Recombinant BCG vaccine candidates

Given the variable protective efficacy provided by Mycobacterium bovis BCG (Bacillus Calmette-Guérin), there is a concerted effort worldwide to develop better vaccines that could be used to reduce the burden of tuberculosis. Recombinant BCG (rBCG) are vaccine candidates that offer some potential in this area. In this paper, we will discuss the molecular methods used to generate rBCG, and the results obtained with some of these new vaccines as compared with the conventional BCG vaccine in diverse animal models. Tuberculosis vaccine candidates based on rBCG are promising candidates, and some of them are now being tested in clinical trials.     

Neural tube defects, micronutrient deficiencies, and Helicobacter pylori: a new hypothesis

BACKGROUND: Previous findings for the Texas Neural Tube Defects Project suggested that while maternal access to nutrients is adequate, bioavailability of nutrients to the fetus is compromised in NTD-affected pregnancies. Helicobacter pylori could cause nutrient loss to the fetus. Folate, B12, and ferritin are depleted in H. pylori infection; these same deficiencies are related to NTD risk. METHODS: Using H. pylori IgG ELISA Test System, we tested for H. pylori serum antibodies in participants in the population-based case-control study component of the Texas Neural Tube Defect Project conducted along the Texas-Mexico border. Case-women had pregnancies affected by NTD (anencephalus, spina bifida, encephalocele) and resided and delivered in one of the 14 Texas-Mexico border counties from 1995 through 2000. Control-women were study area residents delivering normal live births during the same period. RESULTS: Of 225 case- and 378 control-women, 103 cases and 156 controls provided questionnaire and H. pylori antibody data. H. pylori seropositivity was modestly associated with NTD-affected pregnancies (OR 1.4; 95% CI: 0.8-2.4). ORs of 2.0 or greater were seen in women younger than age 25 and with less than 7 years education. CONCLUSIONS: Our findings intimate that H. pylori could play a role in NTD causation in certain populations. While results did not provide compelling support for this proposal, subgroup findings prompt us to advocate an evaluation of this hypothesis in developing nations among populations with higher prevalence of H. pylori, marginal nutrient intake, and young childbearing age.     

Interaction of Photoprotective and Acclimation Mechanisms in Ulva rigida (Chlorophyta) in Response to Diurnal Changes in Solar Radiation in Southern Chile

Species of the genus Ulva (Chlorophyta) are regarded as opportunistic organisms, which efficiently adjust their metabolism to the prevailing environmental conditions. In this study, changes in chlorophyll‐a fluorescence‐based photoinhibition of photosynthesis, electron transport rates, photosynthetic pigments, lipid peroxidation, total phenolic compounds, and antioxidant metabolism were investigated during a diurnal cycle of natural solar radiation in summer (for 12 h) under two treatments: photosynthetically active radiation (PAR: 400–700 nm) and PAR+ ultraviolet (UV) radiation (280–700 nm). In the presence of PAR alone, Ulva rigida showed dynamic photoinhibition, and photosynthetic parameters and pigment concentrations decreased with the intensification of the radiation. On the other hand, under PAR+UV conditions a substantial decline up to 43% was detected and an incomplete fluorescence recovery, also, P‐I curve values remained low in relation to the initial condition. The phenolic compounds increased their concentration only in UV radiation treatments without showing a correlation with the antioxidant activity. The enzimatic activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) increased over 2‐fold respect at initial values during the onset of light intensity. In contrast, catalase (CAT) increased its activity rapidly in response to the radiation stress to reach maxima at 10 a.m. and decreasing during solar. The present study suggests that U. rigida is capable of acclimating to natural radiation stress relies on a concerted action of various physiological mechanisms that act at different times of the day and under different levels of environmental stress.     

Hyperglycemia differentially affects proliferation,apoptosis, and BNIP3 and p53 mRNA expression of human umbilical cord Wharton's jelly cells from non-diabetic and diabetic pregnancies

Diabetes in pregnancy constitutes an unfavorable environment for embryonic and fetal development, where the child has a higher risk of perinatal morbidity and mortality, with high incidence of congenital malformations and predisposition to long-term metabolic diseases that increase with a hypercaloric diet. To analyze whether hyperglycemia differentially affects proliferation, apoptosis, and mRNA expression in cells from children of normoglycemic pregnancies (NGPs) and diabetes mellitus pregnancies (DMPs), we used umbilical cord Wharton jelly cells as a research model. Proliferation assays were performed to analyze growth and determine the doubling time, and the rate of apoptosis was determined by flow cytometry-annexin-V assays. AMPK, BNIP3, HIF1α, and p53 mRNA gene expression was assessed by semi-quantitative RT-PCR. We found that hyperglycemia decreased proliferation in a statistically significant manner in NGP cells treated with 40?mM D-glucose and in DMP cells treated with 30 and 40?mM D-glucose. Apoptosis increased in hyperglycemic conditions in NGP and DMP cells. mRNA expression of BNIP3 and p53 was significantly increased in cells from DMPs but not in cells from NGPs. We found evidence that maternal irregular metabolic conditions, like diabetes with hyperglycemia in culture, affect biological properties of fetal cells. These observations could be a constituent of fetal programming.     

Sperm quality of Colossoma macropomum after room‐temperature and cold storage

The objective of this study was to evaluate the effects of cold and room‐temperature storage on the quality of Colossoma macropomum sperm. The experiment was carried out in December (end of Spring), in Nova Mutum‐MT, Brazil, involving nine C. macropomum males (4 years old; 6.4 ± 1.5 kg average weight). The fish were selected and transferred to masonry tanks (4 m³) in a laboratory (water renewal rate: 10 L/s; average water temperature: 28°C). Subsequently, reproduction was induced using 2.5 mg of crude carp pituitary extract/kg and the semen was harvested 240 degree hours after hormonal induction. The following sperm characteristics were analyzed every 5 hr using Image J/casa software: total motility (MOT), curvilinear velocity (VCL), average path velocity (VAP), straight‐line velocity (VSL), straightness of sperm path (STR), wobble (WOB), progressive motility (PROG), beat cross frequency (BCF) and total number of spermatozoa (NSPZ). A fresh sample of semen from each animal was kept at room temperature (25.3 ± 1.2°C). For analysis of cooled semen, syringes were kept in cooling boxes at an average temperature of 16.9 ± 2.1°C. The reduction (p < 0.05) of MOT in semen kept at room temperature occurred at 10 hr (13.95%); in cooled semen, however, MOT declined at 15 hr (76.87%). At 15 hr, there was practically no MOT in the semen kept at room temperature (0.20%), whereas in the cooled semen this situation was observed only at 35 hr (2.91%) The MOT of cooled sperm was higher (p < 0.05) at all times (except zero time), compared with the semen maintained at room temperature. At 15 hr, the cooled spermatozoa showed higher (p < 0.05) VCL (142.18 μm/s) and BCF (29.72 Hz) than those maintained at room temperature (VCL: 51.18 μm/s; BCF: 19.57 Hz). After 15 hr, only the cooled sperm showed quality. In conclusion, semen cooling allows for extending the viability of C. macropomum spermatozoa from 5 to 10 hr without compromising their quality in most characteristics. At 15 and 25 hr of cooling, sperm viability is still observed, though with decreased quality.     

In Vitro Interactions of Amphotericin B Combined with Non-antifungal Agents Against Rhodotorula mucilaginosa Strains

Rhodotorula species are emerging as opportunistic pathogens, causing catheter-associated fungemia in patients with compromised immunity. R. mucilaginosa is considered the most common species involved in human infections. Correct identification and susceptibility testing of Rhodotorula isolates recovered from the blood stream or central nervous system are essential to determine the best management of this unusual infection. The antifungal susceptibility tests showed that Rhodotorula was susceptible to low concentrations of amphotericin B (AMB) but was less susceptible to voriconazole. Combinations of AMB plus several non-antifungal medications were evaluated against 35 susceptible (Rm AMB-S) and resistant (Rm AMB-R) clinical Rhodotorula isolates using the broth microdilution checkerboard technique. We showed that in vitro exposure to increasing concentrations of AMB changed the susceptibility profile to these strains, which were named the Rm AMB-R group. The most synergistic interactions were AMB?+?simvastatin, followed by AMB?+?amlodipine and AMB?+?warfarin. Synergism and antagonism were observed in both groups for the combination AMB?+?cyclosporine A. AMB combined with a fluoroquinolone (AMB?+?levofloxacin) also demonstrated antagonism for the Rm AMB-S strains, but a high percentage of synergistic interactions was observed for the Rm AMB-R group. A combination drug approach can provide a different strategy to treat infections caused by AMB-resistant R. mucilaginosa.

     

Predicting dengue incidence leveraging internet-based data sources. A case study in 20 cities in Brazil

The dengue virus affects millions of people every year worldwide, causing large epidemic outbreaks that disrupt people’s lives and severely strain healthcare systems. In the absence of a reliable vaccine against dengue or an effective treatment to manage the illness in humans, most efforts to combat dengue infections have focused on preventing its vectors, mainly the Aedes aegypti mosquito, from flourishing across the world. These mosquito-control strategies need reliable disease activity surveillance systems to be deployed. Despite significant efforts to estimate dengue incidence using a variety of data sources and methods, little work has been done to understand the relative contribution of the different data sources to improved prediction. Additionally, scholarship on the topic had initially focused on prediction systems at the national- and state-levels, and much remains to be done at the finer spatial resolutions at which health policy interventions often occur. We develop a methodological framework to assess and compare dengue incidence estimates at the city level, and evaluate the performance of a collection of models on 20 different cities in Brazil. The data sources we use towards this end are weekly incidence counts from prior years (seasonal autoregressive terms), weekly-aggregated weather variables, and real-time internet search data. We find that both random forest-based models and LASSO regression-based models effectively leverage these multiple data sources to produce accurate predictions, and that while the performance between them is comparable on average, the former method produces fewer extreme outliers, and can thus be considered more robust. For real-time predictions that assume long delays (6–8 weeks) in the availability of epidemiological data, we find that real-time internet search data are the strongest predictors of dengue incidence, whereas for predictions that assume short delays (1–3 weeks), in which the error rate is halved (as measured by relative RMSE), short-term and seasonal autocorrelation are the dominant predictors. Despite the difficulties inherent to city-level prediction, our framework achieves meaningful and actionable estimates across cities with different demographic, geographic and epidemic characteristics.