Depressive symptoms in asymptomatic stage B heart failure with Type II diabetic mellitus.

BackgroundThe presence of concomitant Type II diabetic mellitus (T2DM) and depressive symptoms adversely affects individuals with symptomatic heart failure (HF).HypothesisIn presymptomatic stage B HF, this study hypothesized the presence of greater inflammation and depressive symptoms in T2DM as compared to non-T2DM Stage B patients.MethodsThis cross-sectional study examined clinical parameters, inflammatory biomarkers, and depressive symptoms in 349 T2DM and non-T2DM men with asymptomatic stage B HF (mean age 66.4 years ±10.1; range 30-91).ResultsFewer diabetic HF patients had left ventricular (LV) systolic dysfunction (P < .05) although more had LV diastolic dysfunction (P < .001). A higher percentage of T2DM HF patients were taking ACE-inhibitors, beta-blockers, calcium channel blockers, statins, and diuretics (P values < .05). T2DM HF patients had higher circulating levels of interleukin-6 (IL-6) (P < .01), tumor necrosis factor-alpha (P < .01), and soluble ST2 (sST2) (P < .01) and reported more somatic/affective depressive symptoms (Beck Depression Inventory II) (P < .05) but not cognitive/affective depressive symptoms (P = .20). Among all patients, in a multiple regression analysis predicting presence of somatic/affective depressive symptoms, sST2 (P = .026), IL-6 (P = .010), B-type natriuretic peptide (P = .016), and sleep (Pittsburgh Sleep Quality Index [P < .001]) were significant predictors (overall model F = 15.39, P < .001, adjusted R2 = .207).ConclusionsSomatic/affective but not cognitive/affective depressive symptoms are elevated in asymptomatic HF patients with T2DM patients. Linkages with elevated inflammatory and cardiac relevant biomarkers suggest shared pathophysiological mechanisms among T2DM HF patients with somatic depression, and these conditions are responsive to routine interventions, including behavioral. Copyright © 2019 John Wiley & Sons, Ltd

Modeling plant ranges over 75 years of climate change in California, USA: temporal transferability and species traits

Species distribution model (SDM) projections under future climate scenarios are increasingly being used to inform resource management and conservation strategies. A critical assumption for projecting climate change responses is that SDMs are transferable through time, an assumption that is largely untested because investigators often lack temporally independent data for assessing transferability. Further, understanding how the ecology of species influences temporal transferability is critical yet almost wholly lacking. This raises two questions. (1) Are SDM projections transferable in time? (2) Does temporal transferability relate to species ecological traits? To address these questions we developed SDMs for 133 vascular plant species using data from the mountain ranges of California (USA) from two time periods: the 1930s and the present day. We forecast historical models over 75 years of measured climate change and assessed their projections against current distributions. Similarly, we hindcast contemporary models and compared their projections to historical data. We quantified transferability and related it to species ecological traits including physiognomy, endemism, dispersal capacity, fire adaptation, and commonness. We found that non-endemic species with greater dispersal capacity, intermediate levels of prevalence, and little fire adaptation had higher transferability than endemic species with limited dispersal capacity that rely on fire for reproduction. We demonstrate that variability in model performance was driven principally by differences among species as compared to model algorithms or time period of model calibration. Further, our results suggest that the traits correlated with prediction accuracy in a single time period may not be related to transferability between time periods. Our findings provide a priori guidance for the suitability of SDM as an approach for forecasting climate change responses for certain taxa

Can the deployment of community health workers for the delivery of HIV services represent an effective and sustainable response to health workforce shortages? Results of a multicountry study

In countries severely affected by HIV/AIDS, shortages of health workers present a major obstacle to scaling up HIV services. Adopting a task shifting approach for the deployment of community health workers (CHWs) represents one strategy for rapid expansion of the health workforce. This study aimed to evaluate the contribution of CHWs with a focus on identifying the critical elements of an enabling environment that can ensure they provide quality services in a manner that is sustainable. The method of work included a collection of primary data in five countries: Brazil, Ethiopia, Malawi, Namibia, and Uganda. The findings show that delegation of specific tasks to cadres of CHWs with limited training can increase access to HIV services, particularly in rural areas and among underserved communities, and can improve the quality of care for HIV. There is also evidence that CHWs can make a significant contribution to the delivery of a wide range of other health services. The findings also show that certain conditions must be observed if CHWs are to contribute to well-functioning and sustainable service delivery. These conditions involve adequate systems integration with significant attention to: political will and commitment; collaborative planning; definition of scope of practice; selection and educational requirements; registration, licensure and certification; recruitment and deployment; adequate and sustainable remuneration; mentoring and supervision including referral system; career path and continuous education; performance evaluation; supply of equipment and commodities. The study concludes that, where there is the necessary support, the potential contribution of CHWs can be optimized and represents a valuable addition to the urgent expansion of human resources for health, and to universal coverage of HIV services

Probing Lorentz and CPT violation with space-based experiments

Space-based experiments offer sensitivity to numerous unmeasured effects involving Lorentz and CPT violation. We provide a classification of clock sensitivities and present explicit expressions for time variations arising in such experiments from nonzero coefficients in the Lorentz- and CPT-violating Standard-Model Extension.Comment: 15 page

ATP-binding cassette transporter A7 enhances phagocytosis of apoptotic cells and associated ERK signaling in macrophages

The mammalian ATP-binding cassette transporters A1 and A7 (ABCA1 and -A7) show sequence similarity to CED-7, a Caenorhabditis elegans gene that mediates the clearance of apoptotic cells. Using RNA interference or gene targeting, we show that knock down of macrophage ABCA7 but not -A1 results in defective engulfment of apoptotic cells. In response to apoptotic cells, ABCA7 moves to the macrophage cell surface and colocalizes with the low-density lipoprotein receptor–related protein 1 (LRP1) in phagocytic cups. The cell surface localization of ABCA7 and LRP1 is defective in ABCA7-deficient cells. C1q is an opsonin of apoptotic cells that acts via phagocyte LRP1 to induce extracellular signal–regulated kinase (ERK) signaling. We show that ERK signaling is required for phagocytosis of apoptotic cells and that ERK phosphorylation in response to apoptotic cells or C1q is defective in ABCA7-deficient cells. These studies reveal a major role of ABCA7 and not -A1 in the clearance of apoptotic cells and therefore suggest that ABCA7 is an authentic orthologue of CED-7

Lorentz and CPT Violation in Neutrinos

A general formalism is presented for violations of Lorentz and CPT symmetry in the neutrino sector. The effective hamiltonian for neutrino propagation in the presence of Lorentz and CPT violation is derived, and its properties are studied. Possible definitive signals in existing and future neutrino-oscillation experiments are discussed. Among the predictions are direction-dependent effects, including neutrino-antineutrino mixing, sidereal and annual variations, and compass asymmetries. Other consequences of Lorentz and CPT violation involve unconventional energy dependences in oscillation lengths and mixing angles. A variety of simple models both with and without neutrino masses are developed to illustrate key physical effects. The attainable sensitivities to coefficients for Lorentz violation in the Standard-Model Extension are estimated for various types of experiments. Many experiments have potential sensitivity to Planck-suppressed effects, comparable to the best tests in other sectors. The lack of existing experimental constraints, the wide range of available coefficient space, and the variety of novel effects imply that some or perhaps even all of the existing data on neutrino oscillations might be due to Lorentz and CPT violation.Comment: 25 pages REVTe

HIV Transmission in a State Prison System, 1988–2005

INTRODUCTION: HIV prevalence among state prison inmates in the United States is more than five times higher than among nonincarcerated persons, but HIV transmission within U.S. prisons is sparsely documented. We investigated 88 HIV seroconversions reported from 1988-2005 among male Georgia prison inmates. METHODS: We analyzed medical and administrative data to describe seroconverters' HIV testing histories and performed a case-crossover analysis of their risks before and after HIV diagnosis. We sequenced the gag, env, and pol genes of seroconverters' HIV strains to identify genetically-related HIV transmission clusters and antiretroviral resistance. We combined risk, genetic, and administrative data to describe prison HIV transmission networks. RESULTS: Forty-one (47%) seroconverters were diagnosed with HIV from July 2003-June 2005 when voluntary annual testing was offered. Seroconverters were less likely to report sex (OR [odds ratio] = 0.02, 95% CI [confidence interval]: 0-0.10) and tattooing (OR = 0.03, 95% CI: <0.01-0.20) in prison after their HIV diagnosis than before. Of 67 seroconverters' specimens tested, 33 (49%) fell into one of 10 genetically-related clusters; of these, 25 (76%) reported sex in prison before their HIV diagnosis. The HIV strains of 8 (61%) of 13 antiretroviral-naïve and 21 (40%) of 52 antiretroviral-treated seroconverters were antiretroviral-resistant. DISCUSSION: Half of all HIV seroconversions were identified when routine voluntary testing was offered, and seroconverters reduced their risks following their diagnosis. Most genetically-related seroconverters reported sex in prison, suggesting HIV transmission through sexual networks. Resistance testing before initiating antiretroviral therapy is important for newly-diagnosed inmates

Gravity, Lorentz Violation, and the Standard Model

The role of the gravitational sector in the Lorentz- and CPT-violating Standard-Model Extension (SME) is studied. A framework is developed for addressing this topic in the context of Riemann-Cartan spacetimes, which include as limiting cases the usual Riemann and Minkowski geometries. The methodology is first illustrated in the context of the QED extension in a Riemann-Cartan background. The full SME in this background is then considered, and the leading-order terms in the SME action involving operators of mass dimension three and four are constructed. The incorporation of arbitrary Lorentz and CPT violation into general relativity and other theories of gravity based on Riemann-Cartan geometries is discussed. The dominant terms in the effective low-energy action for the gravitational sector are provided, thereby completing the formulation of the leading-order terms in the SME with gravity. Explicit Lorentz symmetry breaking is found to be incompatible with generic Riemann-Cartan geometries, but spontaneous Lorentz breaking evades this difficulty.Comment: 21 pages REVTeX, references added, accepted in Physical Review

The Pace of Prostatic Intraepithelial Neoplasia Development Is Determined by the Timing of Pten Tumor Suppressor Gene Excision

Loss of the PTEN tumor suppressor is a common occurrence in human prostate cancer, particularly in advanced disease. In keeping with its role as a pivotal upstream regulator of the phosphatidylinositol 3-kinase signaling pathway, experimentally-induced deletion of Pten in the murine prostate invariably results in neoplasia. However, and unlike humans where prostate tumorigenesis likely evolves over decades, disease progression in the constitutively Pten deficient mouse prostate is relatively rapid, culminating in invasive cancer within several weeks post-puberty. Given that the prostate undergoes rapid androgen-dependent growth at puberty, and that Pten excisions during this time might be especially tumorigenic, we hypothesized that delaying prostate-specific Pten deletions until immediately after puberty might alter the pace of tumorigenesis. To this end we generated mice with a tamoxifen-inducible Cre recombinase transgene enabling temporal control over prostate-specific gene alterations. This line was then interbred with mice carrying floxed Pten alleles. Despite evidence of increased Akt/mTOR/S6K axis activity at early time points in Pten-deficient epithelial cells, excisions induced in the post-pubertal (6 wk-old) prostate yielded gradual acquisition of a range of lesions. These progressed from pre-malignant changes (nuclear atypia, focal hyperplasia) and low grade prostatic intraepithelial neoplasia (PIN) at 16–20 wks post-tamoxifen exposure, to overtly malignant lesions by ∼1 yr of age, characterized by high-grade PIN and microinvasive carcinoma. In contrast, when Pten excisions were triggered in the pre-pubertal (2 week-old) prostate, neoplasia evolved over a more abbreviated time-frame, with a spectrum of premalignant lesions, as well as overt PIN and microinvasive carcinoma by 10–12 wks post-tamoxifen exposure. These results indicate that the developmental stage at which Pten deletions are induced dictates the pace of PIN development