title
stringlengths 0
1.91k
⌀ | abstract
stringlengths 0
17k
⌀ | keywords
stringlengths 0
7.81k
| source_name
stringclasses 6
values |
|---|---|---|---|
Neuregulin-1 improves right ventricular function and attenuates experimental pulmonary arterial hypertension. | Pulmonary arterial hypertension (PAH) is a serious disease that affects both the pulmonary vasculature and the right ventricle (RV). Current treatment options are insufficient. The cardiac neuregulin (NRG)-1/ErbB system is deregulated during heart failure, and treatment with recombinant human NRG-1 (rhNRG-1) has been shown to be beneficial in animal models and in patients with left ventricular (LV) dysfunction. This study aimed to evaluate the effects of rhNRG-1 in RV function and pulmonary vasculature in monocrotaline (MCT)-induced PAH and RV hypertrophy (RVH). Male wistar rats (7- to 8-weeks old, n = 78) were injected with MCT (60 mg/kg, s.c.) or saline and treated with rhNRG-1 (40 µg/kg/day) or vehicle for 1 week, starting 2 weeks after MCT administration. Another set of animals was submitted to pulmonary artery banding (PAB) or sham surgery, and followed the same protocol. MCT administration resulted in the development of PAH, pulmonary arterial and RV remodelling, and dysfunction, and increased RV markers of cardiac damage. Treatment with rhNRG-1 attenuated RVH, improved RV function, and decreased RV expression of disease markers. Moreover, rhNRG-1 decreased pulmonary vascular remodelling and attenuated MCT-induced endothelial dysfunction. The anti-remodelling effects of rhNRG-1 were confirmed in the PAB model, where rhNRG-1 treatment was able to attenuate PAB-induced RVH. rhNRG-1 treatment attenuates pulmonary arterial and RV remodelling, and dysfunction in a rat model of MCT-induced PAH and has direct anti-remodelling effects on the pressure-overloaded RV. | Cardiac hypertrophy;Endothelial dysfunction;Neuregulin;Pulmonary hypertension;Right ventricular function | pubmed |
Spoilage of vacuum-packed beef by the yeast Kazachstania psychrophila. | A survey of the psychrotolerant yeast microbiota of vacuum-packed beef was conducted between 2010 and 2012. Chilled vacuum-packed beef (n = 50) sampled from 15 different producers was found to have a mean psychrotolerant yeast count of 3.76 log cfu per cm(2). During this assessment, a recently described yeast named Kazachstania psychrophila was shown to be associated with this product. In order to gain basic knowledge about the spoilage potential of K. psychrophila in vacuum-packed beef, challenge studies were performed and the survival of three different K. psychrophila strains was analyzed during storage of artificially contaminated beef. Beef samples were inoculated with the yeasts at a contamination level of 2 log cfu per cm(2). Survival and growth of K. psychrophila strains was monitored on malt extract agar at regular intervals over 84 days. Kazachstania levels rapidly increased about 5 log units within 16 days under chill conditions (4 °C). Gas bubbles were observed after 16 days, while discoloration and production of off-flavors became evident after 42 days in inoculated samples. This study demonstrates for the first time, that the psychrotolerant yeast K. psychrophila is a dominant spoilage microorganism of vacuum-packed beef products stored at low temperatures, causing sensory defects which result in reduced shelf life, and consequently in considerable economic losses. | Beef microbiota;Food;Meat spoilage;Saccharomycetaceae | pubmed |
An Integrated Predictive Model of Population Serum 25-Hydroxyvitamin D for Application in Strategy Development for Vitamin D Deficiency Prevention. | To enable food-based strategies for the prevention of vitamin D deficiency to be evidence-based, there is a need to develop integrated predictive models of population serum 25-hydroxyvitamin D [25(OH)D] that are responsive to both solar and dietary inputs of vitamin D. The objectives of this work were to develop and validate an integrated mathematical model with the use of data on UVB availability, exposure, and dietary intake to predict serum 25(OH)D concentrations in a nationally representative sample of adults, and then test the model's performance with the use of 3 hypothetical fortification scenarios as exemplars. Data on UVB availability and hours of sunlight in Ireland were used in a mathematical model to predict serum 25(OH)D in Irish adults aged 18-64 y. An equation from our dose-related vitamin D supplementation trial in adults was developed and integrated into the model, which allowed us to predict the impact of changes in dietary vitamin D on the contribution to annual serum 25(OH)D concentrations, accounting for seasonality of UVB availability. Recently published estimates of the impact of 3 vitamin D food fortification scenarios on vitamin D intake in a representative sample of Irish adults were used in the model as a test. The UVB- and vitamin D intake-serum 25(OH)D components of the integrated model were both validated with the use of independent data. The model predicted that the percentage of vitamin D deficiency [serum 25(OH)D <30 nmol/L] in the adult population during an extended winter period was 18.1% (vs. 18.6% measured), which could be reduced in a stepwise manner with the incorporation of an increased number of vitamin D-fortified foods, down to 6.6% with the inclusion of enhanced fortified dairy-related products, fat spreads, fruit juice and drinks, and cereal products. Mathematical models have the ability to inform how vitamin D food fortification in various constructs may affect population serum 25(OH)D concentrations and the prevalence of vitamin D deficiency. | UVB;deficiency;food fortification;mathematical modeling;vitamin D | pubmed |
Simple observation of <i>Streptococcus mutans</i> biofilm by scanning electron microscopy using ionic liquids. | Scanning electron microscopy (SEM) has been successfully used to image biofilms because of its high resolution and magnification. However, conventional SEM requires dehydration and metal coating of biological samples before observation, and because biofilms consist mainly of water, sample dehydration may influence the biofilm structure. When coated with an ionic liquid, which is a kind of salt that exists in the liquid state at room temperature, biological samples for SEM observation do not require dehydration or metal coating because ionic liquids do not evaporate under vacuum conditions and are electrically conductive. This study investigates the ability of ionic liquids to allow SEM observation of <i>Streptococcus mutans</i> biofilms compared with conventional coating methods. Two hydrophilic and two hydrophobic ionic liquids, all of which are electronic conductors, are used. Compared with samples prepared by the conventional method, the ionic-liquid-treated samples do not exhibit a fibrous extracellular matrix structure and cracking on the biofilm surface. The hydrophilic ionic liquids give clearer images of the biofilm structure than those of the hydrophobic ionic liquids. This study finds that ionic liquids are useful for allowing the observation of biofilms by SEM without preparation by dehydration and metal coating. | Biofilm;Extracellular polymeric substance;Ionic liquid;Scanning electron microscopy;Streptococcus mutans | pubmed |
PIF direct immune regulation: Blocks mitogen-activated PBMCs proliferation, promotes TH2/TH1 bias, independent of Ca(2+). | PreImplantation Factor (PIF(9&15)) secreted by viable embryos exerts an essential transplant acceptance and immune regulatory role in pregnancy. Synthetic PIF replicates endogenous PIF's effect in pregnant and non-pregnant immune disorder models. PIF binds macrophages to regulate CD3/CD28-induced T-cell response. We present evidence that PIF regulates the co-stimulatory T-cell receptor, CD2, which binds to and is activated by phytohemagglutinin (PHA), a potent mitogen, confirming PIF's ability to systemically respond to diverse immune stimulants. PIF's effect on PHA-activated PBMC (male and non-pregnant females) proliferation and cytokine secretion was tested, showing that both PIF(9&15) block PHA-induced PBMC proliferation and promote anti-inflammatory IL10 secretion, while reducing pro-inflammatory IFNγ secretion. Thus favoring a T(H)2 cytokine bias. Surface plasmon resonance spectroscopy, immunocytochemistry and Flex station experiments reveal that PIF effect is direct. PIF targets intracellular targets but does not affect early Ca(2+) mobilization. By promoting the CD2 receptor in activated T-cells and through inhibition of co-ligand CD58 expression, PIF regulates antigen-presenting cell (APC)-T-cell interactions required for PHA action. Structure-based design demonstrated that PIF15 offers improved target specificity as compared to PIF9. Collectively, PIF directly regulates mitogen-induced PBMC activation. Results support PIF translation for therapy of immune disorders. | Direct effect;Embryo tolerance;PreImplantation Factor (PIF);Systemic immune regulation | pubmed |
Current smoking is associated with lower seminal vesicles and ejaculate volume, despite higher testosterone levels, in male subjects of infertile couples. | What is the impact of smoking behaviour on seminal, hormonal and male genital tract ultrasound parameters in subjects seeking medical care for couple infertility? In males of infertile couples, current smokers (CS), when compared with non-smokers, show lower ejaculate and ultrasound-derived seminal vesicles (SV) volume, despite higher testosterone levels. Data on the effects of smoking on male fertility are conflicting. A correlation between smoking and reduced semen parameters has been reported, however, with a high heterogeneity among studies. An association between smoking behaviour and higher testosterone levels in men has been described in several, but not all, the previous studies. No study has systematically evaluated the impact of smoking on the male genital tract ultrasound characteristics. Retrospective cross-sectional analysis of a consecutive series of 426 subjects seeking medical care for couple infertility from January 2010 to July 2013. From the entire cohort, 394 men (age 36.0 ± 8.0 years) free of genetic abnormalities were selected. All subjects underwent a complete andrological and physical examination, biochemical and hormonal assessment, scrotal and transrectal colour-Doppler ultrasound and semen analysis (including seminal interleukin-8 levels, sIL-8) within the same day. Among the patients evaluated, 229 were never smokers (NS), 56 past smokers (PS) and 109 CS. When CS were compared with the rest of the sample (non-smokers, NS + PS), in a multivariate model (analysis of covariance, ANCOVA) adjusted for age, lifestyle (including alcohol, cannabis and physical activity), BMI and sex hormone-binding globulin, significantly higher androgen (total testosterone, P = 0.001; calculated free testosterone, P < 0.005) and lower FSH (P < 0.05) levels were observed in CS. However, when total testosterone was also included in the multivariate model as a further covariate, the difference in FSH levels was not confirmed. In a similar model, a lower ejaculate volume (P < 0.01) and a higher prevalence of normal sperm morphology (P < 0.02) were also detected in CS in comparison with the rest of the sample. However, when total testosterone was also included in the multivariate model as a further covariate, only the difference in ejaculate volume between CS and non-smokers was confirmed (-0.61 ± 0.23 ml, P < 0.01). Finally, CS showed lower total SV volume, before and after ejaculation, even after adjusting for confounders (P = 0.02 and <0.01, respectively). Similar results were observed when the reported number of cigarettes smoked or the number of pack-years was considered separately. The present results are derived from patients consulting an Andrology Clinic for couple infertility, who could have different characteristics from the general male population or males consulting general practitioners for reasons other than couple infertility. In addition, we did not have a true control group composed of age-matched, apparently healthy, fertile men, and therefore true normative data of sonographic parameters cannot be inferred. Due to the cross-sectional nature of our study, neither a causality hypothesis nor mechanistic models can be drawn. Finally, this is a retrospective study, and further prospective studies are required. We report an apparent paradox in CS: lower SV volume despite higher testosterone levels. Our data suggest that smoking may negatively affect SV volume in an independent manner, as the difference between CS and non-smokers retained significance after adjusting for confounders including testosterone. This is the first study reporting such ultrasound evidence. How this new smoking-related alteration, along with low semen volume, impacts male fertility needs to be addressed by further studies. No funding was received for the study. None of the authors have any conflict of interest to declare. | ejaculate volume;infertile men;seminal vesicles;smoking;testosterone;ultrasound | pubmed |
Magnetic "Molecular Oligomers" Based on Decametallic Supertetrahedra: A Giant Mn49 Cuboctahedron and its Mn25Na4 Fragment. | Two nanosized Mn49 and Mn25Na4 clusters based on analogues of the high-spin (S=22) [Mn(III)6Mn(II)4(μ4-O)4](18+) supertetrahedral core are reported. Mn49 and Mn25Na4 complexes consist of eight and four decametallic supertetrahedral subunits, respectively, display high virtual symmetry (O(h)), and are unique examples of clusters based on a large number of tightly linked high nuclearity magnetic units. The complexes also have large spin ground-state values (Mn49: S=61/2; Mn25Na4: S=51/2) with the Mn49 cluster displaying single-molecule magnet (SMM) behavior and being the second largest reported homometallic SMM. | O ligands;cluster compounds;magnetic properties;manganese;single-molecule magnets | pubmed |
Development of risk perception and substance use of tobacco, alcohol and cannabis among adolescents and emerging adults: evidence of directional influences. | While several studies have investigated the relationship between risk perception and substance use, surprisingly little is known about mutual influences between both variables over time. The present study aimed to explore two different hypotheses separately for tobacco, alcohol and cannabis: influences from risk perception on behavior (motivational hypothesis) and influences from behavior on risk perception (risk reappraisal hypothesis). A prospective and longitudinal cross-lagged panel design was used with substance use and risk perception measured five times over the course of 10 years. Participants were 318 German youths aged 14-15 at the beginning of the study. Risk perception and substance use frequency were measured using self-reports. Structural equation modeling indicated significant influences of risk perception on substance use behavior for all substances, which supports the motivational hypothesis. Changes in risk perception predict changes in future substance use of tobacco, alcohol and cannabis. Specifically for cannabis, influences of substance use on risk perception can also be shown, thus, supporting the risk reappraisal hypothesis. While there is support for the rationale behind adequate risk perception as a goal of preventive interventions, the possibility of risk reappraisal should not be neglected, especially regarding illicit substances. | alcohol;cannabis;cross-lagged;longitudinal;risk perception;tobacco | pubmed |
The complete mitogenome of Fusarium culmorum. | The structure of the Fusarium culmorum mitogenome is similar to that of closely related Fusarium spp.: it has a total length of 103,844 bp, the base composition of the genome is the following: A (35.4%), T (32.9%), C (14.6%), and G (17.1%). The mitogenome contains 13 protein-coding genes, 2 ribosomal RNA (rRNA), and 28 transfer RNA (tRNA) genes, all coded on the same strand of DNA. The gene order is identical to that of the other Fusarium and Hypocreales mitogenomes. Maximum likelihood and Bayesian analysis based on the concatenated amino acid dataset of mitochondrial protein-coding genes confirmed close genetic relationship of F. culmorum to the other type B trichothecene producers F. graminearum and F. gerlachii. | Fungi;Fusarium culmorum;mitogenome | pubmed |
Growth and bone health in paediatric patients with Crohn's disease receiving subcutaneous tumor necrosis factor antibody. | To study whether adalimumab (ADA) was associated with improvement in growth, bone mineral density (BMD) and bone metabolism. In children with Crohn's disease (CD) there is a high prevalence of growth failure and reduced BMD. Treatment with infliximab is associated with an improvement in growth. Anthropometry, paediatric CD activity index (PCDAI), bone markers and BMD was measured in 18 patients (72% females) one year before and after start of ADA with a median age of 14.4 years (range: 5-19 years) at treatment start. Outcomes were indicators of growth with treatment as well as interval growth. Eleven (61%) children experienced catch-up growth after ADA. PCDAI significantly decreased from 52.1 ± 16 to 30.4 ± 23 (P ≤ 0.001). Post ADA, body mass index (BMI) standard deviation score (SDS) 0.1[range: 2.7-(-0.8)] vs -1 [range: 0.1-(-3.6)], P = 0.04 and ∆BMI SDS in children 0.3 [range: 0.7-(-0.2)] vs -1.1 [range: 1.2-(-2.3)], P = 0.01 in remission were significantly higher compared to those with moderate to severe inflammation. The main predictors for growth were 25-hydroxycholecalciferol and for bone mineralisation weight and height SDS. ADA had no significant influence on bone markers and BMD. Next to improvement of PCDAI, half of the children achieved a positive catch-up growth. A better nutritional status with improvement in BMI and weight is positive predictor for improved growth and bone mineralisation. | Adalimumab;Bone health;Crohn’s disease;Growth;Paediatrics | pubmed |
Fabrication of 2D Heterojunction in Graphene via Low Energy N2(+) Irradiation. | Substitutional doping in graphene is locally induced with very low energy nitrogen ions. Irradiated and nonirradiated areas exhibit different charge carrier densities and are separated by a sharp boundary, stable up to 750 °C. The way towards lithographic control of the electronic properties of graphene by ion irradiation is paved, providing a proof of principle for the fabrication of 2D graphene-based heterojunctions. | 2D circuits;graphene;heterojunctions;ion implantation;localized doping | pubmed |
Biothreat Reduction and Economic Development: The Case of Animal Husbandry in Central Asia. | Improving human welfare is a critical global concern, but not always easy to achieve. Complications in this regard have been faced by the states of the Former Soviet Union, where socialist-style economic institutions have disappeared, and the transition to a market economy has been slow in coming. Lack of capital, ethnic conflict, and political instability have at times undermined the institutional reform that would be necessary to enable economic efficiency and development. Nowhere are such challenges more pronounced than in the new nation states of central Asia, including Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. Here, a severe climate limits agriculture, and industrialization has been inhibited by lack of infrastructure, low levels of human capital, and a scarcity of financial resources. These conditions are aggravated by the fact that the central Asian states are landlocked, far from centers of market demand and capital availability. Despite these daunting barriers, development potential does exist, and the goal of the paper is to consider central Asia's pastoral economy, with a focus on Kazakhstan, which stands poised to become a regional growth pole. The article pursues its goal as follows. It first addresses the biothreat situation to central Asian livestock herds, the most significant existing impediment to realizing the full market potential of the region's animal products. Next, it provides an outline of interventions that can reduce risk levels for key biothreats impacting central Asia, namely foot and mouth disease (FMD), which greatly impacts livestock and prohibits export, and Brucellosis, a bacterial zoonosis with high incidence in both humans and livestock in the region. Included is an important success story involving the FMD eradication programs in Brazil, which enabled an export boom in beef. After this comes a description of the epidemiological situation in Kazakhstan; here, the article considers the role of wildlife in acting as a possible disease reservoir, which presents a conservation issue for the Kazakhstani case. This is followed by a discussion of the role of science in threat reduction, particularly with respect to the potential offered by geospatial technologies to improve our epidemiological knowledge base. The article concludes with an assessment of the research that would be necessary to identify feasible pathways to develop the economic potential of central Asian livestock production as changes in policy are implemented and livestock health improves. | biothreats;central Asia;conservation of natural resources;economic development;geospatial analysis | pubmed |
Auditory memory function in expert chess players. | Chess is a game that involves many aspects of high level cognition such as memory, attention, focus and problem solving. Long term practice of chess can improve cognition performances and behavioral skills. Auditory memory, as a kind of memory, can be influenced by strengthening processes following long term chess playing like other behavioral skills because of common processing pathways in the brain. The purpose of this study was to evaluate the auditory memory function of expert chess players using the Persian version of dichotic auditory-verbal memory test. The Persian version of dichotic auditory-verbal memory test was performed for 30 expert chess players aged 20-35 years and 30 non chess players who were matched by different conditions; the participants in both groups were randomly selected. The performance of the two groups was compared by independent samples t-test using SPSS version 21. The mean score of dichotic auditory-verbal memory test between the two groups, expert chess players and non-chess players, revealed a significant difference (p≤ 0.001). The difference between the ears scores for expert chess players (p= 0.023) and non-chess players (p= 0.013) was significant. Gender had no effect on the test results. Auditory memory function in expert chess players was significantly better compared to non-chess players. It seems that increased auditory memory function is related to strengthening cognitive performances due to playing chess for a long time. | Auditory Memory;Chess Players;Dichotic | pubmed |
Effects of substitution groups of glutamide-derived molecular gels on molecular shape recognition. | We have reported that self-assembling glutamide lipid-grafted porous silica particles show high selectivity towards polycyclic aromatic hydrocarbons (PAHs) and bio-molecules. This enhancement of molecular recognition is brought about by the formation of a highly ordered structure in the glutamide lipid through intermolecular hydrogen bonding. To utilise, for selective separations, the highly oriented structure of glutamide lipids on the silica surface, in this study, we synthesised four glutamide lipids with different substitution groups and studied the separation behaviours of the glutamide lipid-grafted porous silica particles as reversed phase high-performance liquid chromatography (RP-HPLC) stationary phases. According to the HPLC studies, the functional group substitutions and the spacer group connecting the glutamide moiety and silica surface had a noticeable effect on the retention behaviours. Particularly, glutamide lipids with a long spacer group (C10) showed a higher selectivity towards positional (o-/m-/p-terphenyl) and geometrical (cis-/trans-stilbene) isomers. Differential scanning calorimetric and Fourier transform infrared spectroscopic studies suggested that the long spacer group induced the assembled structure of the glutamide lipid on the silica surface. Interestingly, the glutamide lipids with dodecyl groups and benzyl groups showed reverse elution orders towards the length to breadth ratio of PAHs. | Molecular gel;Polycyclic aromatic hydrocarbons;Stationary phases, Liquid chromatography;π–π interaction | pubmed |
Complete mitochondrial genome of Drosophila albomicans. | Drosophila albomicans has been widely used as an important animal model for chromosome evolution. In this study, the mitochondrial genome sequence of this species is determined and described for the first time. The mitochondrial genome (15 849 bp) encompasses two rRNA, 22 tRNA, and 13 protein-coding genes. Genome content and structure are similar to those reported from other Drosophila mitochondrial genomes. Phylogeny analysis indicates that D. albomicans have a closer genetic relationship with Drosophil aincompta and Drosophil alittoralis. This mitochondrial genome is potentially important for studying molecular evolution and conservation genetics in Drosophila genus. | Chromosome evolution;Drosophila albomicans;mitogenome | pubmed |
Carnosine and vitamin E--a promising pair in the combat against testicular oxidative stress in aged rats. | Oxidative stress is considered to play a key role in ageing. Carnosine alone or together with vitamin E may prove to be helpful in dealing with problems of ageing through its antioxidant activity. Testis, by producing steroids and possessing a poor antioxidant system may become a strong target for the chronic oxidative stress generated during ageing. Therefore we investigated the in vivo effect of carnosine alone or together with vitamin E on testicular oxidative stress in aged rats. In this study, young (5 months) and aged (22 months) Wistar rats were used. Carnosine (250 mg kg(-1); i.p.; 5 days per week) and vitamin E (200 mg kg(-1); i.m.; twice per week) were given to aged rats for 2 months. Increased testicular lipid peroxidation and superoxide dismutase activity in aged rats were declined to the levels of young ones by both treatments. Decreased glutathione peroxidase and glutathione transferase activities returned to the level of young's only by carnosine plus vitamin E treatment. Histopathological evaluation described by Johnsen's score, also showed significant improvement with preserved spermatogenesis. Carnosine plus vitamin E treatment appears to stage a powerful performance by attenuating testicular oxidative stress and sparing the antioxidant system. | Aged rat;carnosine;testicular oxidative stress;vitamin E | pubmed |
Mapping cell populations in flow cytometry data for cross-sample comparison using the Friedman-Rafsky test statistic as a distance measure. | Flow cytometry (FCM) is a fluorescence-based single-cell experimental technology that is routinely applied in biomedical research for identifying cellular biomarkers of normal physiological responses and abnormal disease states. While many computational methods have been developed that focus on identifying cell populations in individual FCM samples, very few have addressed how the identified cell populations can be matched across samples for comparative analysis. This article presents FlowMap-FR, a novel method for cell population mapping across FCM samples. FlowMap-FR is based on the Friedman-Rafsky nonparametric test statistic (FR statistic), which quantifies the equivalence of multivariate distributions. As applied to FCM data by FlowMap-FR, the FR statistic objectively quantifies the similarity between cell populations based on the shapes, sizes, and positions of fluorescence data distributions in the multidimensional feature space. To test and evaluate the performance of FlowMap-FR, we simulated the kinds of biological and technical sample variations that are commonly observed in FCM data. The results show that FlowMap-FR is able to effectively identify equivalent cell populations between samples under scenarios of proportion differences and modest position shifts. As a statistical test, FlowMap-FR can be used to determine whether the expression of a cellular marker is statistically different between two cell populations, suggesting candidates for new cellular phenotypes by providing an objective statistical measure. In addition, FlowMap-FR can indicate situations in which inappropriate splitting or merging of cell populations has occurred during gating procedures. We compared the FR statistic with the symmetric version of Kullback-Leibler divergence measure used in a previous population matching method with both simulated and real data. The FR statistic outperforms the symmetric version of KL-distance in distinguishing equivalent from nonequivalent cell populations. FlowMap-FR was also employed as a distance metric to match cell populations delineated by manual gating across 30 FCM samples from a benchmark FlowCAP data set. An F-measure of 0.88 was obtained, indicating high precision and recall of the FR-based population matching results. FlowMap-FR has been implemented as a standalone R/Bioconductor package so that it can be easily incorporated into current FCM data analytical workflows. | Friedman-Rafsky test;cell population matching;cross-sample comparison;flow cytometry;minimum spanning tree;single-cell analysis | pubmed |
Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin. | Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model. | botulinum neurotoxin;combinatorial screening;epitope targeting;peptides;target-guided synthesis | pubmed |
Temporal and Spatial Analysis of the New World Screwworm (Cochliomyia hominivorax) in Darien and Embera, Panama (2001-2011). | Larvae (maggots) of Cochliomyia hominivorax, the New World Screwworm fly, are voracious consumers of living flesh that have a negative economic impact by decreasing productivity, predisposing to other pathogens, and, in severe cases, causing death of domestic livestock. Screwworm caused extensive financial losses to the livestock industry in North America prior to its eradication. Sterile insect technique (SIT) was used to eradicate screwworm throughout North and Central America and continues to be the main tool to control it in eastern Panama. The goal of this study was to evaluate the temporal and spatial trends of screwworm myiasis cases reported in the Province of Darien and Comarca Embera (border with Colombia), Panama, from 2001 to 2011. We hypothesized that screwworm cases would vary seasonally and be spatially clustered near Colombia as a result of effective eradication strategies in Panama and the presence of an autochthonous population of flies in western Colombia. Temporal and spatial data were retrieved from COPEG-USDA records (Panama) and analysed by anova, Ripley's K function, discrete Poisson spatial statistic scan and Getis-Ord Gi*. No significant temporal trend was found, but cases were spatially distributed in four clusters. One cluster of cases occurred from 2001 to 2003 and was considered a focal temporal and spatial cluster. One cluster occurred in 2001 and 2007 indicating more rare outbreaks in an area with fewer cattle. The two remaining clusters contained cases from 2004 to 2011 and 2001 to 2011 suggesting regular breaks in the control barrier due to occasional failures of the SIT programme, difficulties implementing border quarantine strategies, livestock smuggling or the movement of infested wildlife. | Panama;clustering;control;maggots;myiasis;screwworm | pubmed |
Alcohol and Difficulty Conceiving in the SUN Cohort: A Nested Case-Control Study. | The role of alcohol on fertility remains unclear. We aimed to investigate the association between alcohol and specific alcoholic beverages consumption and the risk of difficulty getting pregnant. We used a case-control study nested within the Seguimiento Universidad de Navarra (SUN) cohort, a prospective, dynamic and multipurpose cohort of 21,705 Spanish university graduates, followed biennially with mailed questionnaires. We identified 686 case-control pairs, matched for age and time in the cohort. Cases were women reporting difficulty getting pregnant. Controls did not consult due to difficulty conceiving and had at least one child during follow-up. After adjustment for potential confounders, we found no association between self-reported difficulty getting pregnant and the number of alcoholic beverages consumed per week, (Odds Ratio [OR] > 5 drinks/week vs. none = 1.04, 95% Confidence Interval [CI] = 0.72-1.51). No association between types of alcoholic beverage and difficulty conceiving (OR > 5 drinks of wine/week vs. none = 1.16, 95% CI = 0.72-1.88; OR > 5 drinks of beer/week vs. none = 1.06, 95% CI = 0.82-1.37; OR > 5 drinks of spirits/week vs. none = 1.24, 95% CI = 0.84-1.64) was observed. In conclusion, we found no association between alcohol intake and risk of consulting a physician due to difficulty conceiving. More studies are needed to clearly elucidate the effects of alcohol intake on women's fertility. In the meantime, recommendations about alcohol intake to couples trying to conceive have to be given cautiously. | alcohol;beer;diet;fertility;nested case-control study;wine | pubmed |
Protein production by <i>Arthrospira</i> (<i>Spirulina</i>) <i>platensis</i> in solid state cultivation using sugarcane bagasse as support. | The genus <i>Arthrospira</i> comprises a group of filamentous multicellular cyanobacteria and can be used for animal feed and human food. Solid state fermentation or cultivation (SSF) involves the use of a culture medium composed of solid material with given moisture content. No studies have been published about the cultivation of microalgae or cyanobacteria on solid medium. Furthermore, although sugar-cane bagasse is used as source of energy in alcohol distilleries in Brazil, the excess could be a support to photosynthetic microorganism growth. The experimental design methodology was used to evaluate the protein production by <i>Arthrospira platensis</i> under SSF using sugarcane bagasse as support, taking into account the moisture content of the medium, light intensity and inoculum concentration. Moisture was found to have a strong influence on the performance of the process. The best conditions were: moisture of 98.8%; inoculum concentration of 0.15 g biomass·kg wet culture medium<sup>-1</sup> and light intensity of 6.0 klx. | Arthrospira (Spirulina) platensis;Experimental design;Solid state cultivation;Sugarcane bagasse | pubmed |
Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy. | The presence of senile plaques is one of the major pathologic hallmarks of the brain with Alzheimer's disease (AD). The plaques predominantly contain insoluble amyloid β-peptide, a cleavage product of the larger amyloid precursor protein (APP). Two enzymes, named β and γ secretase, generate the neurotoxic amyloid-β peptide from APP. Mature APP is also turned over endogenously by autophagy, more specifically by the endosomal-lysosomal pathway. A defective lysosomal system is known to be pathogenic in AD. Modulation of NF-E2 related factor 2 (Nrf2) has been shown in several neurodegenerative disorders, and Nrf2 has become a potential therapeutic target for various neurodegenerative disorders, including AD, Parkinson's disease, and amyotrophic lateral sclerosis. In the current study, we explored the effect of genetic ablation of Nrf2 on APP/Aβ processing and/or aggregation as well as changes in autophagic dysfunction in APP/PS1 mice. There was a significant increase in inflammatory response in APP/PS1 mice lacking Nrf2. This was accompanied by increased intracellular levels of APP, Aβ (1-42), and Aβ (1-40), without a change total full-length APP. There was a shift of APP and Aβ into the insoluble fraction, as well as increased poly-ubiquitin conjugated proteins in mice lacking Nrf2. APP/PS1-mediated autophagic dysfunction is also enhanced in Nrf2-deficient mice. Finally, neurons in the APP/PS1/Nrf2-/- mice had increased accumulation of multivesicular bodies, endosomes, and lysosomes. These outcomes provide a better understanding of the role of Nrf2 in modulating autophagy in an AD mouse model and may help design better Nrf2 targeted therapeutics that could be efficacious in the treatment of AD. | Amyloid precursor protein (APP);Amyloid β peptide;Autophagy;mTOR pathway;p62/SQSTM | pubmed |
Flow Effects on the Controlled Growth of Nanostructured Networks at Microcapillary Walls for Applications in Continuous Flow Reactions. | Low-cost microfluidic devices are desirable for many chemical processes; however, access to robust, inert, and appropriately structured materials for the inner channel wall is severely limited. Here, the shear force within confined microchannels was tuned through control of reactant solution fluid-flow and shown to dramatically impact nano- through microstructure growth. Combined use of experimental results and simulations allowed controlled growth of 3D networked Zn(OH)F nanostructures with uniform pore distributions and large fluid contact areas on inner microchannel walls. These attributes facilitated subsequent preparation of uniformly distributed Pd and PdPt networks with high structural and chemical stability using a facile, in situ conversion method. The advantageous properties of the microchannel based catalytic system were demonstrated using microwave-assisted continuous-flow coupling as a representative reaction. High conversion rates and good recyclability were obtained. Controlling materials nanostructure via fluid-flow-enhanced growth affords a general strategy to optimize the structure of an inner microchannel wall for desired attributes. The approach provides a promising pathway toward versatile, high-performance, and low-cost microfluidic devices for continuous-flow chemical processes. | 3D networks;flow chemistry;microfluidic reactions;shear stress | pubmed |
Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart. | Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2(+) CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2(+) CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2(+) CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRα, ISL1, or WT1. W8B2(+) CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2(+) CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2(+) CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (∼40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2(+) CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67(+) cTnT(+) cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163(+) cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2(+) CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction. | Adult stem cells;Heart;Mesenchymal stem cell;Myocardial infarction;W8B2 | pubmed |
Coffee bean polyphenols ameliorate postprandial endothelial dysfunction in healthy male adults. | To reveal the effect of coffee bean polyphenols (CBPs) on blood vessels, this study aimed to investigate the effect of CBPs on acute postprandial endothelial dysfunction. Thirteen healthy non-diabetic men (mean age, 44.9 ± 1.4 years) consumed a test beverage (active: containing CBPs, placebo: no CBPs) before a 554-kcal test meal containing 14 g of protein, 30 g of fat and 58 g of carbohydrates. Then, a crossover analysis was performed to investigate the time-dependent changes in flow-mediated dilation (FMD) in the brachial artery. In the active group, the postprandial impairment of FMD was significantly improved, the two-hour postprandial nitric oxide metabolite levels were significantly increased and the six-hour postprandial urinary 8-epi-prostaglandin F2α levels were significantly reduced compared to the placebo group. The test meal increased the levels of blood glucose, insulin and triglycerides in both groups with no significant intergroup differences. These findings indicate that CBPs intake ameliorates postprandial endothelial dysfunction in healthy men. | Chlorogenic acid;coffee;endothelial function;flow-mediated dilation;nitric oxide;polyphenol | pubmed |
Artificial oocyte activation: evidence for clinical readiness. | Artificial oocyte activation using Ca(2+)ionophores or similar compounds is a widely applied technique in IVF laboratories. This is all the more interesting as most of the agents aiming for intracellular Ca(2+) increase do not result in physiological Ca(2+) oscillations but much rather cause a single Ca(2+) transient. Two observations from mammals may explain why a rather non-physiological single Ca(2+) peak caused by ionophores is sufficient to rescue cycles showing severe male factor infertility, deficient oocyte maturation, developmental problems in humans, or both. On the one hand, it has been shown that it is mainly the initial Ca(2+) rise that drives further downstream events, in particular calcium/calmodulin-dependent protein kinase II (CaMKII) action, and on the other, it is possible that this enzyme remains active even in the absence of Ca(2+). It therefore seems that mammalian oocytes can respond to a wide range of intracellular Ca(2+) signals and have a surprisingly high degree of tolerance for changes in cytosolic Ca(2+). As epigenetic consequences or differences in gene expression have not been studied to date, artificial oocyte activation has to be considered as experimental and should only be applied with a proper indication. | ICSI;artificial oocyte activation;ionophore | pubmed |
Pipeline embolization device thrombosis induced peri-construct collateral channels. | More than half a decade of experience and follow-up has now been accumulated with regard to flow diversion as a treatment for intracranial aneurysms; however, many uncertainties, such as the nature of aneurysmal remnants and the meaning of non-regressed, non-perfused aneurysmal masses, are still unknown. Here we discuss a 22-year-old man who presented with a grade 1 subarachnoid hemorrhage secondary to a dissecting right anterior cerebral artery aneurysm who was subsequently treated with a Pipeline Embolization Device construct. After ceasing dual antiplatelet therapy himself, he was found on MRI to have an area of increased aneurysmal remnant reperfusion. This was found to connect to multiple channels which reconstituted flow within the distal construct on angiography. The central area of construct thrombosis could not be visualized on MRI. The finding suggests that non-opacified aneurysmal remnants that have not regressed are biologically active and raises concerns regarding using MRI for long term follow-up. | Aneurysm;Angiography;Blood Flow;Flow Diverter;MRI | pubmed |
Animal models of obsessive-compulsive disorder: utility and limitations. | Obsessive-compulsive disorder (OCD) is a disabling and common neuropsychiatric condition of poorly known etiology. Many attempts have been made in the last few years to develop animal models of OCD with the aim of clarifying the genetic, neurochemical, and neuroanatomical basis of the disorder, as well as of developing novel pharmacological and neurosurgical treatments that may help to improve the prognosis of the illness. The latter goal is particularly important given that around 40% of patients with OCD do not respond to currently available therapies. This article summarizes strengths and limitations of the leading animal models of OCD including genetic, pharmacologically induced, behavioral manipulation-based, and neurodevelopmental models according to their face, construct, and predictive validity. On the basis of this evaluation, we discuss that currently labeled "animal models of OCD" should be regarded not as models of OCD but, rather, as animal models of different psychopathological processes, such as compulsivity, stereotypy, or perseverance, that are present not only in OCD but also in other psychiatric or neurological disorders. Animal models might constitute a challenging approach to study the neural and genetic mechanism of these phenomena from a trans-diagnostic perspective. Animal models are also of particular interest as tools for developing new therapeutic options for OCD, with the greatest convergence focusing on the glutamatergic system, the role of ovarian and related hormones, and the exploration of new potential targets for deep brain stimulation. Finally, future research on neurocognitive deficits associated with OCD through the use of analogous animal tasks could also provide a genuine opportunity to disentangle the complex etiology of the disorder. | behavioral model;compulsivity;genetic model;obsessive-compulsive disorder (OCD);perseverance;pharmacological model | pubmed |
Decreased visceral fat area correlates with improved arterial stiffness after Roux-en-Y gastric bypass in Chinese obese patients with type 2 diabetes mellitus: a 12-month follow-up. | Associations between demographic data and arterial stiffness have not been examined adequately in Chinese obese patients with type 2 diabetes (T2DM) who underwent Roux-en-Y gastric bypass (RYGB). This study was designed to examine changes in body fat distribution and metabolic parameters after RYGB and whether these changes correlated with improved arterial stiffness. The study was performed at the authors' academic university-affiliated hospital. A retrospective review of 42 Chinese patients with a diagnosis of obesity and T2DM and 22 health controls was conducted, focusing on metabolic outcomes and aortic pulse wave velocity (PWV) before and 12 months after RYGB. At baseline, PWV in the study group was significantly greater than in the control group (6.9±1.5 versus 5.8±.6 ms, respectively; P<.01). PWV was negatively correlated with age, systolic blood pressure, diastolic blood pressure, visceral fat area (VFA), and leptin level (r = .47, P<.01; r = .39, P<.01; r = .31, P = .03; r = .47, P<.01; and r = .30, P = .03, respectively). Multiple stepwise regression found that age and VFA were independently associated with PWV (β = .40, P<.01; β = .30, P = .02, respectively). PWV, body mass index, VFA, and metabolic profiles all improved significantly 12 months after RYGB. The change in PWV was positively correlated with changes in VFA and the leptin level (r = .40, P = .03; r = .40, P = .02, respectively). Decreased VFA resulting from RYGB correlated with improved arterial stiffness in obese Chinese patients with T2DM. Leptin might be an important factor linking PWV and visceral fat accumulation. | Gastric bypass;Intra-abdominal fat;Leptin;Obesity;Vascular stiffness | pubmed |
Characterization of phenotypic and genotypic drug resistance patterns of Mycobacterium tuberculosis isolates from a city in Mexico. | The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains has become a worldwide health care problem, making treatment of tuberculosis difficult. The aim of this study was to determine phenotypic resistance and gene mutations associated with MDR of clinical isolates of Mycobacterium tuberculosis from Guadalajara, Mexico. One hundred and five isolates were subjected to drug susceptibility testing to first line drugs using the proportion and Mycobacteria Growth Indicator Tube (MGIT) methods. Genes associated with isoniazid (inhA, katG, ahpC) and rifampicin (rpoB) resistance were analyzed by either pyrosequencing or PCR-RFLP. Resistance to any drug was detected in 48.6% of isolates, of which 40% were isoniazid-resistant, 20% were rifampicin-resistant and 19% were MDR. Drug-resistant isolates had the following frequency of mutations in rpoB (48%), katG (14%), inhA (26%), ahpC (26%). Susceptible isolates also had a mutation in ahpC (29%). This is the first analysis of mutations associated with MDR of M. tuberculosis in Guadalajara. Commonly reported mutations worldwide were found in rpoB, katG and inhA genes. Substitution C to T in position -15 of the ahpC gene may possibly be a polymorphism. | Isoniazid;Isoniazida;Multidrug-resistant;Multifarmacorresistente;Mutación;Mutation;Mycobacterium tuberculosis;Rifampicin;Rifampicina | pubmed |
The multigene families of actinoporins (part I): Isoforms and genetic structure. | Actinoporins are basic pore-forming proteins produced by sea anemones, with molecular weight around 20 kDa showing high affinity for sphingomyelin-containing membranes. Most sea anemones produce more than one actinoporin isoform differing in isoelectric point, molecular weigth and cytolytic activity. Examples of sea anemones with actinoporin isoforms are: Actinia equina with at least five isoform genes; Actinia tenebrosa, three isoforms; Actinia fragacea, five isoforms; Actineria villosa, Phyllodiscus semoni, Stichodactyla helianthus and Oulactis orientalis, with two isoforms each one, and Heteractis crispa with twenty-four isoforms. Additionally, thirty-four different amino acid sequences were deduced from fifty-two nucleotide sequences of Heteractis magnifica toxins suggesting the presence of a large number of isoforms or allelic variants. Many amino acidic changes in the isoforms are located in important regions for pore formation. The genetic structure of actinoporins comprises a pre-propeptide and a mature toxin region; therefore, actinoporins could be synthetized in the Golgi apparatus as precursor forms. The subsequent maturation of the toxins involves a proteolytic processing during secretion. Here we hypothesize that sea anemones could have suffered duplication, conversion and mutation of genes that produced multigene families as an efficient response to evolutionary pressure, leading to successful strategies of predatory and defensive function. | Actinoporins;Isoforms;Multigene-families;Pore-forming toxin | pubmed |
Characteristics and outcomes of women veterans undergoing cardiac catheterization in the Veterans Affairs Healthcare System: insights from the VA CART Program. | The number of women veterans is increasing, yet little is known about their cardiovascular risk factors, coronary anatomy, cardiac treatments, and outcomes after cardiac catheterization. Prior studies have shown that nonveteran women have more risk factors, receive less aggressive treatment, and have worse outcomes, despite having less obstructive coronary artery disease than men. Whether these differences exist among women veterans in the veterans affairs healthcare system is unknown. Data on 85 936 veterans (3181 women) undergoing initial cardiac catheterization between October 1, 2007, and September 30, 2012, were examined using the national veterans affairs Clinical Assessment Reporting and Tracking (CART) Program. Sex differences in demographics, indications, coronary anatomy, cardiac treatments, and outcomes were analyzed. Women veterans were younger (56.9 versus 63.0 years, P<0.0001) with fewer traditional cardiovascular risk factors, but with more obesity, depression, and posttraumatic stress disorder than men. Women had lower rates of obstructive coronary artery disease than men (22.6% versus 53.3%). Rates of procedural complications were similar in both genders. Adjusted outcomes at 1 year showed women had lower mortality (hazard ratio, 0.74; confidence interval, 0.60-0.92) and less all-cause rehospitalization (hazard ratio, 0.87; confidence interval, 0.82-0.93), but no difference in rates of unplanned percutaneous coronary intervention. Women veterans undergoing catheterization are younger, have more obesity, depression, and posttraumatic stress disorder, less obstructive coronary artery disease, and similar long-term outcomes, compared with men. These findings suggest a significant portion of women veterans may have chest pain not attributable to obstructive coronary artery disease. Further research into possible causes, such as endothelial dysfunction or concurrent psychological comorbidities, is needed. | cardiac catheterization;coronary artery disease;outcomes research;sex;women | pubmed |
Hydroxyapatite-titanium bulk composites for bone tissue engineering applications. | The research work on bulk hydroxyapatite (HA)-based composites are driven by the need to develop biomaterials with better mechanical properties without compromising its bioactivity and biocompatibility properties. Despite several years of research, the mechanical properties of the HA-based composites still need to be enhanced to match the properties of natural cortical bone. In this regard, the scope of this review on the HA-based bulk biomaterials is limited to the processing and the mechanical as well as biocompatibility properties for bone tissue engineering applications of a model system that is hydroxyapatite-titanium (HA-Ti) bulk composites. It will be discussed in this review how HA-Ti based bulk composites can be processed to have better fracture toughness and strength without compromising biocompatibility. The advantages of the functionally gradient materials to integrate the mechanical and biocompatibility properties is a promising approach in hard tissue engineering and has been emphasized here in reference to the limited literature reports. On the biomaterials fabrication aspect, the recent results are discussed to demonstrate that advanced manufacturing techniques, like spark plasma sintering can be adopted as a processing route to restrict the sintering reactions, while enhancing the mechanical properties. Various toughening mechanisms related to careful tailoring of microstructure are discussed. The in vitro cytocompatibilty, cell fate processes as well as in vivo biocompatibility results are also reviewed and the use of flow cytometry to quantify in vitro cell fate processes is being emphasized. | biocompatibility;composite;fracture toughness;hydroxyapatite;titanium | pubmed |
MAN1B1 Mutation Leads to a Recognizable Phenotype: A Case Report and Future Prospects. | Intellectual disability (ID) is one of the most common reasons for referral to genetic counseling. Nevertheless, in over 50% of the cases no diagnosis can be made. Here, we present how exome sequencing in combination with medical genetics evaluation led to the identification of a known pathogenic homozygous mutation in MAN1B1 in a consanguineous Turkish family. The phenotype comprised mild ID, truncal obesity and facial dysmorphism, comparable to that of the patients in the 3 recent publications on mutations in this gene. Clinically, the majority of patients in the literature showed congenital disorder of glycosylation syndrome type 2. In this study, we summarize the current knowledge about MAN1B1 mutations from the literature as well as databases and suggest that exome sequencing should be implemented in a larger scale in routine diagnostics, since autosomal recessive ID has proven to be extremely heterogeneous. Even syndromic patterns may only become recognizable retrospectively. | CDG syndrome;Intellectual disability;MAN1B1;Mental retardation | pubmed |
Auraptene consolidates memory, reverses scopolamine-disrupted memory in passive avoidance task, and ameliorates retention deficits in mice. | Auraptene (7-geranyloxycoumarin) (AUR), from Citrus species has shown anti-inflammatory, neuroprotective, and acetylcholinesterase (AChE) and beta-secretase inhibitory effects. Scopolamine is a nonselective muscarinic receptor antagonist which causes short-term memory impairments and is used for inducing animal model of Alzheimer's disease (AD). This research aimed to investigate the effect of AUR on scopolamine-induced avoidance memory retention deficits in step-through task in mice. The effect of four-day pre-training injections of AUR (50, 75, and 100 mg/kg, subcutaneous (SC)) and scopolamine (1 mg/kg, IP), and their co-administration on avoidance memory retention in step-through passive avoidance task, was investigated by measuring the latency to enter to the dark chamber. Pre-training administration of AUR caused significant increase in step-through latency in comparison with control group, 48, 96, and 168 hr after training trial. The findings of this study showed that scopolamine (1 mg/kg, IP, for four consecutive days) impaired passive avoidance memory retention compared to saline-treated animals. Step-through passive avoidance task results showed that AUR markedly reversed scopolamine-induced avoidance memory retention impairments, 24 and 168 hr after training trial in step-through task. Results from co-administration of AUR and scopolamine showed that AUR reversed scopolamine-induced passive avoidance memory retention impairments. | Auraptene;Avoidance memory retention;Mice;Scopolamine;Shuttle box | pubmed |
The Sensitivity to Change and Responsiveness of the Adult Responses to Children's Symptoms in Children and Adolescents With Chronic Pain. | To examine the sensitivity to change and responsiveness of the Adult Responses to Children's Symptoms (ARCS) among parents of youth with chronic pain. Participants included 330 youth (89 children aged 7-11 years, 241 children aged 12-17 years) and their parents who participated in randomized controlled trials of family-based cognitive-behavioral therapy for chronic pain. Child pain and disability, parental emotional functioning, and parental responses to child pain were assessed at baseline and posttreatment. The Protect and Monitor scales of the ARCS were sensitive to change following intervention for both developmental groups, with clinically meaningful reductions in these behaviors, thereby demonstrating responsiveness. Among the adolescent sample, greater change on some ARCS scales was associated with better parental emotional functioning and lower child pain at posttreatment. Findings support the sensitivity to change and responsiveness of the Protect and Monitor scales among parents of youth with chronic pain. | ARCS;adolescents;children;chronic pain;monitor;parental responses;pediatric pain;protect. | pubmed |
A constructivist theoretical proposition of cultural competence development in nursing. | Cultural competence development in healthcare professions is considered an essential condition to promote quality and equity in healthcare. Even if cultural competence has been recognized as continuous, evolutionary, dynamic, and developmental by most researchers, current models of cultural competence fail to present developmental levels of this competence. These models have also been criticized for their essentialist perspective of culture and their limited application to competency-based approach programs. To our knowledge, there have been no published studies, from a constructivist perspective, of the processes involved in the development of cultural competence among nurses and undergraduate student nurses. The purpose of this study was to develop a theoretical proposition of cultural competence development in nursing from a constructivist perspective. We used a grounded theory design to study cultural competence development among nurses and student nurses in a healthcare center located in a culturally diverse urban area. Data collection involved participant observation and semi-structured interviews with 24 participants (13 nurses and 11 students) working in three community health settings. The core category, 'learning to bring the different realities together to provide effective care in a culturally diverse context', was constructed using inductive qualitative data analysis. This core category encompasses three dimensions of cultural competence: 'building a relationship with the other', 'working outside the usual practice framework', and 'reinventing practice in action.' The resulting model describes the concurrent evolution of these three dimensions at three different levels of cultural competence development. This study reveals that clinical experience and interactions between students or nurses and their environment both contribute significantly to cultural competence development. The resulting theoretical proposition of cultural competence development could be used not only to guide initial and continuing nursing education, but also to help redefine quality of care in a culturally diverse context. | Competence development model;Constructivism;Cultural competence;Grounded theory;Nursing education;Qualitative data analysis | pubmed |
Protocol of a cluster randomized trial evaluation of a patient and carer-centered system of longer-term stroke care (LoTS care). | Despite recognition of the importance of the longer-term consequences of stroke, services addressing these needs remain poorly developed. There are persuasive arguments that a community-based orientation to poststroke care, to assess, support, and coordinate relevant services, might be more helpful in minimizing longer-term stroke morbidity. To address this, an evidence-based system of care has been developed that aims to meet the longer-term needs for stroke survivors and their carers living at home in the community. The study aims to evaluate the clinical and cost-effectiveness of a purposely developed system of care for stroke patients and their carers living in the community. This is a cluster randomized, controlled trial. The trial aimed to recruit 800 patients (and their carers, if appropriate) in 32 stroke services across the United Kingdom. The system of care is delivered by health professionals undertaking a community-based liaison or coordinating role for stroke patients (termed 'stroke care coordinators'). Stroke care coordinators in stroke services randomized to the intervention group were trained to deliver the system of care, while those randomised to the control group continued to deliver current practice. The primary outcome is patient emotional health measured using the General Health Questionnaire 12 at six-months after recruitment. Secondary outcomes include cost-effectiveness, patient functional health and carer emotional health, with final follow-up at 12 months. Thirty-two stroke services were randomized and 800 patients and 208 carers were recruited from 29 services. Follow-up is ongoing, and trial results are expected in early 2013. | community;longer-term;rehabilitation;stroke | pubmed |
Spleen Tyrosine Kinase (Syk) Mediates IL-1β Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection. | Approximately 500,000 people are hospitalized with severe dengue illness annually. Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is believed to contribute to the pathogenic cytokine storm described in severe dengue patients, but the precise signaling pathways contributing to elevated cytokine production are not elucidated. IL-1β is a potent inflammatory cytokine that is frequently elevated during severe dengue, and the unique dual regulation of IL-1β provides an informative model to study ADE-induced cytokines. This work utilizes patient-derived anti-DENV mAbs and primary human monocytes to study ADE-induced IL-1β and other cytokines. ADE of DENV serotype 2 (DENV-2) elevates mature IL-1β secretion by monocytes independent of DENV replication by 4 h postinoculation (hpi). Prior to this, DENV immune complexes activate spleen tyrosine kinase (Syk) within 1 hpi. Syk induces elevated IL1B, TNF, and IL6 mRNA by 2 hpi. Syk mediates elevated IL-1β secretion by activating ERK1/2, and both Syk and ERK1/2 inhibitors ablated ADE-induced IL-1β secretion. Maturation of pro-IL-1β during ADE requires caspase-1 and NLRP3, but caspase-1 is suboptimally increased by ADE and can be significantly enhanced by a typical inflammasome agonist, ATP. Importantly, this inflammatory Syk-ERK signaling axis requires DENV immune complexes, because DENV-2 in the presence of serotype-matched anti-DENV-2 mAb, but not anti-DENV-1 mAb, activates Syk, ERK, and IL-1β secretion. This study provides evidence that DENV-2 immune complexes activate Syk to mediate elevated expression of inflammatory cytokines. Syk and ERK may serve as new therapeutic targets for interfering with ADE-induced cytokine expression during severe dengue. | Fc-gamma receptor;caspase 1 (CASP1);cytokine induction;extracellular signal-regulated kinase (ERK);flavivirus;inflammasome;innate immunity;interleukin 1 (IL-1);monocyte;spleen tyrosine kinase (Syk) | pubmed |
In vitro functional response of human tendon cells to different dosages of low-frequency pulsed electromagnetic field. | Chronic tendinopathy is a degenerative process causing pain and disability. Current treatments include biophysical therapies, such as pulsed electromagnetic fields (PEMF). The aim of this study was to compare, for the first time, the functional in vitro response of human tendon cells to different dosages of PEMF, varying in field intensity and duration and number of exposures. Tendon cells, isolated from human semitendinosus and gracilis tendons (hTCs; n = 6), were exposed to different PEMF treatments (1.5 or 3 mT for 8 or 12 h, single or repeated treatments). Scleraxis (SCX), COL1A1, COL3A1 and vascular endothelial growth factor-A (VEGF-A) expression and cytokine production were assessed. None of the different dosages provoked apoptotic events. Proliferation of hTCs was enhanced by all treatments, whereas only 3 mT-PEMF treatment increased cell viability. However, the single 1.5 mT-PEMF treatment elicited the highest up-regulation of SCX, VEGF-A and COL1A1 expression, and it significantly reduced COL3A1 expression with respect to untreated cells. The treated hTCs showed a significantly higher release of IL-1β, IL-6, IL-10 and TGF-β. Interestingly, the repeated 1.5 mT-PEMF significantly further increased IL-10 production. 1.5 mT-PEMF treatment was able to give the best results in in vitro healthy human tendon cell culture. Although the clinical relevance is not direct, this investigation should be considered an attempt to clarify the effect of different PEMF protocols on tendon cells, in particular focusing on the potential applicability of this cell source for regenerative medicine purpose, both in surgical and in conservative treatment for tendon disorders. | Anti-inflammatory action;Human tendon cells;PEMF dosage;Pulsed electromagnetic field;Tendon markers | pubmed |
Allogeneic hematopoietic stem cell transplantation for non-malignant hematological disorders. | Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a geno-identical matched sibling (MSD) is one of the most successful therapies in patients with non-malignant hematological disorders. This study included 273 patients with severe aplastic anemia (SAA), 152 patients with B-Thalassemia major (BTM), 31 patients with Fanconi's anemia (FA), 20 patients with congenital immunodeficiency diseases (ID), and 13 patients with inherited metabolic disorders (IMD) allografted from a MSD. In SAA, the 8-year overall survival (OS) of the whole group patients was 74%. OS was significantly better in patients conditioned with fludarabine and cyclophosphamide (Flu/Cy) than in those who received cyclophosphamide and antithymocyte globulin (Cy/ATG) (p = 0.021). Acute graft-versus-host disease (aGVHD) grade II-IV occurred in 15% while chronic GVHD (cGVHD) occurred in 28%. In BTM, the 12-year disease-free survival (DFS) of the whole group of BTM patients was 72.4%. DFS was 74% for peripheral blood stem cell (PBSC) group compared to 64% in the BM stem cell group. The incidence of graft rejection was significantly lower in patients who received PBSC than in those who received BM (9% vs 25%) (p = 0.036). AGVHD grade II-IV and cGVHD occurred in 15% and 12% of the whole group of BTM patients respectively. In FA, the 5-year OS was 64.5%. Graft rejection occurred in 10% of patients. Grade II-IV aGVHD occurred in 16% while cGVHD occurred in 4%. In ID, the 5-year OS was 62%. Graft rejection occurred in two (10%) patients. Three patients (15%) developed grade II-IV aGVHD, 2 of them progressed to secondary cGVHD. In IMD, OS was 46% at 5 years. Graft rejection occurred in 8% of patients. AGVHD grade II-IV occurred in 15% while cGVHD occurred in 14%. In conclusion, Allo-HSCT provides a higher DFS rate over conventional therapies for patients with non-malignant hematological disorders with prolonged survival. | B-thalassemia major;Fanconi’s anemia;Hematopoietic stem cell transplantation;Immunodeficiency diseases;Inherited metabolic disorders | pubmed |
In cellulo phosphorylation of XRCC4 Ser320 by DNA-PK induced by DNA damage. | XRCC4 is a protein associated with DNA Ligase IV, which is thought to join two DNA ends at the final step of DNA double-strand break repair through non-homologous end joining. In response to treatment with ionizing radiation or DNA damaging agents, XRCC4 undergoes DNA-PK-dependent phosphorylation. Furthermore, Ser260 and Ser320 (or Ser318 in alternatively spliced form) of XRCC4 were identified as the major phosphorylation sites by purified DNA-PK in vitro through mass spectrometry. However, it has not been clear whether these sites are phosphorylated in vivo in response to DNA damage. In the present study, we generated an antibody that reacts with XRCC4 phosphorylated at Ser320 and examined in cellulo phosphorylation status of XRCC4 Ser320. The phosphorylation of XRCC4 Ser320 was induced by γ-ray irradiation and treatment with Zeocin. The phosphorylation of XRCC4 Ser320 was detected even after 1 Gy irradiation and increased in a manner dependent on radiation dose. The phosphorylation was observed immediately after irradiation and remained mostly unchanged for up to 4 h. The phosphorylation was inhibited by DNA-PK inhibitor NU7441 and was undetectable in DNA-PKcs-deficient cells, indicating that the phosphorylation was mainly mediated by DNA-PK. These results suggested potential usefulness of the phosphorylation status of XRCC4 Ser320 as an indicator of DNA-PK functionality in living cells. | DNA double-strand break repair;DNA-dependent protein kinase (DNA-PK);XRCC4;non-homologous end joining (NHEJ);phosphorylation | pubmed |
Effect of body condition and season on yield and quality of in vitro produced bovine embryos. | The aim of our study was to examine the effects of cow's body condition score (BCS; scale 1-5) and season on the quality of bovine in vitro produced embryos. The proportion of good quality oocytes (Q1 and Q2) was higher (P < 0.05) in the BCS 2 (57.60%) and BCS 3 (60.90%) groups compared with the BCS 1 (43.60%) group. There were no statistical differences in embryo cleavage and blastocyst rate among the BCS groups. The highest total cell number (TCN, DAPI stain) of blastocysts (P < 0.05), recorded in BCS 1 (122.27 ± 6.90) in comparison with BCS 2 (101.8 ± 3.60) or BCS 3 (105.44 ± 3.70) groups, was related to higher dead cell (DCI, TUNEL) index in this group (7.07%) when compared with BCS 2 (6.54%) or BCS 3 (6.06%), respectively. The yield of good quality oocytes during spring was lower (P < 0.05) compared with the summer season. There were significant differences (P < 0.05) in maturation and cleavage rates between autumn and summer (73.42%, 76.2% vs. 85.0%, 41.8%, respectively). The highest (P < 0.01) blastocyst rate was noted during spring and summer months. Significant difference (P < 0.05) in the TCN among spring (99.38 ± 3.90), autumn (110.1 ± 4.58) or summer (108.96 ± 3.52) was observed. The highest proportion of embryos with the best (grade I) actin cytoskeleton (phalloidin-TRITC) quality was noted during the summer months. Our results indicate that body condition affects the initial quality of oocytes, but does not affect embryo cleavage, blastocyst rate and actin quality. This finding may suggest that development in vitro can mask the influence of BCS. The season affects yield and quality of blastocysts in the way that the autumn period is more favorable for embryo development. | Body condition;Cow;Embryo quality;IVP;Oocytes | pubmed |
Simultaneous measurement of 3D zooplankton trajectories and surrounding fluid velocity field in complex flows. | We describe an automated, volumetric particle image velocimetry (PIV) and tracking method that measures time-resolved, 3D zooplankton trajectories and surrounding volumetric fluid velocity fields simultaneously and non-intrusively. The method is demonstrated for groups of copepods flowing past a wall-mounted cylinder. We show that copepods execute escape responses when subjected to a strain rate threshold upstream of a cylinder, but the same threshold range elicits no escape responses in the turbulent wake downstream. The method was also used to document the instantaneous slip velocity of zooplankton and the resulting differences in trajectory between zooplankton and non-inertial fluid particles in the unsteady wake flow, showing the method's capability to quantify drift for both passive and motile organisms in turbulent environments. Applications of the method extend to any group of organisms interacting with the surrounding fluid environment, where organism location, larger-scale eddies and smaller-scale fluid deformation rates can all be tracked and analyzed. | 3D PTV;Infrared;Plankton drift;Tomographic PIV;Turbulence–organism interaction | pubmed |
Photoelastic analysis of stresses transmitted by complete dentures lined with hard or soft liners. | Stresses transmitted on the alveolar bone ridge by lined conventional complete mandibular dentures can decrease the bone absorption level. The aim of this in vitro study was to evaluate the stresses induced on the alveolar bone ridge of lined conventional complete mandibular dentures by using photoelastic analysis. One maxillary and three mandibular conventional dentures were developed for the following treatments: 1 - Unlined denture (control), 2 - Denture lined with resin-based material, and 3 - Denture lined with silicone-based material. The photoelastic analysis took place with the dentures in the position of maximum intercuspation, and the mandibular photoelastic models were axially loaded with 10 kgf (98 N). Unlined denture (control) presented stresses along the model, especially on the anterior and left lateral sides with less stresses on the right side. On the left lateral side, the denture base lined with resin-based material demonstrated similar stresses to that of the control; however, lower stresses occurred in the premolar and retromolar regions. Denture bases lined with silicone-based material showed decreased fringe orders and homogeneous distribution of induced stresses. Both lined dentures exhibited lower stresses when compared to unlined dentures. Silicone-based material provided a more homogeneous distribution of stresses. | Acrylic resin;Complete denture;Liner material;Photoelastic model | pubmed |
Atypical Fractures are Mainly Subtrochanteric in Singapore and Diaphyseal in Sweden: A Cross-Sectional Study. | We have previously noted a dichotomy in the location of atypical fractures along the femoral shaft in Swedish patients, and a mainly subtrochanteric location of atypical fractures in descriptions of patients from Singapore. These unexpected differences were now investigated by testing the following hypotheses in a cross-sectional study: first, that there is a dichotomy also in Singapore; second, that the relation between subtrochanteric and diaphyseal location is different between the two countries; third, that the location is related to femoral bow. The previously published Swedish sample (n = 151) was re-measured, and a new Singaporean sample (n = 75) was established. Both samples were based on radiographic classification of all femoral fractures in women above 55 years of age. The distance between the fracture line and the lesser trochanter was measured. Femoral bow was classified as present or absent on frontal radiographs. Frequency distribution of the measured distances was analyzed using the Bayesian information criterion to choose the best description of the observed variable distribution in terms of a compilation of normally distributed subgroups. The analysis showed a clear dichotomy of the fracture location: either subtrochanteric or diaphyseal. Subtrochanteric fractures comprised 48% of all fractures in Singapore, and 17% in Sweden (p = 0.0001). In Singapore, femoral bow was associated with more fractures in the diaphyseal subgroup (p = 0.0001). This was not seen in Sweden. A dichotomous location of atypical fractures was confirmed, because it was found also in Singapore. The fractures showed a different localization pattern in the two countries. This difference may be linked to anatomical variations, but might also be related to cultural differences between the two populations that influence physical activity. | ANTIRESORPTIVES;BIOMECHANICS;INJURY/FRACTURE HEALING;OSTEOPOROSIS;RADIOLOGY | pubmed |
The characteristics of TAG and EPA accumulation in Nannochloropsis oceanica IMET1 under different nitrogen supply regimes. | The strategy of nitrogen limitation has been widely applied to enhance lipid production in microalgae. The changes of cellular composition, and the characteristics of triacylglycerol (TAG) and eicosapentaenoic acid (EPA) accumulation in Nannochloropsis oceanica IMET1 were investigated. The results revealed that after nitrogen limitation TAG rather than carbohydrate was the dominant carbon sink in N. oceanica IMET1. Different nitrogen supplementation strategies were applied in order to achieve high TAG and EPA productivity, respectively. Limited nitrogen was supplied to improve TAG production, and a maximum productivity of 29.44 mg L(-1) d(-1) was obtained, which was a 6.74-fold increase compared to nitrogen-depleted cultivation. The highest EPA productivity of 7.66 mg L(-1) d(-1) was achieved under nitrogen-replete cultivation, which is different from the condition for TAG maximum productivity because the EPA is in glycolipids and phospholipids mainly. The fatty acid composition analysis identified the source of acyl group in TAG accumulation. | EPA;Fatty acid composition;Nannochloropsis oceanica IMET1;Nitrogen limitation;TAG | pubmed |
Semiautomated hybrid algorithm for estimation of three-dimensional liver surface in CT using dynamic cellular automata and level-sets. | Liver segmentation continues to remain a major challenge, largely due to its intense complexity with surrounding anatomical structures (stomach, kidney, and heart), high noise level and lack of contrast in pathological computed tomography (CT) data. We present an approach to reconstructing the liver surface in low contrast CT. The main contributions are: (1) a stochastic resonance-based methodology in discrete cosine transform domain is developed to enhance the contrast of pathological liver images, (2) a new formulation is proposed to prevent the object boundary, resulting from the cellular automata method, from leaking into the surrounding areas of similar intensity, and (3) a level-set method is suggested to generate intermediate segmentation contours from two segmented slices distantly located in a subject sequence. We have tested the algorithm on real datasets obtained from two sources, Hamad General Hospital and medical image computing and computer-assisted interventions grand challenge workshop. Various parameters in the algorithm, such as [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text], play imperative roles, thus their values are precisely selected. Both qualitative and quantitative evaluation performed on liver data show promising segmentation accuracy when compared with ground truth data reflecting the potential of the proposed method. | computed tomography;dynamic cellular automata;graph cut;image segmentation;stochastic resonance | pubmed |
Adolescent Self-Reported Physical Activity and Autonomy: A Case for Constrained and Structured Environments? | The provision of autonomy supportive environments that promote physical activity engagement have become popular in contemporary youth settings. However, questions remain about whether adolescent perceptions of their autonomy have implications for physical activity. The purpose of this investigation was to examine the association between adolescents' self-reported physical activity and their perceived autonomy. Participants (n = 384 adolescents) aged between 12 and 15 years were recruited from six secondary schools in metropolitan Brisbane, Australia. Self-reported measures of physical activity and autonomy were obtained. Logistic regression with inverse probability weights were used to examine the association between autonomy and the odds of meeting youth physical activity guidelines. Autonomy (OR 0.61, 95% CI 0.49-0.76) and gender (OR 0.62, 95% CI 0.46-0.83) were negatively associated with meeting physical activity guidelines. However, the model explained only a small amount of the variation in whether youth in this sample met physical activity guidelines (R(2) = 0.023). For every 1 unit decrease in autonomy (on an index from 1 to 5), participants were 1.64 times more likely to meet physical activity guidelines. The findings, which are at odds with several previous studies, suggest that interventions designed to facilitate youth physical activity should limit opportunities for youth to make independent decisions about their engagement. However, the small amount of variation explained by the predictors in the model is a caveat, and should be considered prior to applying such suggestions in practical settings. Future research should continue to examine a larger age range, longitudinal observational or intervention studies to examine assertions of causality, as well as objective measurement of physical activity. Key pointsAutonomy was negatively associated with meeting physical activity recommendationsThe findings suggest that more structured environments would facilitate physical activityThe small amount of variation explained by the predictors in the model is a caveat. | Adolescent;autonomy;physical activity;self-determination theory;self-report | pubmed |
Surgical Management of Benign Biliary Stricture in Chronic Pancreatitis: A Single-Center Experience. | Biliary stricture in chronic pancreatitis (CP) is not uncommon. Previously, all cases were managed by surgery. Nowadays, three important modes of treatment in these patients are observation, endoscopic therapy, and surgery. In the modern era, surgery is recommended only in a subset of patients who develop biliary symptoms or those who have asymptomatic biliary stricture and require surgery for intractable abdominal pain. We want to report on our experience regarding surgical management of CP-induced benign biliary stricture. Over a period of 5 years, we have managed 340 cases of CP at our institution. Bile duct stricture was found in 62 patients. But, surgical intervention was required in 44 patients, and the remaining 18 patients were managed conservatively. Demographic data, operative procedures, postoperative complications, and follow-up parameters of these patients were collected from our prospective database. A total 44 patients were operated for biliary obstruction in the background of CP. Three patients were excluded, so the final analysis was based on 41 patients. The indication for surgery was symptomatic biliary stricture in 27 patients and asymptomatic biliary stricture with intractable abdominal pain in 14 patients. The most commonly performed operation was Frey's procedure. There was no inhospital mortality. Thirty-five patients were well at a mean follow-up of 24.4 months (range 3 to 54 months). Surgery is still the best option for CP-induced benign biliary stricture, and Frey's procedure is a versatile operation unless you suspect malignancy as the cause of biliary obstruction. | Biliary stricture;Chronic pancreatitis;Frey’s procedure;Jaundice | pubmed |
Competitive assessments of pulmonary embolism: Noninvasiveness versus the golden standard. | Diagnosis of suspected pulmonary embolism (PE) is crucial as undiagnosed and over-diagnosis can both lead to serious consequences. Contemporary diagnostic approach of PE is a sequential combination assessment beginning with clinical assessment, validated with D-dimer measurement and confirmed with pulmonary angiography or imaging. Since the invasive pulmonary angiography is risky and costly, imaging is a warranted tool in the diagnosis procedure. CT pulmonary angiography is a less-invasive method with general availability, studies provide favorable evidences for CT pulmonary angiography as a stand-alone test for excluding PE, and it has become the first choice of tests in emergency department for suspected PE in most centers. Ventilation/perfusion single-photon emission CT signifies a new era in nuclear medicine. It has excellent sensitivity and specificity, fast procedure, low radiation exposure, few complications and contradictions. Besides, MR angiography is another possible and promising approach for diagnosis of suspected PE with much safer contrast agents than CT and no ionizing radiation. With wide availability and less invasive effects, imaging becomes a firsthand tool to obtain optimal accuracy in the diagnosis work up in clinic nowadays. This review summarizes the current methods in diagnosing PE and the update of imaging assessments of the disease. | Pulmonary embolism;diagnosis;imaging | pubmed |
Observational scores of dampness and mold associated with measurements of microbial agents and moisture in three public schools. | We examined associations between observational dampness scores and measurements of microbial agents and moisture in three public schools. A dampness score was created for each room from 4-point-scale scores (0-3) of water damage, water stains, visible mold, moldy odor, and wetness for each of 8 room components (ceiling, walls, windows, floor, ventilation, furniture, floor trench, and pipes), when present. We created mixed microbial exposure indices (MMEIs) for each of 121 rooms by summing decile ranks of 8 analytes (total culturable fungi; total, Gram-negative, and Gram-positive culturable bacteria; ergosterol; (1→3)-β-D-glucan; muramic acid; and endotoxin) in floor dust. We found significant (P ≤ 0.01) linear associations between the dampness score and culturable bacteria (total, Gram-positive, and Gram-negative) and the MMEIs. Rooms with dampness scores greater than 0.25 (median) had significantly (P < 0.05) higher levels of most microbial agents, MMEIs, and relative moisture content than those with lower scores (≤0.25). Rooms with reported recent water leaks had significantly (P < 0.05) higher dampness scores than those with historical or no reported water leaks. This study suggests that observational assessment of dampness and mold using a standardized form may be valuable for identifying and documenting water damage and associated microbial contamination. | Assessment;Building;Dampness;Microbial;Mold;School | pubmed |
The role of TRPC6 in oxidative stress-induced podocyte ischemic injury. | Increasing evidence suggests that ischemia and hypoxia serve important functions in the development of renal diseases. However, the underlying mechanism of ischemic injury has not been fully understood. In this study, we found that renal ischemia-reperfusion injury induced podocyte effacement and the upregulation of TRPC6 mRNA and protein expression. In in vitro experiments, oxygen glucose deprivation (OGD) treatment enhanced the expression of TRPC6 and TRPC6-dependent Ca(2+) influx. TRPC6 knockdown by siRNA interference attenuated the OGD-induced [Ca(2+)]i and actin assembly. OGD treatment also increased ROS production. Furthermore, inhibition of ROS activity by N-acetyl-l-cysteine (NAC) eliminated the OGD-induced increase in TRPC6 expression and Ca(2+) influx. H2O2 treatment, which results in oxidative stress, also increased TRPC6 expression and Ca(2+) influx. We conclude that TRPC6 upregulation is involved in Ca(2+) signaling and actin reorganization in podocytes after OGD. These findings provide new insight into the mechanisms underlying the cellular response of podocytes to ischemic injury. | Actin cytoskeleton;OGD;Podocytes;ROS;Renal ischemia-reperfusion injury;TRPC6 | pubmed |
Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis. | Rapidly progressive interstitial lung disease (RP-ILD) is an intractable and fatal complication of juvenile dermatomyositis (JDM). This study evaluated serum levels of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in JDM patients with complicating ILD, and their association with ILD phenotypes, clinical variables, and anti-melanoma differentiation-associated gene 5 (MDA5). We measured the levels of BAFF, APRIL, and anti-MDA5 in the sera of 23 JDM patients with ILD [8 in the RP-ILD group and 15 in the chronic ILD (C-ILD) group], 17 JDM patients without ILD (non-ILD group), and 10 age-matched controls, using the ELISA method. ILD was identified by high-resolution computed tomography. Serum BAFF titers were significantly higher in the JDM patients with RP-ILD versus those with C-ILD (p = 0.011) and in healthy controls (p = 0.0004). The C-ILD group had significantly higher levels of BAFF versus controls (p ≤ 0.0001). Serum APRIL was markedly elevated in the RP-ILD group as compared with the C-ILD group (p = 0.003) and controls (p = 0.006). In patients with ILD, both BAFF and APRIL levels were correlated with serum Krebs von den Lungen-6 and interleukin 18. Subjects with high titer anti-MDA5 (> 200 U) had higher levels of BAFF and APRIL than those with low titer anti-MDA5 (< 100 U; p = 0.019 and p = 0.0029, respectively), which may have been due to a relationship between RP-ILD and high anti-MDA5 titer. Our findings of markedly elevated levels of BAFF and APRIL in patients with RP-ILD JDM suggest the potential importance of these cytokines in the diagnosis and treatment of RP-ILD accompanying JDM. | ANTI-MDA5;B CELL ACTIVATING FACTOR;INTERSTITIAL LUNG DISEASE;JUVENILE DERMATOMYOSITIS;PROLIFERATION-INDUCING LIGAND | pubmed |
Reduction of the ages at diagnosis and operation of biliary atresia in Taiwan: A 15-year population-based cohort study. | To describe the ages at diagnosis and operation of biliary atresia (BA) and its incidence over a 15-year period in Taiwan. This was a population-based cohort study. BA cases were identified from the Taiwan National Health Insurance Research Database based on the International Classification of Diseases, Ninth Revision (ICD-9) code of BA 751.61 plus Kasai operation (ICD-9 procedure code 51.37) or liver transplantation (LT, ICD-9 procedure code 50.5). The patients' characteristics including sex, age at diagnosis, age at receiving Kasai operation and age at receiving LT were compared among three birth cohorts: (1) 1997 to 2001; (2) 2002 to 2006; and (3) 2007 to 2011. There were a total of 540 BA cases (275 females) with an incidence of 1.62 per 10000 live births. No seasonality of BA was noted. The mean ages at diagnosis of three cohorts were 57.9, 55.6 and 52.6 d. A linear regression model demonstrated a decreasing trend of the mean age at diagnosis (1.27 d per year). The proportion of BA cases that received the Kasai operation within 60 d of age increased from 76% to 81%. A total of 189 (35%) BA patients underwent LT. The mean age at LT was reduced from 3-year-old to 1-year-old. The rates of LT were 25.6% and 32.3% in patients who received the Kasai operation within 60 d or after 60 d of age, respectively. All patients who did not undergo a Kasai operation eventually required LT. The ages at diagnosis and operation in BA cases have decreased over time. Kasai operation performed at younger age reduces the need for LT. The incidence of BA in Taiwan fluctuates, but without certain trend. | Age;Biliary atresia;Kasai operation;Liver transplantation;Stool color card | pubmed |
Immunosensing of Atrazine with Antibody-Functionalized Cu-MOF Conducting Thin Films. | This work reports the assembly of thin films of a silica (SiO2)-modified copper-metal organic framework, Cu3(BTC)2 [Cu3(BTC)2@SiO2, BTC = benzene-1,3,5-tricarboxylic acid] on a conducting substrate of NH2-BDC [NH2-BDC = 2-aminobenzene-1,4-dicarboxylic acid] doped polyaniline (PANI). Assembled Cu3(BTC)2@SiO2/BDC-PANI thin films displayed electrical conductivity in the range of 35 μA. These thin films were conjugated with antiatrazine antibodies to create a novel immunosensing platform. Various structural and spectral characteristics of the synthesized material and its bioconjugate were investigated. The developed immunosensor was used for the conductometric sensing of atrazine. The detection of atrazine was achieved with a high sensor sensitivity (limit of detection = 0.01 nM) and specificity in the presence of diverse pesticides (e.g., endosulfan, parathion, paraoxon, malathion, and monochrotophos). | MOF;atrazine;conducting;polyaniline;sensor;thin films | pubmed |
Delayed/back up antibiotic prescriptions: what do the public think? | To describe the general public's understanding, acceptance and use of delayed antibiotics. Face to face computer-assisted survey using an Ipsos MORI Capibus survey. Randomly selected households in England using multistage sampling. A representative sample of 1625 adults aged over 15 years and recruited from household visits in England, using age and gender quotas for each area. The survey was undertaken in January 2014. Weights based on gender, age, ethnicity, working status, social grade, housing tenure and Government Office Region corrected for selection biases, so that results are broadly representative of the population. Proportion of respondents; understanding the meaning of the term delayed antibiotic prescription and how the strategy is used in general practice; in favour of, or opposed to clinicians offering them a delayed antibiotic; reporting receipt, use and acceptability of delayed antibiotic prescriptions in the past year. 17% reported fully understanding the meaning of delayed antibiotic prescription and strategy use in general practice;72% were unaware of the term or strategy; 36-39% were in favour of, and 28-30% opposed to clinicians offering them a delayed antibiotic for throat, urine, ear or chest infections. Half of those who were fully aware of the term and practice were in favour of delayed antibiotics. Women, and older respondents, were more strongly opposed to delayed prescribing. Only 4% of all respondents, and 15% of those prescribed an antibiotic, reported being offered a delayed antibiotic in the last year. Wider understanding and acceptance of delayed prescribing may facilitate increased uptake. Further research is needed to determine why groups are so strongly in favour or opposed to delayed prescribing. | INFECTIOUS DISEASES;MICROBIOLOGY;PRIMARY CARE;PUBLIC HEALTH;antibiotics;antimicrobials | pubmed |
Production of Interspecific Germline Chimeras via Embryo Replacement. | In avian species, primordial germ cells (PGCs) use the vascular system to reach their destination, the genital ridge. Because of this unique migratory route of avian germ cells, germline chimera production can be achieved via germ cell transfer into a blood vessel. This study was performed to establish an alternative germ cell-transfer system for producing germline chimeras by replacing an original host embryo with a donor embryo, while retaining the host extraembryonic tissue and yolk, before circulation. First, to test the migratory capacity of PGCs after embryo replacement, Korean Oge (KO) chick embryos were used to replace GFP transgenic chick embryos. Four days after replacement, GFP-positive cells were detected in the replaced KO embryonic gonads, and genomic DNA PCR analysis with the embryonic gonads demonstrated the presence of the GFP transgene. To produce an interspecific germline chimera, the original chick embryo proper was replaced with a quail embryo onto the chick yolk. To detect the gonadal PGCs in the 5.5-day-old embryonic gonads, immunohistochemistry was performed with monoclonal antibodies specific to either quail or chick PGCs, i.e., QCR1 and anti-stage-specific embryonic antigen-1 (SSEA-1), respectively. Both the QCR1-positive and SSEA-1-positive cells were detected in the gonads of replaced quail embryos. Forty percent of the PGC population in the quail embryos was occupied by chick extraembryonically derived PGCs. In conclusion, replacement of an embryo onto the host yolk before circulation can be applied to produce interspecies germline chimeras, and this germ cell-transfer technology is potentially applicable for reproduction of wild or endangered bird species. | chicken;embryo replacement;interspecies germline chimera;primordial germ cell;quail | pubmed |
Thoracic Spine Manipulation in Individuals With Subacromial Impingement Syndrome Does Not Immediately Alter Thoracic Spine Kinematics, Thoracic Excursion, or Scapular Kinematics: A Randomized Controlled Trial. | Randomized controlled trial. To determine if thoracic spinal manipulative therapy (SMT) alters thoracic kinematics, thoracic excursion, and scapular kinematics compared to a sham SMT in individuals with subacromial impingement syndrome, and also to compare changes in patient-reported outcomes between treatment groups. Prior studies indicate that thoracic SMT can improve pain and disability in individuals with subacromial impingment syndrome. However, the mechanisms underlying these benefits are not well understood. Participants with shoulder impingement symptoms (n = 52) were randomly assigned to receive a single session of thoracic SMT or sham SMT. Thoracic and scapular kinematics during active arm elevation and overall thoracic excursion were measured before and after the intervention. Patient-reported outcomes measured were pain (numeric pain-rating scale), function (Penn Shoulder Score), and global rating of change. Following the intervention, there were no significant differences in changes between groups for thoracic kinematics or excursion, scapular kinematics, and patient-reported outcomes (P>.05). Both groups showed an increase in scapular internal rotation during arm raising (mean, 0.9°; 95% confidence interval [CI]: 0.3°, 1.6°; P = .003) and lowering (0.8°; 95% CI: 0.0°, 1.5°; P = .041), as well as improved pain reported on the numeric pain-rating scale (1.2 points; 95% CI: 0.3, 1.8; P<.001) and function on the Penn Shoulder Score (9.1 points; 95% CI: 6.5, 11.7; P<.001). Thoracic spine extension and excursion did not change significantly following thoracic SMT. There were small but likely not clinically meaningful changes in scapular internal rotation in both groups. Patient-reported pain and function improved in both groups; however, there were no significant differences in the changes between the SMT and the sham SMT groups. Overall, patient-reported outcomes improved in both groups without meaningful changes to thoracic or scapular motion. Therapy, level 1b-. | biomechanics;manual therapy;thrust | pubmed |
Comparison of weekly versus triweekly cisplatin delivered concurrently with radiation therapy in patients with locally advanced nasopharyngeal cancer: A multicenter randomized phase II trial (KCSG-HN10-02). | Triweekly delivery of cisplatin concurrent with a course of radiation therapy (RT) has been the standard regimen for treatment of locally advanced nasopharyngeal carcinoma (NPC) despite a high level of concern regarding treatment-related complications. We conducted a randomized phase II study to compare weekly and triweekly cisplatin delivery during RT with respect to efficacy and toxicity profiles. Patients with locally advanced NPC (stage II-IVb) were randomly assigned to a regimen of either seven doses of cisplatin (40 mg/m(2)) given once a week or three doses of cisplatin (100mg/m(2)) given every 3 weeks concurrently during RT. Of 109 eligible patients, 53 were assigned to the weekly regimen and 56 to the triweekly regimen. The two groups were comparable with respect to demographic and clinical characteristics. There were no significant differences in mean RT dose (68.3 Gy vs. 67.3 Gy, p=0.559) and mean cisplatin dose (248.9 mg/m(2)vs. 256.6 mg/m(2), p=0.433) between the two regimens. The primary endpoint was 3-year progression-free survival, which was not different between the regimens (64.9% vs. 63.8%, p=0.074). Overall, the occurrence of grade 3-4 toxicities was similar between the two arms (47.2% vs. 39.3%, p=0.443). Quality of life (QoL) related to functional outcomes 3 weeks after treatment completion was better for the weekly regimen. Although no definitive conclusions can be made, a once-weekly cisplatin regimen appears to be associated with improved QoL and is not inferior to the standard triweekly regimen with respect to efficacy and toxicity profiles. | Concurrent chemoradiation therapy;Efficacy;Nasopharyngeal cancer;Quality of life;Toxicity | pubmed |
Role of tissue eosinophils in oral Leukoplakia: A pilot study. | Tissue eosinophilia in oral squamous cell carcinoma has been well - recognized. Studies have reported both favorable and unfavorable prognoses associated with tissue eosinophils in oral squamous cell carcinoma. However, the role of eosinophils in the development of tumor is still unclear. The present study was an attempt to elucidate the potential role of tissue eosinophils in oral leukoplakia, a potentially malignant lesion. To count eosinophils in tissues of normal subjects and oral leukoplakia cases. To compare tissue eosinophil count (TEC) between normal and oral leukoplakia cases. To compare TEC between dysplastic and non-dysplastic cases of oral leukoplakia and to correlate with degree of epithelial dysplasia. A total of 85 cases (59 cases of oral leukoplakia and 26 normal oral tissues) constituted the study material. Tissue eosinophils were counted in 10 different high- power fields. Non-parametric tests (Mann-Whitney U-test, Kruskal-Wallis test, Mann-Whitney post hoc analysis and Spearman's correlation statistics). Mean eosinophil count (MEC) in oral leukoplakia cases was significantly more when compared to normal subjects. MEC in dysplastic cases of oral leukoplakia was significantly more when compared to those without epithelial dysplasia (Mann-Whitney U-test). Furthermore, MEC was directly proportional to the degree of epithelial dysplasia (Spearman's correlation statistics). TEC may be used as an adjunct to predict the malignant transformation of dysplastic cases of oral leukoplakia. Eosinophilic infiltration in oral dysplastic cases should prompt a thorough evaluation for invasiveness, especially when features of invasion are absent or suspected in smaller biopsy specimens. Use of TEC as a prognostic indicator demands larger sample size and mandates long-term follow-up. | Eosinophil;epithelial dysplasia;oral leukoplakia | pubmed |
Diagnosis of Cetacean morbillivirus: A sensitive one step real time RT fast-PCR method based on SYBR(®) Green. | Cetacean morbillivirus (CeMV) (family Paramyxoviridae, genus Morbillivirus) is considered the most pathogenic virus of cetaceans. It was first implicated in the bottlenose dolphin (Tursiops truncatus) mass stranding episode along the Northwestern Atlantic coast in the late 1980s, and in several more recent worldwide epizootics in different Odontoceti species. This study describes a new one step real-time reverse transcription fast polymerase chain reaction (real-time RT-fast PCR) method based on SYBR(®) Green to detect a fragment of the CeMV fusion protein gene. This primer set also works for conventional RT-PCR diagnosis. This method detected and identified all three well-characterized strains of CeMV: porpoise morbillivirus (PMV), dolphin morbillivirus (DMV) and pilot whale morbillivirus (PWMV). Relative sensitivity was measured by comparing the results obtained from 10-fold dilution series of PMV and DMV positive controls and a PWMV field sample, to those obtained by the previously described conventional phosphoprotein gene based RT-PCR method. Both the conventional and real-time RT-PCR methods involving the fusion protein gene were 100- to 1000-fold more sensitive than the previously described conventional RT-PCR method. | Cetacean morbillivirus diagnosis;Fusion protein gene;Molecular epidemiology;Real-time RT-PCR | pubmed |
Apocynin attenuates testicular ischemia-reperfusion injury in rats. | This study was designed to examine the possible protective effect of apocynin, a NADPH oxidase inhibitor, against torsion/detorsion (T/D) induced ischemia/reperfusion (I/R) injury in testis. Male Wistar albino rats were divided into sham-operated control, and either vehicle, apocynin 20mg/kg- or apocynin 50mg/kg-treated T/D groups. In order to induce I/R injury, left testis was rotated 720° clockwise for 4 hours (torsion) and then allowed reperfusion (detorsion) for 4 hours. Left orchiectomy was done for the measurement of tissue malondialdehyde (MDA), glutathione (GSH) levels, myeloperoxidase (MPO) activity, and luminol, lucigenin, nitric oxide (NO) and peroxynitrite chemiluminescences (CL). Testicular morphology was examined by light microscopy. I/R caused significant increases in tissue luminol, lucigenin, nitric oxide and peroxynitrite CL demonstrating increased reactive oxygen and nitrogen metabolites. As a result of increased oxidative stress tissue MPO activity, MDA levels were increased and antioxidant GSH was decreased. On the other hand, apocynin treatment reversed all these biochemical indices, as well as histopathological alterations that were induced by I/R. According to data, although lower dose of apocynin tended to reverse the biochemical parameters, high dose of apocynin provides better protection since values were closer to the control levels. Findings of the present study suggest that NADPH oxidase inhibitor apocynin by inhibiting free radical generation and increasing antioxidant defense exerts protective effects on testicular tissues against I/R. The protection with apocynin was more pronounced with high dose. | Apocynin;Reperfusion injury;Spermatic cord torsion;Testis | pubmed |
Cognitive behavioral therapy for early adolescents with autism spectrum disorders and clinical anxiety: a randomized, controlled trial. | Clinically elevated anxiety is a common, impairing feature of autism spectrum disorders (ASD). A modular CBT program designed for preteens with ASD, Behavioral Interventions for Anxiety in Children with Autism (BIACA; Wood et al., 2009) was enhanced and modified to address the developmental needs of early adolescents with ASD and clinical anxiety. Thirty-three adolescents (11-15 years old) were randomly assigned to 16 sessions of CBT or an equivalent waitlist period. The CBT model emphasized exposure, challenging irrational beliefs, and behavioral supports provided by caregivers, as well as numerous ASD-specific treatment elements. Independent evaluators, parents, and adolescents rated symptom severity at baseline and posttreatment/postwaitlist. In intent-to-treat analyses, the CBT group outperformed the waitlist group on independent evaluators' ratings of anxiety severity on the Pediatric Anxiety Rating Scale (PARS) and 79% of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment, as compared to only 28.6% of the waitlist group. Group differences were not found for diagnostic remission or questionnaire measures of anxiety. However, parent-report data indicated that there was a positive treatment effect of CBT on autism symptom severity. The CBT manual under investigation, enhanced for early adolescents with ASD, yielded meaningful treatment effects on the primary outcome measure (PARS), although additional developmental modifications to the manual are likely warranted. Future studies examining this protocol relative to an active control are needed. | anxiety disorders;autism spectrum disorders;cognitive behavioral therapy;parent-training | pubmed |
Old processes, new perspectives: Familiarity is correlated with (not independent of) recollection and is more (not equally) variable for targets than for lures. | According to dual-process models of memory, recognition is subserved by two processes: recollection and familiarity. Many variants of these models assume that recollection and familiarity make stochastically independent contributions to performance in recognition tasks and that the variance of the familiarity signal is equal for targets and for lures. Here, we challenge these 'common-currency' assumptions. Using a model-comparison approach, featuring the Continuous Dual Process (CDP; Wixted & Mickes, 2010) model as the protagonist, we show that when these assumptions are relaxed, the model's fits to individual participants' data improve. Furthermore, our analyses reveal that across items, recollection and familiarity show a positive correlation. Interestingly, this across-items correlation was dissociated from an across-participants correlation between the sensitivities of these processes. We also find that the familiarity signal is significantly more variable for targets than for lures. One striking theoretical implication of these findings is that familiarity-rather than recollection, as most models assume-may be the main contributor responsible for one of the most influential findings of recognition memory, that of subunit zROC slopes. Additionally, we show that erroneously adopting the common-currency assumptions, introduces severe biases to estimates of recollection and familiarity. | Aggregation bias;Continuous dual processes model;Familiarity;Functional independence;Recollection;Stochastic independence | pubmed |
2015 SPCTPD/ACC/AAP/AHA Training Guidelines for Pediatric Cardiology Fellowship Programs (Revision of the 2005 Training Guidelines for Pediatric Cardiology Fellowship Programs): Introduction. | SPCTPD/ACC/AAP/AHA Training Statement;clinical competence;fellowship training;pediatric cardiology;quality improvement | pubmed |
|
Metabolic regulation of mesenchymal stem cell in expansion and therapeutic application. | Human mesenchymal or stromal cells (hMSCs) isolated from various adult tissues are primary candidates in cell therapy and tissue regeneration. Despite promising results in preclinical studies, robust therapeutic responses to MSC treatment have not been reproducibly demonstrated in clinical trials. In the translation of MSC-based therapy to clinical application, studies of MSC metabolism have significant implication in optimizing bioprocessing conditions to obtain therapeutically competent hMSC population for clinical application. In addition, understanding the contribution of metabolic cues in directing hMSC fate also provides avenues to potentiate their therapeutic effects by modulating their metabolic properties. This review focuses on MSC metabolism and discusses their unique metabolic features in the context of common metabolic properties shared by stem cells. Recent advances in the fundamental understanding of MSC metabolic characteristics in relation to their in vivo origin and metabolic regulation during proliferation, lineage-specific differentiation, and exposure to in vivo ischemic conditions are summarized. Metabolic strategies in directing MSC fate to enhance their therapeutic potential in tissue engineering and regenerative medicine are discussed. | apoptosis;differentiation;energy metabolism;expansion;glucose;hypoxia;mesenchymal stem or stromal cells;transplantation | pubmed |
Photonics meets connectomics: case of diffuse, long-range horizontal projections in rat cortex. | Recent years have seen progress in characterizing connections between different regions of the rodent brain to establish a "connectome." This effort involves systematically collected new data together with tools to characterize network relationships in new and preexisting data. The choices made during data collection, analysis, and display in order to generate these connectomes have emphasized dense, specific connections between cortical regions defined using a priori parcellation schemes that may obscure certain spatial relationships in the data. One example of a pattern of connectivity not clearly evident in these connectomes is a diffusely radiating, apparently nonspecific, border-crossing, long-range horizontal axonal projection that is related to horizontal spreads of evoked activity in the rat cortex. Here, we describe the horizontal projection system and explore evidence for this projection within the connectome data. We consider how the differences in optical and histological methodologies and analyses used for the connectome studies and our own studies lead to different emphases concerning this important horizontal projection pattern. | adeno-associated virus;biotinylated dextran amine;connectome;cortex;horizontal axons;tractography | pubmed |
Carl Djerassi: 'father of the pill' and renaissance man. | historical | pubmed |
|
In Vivo Comparison of the Masticatory Efficiency of Artificial Teeth with Two Different Cusp Heights in Complete Dentures: A Preliminary Study. | The goal of complete denture rehabilitation is to restore facial esthetics and masticatory function to edentulous patients. Several types of artificial teeth with different occlusal anatomy are available. Theoretically, teeth with a higher cusp height provide improved masticatory efficiency. The aim of this study was to compare the masticatory efficiency of complete denture wearers using artificial teeth with two cusp heights. Sixteen complete denture wearers were given complete dentures with Heraeus Premium teeth. Fifteen days after denture installation, a first masticatory efficiency test was performed with Optocal. A new pair of complete dentures with Dentsply Biotone teeth was then given to each participant to replace the first set. This second set was fabricated by duplicating the same models used to fabricate the first set of dentures. Fifteen days after installation of the dentures with Biotone teeth, a second masticatory efficiency test was performed with Optocal. On both tests, the comminuted material was treated and sieved through a stack of sieves under vibration. The content of each sieve was weighed, and the obtained data were tabulated. Statistical analysis was performed using the Kolmogorov-Smirnov and Wilcoxon tests. Mean and standard deviation of participants' masticatory efficiency, as measured by X<sub>50</sub> particle size (mm), were 8.39 and 5.59 for dentures with Premium teeth, and 8.56 and 5.84 for dentures with Biotone teeth. According to the results, there were no differences (p < 0.05) in the masticatory efficiency of the complete denture sets using teeth with the two cusp heights. | Denture;artificial;complete;mastication;tooth | pubmed |
A New Method Combining Finite Element Analysis and Digital Image Correlation to Assess Macroscopic Mechanical Properties of Dentin. | A literature review points out a large discrepancy in the results of the mechanical tests on dentin that can be explained by stress and strain assessment during the tests. Errors in these assessments during mechanical tests can lead to inaccurate estimation of the mechanical properties of the tested material. On top of that, using the beam theory to analyze the bending test for thick specimens will increase these experimental errors. After summarizing the results of mechanical tests on dentin in the literature, we focus on bending tests and compare the stress assessment obtained by finite element analysis (FEA) and by beam theory application. We show that the difference between the two methods can be quite large in some cases, leading us to prefer the use of FEA to assess stresses. We then propose a new method based on coupling finite element analysis and digital image correlation (DIC) to more accurately evaluate stress distributions, strain distributions and elastic modulus in the case of a three-point bending test. To illustrate and prove the feasibility of the method, it is applied on a dentinal sample so that mean elastic modulus and maximum tensile stress are obtained (11.9 GPa and 143.9 MPa). Note that the main purpose of this study is to focus on the method itself, and not to provide new mechanical values for dentin. When used in standard mechanical testing of dentin, this kind of method should help to narrow the range of obtained mechanical properties values. | dentin;digital image correlation;finite element analysis;mechanical properties;stress and strain assessment;three-point bending test | pubmed |
Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly. | Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with both vascular and amyloid pathologies, the effect of both pathologies on cognition was additive and not synergistic. For a 79-year-old subject, the predicted annual rate of global z-score decline was -0.02 if on neither pathway, -0.07 if on the vascular pathway, -0.08 if on the amyloid pathway and -0.13 if on both pathways. The main conclusions of this study were: (i) amyloid and vascular pathologies seem to be at least partly independent processes that both affect longitudinal cognitive trajectories adversely and are major drivers of cognitive decline in the elderly; and (ii) cognitive reserve seems to offset the deleterious effect of both pathologies on the cognitive trajectories. | ageing;cognitive neurology;neuro protective strategies;neuroimaging | pubmed |
Use of Transthoracic Echocardiography in the Management of Low-Risk Staphylococcus aureus Bacteremia: Results From a Retrospective Multicenter Cohort Study. | The aim of this study was to develop a prediction model to identify patients with low-risk Staphylococcus aureus bacteremia (SAB), in whom infective endocarditis (IE) can be ruled out based on transthoracic echocardiogram (TTE). S. aureus is a major cause of bacteremia and often leads to IE. Current guidelines recommend performing transesophageal echocardiography on all patients or treating all patients empirically with prolonged intravenous antibiotics; however, this approach is resource intensive, many physicians do not adhere to guidelines, and recent studies suggest that low-risk patients may not require transesophageal echocardiography. We conducted a retrospective cohort study of 833 consecutive hospitalized patients with SAB from 7 academic and community hospitals in Toronto, Canada, over a 3-year period (2007 to 2010). Patients who received a TTE within 28 days of bacteremia (n = 536) were randomly divided into derivation and validation cohorts. Multivariable logistic regression analysis was used to determine high-risk criteria for IE in the derivation cohort, and criteria were then applied to the validation cohort to determine diagnostic properties. Four high-risk criteria predicted IE: indeterminate or positive TTE (p < 0.001), community-acquired bacteremia (p = 0.034), intravenous drug use (p < 0.001), and high-risk cardiac condition (p < 0.004). In the validation cohort, the presence of any 1 of the high-risk criteria had 97% sensitivity (95% confidence interval [CI]: 87% to 100%) and 99% negative predictive value (95% CI: 96% to 100%) for IE. The negative likelihood ratio was 0.05 (95% CI: 0.007 to 0.35). A normal TTE ruled out IE in patients without community-acquired SAB, high-risk cardiac conditions, and intravenous drug use. This study provides evidence that clinical risk stratification combined with a normal TTE may be adequate to rule out IE in most patients with SAB. | Staphylococcus aureus;bacteremia;echocardiogram;endocarditis | pubmed |
Roaring lions and chirruping lemurs: How the brain encodes sound objects in space. | The dual-stream model of auditory processing postulates separate processing streams for sound meaning and for sound location. The present review draws on evidence from human behavioral and activation studies as well as from lesion studies to argue for a position-linked representation of sound objects that is distinct both from the position-independent representation within the ventral/What stream and from the explicit sound localization processing within the dorsal/Where stream. | Auditory cortex;Auditory scene analysis;Auditory streaming;Human;Sound object segregation;Sound recognition | pubmed |
DNA barcoding for squids of the family Gonatidae (Cephalopoda: Teuthida) from the boreal North Pacific. | A fragment of cytochrome c oxidase I was used to assess whether species of the squid family Gonatidae from the North Pacific could be identified using DNA barcoding approach. Pairwise intra- and interspecific p-distances were assessed, and systematic relationships among species were estimated by NJ analysis. Examined species formed well-differentiated species-specific clades on the neighbor-joining and Bayesian trees. Multiple taxa formed clades supported by both tree topologies and species hypothesis-free ABGD method. Species morphologically identified as Gonatus tinro and Gonatopsis okutanii demonstrated intraspecific level of molecular genetic divergence (0.2-0.3%) indicating that they are conspecific. Genetic differences between the G. berryi clade and a squid morphologically close to that species may indicate a new cryptic species. High levels (>6.2%) of genetic differentiation within B. borealis suggested the existence of two cryptic species. This study confirms the usefulness of DNA barcoding for identifying species as well as discovering cryptic diversity in the gonatid squids, and indicates the need for further deeper insights into the phylogeny of the Gonatidae. | Cytochrome c oxidase subunit I;genetic distance;phylogeny;species identification | pubmed |
A large-scale analysis of autophagy-related gene expression identifies new regulators of autophagy. | Autophagy is a pathway mediating vacuolar degradation and recycling of proteins and organelles, which plays crucial roles in cellular physiology. To ensure its proper cytoprotective function, the induction and amplitude of autophagy are tightly regulated, and defects in its regulation are associated with various diseases. Transcriptional control of autophagy is a critical aspect of autophagy regulation, which remains largely unexplored. In particular, very few transcription factors involved in the activation or repression of autophagy-related gene expression have been characterized. To identify such regulators, we analyzed the expression of representative ATG genes in a large collection of DNA-binding mutant deletion strains in growing conditions as well as after nitrogen or glucose starvation. This analysis identified several proteins involved in the transcriptional control of ATG genes. Further analyses showed a correlation between variations in expression and autophagy magnitude, thus identifying new positive and negative regulators of the autophagy pathway. By providing a detailed analysis of the regulatory network of the ATG genes our study paves the way for future research on autophagy regulation and signaling. | autophagy;gene expression;stress;transcription factor;yeast | pubmed |
Gas6/Axl in arginine-starvation therapy. | ADI-PEG20;Axl;Gas6;arginine-starvation;melanoma | pubmed |
|
Telocytes in minor salivary glands of primary Sjögren's syndrome: association with the extent of inflammation and ectopic lymphoid neogenesis. | It has been recently reported that telocytes, a stromal (interstitial) cell subset involved in the control of local tissue homeostasis, are hampered in the target organs of inflammatory/autoimmune disorders. Since no data concerning telocytes in minor salivary glands (MSGs) are currently available, aim of the study was to evaluate telocyte distribution in MSGs with normal architecture, non-specific chronic sialadenitis (NSCS) and primary Sjögren's syndrome (pSS)-focal lymphocytic sialadenitis. Twelve patients with pSS and 16 sicca non-pSS subjects were enrolled in the study. MSGs were evaluated by haematoxylin and eosin staining and immunofluorescence for CD3/CD20 and CD21 to assess focus score, Tarpley biopsy score, T/B cell segregation and germinal center (GC)-like structures. Telocytes were identified by immunoperoxidase-based immunohistochemistry for CD34 and CD34/platelet-derived growth factor receptor α double immunofluorescence. Telocytes were numerous in the stromal compartment of normal MSGs, where their long cytoplasmic processes surrounded vessels and encircled both the excretory ducts and the secretory units. In NSCS, despite the presence of a certain degree of inflammation, telocytes were normally represented. Conversely, telocytes were markedly reduced in MSGs from pSS patients compared to normal and NSCS MSGs. Such a decrease was associated with both worsening of glandular inflammation and progression of ectopic lymphoid neogenesis, periductal telocytes being reduced in the presence of smaller inflammatory foci and completely absent in the presence of GC-like structures. Our findings suggest that a loss of MSG telocytes might have important pathophysiological implications in pSS. The specific pro-inflammatory cytokine milieu of pSS MSGs might be one of the causes of telocyte loss. | focal lymphocytic sialadenitis;immunohistochemistry;minor salivary glands;primary Sjögren's syndrome;stromal cells;telocytes | pubmed |
Brainstem auditory evoked potentials in children with lead exposure. | Earlier studies have demonstrated an auditory effect of lead exposure in children, but information on the effects of low chronic exposures needs to be further elucidated. To investigate the effect of low chronic exposures of the auditory system in children with a history of low blood lead levels, using an auditory electrophysiological test. Contemporary cross-sectional cohort. Study participants underwent tympanometry, pure tone and speech audiometry, transient evoked otoacoustic emissions, and brainstem auditory evoked potentials, with blood lead monitoring over a period of 35.5 months. The study included 130 children, with ages ranging from 18 months to 14 years, 5 months (mean age 6 years, 8 months ± 3 years, 2 months). The mean time-integrated cumulative blood lead index was 12 μg/dL (SD ± 5.7, range: 2.433). All participants had hearing thresholds equal to or below 20 dBHL and normal amplitudes of transient evoked otoacoustic emissions. No association was found between the absolute latencies of waves I, III, and V, the interpeak latencies I-III, III-V, and I-V, and the cumulative lead values. No evidence of toxic effects from chronic low lead exposures was observed on the auditory function of children living in a lead contaminated area. | Audiometria de tons puros;Brainstem auditory evoked potentials;Intoxicação por chumbo;Lead poisoning;Potenciais evocados auditivos do tronco encefálico;Pure-tone audiometry;Toxicidade;Toxicity | pubmed |
Particulated articular cartilage for symptomatic chondral defects of the knee. | The treatment of focal cartilage defects in the knee remains a challenging clinical problem. One relatively new unique treatment option is particulated articular cartilage, which includes autograft and off-the-shelf allogeneic juvenile grafts. The use of particulated cartilage has the advantage of being a single-stage procedure. In the case of autograft, it is cost efficient, while in the juvenile allograft form, it may have increased proliferative and restorative potentials. Laboratory and clinical data are limited for particulated cartilage grafts; however, there are promising histologic and clinical outcomes. This review provides a summary of the indications, surgical technique, and most up-to-date research on particulated cartilage for the repair of symptomatic chondral defects in the knee. | Cartilage repair;Cartilage transplant;Juvenile cartilage;Particulated cartilage;Tissue regeneration | pubmed |
Pharmacological targeting of PI3K isoforms as a therapeutic strategy in chronic lymphocytic leukaemia. | PI3Kδ inhibitors such as idelalisib are providing improved therapeutic options for the treatment of chronic lymphocytic leukaemia (CLL). However under certain conditions, inhibition of a single PI3K isoform can be compensated by the other PI3K isoforms, therefore PI3K inhibitors which target multiple PI3K isoforms may provide greater efficacy. The development of compounds targeting multiple PI3K isoforms (α, β, δ, and γ) in CLL cells, in vitro, resulted in sustained inhibition of BCR signalling but with enhanced cytotoxicity and the potential for improve clinical responses. This review summarises the progress of PI3K inhibitor development and describes the rationale and potential for targeting multiple PI3K isoforms. | CLL;Duvelisib;Idelalisib;PI3K | pubmed |
Against Permitted Exploitation in Developing World Research Agreements. | This paper examines the moral force of exploitation in developing world research agreements. Taking for granted that some clinical research which is conducted in the developing world but funded by developed world sponsors is exploitative, it asks whether a third party would be morally justified in enforcing limits on research agreements in order to ensure more fair and less exploitative outcomes. This question is particularly relevant when such exploitative transactions are entered into voluntarily by all relevant parties, and both research sponsors and host communities benefit from the resulting agreements. I show that defenders of the claim that exploitation ought to be permitted rely on a mischaracterization of certain forms of interference as unjustly paternalistic and two dubious empirical assumptions about the results of regulation. The view I put forward is that by evaluating a system of constraints on international research agreements, rather than individual transaction-level interference, we can better assess the alternatives to permitting exploitative research agreements. | clinical trials;developing world bioethics;exploitation;research ethics | pubmed |
A pathway underlying the impact of CPAP adherence on intimate relationship with bed partner in men with obstructive sleep apnea. | Our aim was to determine the pathway underlying the effects of continuous positive airway pressure (CPAP) adherence on intimate relationship with bed partner in men with obstructive sleep apnea (OSA). We hypothesized that CPAP with good adherence affected the intimate relationship with bed partner directly and indirectly, and it was mediated through daytime sleepiness and activity level in men with OSA. Data were obtained from an education program for enhancing CPAP adherence. Men who were newly diagnosed of OSA and CPAP therapy naïve were recruited in a tertiary teaching hospital. Self-reported quality of life [Functional Outcomes of Sleep Questionnaire], daytime sleepiness [Epworth Sleepiness Scale (ESS)], and negative emotion symptoms [depression, anxiety, stress scale] were assessed before and after CPAP treatment at 1-year assessment. Seventy-three men were included in the data analysis, with a mean ± SD age of 52 ± 10 years, body mass index of 29.0 ± 5.2 kg/m(2), ESS of 9.5 ± 5.6, and median [interquartile range(IR)] apnea and hypopnea index of 31 (21, 56) events/h. The median (IR) CPAP daily usage was 4.3(0, 6.1) h/day. From the path analysis, CPAP therapy was shown to improve intimate relationship directly (ß = 0.185) and indirectly (ß = 0.050) by reducing daytime sleepiness and increasing activity level. However, negative emotion symptoms were not the mediators between CPAP adherence and the intimate relationship. CPAP therapy with good adherence is related directly and indirectly to a better intimate relationship with bed partner in men with OSA. It was possibly attributed to reduced daytime sleepiness and increased activity level. | CPAP adherence;Continuous positive airway pressure;Intimate relationship;Sleep apnea | pubmed |
Mec1-dependent phosphorylation of Mms21 modulates its SUMO ligase activity. | The SUMO ligase Mms21, which is a subunit of the Smc5/6 complex, is required for DNA repair. Here we present results showing that Mms21 was phosophorylated during S-phase in a manner dependent on the DNA damage kinase Mec1. Phosphorylation of Mms21 occurred in unchallenged cells, but was more abundant in the presence of DNA damaging agents. Mass spectrometry identified five phosphorylated serines organized in two regions of Mms21, and two C-terminal serines, S260 and S261, formed part of a Mec1/Tel1 consensus motif. Nonphosphorylatable substitutions of the C-terminal serines, inactivation of Mec1 or removal of the Mms21 C-terminus all abolished Mms21 phosphorylation. Additionally, strains carrying Mms21 phosphoablative alleles displayed reduced SUMO ligase activity, sensitivity to MMS and an increased rate of chromosome loss in the presence of MMS. We propose that one function of S260 S261 phosphorylation is to positively regulate the SUMO ligase activity of Mms21 and thereby promote genomic stability. | Mec1;Mms21;Phosphorylation;SUMOylation;Smc5/6 | pubmed |
UTE imaging in the musculoskeletal system. | Tissues, such as bone, tendon, and ligaments, contain a high fraction of components with "short" and "ultrashort" transverse relaxation times and therefore have short mean transverse relaxation times. With conventional magnetic resonance imaging (MRI) sequences that employ relatively long echo times (TEs), there is no opportunity to encode the decaying signal of short and ultrashort T2 /T2 * tissues before it has reached zero or near zero. The clinically compatible ultrashort TE (UTE) sequence has been increasingly used to study the musculoskeletal system. This article reviews the UTE sequence as well as various modifications that have been implemented since its introduction. These modifications have been used to improve efficiency or contrast as well as provide quantitative analysis. This article reviews several clinical musculoskeletal applications of UTE. | bicomponent analysis;musculoskeletal tissues;quantitative MRI;ultrashort TE | pubmed |
Determination of nonlinear genetic architecture using compressed sensing. | One of the fundamental problems of modern genomics is to extract the genetic architecture of a complex trait from a data set of individual genotypes and trait values. Establishing this important connection between genotype and phenotype is complicated by the large number of candidate genes, the potentially large number of causal loci, and the likely presence of some nonlinear interactions between different genes. Compressed Sensing methods obtain solutions to under-constrained systems of linear equations. These methods can be applied to the problem of determining the best model relating genotype to phenotype, and generally deliver better performance than simply regressing the phenotype against each genetic variant, one at a time. We introduce a Compressed Sensing method that can reconstruct nonlinear genetic models (i.e., including epistasis, or gene-gene interactions) from phenotype-genotype (GWAS) data. Our method uses L1-penalized regression applied to nonlinear functions of the sensing matrix. The computational and data resource requirements for our method are similar to those necessary for reconstruction of linear genetic models (or identification of gene-trait associations), assuming a condition of generalized sparsity, which limits the total number of gene-gene interactions. An example of a sparse nonlinear model is one in which a typical locus interacts with several or even many others, but only a small subset of all possible interactions exist. It seems plausible that most genetic architectures fall in this category. We give theoretical arguments suggesting that the method is nearly optimal in performance, and demonstrate its effectiveness on broad classes of nonlinear genetic models using simulated human genomes and the small amount of currently available real data. A phase transition (i.e., dramatic and qualitative change) in the behavior of the algorithm indicates when sufficient data is available for its successful application. Our results indicate that predictive models for many complex traits, including a variety of human disease susceptibilities (e.g., with additive heritability h (2)∼0.5), can be extracted from data sets comprised of n ⋆∼100s individuals, where s is the number of distinct causal variants influencing the trait. For example, given a trait controlled by ∼10 k loci, roughly a million individuals would be sufficient for application of the method. | Compressed sensing;Genomics;Nonlinear interactions | pubmed |
Diffusion-weighted magnetic resonance imaging for the prediction of pathologic response to neoadjuvant chemoradiotherapy in esophageal cancer. | To explore the value of diffusion-weighted magnetic resonance imaging (DW-MRI) for the prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer. In 20 patients receiving nCRT for esophageal cancer DW-MRI scanning was performed before nCRT, after 8-13 fractions, and before surgery. The median tumor apparent diffusion coefficient (ADC) was determined at these three time points. The predictive potential of initial tumor ADC, and change in ADC (ΔADC) during and after treatment for pathologic complete response (pathCR) and good response were assessed. Good response was defined as pathCR or near-pathCR (tumor regression grade [TRG] 1 or 2). A pathCR after nCRT was found in 4 of 20 patients (20%), and 8 patients (40%) showed a good response to nCRT. The ΔADCduring was significantly higher in pathCR vs. non-pathCR patients (34.6%±10.7% [mean±SD] vs. 14.0%±13.1%, p=0.016), as well as in good vs. poor responders (30.5%±8.3% vs. 9.5%±12.5%, p=0.002). The ΔADCduring was predictive of residual cancer at a threshold of 29% (sensitivity of 100%, specificity of 75%, PPV of 94%, and NPV of 100%), and for poor pathologic response at a threshold of 21% (sensitivity of 82%, specificity of 100%, PPV of 100%, and NPV of 80%). In this exploratory study, the treatment-induced change in ADC during the first 2-3weeks of nCRT for esophageal cancer seemed highly predictive of histopathologic response. Larger series are warranted to verify these results. | Chemoradiotherapy;Diffusion-weighted MRI;Esophageal cancer;Functional imaging;Neoadjuvant therapy | pubmed |
Mycobacterium avium-intracellulare brain abscesses in an HIV-infected patient. | The Mycobacterium avium-intracellulare complex (MAC) is an uncommon cause of brain abscesses even in patients with acquired immunodeficiency syndrome (AIDS). We present a case of a multiple MAC brain abscesses, confirmed by brain biopsy and culture, in a patient with AIDS. The patient's initial symptoms were weakness, confusion and headaches. The patient was initially treated for toxoplasmosis and pyogenic bacterial brain abscesses with no resolution. Following treatment for MAC the patient's abscesses resolved. | Brain abscess;HIV/AIDS;Mycobacterium avium–intracellulare | pubmed |
Hidden founder effects: small-scale spatial genetic structure in recently established populations of the grassland specialist plant Anthyllis vulneraria. | The long-term establishment success of founder plant populations has been commonly assessed based on the measures of population genetic diversity and among population genetic differentiation, with founder populations expected to carry sufficient genetic diversity when population establishment is the result of many colonists from multiple source populations (the 'migrant pool' colonization model). Theory, however, predicts that, after initial colonization, rapid population expansion may result in a fast increase in the extent of spatial genetic structure (SGS), independent of extant genetic diversity. This SGS can reduce long-term population viability by increasing inbreeding. Using 12 microsatellite markers, we inferred colonization patterns in four recent populations of the grassland specialist plant Anthyllis vulneraria and compared the extent of SGS between recently established and old populations. Assignment analyses of the individuals of recent population based on the genetic composition of nine adjacent putative source populations suggested the occurrence of the 'migrant pool' colonization model, further confirmed by high genetic diversity within and low genetic differentiation among recent populations. Population establishment, however, resulted in the build-up of strong SGS, most likely as a result of spatially restricted recruitment of the progeny of initial colonists. Although reduced, significant SGS was nonetheless observed to persist in old populations. The presence of SGS was in all populations associated with elevated inbreeding coefficients, potentially affecting the long-term viability of these populations. In conclusion, this study illustrates the importance of studying SGS next to population genetic diversity and differentiation to adequately infer colonization patterns and long-term establishment success of plant species. | assignment analysis;calcareous grassland;colonization;founder effects;microsatellites;point-pattern analysis | pubmed |
Hydrogen sulfide in renal physiology, disease and transplantation--the smell of renal protection. | Hydrogen sulfide (H2S), the third gasotransmitter, next to nitric oxide and carbon monoxide, is a key mediator in physiology and disease. It is involved in homeostatic functions, such as blood pressure control, electrolyte balance and apoptosis, and regulates pathological mechanisms, including oxidative stress and inflammation. Besides, it is believed to serve as an oxygen sensor under ischemic conditions. The kidney plays a decisive role in many of these processes, indicating an interplay between H2S and renal (patho)physiology. In this review we focus on the (protective) functions of H2S in the kidney. We first discuss endogenous renal H2S production and signaling and elaborate on its regulatory functions in renal physiology. Next, we present data on the role of aberrant H2S levels in the onset and progression of renal disease and suggest the use of H2S metabolites as biomarkers. Finally, we describe that exogenous H2S can protect the kidney against various forms of injury and conclude that modulation of renal H2S levels holds promise for renal patients in the future. | 3MST;CBS;CSE;H(2)S;Ischemia-reperfusion;Kidney disease | pubmed |
The role and mechanism of WEE1 on the cisplatin resistance reversal of the HepG2/DDP human hepatic cancer cell line. | Drug resistance to cisplatin with continuous drug treatment is one of the most common causes of chemotherapy failure in hepatic carcinoma. Accumulating evidence suggests that WEE1 G2 checkpoint kinase (WEE1) is involved in cisplatin resistance, which has been demonstrated to correlate with cancer initiation and progression. However, the role and molecular mechanism of WEE1 in the drug resistance of hepatic cancer remains unclear. In the present study, using the WEE-knockdown hepatic cancer cell line HepG2/DDP, the role of WEE1 and its molecular mechanism were investigated. It was demonstrated that silencing WEE1 expression resulted in an increased cisplatin sensitivity of HepG2/DDP, in addition to an increased rate of apoptosis and intracellular concentration of rhodamine 123. The expression levels of P-gp, MDR1, MRP1, LRP, BCL-2, survivin and GST in WEE1-silenced HepG2/DDP cells were significantly reduced, and phosphorylation levels of MEK and ERK were significantly downregulated. The results demonstrated that WEE1 negatively regulated the multidrug resistance potential of human hepatic cancer cells by modulating the expression of relevant drug resistance genes and the activity of the MEK/ERK pathway. Therefore, WEE1 may be a monitoring bio-marker for drug resistance, and a therapeutic target in hepatic cancer. | WEE1;cisplatin resistance;hepatic cancer | pubmed |
Synbiotic containing Bacillus coagulans and fructo-oligosaccharides for functional abdominal pain in children. | We evaluated the effectiveness of a synbiotic in the treatment of childhood functional abdominal pain (FAP). Probiotics are effective in the treatment of functional gastrointestinal disorders in adult patients, but there is lack of information in children. Children with FAP, based on the Rome III criteria (n = 115, aged 6-18 years), were randomized to receive either synbiotic (Bacillus coagulans, Unique IS-2, 150 million spore plus FOS, 100 mg) twice daily or placebo for four weeks. Treatment response was defined as ≥ 2-point reduction in the 6-point self-rated pain scale or "no pain". Physician-rated global severity and improvement were also evaluated. Patients were followed for a total of 12 weeks. Eighty-eight patients completed the trial (45 with synbiotic). Response rate was higher with synbiotic than placebo after medication (60% vs. 39.5%, P = 0.044), but was not different between the two groups at week 12 (64.4% vs. 53.4%, P = 0.204). Difference between the two groups regarding the physician-rated global severity over the study period was not statistically significant (z = -1.87, P = 0.062). There was no significant difference between the two groups in physician-rated global improvement (week 4, P = 0.437; week 12, P = 0.111). Receiving synbiotic (OR 2.608, 95% CI: 1.01-6.68) and baseline pain score (OR 2.21, 95% CI: 1.19-4.10) were predictors of treatment response after medication. The synbiotic containing Bacillus coagulans and FOS seems to be effective in the treatment of childhood FAP. Further trials are recommended in this regard. | Abdominal pain;Child;Prebiotic;Probiotic;Synbiotic | pubmed |
Prevalence of virulence factors and phylogenetic characterization of uropathogenic Escherichia coli causing urinary tract infection in patients with and without diabetes mellitus. | We aimed to determine the virulence factor profile and phylogenetic grouping of uropathogenic Escherichia coli (UPEC) causing urinary tract infection (UTI) in patients with and without diabetes mellitus (DM). A total of 280 UPEC were collected from the urine samples of patients with DM (n=126) and patients suffering from non-DM UTIs (n=154). All isolates were subjected to phenotypic and genotypic virulence factor profile and phylogenetic grouping. There was no significant difference in phenotypic virulence factors of UPEC causing UTI from patients with and without DM; alpha-haemolysin (DM=52, 41.2%; non-DM=69, 44.8%), mannose resistant haemagglutination (DM=6, 36.2%; non-DM=64, 41.5%), biofilm production (DM=33.3%; non-DM=25.9%), serum resistance (DM=27, 21.4%; non-DM=46, 29.8%), cell surface hydrophobicity (DM=22, 17.1%; non-DM=18, 11.6%) and mannose sensitive hemagglutnation (DM=18, 14.2%; non-DM=29, 18.8%). Among the genotypic virulence markers, papC gene was most prevalent in both patients with DM (n=65, 51.6%) and without DM (n=88, 57.1%), followed by hlyD gene (DM=36, 28.6%; non-DM=52, 33.8%). Only cnf-1 gene was observed to be significantly associated (p<0.05) with the non-DM status (n=35, 22.7%) than DM (n=15, 11.9%). Irrespective of the diabetic status, majority of the UPEC isolates (approximately 50%) belonged to phylogenetic group B2 predominantly harboring the virulence genes papC, hlyD and cnf-1. This study demonstrates that there may not be a differential selection of virulence properties of UPEC causing UTI in patients with DM and in the general population. | India;Phylogenetic characterization;Urinary tract infections;Uropathogenic Escherichia coli;Urovirulence genes | pubmed |
Immune mechanism-targeted treatment of experimental epidermolysis bullosa acquisita. | Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous dermatosis characterized by chronic mucocutaneous blistering caused by autoantibodies directed against type VII collagen. EBA causes a high morbidity and is difficult to treat. Model systems have significantly broadened our understanding of EBA pathogenesis, leading to the identification of numerous therapeutic targets. Of these, so far, a few have been evaluated for their therapeutic potential in preclinical models. In mice, EBA can be induced by transfer of anti-type VII collagen antibodies or by immunization with the protein. The latter model, immunization-induced EBA, is ideal to test drugs for their therapeutic efficacy. Here, mice with already established disease can be treated for prolonged periods. Albeit time consuming, results from immunization-induced EBA will pave the way for clinical application in patients. As the key pathogenic principle, that is, autoantibody-induced, leukocyte-mediated tissue injury and inflammation, is shared by other diseases, these findings may have translational applications beyond EBA. | GM-CSF;PI3K;anakinra;animal models;cell signaling;cytokines;epidermolysis bullosa acquisita;p38 MAPK;treatment | pubmed |
The effect of scapular posterior tilt exercise, pectoralis minor stretching, and shoulder brace on scapular alignment and muscles activity in subjects with round-shoulder posture. | There are various methods for rehabilitating round-shoulder posture (RSP), including strengthening exercises, stretching, and using a shoulder brace or taping to correct the altered posture. However, no study has determined which intervention is the most effective of the three methods to decrease RSP (intervention #1: scapular posterior tilting exercise alone [hereafter, SPT], intervention #2: the scapular posterior tilting exercise after PM stretching [PM stretch+SPT], and intervention #3: the scapular posterior tilting exercise with use of a shoulder brace [SPT+brace]). The purpose of this study was to compare the SPT, PM stretch+SPT, and SPT+brace on RSP, PM index (PMI), and lower trapezius (LT) and serratus anterior (SA) activity in subjects with RSP. In total, fifteen young men with RSP, participated in the study (21.46 ± 2.30 years old). RSP was confirmed using a caliper measure. Surface electromyography (SEMG) data for LT and SA activity were collected during the three interventions, and the SEMG data are expressed as a percentage of the maximal voluntary isometric contraction (%MVIC). RSP was significantly less in the PM stretch+SPT and SPT+brace than in the SPT (P<0.05). PMI was significantly greater in the PM stretch+SPT and SPT+brace than in the SPT (P<0.05). LT activity was significantly greater in the PM stretch+SPT than in the SPT or SPT+brace in subjects with RSP (P<0.05). The PM stretching exercise and application of a shoulder brace may help correct RSP and restore the length of the PM. The posterior tilting exercise after PM stretching was the most effective method for eliciting greater LT muscle activation among the interventions tested. | Pectoralis minor stretching;Round-shoulder posture;Scapular posterior tilting exercise;Shoulder brace | pubmed |
Reference genes for valid gene expression studies on rat dental, periodontal and alveolar bone tissue by means of RT-qPCR with a focus on orthodontic tooth movement and periodontitis. | To obtain valid results in relative gene/mRNA-expression analyses by RT-qPCR, a careful selection of stable reference genes is required for normalization. Currently there is little information on reference gene stability in dental, periodontal and alveolar bone tissues of the rat, especially regarding orthodontic tooth movement and periodontitis. We therefore aimed to identify the best selection and number of reference genes under these experimental as well as physiological conditions. In 7 male Fischer344-rats the upper left first and second molars were moved orthodontically for 2 weeks and in 7 more animals additionally subjected to an experimental periodontitis, whereas 7 animals were left untreated. Tissue samples of defined size containing both molars (without crowns) as well as the adjacent periodontal and alveolar bone tissue were retrieved and RNA extracted for RT-qPCR analyses. Nine candidate reference genes were evaluated and ranked according to their expression stability by 4 different algorithms (geNorm, NormFinder, BestKeeper, comparative ΔCq). PPIB/YWHAZ were the most stabile reference genes for the combined dental, periodontal and alveolar bone tissue of the rat overall, in untreated animals and rats with additional periodontitis, whereas PPIB/B2M performed best in orthodontically treated rats with YWHAZ ranking third. Gene-stability ranking differed considerably between investigated groups. A combination of two reference genes was found to be sufficient for normalization in all cases. The substantial differences in expression stability emphasize the need for valid reference genes, when aiming for meaningful results in relative gene expression analyses. Our results should enable researchers to optimize gene expression analysis in future studies by choosing the most suitable reference genes for normalization. | Dental research;Gene expression;Gene expression regulation;Orthodontics;Periodontitis;RT-qPCR;Rats, Inbred F344 | pubmed |
Comparative evaluation of the amount of gingival displacement produced by three different gingival retraction systems: An in vivo study. | Tetrahydrozoline has been introduced as new gingival retraction agent but its clinical efficacy with widely used conventional retraction agents has not been tested. The study was designed to clinically evaluate efficacy of newer retraction agent tetrahydrozoline with two widely used retraction systems i.e., Expasyl retraction system and medicated retraction cords on basis of amount of gingival retraction. 30 subjects were selected according to inclusion and exclusion criteria. Maxillary Impressions were made with irreversible hydrocolloid for all subjects. Tray material was used for making the special tray. Latin Block Design was Used in the Study to avoid tissue fatigue. Retraction was done with aluminium chloride; Tetrahydrozoline and Expasyl according to Latin block design. Impressions were poured with die stone. Casts were retrieved and sections were made with die cutter. 3 mm thin slices were obtained. Each slice was used to measure the amount of retraction under stereomicroscope under 20x and images were transferred to image analyser. The amount of gingival retraction obtained by using aluminium chloride as gingival retraction agent was maximum (148238.33 μm(2)) compared to tetrahydrozoline (140737.87 μm(2)) and Expasyl (67784.90 μm(2)). | Aluminum chloride;expasyl;gingival displacement;tetrahydrozoline | pubmed |
Rapid SERS monitoring of lipid-peroxidation-derived protein modifications in cells using photonic crystal fiber sensor. | We proposed a side channel photonic crystal fiber (SC-PCF) based Surface enhanced Raman spectroscopy (SERS) platform which is able to accurately monitor lipid peroxidation derived protein modifications in cells. This platform incorporates linoleamide alkyne (LAA), which is oxidized and subsequently modifies proteins in cells with alkyne functional group upon lipid peroxidation. By loading the side channel of SC-PCF with a mixture of gold nanoparticles and LAA treated cells, and subsequently measuring the interference-free alkyne Raman peak from these proteins in cells, strong SERS signal was obtained. The platform provides a method for the rapid monitoring of lipid peroxidation derived protein modification in cells. | HepG2 cell;Surface enhanced Raman spectroscopy;gold nanoparticles;linoleamide alkyne;lipid peroxidation;side channel PCF | pubmed |
Population pharmacokinetics of naloxegol in a population of 1247 healthy subjects and patients. | Naloxegol, a polyethylene glycol conjugated derivative of the opioid antagonist naloxone, is in clinical development for treatment of opioid-induced constipation (OIC). The aim of the study was to develop a population pharmacokinetic model describing the concentration vs. time profile of orally administered naloxegol, and determine the impact of pre-specified demographic and clinical factors and concomitant medication on population estimates of apparent clearance (CL/F) and apparent central compartment volume of distribution (Vc /F). Analysis included 12,844 naloxegol plasma concentrations obtained from 1247 healthy subjects, patients with non-OIC and patients with OIC in 14 phase 1, 2b and 3 clinical studies. Pharmacokinetic analysis used the non-linear mixed effects modelling program. Goodness of fit plots and posterior predictive checks were conducted to confirm concordance with observed data. The final model was a two compartment disposition model with dual absorptions, comprising one first order absorption (ka1 4.56 h(-1) ) and one more complex absorption with a transit compartment (ktr 2.78 h(-1) ). Mean (SE) parameter estimates for CL/F and Vc /F, the parameters assessed for covariate effects, were 115 (3.41) l h(-1) and 160 (27.4) l, respectively. Inter-individual variability was 48% and 51%, respectively. Phase of study, gender, race, concomitant strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers, P-glycoprotein inhibitors or inducers, naloxegol formulation, baseline creatinine clearance and baseline opioid dose had a significant effect on at least one pharmacokinetic parameter. Simulations indicated concomitant strong CYP3A4 inhibitors or inducers had relevant effects on naloxegol exposure. Administration of strong CYP3A4 inhibitors or inducers had a clinically relevant influence on naloxegol pharmacokinetics. | NKTR-118;naloxegol;nonmem;pharmacokinetics | pubmed |
Predictors for Surgery in Shoulder Instability: A Retrospective Cohort Study Using the FEDS System. | Shoulder instability is a common cause of pain and dysfunction in young, active patients. While studies have analyzed risk factors for recurrent instability and failure after instability surgery, few have examined which variables are associated with initial surgery in this patient population. To identify variables that may be associated with surgical intervention in patients with shoulder instability in the context of the FEDS (frequency, etiology, direction, severity) classification, a system that may be useful in the surgical treatment of shoulder instability patients. Cohort study (prognosis); Level of evidence, 2. A database of patients treated for shoulder instability from 3 separate institutions from 2005 to 2010 was generated using International Classification of Diseases-9th Revision data. Data were collected via retrospective review. Injury data were categorized according to the FEDS system. Data were analyzed for significance, with the primary outcome of surgical intervention. Summary statistics were used to assess which variables were associated with eventual surgery. To test the unadjusted bivariate associations between shoulder surgery and each data point, Pearson chi-square tests were used for categorical variables and Wilcoxon tests were used for continuous variables. Over the study time period, 377 patients were treated for shoulder instability. Patients who had surgery were more likely younger, had recurrent instability, and had their initial injury while playing a sport. Most patients had anterior instability; however, there was a greater proportion of posterior instability patients in the operative group. Severity of dislocation, measured by whether the patient required help to relocate the shoulder, was not significantly associated with eventual surgery. While imaging was not available for all patients, surgical patients were more likely to have magnetic resonance imaging findings of anterior labral injury and less likely to have a supraspinatus or subscapularis tear. Patients who underwent surgery for shoulder instability were younger, more likely to have experienced recurrent instability, and more likely to have sustained their original injury while playing sports. The FEDS classification, particularly the frequency and etiology of the patient's shoulder instability, may be helpful in identifying patients with a higher likelihood of undergoing surgical treatment. | FEDS classification;shoulder instability;shoulder instability surgery | pubmed |
Subsets and Splits