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BackgroundUnderstanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population.MethodsAn observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay.ResultsThe median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt.ConclusionsThese findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.

This study investigated effects of mindfulness training on resilience, self-confidence and emotion regulation of elite football players as well as mediating role of locus of control. The study recruited 34 participants which were assigned into experimental (n=17) and control (n=17) groups. Age ranged between 16 and 32years (M age = 22.6years, SD = 1.47). The experimental group received 8 weeks mindfulness acceptance commitment (MAC) intervention program, while control group received no intervention. Participants completed Five Facet Mindfulness Questionnaire (FFMQ), The Connor-Davidson Resilience scale (CD-RISC), Trait Sport Confidence Inventory (TSCI), Emotion Regulation Questionnaire (ERQ) and Adapted Levenson Multidimensional Locus of control scales (ALMLC). Both groups completed the questionnaire at pre-test and post-test evaluation. Descriptive data employed mean and standard deviation, while Structural Equation Modelling (SEM) of Sӧrbom's method (alternative to analysis of covariance) was used for analysis of hypothesis. Finding of the study showed that there is significant direct and indirect effect of mindfulness acceptance commitment on resilience, self-confidence and emotion regulation on elite football players. The findings further showed that there is significant difference between the pre-test scores and post-test scores of intervention group and control group. The intervention group mean scores on resilience, self-confidence and emotion regulation are higher than the control group counterparts. This shows that MAC program is effective in increasing resilience, self-confidence and emotion regulation of elite football players concurrently which in turn could improve performance and attain success.

Thermoluminescent (TL) characteristics of clay samples from Ijero-Ekiti and Isan-Ekiti, Ekiti State, Nigeria were studied for application in retrospective dosimetry. In order to increase the potentials of the clay material for relevant radiation measurement applications, characteristic glow curves of samples from the clay deposits have been obtained using a Victoreen (2800M) TL reader and the TL properties subsequently examined. The variable heating rate method was used to determine the glow peak shape and intensity by estimating the activation energy or trap depth, E and the frequency factor, S. Most samples demonstrated the dependence of their glow curve on the heating rate, with the peak temperature, Tm increasing with the heating rate. These glow peaks were noted to be a complex trapping system, consisting of several overlapping first order peaks and each with different TL behaviour, except for certain samples, which showed independence of peak temperature with dose. While recommending further heating protocol to isolate each peak for the calculation of other kinetic parameters, we present an approximate 0.29–0.84 eV for E and 3.7 × 101 to 4.0 × 106 s−1 for S. Though the samples with the TL dosimetric property of increased peak intensity with increasing excitation dose could be considered for TL applications, the reduction in TL intensity must be considered for high heating rates applications. Keywords: Clay, Thermoluminescence applications, Kinetic parameters, Trapping centres

BackgroundAnti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction.Patients and methodsWe conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation.ResultsWe studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2).Conclusions: ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

BackgroundChronic inflammation and immune activation are reported to play a key role in the etiology of non-Hodgkin lymphoma (NHL). We conducted a meta-analysis on the associations between prediagnosis circulating levels of immune stimulatory markers, interleukin 6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), CXCL13, soluble CD23 (sCD23), sCD27, sCD30, and the risk of NHL.MethodsRelevant studies were identified from PubMed, EMBASE, and Web of Science up to January 1, 2017. We calculated summary odds ratio (OR) estimates for the association between one natural log increase in concentration of each biomarker and NHL using random-effects models for NHL as a composite outcome and for several histological subtypes of NHL.ResultsSeventeen nested case control studies were included. Elevated levels of several biomarkers were more strongly associated with increased odds of NHL: TNF-α, OR = 1.18 (95% confidence interval [CI] = 1.04 to 1.34); CXCL13, OR = 1.47 (95% CI = 1.03 to 2.08); sCD23, OR = 1.57 (95% CI = 1.21 to 2.05); sCD27, OR = 2.18 (95% CI = 1.20 to 3.98); sCD30, OR = 1.65 (95% CI = 1.22 to 2.22). In stratified analyses, IL-6, TNF-α, sCD27, and sCD30 were more strongly associated with NHL in HIV-infected individuals compared to HIV-uninfected individuals. Between-study heterogeneity was observed across multiple biomarkers for overall NHL and by subtypes.ConclusionThis meta-analysis provides evidence that elevated circulating levels of TNF-α, CXCL13, sCD23, sCD27, and sCD30 are consistently associated with an increased risk of NHL, suggesting the potential utility of these biomarkers in population risk stratification and prediction.

BackgroundMethamphetamine use increases the risk of HIV-1 infection among seronegative users and can exacerbate disease progression in HIV-positive users. The biological mechanisms underlying these associations remain unclear. In this cross-sectional pilot study, we examine the associations between recent methamphetamine use and inflammation in the rectal mucosa and peripheral blood compartments in HIV-1 seropositive and seronegative men who have sex with men.MethodsHIV-seronegative and HIV-seropositive men who have sex with men participants were enrolled (N = 24). Recent methamphetamine use was determined by urine drug screen. Cytokines were quantified using multiplex arrays from collected plasma and rectal sponge samples, and peripheral blood T-cell activation was assessed by flow cytometry.ResultsMethamphetamine use was associated with consistently increased rectal inflammatory cytokines, specifically interleukin-6 and tumor necrosis factor-alpha, regardless of HIV-1 serostatus in this pilot study. This association was significant after adjusting for age, HIV-serostatus, and receptive anal intercourse frequency using regression analysis. Similar increases were not uniformly observed in peripheral blood.ConclusionsMethamphetamine use is associated with increased local mucosal inflammatory cytokine production. These findings may help explain the increased HIV-1 risk seen in methamphetamine users and contribute to increased inflammation among HIV-seropositive users.

Aim: To explore frontline health professionals' current understanding of non‐fatal strangulation and their need for and support for a comprehensive education and screening package to support health delivery. Design: A descriptive mixed‐method approach was chosen to analyse responses to an anonymous, online survey consisting of ten Likert scale, open‐ended and five demographic questions. 103 frontline health professionals (nurses, doctors, paramedics, midwives) participated in this study. Methods: Content analysis of the Likert scale and open‐ended questions describing the subjective experiences and perceptions of the participants was undertaken along with percentage and frequency counts of the rated Likert responses. Results: The findings identified that 51.1% of health professionals do not ask about strangulation routinely and that 59% of health professionals reported receiving no formal education or professional development on NFS to enhance their knowledge or inform clinical practice. No health professionals identified mild traumatic brain injury as a consequence or sign of strangulation, nor did they identify an understanding that 50% of people may have no visible injuries after being strangled. Health professionals also do not routinely document the different agencies referred to or involved in supporting the person who experienced NFS. Conclusion: Findings suggest that frontline health professionals lack the confidence, skills and education needed to meet medical obligations to their patients and to fulfil their duty to 'do no harm'. Frontline health professionals would welcome a comprehensive education and screening package to guide recognition and response to non‐fatal strangulation in their clinical settings. Where and on Whom Will the Research Have an Impact?: The purpose of the study was to understand and explore health professionals' knowledge about non‐fatal strangulation so that improved education around better screening, and management of trauma‐focused care to people who have been subjected to non‐fatal strangulation could occur. No Patient or Public Contribution: This review contains no patient or public contribution since it examines health professionals' knowledge of identifying non‐fatal strangulation and the screening and assessment tools used in clinical practice. [ABSTRACT FROM AUTHOR]

BackgroundSolid organ transplant recipients have heightened risk for diffuse large B cell lymphoma (DLBCL). The role of donor-recipient HLA mismatch and recipient HLA type on DLBCL risk are not well established.MethodsWe examined 172 231 kidney, heart, pancreas, and lung recipients transplanted in the United States between 1987 and 2010, including 902 with DLBCL. Incidence rate ratios (IRRs) were calculated using Poisson regression for DLBCL risk in relation to HLA mismatch, types, and zygosity, adjusting for sex, age, race/ethnicity, year, organ, and transplant number.ResultsCompared with recipients who had 2 HLA-DR mismatches, those with zero or 1 mismatch had reduced DLBCL risk, (zero: IRR, 0.76, 95% confidence interval [95% CI], 0.61-0.95; one: IRR, 0.83; 95% CI, 0.69-1.00). In stratified analyses, recipients matched at either HLA-A, -B, or -DR had a significantly reduced risk of late-onset (>2 years after transplantation), but not early-onset DLBCL, and there was a trend for decreasing risk with decreasing mismatch across all 3 loci (P = 0.0003). Several individual recipient HLA-A, -B, -C, -DR, and -DQ antigens were also associated with DLBCL risk, including DR13 (IRR, 0.74; 95% CI, 0.57-0.93) and B38 (IRR, 1.48; 95% CI, 1.10-1.93), confirming prior findings that these 2 antigens are associated with risk of infection-associated cancers.ConclusionsIn conclusion, variation in HLA is related to susceptibility to DLBCL, perhaps reflecting intensity of immunosuppression, control of Epstein-Barr virus infection among transplant recipients or chronic immune stimulation.