Neighborhood Safety Concerns and Daily Well-Being: A National Diary Study

People living in unsafe neighborhoods often report poor health. The reasons for this are multi-faceted, but one possibility is that unsafe neighborhoods create a situation of chronic stress, which may deplete people\u27s resources to cope with the daily stressors of life. How people respond to daily stressors (e.g., with increased self-reported negative affect and physical symptoms) is positively associated with health problems and may thus be one pathway linking perceptions of neighborhood safety to poor health. The current study investigated the relationship between neighborhood safety concerns, daily stressors, affective well-being, and physical health symptoms in a national sample of adults from the Midlife in the United States Study II (n = 1748). In 2004, participants reported neighborhood safety concerns and history of chronic stress exposure. Across eight days, they also reported daily stressors, physical symptoms and negative affect. Greater neighborhood safety concerns were associated with higher negative affect and more physical symptoms, adjusting for other sources of chronic stress. Moreover, lower perceived neighborhood safety was related to greater increases in negative affect and physical symptoms on days during which stressors were reported, even after accounting for established interactions between daily stressors and other sources of chronic stress. Exposure to neighborhoods perceived as unsafe is associated with poorer daily well-being and exacerbated responses to daily stressors, which may serve as an individual-level pathway contributing to poorer health among people living in neighborhoods perceived as unsafe

Affective Reactions to daily interpersonal stressors: Moderation by family involvement and gender

The goal of this study was to examine whether family involvement and gender moderated daily changes in affect associated with interpersonal stressors. Adults ( N = 2022; Mage = 56.25, Median = 56, SD = 12.20, Range = 33–84) from the second wave of the National Study of Daily Experiences participated in eight consecutive daily diaries. Each day they reported whether a daily interpersonal stressor occurred, whether family was involved, and their positive and negative affect. Results from multilevel models indicated that family involvement did not significantly moderate daily interpersonal stressor-affect associations; however, gender was a significant moderator in some instances. Women showed greater increases in negative affective reactivity to arguments and avoided arguments compared to men. Further, compared to men, women reported larger decreases in positive affective reactivity, but only for avoided arguments. Neither family involvement, gender, nor the interaction between family involvement and gender predicted affective residue. Gender differences in daily interpersonal stressors and affective reactivity may be attributable to overarching gender norms and roles that are still salient in the U.S. Our results suggest that daily interpersonal stressors may be detrimental to affective well-being, regardless of family involvement. Future work should explore associations between daily interpersonal stressors and family involvement by specific relationship roles, such as mother or spouse, for a more comprehensive understanding of what stressor characteristics impact daily affective well-being

How Do Marital Transitions Affect Self-Perceptions of Aging?

Objectives We analyzed whether marital status and experiences of marital loss or gain were associated with self-perceptions of aging (SPA), a major psychosocial mechanism of healthy aging. Method We used data from 7028 participants of the Health and Retirement Study. Participants reported their marital status and their positive and negative SPA on two occasions 4 years apart. We ran general linear models to analyze differences in SPA between men and women who remained married, became divorced or widowed, or remarried following divorce or widowhood. Results Participants who experienced marital loss had lower positive SPA than participants who remained marred. Participants who experienced marital gain had lower negative SPA than participants who remained married. None of the associations differed between men and women. Discussion Results suggest that it may not be marital status itself, but rather the transition into or out of marriage, that impacts how people appraise their own aging

Daily Stress Processes as Potential Intervention Targets to Reduce Gender Differences and Improve Mental Health Outcomes in Mid- and Later Life.

The current study examines daily stress processes as risk factors for comprised mental health in midlife and later life, specifically for gender differences in depression risk. Using data from the Midlife in the United States (MIDUS) study and the National Study of Daily Experiences (NSDE), we examine (1) gender differences in depression; (2) the prospective effects of differential exposure and affective responses on 10-year depression status; (3) gender differences in daily stress-depression links. Furthermore, we explore whether the protective factor of help-seeking behavior moderates the effects of daily stress on depression. Participants included 1289 (mage = 55; SD = 12; range = 34-83; 56% female) individuals who completed the second waves of MIDUS and the 8-day NSDE daily diary protocol and participated in the third wave of MIDUS approximately 10 years later. Respondents completed assessments of depression and their seeking assistance from a psychiatrist, mental health professional, counselor, or religious leader. Covariate-adjusted logistic regression analyses revealed increased odds of depression among women compared to men, but no significant gender difference after taking daily stress into account. Higher levels of stressor exposure, negative affect, and affective reactivity were associated with increased odds of depression for both men and women. Compared to those who did not engage in help-seeking behavior, those who did had significantly greater odds of depression, and there were asymmetric patterns of daily stress effects across groups. These findings highlight differential exposure, negative affect, and affective responses to daily stress as potentially accessible intervention targets for reducing stress in daily life and mitigating longer-term depression risk during mid- and later life

Computing Components of Everyday Stress Responses: Exploring Conceptual Challenges and New Opportunities

Repeated assessments in everyday life enables collecting ecologically valid data on dynamic, within-persons processes. These methods have widespread utility and application and have been extensively used for the study of stressors and stress responses. Enhanced conceptual sophistication of characterizing intraindividual stress responses in everyday life would help advance the field. This article provides a pragmatic overview of approaches, opportunities, and challenges when intensive ambulatory methods are applied to study everyday stress responses in “real time.” We distinguish between three stress-response components (i.e., reactivity, recovery, and pileup) and focus on several fundamental questions: (a) What is the appropriate stress-free resting state (or “baseline”) for an individual in everyday life? (b) How does one index the magnitude of the initial response to a stressor (reactivity)? (c) Following a stressor, how can recovery be identified (e.g., when the stress response has completed)? and (d) Because stressors may not occur in isolation, how can one capture the temporal clustering of stressors and/or stress responses (pileup)? We also present initial ideas on applying this approach to intervention research. Although we focus on stress responses, these issues may inform many other dynamic intraindividual constructs and behaviors (e.g., physical activity, physiological processes, other subjective states) captured in ambulatory assessment

cDNA sequencing improves the detection of P53 missense mutations in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Recently published data showed discrepancies beteween <it>P53 </it>cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers.</p> <p>Methods</p> <p>To this end, we analyzed 23 colorectal cancers for <it>P53 </it>mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry.</p> <p>Results</p> <p>We found <it>P53 </it>gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of <it>P53 </it>mRNA was present in samples with and without <it>P53 </it>mutations.</p> <p>Conclusion</p> <p>In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated <it>P53 </it>mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without <it>P53 </it>mutation (normal cells and cells showing <it>K-RAS </it>and/or <it>APC </it>but not <it>P53 </it>mutation) in samples presenting <it>P53 </it>mutation; 3, heterozygous or hemizygous mutations of <it>P53 </it>gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in <it>P53 </it>cDNA and DNA sequencing analysis.</p

Glioblastoma-derived spheroid cultures as an experimental model for analysis of EGFR anomalies

Glioblastoma cell cultures in vitro are frequently used for investigations on the biology of tumors or new therapeutic approaches. Recent reports have emphasized the importance of cell culture type for maintenance of tumor original features. Nevertheless, the ability of GBM cells to preserve EGFR overdosage in vitro remains controversial. Our experimental approach was based on quantitative analysis of EGFR gene dosage in vitro both at DNA and mRNA level. Real-time PCR data were verified with a FISH method allowing for a distinction between EGFR amplification and polysomy 7. We demonstrated that EGFR amplification accompanied by EGFRwt overexpression was maintained in spheroids, but these phenomena were gradually lost in adherent culture. We noticed a rapid decrease of EGFR overdosage already at the initial stage of cell culture establishment. In contrast to EGFR amplification, the maintenance of polysomy 7 resulted in EGFR locus gain and stabilization even in long-term adherent culture in serum presence. Surprisingly, the EGFRwt expression pattern did not reflect the latter phenomenon and we observed no overexpression of the tested gene. Moreover, quantitative analysis demonstrated that expression of the truncated variant of receptor—EGFRvIII was preserved in GBM-derived spheroids at a level comparable to the initial tumor tissue. Our findings are especially important in the light of research using glioblastoma culture as the experimental model for testing novel EGFR-targeted therapeutics in vitro, with special emphasis on the most common mutated form of receptor—EGFRvIII

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets

Persons as Contexts: Evaluating Between-Person and Within-Person Effects in Longitudinal Analysis

Relationships among multiple variables over time are of interest in many developmental areas and are frequently examined using time-varying predictors in multilevel models. Yet an incomplete specification of time-varying predictors will usually result in biased model effects. Specifically, the impact of constant, between-person sources of variation must be differentiated from the impact of time-specific, within-person sources of variation -that is, persons should be modeled as contexts. The current didactic article expands upon previous work to address why and how to model persons as contexts in longitudinal analysis. An electronic appendix of syntax for estimating these models is also provided

Cell-Free DNA: Potential Application in COVID-19 Diagnostics and Management

WHO has declared COVID-19 as a worldwide, public health emergency. The elderly, pregnant women, and people with associated co-morbidities, including pulmonary disease, heart failure, diabetes, and cancer are the most predisposed population groups to infection. Cell-free DNA is a very commonly applied marker, which is elevated in various pathological conditions. However, it has a much higher sensitivity than standard biochemical markers. cfDNA appears to be an effective marker of COVID-19 complications, and also serves as a marker of certain underlying health conditions and risk factors of severe illness during COVID-19 infection. We aimed to present the possible mechanisms and sources of cfDNA released during moderate and severe infections. Moreover, we attempt to verify how efficiently cfDNA increase could be applied in COVID-19 risk assessment and how it corresponds with epidemiological data