Dietary intake and stress fractures among elite male combat recruits

<p>Abstract</p> <p>Background</p> <p>Appropriate and sufficient dietary intake is one of the main requirements for maintaining fitness and health. Inadequate energy intake may have a negative impact on physical performance which may result in injuries among physically active populations. The purpose of this research was to evaluate a possible relationship between dietary intake and stress fracture occurrence among combat recruits during basic training (BT).</p> <p>Methods</p> <p>Data was collected from 74 combat recruits (18.2 ± 0.6 yrs) in the Israeli Defense Forces. Data analyses included changes in anthropometric measures, dietary intake, blood iron and calcium levels. Measurements were taken on entry to 4-month BT and at the end of BT. The occurrence of stress reaction injury was followed prospectively during the entire 6-month training period.</p> <p>Results</p> <p>Twelve recruits were diagnosed with stress fracture in the tibia or femur (SF group). Sixty two recruits completed BT without stress fractures (NSF). Calcium and vitamin D intakes reported on induction day were lower in the SF group compared to the NSF group-38.9% for calcium (589 ± 92 and 964 ± 373 mg·d^-1, respectively, <it>p </it>< 0.001), and-25.1% for vitamin D (117.9 ± 34.3 and 157.4 ± 93.3 IU·d^-1, respectively, <it>p </it>< 0.001). During BT calcium and vitamin D intake continued to be at the same low values for the SF group but decreased for the NSF group and no significant differences were found between these two groups.</p> <p>Conclusions</p> <p>The development of stress fractures in young recruits during combat BT was associated with dietary deficiency before induction and during BT of mainly vitamin D and calcium. For the purpose of intervention, the fact that the main deficiency is before induction will need special consideration.</p

Assessing socioeconomic health care utilization inequity in Israel: impact of alternative approaches to morbidity adjustment

<p/> <p>Background</p> <p>The ability to accurately detect differential resource use between persons of different socioeconomic status relies on the accuracy of health-needs adjustment measures. This study tests different approaches to morbidity adjustment in explanation of health care utilization inequity.</p> <p>Methods</p> <p>A representative sample was selected of 10 percent (~270,000) adult enrolees of Clalit Health Services, Israel's largest health care organization. The Johns-Hopkins University Adjusted Clinical Groups^®were used to assess each person's overall morbidity burden based on one year's (2009) diagnostic information. The odds of above average health care resource use (primary care visits, specialty visits, diagnostic tests, or hospitalizations) were tested using multivariate logistic regression models, separately adjusting for levels of health-need using data on age and gender, comorbidity (using the Charlson Comorbidity Index), or morbidity burden (using the Adjusted Clinical Groups). Model fit was assessed using tests of the Area Under the Receiver Operating Characteristics Curve and the Akaike Information Criteria.</p> <p>Results</p> <p>Low socioeconomic status was associated with higher morbidity burden (1.5-fold difference). Adjusting for health needs using age and gender or the Charlson index, persons of low socioeconomic status had greater odds of above average resource use for all types of services examined (primary care and specialist visits, diagnostic tests, or hospitalizations). In contrast, after adjustment for overall morbidity burden (using Adjusted Clinical Groups), low socioeconomic status was no longer associated with greater odds of specialty care or diagnostic tests (OR: 0.95, CI: 0.94-0.99; and OR: 0.91, CI: 0.86-0.96, for specialty visits and diagnostic respectively). Tests of model fit showed that adjustment using the comprehensive morbidity burden measure provided a better fit than age and gender or the Charlson Index.</p> <p>Conclusions</p> <p>Identification of socioeconomic differences in health care utilization is an important step in disparity reduction efforts. Adjustment for health-needs using a comprehensive morbidity burden diagnoses-based measure, this study showed relative underutilization in use of specialist and diagnostic services, and thus allowed for identification of inequity in health resources use, which could not be detected with less comprehensive forms of health-needs adjustments.</p

Identification of Candidate Growth Promoting Genes in Ovarian Cancer through Integrated Copy Number and Expression Analysis

Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (>40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r≥0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2

Enhanced production yields of rVSV-SARS-CoV-2 vaccine using Fibra-Cel® macrocarriers

The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension. However, the titers were limited by both the carrier surface area and shear forces. Here, we describe the development of a bioprocess for rVSV-ΔG-spike production in serum-free Vero cells using porous Fibra-Cel® macrocarriers in fixed-bed BioBLU®320 5p bioreactors, leading to high-end titers. We identified core factors that significantly improved virus production, such as the kinetics of virus production, the use of macrospargers for oxygen supply, and medium replenishment. Implementing these parameters, among others, in a series of GMP production processes improved the titer yields by at least two orders of magnitude (2e9 PFU/mL) over previously reported values. The developed process was highly effective, repeatable, and robust, creating potent and genetically stable vaccine viruses and introducing new opportunities for application in other viral vaccine platforms

Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission

The eIF4E-binding proteins (4E-BPs) repress translation initiation by preventing eIF4F complex formation. Of the three mammalian 4E-BPs, only 4E-BP2 is enriched in the mammalian brain and plays an important role in synaptic plasticity and learning and memory formation. Here we describe asparagine deamidation as brain-specific posttranslational modification of 4E-BP2. Deamidation is the spontaneous conversion of asparagines to aspartates. Two deamidation sites were mapped to an asparagine-rich sequence unique to 4E-BP2. Deamidated 4E-BP2 exhibits increased binding to the mammalian Target of Rapamycin (mTOR)-binding protein raptor, which effects its reduced association with eIF4E. 4E-BP2 deamidation occurs during postnatal development, concomitant with the attenuation of the activity of the PI3K-Akt-mTOR signalling pathway. Expression of deamidated 4E-BP2 in 4E-BP2−/− neurons yielded mEPSCs exhibiting increased charge transfer with slower rise and decay kinetics, relative to the wild type form. 4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signalling

Pre- and postsynaptic actions of pentobarbital on corticothalamic transmission

This thesis examined the pre- and postsynaptic actions of an anesthetic barbiturate, pentobarbital, on neurons of the corticothalamocortical system in vitro. The in vivo system mediates conscious and sleep states. The thesis focuses on pentobarbital actions that induce network oscillations, and modify responses of single thalamocortical neurons to corticothalamic stimulus trains. The thesis addressed the following: (1) does pentobarbital induce oscillations in thalamic slices? (2) what receptors contribute to oscillations? (3) how does pentobarbital interact with modulators of excitability? (4) what are pentobarbital effects on post- and presynaptic parameters of glutamatergic transmission during short-term depression (STD)? (5) how do the effects of pentobarbital on STD compare with selective action potential blockade? (6) given the well-known actions of pentobarbital on metabolism, do its effects on STD mimic glucose deprivation? Pentobarbital at a subanesthetic concentration induced 1-15 Hz oscillations, requiring glutamatergic excitation, but not elevated temperature or low extracellular [Mg²⁺]. Glycine receptors mediated oscillations in ventrobasal nuclei, disconnected from nucleus reticularis thalami (nRT). γ-aminobutyrate (GABA) receptors mediated oscillations in isolated nRT. By acting on N-methyl-D-aspartate (NMDA) receptors, spermine modulated membrane rectification, firing threshold, and decay of excitatory postsynaptic potentials (EPSPs). These interactions occurred at the polyamine site on NMDA receptors. Pentobarbital enhanced STD of excitatory postsynaptic currents (EPSCs) by decreasing quantal size. These use-dependent effects persisted during blockade of desensitization and saturation of glutamate receptors and hence, likely were presynaptic. Pentobarbital decreased apparent quantal size and amplitude in the post-stimulus train, evoked miniature EPSCs (minEPSCs) but not ongoing, pre-train minEPSCs, reaffirming a presynaptic action. Pentobarbital eliminated EPSC facilitation early in a train, due to high extracellular [K⁺] ([K⁺][sub e]). Partial blockade of action potentials by tetrodotoxin reduced the apparent quantal size and evoked minEPSC size, without effect on pre-stimulation minEPSC. Like pentobarbital, glucose deprivation reduced quantal size and rundown of quantal contents. Glucose deprivation abolished STD and intra-train, post-gap jump in EPSC amplitude. In summary, this thesis describes several new types of synaptic modulation by pentobarbital that complement known postsynaptic mechanisms of anesthesia. The analysis techniques provide a new approach for examining the pre- and postsynaptic drug effects on transmission in the brain.Medicine, Faculty ofGraduat

The response of the central nervous system to experimental colitis

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The COP9 signalosome mediates the Spt23 regulated fatty acid desaturation and ergosterol biosynthesis

The COP9 signalosome (CSN) is a conserved eukaryotic complex, essential for vitality in all multicellular organisms and critical for the turnover of key cellular proteins through catalytic and non-catalytic activities. Saccharomyces cerevisiae is a powerful model organism for studying fundamental aspects of the CSN complex. This CSN includes a conserved enzymatic core but lacks few subunits that participate in non-catalytic activities, probably explaining its non-essentiality for life. A previous transcriptomic analysis of an S. cerevisiae strain deleted in the CSN5/RRI1 gene lacking CSN catalytic subunit, revealed a downregulation of genes involved in lipid metabolism. We now show that the S. cerevisiae CSN holocomplex is essential for cellular lipid homeostasis. Defects in CSN assembly or activity lead to decreased quantities of ergosterol and unsaturated fatty acids; vacuole defects; diminished lipid droplets size; and to accumulation of endoplasmic reticulum stress. The molecular mechanism behind these findings depends on CSN involvement in upregulating mRNA expression of SPT23. Spt23 is a novel activator of lipid desaturation and ergosterol biosynthesis. Our data reveal for the first time a functional link between the CSN holocomplex and Spt23. Moreover, CSN-dependent upregulation of SPT23 transcription is necessary for the fine-tuning of lipid homeostasis and for cellular health