Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.

BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Effects of Capsiate Supplementation on Maximal Voluntary Contraction in Healthy Men.

This study aimed to investigate the effects of acute capsaicin analog (Capsiate - CAP) supplementation on maximal voluntary isometric contraction (MVIC) performance in healthy young men. Thirteen subjects (25.2±3.2 yrs) participated in the present study. In two different days separated by one week, the subjects ingested capsiate (12 mg) or placebo (starch: 12 mg) 45 minutes before a MVIC test. The MVIC test consisted of five 10-second knee extension maximal isometric contractions with 45 seconds of recovery between efforts. The peak force, mean force, minimum force, fatigue index, and area under the curve of each contraction were calculated. Main condition effect was found, with higher values of peak force (+4.83%, F=6.867, p=0.02), fatigue index (+8.96%, F=5.228, p=0.041), and area under the curve (+4.19%, F=4.774, p=0.04) for CAP compared to placebo, however, no interaction effect was found for any variable (F=0.090 to 1.356, p≥0.276). In summary, healthy young men produced higher maximal isometric force and delayed fatigue in the CAP condition compared to placebo condition (condition effect) but without significant difference between each effort.

Acute Capsaicin Supplementation Improved Resistance Exercise Performance Performed After a High-Intensity Intermittent Running in Resistance-Trained Men.

ABSTRACT: de Freitas, MC, Cholewa, JM, Panissa, VLG, Toloi, GG, Netto, HC, Zanini de Freitas, C, Freire, RV, Lira, FS, and Rossi, FE. Acute capsaicin supplementation improved resistance exercise performance performed after a high-intensity intermittent running in resistance-trained men. J Strength Cond Res 36(1): 130-134, 2022-We sought to investigate the acute effects of capsaicin supplementation on the rate of perceived exertion (RPE) and heart rate during high-intensity intermittent exercise (HIIE) and resistance exercise performance executed after HIIE in resistance-trained men. Eleven resistance-trained men completed 2 randomized, double-blind trials: capsaicin condition or a placebo condition. The concurrent exercise session was composed of a 5-km intermittent run (1:1 effort and passive recovery ratio) and subsequent resistance exercise (4 × 70% of 1RM until muscle failure in the half-squat exercise). Heart rate was recorded during HIIE and after the protocol RPE (0-10 scale) was accessed. The resistance exercise performance was analyzed by the maximum number of repetitions performed for each set and the total volume (repetitions × weight lifted). During HIIE, the RPE (capsaicin = 7 ± 1 vs. placebo = 8 ± 1 points, t = -3.674, p = 0.005) and mean heart rate (capsaicin = 153 ± 13 vs. placebo = 158 ± 12 bpm, t = -2.292, p = 0.048) were significantly lower in the capsaicin compared with placebo condition. For subsequent resistance exercise, there was a significant decrease in volume across time (F = 19.889, p < 0.001, η2= 0.69) with maximal number of repetitions performed in capsaicin than placebo condition (2,077.6 ± 465.2 kg vs. 1,838.9 ± 624.1 kg, p = 0.028, d = 0.43), but the condition vs. set was not significant (F = 0.582, p = 0.632, η2= 0.06). Acute capsaicin supplementation induced a lower mean heart rate and RPE during HIIE and improved subsequent resistance exercise performance in resistance-trained men.

Evaluation of the drinking water quality surveillance system in the metropolitan region of Rio de Janeiro.

The present work evaluated the surveillance of the drinking water quality information system database and correlated the findings of the microbiological analysis with the distribution of intestinal protozoa from the metropolitan region of Rio de Janeiro. From the database, we obtained 1,654 georeferenced monitoring stations that were used in the analysis. The results indicate that the minimum number of samples collected per parameter (free residual chlorine, turbidity, counts of total and fecal coliforms (Escherichia coli)) was not fulfilled, the collection of samples throughout the year was irregular and the representability of sampling points considered strategic was low (48% of municipalities). Besides, municipalities with a high prevalence for intestinal parasite protozoa were also the ones that had the highest counts for coliforms and the reverse can also be observed, indicating a transmission through contaminated drinking water. Despite the increased participation of municipalities in water surveillance actions during the studied period, it is necessary to implement managerial measures to improve the system, aiming to correct flaws and inconsistencies in the application of the water quality monitoring protocol.

Postactivation Potentiation Improves Acute Resistance Exercise Performance and Muscular Force in Trained Men.

ABSTRACT: Conrado de Freitas, M, Rossi, FE, Colognesi, LA, de Oliveira, JVNS, Zanchi, NE, Lira, FS, Cholewa, JM, and Gobbo, LA. Postactivation potentiation improves acute resistance exercise performance and muscular force in trained men. J Strength Cond Res 35(5): 1357-1363, 2021-The purpose of this study was to investigate the effects of heavy back squat (90% one repetition maximum [1RM]) postactivation potentiation (PAP) on acute resistance exercise performance and force production in recreationally trained men, and to verify the relationship between maximal strength and the PAP response. Ten resistance-trained men randomly completed 4 experimental trials: (a) back squats without PAP (No-PAP), (b) back squats with PAP, (c) maximum voluntary isometric contraction (MVIC) of the quadriceps without PAP, and (d) MVIC with PAP. Back squats were performed with 4 sets at 70% of 1 RM with 2 minutes of rest interval. The number of squats repetitions performed was recorded for each set, and a total number of repetitions were calculated to analyze performance. Maximum voluntary isometric contraction was measured using electronic dynamometer, and the peak force and mean force were recorded. Blood lactate concentration was analyzed presquat and postsquat exercise. Repetitions performed in the first set was significantly (p < 0.001) greater in the PAP condition (22.00 ± 5.14) compared with No-PAP (15.50 ± 5.10), which resulted in significantly (p = 0.001) more total repetitions performed in the PAP (56.20 ± 17.3) condition compared with No-PAP (48.80 ± 14.5). Maximum voluntary isometric contraction peak was higher in PAP than in No-PAP (PAP = 765.7 ± 147.8 vs. No-PAP = 696.8 ± 131.5 N, p = 0.006). No significant correlations were observed between back squat 1RM relative to body mass and the PAP response in squat and MVIC. There were no significant differences in lactate concentration between conditions. In conclusion, PAP resulting from a heavy load prior back squat exercise improved total volume during resistance exercise. In addition, PAP was effective to increase force production during MVIC, but there was no relationship between relative 1RM values and the PAP response in trained men.

Appetite Is Suppressed After Full-Body Resistance Exercise Compared With Split-Body Resistance Exercise: The Potential Influence of Lactate and Autonomic Modulation.

ABSTRACT: Conrado de Freitas, M, Ricci-Vitor, AL, de Oliveira, JVNS, Quizzini, GH, Vanderlei, LCM, Silva, BSA, Zanchi, NE, Cholewa, JM, Lira, FS, and Rossi, FE. Appetite is suppressed after full-body resistance exercise compared with split-body resistance exercise: the potential influence of lactate and autonomic modulation. J Strength Cond Res 35(9): 2532-2540, 2021-The purposes of this study were to investigate the effects of full- vs. split-body resistance training on appetite and leptin response and to verify the potential involvement of lactate and autonomic modulation during this response in trained men. Twelve recreationally resistance-trained men (age = 26.1 ± 5.5 years) performed 3 randomized trials in 3 conditions: upper body (UB), lower body (LB), and full body (FB). The subjective rating of hunger was obtained through a visual analog scale. Leptin and lactate concentration were evaluated at rest, immediately after exercise, and during recovery. Heart rate variability in the time and frequency domains was recorded at baseline and during recovery (until 60 minutes after exercise) to assess autonomic modulation. The FB condition induced lower subjective hunger ratings than the UB at Post-1 hour (p < 0.05) and a significant difference in the area under the curve between conditions (p = 0.028) with lower hunger sensation for FB in relation to UB (p = 0.041). The FB presented greater lactate concentration and induced slower heart rate variability recovery in relation to UB and LB conditions (p < 0.05), and heart rate variability remained lower until 60 minutes after exercise compared with rest only in the FB condition. There was a significant negative correlation between subjective hunger ratings and lactate concentration only for the FB condition (r = -0.72, p = 0.028). Full-body resistance exercise induced lower subjective hunger ratings after exercise in relation to UB resistance exercise. The FB also induced higher lactate production and slower recovery of autonomic modulation compared with the UB and LB conditions. Future research is necessary to investigate a mechanistic relationship between lactate concentrations and hunger suppression after resistance exercise.

Comparison Between Full-Body vs. Split-Body Resistance Exercise on the Brain-Derived Neurotrophic Factor and Immunometabolic Response.

Lira, FS, Conrado de Freitas, M, Gerosa-Neto, J, Cholewa, JM, and Rossi, FE. Comparison between full-body vs. split-body resistance exercise on the brain-derived neurotrophic factor immunometabolic response. J Strength Cond Res 34(11): 3094-3102, 2020-Intense aerobic exercise seems to increase serum concentrations of brain-derived neurotrophic factor (BDNF) in conjunction with increasing lactate; however, less is known about the BDNF response to differing resistance exercise protocols. We hypothesized that full-body (FB) resistance exercise will elicit a greater increase in serum BDNF and lactate compared with split-body resistance exercise. Twelve recreationally resistance-trained men (age = 25.3 ± 5.9 years) performed 3 randomized trials of 18 sets of exercise: upper-body (UB), lower-body (LB), and FB conditions. Serum BDNF levels were assessed at rest, immediately Post-exercise, Post-1 hour, and Post-2 hours during recovery. Lactate concentration was evaluated at rest, after 9 sets, Post-exercise, Post-5, Post-10, and Post-30 minutes during recovery. In addition, interleukin (IL-6 and IL-10) and the IL-6/IL-10 ratio were calculated. Lactate concentration and total volume were greater in the FB condition compared with LB and UB (p < 0.05). For BDNF, effect sizes were largest in the LB (1.4), followed by the FB (0.75), and moderate to UB (0.33), although no significant differences were observed between conditions. There was a statistically significant relationship between lactate and BDNF only for LB condition (rho = 0.72; p = 0.013). There were a greater IL-10 Post-1 hour for FB condition compared with UB and LB (p < 0.001), and lower IL-6/IL-10 ratio in FB compared with UB (p < 0.001). Lower body induced a great BDNF response, and FB resistance exercise elicited a greater increase of serum cytokines than UB in trained men. We speculate that the volume of work performed by larger muscles has a larger influence on BDNF than overall volume.

Capsaicin supplementation increases time to exhaustion in high-intensity intermittent exercise without modifying metabolic responses in physically active men.

PURPOSE: The purpose of this study was to investigate the acute effect of capsaicin supplementation on performance and physiological responses during high-intensity intermittent exercise (HIIE). METHOD: Thirteen physically active men (age = 24.4 ± 4.0 years; height = 176.4 ± 6.9 cm; body mass = 78.7 ± 13.8 kg; running training per week = 3.9 ± 0.9 h) performed an incremental running test to determine peak oxygen uptake ([Formula: see text]) and the speed associated with [Formula: see text] (s[Formula: see text]). Thereafter, subjects completed two randomized, double-blind HIIE (15s:15 s at 120% s[Formula: see text]) trials 45-min after consuming capsaicin (12 mg) or an isocaloric placebo. Time to exhaustion, blood lactate concentration, oxygen consumption during and 20 min post-exercise, energy expenditure, time spent above 90% of [Formula: see text], and the rate of perceived exertion were evaluated. RESULTS: There was no difference between capsaicin and placebo for any variable except time to exhaustion [capsaicin: 1530 ± 515 s (102 efforts) vs placebo: 1342 ± 446 s (89 efforts); p < 0.001]. CONCLUSION: In conclusion, capsaicin supplementation increased time to exhaustion in high-intensity intermittent exercise without modifying the metabolic response of exercise or the rate of perceived exertion in physically active men. Capsaicin could be used to increase the training load during specific exercise training sessions.

A Single Dose of Oral ATP Supplementation Improves Performance and Physiological Response During Lower Body Resistance Exercise in Recreational Resistance-Trained Males.

Freitas, MC, Cholewa, JM, Gerosa-Neto, J, Gonçalves, DC, Caperuto, EC, Lira, FS, and Rossi, FE. A single dose of oral ATP supplementation improves performance and physiological response during lower body resistance exercise in recreational resistance-trained males. J Strength Cond Res 33(12): 3345-3352, 2019-The aim of this study was to investigate the acute effect of adenosine-5'-triphosphate (ATP) supplementation on performance and physiological responses during resistance exercise in recreationally resistance-trained males. Eleven men (age = 27.5 ± 5.5 years, mass = 83.4 ± 9.8 kg, height = 182 ± 0.04 cm) completed 2 randomized, double-blind trials: ATP supplement condition (ATP = 400 mg) or a placebo condition. Thirty minutes after supplement consumption, subjects performed 4 sets of half-squats until momentary muscular failure at 80% of the 1 repetition maximum with 2 minutes of recovery between sets. The total number of repetitions, blood pressure, heart rate, blood lactate, and oxygen consumption were evaluated. The total weight lifted were higher for the ATP condition compared with placebo (Placebo = 3,995.7 ± 1,137.8, ATP = 4,967.4 ± 1,497.9 kg; p = 0.005). Heart rate was higher at set-4 for ATP compared with placebo (p < 0.001) and oxygen consumption during exercise was greater for ATP (p = 0.021). There were no differences between conditions for lactate and blood pressure. In summary, a single oral dose of ATP supplementation improved lower-body resistance training performance and energy expenditure in recreational resistance-trained males.

Intermittent resistance exercise and obesity, considered separately or combined, impair spermatic parameters in adult male Wistar rats.

Obesity and absence of physical exercise are global problems that affect concentration and sperm quality in the male reproductive system. The purpose of this study was to examine the effect of obesity and resistance training, considered separately or in association, on testicular function and reproductive capacity. Twenty pubertal male Wistar rats were distributed into four groups: control (C) and exercise (E) groups that received standard rat chow; and obese (O) and obese with exercise (OE) groups that received a high-fat diet. All the groups received filtered water during the experimental conditions. Groups E and OE were submitted to 8 weeks of high-intensity intermittent training. Afterwards, testes were collected for sperm count, spermatogenic kinetics, histopathology, morphometry and immunodetection of androgen receptors (AR). The vas deferens was collected for sperm morphology. The results showed that obesity increased body weight, naso-anal length, liver and epididymal fat weight, abnormal spermatozoa and immunodetectable AR. Intermittent exercise decreased daily sperm production (DSP), sperm count and normal spermatozoa, whereas the number of tubules with immunodetectable AR increased. The combination of obesity and intermittent training led to reduced sperm count and DSP, although abnormal spermatozoa and the number of tubules with immunodetectable AR increased. Thus, in conclusion, both obesity and resistance training impaired testicular function during puberty in rats; and this type of exercise has also been shown to be detrimental to testicular physiology.

Acute Capsaicin Supplementation Improves 1,500-m Running Time-Trial Performance and Rate of Perceived Exertion in Physically Active Adults.

de Freitas, MC, Cholewa, JM, Gobbo, LA, de Oliveira, JVNS, Lira, FS, and Rossi, FE. Acute capsaicin supplementation improves 1,500-m running time-trial performance and rate of perceived exertion in physically active adults. J Strength Cond Res 32(2): 572-577, 2018-The purpose of this study was to investigate the acute effect of capsaicin supplementation on performance, rate of perceived exertion (RPE), and blood lactate concentrations during short-duration running in physically active adults. Ten physically active men (age = 23.5 ± 1.9 years, mass = 78.3 ± 12.4 kg, and height = 177.9 ± 5.9 cm) completed 2 randomized, double-blind trials: Capsaicin condition (12 mg) or a placebo condition. Forty-five minutes after supplement consumption, the participants performed a 1,500-m running time trial. Time (in seconds) was recorded. Blood lactate concentration was analyzed at rest, immediately after exercise, after 5, 10, and 30 minutes during recovery and the RPE was collected after exercise. The time was significantly (t = 3.316, p = 0.009) lower in the capsaicin (371.6 ± 40.8 seconds) compared with placebo (376.7 ± 39 seconds). Rate of perceived exertion was significantly (t = 2.753, p = 0.022) less in the capsaicin (18.0 ± 1.9) compared with the placebo (18.8 ± 1.3). Lactate increased across time for both conditions without significant differences between (p > 0.05). In summary, acute capsaicin supplementation improves middle distance running (1,500 m) performance and reduced RPE in physically active adults.

Acute Capsaicin Supplementation Improves Resistance Training Performance in Trained Men.

Conrado de Freitas, M, Cholewa, JM, Freire, RV, Carmo, BA, Bottan, J, Bratfich, M, Della Bandeira, MP, Gonçalves, DC, Caperuto, EC, Lira, FS, and Rossi, FE. Acute capsaicin supplementation improves resistance training performance in trained men. J Strength Cond Res 32(8): 2227-2232, 2018-The purpose of this study was to investigate the acute effect of capsaicin supplementation on performance, rate of perceived exertion (RPE), and blood lactate concentrations during resistance exercise in healthy trained young men. Ten resistance-trained men (age = 22.7 ± 4.0 years, mass = 82.3 ± 9.6 kg, and height = 175 ± 0.1 cm) completed 2 randomized, double-blind trials: capsaicin condition (12 mg) or a placebo condition. Forty-five minutes after supplement consumption, subjects performed 4 sets until movement failure in the squat exercise at 70% of 1 repetition maximum with 90 seconds of rest interval between sets. The total mass lifted (total repetitions × mass lifted) was calculated. The RPE was recorded after the last set. Blood lactate was analyzed after each set of exercise, immediately postexercise, and after 3, 5, and at 30 minutes during recovery. The number of repetitions in each set decreased significantly after all sets compared with set-1 and after set-3 and set-4 in relation to set-2 (p < 0.001); however, total mass lifted was higher in capsaicin compared with placebo (3,919.4 ± 1,227.4 kg vs. 3,179.6 ± 942.4 kg, p = 0.002). Blood lactate increased significantly after each set (p < 0.001); however, there were no differences between conditions. Rate of perceived exertion was significantly less for the capsaicin condition than placebo (17.2 ± 1.0 vs. 18.3 ± 1.7, p = 0.048). In summary, acute capsaicin supplementation improves lower-body resistance training performance in trained young men.

Patient-Reported Barriers to Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. METHODS AND FINDINGS: We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children. CONCLUSIONS: Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence.

Antiretroviral therapy status among people who died of AIDS-related causes from 2009 to 2013 in Brazil: a population-based study.

OBJECTIVE: To describe the antiretroviral therapy status of people living with HIV (PLHIV) who died of AIDS-related causes between 2009 and 2013. METHODS: We conducted a cross-sectional, population-based study. Data were obtained by linking the mortality information system and the national ART dispensing database. Trends were modelled using linear regression analysis. RESULTS: A total of 61 425 AIDS-related deaths were registered in Brazil between 2009 and 2013. Median age at death was 41 years (IQR: 33-49), and 65.7% (40 337) of deaths were among men; 47.2% (29 004) of PLHIV who died during the study period had never started treatment, 7.0% (4274) had discontinued it, 15.9% (9775) were on ART for 6 months or less and 29.9% (18 372) were on ART for more than 6 months. Only 1.3% of PLHIV were on third-line ARV regimens when they died. CONCLUSIONS: AIDS-related mortality remains a challenge even in a context of sustained universal access to antiretroviral treatment due to failure of service provision, not to therapy failure. Robust health policies closing gaps in the HIV continuum of care are crucial to further reduce mortality.

Genetic diversity analysis of two commercial breeds of pigs using genomic and pedigree data.

BACKGROUND: Genetic improvement in livestock populations can be achieved without significantly affecting genetic diversity if mating systems and selection decisions take genetic relationships among individuals into consideration. The objective of this study was to examine the genetic diversity of two commercial breeds of pigs. Genotypes from 1168 Landrace (LA) and 1094 Large White (LW) animals from a commercial breeding program in Brazil were obtained using the Illumina PorcineSNP60 Beadchip. Inbreeding estimates based on pedigree (F x) and genomic information using runs of homozygosity (F ROH) and the single nucleotide polymorphisms (SNP) by SNP inbreeding coefficient (F SNP) were obtained. Linkage disequilibrium (LD), correlation of linkage phase (r) and effective population size (N e ) were also estimated. RESULTS: Estimates of inbreeding obtained with pedigree information were lower than those obtained with genomic data in both breeds. We observed that the extent of LD was slightly larger at shorter distances between SNPs in the LW population than in the LA population, which indicates that the LW population was derived from a smaller N e . Estimates of N e based on genomic data were equal to 53 and 40 for the current populations of LA and LW, respectively. The correlation of linkage phase between the two breeds was equal to 0.77 at distances up to 50 kb, which suggests that genome-wide association and selection should be performed within breed. Although selection intensities have been stronger in the LA breed than in the LW breed, levels of genomic and pedigree inbreeding were lower for the LA than for the LW breed. CONCLUSIONS: The use of genomic data to evaluate population diversity in livestock animals can provide new and more precise insights about the effects of intense selection for production traits. Resulting information and knowledge can be used to effectively increase response to selection by appropriately managing the rate of inbreeding, minimizing negative effects of inbreeding depression and therefore maintaining desirable levels of genetic diversity.

An Approach to Establishing Diagnostic Reference Levels in Interventional Pediatric Cardiology from Different Regions of Brazil.

Diagnostic reference levels (DRLs) are a pivotal strategy to be implemented since pediatric interventional cardiology procedures are increasing. This work aimed to propose an initial set of Brazilian DRLs for pediatric interventional diagnostic and therapeutic (D&T) procedures. A retrospective study was carried out in four Brazilian states, distributed across the three regions of the country. Data were collected from pediatric patients undergoing cardiac interventional procedures (CIPs), including their age and anthropometric characteristics, and at least four parameters (number of images, exposure time, air kerma-area product-PKA, and cumulative air kerma). Data from 279 patients undergoing CIPs were gathered (147 diagnostic and 132 therapeutic procedures). There were no significant differences in exposure time and the number of images between the D&T procedures. A wide range of PKA was observed when the therapeutic procedures were compared to diagnostics for all age groups. There were significant differences between the D&T procedures, whether grouping data by patient weight or age. In terms of cumulative air kerma, it was noted that no value exceeded the level to trigger a monitoring process for patients. This study shows that it is possible to adopt them as the first proposal to establish national DRLs considering pediatric patient groups.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Towards an improved investment approach for an effective response to HIV/AIDS.

Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US$22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at $1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.

Exploring chemical diversity in Glycine max cultivars: A multivariate approach in the search for bioactive compounds against Spodoptera cosmioides.

Soybean crop is regulated by abiotic and biotic stresses with great potential in reducing grain yield and quality. The selection of resistant cultivars is a promising approach for mitigating these damages. We evaluated the chemical profile of Glycine max leaves from different cultivars in order to explore their defense mechanisms against Spodoptera cosmioides caterpillars. We optimized solid-liquid extraction techniques using ultrasound bath and static headspace extraction. Additionally, we developed an approach based on liquid and gas chromatography for analyzing the chemical profile of G. max cultivars. The principal component analysis allowed the classification of transgenic cultivars, which are classified as susceptible to S. cosmioides, from those obtained by genetic improvement and resistant to the insect. Differences were observed in the abundance of phenolic glycosides, lipids, aldehydes, and alcohols. More specifically, S. cosmioides resistant cultivars presented molecules related to the jasmonic and salicylic acid pathways. Such data can contribute to a molecular understanding of phenotypic diversity in soybean cultivars, from plant quality to resistance mechanisms and adaptation, to environmental stress and herbivory.