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Background The non-breast non-ovarian cancers associated with BRCA1 and BRCA2 pathogenic variants (PVs) are controversial. We aimed to examine this using a prospective cohort design. Methods This study included 1260 BRCA1 and 1058 BRCA2 PV carriers (91% were females) from two consortia: the Breast Cancer Family Registry (BCFR) and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Follow-Up Study (kConFab-FUS). The carriers were free of cancer other than breast or ovarian cancer at baseline and had a median baseline age of 45.5 years. For 16 types of non-breast, non-ovarian cancers, standardized incidence ratios (SIRs) relative to population incidence, the probabilities of relative risk effect size > 2 (i.e., moderate risk) and cumulative risks to age 80 years were estimated. Results During a median follow-up time of 11.4 years, 161 non-breast, non-ovarian cancers were observed. For BRCA1 PV carriers, little evidence of increased risk was observed. The prostate, pancreatic, and all non-pancreatic cancer SIRs were 1.7 (95% CI 0.7–4.2), 1.1 (95% CI 0.3–4.6) and 0.85 (95% CI 0.68–1.06), respectively; the probabilities of relative risk > 2 were 0 and 67% for prostate and pancreatic cancers, respectively. For BRCA2 PV carriers, increased risks of pancreatic (SIR = 6.6, 95% CI 3.8–11.6), prostate (SIR = 3.6, 95% CI 1.9–6.8) and stomach (SIR = 3.1, 95% CI 1.01–9.8) cancer were observed, with a cumulative risk to age 80 years of 8.3, 82.0, and 1.6%, respectively. For all the other non-breast, non-ovarian cancers combined, the SIR was 0.85 (95% CI 0.66–1.10). Conclusions Apart from pancreatic, prostate, and possibly stomach cancers for BRCA2 PV carriers, and possibly pancreatic cancer for BRCA1 PV carriers, there is no evidence that BRCA1 and BRCA2 PV carriers have substantially increased risks of other non-breast, non-ovarian cancers. Our prospective risk estimates are informative for cancer risk assessment for people with BRCA1 and BRCA2 PVs.

Adopted individuals have an increased risk for a variety of psychopathological disorders. Studies of the effects adoption in humans are difficult to perform because of the difficulty separating genetic risk and treatment effects. This is a developmental study investigating the effects of at birth adoption using a nonhuman primate model. Three experimental paradigms were used to assess maternal treatment, stress-related behavior, and physiology late in infancy and again later in life. Rhesus monkeys were reared for their first six months of life by either their biological mother or an unrelated, lactating adult female. Adoptions occurred immediately following birth. At six months of age, both groups were exposed to four, 4-day mother-infant separations. Behavioral observations and plasma stress hormones were used to compare the two group's responses to the separation stressor. Maternal treatments were also compared. In a second experiment performed about three years later when subjects were adolescents or young adults, an unfamiliar intruder was placed outside their home pen and stress-related behavioral responses were again measured. In the third experiment, adolescent subjects were allowed free access to a sweetened alcohol solution and daily alcohol consumption was measured across 8-10 weeks. Analyses showed that adopted subjects exhibited more behavior withdrawal and higher ACTH during the Acute and Chronic phases of the separation than infants reared by their biological mothers. This persisted when subjects were again tested with an intruder stressor 1-3 years later, with adopted subjects still showing more behavioral withdrawal during the Intruder Challenge stressor. Adopted subjects also differ in their relationship with their mother, showing more independence at an early age in non-stressful environments. Paradoxically, alcohol intake was lower in adolescents raised by an adoptive mother. Differences in maternal treatment and mismatches in temperament between the adopted mother and her infant are potential mechanisms that lead to the increased stress and anxiety in subjects raised by an adopted mother.

Purpose: Medication errors related to hospital discharge result in rehospitalization and emergency department (ED) visits, yet no systematic approach has been implemented nationally to decrease these medication errors. Pharmacist involvement during postdischarge transitions of care may be an important strategy to prevent and correct medication discrepancies and reduce costly rehospitalization and ED visits. Methods: This prospective, randomized, open-label, pilot study evaluated the effect of a pharmacy clinic visit focused on medication reconciliation and patient education after hospital discharge on the incidence of rehospitalization and ED visits and the resolution of medication discrepancies. Results: Of the 61 subjects included in the study, 33 (54%) had medication discrepancies identified at discharge. Fifty percent of medication discrepancies were resolved in subjects randomized to the pharmacist intervention arm compared with 9.5% in the usual care arm (P = .015). Patients randomized to the intervention arm had significantly lower rates of the primary composite outcome of 30-day rehospitalization and ED visits compared with the usual care arm (0% vs 40.5%, P < .001). Conclusion: A pharmacist-driven intervention focused on patient education and medication reconciliation after discharge improved medication use and reduced health care resource utilization in this pilot study.

Collaborative review of molecular profiling data by multidisciplinary molecular tumor boards (MTB) is increasingly important for improving patient management and outcomes, though currently relies nearly exclusively on nucleic acid next-generation sequencing (NGS) and limited panels of immunohistochemistry-based protein abundance data. We examined the feasibility of incorporating real-time laser microdissection (LMD) enrichment of tumor epithelium and commercial CLIA-based reverse phase protein array (RPPA) protein drug target expression/activation profiling into our cancer center’s MTB to complement standard clinical NGS-based profiling. The LMD-RPPA workflow was performed within a therapeutically permissive timeframe with a median dwell time of nine days, during which specimens were processed outside of standard clinical workflows. The RPPA-generated data supported additional and/or alternative therapeutic considerations for 54% of profiled patients following review by the MTB. These findings suggest that integrating proteomic/phosphoproteomic and NGS-based genomic data creates opportunities to further personalize clinical decision-making for precision oncology.

Animal-associated microbiomes are integral to host health, yet key biotic and abiotic factors that shape host-associated microbial communities at the global scale remain poorly understood. We investigated global patterns in amphibian skin bacterial communities, incorporating samples from 2,349 individuals representing 205 amphibian species across a broad biogeographic range. We analysed how biotic and abiotic factors correlate with skin microbial communities using multiple statistical approaches. Global amphibian skin bacterial richness was consistently correlated with temperature-associated factors. We found more diverse skin microbiomes in environments with colder winters and less stable thermal conditions compared with environments with warm winters and less annual temperature variation. We used bioinformatically predicted bacterial growth rates, dormancy genes and antibiotic synthesis genes, as well as inferred bacterial thermal growth optima to propose mechanistic hypotheses that may explain the observed patterns. We conclude that temporal and spatial characteristics of the host’s macro-environment mediate microbial diversity. Data on the richness and composition of the skin microbiome from 2,349 individual amphibians, representing 205 species across a broad geographic range, is compared with local biotic and abiotic environmental factors.

The recent successes of HER2-targeting agents, even in tumors characterized by FDA-approved molecular testing as HER2-negative or non-amplified, have underscored the limitations of current diagnostic approaches for accurately identifying patients with actionable HER2/EGFR activation/phosphorylation. We therefore performed a multi-omic investigation integrating clinical next-generation sequencing with a CLIA-certified reverse-phase protein array (RPPA) assay and laser microdissection-enriched tumor samples to characterize ERBB2 /HER2 at the DNA, RNA, protein, and phosphoprotein level in patients with advanced pan-cancer solid tumor malignancies. Functional pathway activation mapping by RPPA revealed several patients with ERBB2 genomic or transcriptomic alterations and/or HER2 Total -positivity by immunohistochemistry who exhibited no significant HER2 Y1248 activation/phosphorylation. In contrast, other patients lacking ERBB2 genomic/transcriptomic alterations demonstrated significant HER2 Y1248 activation/phosphorylation with co-activation of EGFR Y1173 , a marker associated with prognostic significance. Our results highlight the weak concordance between ERBB2 genomic/transcriptomic alterations and downstream activation of HER family signaling and support the inclusion of functional proteomic/phosphoproteomic analysis as an essential component of precision oncology pipelines to more accurately guide selection of HER2- and EGFR-targeted therapies.