Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).

The relevancy of massive health education in the Brazilian prison system: The course "health care for people deprived of freedom" and its impacts.

Introduction: Brazil has one of the largest prison populations globally, with over 682,000 imprisoned people. Prison health is a public health emergency as it presents increasingly aggravating disease rates, mainly sexually transmitted infections (STI). And this problem already affects both developed and developing nations. Therefore, when thinking about intervention strategies to improve this scenario in Brazil, the course "Health Care for People Deprived of Freedom" (ASPPL), aimed at prison health, was developed. This course was implemented in the Virtual Learning Environment of the Brazilian Health System (AVASUS). Given this context, this study analyzed the aspects associated with massive training through technological mediation and its impacts on prison health. Methods: This cross-sectional study analyzed data from 8,118 ASPPL course participants. The data analyzed were collected from six sources, namely: (i) AVASUS, (ii) National Registry of Health Care Facilities (CNES), (iii) Brazilian Occupational Classification (CBO), (iv) National Prison Department (DEPEN); (v) Brazilian Institute of Geography and Statistics (IBGE); and the (iv) Brazilian Ministry of Health (MoH), through the Outpatient Information System of the Brazilian National Health System (SIA/SUS). A data processing pipeline was conducted using Python 3.8.9. Results: The ASPPL course had 8,118 participants distributed across the five Brazilian regions. The analysis of course evaluation by participants who completed it shows that 5,190 (63.93%) reported a significant level of satisfaction (arithmetic mean = 4.9, median = 5, and standard deviation = 0.35). The analysis revealed that 3,272 participants (40.31%) are health workers operating in distinct levels of care. The prison system epidemiological data shows an increase in syphilis diagnosis in correctional facilities. Conclusions: The course enabled the development of a massive training model for various health professionals at all care levels and regions of Brazil. This is particularly important in a country with a continental size and a large health workforce like Brazil. As a result, social and prison health impacts were observed.

The impact of sporotrichosis in HIV-infected patients: a systematic review.

Sporotrichosis is a fungal infection of man and animals caused by Sporothrix complex. It usually presents as a lymphocutaneous form, but disseminated disease may occur. Given the paucity of data about HIV/AIDS and sporotrichosis co-infection, a systematic review of reported cases of HIV-associated sporotrichosis found via Pubmed (1984-2013) was done. A total of 39 papers were included, and 58 patients' data analyzed. Thirty-three (56.9 %) cases were from Brazil and 18 (31 %) from the USA. Patients' mean age was 37.8 ± 10.4 years; males predominated (84.5 %). The median CD4(+) cell count was 97 cells/mm(3). The most common clinical forms were disseminated and disseminated cutaneous with 33 (56.9 %) and 10 (17.5 %) patients, respectively. There was a correlation between CD4(+) count and clinical categories (p = 0.002). Mortality was 30 % and there was a correlation between central nervous system involvement and death (p < 0.001).

Characterization of adipose-derived stem cells of anatomical region from mice.

BACKGROUND: Stem cells constitute a group of great capacity for self-renewal, long-term viability, and multi-lineage potential. Several studies have provided evidence that adipose tissue represents an alternative source of stem cells, with the main benefit of adipose-derived stem cells being that they can be easily harvested from patients by a simple minimally invasive method and can be easily cultured. The aim of this study was to establish a culture protocol for obtaining and characterizing adipose-derived stem cells (ADSCs) from C57BL/6 J mice. RESULTS: The results showed that the yield, viability, and cell morphology obtained differ according to the age of isolated anatomic regions of the adipose tissue from ovarian and epididymis. The results of determination of cyclin D1 showed uniformity in the expression between different populations of ADSCs. A significant increase in the expression of caspase-3 active, was also observed in large cell populations from mice after 120 days. ADSCs were positive for mesenchymal markers CD90 and CD105, Nanog, SSEA-1, CD106, and VEGFR-1, and negative for hematopoietic markers CD34 and CD45. A large number of cells in S + G2/M phases was also observed for both sexes, demonstrating high proliferative capacity of ADSCs. CONCLUSIONS: We observed that the adipose tissue of C57BL/6 J mice, isolated from the studied anatomic regions, is a promising source for obtaining pluripotent mesenchymal stem cells with high viability and proliferative response.

Absorción de nutrientes en corderos alimentados con dietas con diferentes cantidades de fósforo / Nutrient absorption in lambs fed diets containing different amounts of phosphorus

Objective. Evaluate the effect of increasing P intake on nutrient digestibility, and compare the true and apparent absorption coefficients of P and Ca in lambs. Materials and methods. Twenty-four Santa Ines sheep, with an average weight of 33.6 ± 1.6 kg, were distributed into four treatments (0, 2, 4 and 6 g/day of supplementary P) with forage: concentrate ratio of 70:30. The study of apparent nutrient digestibility was conducted during the first week, using the total feces collection method. During the second week, after injection of 7.4 MBq of 32P and 7.7 MBq of 45Ca, apparent (AAC) and true (TAC) absorption coefficients of P and Ca were determined. The lambs were kept in metabolic cages. Results. The increase in P intake did not affect (p>0.05) dry matter, crude protein, NDF or ADF digestibility, but the TAC of P and Ca and mineral matter digestibility decreased. The AAC was not affected (p=0.10). A cubic relationship was observed between P intake and TAC (TAC=2.16–1.95X+0.55X2-0.04X3; R2=0.38) and linear relationship with the TAC of Ca (TAC=0.559–0.03X; R2=0.26). TAC and AAC values were different (p<0.001). Conclusions. The increase in P intake doesn’t impact organic matter digestibility, but does affect P and Ca absorption. Apparent digestibility is not a reliable parameter to determine the efficiency of P and Ca absorption.

Objetivo. Evaluar el efecto del incremento en la ingestión de P sobre la digestibilidad de los nutrientes, y comparar los coeficientes de digestibilidad real y aparente de Ca y P en ovinos. Materiales y métodos. Veinticuatro ovinos de la raza Santa Inés, con 33.6±1.6 kg de peso, fueron asignados a cuatro tratamientos (0, 2, 4 y 6 g/día de P suplementario) con relación forraje:concentrado de 70:30. El estudio de digestibilidad aparente de los nutrientes se realizó la primera semana usando el método de colecta total de heces. La segunda semana, luego de inyectar 7.4 MBq de 32P y 7.7 MBq de 45Ca, se realizó el estudio de absorción real (CAV) y aparente (AAC), en jaulas de estudio de metabolismo. Resultados. El incremento en la ingestión de P no afectó (p>0.05) la digestibilidad aparente de la materia seca, proteína bruta, FDN o FDA. El CAV de Ca y de P y la digestibilidad de la materia mineral presentaron una reducción. EL AAC no fue afectado (p=0.10). La ecuación CAV=2.16–1.95X+0.55X2-0.04X3 (R2 = 0.38) explicó la relación entre el CAV de P y el incremento en su ingestión, y la ecuación TAC=0.559 – 0.03X (R2=0.26), la relación entre el CAV de Ca y la ingestión de P. Los valores de AAC y CAV difirieron entre sí (p<0.001). Conclusiones. La ingestión de P no afectó la digestibilidad de la fracción orgánica del alimento, pero sí la absorción de P y Ca. El coeficiente de absorción aparente no fue un parámetro confiable para determinar la eficiencia de absorción de P y Ca.

Differences in Cucurbit[7]uril: Surfactant Complexation Promoted by the Cationic Head Group.

The formation of host/guest complexes between cucurbit[7]uril (CB7) and tetradecyltrialkylammonium bromide surfactants with trimethyl (C14 TMA+ ), triethyl (C14 TEA+ ), and tripropyl (C14 TPA+ ) head groups was studied. Complexation was studied by ESI-MS, isothermal titration calorimetry (ITC), and NMR spectroscopy. The structure of the complexes is strongly dependent on the surfactant head group. Both 1:1 and 2:1 complexes are formed with all cationic surfactants. The magnitude of the K1:1 binding constants decreases with the alkyl length of the head group, whereas that of the K2:1 binding constants is independent of the nature of the surfactant head group. Distinct structures were found for the 1:1 and 2:1 complexes. C14 TMA+ and C14 TPA+ surfactants form 1:1 inclusion complexes that comprise the head group close to the CB7 portal and 2:1 external complexes with both host molecules near the head group. The 1:1 complexes between C14 TEA+ and CB7 showed that the head group was centered inside the CB7 cavity, whereas in the 2:1 complex the second molecule of CB7 was located at the end of the main alkyl chain.

Cucurbit[7]uril: surfactant host-guest complexes in equilibrium with micellar aggregates.

In order to compare the formation of host-guest complexes between ß-cyclodextrin (ß-CD) or cucurbit[7]uril (CB7) and cationic surfactants we studied the hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC). The selected surfactants allowed the length of the hydrocarbon chain to be varied between 6 and 18 carbon atoms. Contrary to the expected behaviour, the values of the binding constants between CB7 and surfactants are independent of the alkyl chain length of the surfactant. In the case of ß-CD, however, a clear dependence of the binding constant on the hydrophobic character of the surfactant was observed. The values obtained with CB7 are significantly higher than those obtained with ß-CD and these differences are explained to be a consequence of electrostatic interactions of the surfactants with the portals of CB7. It was found that a small percentage of uncomplexed CB7 was in equilibrium with the cationic micelles and this percentage increased on increasing the hydrophobic character of the surfactant.

Importance of phenols structure on their activity as antinitrosating agents: A kinetic study.

OBJECTIVE: Nitrosative deamination of DNA bases induced by reaction with reactive nitrogen species (RNS) has been pointed out as a probable cause of mutagenesis. (Poly)phenols, present in many food items from the Mediterranean diet, are believed to possess antinitrosating properties due to their RNS scavenging ability, which seems to be related to their structure. It has been suggested that phenolic compounds will react with the above-mentioned species more rapidly than most amino compounds, thus preventing direct nitrosation of the DNA bases and their transnitrosation from endogenous N-nitroso compounds, or most likely from the transient N-nitrosocompounds formed in vivo. MATERIALS AND METHODS: In order to prove that assumption, a kinetic study of the nitroso group transfer from a N-methyl-N-nitrosobenzenesulfonamide (N-methyl-N-nitroso-4-methylbenzenesulfonamide, MeNMBS) to the DNA bases bearing an amine group and to a series of phenols was carried out. In the transnitrosation of phenols, the formation of nitrosophenol was monitored by Ultraviolet (UV) / Visible spectroscopy, and in the reactions of the DNA bases, the consumption of MeNMBS was followed by high performance liquid chromatography (HPLC). RESULTS: The results obtained point to the transnitrosation of DNA bases being negligible, as well as that of phenols bearing electron-withdrawing groups. Phenols with methoxy substituents in positions 2, 4, and / or 6, although they seemed to react, did not afford the expected product. Phenols with electron-releasing substituents, unless these blocked the oxygen atom, reacted with our model compound at an appreciable rate. O-nitrosation of the phenolate ion followed by rearrangement of the C-nitrosophenol seemed to be involved. CONCLUSION: This study provided evidence that the above compounds might actually act as antinitrosating agents in vivo.

Equilibrium constants and protonation site for N-methylbenzenesulfonamides.

The protonation equilibria of four substituted N-methylbenzenesulfonamides, X-MBS: X = 4-MeO (3a), 4-Me (3b), 4-Cl (3c) and 4-NO(2) (3d), in aqueous sulfuric acid were studied at 25 °C by UV-vis spectroscopy. As expected, the values for the acidity constants are highly dependent on the electron-donor character of the substituent (the pK(BH+) values are -3.5 ± 0.2, -4.2 ± 0.2, -5.2 ± 0.3 and -6.0 ± 0.3 for 3a, 3b, 3c and 3d, respectively). The solvation parameter m* is always higher than 0.5 and points to a decrease in the importance of solvation on the cation stabilization as the electron-donor character of the substituent increases. Hammett plots of the equilibrium constants showed a better correlation with the σ(+) substituent parameter than with σ, which indicates that the initial protonation site is the oxygen atom of the sulfonyl group.