Bioactive flavanones from Luma chequen

A bioassay-guided chemical study of a methanolic extract of fresh leaves of Luma chequen led to the isolation of lumaflavanones A (1), B (2) and C (3) whose structures are proposed on the basis of NMR spectroscopic data. The structure of lumaflavanone A was confirmed by X-ray analysis. Antifeedant (Spodoptera littoralis), brine shrimp (Artemia salina) and fungistatic (Botrytis cinerea) bioassays showed that while 3 was the most active in the first two assays the mixture of 1 and 2 was more effective as a fungistatic

Difusión y localización industrial en España durante el primer tercio del siglo XX.

El propósito del trabajo es estudiar la difusión de los cambios hacia una estructura industrial manufacturera diversificada en las diferentes regiones españolas durante el primer tercio del siglo XX y la evaluación de los factores que explican el crecimiento de la industria manufacturera de estas regiones. Los factores considerados son las economías de localización (externalidades marshallianas) y las economías de urbanización (externalidades de Jacobs). Como no existe un censo industrial en España, se ha estimado una reconstrucción de los impuestos directos industriales en 1913 y 1929 para 50 provincias y 20 manufacturas. En este período de creación de una importante base manufacturera para realizar el proceso de industrialización la mayoría de las regiones no incrementaron su especialización e incluso las economías de urbanización fueron positivas para el crecimiento manufacturero entre 1913 y 1929The aim of this work is to study the diffusion of the changes towards a diversified manufacturing structure in the different Spanish regions during me first third of the XXth century and the evaluation of the factors which explain the manufacturing industrial growth of these regions. The considerated factors are the localizatíon economies (Marshall's extemalities of specialization) and the urbanization economies (extemalities of diversity or Jacobs's extemalities). Chving to the non-existence of an industrial census in Spain, we estímate a data set based on a reconstruction of the industrial direct taxes in 1913 and 1929, for 50 provinces and 20 manufactures. We find that in this period of creating of an important manufacturing basis to realize the industrialization process, the different regions did not increase their specialization and, the urbanization economies were even positive to the manufacture growth between 1913 and [email protected]

The c-Rel Subunit of NF-κB Regulates Epidermal Homeostasis and Promotes Skin Fibrosis in Mice

The five subunits of transcription factor NF-κB have distinct biological functions. NF-κB signaling is important for skin homeostasis and aging, but the contribution of individual subunits to normal skin biology and disease is unclear. Immunohistochemical analysis of the p50 and c-Rel subunits within lesional psoriatic and systemic sclerosis skin revealed abnormal epidermal expression patterns, compared with healthy skin, but RelA distribution was unaltered. The skin of Nfkb1−/− and c-Rel−/− mice is structurally normal, but epidermal thickness and proliferation are significantly reduced, compared with wild-type mice. We show that the primary defect in both Nfkb1−/− and c-Rel−/− mice is within keratinocytes that display reduced proliferation both in vitro and in vivo. However, both genotypes can respond to proliferative stress, with 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperproliferation and closure rates of full-thickness skin wounds being equivalent to those of wild-type controls. In a model of bleomycin-induced skin fibrosis, Nfkb1−/− and c-Rel−/− mice displayed opposite phenotypes, with c-Rel−/− mice being protected and Nfkb1−/− developing more fibrosis than wild-type mice. Taken together, our data reveal a role for p50 and c-Rel in regulating epidermal proliferation and homeostasis and a profibrogenic role for c-Rel in the skin, and identify a link between epidermal c-Rel expression and systemic sclerosis. Modulating the actions of these subunits could be beneficial for treating hyperproliferative or fibrogenic diseases of the skin

Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Background. Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/microL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods. We conducted a retrospective study including all ART-naive adults with CD4 <150 cells/microL prospectively enrolled in the Kilombero and Ulanga Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of death or loss to follow-up (LFU) by CRAG status and fluconazole use. Results. Of 750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/microL. Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG-negative patients were dead or LFU (P<.001), with no differences across CD4 strata. Cryptococcal antigen positivity was an independent predictor of death or LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions. Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150 cells/microL, and fluconazole increased survival or retention-in-care, suggesting that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG screening threshold of CD4 <100 cells/microL missed 18% of CRAG-positive patients, suggesting guidelines should consider a higher threshold

Fiscal Policy, Trigger Points and Interest Rates: Additional Evidence From the U.S.

We empirically investigate whether the relationship between interest rates and public deficits/debt may be nonlinear for the U.S. Using threshold estimation, we find evidence of level-dependent effects on interest rates, implying a significant effect of projected deficits and debt in the U.S. only if the deficit surpasses approximately 5% of GDP

Examining oral pre-exposure prophylaxis (PrEP) literacy among participants in an HIV vaccine trial preparedness cohort study

Background: PrEP literacy is influenced by many factors including the types of information available and how it is interpreted. The level of PrEP literacy may influence acceptability and uptake. Methods: We conducted 25 in-depth interviews in a HIV vaccine trial preparedness cohort study. We explored what participants knew about PrEP, sources of PrEP knowledge and how much they know about PrEP. We used the framework approach to generate themes for analysis guided by the Social Ecological Model and examined levels of PrEP literacy using the individual and interpersonal constructs of the SEM. Results: We found that PrEP awareness is strongly influenced by external factors such as social media and how much participants know about HIV treatment and prevention in the local community. However, while participants highlighted the importance of the internet/social media as a source of information about PrEP they talked of low PrEP literacy in their communities. Participants indicated that their own knowledge came as a result of joining the HIV vaccine trial preparedness study. However, some expressed doubts about the effectiveness of the drug and worried about side effects. Participants commented that at the community level PrEP was associated with being sexually active, because it was used to prevent the sexual transmission of HIV. As a result, some participants commented that one could feel judged by the health workers for asking for PrEP at health facilities in the community. Conclusion: The information collected in this study provided an understanding of the different layers of influence around individuals that are important to address to improve PrEP acceptability and uptake. Our findings can inform strategies to address the barriers to PrEP uptake, particularly at structural and community levels. Trial registration: https://clinicaltrials.gov/ct2/show/NCT0406688

Bioactive polychlorinated bibenzyls from the liverwort Riccardia polyclada

3 pages, 2 tables.-- PMID: 18020419 [PubMed].-- Printed version published on Dec 28, 2007.GC-MS and 1H NMR spectroscopic profiling of a CDCl3 extract of the liverwort Riccardia polyclada (syn. R. umbrosa) revealed the presence of four main compounds bearing several chlorine atoms on a bibenzyl skeleton. Separation of a CH2Cl2 extract was achieved using preparative TLC, and structures 1–4 were proposed on the basis of spectroscopic evidence. Compounds 1–4 were active in a brine shrimp lethality bioassay (Artemia salina). In addition, 2 and 4 displayed moderate antifeedant activity in disk-choice bioassays with Spodoptera littoralis larvae and inhibited the growth of Cladosporium herbarum cultures on TLC plates.This research was supported by a grant from the Chemistry Department of the Facultad de Ciencias, Universidad de Chile, and by a Higher Education Link (SAN/984/117) from the British Council in Santiago. Financial support of CYTED (Spain) and Xarxa de Productes Naturals (Barcelona, Spain) is also acknowledged.Peer reviewe

Burden of serious fungal infections in Tanzania.

The incidence and prevalence of fungal infections in Tanzania remains unknown. We assessed the annual burden in the general population and among populations at risk. Data were extracted from 2012 reports of the Tanzanian AIDS program, WHO, reports, Tanzanian census, and from a comprehensive PubMed search. We used modelling and HIV data to estimate the burdens of Pneumocystis jirovecii pneumonia (PCP), cryptococcal meningitis (CM) and candidiasis. Asthma, chronic obstructive pulmonary disease and tuberculosis data were used to estimate the burden of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Burdens of candidaemia and Candida peritonitis were derived from critical care and/or cancer patients' data. In 2012, Tanzania's population was 43.6 million (mainland) with 1 500 000 people reported to be HIV-infected. Estimated burden of fungal infections was: 4412 CM, 9600 PCP, 81 051 and 88 509 oral and oesophageal candidiasis cases respectively. There were 10 437 estimated posttuberculosis CPA cases, whereas candidaemia and Candida peritonitis cases were 2181 and 327 respectively. No reliable data exist on blastomycosis, mucormycosis or fungal keratitis. Over 3% of Tanzanians suffer from serious fungal infections annually, mostly related to HIV. Cryptococcosis and PCP are major causes of mycoses-related deaths. National surveillance of fungal infections is urgently needed