Social status is one of the strongest predictors of human disease risk and mortality, and it also influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined genomics with a social status manipulation in female rhesus macaques to investigate how status alters immune function. We demonstrate causal but largely plastic social status effects on immune cell proportions, cell type–specific gene expression levels, and the gene expression response to immune challenge. Further, we identify specific transcription factor signaling pathways that explain these differences, including low-status–associated polarization of the Toll-like receptor 4 signaling pathway toward a proinflammatory response. Our findings provide insight into the direct biological effects of social inequality on immune function, thus improving our understanding of social gradients in health.
Introduction Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been proposed as an effective non-invasive treatment option for erectile dysfunction (ED). Aim To use systematic review and meta-analysis to assess the efficacy of Li-ESWT by comparing change in erectile function as assessed by the erectile function domain of the International Index of Erectile Function (IIEF-EF) in men undergoing Li-ESWT vs sham therapy for the treatment of ED. Methods Systematic search was conducted of MEDLINE, EMBASE, and ClinicalTrials.gov for randomized controlled trials that were published in peer-reviewed journals or presented in abstract form of Li-ESWT used for the treatment of ED from January 2010 through March 2016. Randomized controlled trials were eligible for inclusion if they were published in the peer-reviewed literature and assessed erectile function outcomes using the IIEF-EF score. Estimates were pooled using random-effects meta-analysis. Main Outcome Measures Change in IIEF-EF score after treatment with Li-ESWT in patients treated with active treatment vs sham Li-ESWT probes. Results Data were extracted from seven trials involving 602 participants. The average age was 60.7 years and the average follow-up was 19.8 weeks. There was a statistically significant improvement in pooled change in IIEF-EF score from baseline to follow-up in men undergoing Li-ESWT vs those undergoing sham therapy (6.40 points; 95% CI = 1.78–11.02; I2 = 98.7%; P < .0001 vs 1.65 points; 95% CI = 0.92–2.39; I2 = 64.6%; P < .0001; between-group difference, P = .047). Significant between-group differences were found for total treatment shocks received by patients (P < .0001). Conclusion In this meta-analysis of seven randomized controlled trials, treatment of ED with Li-ESWT resulted in a significant increase in IIEF-EF scores.
Background Depression is common during and after breast cancer treatment. However, the role of specific therapeutic modalities and related biological mechanisms remains unclear. Radiation is an essential component of breast conserving therapy and may contribute to depression in breast cancer patients through activation of inflammatory pathways. Methods Depressive symptoms and inflammatory mediators including nuclear factor kappa B (NF-kB) were assessed at baseline (before radiation), during, and 6 weeks after radiation in 64 women with Stage 0–IIIA breast cancer. Results No significant increases in depressive symptoms occurred during or after radiation, although a number of patients exhibited moderate-to-severe depression throughout the study. Multivariate analyses of baseline factors predictive of depression revealed that educational status, perceived stress, prior chemotherapy and peripheral blood NF-kB DNA binding were all independent predictors of persistent depressive symptoms following radiation (all p<0.05). Of these factors, only prior chemotherapy was associated with inflammatory mediators including NF-kB DNA binding, soluble tumor necrosis factor-alpha receptor 2 and interleukin-6, which in univariate analyses predicted depressive symptoms following radiation (all p<0.05). Chemotherapy-treated patients also exhibited an overrepresentation of gene transcripts regulated by NF-KB. Conclusions Radiation was not associated with increased depressive symptoms, but of disease and treatment-related factors, prior chemotherapy predicted significant depression following radiation. Longitudinal studies are warranted to investigate the relationship among prior chemotherapy, inflammation, and persistent depression following breast cancer treatment.
Field studies of wild vertebrates are frequently associated with extensive collections of banked fecal samples—unique resources for understanding ecological, behavioral, and phylogenetic effects on the gut microbiome. However, we do not understand whether sample storage methods confound the ability to investigate interindividual variation in gut microbiome profiles. Here, we extend previous work on storage methods for gut microbiome samples by comparing immediate freezing, the gold standard of preservation, to three methods commonly used in vertebrate field studies: lyophilization, storage in ethanol, and storage in RNAlater. We found that the signature of individual identity consistently outweighed storage effects: alpha diversity and beta diversity measures were significantly correlated across methods, and while samples often clustered by donor, they never clustered by storage method. Provided that all analyzed samples are stored the same way, banked fecal samples therefore appear highly suitable for investigating variation in gut microbiota. Our results open the door to a much-expanded perspective on variation in the gut microbiome across species and ecological contexts.
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