194 research outputs found

    Sex differences in time to task failure and blood flow for an intermittent isometric fatiguing contraction

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    The purpose of this study was to compare the time to task failure, postcontraction hyperemia, and vascular conductance of young men and women for a submaximal intermittent fatiguing contraction performed with the handgrip muscles. Twenty men and 20 women (mean SD: 22 4 years) performed an isometric contraction at 50% of maximal voluntary contraction (MVC) (6-s contraction, 4-s rest) until task failure. Forearm venous occlusion plethysmography was used to estimate the peak blood flow (after 10-min occlusion) and blood flow at rest after 6-s submaximal contractions of varying intensities, and during an intermittent fatiguing contraction at 1-min intervals and task failure. The time to task failure was longer for the women compared with the men (408 205 s vs. 297 57 s, P 0.05). Postcontraction hyperemia and vascular conductance were greater for men than for women after nonfatiguing 6-s submaximal contractions performed at 20%, 40%, 50%, 60%, and 80% of MVC force (P 0.05). In contrast, hyperemia and vascular conductance were similar for both genders when measured at 50 s into the fatiguing contraction, at each minute thereafter, and at task failure. Regression analysis indicated that the rate of electromyographic activity and perceived exertion were the significant predictors of the time to task failure. The longer time to task failure for women compared with men for an intermittent fatiguing contraction with handgrip muscles was not explained by postcontraction hyperemia or vascular conductance with fatigue

    Early microrecanalization of vas deferens following biodegradable graft implantation in bilaterally vasectomized rats

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    We evaluated a biodegradable graft for reconstruction of rat vasa deferentia with long obstructed or missing segments. A total of 47 Sprague-Dawley rats underwent bilateral vasectomy and were divided into groups according to length of the vas deferens affected (0.5, 1, 1.5 cm). After 8 weeks, poly-(D,L-lactide) (PDLA) grafts were used to reconnect the vas deferens. Grafts and adjoining vasa deferentia were excised 8 and 12 weeks later and evaluated microscopically. At 8 weeks, microscopic changes included a robust inflammatory response around the grafts. All grafts were still intact but in the early stages of degradation. No microtubules, indicative of vas deferens recanalization, were identified. One specimen showed evidence of healing and neovascularization at the interface zone between the vas deferens and the graft. At 12 weeks, grafts were further degraded but still present. Microscopic evaluation showed decreased inflammation. Seven specimens showed neovascularization at the interface zone; two of these showed distinct epithelialized vas deferens microcanals at the graft edges. One specimen showed a microcanal spanning the entire 0.5-cm graft. A time period of 8 weeks is not ample enough for vas deferens regeneration in the setting of a biodegradable PDLA graft; however, early evidence of re-growth was seen at 12 weeks. A longer healing time should permit further biodegradation of the graft, as well as re-growth and possible eventual reconnection of the vas deferens, allowing passage of sperm. These findings suggest a potential role for biodegradable grafts in the reconstruction of vas deferens with long obstructed segments

    Gestational Age at Birth and Risk of Developmental Delay: The Upstate KIDS Study

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    Objective—To model the association between gestational age at birth and early child development through 3 years of age. Study Design—Development of 5868 children in Upstate KIDS (New York State; 2008–2014) was assessed at 7 time-points using the Ages and Stages Questionnaire (ASQ). The ASQ was implemented using gestational age corrected dates of birth at 4, 8, 12, 18, 24, 30, and 36 months. Whether children were eligible for developmental services from the Early Intervention Program (EIP) was determined through linkage. Gestational age was based on vital records. Statistical models adjusted for covariates including sociodemographic factors, maternal smoking and plurality. Results——Compared to gestational age of 39 weeks, adjusted odds ratios (aOR) and 95% confidence intervals of failing the ASQ for children delivered at \u3c 32, 32–34, 35–36, 37, 38, and 40 weeks gestational age were: 5.32 (3.42, 8.28), 2.43 (1.60, 3.69), 1.38 (1.00, 1.90), 1.37 (0.98, 1.90), 1.29 (0.99, 1.67), 0.73 (0.55, 0.96), and 0.51 (0.32, 0.82). Similar risks of being eligible for EIP services were observed (aOR: 4.19, 2.10, 1.29, 1.20, 1.01, 1.00 (ref), 0.92, 0.78, respectively for \u3c 32, 32–34, 37, 38, 39 (ref), 40, 41 weeks). Conclusion—Gestational age was inversely associated with developmental delays for all gestational ages. Evidence from our study is potentially informative for low-risk deliveries at 39 weeks but it is notable that deliveries at 40 weeks exhibited further lower risk

    A scoping review of biopsychosocial risk factors and co-morbidities for common spinal disorders

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    OBJECTIVE: The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders. METHODS: A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities. RESULTS: Of 3,453 candidate papers, 145 met study criteria and were included in this review. Risk factors were reported for group 1: non-specific low back pain (smoking, overweight/obesity, negative recovery expectations), non-specific neck pain (high job demands, monotonous work); group 2: degenerative spinal disease (workers\u27 compensation claim, degenerative scoliosis), and group 3: spinal tuberculosis (age, imprisonment, previous history of tuberculosis), spinal cord injury (age, accidental injury), vertebral fracture from osteoporosis (type 1 diabetes, certain medications, smoking), and neural tube defects (folic acid deficit, anti-convulsant medications, chlorine, influenza, maternal obesity). A range of comorbidities was identified for spinal disorders. CONCLUSION: Many associated factors for common spinal disorders identified in this study are modifiable. The most common spinal disorders are co-morbid with general health conditions, but there is a lack of clarity in the literature differentiating which conditions are merely comorbid versus ones that are risk factors. Modifiable risk factors present opportunities for policy, research, and public health prevention efforts on both the individual patient and community levels. Further research into prevention interventions for spinal disorders is needed to address this gap in the literature

    Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation

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    Mutations or duplications in MECP2 cause Rett and Rett-like syndromes, neurodevelopmental disorders characterized by mental retardation, motor dysfunction, and autistic behaviors. MeCP2 is expressed in many mammalian tissues and functions as a global repressor of transcription; however, the molecular mechanisms by which MeCP2 dysfunction leads to the neural-specific phenotypes of RTT remain poorly understood. Here, we show that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism. MeCP2 S421 phosphorylation is induced selectively in the brain in response to physiological stimuli. Significantly, we find that S421 phosphorylation controls the ability of MeCP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of Bdnf transcription. These findings suggest that, by triggering MeCP2 phosphorylation, neuronal activity regulates a program of gene expression that mediates nervous system maturation and that disruption of this process in individuals with mutations in MeCP2 may underlie the neural-specific pathology of RTT

    Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

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    BACKGROUND: Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). METHODS: TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. RESULTS: MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4 expression. Furthermore, a DcR2 siRNA approach lowered TRAIL-R4 expression on surface and this sensitized MCF7 cells to TRAIL. CONCLUSION: The expression of TRAIL-R4 decoy receptor appeared to be well correlated with TRAIL resistance encountered in breast cancer cells. Both adenovirus mediated IKKβKA expression and a DcR2 siRNA approach sensitized MCF7 breast cancer cells to TRAIL

    Minimizing Errors in RT-PCR Detection and Quantification of SARS-CoV-2 RNA for Wastewater Surveillance

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    Wastewater surveillance for pathogens using the reverse transcription-polymerase chain reaction (RT-PCR) is an effective, resource-efficient tool for gathering additional community-level public health information, including the incidence and/or prevalence and trends of coronavirus disease-19 (COVID-19). Surveillance of SARS-CoV-2 in wastewater may provide an early-warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is rapidly increasing. However, there are no standardized protocols nor harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can lead to false-positive and -negative errors in the surveillance of SARS-CoV-2, culminating in recommendations and strategies that can be implemented to identify and mitigate these errors. Recommendations include, stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, amplification inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly during a low incidence of SARS-CoV-2 in wastewater. Corrective and confirmatory actions must be in place for inconclusive and/or potentially significant results (e.g., initial onset or reemergence of COVID-19 in a community). It will also be prudent to perform inter-laboratory comparisons to ensure results are reliable and interpretable for ongoing and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance was demonstrated during this global crisis. In the future, wastewater will play an important role in the surveillance of a range of other communicable diseases.Highlights: Harmonized QA/QC procedures for SARS-CoV-2 wastewater surveillance are lacking; Wastewater analysis protocols are not optimized for trace analysis of viruses; False-positive and -negative errors have consequences for public health responses; Inter-laboratory studies utilizing standardized reference materials and protocols are needed.info:eu-repo/semantics/publishedVersio
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