Prospects for Controlling Hepatitis B Globally.

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

Pre-exposure prophylaxis of non-HIV viral infections and the role of long-acting antivirals.

Viruses cause a large burden of human infectious diseases. During the past 50 years, antivirals have been developed to treat many pathogenic viruses, including herpesviruses, retroviruses, hepatitis viruses, and influenza. Besides being used as treatment, antivirals have shown efficacy for preventing certain viral infections. Following the success in the HIV field, a renewed interest has emerged on the use of antivirals as prophylaxis for other viruses. The development of formulations with extended half-life has pushed further this consideration in persons at risk for a wide range of viral infections. In this way, long-acting antivirals might behave as "chemovaccines" when classical vaccines do not exist, cannot be recommended, immune responses are suboptimal, escape mutants emerge, and/or immunity wanes. Five main caveats would temper its use, namely, selection of drug resistance, drug interactions, short- and long-term side effects, potential teratogenicity in women of child-bearing age, and high cost. Herein, we discuss the prospects for long-acting antivirals as prophylaxis of human viral infections other than HIV.

Safety considerations in the management of hepatitis C and HIV co-infection.

INTRODUCTION: Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise. AREAS COVERED: Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023. EXPERT OPINION: The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.

Morphological and histochemical characterisation of the mucosa of the digestive tract in matrinxã Brycon amazonicus (Teleostei: Characiformes).

This study describes anatomical, histological and histochemical features of the digestive tract mucosal layer of the matrinxã Brycon amazonicus, an omnivorous freshwater fish endemic from the Amazon basin. This species presents short thick oesophagus with longitudinal folds, that allow the passage of large food items. The mucosa is lined with a stratified secretory epithelium rich in goblet cells that secrete neutral and acid mucins. The two mucin types provide different viscosity in anterior and posterior oesophagus related to the protective and lubricant functions, respectively. The stomach is a highly distensible Y-shaped saccular organ. Here, it is proposed that this anatomical shape plays an essential role in food storage when food availability is abundant. The stomach mucosa is composed of epithelial cells with intense neutral mucin secretion to protects against gastric juice. The intestine is slightly coiled and presents internally a complex pattern of transversal folds that increases the absorption surface and the retention time of food. Goblet cells in the intestine secrete acid and neutral mucins that lubricate the epithelium and aid in the digestive processes. In the rectum, an increase in goblet cells population occurs that may be related to better lubrication.

Sex, diurnal variation and retention interval differently affect performance of marmoset monkeys in a recognition memory task for object location.

In the spontaneous object-location (SOL) task, the ability to recognize where stimuli were located in a past encounter is assessed. Even if widely used in rodents, several aspects can affect task performance. It is thus important to assess potentially intervening variables in the new monkey SOL task. Here we assessed whether sex (male vs. females), circadian time (morning vs. afternoon) and retention interval (24 vs. 48 h) affect the performance of adult marmosets in this task. Two identical stimuli were initially explored on a 10-min sample trial. Thereafter, preferential exploration of the displaced vs. the stationary object was analyzed on a 10-min test trial. Both sexes similarly explored the displaced object quicker and longer than the stationary item after a 24 h inter-trial interval. This response pattern was also seen when males were similarly assessed in the morning or afternoon. However, males tested after 48 h explored both objects equally and after a similar latency, yet spent more time where the displaced item had been previously located. Task performance was not related to object exploration during encoding and general activity remained constant. Therefore, sex and diurnal variation in circadian time had no effect on this version of the task, whereas place memory naturally decayed after 24 h. Our results underscore the importance of alternative task parameters to evaluate memory decay. Given the widespread use of spontaneous recognition tasks, a more ecologically-inclined task in monkeys will help translate animal data to clinical research.

Yellow fever outbreak in a rural-urban mixed community of Espírito Santo, Brazil: epidemiological aspects.

OBJECTIVE: To describe the epidemiological aspects of an outbreak of yellow fever (YF) that occurred in the state of Espírito Santo, Brazil, from 1 January 2017 - 31 July 2017. METHODS: A descriptive, quantitative, retrospective approach analyzed secondary data obtained from the national notification systems, Information System of Diseases Notifications (SINAN), Laboratory Environment Manager (GAL), and the Espírito Santo Health Secretariat (SESA). RESULTS: From 1 January 2017 - 8 July 2017, a total of 824 cases were reported in Espírito Santo, 307 (37%) of which were confirmed as YF. Of these, 95 (30.9%) died from the disease. Men were those most affected, corresponding to 244 (79.5%) cases, and women to 63 (20.5%) cases. The greatest incidence rate registered was in the city of Santa Leopoldina (380.2 cases/100 000 inhabitants). The outbreak evolved rapidly and a response was possible due to a multidisciplinary group created specifically to tackle the YF outbreak. CONCLUSIONS: The data were received and analyzed quickly and the response, consisting of immediate treatment of the cases and a blocking vaccination strategy, was developed to halt the progression of this fatal disease. In spite of these efforts, the case fatality rate of yellow fever remained high.

Yellow fever outbreak in a rural-urban mixed community of Espírito Santo, Brazil: epidemiological aspects

[ABSTRACT]. Objective. To describe the epidemiological aspects of an outbreak of yellow fever (YF) that occurred in the state of Espírito Santo, Brazil, from 1 January 2017 – 31 July 2017. Methods. A descriptive, quantitative, retrospective approach analyzed secondary data obtained from the national notification systems, Information System of Diseases Notifications (SINAN), Laboratory Environment Manager (GAL), and the Espírito Santo Health Secretariat (SESA). Results. From 1 January 2017 – 8 July 2017, a total of 824 cases were reported in Espírito Santo, 307 (37%) of which were confirmed as YF. Of these, 95 (30.9%) died from the disease. Men were those most affected, corresponding to 244 (79.5%) cases, and women to 63 (20.5%) cases. The greatest incidence rate registered was in the city of Santa Leopoldina (380.2 cases/100 000 inhabitants). The outbreak evolved rapidly and a response was possible due to a multidisciplinary group created specifically to tackle the YF outbreak. Conclusions. The data were received and analyzed quickly and the response, consisting of immediate treatment of the cases and a blocking vaccination strategy, was developed to halt the progression of this fatal disease. In spite of these efforts, the case fatality rate of yellow fever remained high.

[RESUMEN]. Objetivo. Describir los aspectos epidemiológicos de un brote de fiebre amarilla ocurrido en el estado de Espírito Santo (Brasil), del 1 de enero al 31 de julio del 2017. Métodos. Por medio de un enfoque descriptivo, cuantitativo y retrospectivo se analizaron los datos secundarios obtenidos a partir de los sistemas de notificación nacionales, el sistema informático de notificación de enfermedades (SINAN), el sistema de gestión del entorno de laboratorio (GAL) y la Secretaría de Salud de Espírito Santo (SESA). Resultados. Del 1 de enero al 8 de julio de 2017 se notificó un total de 824 casos de fiebre amarilla en Espírito Santo, de los cuales 307 (37%) fueron confirmados. De estos, 95 (30,9%) murieron por causa de la enfermedad. El mayor número de afectados correspondió a la población masculina, con 244 casos (79,5%), mientras que 63 casos (20,5%) fueron mujeres. La tasa de incidencia más alta registrada se observó en la ciudad de Santa Leopoldina (380,2 casos/100 000 habitantes). El brote evolucionó rápidamente y se logró darle respuesta gracias a un grupo multidisciplinario formado específicamente para contrarrestar este brote de fiebre amarilla. Conclusiones. Los datos se recibieron y analizaron rápidamente. La respuesta para detener la progresión de esta enfermedad mortal consistió en un tratamiento inmediato de los casos y una estrategia de vacunación de bloqueo. A pesar de estos esfuerzos, la tasa de letalidad de la fiebre amarilla continuó siendo alta.

[RESUMO]. Objetivo. Descrever os aspectos epidemiológicos de um surto de febre amarela ocorrido no Estado de Espírito Santo, Brasil, no período de 1o de janeiro de 2017 a 31 de julho de 2017. Métodos. O estudo se baseou em um enfoque descritivo, quantitativo e retrospectivo para analisar dados secundários obtidos dos sistemas nacionais de notificação: Sistema de Informação de Agravos de Notificação (SINAN), sistema Gerenciador de Ambiente Laboratorial (GAL) e Secretaria de Estado da Saúde de Espírito Santo (SESA). Resultados. No período de 1o de janeiro de 2017 a 8 de julho de 2017, 824 casos foram notificados no Espírito Santo, sendo 307 (37%) confirmados como febre amarela. Ocorreram 95 casos de morte pela doença (30,9%). O sexo masculino foi o mais afetado, sendo registrados 244 casos (79,5%) no sexo masculino e 63 casos (20,5%) no sexo feminino. A taxa de incidência mais alta foi verificada na cidade de Santa Leopoldina, com 380,2 casos por 100 mil habitantes. O surto progrediu rapidamente e a resposta foi possível com a ação de um grupo multidisciplinar formado para combater o surto de febre amarela. Conclusões. Os dados foram obtidos e analisados com rapidez e a resposta, consistindo de tratamento imediato dos casos e uma estratégia de vacinação de bloqueio, visou deter a progressão desta doença fatal. Apesar dos esforços, a taxa de letalidade da febre amarela continuou alta.

Cardiometabolic and Muscular Fatigue Responses to Different CrossFit® Workouts.

CrossFit® consists of workouts of the day (WODs) in which different exercises are conducted at high intensity with minimal or no rest periods. This study sought to quantify exercise intensity and muscular fatigue in the three CrossFit® session modalities: gymnastics (G), metabolic conditioning (M) and weightlifting (W). Thirty two, young, strength-trained, healthy men completed the three WODs: G ("Cindy"), M (double skip rope jumps) and W (power cleans). The variables measured in the sessions were: mean heart rate (HR), rate of perceived exertion (RPE), blood lactate [lactate], and jump height (H), average power (AP) and maximum take-off velocity (Vmax) in a counter movement jump test. In all three WODs, elevated HR values (≥90% of the theoretical HRmax) were recorded at the time points mid-session and end-session. Mean RPEs were 17.6 ± 1.6 (G WOD), 16.0 ± 2.3 (M WOD), and 15.7 ± 2.0 (W WOD). Postexercise [lactate] was higher than 10 mmol·L-1 for the three WODs. Following the G ("Cindy") and W (power cleans) WODs, respectively, significant muscular power losses were observed in H (7.3% and 8.1%), Vmax (13.8% and 3.3%), AP relative (4.6% and 8.3%) and AP total (4.2% and 8.2%) while losses in the M WOD were not significant (p > 0.05). A vigorous intensity of exercise was noted in all three WODs, with greater mean HRs detected in the "Cindy" and skip rope WODs than power clean WOD. Muscular fatigue was produced in response to the "Cindy" and power clean WODs but not the skip rope WOD.

Effects of ß-alanine supplementation during a 5-week strength training program: a randomized, controlled study.

BACKGROUND: ß-Alanine (BA) is a non-essential amino acid that has been shown to enhance exercise performance. The purpose of this investigation was to determine if BA supplementation improved the adaptive response to five weeks of a resistance training program. METHODS: Thirty healthy, strength-trained individuals were randomly assigned to the experimental groups placebo (PLA) or BA. Over 5 weeks of strength training, subjects in BA took 6.4 g/day of BA as 8 × 800 mg doses each at least 1.5 h apart. The training program consisted of 3 sessions per week in which three different leg exercises were conducted as a circuit (back squat, barbell step ups and loaded jumping lunges). The program started with 3 sets of 40 s of work per exercise and rest periods between sets of 120 s in the first week. This training volume was then gradually built up to 5 sets of 20 s work/60 s rest in the fifth week. The work load during the program was set by one of the authors according to the individual's perceived effort the previous week. The variables measured were average velocity, peak velocity, average power, peak power, and load in kg in a back squat, incremental load, one-repetition maximum (1RM) test. In addition, during the rest period, jump ability (jump height and power) was assessed on a force platform. To compare data, a general linear model with repeated measures two-way analysis of variance was used. RESULTS: Significantly greater training improvements were observed in the BA group versus PLA group (p = 0.045) in the variables average power at 1RM (BA: 42.65%, 95% CI, 432.33, 522.52 VS. PLA: 21.07%, 95% CI, 384.77, 482.19) and average power at maximum power output (p = 0.037) (BA: 20.17%, 95% CI, 637.82, 751.90 VS. PLA; 10.74%, 95% CI, 628.31, 751.53). The pre- to post training average power gain produced at 1RM in BA could be explained by a greater maximal strength gain, or load lifted at 1RM (p = 0.014) (24 kg, 95% CI, 19.45, 28.41 VS. 16 kg, 95% CI, 10.58, 20.25) and in the number of sets executed (p = 0.025) in the incremental load test (BA: 2.79 sets, 95% CI, 2.08, 3.49 VS. PLA: 1.58 sets, 95% CI, 0.82, 2.34). CONCLUSIONS: ß-Alanine supplementation was effective at increasing power output when lifting loads equivalent to the individual's maximal strength or when working at maximum power output. The improvement observed at 1RM was explained by a greater load lifted, or strength gain, in response to training in the participants who took this supplement.

Effects of Beetroot Juice Supplementation on a 30-s High-Intensity Inertial Cycle Ergometer Test.

Background: Beetroot juice (BJ) is rich in inorganic nitrates and has proved effective at increasing blood nitric oxide (NO) levels. When used as a supplement BJ has shown an ergogenic effect on cardiorespiratory resistance exercise modalities, yet few studies have examined its impact on high intensity efforts. Objective: To assess the effects of BJ intake on anaerobic performance in a Wingate test. Methods: Fifteen trained men (age 21.46 ± 1.72 years, height 1.78 ± 0.07 cm and weight 76.90 ± 8.67 kg) undertook a 30-s maximum intensity test on an inertial cycle ergometer after drinking 70 mL of BJ (5.6 mmol NO3-) or placebo. Results: Despite no impacts of BJ on the mean power recorded during the test, improvements were produced in peak power (6%) (p = 0.034), average power 0-15 s (6.7%) (p = 0.048) and final blood lactate levels (82.6%) (p < 0.001), and there was a trend towards a shorter time taken to attain peak power (-8.4%) (p = 0.055). Conclusions: Supplementation with BJ has an ergonomic effect on maximum power output and on average power during the first 15 s of a 30-s maximum intensity inertial cycle ergometer test.

Differential modulatory effects of cocaine on marmoset monkey recognition memory.

Acute and repeated exposure to cocaine alters the cognitive performance of humans and animals. How each administration schedule affects the same memory task has yet to be properly established in nonhuman primates. Therefore, we assessed the performance of marmoset monkeys in a spontaneous object-location (SOL) recognition memory task after acute and repeated exposure to cocaine (COC; 5mg/kg, ip). Two identical neutral stimuli were explored on the 10-min sample trial, after which preferential exploration of the displaced vs the stationary object was analyzed on the 10-min test trial. For the acute treatment, cocaine was given immediately after the sample presentation, and spatial recognition was then tested after a 24-h interval. For the repeated exposure schedule, daily cocaine injections were given on 7 consecutive days. After a 7-day drug-free period, the SOL task was carried out with a 10-min intertrial interval. When given acutely postsample, COC improved the marmosets' recognition memory, whereas it had a detrimental effect after the repeated exposure. Thus, depending on the administration schedule, COC exerted opposing effects on the marmosets' ability to recognize spatial changes. This agrees with recent studies in rodents and the recognition impairment seen in human addicts. Further studies related to the effects of cocaine's acute×prior drug history on the same cognitive domain are warranted.

Scopolamine Induces Deficits in Spontaneous Object-Location Recognition and Fear-Learning in Marmoset Monkeys.

The non-selective muscarinic receptor antagonist scopolamine (SCP) induces memory deficits in both animals and humans. However, few studies have assessed the effects of amnesic agents on memory functions of marmosets - a small-bodied neotropical primate that is becoming increasingly used as a translational model for several neuropathologies. Here we assessed the effects of an acute SCP administration (0.03 mg/kg, sc) on the behavior of adult marmoset monkeys in two tasks. In the spontaneous object-location (SOL) recognition task, two identical neutral stimuli were explored on the sample trial, after which preferential exploration of the displaced versus the stationary object was analyzed on the test trial. In the fear-motivated behavior (FMB) procedure, the same subjects were submitted to an initial baseline trial, followed by an exposure period to a snake model and lastly a post-exposure trial. All trials and inter-trial intervals lasted 10 min for both tests. Results showed that on the SOL test trial, the saline group explored the displaced object significantly longer than its identical stationary counterpart, whereas SCP-treated marmosets explored both objects equivalently. In the FMB test, the saline group - but not the SCP-treated animals - spent significantly less time where the stimulus had been specifically encountered and more time being vigilant of their surroundings, compared to pre-exposure levels. Drug-related effects on general activity, overall exploration (SOL task) and behavioral response to the aversive stimulus (FMB task) were not observed. SCP thus impaired the marmosets' short-term ability to detect changes associated with the spatial location of ethologically irrelevant (SOL task) and relevant stimuli (FMB task). Similar results have been reported in other animal species. Marmosets may thus help reduce the translational gap between pre-clinical studies and memory-associated human pathologies.

[Knowledge about tuberculosis by doctors and nurses, who work in the Family Health Strategy in the city of Vitória, Espírito Santo State: a cross-sectional study]. / O conhecimento de enfermeiros e médicos que trabalham na Estratégia de Saúde da Família acerca da tuberculose no município de Vitória (ES): um estudo de corte transversal.

Brazil is in 14th among the 23 countries responsible for 80% of the tuberculosis (TB) cases in the world. Aiming to understand the maintenance of these indexes, this study was developed to identify if the knowledge about tuberculosis by doctors and nurses, who work in the Family Health Strategy in the city of Vitória (ES), would be a factor in the mediation of the prevention processes, diagnosis and treatment of the Tuberculosis. This is a cross-sectional study, with a sample size of 50 professionals. The collected data had been analyzed using the Chi-square and Fisher Exact tests with significance level of 0.05. Regarding the transmission and diagnosis of the Tuberculosis, there was no statistically significant difference between doctors and nurses. Only one variable presented a statistical difference: 41% of doctors and 15% of the nurses (p<0.05) mentioned that the patient must be attended in a place of choice of the doctor or nurse, and still, 4% of the total of the sample had answered that the supervision cannot be made by a member of the family. The research proves that doctors and nurses has knowledge to reduce the indexes of Tuberculosis, even so is indispensable the continuous study and qualification of these professionals.