Background: Becoming a father is a critical period of life transition. Evidence suggests that a lifetime history of mental health disorder/s and elevated depressive symptoms prior to conception increase risk for men's post-natal depression. Less is understood about the role of positive mental health, or wellbeing, as a protective factor for future depressive outcomes during the transition to fatherhood.
View Article and Find Full Text PDFBackground: Truck drivers are a vital workforce, but have higher rates of obesity and other chronic diseases than the general population. The occupation's sedentary nature, limited physical activity opportunities and access to healthy food, and irregular sleeping patterns contribute to poor health. This systematic review and meta-analysis aimed to evaluate the effectiveness of interventions on health behaviours and cardiometabolic biomarkers of health in truck drivers.
View Article and Find Full Text PDFWhile the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC.
View Article and Find Full Text PDFSingle-session meditation augmentation of sport-specific skill performance was tested with elite junior tennis athletes. Athletes completed one of two styles of mindfulness meditation (focused-attention or open-monitoring) or a control listening condition prior to performing an implicitly sequenced tennis serve return task involving the goal of hitting a target area placed on the service court. Unbeknownst to athletes, six distinct serves followed a repeating second-order conditional sequence for two task blocks before the sequence was altered in a third transfer block.
View Article and Find Full Text PDFWearable activity trackers offer an appealing, low-cost tool to address physical inactivity. This systematic review of systematic reviews and meta-analyses (umbrella review) aimed to examine the effectiveness of activity trackers for improving physical activity and related physiological and psychosocial outcomes in clinical and non-clinical populations. Seven databases (Embase, MEDLINE, Ovid Emcare, Scopus, SPORTDiscus, the Cochrane Library, and Web of Science) were searched from database inception to April 8, 2021.
View Article and Find Full Text PDFThe androgen receptor (AR) is a master transcription factor that regulates prostate cancer (PC) development and progression. Inhibition of AR signaling by androgen deprivation is the first-line therapy with initial efficacy for advanced and recurrent PC. Paradoxically, supraphysiological levels of testosterone (SPT) also inhibit PC progression.
View Article and Find Full Text PDFc-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC is overexpressed in both early and metastatic disease and associated with poor survival, its impact on prostate transcriptional reprogramming remains elusive. We demonstrate that MYC overexpression significantly diminishes the androgen receptor (AR) transcriptional program (the set of genes directly targeted by the AR protein) in luminal prostate cells without altering AR expression.
View Article and Find Full Text PDFPurpose: Fragility fractures are a significant source of morbidity and have high associated mortality. Identifying risk factors for poor outcomes is essential for guiding treatment and for setting expectations for patients and their families. Although fragility hip fractures have been abundantly explored, there is a paucity of information regarding proximal humerus fractures (PHFs).
View Article and Find Full Text PDFPromoting athlete wellbeing has become a priority in elite sport, and the COVID-19 pandemic has accentuated the need for a comprehensive understanding of risk and protective factors. Existing sport research has not yet considered whether specific cognitive factors such as dispositional mindfulness and executive function may protect athletes against psychological distress. In a sample of high-performance Australian football athletes ( = 27), we administered measures of dispositional mindfulness (MAAS), executive function (AOSPAN; eStroop), and psychological distress (APSQ) at pre-season, coinciding with the initial (2020) COVID-19-related sport shutdown in Australia.
View Article and Find Full Text PDFAlthough sport participation is intrinsically motivating and improves the physical health of middle-aged men, its influence on subjective health measures, such as health-related quality of life, self-rated health, or well-being is unclear. The purpose of this scoping review was to describe the existing literature that has assessed male sport participants and their subjective health. MEDLINE, Embase, Emcare, PsycInfo, SPORTDiscus, Cochrane Library, and Web of Science were searched, and reference lists of included studies were pearled.
View Article and Find Full Text PDFThe encapsulation of biologic molecules using a microfluidic platform is a procedure that has been understudied but shows great promise from initial reported studies. The study focusses upon the encapsulation of bovine serum albumin (BSA) under various parameters and using multiple phospholipids to identify optimal conditions for the manufacturing of protein loaded lipid nanoparticles. Additionally, encapsulation of the enzyme trypsin (TRP) has been investigated to show the eligibility of the system to other biological medications.
View Article and Find Full Text PDFGenome-wide association studies (GWASs) of prostate cancer have identified >250 significant risk loci, but the causal variants and mechanisms for these loci remain largely unknown. Here, we sought to identify and characterize risk-harboring regulatory elements by integrating epigenomes from primary prostate tumor and normal tissues of 27 individuals across the H3K27ac, H3K4me3, and H3K4me2 histone marks and FOXA1 and HOXB13 transcription factors. We identified 7,371 peaks with significant allele specificity (allele-specific quantitative trait locus [asQTL] peaks).
View Article and Find Full Text PDFThere are no biomarkers predictive of resistance to docetaxel or cabazitaxel validated for patients with metastatic castration-resistant prostate cancer (mCRPC). We assessed the association between amplification and primary resistance to docetaxel or cabazitaxel for patients with mCRPC, using circulating cell-free DNA (cfDNA). Patients with ≥1 plasma sample drawn within 12 months before starting docetaxel (cohort A) or cabazitaxel (cohort B) for mCRPC were identified from the Dana-Farber Cancer Institute IRB approved database.
View Article and Find Full Text PDFLineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive variant of prostate cancer that aberrantly expresses genes characteristic of neuroendocrine (NE) tissues and no longer depends on androgens.
View Article and Find Full Text PDFEpigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from normal prostate epithelium to localized PCa to metastases-in specimens derived from human tissue. We discovered that reprogrammed AR sites in metastatic PCa are not created de novo; rather, they are prepopulated by the transcription factors FOXA1 and HOXB13 in normal prostate epithelium.
View Article and Find Full Text PDFAlthough quantitative trait locus (QTL) associations have been identified for many molecular traits such as gene expression, it remains challenging to distinguish the causal nucleotide from nearby variants. In addition to traditional QTLs by association, allele-specific (AS) QTLs are a powerful measure of cis-regulation that are concordant with traditional QTLs but typically less susceptible to technical/environmental noise. However, existing methods for estimating causal variant probabilities (i.
View Article and Find Full Text PDFOncogenesis is driven by germline, environmental and stochastic factors. It is unknown how these interact to produce the molecular phenotypes of tumors. We therefore quantified the influence of germline polymorphisms on the somatic epigenome of 589 localized prostate tumors.
View Article and Find Full Text PDFRepetitive hypoxia is a key feature of obstructive sleep apnoea (OSA), a condition characterized by intermittent airways obstruction. Patients with OSA present with persistent increases in sympathetic activity and commonly develop hypertension. The objectives of this study were to determine if the persistent increases in sympathetic nerve activity, known to be induced by acute intermittent hypoxia (AIH), are mediated through activation of the pituitary adenylate cyclase activating polypeptide (PACAP) signaling system.
View Article and Find Full Text PDFPurpose: Defects in genes in the DNA repair pathways significantly contribute to prostate cancer progression. We hypothesize that overexpression of DNA repair genes may also drive poorer outcomes in prostate cancer. The ribonucleotide reductase small subunit M2 (RRM2) is essential for DNA synthesis and DNA repair by producing dNTPs.
View Article and Find Full Text PDFBackground: Tumor content in circulating cell-free DNA (cfDNA) is a promising biomarker, but longitudinal dynamics of tumor-derived and non-tumor-derived cfDNA through multiple courses of therapy have not been well described.
Methods: CfDNA from 663 plasma samples from 140 patients with castration-resistant prostate cancer (CRPC) was subject to sparse whole genome sequencing. Tumor fraction (TFx) estimated using the computational tool ichorCNA was correlated with clinical features and responses to therapy.
Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus presumably targeting the AR gene. Here, we identify and characterize a somatically acquired AR enhancer located 650 kb centromeric to the AR.
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