Further evidence for loss-of-function mutations in the CEACAM16 gene causing nonsyndromic autosomal recessive hearing loss in humans.

Mutations in the CEACAM6 gene were first described as causing autosomal dominant nonsyndromic hearing loss, but two splice-altering variants have been recently described as causing autosomal recessive nonsyndromic hearing loss. We describe the novel and extremely rare loss-of-function variant c.436 C > T/p.(Arg146Ter) in the CEACAM16 gene segregating with post-lingual progressive autosomal recessive hearing loss. This variant is predicted to significantly reduce the size of the wild type protein. Our results give additional support that loss-of-function variants in CEACAM16 cause autosomal recessive hearing loss in humans.

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors.

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property-free knowledge base for future anticoronavirus drug discovery.

Frequency and origin of the c.2090T>G p.(Leu697Trp) MYO3A variant associated with autosomal dominant hearing loss.

We recently described a novel missense variant [c.2090T>G:p.(Leu697Trp)] in the MYO3A gene, found in two Brazilian families with late-onset autosomal dominant nonsyndromic hearing loss (ADNSHL). Since then, with the objective of evaluating its contribution to ADNSHL in Brazil, the variant was screened in additional 101 pedigrees with probable ADNSHL without conclusive molecular diagnosis. The variant was found in three additional families, explaining 3/101 (~3%) of cases with ADNSHL in our Brazilian pedigree collection. In order to identify the origin of the variant, 21 individuals from the five families were genotyped with a high-density SNP array (~600 K SNPs- Axiom Human Origins; ThermoFisher). The identity by descent (IBD) approach revealed that many pairs of individuals from the different families have a kinship coefficient equivalent to that of second cousins, and all share a minimum haplotype of ~607 kb which includes the c.2090T>G variant suggesting it probably arose in a common ancestor. We inferred that the mutation occurred in a chromosomal segment of European ancestry and the time since the most common ancestor was estimated in 1100 years (CI = 775-1425). This variant was also reported in a Dutch family, which shares a 87,121 bp haplotype with the Brazilian samples, suggesting that Dutch colonists may have brought it to Northeastern Brazil in the 17th century. Therefore, the present study opens new avenues to investigate this variant not only in Brazilians but also in European families with ADNSHL.

Work activity and musculoskeletal symptoms in female cashiers.

Introduction: Musculoskeletal symptoms affect several professional categories, including cashiers, who make repetitive movements. Irregular ergonomic aspects referring to poor postures cause physical and mental debilitation, leading to work-related musculoskeletal disorders. Objectives: To correlate musculoskeletal disorders with an ergonomic analysis of the workstation used by cashiers. Methods: A cross-sectional study was conducted for evaluation of female cashiers working at a supermarket chain in the city of Goiânia, state of Goiás, Brazil. The Nordic Musculoskeletal Questionnaire (NMQ), Portuguese version, was used. To assess the ergonomic position of cashiers, the Rapid Upper Limb Assessment (RULA) tool was administered. Results: A high prevalence of musculoskeletal pain was demonstrated in the neck, shoulders, wrists/hands, and lower and upper back in cashiers. A final RULA score of 6 was obtained, equivalent to action level 3, which indicates that a more detailed investigation and short-term changes are needed. In the RULA assessment, there was a significant correlation between legs and lower back; in the NMQ assessment, there were correlations between trunk and shoulder and between neck and elbow, among other correlations that contribute to the emergence of work-related musculoskeletal disorders. Conclusions: Musculoskeletal complaints correlated with an ergonomic risk of the workstation. Thus, interventions such as workplace kinesiotherapy and urgent changes in the workstation are needed to comply with the requirements of the Brazilian Regulatory Standard No. 17 and improve the workplace for cashiers.

[Quality of life of the work of physical therapy course teachers in Goiânia in the State of Goiás, Brazil]. / Qualidade de vida no trabalho de fisioterapeutas docentes no município de Goiânia, Goiás, Brasil.

The scope of this article is to analyze the quality of work life of the physical therapy course teachers in the city of Goiânia in the state of Goiás. It involved a cross-sectional study of 65 physical therapy teachers in Goiânia. The participants who had worked for less than six months in the profession and those who failed to fill out the questionnaire in full were excluded from the research. A socio-demographic and the Total Quality of Work Life (TQWL-42) questionnaire were used to assess the quality of work life. It was established that the teachers who taught in graduate courses and who held management positions presented significantly better averages than those who only taught in undergraduate courses. Satisfaction with income and with the teaching activity also showed significant results influencing the quality of work life of the participants. Work in positions and locations that allow greater autonomy, status and remuneration, as well as subjective evaluation of satisfaction with income and teaching work, influenced the quality of work life of physical therapy teachers.

O objetivo deste artigo é avaliar a qualidade de vida no trabalho de fisioterapeutas docentes de cursos de fisioterapia no município de Goiânia-GO. Trata-se de um estudo transversal com 65 docentes. Foram incluídos fisioterapeutas docentes do curso de fisioterapia no município de Goiânia. Foram excluídos aqueles que estavam afastados, com menos de seis meses de atividade e que responderam os questionários de forma incompleta. Utilizou-se um questionário sociodemográfico e o Total Quality of Work Life (TQWL-42) para avaliação da qualidade de vida no trabalho. Verificou-se que os docentes que atuavam em pós-graduação, ou exerciam cargo de chefia apresentaram médias significativamente melhores que aqueles que atuavam apenas na graduação. A satisfação com a renda e com a atividade docente também apresentou resultados significativos, influenciando a qualidade de vida no trabalho dos participantes. A atuação em cargos e locais que permitem maior autonomia, posição social e remuneração, assim como a avaliação subjetiva da satisfação com a renda e com a atuação na docência, influenciaram a qualidade de vida no trabalho dos fisioterapeutas docentes.

Poisoning by Brunfelsia uniflora in sheep and donkeys.

Farmers in the State of Piauí in northeastern Brazil reported nervous signs in ruminants and donkeys after ingestion of Brunfelsia uniflora at the start of the rainy season when the plant is flowering. Leaves of the plant, collected at the start or at the end of the rainy season, were administered in single doses of 5-20 g/kg body weight to 8 sheep and 3 donkeys. Two sheep and 1 donkey that ingested 10 g/kg of the plant in November at the start of the rainy season, when the plant was flowering, developed severe convulsions and diarrhea. One sheep was euthanized and autopsied, and no significant lesions were found. The other sheep and the donkey recovered. Four sheep and one donkey that ingested 10 or 20 g/kg of leaves collected in April, at the end of the rainy season, did not show clinical signs. One donkey that ingested 5 g/kg of leaves collected in November developed diarrhea and recovered. These results demonstrate the toxicity of B. uniflora for livestock and suggest that the plant is toxic at these doses only during the start of the rainy season.

The first South American case of pre-implantation genetic diagnosis to select compatible embryo for cord blood transplantation as treatment for sickle cell anemia.

Sickle cell anemia is an inherited systemic hemoglobinopathy that affects hemoglobin production in red blood cells, leading to early morbidity and mortality. It is caused by a homozygous nucleotide substitution (c.20A>T) in the ß-globin gene (HBB) that changes a glutamic acid to a valine in the protein. We present a case report of a fertile couple, both carriers of the sickle cell anemia mutation, with one affected daughter. Six cycles of assisted reproductive techniques were performed, resulting in 53 embryos in cleavage stage. Each embryo was biopsied and analyzed for pre-implantation genetic diagnosis (PGD) by fluorescent polymerase chain reaction, using polymorphic markers of the region of interest followed by capillary electrophoresis in an automated genetic analyzer. HLA Compatible and normal embryos for the mutation represented 3 (5.66%); while the carriers and compatible 6 (11.32%); therefore, embryos matching those of the affected daughter represented 9 (16.98%). A selected embryo in blastocyst stage was transferred, resulting in a healthy male newborn, who had the umbilical cord blood cells collected and stored. The affected daughter was immunosuppressed and received transplanted cells from the umbilical cord blood of her brother; the treatment was successful. Embryo selection using PGD technologies represent the most effective treatment plan for parents who want to have a healthy child, and it could cure another child already affected by inherited hemoglobinopathy.

High-fat diet-induced downregulation of anorexic leukemia inhibitory factor in the brain stem.

OBJECTIVE: High-fat diet (HFD) is known to induce low-grade hypothalamic inflammation. Whether inflammation occurs in other brain areas remains unknown. This study tested the effect of short-term HFD on cytokine gene expression and identified leukemia inhibitory factor (LIF) as a responsive cytokine in the brain stem. Thus, functional and cellular effects of LIF in the brain stem were investigated. METHODS: Male rats were fed chow or HFD for 3 days, and then gene expression was analyzed in different brain regions for IL-1ß, IL-6, TNF-α, and LIF. The effect of intracerebroventricular injection of LIF on chow intake and body weight was also tested. Patch clamp recording was performed in the nucleus tractus solitarius (NTS). RESULTS: HFD increased pontine TNF-α mRNA while downregulating LIF in all major parts of the brain stem, but not in the hypothalamus or hippocampus. LIF injection into the cerebral aqueduct suppressed food intake without conditioned taste aversion, suggesting that LIF can induce anorexia via lower brain regions without causing malaise. In the NTS, a key brain stem nucleus for food intake regulation, LIF induced acute changes in neuronal excitability. CONCLUSIONS: HFD-induced downregulation of anorexic LIF in the brain stem may provide a permissive condition for HFD overconsumption. This may be at least partially mediated by the NTS.

Qualidade de vida no trabalho de fisioterapeutas docentes no município de Goiânia, Goiás, Brasil / Quality of life of the work of physical therapy course teachers in Goiânia in the State of Goiás, Brazil

Resumo O objetivo deste artigo é avaliar a qualidade de vida no trabalho de fisioterapeutas docentes de cursos de fisioterapia no município de Goiânia-GO. Trata-se de um estudo transversal com 65 docentes. Foram incluídos fisioterapeutas docentes do curso de fisioterapia no município de Goiânia. Foram excluídos aqueles que estavam afastados, com menos de seis meses de atividade e que responderam os questionários de forma incompleta. Utilizou-se um questionário sociodemográfico e o Total Quality of Work Life (TQWL-42) para avaliação da qualidade de vida no trabalho. Verificou-se que os docentes que atuavam em pós-graduação, ou exerciam cargo de chefia apresentaram médias significativamente melhores que aqueles que atuavam apenas na graduação. A satisfação com a renda e com a atividade docente também apresentou resultados significativos, influenciando a qualidade de vida no trabalho dos participantes. A atuação em cargos e locais que permitem maior autonomia, posição social e remuneração, assim como a avaliação subjetiva da satisfação com a renda e com a atuação na docência, influenciaram a qualidade de vida no trabalho dos fisioterapeutas docentes.

Abstract The scope of this article is to analyze the quality of work life of the physical therapy course teachers in the city of Goiânia in the state of Goiás. It involved a cross-sectional study of 65 physical therapy teachers in Goiânia. The participants who had worked for less than six months in the profession and those who failed to fill out the questionnaire in full were excluded from the research. A socio-demographic and the Total Quality of Work Life (TQWL-42) questionnaire were used to assess the quality of work life. It was established that the teachers who taught in graduate courses and who held management positions presented significantly better averages than those who only taught in undergraduate courses. Satisfaction with income and with the teaching activity also showed significant results influencing the quality of work life of the participants. Work in positions and locations that allow greater autonomy, status and remuneration, as well as subjective evaluation of satisfaction with income and teaching work, influenced the quality of work life of physical therapy teachers.

Beauveria bassiana strains for biological control of Cosmopolites sordidus (Germ.) (Coleoptera: Curculionidae) in plantain.

The objective of this study was to select strains of Beauveria bassiana for controlling Cosmopolites sordidus (Germ.) in plantain farms (cv. Terra) of the "Recôncavo" and southern regions in the state of Bahia, Brazil. The virulence of 32 B. bassiana isolates against C. sordidus was determined under laboratory conditions. Three isolates (CNPMF 407, CNPMF 218, and CNPMF 416) were selected for evaluation under field conditions in plantations located in the counties of Mutuípe and Wenceslau Guimarães. Population of C. sordidus was estimated every 15 days by using pseudostem traps. The efficiency of the three strains of B. bassiana was compared to chemical control (carbofuran, 4 g/trap) and absence of control. Carbofuran caused around 90% of adult mortality after 12 months, with a reduction in the population of C. sordidus since the first evaluation. A low number of trapped insects was observed in the fungus-treated plots, suggesting the efficiency of the isolates in controlling the C. sordidus population. The strain CNPMF 218 was the most efficient in controlling C. sordidus adults in both locations, causing around 20% mortality, leading to 40% population size reduction after 12 months.

Estresse parental em mães de bebês, crianças e adolescentes com queimadura / Parental stress in mothers of babies, children and adolescent with burning / Estrés en madres de lactantes, niños y adolescents con quemadura

Objetivo: Avaliar a prevalência de estresse parental de mães de filhos queimados em tratamento no Pronto Socorro para Queimaduras de Goiânia, GO. Método: Participaram 53 mães de bebês, crianças e/ou adolescentes queimados que responderam o Questionário Sociodemográfico, o Questionário de Classificação Econômica da Associação Brasileira de Empresas de Pesquisa e o Índice de Estresse Parental na forma curta (PSI/SF). Foram incluídas mães acima de 18 anos, com filhos queimados de zero a 18 anos, e que estavam em tratamento na instituição. Foram excluídas as mães que possuíam alguma doença concomitante, e as que tinham mais de um filho queimado. A análise estatística foi realizada considerando um intervalo de confiança de 95% e um nível de significância de 5% (p<0,05). Resultados: A maior prevalência de queimaduras foi de segundo grau (43,4%), com porcentagem de até 5% do corpo queimado (52,8%), sendo que o ferro quente foi o principal agente causador (45,3%). De acordo com os níveis de estresse das mães em cada subescala e pontuação total do questionário PSI/SF, verificou-se que 34% das mães possuíam estresse na subescala sofrimento parental. Porém, a subescala criança difícil foi relatada por 30,2% das genitoras. As variáveis que interferiram significativamente no nível do estresse parental foram: escolaridade da mãe e do filho, agente da queimadura, dados socioeconômicos e atividades de lazer. Conclusões: As subescalas criança difícil e o sofrimento parental são os principais fatores relacionados à influência do estresse parental no âmbito sociodemográfico e familiar das mães que tinham filhos em tratamento de queimadura.

Objective: To measure the prevalence of parental stress of mothers of burned children who do treatment in Pronto Socorro para Queimaduras de Goiânia, GO. Methods: Participated 53 mothers of babies, children and/or adolescent who answered the Sociodemographic Questionnaire, the Questionnaire of Economic Classification of Associação Brasileira de Empresas de Pesquisa and the Parental Stress Index in the short form (PSI / SF). In total mothers over 18 years with burned children among 0-18 years were included, who were treated at the institution. Mothers were excluded if they had any concomitant illness, and who had more than one child burned. Statistical analysis was performed considering a 95% confidence interval and a significance level of 5% (p<0.05). Results: The most prevalent were 2nd grade burns (43.4%), a percentage of up to 5% of burnt body (52.8%), and the hot iron was the main causative agent (45.3%). According to the stress levels of mothers in each subscale and total score of the PSI / SF questionnaire, it was found that 34% of mothers had stress subscale parental suffering. But the subscale difficult child was reported by 30.2% of the progenitors. The variables that significantly interfered with parenting stress level were: education of the mother and child, burning agent, socioeconomic data and leisure activities. Conclusion: Subscales difficult child and parental distress are the main factors related to the influence of parental stress in the sociodemographic and family context of mothers who have children in burn treatment.

Objetivo: Evaluar la prevalencia de estrés parental de madres de hijos quemados en tratamiento en Pronto Socorro para Queimaduras de Goiânia, GO. Métodos: 53 madres de lactantes, niños y/o adolescentes quemados que contestaron el Cuestionario Sociodemográfico, el Cuestionario de Clasificación Económica de la Associação Brasileira de Empresas de Pesquisa y el Índice de Estrés Parental-Forma Corta (PSI/SF). Incluyeron madres mayores 18 años con niños quemados de 0-18 años, tratados en la institución. Madres que tenían alguna enfermedad concomitante o/y que había más de un niño quemado fueron excluidas. El análisis estadístico se realizó considerando un intervalo de confianza del 95% y un nivel de significación del 5% (p<0,05). Resultados: La quemadura más frecuente fue de 2º grado (43,4%), un porcentaje de hasta el 5% del cuerpo quemado (52,8%), y el hierro caliente era el principal agente causal (45,3%). De acuerdo con los niveles de estrés parental en cada subescala y la puntuación total de la PSI/SF, se encontró que el 34% de las madres tenía el sufrimiento de los padres subescala de estrés. Pero subescala difícil niño fue informado por el 30,2% de las progenitoras. Las variables que significativamente interfieren con el nivel de estrés parental fueron: la educación de la madre y el niño, el agente quemar, datos socioeconómicos y de ocio. Conclusión: Subescalas niño difícil y angustia parental fueron los principales factores relacionados con la influencia del estrés parental en el entorno sociodemográfico y familiar de las madres que tienen hijos en el tratamiento de quemaduras.

Clareamento da melanina na epiderme do lobo-marinho-sul-americano e sua aplicação na imunohistoquímica enzimática / Bleaching of melanin in the epidermis of south American fur seal and its application on enzyme immunohistochemistry

O Lobo-marinho-sul-americano (Arctocephalus australis) é um mamífero marinho anfíbio distribuído ao longo da Costa do Atlântico e do Pacífico da América do Sul. Esta espécie está bem adaptada a diferentes habitats devido à morfologia dos membros em forma de nadadeira e de seu sistema tegumentar. Estudos imuno-histoquímicos são importantes para avaliar os mecanismos de adaptação da pele devido a diferencial expressão dos antígenos presentes no tecido dependendo da região da superfície corporal. Entretanto, sua epiderme altamente pigmentada (melanina) impede a visualização dos marcadores cromógenos utilizados na imunohistoquímica. Neste trabalho foi desenvolvido um método de clarear a melanina para permitir a visualização dos cromógenos sem alterar a afinidade antígeno-anticorpo para a imuno-histoquímica. A análise do índice do PCNA (proliferating cell nuclear antigen) na epiderme de A. australis, com diaminobenzidina (DAB) como cromógeno foi usada para testar o método. O clareamento da melanina permitiu obter o índice de proliferação celular na epiderme e evitar resultados falso-positivos sem afetar os resultados imuno-histoquímicos.

The South American fur seal (Arctocephalus australis) is an amphibious marine mammal distributed along the Atlantic and Pacific coasts of South America. The species is well adjusted to different habitats due to the morphology of its fin-like members and due to some adaptations in their integumentary system. Immunohistochemical studies are very important to evaluate the mechanisms of skin adaptation due the differential expression of the antigens present in the tissue depending of the region of the body surface. However, its strongly pigmented (melanin) epidermis prevents the visualization of the immunohistochemical chromogens markers. In this study a melanin bleaching method was developed aimed to allow the visualization of the chromogens without interfering in the antigen-antibody affinity for immunohistochemistry. The analysis of PCNA (proliferating cell nuclear antigen) index in the epidermis of A. australis by immunohistochemistry with diaminobenzidine (DAB) as chromogen was used to test the method. The bleaching of the melanin allowed to obtain the cell proliferation index in epidermis and to avoid false positive results without affecting the immunohistochemical results.

Desempenho funcional de crianças com paralisia cerebral participantes de tratamento multidisciplinar / Functional performance of children with cerebral palsy undergoing multidisciplinary treatment

A paralisia cerebral (PC) é um conjunto de desordens posturais e do movimento que causam limitações funcionais; é atribuída a distúrbios não progressivos, porém mutáveis, decorrentes de lesão do cérebro imaturo. Os objetivos do estudo foram identificar as dimensões funcionais comprometidas e observar a evolução da função motora grossa de crianças com PC submetidas a tratamento multidisciplinar em um intervalo de quatro meses. A amostra foi composta por 27crianças com PC (média de idade 7,6 anos) que freqüentavam a Associação Pestalozzi de Goiânia, GO. O nível de comprometimento das crianças foi atribuído segundo o sistema de classificação da função motora grossa GMFCS (Gross motorfunction classification system); a medida de função motora grossa GMFM (Grossmotor function measure) foi aplicada no início do estudo e após quatro meses. Os resultados mostram que 55,6% das crianças estavam nos níveis IV e V do GMFCS; foi verificada evolução da função motora grossa em todas as dimensões avaliadas pela GMFM, exceto na postura sentada – sugerindo que as transferências de postura e a locomoção devem ser focalizadas no tratamento multidisciplinar dessas crianças com CP.

Cerebral palsy (CP) is described as a set of postural and movement disorders that cause functional limitations; it is assigned to non-progressive, changeable disorders due to immature brain injury. The purpose of the study was to assess functional dimensions affected and the evolution over a four-month period of gross motor function of children with CP undergoing multidisciplinary treatment. The sample was made up by 27 children (mean age 7.6 years) who attended thePestalozzi Association of Goiania, GO. Severity level was assessed by the Gross Motor Function Classification System (GMFCS); the Gross Motor Function Measure(GMFM) was applied at study onset and four months later. Results show that 55.6%of children were in GMFCS levels IV and V; children showed a positive gross motor function evolution in all GMFM dimensions, except in the skills at the sitting position– suggesting that position changes and locomotion should be focussed in multidisciplinary treatment of these children with CP.