Loneliness, social support and cardiovascular reactivity to laboratory stress

Self-reported or explicit loneliness and social support have been inconsistently associated with cardiovascular reactivity (CVR) to stress. The present study aimed to adapt an implicit measure of loneliness, and use it alongside the measures of explicit loneliness and social support, to investigate their correlations with CVR to laboratory stress. Twenty-five female volunteers aged between 18 and 39 years completed self-reported measures of loneliness and social support, and an Implicit Association Test (IAT) of loneliness. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) reactivity indices were measured in response to psychosocial stress induced in the laboratory. Functional support indices of social support were significantly correlated with CVR reactivity to stress. Interestingly, implicit, but not explicit, loneliness was significantly correlated with DBP reactivity after one of the stressors. No associations were found between structural support and CVR indices. Results are discussed in terms of validity of implicit versus explicit measures and possible factors that affect physiological outcomes

Treatment with a BH3 mimetic overcomes the resistance of latency III EBV (+) cells to p53-mediated apoptosis

P53 inactivation is often observed in Burkitt's lymphoma (BL) cells due to mutations in the p53 gene or overexpression of its negative regulator, murine double minute-2 (MDM2). This event is now considered an essential part of the oncogenic process. Epstein–Barr virus (EBV) is strongly associated with BL and is a cofactor in its development. We previously showed that nutlin-3, an antagonist of MDM2, activates the p53 pathway in BL cell lines harboring wild-type p53. However, nutlin-3 strongly induced apoptosis in EBV (−) or latency I EBV (+) cells, whereas latency III EBV (+) cells were much more resistant. We show here that this resistance to apoptosis is also observed in latency III EBV (+) lymphoblastoid cell lines. We also show that, in latency III EBV (+) cells, B-cell lymphona 2 (Bcl-2) is selectively overproduced and interacts with Bcl-2-associated X protein (Bax), preventing its activation. The treatment of these cells with the Bcl-2-homology domain 3 mimetic ABT-737 disrupts Bax/Bcl-2 interaction and allows Bax activation by nutlin-3. Furthermore, treatment with these two compounds strongly induces apoptosis. Thus, a combination of Mdm2 and Bcl-2 inhibitors might be a useful anti-cancer strategy for diseases linked to EBV infection

Psychological correlates of self-reported functional limitation in patients with ankylosing spondylitis

Abstract Introduction Functional status is an integral component of health-related quality of life in patients with ankylosing spondylitis (AS). The purpose of this study was to investigate the role of psychological variables in self-reported functional limitation in patients with AS, while controlling for demographic and medical variables. Methods 294 AS patients meeting modified New York Criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality and helplessness at the baseline visit. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of correlation of psychological variables with functional limitation, as measured by the Bath AS Functional Index (BASFI). Results In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASFI scores, adding an additional 24% to the overall R-square beyond that accounted by demographic and medical variables (R-square 32%), resulting in a final R-square of 56%. Specifically, arthritis helplessness, depression and passive coping beside age, ESR and the Bath AS Radiograph Index accounted for a significant portion of the variance in BASFI scores in the final model. Conclusions Arthritis helplessness, depression, and passive coping accounted for significant variability in self-reported functional limitation beyond demographic and clinical variables in patients with AS. Psychological health should be examined and accounted for when assessing functional status in the AS patients

C-Terminal Substitution of MDM2 Interacting Peptides Modulates Binding Affinity by Distinctive Mechanisms

The complex between the proteins MDM2 and p53 is a promising drug target for cancer therapy. The residues 19–26 of p53 have been biochemically and structurally demonstrated to be a most critical region to maintain the association of MDM2 and p53. Variation of the amino acid sequence in this range obviously alters the binding affinity. Surprisingly, suitable substitutions contiguous to this region of the p53 peptides can yield tightly binding peptides. The peptide variants may differ by a single residue that vary little in their structural conformations and yet are characterized by large differences in their binding affinities. In this study a systematic analysis into the role of single C-terminal mutations of a 12 residue fragment of the p53 transactivation domain (TD) and an equivalent phage optimized peptide (12/1) were undertaken to elucidate their mechanistic and thermodynamic differences in interacting with the N-terminal of MDM2. The experimental results together with atomistically detailed dynamics simulations provide insight into the principles that govern peptide design protocols with regard to protein-protein interactions and peptidomimetic design

Variability in depression prevalence in early rheumatoid arthritis: a comparison of the CES-D and HAD-D Scales

<p>Abstract</p> <p>Background</p> <p>Depression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression.</p> <p>Methods</p> <p>Data from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression.</p> <p>Results</p> <p>Ninety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D.</p> <p>Conclusion</p> <p>The CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates.</p

A longitudinal evaluation of the Center for Epidemiologic Studies-Depression scale (CES-D) in a Rheumatoid Arthritis Population using Rasch Analysis

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Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries

Importance: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent. / Objective: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa. / Design, Setting, and Participants: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection. / Exposures: Age, sex, preexisting comorbidities, and region of residence. / Main Outcomes and Measures: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay. / Results: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge. / Conclusions and Relevance: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region

The effect of social relationships on survival in elderly residents of a Southern European community: a cohort study

<p>Abstract</p> <p>Background</p> <p>Comparative evidence regarding the effects of social relationships on mortality in Mediterranean communities will increase our knowledge of their strengths and the ways in which they influence longevity across cultures. Men and women may benefit differently from social relationships because of cultural differences in gender roles. Psychosocial mechanisms such as social support, which may explain the effects of social networks, may also vary by culture.</p> <p>Methods</p> <p>Detailed information on the social relationships of a representative sample of 1,174 community-dwelling older adults was collected in Leganés, a city in central Spain. Mortality over a 6-year follow-up period was ascertained. Information on socio-demographic, health and disability variables was also collected. Cox proportional hazards models were fitted separately for men and women and for the combined sample.</p> <p>Results</p> <p>Having a confidant was associated with a 25% (95% CI 5–40%) reduction in the mortality risk. The hazard ratio for lack of social participation was 1.5 (95% CI 1.3–1.7). Being engaged in meaningful roles protected against mortality, while receipt of emotional support did not affect survival. These results were comparable for men and women. Having contact with all family ties was associated with reduced mortality only in men. Structural aspects of social networks make a unique contribution to survival, independently of emotional support and the role played in the lives of significant others.</p> <p>Conclusion</p> <p>In this elderly Southern European population, the beneficial effects of social networks, social participation, engagement in the life of significant others and having a confidant call for public policies that foster intergenerational and community exchanges.</p

Rapid and bi-directional regulation of AMPA receptor phosphorylation and trafficking by JNK

Jun N-terminal kinases (JNKs) are implicated in various neuropathological conditions. However, physiological roles for JNKs in neurons remain largely unknown, despite the high expression level of JNKs in brain. Here, using bioinformatic and biochemical approaches, we identify the AMPA receptor GluR2L and GluR4 subunits as novel physiological JNK substrates in vitro, in heterologous cells and in neurons. Consistent with this finding, GluR2L and GluR4 associate with specific JNK signaling components in the brain. Moreover, the modulation of the novel JNK sites in GluR2L and GluR4 is dynamic and bi-directional, such that phosphorylation and de-phosphorylation are triggered within minutes following decreases and increases in neuronal activity, respectively. Using live-imaging techniques to address the functional consequence of these activity-dependent changes we demonstrate that the novel JNK site in GluR2L controls reinsertion of internalized GluR2L back to the cell surface following NMDA treatment, without affecting basal GluR2L trafficking. Taken together, our results demonstrate that JNK directly regulates AMPA-R trafficking following changes in neuronal activity in a rapid and bi-directional manner

Monoterpene Variation Mediated Attack Preference Evolution of the Bark Beetle Dendroctonus valens

Several studies suggest that some bark beetle like to attack large trees. The invasive red turpentine beetle (RTB), Dendroctonus valens LeConte, one of the most destructive forest pests in China, is known to exhibit this behavior. Our previous study demonstrated that RTBs preferred to attack large-diameter trees (diameter at breast height, DBH ≥30 cm) over small-diameter trees (DBH ≤10 cm) in the field. In the current study, we studied the attacking behavior and the underlying mechanisms in the laboratory. Behavioral assays showed that RTBs preferred the bark of large-DBH trees and had a higher attack rate on the bolts of these trees. Y-tube assays showed that RTBs preferred the volatiles released by large-DBH trees to those released by small-DBH trees. Subsequent analysis revealed that both large- and small-DBH trees had the same composition of monoterpenes, but the concentration of each component differed; thus it appeared that the concentrations acted as cues for RTBs to locate the right-sized host which was confirmed by further behavioral assays. Moreover, large-DBH pine trees provided more spacious habitat and contained more nutrients, such as nitrogen, than did small-DBH pine trees, which benefited RTBs' fecundity and larval development. RTBs seem to have evolved mechanisms to locate those large hosts that will allow them to maximize their fitness. Monoterpene variation mediated attack preference implies the potential for the management of RTB