Detection of the pandemic norovirus variant GII.4 Sydney 2012 in Rio Branco, state of Acre, northern Brazil

Noroviruses (NoVs) are important cause of gastroenteritis in humans worldwide. Genotype GII.4 is responsible for the majority of outbreaks reported to date. This study describes, for the first time in Brazil, the circulation of NoV GII.4 variant Sydney 2012 in faecal samples collected from children aged less than or equal to eight years in Rio Branco, state of Acre, northern Brazil, during July-September 2012

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

PERFIL CLÍNICO E EPIDEMIOLÓGICO DE PACIENTES COM QPCR POSITIVO DURANTE O SURTO DE MONKEYPOX NOS ANOS DE 2022 E 2023 NO ESTADO DO PARÁ

Introdução/objetivo: Popularmente conhecida como varíola dos macacos a monkeypox (MPOX) é uma zoonose ocasionada por um Orthopoxyvirus (OPXV) que teve seu primeiro caso descrito em humanos na República Democrática do Congo em 1970, tornando-se posteriormente endêmico em países da África Central e Ocidental. Em maio de 2022 foi relatada a detecção em vários países não endêmicos onde não se tinham ligações epidemiológicas conhecidas e o número de casos continuou a aumentar com a contínua transmissão em todo o mundo, no Brasil o primeiro caso foi confirmado em junho de 2022, logo após foi instituída a vigilância de rotina dos casos suspeitos. Diante disto, este estudo objetivou descrever a prevalência, as características epidemiológicas e clínicas dos casos confirmados de MPOX no Estado do Pará. Métodos: Para isso, foram analisadas amostras de swab de lesão coletadas de casos suspeitos e que deram entrada no Laboratório de Enterovírus (LEV) do Instituto Evandro Chagas (IEC) que atua como referência laboratorial para o Monkeypox no Estado do Pará no período de julho de 2022 a junho de 2023. Foi realizado o levantamento e tabulação das informações epidemiológicas e clínicas dos casos, após isso as amostras foram extraídas e testadas por Reação em Cadeia mediada pela Polimerase em tempo real (qPCR) utilizando oligonucleotídeos e sondas específicas para detecção de MPOX. Resultado: Das 284 amostras recebidas 45,8% (130) foram confirmadas, onde 95% (124) pertenciam a pacientes do sexo masculino tendo o grupo etário de 20 a 29 anos com 86% (61) dos casos. Os sintomas mais comuns relatados foram febre (78,4%), lesão cutânea (62,3%), cefaléia (60%) e adenomegalia (38,4%). Dos pacientes positivos 86% (112) se enquadram no grupo de homens que fazem sexo com homens, 52% (68) são pessoas que vivem com HIV e 18% (24) possuem alguma infecção sexualmente transmissível ativa, sendo a sífilis a mais prevalente com 91,6% (22) dos casos. Foi registrado a hospitalização e posterior óbito de um paciente que vivia com HIV e possuía sífilis ativa. Conclusão: Diante disto, pode-se avaliar que o perfil clínico e epidemiológico dos pacientes no Estado do Pará se assemelha com os descritos em literatura em todo o mundo, logo, torna-se fundamental a vigilância epidemiológica deste patógeno uma vez que atual e rápida disseminação e evolução do MPOX não têm precedentes e representa uma ameaça contínua à saúde pública

Detection of the pandemic norovirus variant GII.4 Sydney 2012 in Rio Branco, state of Acre, northern Brazil

Noroviruses (NoVs) are important cause of gastroenteritis in humans worldwide. Genotype GII.4 is responsible for the majority of outbreaks reported to date. This study describes, for the first time in Brazil, the circulation of NoV GII.4 variant Sydney 2012 in faecal samples collected from children aged less than or equal to eight years in Rio Branco, state of Acre, northern Brazil, during July-September 2012

Análise de recombinantes de norovírus incomuns de Manaus, Amazon região, Brasil: GII. P22 / GII. 5, GII. P7 / GII. 6 e GII. Pg / GII. 1

Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Norovirus (NoV) is responsible for outbreaks and sporadic cases of nonbacterial acute gastroenteritis in humans worldwide. The virus consists of small round particles containing a single-stranded RNA genome that is divided into three Open Reading Frames. NoV evolves via mechanisms of antigenic drift and recombination, which lead to the emergence of new strains that are capable of causing global epidemics. Recombination usually occurs in the ORF1/ORF2 overlapping region and generates strains with different genotypes in the polymerase and capsid region. The primary objective of this study was to analyze recombination in positive-NoV samples. Specimens were collected during 2011, 2012 and 2014, from children under two years of age presenting gastrointestinal symptoms such as vomiting and diarrhea. The partial polymerase (B region), capsid (D region) genes and the ORF1-ORF2 overlap regions were sequenced in each sample. The recombinant analyses were performed in the Simplot software v.3.5.1 and RDP4 Beta v. 4.6 program. These analyses showed that GII.Pg/GII.1, GII.P7/GII.6, and GII.P22/GII.5 were recombinant strains. To our knowledge, this is the first time that the GII.P22/GII.5 and GII.Pg/GII.1 strains were described in South America and the GII.P7/GII.6 was detected in Northern of Brazil

Retrospective molecular analysis of norovirus recombinant strains in the amazon region, Brazil

Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Iniciação Científica. Ananindeua, PA, Brasil.Federal University of Pará. Postgraduate Program in Biology of Infectious and Parasitic Agents. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Background: Noroviruses are enteric viruses that cause acute gastroenteritis worldwide. Over two decades, GII.4 genotype was responsible for most cases. However, recombinant strains have emerged and changed the epidemiological context of these infections. Objectives: The aim of this study was to identify the recombinant genetic strains of norovirus causing gastroenteritis in Brazilian children from the Amazon region. Methods: We analyzed 534 cases of gastroenteritis between 2015 and 2016. Genotypic characterization was performed by partial sequencing of ORF1 and ORF2. Evolutionary history was inferred by Bayesian inference using MrBayes. Recombinant strains were confirmed by Simplot and RDP4 analysis. Findings: We performed viral detection tests and identified a norovirus frequency of 31.8% (175/534). Based on viral RdRp and VP1 genes, nine genotypes were identified: GIIP31/GII.4, GII·P16/GII.4, GII·P7/GII.6, GII·P21/GII.13, GII·P33/GII.1, GII·P17/GII.17, GI·P7/GI.7, GII·P4/NT, and GII.7/NT. The phylogenetic tree showed evolutionary relationships among the genotypes, including the recombinant strains. This is the first description of GII·P33/GII.1 and GII·P21/GII.13 genotypes in Brazil. Conclusion: Norovirus evolution has been characterized by the continuous replacement of variants that have new antigenic properties. In recent years, recombinant strains have displaced GII.4, improving the viral fitness and influencing the viral transmissibility and pathogenicity

Caliciviruses in hospitalized children, São Luís, Maranhão, 1997–1999: detection of norovirus GII.12

Universidade do Estado do Pará. Programa de Pós-Graduação em Biologia Parasitária na Amazônia. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Programa de Pós-Graduação em Virologia. Ananindeua, PA, Brasil.Faculdade Integrada Brasil Amazônia. Belém, Pará, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Universidade Federal do Maranhão. São Luís, Maranhão, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Gastroenteritis is one of the most common diseases during childhood, with norovirus (NoV) and sapovirus (SaV) being two of its main causes. This study reports for the first time the incidence of these viruses in hospitalized children with and without gastroenteritis in São Luís, Maranhão. A total of 136 fecal samples were tested by enzyme immunoassays (EIA) for the detection of NoV and by reverse transcription-polymerase chain reaction (RT-PCR) for detection of both NoV and SaV. Positive samples for both agents were subjected to sequencing. The overall frequency of NoV as detected by EIA and RT-PCR was 17.6 percent (24/136) and 32.6 percent (15/46), respectively in diarrheic patients and 10.0 percent (9/90) in non-diarrheic patients (p < 0.01). Of the diarrheic patients, 17 percent had fever, vomiting and anorexia, and 13 percent developed fever, vomiting and abdominal pain. Of the 24 NoV-positive samples, 50 percent (12/24) were sequenced and classified as genotypes GII.3 (n = 1), GII.4 (6), GII.5 (1), GII.7 (2), GII.12 (1) and GII.16 (1). SaV frequency was 9.8 percent (11/112), with 22.6 percent (7/31) in diarrheic patients and 4.9 percent (4/81) in nondiarrheic (p = 0.04) ones. In diarrheic cases, 27.3 percent had fever, vomiting and anorexia, whereas 18.2 percent had fever, anorexia and abdominal pain. One SaV-positive sample was sequenced and classified as GII.1. These results show a high genetic diversity of NoV and higher prevalence of NoV compared to SaV. Our data highlight the importance of NoV and SaV as enteropathogens in São Luís, Maranhão