mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity

The epithelial Na⁺ channel (ENaC) is essential for Na⁺ homeostasis, and dysregulation of this channel underlies many forms of hypertension. Recent studies suggest that mTOR regulates phosphorylation and activation of serum/glucocorticoid regulated kinase 1 (SGK1), which is known to inhibit ENaC internalization and degradation; however, it is not clear whether mTOR contributes to the regulation of renal tubule ion transport. Here, we evaluated the effect of selective mTOR inhibitors on kidney tubule Na⁺ and K⁺ transport in WT and Sgk1^–/– mice, as well as in isolated collecting tubules. We found that 2 structurally distinct competitive inhibitors (PP242 and AZD8055), both of which prevent all mTOR-dependent phosphorylation, including that of SGK1, caused substantial natriuresis, but not kaliuresis, in WT mice, which indicates that mTOR preferentially influences ENaC function. PP242 also substantially inhibited Na⁺ currents in isolated perfused cortical collecting tubules. Accordingly, patch clamp studies on cortical tubule apical membranes revealed that mTOR inhibition markedly reduces ENaC activity, but does not alter activity of K⁺ inwardly rectifying channels (ROMK channels). Together, these results demonstrate that mTOR regulates kidney tubule ion handling and suggest that mTOR regulates Na⁺ homeostasis through SGK1-dependent modulation of ENaC activity.     

Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease

A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease-associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease-associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease-associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.     

The Syndemic Condition of Psychosocial Problems and HIV Risk Among Male Sex Workers in Ho Chi Minh City,Vietnam

In Vietnam, the co-occurrence (i.e., “syndemic”) of psychosocial factors (e.g., depression and substance use) may disproportionately burden male sex workers and increase their HIV risk. A comprehensive survey was conducted among 300 male sex workers in Ho Chi Minh City, Vietnam in 2010. We performed logistic regression to examine the association between the syndemic variable—a count score of the number of five psychosocial conditions endorsed—and unprotected anal sex (UAS) in the past. One-third of participants reported any UAS, and 42 % reported ≥2 psychosocial health problems. In multivariable models, experiencing ≥4 psychosocial health problems was significantly associated with UAS. Every unit increase in number of psychosocial health problems was associated with a 25–30 % increase in odds of UAS. Understanding the syndemic condition and its association with HIV risk among male sex workers in Vietnam may lead to the development of more effective, comprehensive interventions.     

Well‐Defined Imidazolium ABA Triblock Copolymers as Ionic‐Liquid‐Containing Electroactive Membranes

Nitroxide‐mediated polymerization (NMP) affords the synthesis of well‐defined ABA triblock copolymers with polystyrene external blocks and a charged poly(1‐methyl‐3‐(4‐vinylbenzyl)­imidazolium bis(trifluoromethane sulfonyl)imide central block. Aqueous size‐exclusion chromatography (SEC) and ¹H NMR spectroscopy studies confirm the control of the composition and block lengths for both the central and external blocks. Dynamic mechanical analysis (DMA) reveals a room temperature modulus suitable for fabricating these triblock copolymers into electroactive devices in the presence of an added ionic liquid. Dielectric relaxation spectroscopy (DRS) elucidates the ion‐transport properties of the ABA triblock copolymers with varied compositions. The ionic conductivity in these single‐ion conductors exhibits Vogel–Fulcher–Tammann (VFT) and Arrhenius temperature dependences, and electrode polarization (EP) analysis determines the number density of simultaneously conducting ions and their mobility. The actuators derived from these triblock copolymer membranes experience similar actuation speeds at an applied voltage of 4 V DC, as compared with benchmark Nafion membranes. These tailorable ABA block copolymers are promising candidates for ionic‐polymer device applications.