Synthesis of recrystallized anatase TiO2 mesocrystals with Wulff shape assisted by oriented attachment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)In this work, we describe a kinetically controlled crystallization process assisted by an oriented attachment (OA) mechanism based on a nonaqueous sol-gel synthetic method (specifically, the reaction of titanium(IV) chloride (TiCl4) with n-octanol) to prepare re-crystallized anatase TiO2 mesocrystals (single crystal). The kinetics study revealed a multi-step and hierarchical process controlled by OA, and a high resolution transmission electron microscopy (HRTEM) analysis clearly shows that the synthesized mesocrystal presents a truncated bipyramidal Wulff shape, indicating that its surface is dominated by {101} facets. This shape is developed during the recrystallization step. The material developed here displayed superior photocatalytic activity under visible light irradiation compared to TiO2-P25 as a benchmarking.3419101916Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FINEPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPESP [98/14324-0

Quality and effectiveness of different approaches to primary care delivery in Brazil

BACKGROUND: Since 1994, Brazil has developed a primary care system based on multidisciplinary teams which include not only a physician and a nurse, but also 4–6 lay community health workers. This system now consists of 26,650 teams, covering 46% of the Brazilian population. Yet relatively few investigations have examined its effectiveness, especially in contrast with that of the traditional multi-specialty physician team approach it is replacing, or that of other existing family medicine approaches placing less emphasis on lay community health workers. Primary health care can be defined through its domains of access to first contact, continuity, coordination, comprehensiveness, community orientation and family orientation. These attributes can be ascertained via instruments such as the Primary Care Assessment Tool (PCATool), and correlated with the effectiveness of care. The objectives of our study are to validate the adult version of this instrument in Portuguese, identify the extent (quality) of primary care present in different models of primary care services, and correlate this extent with measures of process and outcomes in patients with diabetes, hypertension and coronary heart disease (CHD). METHODS/DESIGN: We are conducting a population-based cross-sectional study of primary care in the municipality of Porto Alegre. We will interview a random sample totaling 3000 adults residing in geographic areas covered by four distinct models of primary care of the Brazilian national health system or, alternatively, by one nationally prominent complementary health care service, as well as the physicians and nurses of the health teams of these services. Interviews query perceived quality of care (PCATool-Adult Version), patient satisfaction, and process indicators of management of diabetes, hypertension and known CHD. We are measuring blood pressure, anthropometrics and, in adults with known diabetes, glycated hemoglobin. DISCUSSION: We hope to contribute not only by validating the PCATool-Adult Version for use in Brazil, but also by furnishing ample data concerning the appropriate mix of health care professionals in the primary care team, a question of international import. Once validated, future use of this instrument should help direct advances aiming at improving the quality of primary care in Brazil

5D gravitational waves from complexified black rings

In this paper we construct and briefly study the 5D time-dependent solutions of general relativity obtained via double analytic continuation of the black hole (Myers-Perry) and of the black ring solutions with a double (Pomeransky-Senkov) and a single rotation (Emparan-Reall). The new solutions take the form of a generalized Einstein-Rosen cosmology representing gravitational waves propagating in a closed universe. In this context the rotation parameters of the rings can be interpreted as the extra wave polarizations, while it is interesting to state that the waves obtained from Myers-Perry Black holes exhibit an extra boost-rotational symmetry in higher dimensions which signals their better behavior at null infinity. The analogue to the C-energy is analyzed.Comment: 18 pages, 4 figures. References added, introduction and conclusions are amended, some issues related to singularity structure and symmetries are discussed. Matches the print version to appear in JHE

Mixtures of Estrogenic Chemicals Enhance Vitellogenic Response in Sea Bass

BACKGROUND: The potential impact of natural and synthetic estrogens on aquatic ecosystems has attracted considerable attention because it is currently accepted that their joint effects are more severe when they are present in mixtures. Although it is well-known that they occur as mixtures in the marine environment, there is little information about the combined effects of estrogenic chemicals on marine biota. OBJECTIVE: In 14-day tests with juvenile sea bass, we analyzed singly and in combination the estrogenic activity of estradiol (E2), ethynylestradiol (EE2), and bisphenol A (BPA) using vitellogenin induction as an end point. METHODS: Fish were exposed to each compound, and on the basis of these concentration-response data, we predicted mixture effects by applying the model of concentration addition. The mixtures were tested using a fixed-ratio design, and the resulting mixture effects were compared to the predictions. RESULTS: EE2 was the most potent steroid, with an EC50 (median effective concentration) of 0.029 μg/L, 3.6 times more potent than E2 (EC50 = 0.104 μg/L); BPA was the least potent chemical, with an EC50 of 77.94 μg/L. The comparative assessment yielded a good agreement between observed and predicted mixture effects. CONCLUSIONS: This study demonstrates the potential hazard of these compounds to seawater life by their ability to act together in an additive manner. It provides evidence that concentration addition can be used as a predictive tool for assessing the combined effects of estrogenic chemicals in marine ecosystems

Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a

Background Typhoid persists as a major cause of global morbidity. While several licensed vaccines to prevent typhoid are available, they are of only moderate efficacy and unsuitable for use in children less than two years of age. Development of new efficacious vaccines is complicated by the human host-restriction of Salmonella enterica serovar Typhi (S. Typhi) and lack of clear correlates of protection. In this study, we aimed to evaluate the protective efficacy of a single dose of the oral vaccine candidate, M01ZH09, in susceptible volunteers by direct typhoid challenge. Methods and Findings We performed a randomised, double-blind, placebo-controlled trial in healthy adult participants at a single centre in Oxford (UK). Participants were allocated to receive one dose of double-blinded M01ZH09 or placebo or 3-doses of open-label Ty21a. Twenty-eight days after vaccination, participants were challenged with 104CFU S. Typhi Quailes strain. The efficacy of M01ZH09 compared with placebo (primary outcome) was assessed as the percentage of participants reaching pre-defined endpoints constituting typhoid diagnosis (fever and/or bacteraemia) during the 14 days after challenge. Ninety-nine participants were randomised to receive M01ZH09 (n = 33), placebo (n = 33) or 3-doses of Ty21a (n = 33). After challenge, typhoid was diagnosed in 18/31 (58.1% [95% CI 39.1 to 75.5]) M01ZH09, 20/30 (66.7% [47.2 to 87.2]) placebo, and 13/30 (43.3% [25.5 to 62.6]) Ty21a vaccine recipients. Vaccine efficacy (VE) for one dose of M01ZH09 was 13% [95% CI -29 to 41] and 35% [-5 to 60] for 3-doses of Ty21a. Retrospective multivariable analyses demonstrated that pre-existing anti-Vi antibody significantly reduced susceptibility to infection after challenge; a 1 log increase in anti-Vi IgG resulting in a 71% decrease in the hazard ratio of typhoid diagnosis ([95% CI 30 to 88%], p = 0.006) during the 14 day challenge period. Limitations to the study included the requirement to limit the challenge period prior to treatment to 2 weeks, the intensity of the study procedures and the high challenge dose used resulting in a stringent model. Conclusions Despite successfully demonstrating the use of a human challenge study to directly evaluate vaccine efficacy, a single-dose M01ZH09 failed to demonstrate significant protection after challenge with virulent Salmonella Typhi in this model. Anti-Vi antibody detected prior to vaccination played a major role in outcome after challenge

Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. (HR 3.40; 95% CI, 1.39–8.32).

Variations in TcdB Activity and the Hypervirulence of Emerging Strains of Clostridium difficile

Hypervirulent strains of Clostridium difficile have emerged over the past decade, increasing the morbidity and mortality of patients infected by this opportunistic pathogen. Recent work suggested the major C. difficile virulence factor, TcdB, from hypervirulent strains (TcdBHV) was more cytotoxic in vitro than TcdB from historical strains (TcdBHIST). The current study investigated the in vivo impact of altered TcdB tropism, and the underlying mechanism responsible for the differences in activity between the two forms of this toxin. A combination of protein sequence analyses, in vivo studies using a Danio rerio model system, and cell entry combined with fluorescence assays were used to define the critical differences between TcdBHV and TcdBHIST. Sequence analysis found that TcdB was the most variable protein expressed from the pathogenicity locus of C. difficile. In line with these sequence differences, the in vivo effects of TcdBHV were found to be substantially broader and more pronounced than those caused by TcdBHIST. The increased toxicity of TcdBHV was related to the toxin's ability to enter cells more rapidly and at an earlier stage in endocytosis than TcdBHIST. The underlying biochemical mechanism for more rapid cell entry was identified in experiments demonstrating that TcdBHV undergoes acid-induced conformational changes at a pH much higher than that of TcdBHIST. Such pH-related conformational changes are known to be the inciting step in membrane insertion and translocation for TcdB. These data provide insight into a critical change in TcdB activity that contributes to the emerging hypervirulence of C. difficile

S100B as a potential biomarker and therapeutic target in multiple sclerosis

Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.This work was supported by Medal of Honor L’Oréal for Women in Science (FCT, UNESCO, L’Óreal) and innovation grant (Ordem dos Farmacêuticos) to AF, a post-doctoral grant from Fundação para a Ciência e Tecnologia (FCT-SFRH/BPD/96794/2013) and a DuPré Grant from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) to AB, and by FCT-Pest- OE/SAU/UI4013 to iMed.ULisboa.info:eu-repo/semantics/publishedVersio