Utilization of a Palliative Care Trigger in the Surgical Intensive Care Unit

Our project aims to expand palliative care availability in the SICU by implementing a consult trigger program. We also aim to learn about and measure compassion fatigue of providers within the SICU

Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

Abstract Background One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. Methods RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. Results These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. Conclusion The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic

Injuries and Training Practices in Competitive Adolescent Distance Runners: A Retrospective Cross-Sectional Study

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Requests to access the data will be considered by the authors, within the constraints of privacy and consent.Background: Distance running is one of the most popular sports around the world. The epidemiology of running-related injury (RRI) has been investigated in adults, but few studies have focused on adolescent distance runners. Objectives: (1) To provide descriptive epidemiology of RRI (risks, rates, body regions/areas, and severity) and examine the training practices (frequency, volume, and intensity) of competitive adolescent distance runners (13-18 years) in England, and (2) to describe potential risk factors of RRI. Methods: A cross-sectional study design was used. Adolescent distance runners (n = 113) were recruited from England Athletics affiliated clubs. Participants voluntarily completed an online questionnaire between April and December 2018. At the time of completion, responses were based on the participant's previous 12-months of distance running participation. Incidence proportions (IP) and incidence rates (IR) were calculated. Results: The IP for "all RRI" was 68% (95% CI: 60-77), while the IR was 6.3/1,000 participation hours (95% CI: 5.3-7.4). The most commonly injured body areas were the knee, foot/toes, and lower leg; primarily caused by overuse. The number of training sessions per week (i.e., frequency) significantly increased with chronological age, while a large proportion of participants (58%) self-reported a high level of specialisation. Conclusions: RRI is common in competitive adolescent distance runners. These descriptive data provide guidance for the development of RRI prevention measures. However, analytical epidemiology is required to provide better insight into potential RRI risk factors in this specific population.Economic and Social Research Council (ESRC

High local substrate availability stabilizes a cooperative trait

Cooperative behavior is widely spread in microbial populations. An example is the expression of an extracellular protease by the lactic acid bacterium Lactococcus lactis, which degrades milk proteins into free utilizable peptides that are essential to allow growth to high cell densities in milk. Cheating, protease-negative strains can invade the population and drive the protease-positive strain to extinction. By using multiple experimental approaches, as well as modeling population dynamics, we demonstrate that the persistence of the proteolytic trait is determined by the fraction of the generated peptides that can be captured by the cell before diffusing away from it. The mechanism described is likely to be relevant for the evolutionary stability of many extracellular substrate-degrading enzymes

Genetic and Non-Genetic Influences during Pregnancy on Infant Global and Site Specific DNA Methylation: Role for Folate Gene Variants and Vitamin B12

Inter-individual variation in patterns of DNA methylation at birth can be explained by the influence of environmental, genetic and stochastic factors. This study investigates the genetic and non-genetic determinants of variation in DNA methylation in human infants. Given its central role in provision of methyl groups for DNA methylation, this study focuses on aspects of folate metabolism. Global (LUMA) and gene specific (IGF2, ZNT5, IGFBP3) DNA methylation were quantified in 430 infants by Pyrosequencing®. Seven polymorphisms in 6 genes (MTHFR, MTRR, FOLH1, CβS, RFC1, SHMT) involved in folate absorption and metabolism were analysed in DNA from both infants and mothers. Red blood cell folate and serum vitamin B12 concentrations were measured as indices of vitamin status. Relationships between DNA methylation patterns and several covariates viz. sex, gestation length, maternal and infant red cell folate, maternal and infant serum vitamin B12, maternal age, smoking and genotype were tested. Length of gestation correlated positively with IGF2 methylation (rho = 0.11, p = 0.032) and inversely with ZNT5 methylation (rho = −0.13, p = 0.017). Methylation of the IGFBP3 locus correlated inversely with infant vitamin B12 concentration (rho = −0.16, p = 0.007), whilst global DNA methylation correlated inversely with maternal vitamin B12 concentrations (rho = 0.18, p = 0.044). Analysis of common genetic variants in folate pathway genes highlighted several associations including infant MTRR 66G>A genotype with DNA methylation (χ2 = 8.82, p = 0.003) and maternal MTHFR 677C>T genotype with IGF2 methylation (χ2 = 2.77, p = 0.006). These data support the hypothesis that both environmental and genetic factors involved in one-carbon metabolism influence DNA methylation in infants. Specifically, the findings highlight the importance of vitamin B12 status, infant MTRR genotype and maternal MTHFR genotype, all of which may influence the supply of methyl groups for DNA methylation. In addition, gestational length appears to be an important determinant of infant DNA methylation patterns

A one-year exercise intervention program in pre-pubertal girls does not influence hip structure

<p>Abstract</p> <p>Background</p> <p>We have previously reported that a one-year school-based exercise intervention program influences the accrual of bone mineral in pre-pubertal girls. This report aims to evaluate if also hip structure is affected, as geometry independent of bone mineral influences fracture risk.</p> <p>Methods</p> <p>Fifty-three girls aged 7 – 9 years were included in a curriculum-based exercise intervention program comprising 40 minutes of general physical activity per school day (200 minutes/week). Fifty healthy age-matched girls who participated in the general Swedish physical education curriculum (60 minutes/week) served as controls. The hip was scanned by dual X-ray absorptiometry (DXA) and the hip structural analysis (HSA) software was applied to evaluate bone mineral content (BMC), areal bone mineral density (aBMD), periosteal and endosteal diameter, cortical thickness, cross-sectional moment of inertia (CSMI), section modulus (Z) and cross-sectional area (CSA) of the femoral neck (FN). Annual changes were compared. Group comparisons were done by independent student's <it>t</it>-test between means and analyses of covariance (ANCOVA). Pearson's correlation test was used to evaluate associations between activity level and annual changes in FN. All children remained at Tanner stage 1 throughout the study.</p> <p>Results</p> <p>No between-group differences were found during the 12 months study period for changes in the FN variables. The total duration of exercise during the year was not correlated with the changes in the FN traits.</p> <p>Conclusion</p> <p>Evaluated by the DXA technique and the HSA software, a general one-year school-based exercise program for 7–9-year-old pre-pubertal girls seems not to influence the structure of the hip.</p

Effect of protocatechuic acid on insulin responsiveness and inflammation in visceral adipose tissue from obese individuals: possible role for PTP1B

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