Investigating the Effects of Heteronormativity and Minority Stress on Mental Health, Well-being, Disclosure, and Concealment of Non-Gay Identifying and [Behaviorally] Bisexual Men

The purpose of this research was to explore social hardships of non-gay identifying, [behaviorally] bisexual, and “other” marginal LGBTQ+ men who are sexually intimate with men in a heteronormative and [toxic] masculine world. Relatedly, hegemonic masculinity dominates the patriarch through regulating behavioral norms that often stigmatize and discriminate opposing traits, ideologies, or groups, such as LGBTQ+. This has been known to affect and mediate health outcomes and “outness.” Therefore, this study explored how minority stressors impact self-concept, mental health, well-being, and motivations to disclose and/or conceal. Data collection involved survey and interview formats (mixed-methods cross-sectional design) that assessed internalized homophobia, conformity to masculine norms, subjective masculinity stress, disclosure, and concealment in relation to lifestyle and social context. While all variables had expected linear associations, not all were causal. Those who conformed to masculine norms significantly experienced internalized stigma/homophobia. Hence, it can be hypothesized that participants who conformed sought to conceal stigma under pressure of heteronormative culture and the patriarch. However, subjective masculinity stress was nonsignificant, exemplifying hegemonic influence as more defining to their self-concept than their own. Further, minority stress constructs (masculine norms, internalized stigma/homophobia, and subjective masculinity stress), when age, regional location, and faith were controlled, significantly predicted less disclosure and more concealment in social contexts. This reinforces the power of modern patriarchy/masculine norms/minority stress and its adverse effects on mental health, well-being, and outness in marginalized populations of LGBTQ+. Relatedly, qualitative data validated these quantitative findings but generally over the lifecycle of “coming out” as opposed to respondents’ current growth and development in outness, mental health, and well-being. However, to further affirm such quantitative findings, both survey and interview data did report distress regarding modern day masculinity and its ill standards that place unrealistic expectations on men, which continue to create disparities among and between many communities and humanity

Prevalence and incidence of carpal tunnel syndrome in US working populations: pooled analysis of six prospective studies

OBJECTIVES: Most studies of carpal tunnel syndrome (CTS) incidence and prevalence among workers have been limited by small sample sizes or restricted to a small subset of jobs. We established a common CTS case definition and then pooled CTS prevalence and incidence data across six prospective studies of musculoskeletal outcomes to measure CTS frequency and allow better studies of etiology. METHODS: Six research groups collected prospective data at >50 workplaces including symptoms characteristic of CTS and electrodiagnostic studies (EDS) of the median and ulnar nerves across the dominant wrist. While study designs and the timing of data collection varied across groups, we were able to create a common CTS case definition incorporating both symptoms and EDS results from data that were collected in all studies. RESULTS: At the time of enrollment, 7.8% of 4321 subjects met our case definition and were considered prevalent cases of CTS. During 8833 person-years of follow-up, an additional 204 subjects met the CTS case definition for an overall incidence rate of 2.3 CTS cases per 100 person-years. CONCLUSIONS: Both prevalent and incident CTS were common in data pooled across multiple studies and sites. The large number of incident cases in this prospective study provides adequate power for future exposure– response analyses to identify work- and non-work-related risk factors for CTS. The prospective nature allows determination of the temporal relations necessary for causal inference

Developing a pooled job physical exposure data set from multiple independent studies: An example of a consortium study of carpal tunnel syndrome

BackgroundSix research groups independently conducted prospective studies of carpal tunnel syndrome (CTS) incidence in 54 US workplaces in 10 US States. Physical exposure variables were collected by all research groups at the individual worker level. Data from these research groups were pooled to increase the exposure spectrum and statistical power.ObjectiveThis paper provides a detailed description of the characteristics of the pooled physical exposure variables and the source data information from the individual research studies.MethodsPhysical exposure data were inspected and prepared by each of the individual research studies according to detailed instructions provided by an exposure subcommittee of the research consortium. Descriptive analyses were performed on the pooled physical exposure data set. Correlation analyses were performed among exposure variables estimating similar exposure aspects.ResultsAt baseline, there were a total of 3010 participants in the pooled physical exposure data set. Overall, the pooled data meaningfully increased the spectra of most exposure variables. The increased spectra were due to the wider range in exposure data of different jobs provided by the research studies. The correlations between variables estimating similar exposure aspects showed different patterns among data provided by the research studies.ConclusionsThe increased spectra of the physical exposure variables among the data pooled likely improved the possibility of detecting potential associations between these physical exposure variables and CTS incidence. It is also recognised that methods need to be developed for general use by all researchers for standardisation of physical exposure variable definition, data collection, processing and reduction

Personal and workplace psychosocial risk factors for carpal tunnel syndrome: a pooled study cohort

BACKGROUND: Between 2001 and 2010, six research groups conducted coordinated multiyear, prospective studies of carpal tunnel syndrome (CTS) incidence in US workers from various industries and collected detailed subject-level exposure information with follow-up symptom, physical examination, electrophysiological measures and job changes. OBJECTIVE: This analysis of the pooled cohort examined the incidence of dominant-hand CTS in relation to demographic characteristics and estimated associations with occupational psychosocial factors and years worked, adjusting for confounding by personal risk factors. METHODS: 3515 participants, without baseline CTS, were followed-up to 7 years. Case criteria included symptoms and an electrodiagnostic study consistent with CTS. Adjusted HRs were estimated in Cox proportional hazard models. Workplace biomechanical factors were collected but not evaluated in this analysis. RESULTS: Women were at elevated risk for CTS (HR=1.30; 95% CI 0.98 to 1.72), and the incidence of CTS increased linearly with both age and body mass index (BMI) over most of the observed range. High job strain increased risk (HR=1.86; 95% CI 1.11 to 3.14), and social support was protective (HR=0.54; 95% CI 0.31 to 0.95). There was an inverse relationship with years worked among recent hires with the highest incidence in the first 3.5 years of work (HR=3.08; 95% CI 1.55 to 6.12). CONCLUSIONS: Personal factors associated with an increased risk of developing CTS were BMI, age and being a woman. Workplace risk factors were high job strain, while social support was protective. The inverse relationship between CTS incidence and years worked among recent hires suggests the presence of a healthy worker survivor effect in the cohort

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents

Discordant Responses Between Primary Head and Neck Tumors and Nodal Metastases Treated With Neoadjuvant Nivolumab: Correlation of Radiographic and Pathologic Treatment Effect.

PD-1 blockade represents a promising treatment in patients with head and neck squamous cell carcinoma (HNSCC). We analyzed results of a neoadjuvant randomized window-of-opportunity trial of nivolumab plus/minus tadalafil to investigate whether immunotherapy-mediated treatment effects vary by site of involvement (primary tumor, lymph nodes) and determine how radiographic tumor shrinkage correlates with pathologic treatment effect. Patients and Methods: Forty-four patients enrolled in trial NCT03238365 were treated with nivolumab 240 mg intravenously on days 1 and 15 with or without oral tadalafil, as determined by random assignment, followed by surgery on day 31. Radiographic volumetric response (RVR) was defined as percent change in tumor volume from pretreatment to posttreatment CT scan. Responders were defined as those with a 10% reduction in the volume of the primary tumor or lymph nodes (LN). Pathologic treatment effect (PTE) was defined as the area showing fibrosis or lymphohistiocytic inflammation divided by total tumor area. Results: Sixteen of 32 patients (50%) with pathologic evidence of LN involvement exhibited discordant PTE between primary sites and LN. In four patients with widely discordant adjacent LN, increased PTE was associated with increased infiltration of tumor CD8+ T cells and CD163+ macrophages, whereas stromal regulatory T cells were associated with low nodal PTE. RVR correlated with PTE at both primary tumor (slope = 0.55, p \u3c 0.001) and in LN (slope = 0.62, p \u3c 0.05). 89% (16/18) of radiographic non-responders with T1-T3 primary sites had no (n = 7) or minimal PTE (n = 9), whereas 15/17 (88%) of radiographic responders had moderate (n = 12) or complete (n = 3) PTE. Conclusion: Nivolumab often induces discordant treatment effects between primary tumor sites and metastatic lymph nodes within subjects. This treatment discordance was also demonstrated in adjacent lymph nodes, which may correlate with local immune cell makeup. Finally, although these data were generated by a relatively small population size, our data support the use of early radiographic response to assess immunotherapy treatment effect in HNSCC

Pooling job physical exposure data from multiple independent studies in a consortium study of carpal tunnel syndrome

Pooling data from different epidemiological studies of musculoskeletal disorders (MSDs) is necessary to improve statistical power and to more precisely quantify exposure–response relationships for MSDs. The pooling process is difficult and time-consuming, and small methodological differences could lead to different exposure–response relationships. A subcommittee of a six-study research consortium studying carpal tunnel syndrome: (i) visited each study site, (ii) documented methods used to collect physical exposure data and (iii) determined compatibility of exposure variables across studies. Certain measures of force, frequency of exertion and duty cycle were collected by all studies and were largely compatible. A portion of studies had detailed data to investigate simultaneous combinations of force, frequency and duration of exertions. Limited compatibility was found for hand/wrist posture. Only two studies could calculate compatible Strain Index scores, but Threshold Limit Value for Hand Activity Level could be determined for all studies. Challenges of pooling data, resources required and recommendations for future researchers are discussed

The Bactofilin Cytoskeleton Protein BacM of Myxococcus xanthus Forms an Extended β-Sheet Structure Likely Mediated by Hydrophobic Interactions

Bactofilins are novel cytoskeleton proteins that are widespread in Gram-negative bacteria. Myxococcus xanthus, an important predatory soil bacterium, possesses four bactofilins of which one, BacM (Mxan_7475) plays an important role in cell shape maintenance. Electron and fluorescence light microscopy, as well as studies using over-expressed, purified BacM, indicate that this protein polymerizes in vivo and in vitro into ~3 nm wide filaments that further associate into higher ordered fibers of about 10 nm. Here we use a multipronged approach combining secondary structure determination, molecular modeling, biochemistry, and genetics to identify and characterize critical molecular elements that enable BacM to polymerize. Our results indicate that the bactofilin-determining domain DUF583 folds into an extended β-sheet structure, and we hypothesize a left-handed β-helix with polymerization into 3 nm filaments primarily via patches of hydrophobic amino acid residues. These patches form the interface allowing head-to-tail polymerization during filament formation. Biochemical analyses of these processes show that folding and polymerization occur across a wide variety of conditions and even in the presence of chaotropic agents such as one molar urea. Together, these data suggest that bactofilins are comprised of a structure unique to cytoskeleton proteins, which enables robust polymerization

Evolution of two actin genes in the sea urchin Strongylocentrotus franciscanus

The complete nucleotide sequences of two chromosomally linked actin genes from the sea urchin Strongylocentrotus franciscanus are presented. The genes are separated by 5.7 kilobases, occur in the same transcriptional orientation, and contain introns in identical positions. The structures and nucleotide sequences of the two genes are extremely similar, suggesting that they arose through a recent duplication. Comparison of the nucleotide sequences of the genes allows inferences to be made about mutational mechanisms active since the duplication event. Whereas point mutations predominate in the coding regions, the introns and flanking DNA are more heavily influenced by a variety of events that cause simultaneous changes in short regions of DNA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48040/1/239_2005_Article_BF02101689.pd