Infertilidade masculina

Between 10 to 15% of couples can be unsuccessful at trying to have children after one year of unprotected sexual intercourse. About 50% of cases of infertility are related to male infertility. The cause of male infertility, in turn, is frequently associated with sperm alterations. Traditionally, male infertility has been considered as a condition that is difficult to be treated. New studies in the field of Genetics have presented findings of deletion or mutation in groups of genes that could have a causal relation to infertility in male patients. Most advancements in the treatment of male infertility are in the area of assisted reproduction, which, in turn, has developed following the progress in technologies of gamete micromanipulation. Our study is aimed at assessing causes of, and treatment for male infertility. Entre 10 a 15% dos casais falham em ter filhos após um ano de intercursos sexuais não protegidos. Cerca de 50% das causas de infertilidade são de origem masculina. Como causa simples de infertilidade, alterações espermáticas são a condição mais freqüente. A infertilidade de causa masculina foi tradicionalmente considerada como uma condição de difícil tratamento. Novos estudos na área da genética têm encontrado deleções ou mutações em grupos de genes que poderiam explicar a infertilidade nesses pacientes. A maior parte dos avanços no tratamento destes casos reside nas técnicas de reprodução assistida, que tiveram seu maior avanço após o desenvolvimento da tecnologia da micromanipulação de gametas. O presente trabalho faz uma análise de causas e de tratamentos para dar solução à infertilidade masculina.

A emergência da nova variante P.1 do SARS-CoV-2 no Amazonas (Brasil) foi temporalmente associada a uma mudança no perfil da mortalidade devido a COVID-19, segundo sexo e idade

Background Since the end of 2020, there has been a great deal of international concern about the variants of SARS-COV-2 B.1.1.7, identified in the United Kingdom; B.1.351 discovered in South Africa and P.1, originating from the Brazilian state of Amazonas. The three variants were associated with an increase in transmissibility and worsening of the epidemiological situation in the places where they expanded. The lineage B.1.1.7 was associated with the increase in case fatality rate in the United Kingdom. There are still no studies on the case fatality rate of the other two variants. The aim of this study was to analyze the mortality profile before and after the emergence of the P.1 strain in the Amazonas state. Methods We analyzed data from the Influenza Epidemiological Surveillance Information System, SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe), comparing two distinct epidemiological periods: during the peak of the first wave, between April and May 2020, and in January 2021 (the second wave), the month in which the new variant came to predominate. We calculated mortality rates, overall case fatality rate and case fatality rate among hospitalized patients; all rates were calculated by age and gender and 95% confidence intervals (95% CI) were determined. Findings We observed that in the second wave there were a higher incidence and an increase in the proportion of cases of COVID-19 in the younger age groups. There was also an increase in the proportion of women among Severe Acute Respiratory Infection (SARI) cases from 40% (2,709) in the first wave to 47% (2,898) in the second wave and in the proportion of deaths due to COVID-19 between the two periods varying from 34% (1,051) to 47% (1,724), respectively. In addition, the proportion of deaths among people between 20 and 59 years old has increased in both sexes. The case fatality rate among those hospitalized in the population between 20 and 39 years old during the second wave was 2.7 times the rate observed in the first wave (female rate ratio = 2.71; 95% CI: 1.9-3.9], p <0.0001; male rate ratio = 2.70, 95%CI:2.0-3.7), and in the general population the rate ratios were 1.15 (95% CI: 1.1-1.2) in females and 0.78 (95% CI: 0.7-0.8) in males]. Interpretation Based on this prompt analysis of the epidemiological scenario in the Amazonas state, the observed changes in the pattern of mortality due to COVID-19 between age groups and gender simultaneously with the emergence of the P.1 strain suggest changes in the pathogenicity and virulence profile of this new variant. Further studies are needed to better understanding of SARS-CoV-2 variants profile and their impact for the health population.Introdução Desde o final de 2020 tem havido grande preocupação internacional com as variantes do SARS-COV-2: B.1.1.7, identificada no Reino Unido; B.1.351, descoberta na África do Sul e P.1, que emergiu inicialmente estado brasileiro do Amazonas. As três variantes foram associadas a aumento na transmissibilidade e piora da situação epidemiológica nos locais onde se expandiram. A linhagem B.1.1.7 foi associada ao aumento da taxa de letalidade no Reino Unido. Ainda não existem estudos conclusivos sobre letalidade das outras duas variantes. O objetivo deste estudo foi analisar o perfil de mortalidade antes e depois da emergência da linhagem P.1 no Amazonas. Métodos Analisamos os dados do sistema nacional de vigilância epidemiológica, comparando dois momentos epidemiológicos distintos: durante o pico da primeira onda, entre abril e maio de 2020, e em janeiro de 2021, mês em que a nova variante passou a predominar. Calculamos as taxas de mortalidade, letalidade e letalidade entre pacientes internados, todas as taxas foram calculadas por idade e por sexo e determinados os intervalos de confiança de 95%. Achados Observamos que na segunda onda houve maior incidência e aumento na proporção de casos de COVID-19 nas faixas etárias mais jovens. Observou-se, também, um aumento na proporção de mulheres entre os casos de SARI de 40% (2.709) na primeira onda para 47% (2.898) na segunda onda e entre mortes por COVID-19 de 34% (1,051) para 47% (1.724), respectivamente. Além disso, a proporção de mortes entre 20 e 59 anos aumentou em ambos os sexos. A letalidade entre os hospitalizados na população entre 20 e 39 anos durante a segunda onda foi 2.7 vezes a primeira onda [razão de taxas sexo feminino=2,71; CI(95%)=1,9-3,9], p<0.0001; razão de taxas sexo masculino=2.70(2.0-3.7)), na população geral as razões de taxa foram 1,15(1,1-1,2) no sexo feminino e 0,78(0,7-0,8) no sexo masculino. Interpretação Observamos mudanças no padrão de mortalidade por COVID-19 entre as faixas etárias e sexo simultaneamente à emergência da linhagem P.1, sugerindo mudanças nos perfis de patogenicidade e virulência, novos estudos são necessários para melhor compreensão das variantes do SARS-CoV-2 e suas consequências na saúde da população

Ligation Tunes Protein Reactivity in an Ancient Haemoglobin: Kinetic Evidence for an Allosteric Mechanism in Methanosarcina acetivorans Protoglobin

Protoglobin from Methanosarcina acetivorans (MaPgb) is a dimeric globin with peculiar structural properties such as a completely buried haem and two orthogonal tunnels connecting the distal cavity to the solvent. CO binding to and dissociation from MaPgb occur through a biphasic kinetics. We show that the heterogenous kinetics arises from binding to (and dissociation from) two tertiary conformations in ligation-dependent equilibrium. Ligation favours the species with high binding rate (and low dissociation rate). The equilibrium is shifted towards the species with low binding (and high dissociation) rates for the unliganded molecules. A quantitative model is proposed to describe the observed carbonylation kinetics

Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi, afflicts from 8 to 15 million people in the Latin America. Chronic chagasic cardiomyopathy (CCC) is the most frequent manifestation of Chagas disease. Currently, patient management only mitigates CCC symptoms. The pathogenic factors leading to CCC remain unknown; therefore their comprehension may contribute to develop more efficient therapies. In patients, high nitric oxide (NO) levels have been associated with CCC severity. In T. cruzi-infected mice, NO, mainly produced via inducible nitric oxide synthase (iNOS/NOS2), is proposed to work in parasite control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, infected rhesus monkeys and iNOS/NOS2-deficient mice were used to explore the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Chronically infected monkeys presented electrical abnormalities, myocarditis and fibrosis, resembling the spectrum of human CCC. Moreover, cardiomyocyte lesion correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue. Our findings support that parasite-driven iNOS/NOS2+ cells accumulation in the cardiac tissue and NO overproduction contribute to cardiomyopathy severity, mainly disturbing the pathway involved in electrical synchrony in T. cruzi infection

Convalescent plasma for COVID-19 in hospitalised patients : an open-label, randomised clinical trial

Background: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients. Methods: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. Results: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48–68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8–12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference −3.7%, 95% CI −18.8–11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups. Conclusions: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone