Ethnicity is associated with alterations in oxytocin relationships to pain sensitivity in women

It is well established that African Americans (AA) experience greater pain associated with a variety of clinical conditions, and greater pain sensitivity to experimental pain tasks relative to non-Hispanic Whites (W). Notably, African Americans do not show the same relationships involving endogenous pain regulatory mechanisms and pain sensitivity documented in Caucasians, including positive associations between blood pressure, norepinephrine, cortisol and greater pain tolerance

Effects of Androgen Receptor and Androgen on Gene Expression in Prostate Stromal Fibroblasts and Paracrine Signaling to Prostate Cancer Cells

The androgen receptor (AR) is expressed in a subset of prostate stromal cells and functional stromal cell AR is required for normal prostate developmental and influences the growth of prostate tumors. Although we are broadly aware of the specifics of the genomic actions of AR in prostate cancer cells, relatively little is known regarding the gene targets of functional AR in prostate stromal cells. Here, we describe a novel human prostate stromal cell model that enabled us to study the effects of AR on gene expression in these cells. The model involves a genetically manipulated variant of immortalized human WPMY-1 prostate stromal cells that overexpresses wildtype AR (WPMY-AR) at a level comparable to LNCaP cells and is responsive to dihydrotestosterone (DHT) stimulation. Use of WPMY-AR cells for gene expression profiling showed that the presence of AR, even in the absence of DHT, significantly altered the gene expression pattern of the cells compared to control (WPMY-Vec) cells. Treatment of WPMY-AR cells, but not WPMY-Vec control cells, with DHT resulted in further changes that affected the expression of 141 genes by 2-fold or greater compared to vehicle treated WPMY-AR cells. Remarkably, DHT significantly downregulated more genes than were upregulated but many of these changes reversed the initial effects of AR overexpression alone on individual genes. The genes most highly effected by DHT treatment were categorized based upon their role in cancer pathways or in cell signaling pathways (transforming growth factor-β, Wnt, Hedgehog and MAP Kinase) thought to be involved in stromal-epithelial crosstalk during prostate or prostate cancer development. DHT treatment of WPMY-AR cells was also sufficient to alter their paracrine potential for prostate cancer cells as conditioned medium from DHT-treated WPMY-AR significantly increased growth of LNCaP cells compared to DHT-treated WPMY-Vec cell conditioned medium

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Monosodium urate deposition in the lumbosacral spine of patients with gout compared with non-gout controls: A dual-energy CT study.

Gout is the most common cause of inflammatory arthritis in adults. Gout predominantly affects the peripheral joints, but an increasing number of published cases report gout affecting the spine. We used dual-energy CT (DECT) to assess the prevalence of monosodium urate (MSU) deposition in the spine of gout patients compared to controls, and to investigate whether gout or spinal MSU deposition is associated with low back pain. 25 controls and 50 gout subjects (non-tophaceous and tophaceous) were enrolled. Demographics, gout history, Aberdeen back pain score, serum urate (sU), ESR and CRP were ascertained. Subjects underwent DECT of the lumbosacral spine, which was analyzed using manufacturer's default post-processing algorithm for MSU deposition as well as a maximally-specific algorithm to exclude potential artifact. 72 subjects were analyzed (25 control, 47 gout). Gout subjects had greater BMI, serum creatinine, sU, CRP, and ESR versus controls. Using the default algorithm, MSU-coded volumes in the lumbosacral spines were significantly higher among the gout subjects vs controls (p = 0.018). 34% of gout subjects vs 4% of controls had spinal MSU-coded deposition (p = 0.0036). Applying the maximally-specific DECT post-processing algorithm, 18% of gout patients vs 0% of controls continued to demonstrate spinal MSU-coded deposition (p = 0.04). Non-tophaceous and tophaceous subjects did not differ in spinal MSU-coded deposition or sU. Gout patients had more back pain than controls. A significant subpopulation of gout patients have spinal MSU-coded lesions. Default and maximally-specific MSU post-processing algorithms yielded different absolute MSU-coded volumes, but similar patterns of results. Gout patients had more back pain than controls. Spinal MSU deposition in gout patients may have implications for clinical picture and treatment