The Risk of Fracture in Patients Undergoing Androgen Deprivation May Be Overstated: Analysis of an Unselected Cohort of Patients

Objective: In this study we examined the prevalence of fracture among men undergoing ADT for prostate cancer to determine if the fracture risk was increased among this population.Background: Androgen deprivation therapy (ADT) is a therapeutic approach for men with various prostate cancer disease states. Treatment-related side effects of ADT include rapid bone loss. Previous studies have found that the bone loss related to ADT leads to the development of fractures. Methods: This is a retrospective cohort study of patients treated with ADT in a radiation oncology and medical oncology practice at an urban academic medical center from 2005 to 2010. Patients with evidence of bone metastases responsive to ADT were included. Those with androgen-independent prostate cancer were excluded. Results: One hundred thirty patients met the inclusion criteria and among them only three fractures occurred during 373 person-years of follow-up. The fracture-free survival (FFS) rate at three years for all was 97.7%. Excluding fractures occurring within six months of ADT initiation, the FFS rate was 100% at three years. No significant difference was demonstrated in those screened with a pretreatment dual-emission X-ray absorptiometry (DEXA) scan; there was no relationship between the number of ADT cycles, recovery of testosterone to normal, or total time on ADT. Older patients, surprisingly, had a lower risk (p = 0.054). Patients with normal bone mineral density (BMD) had an FFS rate of 93.8% at three years, osteopenic patients had 94.7%, and patients with osteoporosis and hormone-responsive metastases had 100%. Conclusion: The prevalence of fracture among this group is significantly less than what has previously been reported for men receiving ADT, potentially suggesting an overstatement of risk in the literature to date. Further prospective study with a larger sample size is needed

Assessing sensitivity and reproducibility of RT-ddPCR and RT-qPCR for the quantification of SARS-CoV-2 in wastewater

Throughout the COVID-19 global pandemic there has been significant interest and investment in using Wastewater-Based Epidemiology (WBE) for surveillance of viral pathogen presence and infections at the community level. There has been a push for widescale implementation of standardized protocols to quantify viral loads in a range of wastewater systems. To address concerns regarding sensitivity, limits of quantification, and large-scale reproducibility, a comparison of two similar workflows using RT-qPCR and RT-ddPCR was conducted. Sixty raw wastewater influent samples were acquired from nine distinct wastewater treatment plants (WWTP's) served by the Hampton Roads Sanitation District (HRSD, Virginia Beach, Virginia) over a 6-month period beginning March 9th, 2020. Common reagents, controls, master mixes and nucleic acid extracts were shared between two individual processing groups based out of HRSD and the UNC Chapel Hill Institute of Marine Sciences (IMS, Morehead City, North Carolina). Samples were analyzed in parallel using One-Step RT-qPCR and One-Step RT-ddPCR with Nucleocapsid Protein 2 (N2) specific primers and probe. Influent SARS-CoV-2 N2 concentrations steadily increased over time spanning a range from non-detectable to 2.13E + 05 copies/L. Systematic dilution of the extracts indicated that inhibitory components in the wastewater matrices did not significantly impede the detection of a positive N2 signal for either workflow. The RT-ddPCR workflow had a greater analytical sensitivity with a lower Limit of Detection (LOD) at 0.066 copies/μl of template compared to RT-qPCR with a calculated LOD of 12.0 copies/μL of template. Interlaboratory comparisons using non-parametric correlation analysis demonstrated that there was a strong, significant, positive correlation between split extracts when employing RT-ddPCR for analysis with a ρ value of 0.86

New hints towards a precision medicine strategy for IDH wild-type glioblastoma.

Glioblastoma represents the most common primary malignancy of the central nervous system in adults and remains a largely incurable disease. The elucidation of disease subtypes based on mutational profiling, gene expression and DNA methylation has so far failed to translate into improved clinical outcomes. However, new knowledge emerging from the subtyping effort in the IDH-wild-type setting may provide directions for future precision therapies. Here, we review recent learnings in the field, and further consider how tumour microenvironment differences across subtypes may reveal novel contexts of vulnerability. We discuss recent treatment approaches and ongoing trials in the IDH-wild-type glioblastoma setting, and propose an integrated discovery stratagem incorporating multi-omics, single-cell technologies and computational approaches

Feeling Bad and Looking Worse: Negative Affect Is Associated with Reduced Perceptions of Face-Healthiness

Some people perceive themselves to look more, or less attractive than they are in reality. We investigated the role of emotions in enhancement and derogation effects; specifically, whether the propensity to experience positive and negative emotions affects how healthy we perceive our own face to look and how we judge ourselves against others. A psychophysical method was used to measure healthiness of self-image and social comparisons of healthiness. Participants who self-reported high positive (N = 20) or negative affectivity (N = 20) judged themselves against healthy (red-tinged) and unhealthy looking (green-tinged) versions of their own and stranger’s faces. An adaptive staircase procedure was used to measure perceptual thresholds. Participants high in positive affectivity were un-biased in their face health judgement. Participants high in negative affectivity on the other hand, judged themselves as equivalent to less healthy looking versions of their own face and a stranger’s face. Affective traits modulated self-image and social comparisons of healthiness. Face health judgement was also related to physical symptom perception and self-esteem; high physical symptom reports were associated a less healthy self-image and high self-reported (but not implicit) self-esteem was associated with more favourable social comparisons of healthiness. Subject to further validation, our novel face health judgement task could have utility as a perceptual measure of well-being. We are currently investigating whether face health judgement is sensitive to laboratory manipulations of mood

Integrating a family-focused approach into child obesity prevention: Rationale and design for the My Parenting SOS study randomized control trial

<p>Abstract</p> <p>Background</p> <p>More than 20% of US children ages 2-5 yrs are classified as overweight or obese. Parents greatly influence the behaviors their children adopt, including those which impact weight (e.g., diet and physical activity). Unfortunately, parents often fail to recognize the risk for excess weight gain in young children, and may not be motivated to modify behavior. Research is needed to explore intervention strategies that engage families with young children and motivate parents to adopt behaviors that will foster healthy weight development.</p> <p>Methods</p> <p>This study tests the efficacy of the 35-week My Parenting SOS intervention. The intervention consists of 12 sessions: initial sessions focus on general parenting skills (stress management, effective parenting styles, child behavior management, coparenting, and time management) and later sessions apply these skills to promote healthier eating and physical activity habits. The primary outcome is change in child percent body fat. Secondary measures assess parent and child dietary intake (three 24-hr recalls) and physical activity (accelerometry), general parenting style and practices, nutrition- and activity-related parenting practices, and parent motivation to adopt healthier practices.</p> <p>Discussion</p> <p>Testing of these new approaches contributes to our understanding of how general and weight-specific parenting practices influence child weight, and whether or not they can be changed to promote healthy weight trajectories.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00998348">NCT00998348</a></p

GRP78 Knockdown Enhances Apoptosis via the Down-Regulation of Oxidative Stress and Akt Pathway after Epirubicin Treatment in Colon Cancer DLD-1 Cells

INTRODUCTION: The 78-kDa glucose-regulated protein (GRP78) is induced in the cancer microenvironment and can be considered as a novel predictor of responsiveness to chemotherapy in many cancers. In this study, we found that intracellular reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation were higher in GRP78 knockdown DLD-1 colon cancer cells compared with scrambled control cells. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with epirubicin in GRP78 knockdown DLD-1 cells enhanced apoptosis and was associated with decreased production of intracellular ROS. In addition, apoptosis was increased by the antioxidants propyl gallate (PG) and dithiothreitol (DTT) in epirubicin-treated scrambled control cells. Epirubicin-treated GRP78 knockdown cells resulted in more inactivated Akt pathway members, such as phosphorylated Akt and GSK-3β, as well as downstream targets of β-catenin expression. Knockdown of Nrf2 with small interfering RNA (siRNA) increased apoptosis in epirubicin-treated GRP78 knockdown cells, which suggested that Nrf2 may be a primary defense mechanism in GRP78 knockdown cells. We also demonstrated that epirubicin-treated GRP78 knockdown cells could decrease survival pathway signaling through the redox activation of protein phosphatase 2A (PP2A), which is a serine/threonine phosphatase that negatively regulates the Akt pathway. CONCLUSIONS: Our results indicate that epirubicin decreased the intracellular ROS in GRP78 knockdown cells, which decreased survival signaling through both the Akt pathway and the activation of PP2A. Together, these mechanisms contributed to the enhanced level of epirubicin-induced apoptosis that was observed in the GRP78 knockdown cells

Testing the lognormality of the galaxy and weak lensing convergence distributions from Dark Energy Survey maps

It is well known that the probability distribution function (PDF) of galaxy density contrast is approximately lognormal; whether the PDF of mass fluctuations derived from weak lensing convergence (kappa_WL) is lognormal is less well established. We derive PDFs of the galaxy and projected matter density distributions via the Counts in Cells (CiC) method. We use maps of galaxies and weak lensing convergence produced from the Dark Energy Survey (DES) Science Verification data over 139 deg^2. We test whether the underlying density contrast is well described by a lognormal distribution for the galaxies, the convergence and their joint PDF. We confirm that the galaxy density contrast distribution is well modeled by a lognormal PDF convolved with Poisson noise at angular scales from 10-40 arcmin (corresponding to physical scales of 3-10 Mpc). We note that as kappa_WL is a weighted sum of the mass fluctuations along the line of sight, its PDF is expected to be only approximately lognormal. We find that the kappa_WL distribution is well modeled by a lognormal PDF convolved with Gaussian shape noise at scales between 10 and 20 arcmin, with a best-fit chi^2/DOF of 1.11 compared to 1.84 for a Gaussian model, corresponding to p-values 0.35 and 0.07 respectively, at a scale of 10 arcmin. Above 20 arcmin a simple Gaussian model is sufficient. The joint PDF is also reasonably fitted by a bivariate lognormal. As a consistency check we compare the variances derived from the lognormal modelling with those directly measured via CiC. Our methods are validated against maps from the MICE Grand Challenge N-body simulation