent first molars that were caries free or only had incipient lesions were included in the study. Follow-up examinations for sealant retention were done after 6 months, 1 year, 2 years and 3 years. The number of children available for reexamination was 129 (after 6 months); 121 (after 1 year); 115 (after 2 years) and 116 (after 3 years). Four dental hygienists were trained in the sealant procedures and did approximately one fourth of the sealants each. RESULTS: After 3 years the glass-ionomer sealant was completely lost in almost 90% of the teeth compared to less than 10% of the resin sealed teeth. After 3 years the relative risk of a tooth sealed with glass-ionomer over that of a tooth sealed with resin was 3.38 (95% CL: 1.98; 5.79). This finding was consistent over type of tooth. CONCLUSIONS: The glass-ionomer sealant tested in the present study had poorer retention and less caries protective effect than the resin-based sealant used. | Dental Fissures |
BACKGROUND/AIMS: The present study aimed to explore the equivalence of CHL and tacrolimus (TAC), despite reports regarding the efficacy and safety of TAC in treating SRNS patients. METHODS: A retrospective cohort study of CHL or TAC treatment was performed by collecting the medical records of SRNS patients with a pathological classification of focal segmental glomurular sclerosis (FSGS) or membranous nephropathy (MN) from December 2008 to December 2014 in a 3A grade hospital in southern China. The treatment regimen includes 6 months of induction therapy and a subsequent 6 to 30 months of maintenance therapy, which were evaluated by the scheduled follow-up and the detection of proteinuria and serum creatinine levels. The treatment outcomes were classified as complete remission, partial remission or no remission. RESULTS: In a total of 146 SRNS patients, CHL treatment showed a higher proportion of complete remission (27.8% vs 14.9%) or partial remission (52.8% vs 37.8%) compared to TAC treatment (P < 0.10) at the stage of induction therapy. The CHL treatment of SRNS patients with FSGS showed better efficacy than treatment of the TAC group, but the difference of efficacy in the pathological type of MN between CHL and TAC group was not significant (P > 0.10). During maintenance therapy, the difference between the CHL and TAC groups was not significant in the SRNS patients with FSGS or MN (P > 0.10). In addition, the difference of adverse effects between CHL and TAC group was not significant (P > 0.10), although there was a slightly higher proportion of nausea and vomiting in the CHL group. CONCLUSION: The non-inferior efficacy of CHL treatment on the SRNS patients with FSGS or MN compared to TAC treatment, which highlighted CHL can be considered to be alternative treatment for SRNS patients in the clinical setting. | Mechlorethamine |
OBJECTIVE: To synthesize the scientific findings on demoralization and spirituality in the oncology context. METHODS: This is an integrative systematic review, in line with the PRISMA 2020 guidelines, as proposed by Whittemore and Knalf (2005). The MEDLINE via PubMed, Scopus, Web of Science, APA PsycNet, CINAHL, Cochrane Library, EMBASE, and LILACS databases were searched without limitations regarding language or year of publication. The studies were screened for inclusion according to the predefined eligibility criteria. Data extraction and evidence quality assessment were performed. RESULTS: Out of the 1587 articles evaluated, 10 studies were included in this review. In general, it was found that demoralization tends to increase with the proximity of death and seems to be inversely related to spirituality, with spiritual well-being being a protective factor against demoralization, while the non-fulfillment of spiritual needs is related to increased demoralization in people with cancer. Furthermore, even among caregivers of people with advanced cancer, demoralization seems to be associated, among other factors, with spiritual suffering. These results should be analyzed with caution, considering that the studies included in this review are all observational studies, which prevents establishing cause and effect relationships. CONCLUSIONS: Demoralization tends to increase with growing frailty and the proximity of death in people with cancer, and it seems to be inversely related to spirituality, both in these patients and in their caregivers. | Demoralization |
The primo vascular system was recently observed in the central nervous systems of rabbits and rats, but no investigations in large animals have been reported. In the present work we found a putative primo vascular system in the spinal cord of a pig. We obtained spines from four healthy pigs and fixed them with paraformaldehyde. The primo vessels were expected to lie in the subarachnoid space between the pia mater and the arachnoid mater. The composite of three membranes (the pia, the arachnoid, and the dura maters) wrapping the spinal cord was peeled off, isolated from the spine, and put on a slide glass. This composite was stained with 4',6'-Diamidino-2-phenylindole (DAPI) and phalloidin to show the nuclei and the f-actin, respectively, in the cells of the primo vessels. We observed eleven pieces of the putative primo vessels in the subarachnoid space of the spines at the thoracic spinal nerve area. They had the typical rod-shaped nuclei distributed in a broken line, and f-actin signals around nuclei. The lengths of the nuclei were 12-15 mum, and the thicknesses of the primo vessels were 8 approximately 20 mum, which were consistent with other primo vessels that had been observed in the various organs of rabbits, rats, and mice. In addition, we observed branching of the primo vessels, which is again an expected result from previous works. In conclusion, a primo vessel was observed in the subarachnoid space of the spinal cord of a pig. This was the first observation of a primo vessel in a large animal, and the staining method used to observe the primo vessel in a fixed sample was newly developed in this work. | Subarachnoid Space |
BACKGROUND: Breast cancer incidence has been associated with hypertension, which might worsen disease prognosis, but few nationwide studies have investigated the association between antihypertensive drug use and breast cancer prognosis. METHODS: A cohort of 73,170 women diagnosed with breast cancer during 1995-2013 identified from the Finnish Cancer Registry was combined with information on antihypertensive drug use during the same time period from a national prescription database. Antihypertensive drugs were analyzed in groups categorized by mechanism of action. Usage of antihypertensive drugs, statins, antidiabetic, and anticoagulative drugs was analyzed as time-dependent exposure to model for simultaneous use of multiple drug groups. Influence of protopathic bias was evaluated in lag-time analyses. RESULTS: In prediagnostic use, only angiotensin receptor (ATR)-blockers were associated with decreased risk of breast cancer death as compared with nonusers (HR: 0.76, 95% confidence interval, CI: 0.69-0.82), and there was an inverse association with cumulative dose of use. Postdiagnostic use of ATR-blockers, angiotensin-converting enzyme (ACE)-inhibitors, beta-blockers, and calcium-channel blockers was dose dependently associated with better breast cancer survival compared with nonusers. The risk decrease was strongest for ATR-blockers (HR: 0.69, 95% CI: 0.63-0.75) and remained for exposures occurring up to 3 years earlier. CONCLUSIONS: Only ATR-blockers were associated with improved breast cancer survival in both prediagnostic and postdiagnostic use. The association was dose dependent and supported by a biological rationale as a causal explanation. In postdiagnostic use, similar reduction was found also for other antihypertensives, supporting a prognostic role of hypertension control. IMPACT: Inhibition of angiotensin receptor subtype 1 (AT(1)) could be a promising novel way to affect breast cancer progression." | Angiotensin Receptor Antagonists |
BACKGROUND: In patients undergoing high-risk surgery, it is recommended to titrate fluid administration using stroke volume or a dynamic variable of fluid responsiveness (FR). However, this strategy usually requires the use of a hemodynamic monitor and/or an arterial catheter. Recently, it has been shown that variations of central venous pressure (DeltaCVP) during an alveolar recruitment maneuver (ARM) can predict FR and that there is a correlation between CVP and peripheral venous pressure (PVP). This prospective study tested the hypothesis that variations of PVP (DeltaPVP) induced by an ARM could predict FR. METHODS: We studied 60 consecutive patients scheduled for high-risk abdominal surgery, excluding those with preoperative cardiac arrhythmias or right ventricular dysfunction. All patients had a peripheral venous catheter, a central venous catheter and a radial arterial catheter linked to a pulse contour monitoring device. PVP was always measured via an 18-gauge catheter inserted at the antecubital fossa. Then an ARM consisting of a standardized gas insufflation to reach a plateau of 30 cmH(2)O for 30 s was performed before skin incision. Invasive mean arterial pressure (MAP), pulse pressure, heart rate, CVP, PVP, pulse pressure variation (PPV), and stroke volume index (SVI) were recorded before ARM (T1), at the end of ARM (T2), before volume expansion (T3), and one minute after volume expansion (T4). Receiver-operating curves (ROC) analysis with the corresponding grey zone approach were performed to assess the ability of âÂÂPVP (index test) to predict FR, defined as an >/= 10% increase in SVI following the administration of a 4 ml/kg balanced crystalloid solution over 5 min. RESULTS: âÂÂPVP during ARM predicted FR with an area under the ROC curve of 0.76 (95%CI, 0.63 to 0.86). The optimal threshold determined by the Youden Index was a âÂÂPVP value of 5 mmHg (95%CI, 4 to 6) with a sensitivity of 66% (95%CI, 47 to 81) and a specificity of 82% (95%CI, 63 to 94). The AUC's for predicting FR were not different between DeltaPVP, DeltaCVP, and PPV. CONCLUSION: During high-risk abdominal surgery, âÂÂPVP induced by an ARM can moderately predict FR. Nevertheless, other hemodynamic variables did not perform better. | Venous Pressure |
The work presents the results of studies on the behaviour of SCC antigen in 52 patients aged 21-70 years, with pathologic changes involving the uterine cervix and classified to the groups of erosion, dysplasia and carcinoma in different stage of advancement. The SCC antigen was determined in patients blood sera by radioimmunologic method, on the basis of Abbott Firm testes. An increase in concentration was observed exceed the norm (2 ng/ml) in cases of CIN and CIS. The rise of marker depended on the stage of the neoplastic process advancement in the uterine cervix. | Uterine Cervical Erosion |
The thalamus is a deep cerebral structure that is crucial for proper neurological functioning as it transmits signals from nearly all pathways in the body. Insult to the thalamus can, therefore, result in complex syndromes involving sensation, cognition, executive function, fine motor control, emotion, and arousal, to name a few. Specific territories in the thalamus that are supplied by deep cerebral arteries have been shown to correlate with clinical symptoms. The aim of this review is to enhance our understanding of the arterial anatomy of the thalamus and the complications that can arise from lesions to it by considering the functions of known thalamic nuclei supplied by each vascular territory. | Diencephalon |
In developing inhibitors of the LIM kinases, the initial lead molecules combined potent target inhibition with potent cytotoxic activity. However, as subsequent compounds were evaluated, the cytotoxic activity separated from inhibition of LIM kinases. A rapid determination of the cytotoxic mechanism and its molecular target was enabled by integrating data from two robust core technologies. High-content assays and gene expression profiling both indicated an effect on microtubule stability. Although the cytotoxic compounds are still kinase inhibitors, and their structures did not predict tubulin as an obvious target, these results provided the impetus to test their effects on microtubule polymerization directly. Unexpectedly, we confirmed tubulin itself as a molecular target of the cytotoxic kinase inhibitor compounds. This general approach to mechanism of action questions could be extended to larger data sets of quantified phenotypic and gene expression data. | Lim Kinases |
In recent years, Cr speciation in dietary supplements has become decisive in the evaluation of their health risks. Despite being an beneficial micronutrient, Cr(III) can be toxic at living organisms at high concentrations, while Cr(VI) is known to be highly toxic and carcinogenic. The main objective of this work was to optimize an analytical methodology for the extraction and accurate quantification of Cr(III) and Cr(VI) in dietary supplements. The extraction of Cr species was carried out with 50mM EDTA solution on a hotplate under optimized conditions. Special attention was paid to bidirectional species transformations. No noticeable oxidation of Cr(III) into Cr(VI) was observed and the reduction to Cr(III) only occurred at very high Cr(VI) concentrations. Cr(III) as Cr(EDTA)(-) complex was chromatographically separated from Cr(VI), retained as CrO4(2-), on an anion exchange column coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The limit of quantification (0.08microgg(-1)) was below the limit established for Cr enriched yeasts by the European Union. Eleven dietary supplements were analyzed and Cr(III) and Cr(VI) quantification was carried out by external calibration monitoring (52)Cr isotope and by speciated isotope dilution mass spectrometry (SIDMS) adding (50)Cr(III) and (53)Cr(VI) spikes. Total Cr was also quantified by ICP-MS and mass balance between total Cr and the sum of Cr(III) and Cr(VI) was achieved. In eight of the eleven tested supplements Cr(III) calculated amounts were higher than those indicated by the manufacturer, but only one of them exceeded the 250microgday(-1) recommended by World Health Organization (WHO). In contrast, it is worth noting that Cr(VI) amounts beyond the recommendations of the European Union for Cr enriched yeasts were found in five supplements. These results revealed that more accurate and rigorous quality assurance protocols should be applied to the testing of the final products, including the analysis of both Cr(III) and Cr(VI). | Chromium Isotopes |
PURPOSE OF REVIEW: Medical decisions concerning active surveillance are complex, especially when evidence on superiority of one of the treatments is lacking. Decision aids have been developed to facilitate shared decision-making on whether to pursue an active surveillance strategy. However, it is unclear how these decision aids are designed and which outcomes are considered relevant. The purpose of this study is to systematically review all decision aids in the field of oncological active surveillance strategies and outcomes used by authors to assess their efficacy. RECENT FINDINGS: A search was performed in Embase, Medline, Web of Science, Cochrane, PsycINFO Ovid and Google Scholar until June 2019. Eligible studies concerned interventions aiming to facilitate shared decision-making for patients confronted with several treatment alternatives, with active surveillance being one of the treatment alternatives. Twenty-three eligible articles were included. Twenty-one articles included patients with prostate cancer, one with thyroid cancer and one with ovarian cancer. Interventions mostly consisted of an interactive web-based decision aid format. After categorization of outcomes, seven main groups were identified: knowledge, involvement in decision-making, decisional conflict, treatment preference, decision regret, anxiety and health-related outcomes. Although active surveillance has been implemented for several malignancies, interventions that facilitate shared decision-making between active surveillance and other equally effective treatment alternatives are scarce. Future research should focus on developing interventions for malignancies like rectal cancer and oesophageal cancer as well. The efficacy of interventions is mostly assessed using short-term outcomes. | Decision Making, Shared |
In this article, the design and synthesis of some novel azasterols is described, followed by their evaluation against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum, the causative agents of human African trypanosomiasis, Chagas disease, leishmaniasis, and malaria, respectively. Some of the compounds showed anti-parasitic activity. In particular, a number of compounds appeared to very potently inhibit the growth of the blood stream form T. b. rhodesiense, with one compound giving an IC50 value of 12 nM. Clear structure activity relationships could be discerned. These compounds represent important leads for further optimization. Azasterols have previously been shown to inhibit sterol biosynthesis in T. cruzi and L. donovani by the inhibition of the enzyme sterol 24-methyltransferase. However, in this case, none of the compounds showed inhibition of the enzyme. Therefore, these compounds have an unknown mode of action. | Azasteroids |
Infection with rubella virus during pregnancy, especially during the first trimester, can result in congenital rubella syndrome (CRS). Serious manifestations of CRS include deafness, cataracts, cardiac defects, mental retardation, and death. In the last major rubella epidemic in the United States, during 1964-1965, an estimated 12.5 million rubella virus infections resulted in 11,250 therapeutic or spontaneous abortions, 2,100 neonatal deaths, and 20,000 infants born with CRS. In 2004, after implementation of a universal vaccination program, elimination of endemic rubella virus transmission was documented in the United States; evidence also suggests that endemic rubella has been eliminated in the entire World Health Organization (WHO) Region of the Americas. However, rubella virus continues to circulate elsewhere in the world, especially in regions where rubella vaccination programs have not been established (e.g., the African Region), placing the United States at risk for imported cases of rubella and CRS. During 2004-2012, 79 cases of rubella and six cases of CRS were reported in the United States; all of the cases were import-associated or from unknown sources. Of the three cases of CRS that occurred in 2012, conditions included cardiac defects, cataracts, hearing impairment, and pericardial effusion in one infant; patent ductus arteriosus, cardiomegaly, thrombocytopenia, and pneumonitis in a second infant; and cataracts, thrombocytopenia, and cardiac defects in a third infant. All three mothers had been in Africa early in their pregnancies. While rubella remains endemic elsewhere in the world, imported CRS will continue to be a public health concern in the United States. | Rubella Syndrome, Congenital |
BACKGROUND: Perianal Paget's disease often coincides with anorectal carcinoma, which extends into the epidermis from a contiguous organ. OBJECTIVE: Our purpose was to present a patient with perianal Paget's disease who had a rectal adenocarcinoma excised 14 years previously in another hospital and to determine whether there is a relationship between the perianal Paget's disease and the rectal adenocarcinoma. METHODS: We examined the resected specimens of the rectal adenocarcinoma and the perianal Paget's disease histologically. RESULTS: In the resected specimen of the rectal adenocarcinoma, Paget cells were present within the anal epidermis adjacent to the rectal adenocarcinoma. The Paget cells showed the same histochemical and immunohistological findings as the adenocarcinoma cells. CONCLUSION: There was a close relationship between the perianal Paget's disease and the rectal adenocarcinoma. It is probable that the Paget cells were derived from direct spread from the rectal adenocarcinoma. | Anal Gland Neoplasms |
The aim of this study is to contribute to the understanding of the mechanisms underlying nanoparticle (NP)-induced embryotoxicity in aquatic organisms. We previously demonstrated that exposure of male gametes to NPs causes non-dose-dependent skeletal damage in sea urchin (Paracentrotus lividus) larvae. In the present study, the molecular mechanisms responsible for these anomalies in sea urchin development from male gametes exposed to cobalt (Co), titanium dioxide (TiO2) and silver (Ag) NPs were investigated by histochemical, immunohistochemical and Western blot analyses. P. lividus sperm were exposed to different NP concentrations (from 0.0001 to 1 mg/L). The distribution of molecules related to skeletogenic cell identification, including ID5 immunoreactivity (IR), wheat germ agglutinin (WGA) affinity and fibronectin (FN) IR, were investigated by confocal laser scanning microscopy at the gastrula (24 h) and pluteus (72 h) stages. Our results identified a spatial correspondence among PMCs, ID5 IR and WGA affinity sites. The altered FN pattern suggests that it is responsible for the altered skeletogenic cell migration, while the Golgi apparatus of the skeletogenic cells, denoted by their WGA affinity, shows different aspects according to the degree of anomalies caused by NP concentrations. The ID5 IR, a specific marker of skeletogenic cells in sea urchin embryos (in particular of the msp130 protein responsible for Ca(2+) and Mg(2+) mineralization), localized in the cellular strands prefiguring the skeletal rods in the gastrula stage and, in the pluteus stage, was visible according to the degree of mineralization of the skeleton. In conclusion, the present study suggests that the investigated NPs suspended in seawater interfere with the bio-mineralization processes in marine organisms, and the results of this study offer a new series of specific endpoints for the mechanistic understanding of NP toxicity. | Paracentrotus |
Anaplasma marginale, A. ovis, and A. phagocytophilum are the causative agents of bovine anaplasmosis, ovine anaplasmosis, and granulocytic anaplasmosis, respectively. The gold standard for diagnosis of post-acute and long-term persistent infections is the serological cELISA, which does not discriminate between Anaplasma species and requires highly equipped laboratories and trained personnel. This study addresses the development of a rapid, isothermal, sensitive, species-specific RPA assays to detect three Anaplasma species in blood and cELISA A. marginale-positive serum samples. Three RPA primer and probe sets were designed targeting msp4 genes of each Anaplasma species and the internal control (GAPDH gene) for each assay. The limit of detection of gel-based or RPA-basic assays is 8.99 x 10(4) copies/microl = A. marginale, 5.04 x 10(6) copies/microl = A. ovis, and 4.58 x 10(3) copies/microl = A. phagocytophilum, and for each multiplex lateral flow or RPA-nfo assays is 8.99 x 10(3) copies/microl of A. marginale, 5.04 x 10(3) copies/microl of A. ovis, 4.58 x 10(3) copies/microl of A. phagocytophilum, and 5.51 x 10(3) copies/microl of internal control (GAPDH). Although none of the 80 blood samples collected from Oklahoma cattle were positive, the RPA-nfo assays detected all A. marginale cattle blood samples with varying prevalence rates of infection, 83% of the 24 cELISA A. marginale-positive serum samples, and all A. phagocytophilum cell culture samples. Overall, although early detection of three Anaplasma species was not specifically addressed, the described RPA technique represents an improvement for detection of three Anaplasma in regions where access to laboratory equipment is limited. | Anaplasma ovis |
Placebos are medication surrogates that are able to improve symptoms in patients when prescribed by a doctor and for a patient, and that cannot be explained by a drug. In clinical testing and presumably also in clinical routine, placebo effects contribute substantially to the efficacy of medicines, at least with every-day diseases and complaints. Placebos on the one hand, and the mechanisms the response on the other, have not interfered with the development on novel drugs in past years, but have also brought about research that investigates its mechanisms and public interest in its clinical use in everyday medicine. Current knowledge grows by about 10.000 publications per year on placebo-controlled studies, and by nearly 100 papers on the placebo effect itself. This review will focus on the history of placebo use in medicine, on ethical issues related to the use of placebos, on methodological problems in placebo-controlled trials and their alternatives, and on mechanisms of the placebo response in clinical and experimental research, e.g. on type, size, dynamics, determinants, and predictors of the placebo response in the literature. | Placebo Effect |
OBJECTIVE: To develop a core set of prenatal and neonatal outcomes for clinical studies evaluating perinatal interventions for congenital diaphragmatic hernia, using a validated consensus-building method. METHODS: An international steering group comprising 13 leading maternal-fetal medicine specialists, neonatologists, pediatric surgeons, patient representatives, researchers and methodologists guided the development of this core outcome set. Potential outcomes were collected through a systematic review of the literature and entered into a two-round online Delphi survey. A call was made for stakeholders with experience of congenital diaphragmatic hernia to review the list and score outcomes based on their perceived relevance. Outcomes that fulfilled the consensus criteria defined a priori were discussed subsequently in online breakout meetings. Results were reviewed in a consensus meeting, during which the core outcome set was defined. Finally, the definitions, measurement methods and aspirational outcomes were defined in online and in-person definition meetings by a selection of 45 stakeholders. RESULTS: Overall, 221 stakeholders participated in the Delphi survey and 198 completed both rounds. Fifty outcomes met the consensus criteria and were discussed and rescored by 78 stakeholders in the breakout meetings. During the consensus meeting, 93 stakeholders agreed eventually on eight outcomes, which constituted the core outcome set. Maternal and obstetric outcomes included maternal morbidity related to the intervention and gestational age at delivery. Fetal outcomes included intrauterine demise, interval between intervention and delivery and change in lung size in utero around the time of the intervention. Neonatal outcomes included neonatal mortality, pulmonary hypertension and use of extracorporeal membrane oxygenation. Definitions and measurement methods were formulated by 45 stakeholders, who also added three aspirational outcomes: duration of invasive ventilation, duration of oxygen supplementation and use of pulmonary vasodilators at discharge. CONCLUSIONS: We developed with relevant stakeholders a core outcome set for studies evaluating perinatal interventions in congenital diaphragmatic hernia. Its implementation should facilitate the comparison and combination of trial results, enabling future research to better guide clinical practice. (c) 2023 International Society of Ultrasound in Obstetrics and Gynecology." | Hernias, Diaphragmatic, Congenital |
A questionnaire including 31 questions was conducted in thirty-one provinces of China's thirty-four provinces. A total of 7212 questionnaires were received in the research and 3775 valid questionnaires were used in the final data analysis. Around 86.0% of the respondents from the selected valid questionnaires liked eating lamb meat. About 66.7% of the respondents from the selected valid questionnaires preferred to use fresh lamb meat for cooking. Stewing was the most popular cooking method for lamb meat consumption in China. Almost 70.0% of the respondents from the selected valid questionnaires preferred to consume local lamb meat rather than imported lamb meat. Food safety, lamb breed and meat origin were the top three factors concerned when the respondents purchase lamb meat. >65.0% of the respondents from the selected valid questionnaires preferred to purchase traceable lamb meat. In conclusion, the development of technologies to maintain fresh lamb meat quality and traceable lamb meat products are required in China. | Meat |
A major development in the field of psychotherapy research is the growing recognition of the need for evidence on the mechanisms of change in psychotherapy. The empirical evidence that psychotherapy has a positive and significant effect must be amplified with data on the mechanisms of action in the various psychotherapies. This special issue is devoted to the articulation of putative mechanisms of change in the psychotherapy of patients with borderline personality disorder by leading researchers in this field." | Borderline Personality Disorder |
Myobloc is the currently available commercial formulation of type B botulinum toxin. Released in the United States in 2000, it is approved by the Food and Drug Administration for the treatment of cervical dystonia. The most commonly used botulinum toxins, the type A toxins (Botox and Dysport), affect the SNAP-25 protein, whereas the type B toxin (Myobloc) affects vesicle-associated membrane protein, also known as synaptobrevin. Both type B and type A are antigenically distinct. This article explains the difference between Myobloc and type A toxins, reviews equivalency and other published studies, and describes practical uses for this product in facial aesthetics. | Metalloproteases |
Edward Spitzka, a prominent New York-based alienist, who spent 3 years in Germany studying psychiatry, published a textbook in 1883-the same year as the first edition of Kraepelin's textbook-that contained detailed descriptions of all the seven psychiatric syndromes that formed the basis of Kraepelin's nosologic synthesis: mania, melancholia, katatonia, secondary deteriorations, hebephrenia, circular insanity, and monomania. A study of this text provides us with a before" picture-a view of the canvas of psychiatric diagnostic categories-from which Kraepelin worked. Studying what Spitzka's diagnostic categories contain and what they are missing highlights the key steps Kraepelin took in the development of his nosologic synthesis. For example, Spitzka does not describe a commonality in symptoms or outcome in katatonia, hebephrenia, and the move severely ill delusional monomaniacs, nor did he link together mania, melancholia, and circular insanity, but instead comments on wide differences in outcome among these three syndromes." | Mania |
Arsenic is present in the environment and has become a worldwide health concern due to its toxicity and carcinogenicity. However, the specific mechanism(s) by which arsenic elicits its toxic effects has yet to be fully elucidated. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been recognized as the master regulator of a cellular defense mechanism against toxic insults. This review highlights studies demonstrating that arsenic activates the Nrf2-Keap1 antioxidant pathway by a distinct mechanism from that of natural compounds such as sulforaphane (SF) found in broccoli sprouts or tert-butylhyrdoquinone (tBHQ), a natural antioxidant commonly used as a food preservative. Evidence also suggests that arsenic prolongs Nrf2 activation and may mimic constitutive activation of Nrf2, which has been found in several human cancers due to disruption of the Nrf2-Keap1 axis. The current literature strongly suggests that activation of Nrf2 by arsenic potentially contributes to, rather than protects against, arsenic toxicity and carcinogenicity. The mechanism(s) by which known Nrf2 activators, such as the natural chemopreventive compounds SF and lipoic acid, protect against the deleterious effects caused by arsenic will also be discussed. These findings will provide insight to further understand how arsenic promotes a prolonged Nrf2 response, which will lead to the identification of novel molecular markers and development of rational therapies for the prevention or intervention of arsenic-induced diseases. The National Institute of Environmental Health Science (NIEHS) Outstanding New Environmental Scientist (ONES) award has provided the opportunity to review the progress both in the fields of arsenic toxicology and Nrf2 biology. Much of the funding has led to (1) the novel discovery that arsenic activates the Nrf2 pathway by a mechanism different to that of other Nrf2 activators, such as sulforaphane and tert-butylhydroquinone, (2) activation of Nrf2 by chemopreventive compounds protects against arsenic toxicity and carcinogenicity both in vitro and in vivo, (3) constitutive activation of Nrf2 by disrupting Keap1-mediated negative regulation contributes to cancer and chemoresistance, (4) p62-mediated sequestration of Keap1 activates the Nrf2 pathway, and (5) arsenic-mediated Nrf2 activation may be through a p62-dependent mechanism. All of these findings have been published and are discussed in this review. This award has laid the foundation for my laboratory to further investigate the molecular mechanism(s) that regulate the Nrf2 pathway and how it may play an integral role in arsenic toxicity. Moreover, understanding the biology behind arsenic toxicity and carcinogenicity will help in the discovery of potential strategies to prevent or control arsenic-mediated adverse effects. | Arsenic Poisoning |
Transdermal cancer therapy faces great challenges in clinical practice due to the low drug transdermal efficiency and the unsatisfactory effect of monotherapy. Herein, we develop a novel bubble pump microneedle system (BPMN-CuS/DOX) by embedding sodium bicarbonate (NaHCO(3)) into hyaluronic acid microneedles (MNs) loaded with fucoidan-based copper sulfide nanoparticles (Fuc-CuS NPs) and doxorubicin (DOX). BPMN-CuS/DOX can generate CO(2) bubbles triggered by an acidic tumor microenvironment for deep and rapid intradermal drug delivery. Fuc-CuS NPs exhibit excellent photothermal effect and Fenton-like catalytic activity, producing more reactive oxygen species (ROS) by photothermal therapy (PTT) and chemodynamic therapy (CDT), which enhances the antitumor efficacy of DOX and reduces the dosage of its chemotherapy (CT). Simultaneously, DOX increases intracellular hydrogen peroxide (H(2)O(2)) supplementation and promotes the sustained production of ROS. BPMN-CuS/DOX significantly inhibits melanoma both in vitro and in vivo by the combination of CDT, PTT, and CT. In short, our study significantly enhances the effectiveness of transdermal drug delivery by constructing BPMNs and provides a promising novel strategy for transdermal cancer treatment with multiple therapies. | Copper Sulfate |
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