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Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50–100), 74 months (47–100) in the adjuvant radiotherapy group and 78 months (52–101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86–95) in the adjuvant radiotherapy group and 90% (85–94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48–1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001). Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. French Health Ministry and Ipsen.

Important factors may influence the bioactive compounds in grapes, including scion–rootstock interaction. Therefore, the bioactive compounds and antioxidant activity in grape skin and pulp fractions of ‘Isabel Precoce’, ‘BRS Carmem’, ‘BRS Cora’, ‘BRS Violeta’ and ‘IAC 138–22 Máximo’ were assessed. These cultivars, from genetic improvement programs in Brazil, have good adaptation to subtropical and tropical climate conditions, and can be widely used by winegrowers aiming at adding value to the grape. All grapevines were grafted onto ‘IAC 766’ and ‘IAC 572’ rootstocks under tropical conditions in Brazil. The highest concentration of bioactive compounds was found in skins of ‘BRS Violeta’, followed by ‘IAC 138–22 Máximo’, both grafted onto ‘IAC 766’. There was a strong correlation between phenolic content and antioxidant properties, since antioxidant activity also decreased in the sequence: ‘BRS Violeta’ > ‘IAC 138–22 Máximo’ > ‘BRS Cora’ > ‘BRS Carmem’ > ‘Isabel Precoce’. Skin from hybrid grapes (‘BRS Violeta’, ‘IAC 138–22 Máximo’, ‘BRS Cora’ and ‘BRS Carmem’) grafted in both rootstocks contains higher levels of (poly)phenolic compounds and antioxidant activity than ‘Isabel Precoce’ ( V . labrusca ). Skin from ‘BRS Violeta’ grafted onto ’IAC 766’ stand out from the others due to their high content of bioactive compounds.

Yellow fever is an acute infectious disease caused by prototype virus of the genus Flavivirus. It is endemic in Africa and South America where it represents a serious public health problem causing epidemics of hemorrhagic fever with mortality rates ranging from 20% to 50%. There is no available antiviral therapy and vaccination is the primary method of disease control. Although the attenuated vaccines for yellow fever show safety and efficacy it became necessary to develop a new yellow fever vaccine due to the occurrence of rare serious adverse events, which include visceral and neurotropic diseases. The new inactivated vaccine should be safer and effective as the existing attenuated one. In the present study, the immunogenicity of an inactivated 17DD vaccine in C57BL/6 mice was evaluated. The yellow fever virus was produced by cultivation of Vero cells in bioreactors, inactivated with β-propiolactone, and adsorbed to aluminum hydroxide (alum). Mice were inoculated with inactivated 17DD vaccine containing alum adjuvant and followed by intracerebral challenge with 17DD virus. The results showed that animals receiving 3 doses of the inactivated vaccine (2μg/dose) with alum adjuvant had neutralizing antibody titers above the cut-off of PRNT50 (Plaque Reduction Neutralization Test). In addition, animals immunized with inactivated vaccine showed survival rate of 100% after the challenge as well as animals immunized with commercial attenuated 17DD vaccine.

Benzodiazepine deprescribing in older adults is a complex process influenced by systemic, structural, cultural, and individual factors. This qualitative study examined the challenges faced by primary care professionals during the implementation of a supervised deprescribing protocol in a municipality in Minas Gerais, Brazil. Through thematic content analysis, based on Bardin’s methodology and relevant theoretical frameworks for primary care, interviews with community health workers and nurses were analyzed to identify barriers related to structure, process, and outcomes. The main structural barriers included high physician turnover and lack of trust in healthcare professionals. Process-related problems involved failures in information flow and internal coordination. Challenges related to outcomes and patients included resistance due to prolonged use and fear of withdrawal symptoms, limited understanding of the dose reduction process, missed appointments, and lack of home support. These interconnected factors significantly compromised the effectiveness of the intervention. In summary, this study adds that, within the Brazilian Unified Health System (SUS), stable teams, protected time for medication review, network-based psychiatrists, and home-based logistics are prerequisites for effective deprescribing; without these governance conditions, isolated education and protocols tend to fail. These measures are essential to promote treatment adherence, ensure patient safety, and achieve sustainable results in health services that aim to implement deprescribing.

The global demand for sustainable energy has accelerated the development of biofuels, aiming to reduce fossil fuel reliance and environmental impact. Second-generation ethanol (2G), produced from lignocellulosic biomass such as sugarcane bagasse and straw, is a promising alternative aligned with the circular economy. Its production relies on pretreatments to improve the enzymatic access to polysaccharides. Among the available methods, the organosolv (O) and hydrothermal (H) pretreatments are effective in separating the biomass into cellulose-rich pulps and hemicellulosic liquors. In this study, these pretreatments were applied to sugarcane bagasse (SCB) and straw (SS), aiming to obtain hemicellulosic fractions for bioconversion. The characterization of pretreated biomasses showed increased cellulose content, indicating successful delignification. After the lignin precipitation, the hemicellulosic liquors were submitted to enzymatic hydrolysis, with increases in the total reducing sugar (TRS) concentrations, from 11.144 to 13.440 g·L−1 (SBO), 16.507 to 22.492 g·L−1 (SBH), 8.560 to 9.478 g·L−1 (SSO), and 14.164 to 22.830 g·L−1 (SSH), with highlights for the hydrothermal pretreated hydrolysates in the improvement of sugar release. HPLC confirmed these gains, notably in the xylose content. The results indicated the potential of hemicellulosic liquors for the fermentation of pentoses, supporting integrated bioethanol production. This approach promotes the efficient use of agro-residues and strengthens the role of biofuels in low-carbon and sustainable energy systems.

Gram-positive and -negative bacteria are dangerous pathogens that may cause human infection diseases, especially due to the increasingly high prevalence of antibiotic resistance, which is becoming one of the most alarming clinical problems. In the search for novel antimicrobial compounds, snake venoms represent a rich source for such compounds, which are produced by specialized glands in the snake’s jawbone. Several venom compounds have been used for antimicrobial effects. Among them are phospholipases A₂, which hydrolyze phospholipids and could act on bacterial cell surfaces. Moreover, metalloproteinases and L-amino acid oxidases, which represent important enzyme classes with antimicrobial properties, are investigated in this study. Finally, antimicrobial peptides from multiple classes are also found in snake venoms and will be mentioned. All these molecules have demonstrated an interesting alternative for controlling microorganisms that are resistant to conventional antibiotics, contributing in medicine due to their differential mechanisms of action and versatility. In this review, snake venom antimicrobial compounds will be focused on, including their enormous biotechnological applications for drug development.

Canis lupus familiaris (domestic dog) represents a reliable sentinel for the occurrence of a well-established transmission cycle of Trypanosoma cruzi among wild mammals in the surroundings and, consequently, where the risk of human infection exists. Serological diagnosis is the chosen method to identify T. cruzi infection in dogs that, in Brazil, rarely present positive parasitological tests. The use of recombinant chimeric parasitic antigens results in a sensitive and specific serological diagnostic test in contrast to the use of crude T. cruzi antigens. Our objective was to evaluate the Chagas/Bio-Manguinhos Lateral Flow Immunochromatographic Rapid Test (Chagas-LFRT) for the diagnosis of T. cruzi infection in domestic dogs and the potential of application of this diagnostic platform to wild canid species. Two recombinant proteins (IBMP-8.1 and IBMP-8.4) that displayed the best performance in the enzyme immunoassay (ELISA) in previous studies were tested in a platform with two diagnostic bands. A panel of 281 dog serum samples was evaluated: 133 positive for T. cruzi by serological diagnosis, including 20 samples with positive blood cultures belonging to different discrete typing units (DTUs); 129 negative samples; and 19 samples from dogs infected by other trypanosomatids: Leishmania infantum , Trypanosoma rangeli , Trypanosoma caninum and Crithidia mellificae , in addition to samples infected by Anaplasma platys , Dirofilaria immitis and Erlichia sp. that were employed to evaluate eventual cross-reactions. We also evaluated the Chagas-LFRT to detect T. cruzi infection in 9 serum samples from six wild canid species. We observed that the intensity pattern of the bands was directly proportional to the serological titer observed in IFAT. The sensitivity was 94%, the specificity was 91% according to the ROC curve, and the defined cutoff was an optical density of 4.8. The agreement obtained was considered substantial by the kappa analysis (84%). From T. cruzi positive hemoculture samples, 88.9% were positive by Chagas-LFRT. The test was efficient in recognizing infections by five of the six T. cruzi DTUs. Cross-reactions were not observed in infections by L. infantum , T. rangeli , T. caninum and D. immitis ; however, they were observed in sera of dogs infected by Crithidia mellificae , Anaplasma sp. and Erlichia sp. A strong reaction was observed when serum samples from wild canids were submitted to the Protein A affinity test, confirming its applicability for these species. This test will allow rapid preventive actions in areas with high risk to the emergence of Chagas disease in a safer, reliable, low-cost and immediate manner, without the need for more complex laboratory tests.

In this work we investigated the effect of hydrothermal treatment and silica addition on the structure and photocatalytic performance of synthesized TiO 2 -based nanocomposites. These materials were prepared by combining sol–gel process and hydrothermal treatment, and no templates or surfactants were used in these syntheses. The optimal synthesis conditions were investigated based on the variation of the preparation parameters. Anatase TiO 2 crystals were synthesized without the need of a hydrothermal treatment, but this process appeared necessary to form an anatase phase with better structural quality and high photoactivity. The heat treatment step induced competitive phenomena toward the TiO 2 structural properties and its photodegradation activity, but it proved to be advantageous as long as the pore structure, anatase phase, and high specific surface area were maintained. The addition of silica was then justified, aiming to stabilize the crystalline structure of TiO 2 upon heat treatment. The ideal molar ratio of Si/(Si + Ti) was 0.2 for samples heat-treated at either 500 or 700 °C. The high photocatalytic efficiency of the synthesized nanocomposites is due to the combined effect of the photoactivity of TiO 2 and adsorption capacity of SiO 2 . When compared with a commercial TiO 2 sample (Degussa Evonik P25), increasing the catalyst loading proved to greatly enhance the performance of the synthesized nanocomposite, whereas the commercial one did not follow the same trend. Highlights TiO 2 -SiO 2 nanocomposites synthesized by sol-gel technique and hydrothermal treatment. Optimization of the photocatalytic activity of hydrothermally treated TiO 2 . Catalyst structure stabilization due to hydrothermal treatment and SiO 2 addition. Highest photocatalytic activity for composite with 20% of SiO 2 and treated at 500 °C. Combined effect of the photoactivity of TiO 2 and adsorption capacity of SiO 2 .

To evaluate the clinical outcomes of supplementary prescribing by pharmacist in reducing blood pressure versus other models of care in patients who recently received medical diagnosis of hypertension. A 24-month pragmatic controlled trial was performed with 225 patients divided into three groups: control 1 (medical centered care), control 2 (pharmacist collaborative care without supplementary prescribing authority) and intervention (pharmacist collaborative care with supplementary prescribing authority). A comparison of values was performed at basal and after 24-months of follow up in each group and differences between groups. We applied the chi-square test, student's t-test for independent samples, one-way anova whenever appropriate. A p value < 0.05 was considered statistically significant. Significant reduction in sbp and dbp was verified in every groups; intervention group showed a significantly higher reduction in the mean blood pressure levels versus control 2 (δ vs. Control 2 group = -14.3 [ci95 % -12.6 to -15.9 mmhg] p = 0.006; δ vs. Control 1 group = -17.8 [ci95 % -13.8 to -19.8 mmhg] p < 0.001) and dbp (δ vs. Control 2 group = -8.9 [ci95 % -7.7 to -10.9 mmhg] p = 0.005; δ vs. Control 1 group = -9.8 [ci95 % -7.7 to -11.5 mmhg] p < 0.001). Intervention group also showed significantly higher reduction in ldl-cholesterol and total cholesterol, versus other groups. Pharmacist collaborative care with supplementary prescribing authority provided better results in the management of blood pressure, ldl-cholesterol and total cholesterol versus other models of care.

In Brazil, hydroelectricity represents close to 70% of the energy consumed in the country. However, hydroelectric plant operations may be affected by the deposit of sediments for erosive processes on reservoir margins. This study presents the results of implementing two semi-rigid erosion control techniques installed on reservoir margins of two Brazilian Hydroelectric Power Plants (HPPs). These techniques were the gabion and gabion mattress used as a mixed technique and geogrid mattress technique. This paper highlights the importance of implementing geotextiles in the construction process of these erosion control techniques, taking advantage of their separation properties. The performance of the techniques was evaluated using qualitative performance variables and by differential bathymetry studies performed in 2016 and 2020 in the experimental units installed in each HPP. Moreover, the degradation of the geotextiles in each installation was evaluated through thermal analysis. The erosion control techniques that showed the best results were gabion and gabion mattress. Regarding the exhumed geotextiles, thermal analyses have shown that the commercial geotextiles that were used can withstand temperatures of up to 200 °C leading to no changes to their structure.