SNP array and FISH analysis of a proband with a 22q13.2- 22qter duplication shed light on the molecular origin of the rearrangement

Background In about one third of healthy subjects, the microscopic analysis of chromosomes reveals heteromorphisms with no clinical implications: for example changes in size of the short arm of acrocentric chromosomes. In patients with a pathological phenotype, however, a large acrocentric short arm can mask a genomic imbalance and should be investigated in more detail. We report the first case of a chromosome 22 with a large acrocentric short arm masking a partial trisomy of the distal long arm, characterized by SNP array. We suggest a possible molecular mechanism underlying the rearrangement. Case presentation We report the case of a 15-year-old dysmorphic girl with low grade psychomotor retardation characterized by a karyotype with a large acrocentric short arm of one chromosome 22. Cytogenetic analysis revealed a normal karyotype with a very intense Q-fluorescent and large satellite on the chromosome 22 short arm. Fluorescence in situ hybridisation analysis showed a de novo partial trisomy of the 22q13.2-qter chromosome region attached to the short arm of chromosome 22. SNP-array analysis showed that the duplication was 8.5 Mb long and originated from the paternal chromosome. Haplotype analysis revealed that the two paternal copies of the distal part of chromosome 22 have the same haplotype and, therefore, both originated from the same paternal chromosome 22. A possible molecular mechanism that could explain this scenario is a break-induced replication (BIR) which is involved in non-reciprocal translocation events. Conclusion The combined use of FISH and SNP arrays was crucial for a better understanding of the molecular mechanism underlying this rearrangement. This strategy could be applied for a better understanding of the molecular mechanisms underlying cryptic chromosomal rearrangements

Assessment of the impact of race and proxies of socioeconomic status on the prevalence and health outcome of peripartum cardiomyopathy (PPCM) using the “All of Us” Databank

Background: Peripartum Cardiomyopathy (PPCM) is a form of cardiomyopathy occurring during the last month of pregnancy or within months after giving birth in women with previously normal hearts. PPCM is an idiopathic systolic dysfunction that causes a reduced left ventricle ejection fraction. The estimated incidence of PPCM worldwide is 1 diagnosis out of 2,000 live births, and the causes of PPCM remain unknown. A retrospective cohort study conducted at the University of Pennsylvania Health System by Getz et al. showed that black race and socioeconomic proxies (like neighborhood disadvantage index (NDI)) were independently associated with sustained cardiac dysfunction (Getz et al., Am Heart J 2021). This study also showed that from all the components of NDI (education, high rental occupied housing, annual income below poverty line, female headed household, adults unemployed, adults on public assistance), low education and high rental occupied housing were significantly associated with sustained cardiac dysfunction. The central aim of the present project is to assess the effect of socioeconomic proxies (including NDI, lack of access to health care and food insecurity) on the prevalence of sustained cardiac dysfunction from PPCM across the US using the “All of Us” databank. A secondary aim is to test the compliance of the All of Us database capacity to interrogate this potential association. Lastly, we aim to compare the results obtained from the All of Us database with the UK Biobank. Methods: The All of Us databank (Ramirez et al., Patterns 2022; The All of US Research Program, NEJM 2019) will be used to conduct a retrospective cohort study to assess how proxies of socioeconomic status may affect the incidence and prevalence of sustained cardiac dysfunction from PPCM across different ethnicities in the US. The All of Us database focuses on enrolling people in the US from diverse groups that have historically been underrepresented in medical research. Therefore, it includes a more diverse population than the population targeted in the retrospective study conducted at the University of Pennsylvania in which only black women from Philadelphia, PA, were included. To further interrogate the impact that geographic location and population ethnicity may have on the prevalence of sustained cardiac dysfunction from PPCM, the results obtained from the “All of Us” database will be compared against data obtained from the UK Biobank. Expected Results: We expect that the socioeconomic proxies interrogated in this study will have a significant impact on the prevalence of sustained cardiac dysfunction from PPCM. Current knowledge is limited on how socioeconomic status affects sustained cardiac dysfunction resulting from PPCM. Previous studies have been done on populations restricted to small geographic areas and did not analyze factors such as food security, access to care, or disability status. Understanding how these factors affect the incidence and prevalence of sustained cardiac dysfunction from PPCM may be used to improve prevention, early diagnosis, and management of PPCM

Assessment of lunch served in the Workers’ Food Program, Brazil

OBJETIVO: Face à expansão do Programa de Alimentação do Trabalhador no País e sua atualização na normatização dos aspectos nutricionais, foi avaliado o consumo alimentar de trabalhadores participantes do programa, por meio da análise nutricional do almoço servido e do estado nutricional da população atendida. MÉTODOS: Realizou-se estudo transversal com amostra representativa dos trabalhadores participantes do Programa de Alimentação do Trabalhador no Distrito Federal (n=1.044) que almoçam em 52 Unidades de Alimentação e Nutrição. Foram avaliadas variáveis socioeconômicas e sociodemográficas, medidas antropométricas para o cálculo do Índice de Massa Corporal e o consumo alimentar obtido pelo método da pesagem e pela observação direta da montagem dos pratos. RESULTADOS: Observou-se que 43% da população estudada apresentam excesso de peso, sendo 33,7% com sobrepeso e 9,3% com obesidade, com maiores percentuais no sexo masculino. A mediana do valor energético do almoço foi de 515 Kcal para as mulheres e de 736 Kcal para os homens. O consumo mediano de fibras foi de 6,0 g para o sexo feminino e de 8,3 g para o sexo masculino, e o consumo mediano de colesterol foi acima de 90 mg nos indivíduos com excesso de peso. CONCLUSÕES: Os resultados indicam risco nutricional nessa população, tradicionalmente considerada sadia, devendo a mesma ser alvo de estratégias com foco na promoção da saúde, salientado-se, assim, a atribuição de educador do nutricionista. ___________________________________________________________________________________________________________________ ABSTRACTOBJECTIVE: In the light of the Workers' Food Program (WFP) growth and its recent review of nutritional parameters regulations, the study aimed at evaluating food intake in WFP through dietary assessment of lunch served in the program and workers' nutritional status. METHODS: A cross-sectional study was carried out in a representative sample of workers in Brasília, Federal District, Brazil. A total of 1,044 subjects who had lunch at 52 food and nutrition units were evaluated. Social-economic and demographic data were collected as well as anthropometric measures for calculating the Body Mass Index. Food intake was assessed by dish weight and direct observation of dish composition. RESULTS: Of all subjects, 43% had excess weight, 33.7% were overweight and 9.3% were obese. Males were most affected. Median lunch energy intake was 515 kcal in women and 736 kcal in men. Median dietary fiber intake was 6.0 g among women and 8.3 g among men, and median cholesterol intake was over 90 mg among subjects with excess weight. CONCLUSIONS: The results indicate that the study population who is often seen as healthy is at nutritional risk. Workers in WFP should be targeted for health promotion strategies using especially nutritionists' skills as educators

Sex, income and level of education associated with physical activity level among workers

OBJETIVO: Analisar fatores socioeconômicos e demográfi cos associados ao nível de atividade física de trabalhadores. MÉTODOS: Estudo transversal realizado no Distrito Federal, de 2000 a 2001, com amostra representativa de trabalhadores de ambos os sexos, vinculados ao Programa de Alimentação do Trabalhador, envolvendo 1.044 trabalhadores. Utilizou-se a regressão logística binária para determinação dos possíveis fatores de risco associados ao nível de atividade física e selecionados pelo processo de “backward elimination”. Efeitos interativos das variáveis foram verifi cados no modelo fi nal por meio da razão de chances, para nível de atividade física >1,4. RESULTADOS: O modelo fi nal incluiu o sexo, a renda e a escolaridade. Indivíduos do sexo masculino que cursaram apenas o primeiro grau e ganhavam menos de quatro salários mínimos eram os que tinham mais chances de apresentar nível de atividade física >1,4. A estimativa das razões de chances indicou que os homens tinham cinco vezes mais chances de apresentar nível de atividade física >1,4, níveis inferiores aos das mulheres. Indivíduos que cursaram apenas o primeiro grau e com renda igual ou inferior a quatro salários mínimos tinham duas vezes mais chances de nível de atividade física ≥1,4 do que indivíduos com renda superior a quatro salários mínimos e curso superior ou pós-graduação. CONCLUSÕES: Os resultados indicam que os fatores associados ao nível de atividade física de trabalhadores são: sexo masculino, escolaridade primeiro grau e renda menor que quatro salários mínimos.OBJECTIVE: To analyze socioeconomic and demographic factors associated with physical activity level among workers. METHODS: Cross-sectional study conducted in Brazil’s Federal District, from 2000 to 2001, with a representative sample of 1,044 workers from both sexes, who are covered by the Programa de Alimentação do Trabalhador (Workers’ Food Program). Binary logistic regression was used to determine possible risk factors associated with physical activity level and selected by the backward elimination process. Interactive effects of the variables were verifi ed in the fi nal model by means of the odds ratio for physical activity level >1.4. RESULTS: The fi nal model included sex, income and level of education. Male individuals who only fi nished elementary school and earned less than four Brazilian minimum wages per month were the most likely to show physical activity level ≥1.4. The odds ratio estimate indicated that men were fi ve times more likely to show physical activity level ≥1.4 than women. Individuals who only fi nished elementary school and had an income equal to or below four minimum wages were two times more likely to show physical activity level ≥1.4 than individuals who earned more than four minimum wages and had a university degree or higher. CONCLUSIONS: Results indicate that the factors associated with physical activity level among workers are the following: male, elementary school level, and income below four Brazilian minimum wages per month

Validation of a food frequency questionnaire for the adult population

OBJETIVO: Investigar a validade e a reprodutibilidade de um questionário de freqüência de consumo alimentar desenvolvido para a população adulta. MÉTODOS: Foram entrevistados, em três momentos, 69 indivíduos, de ambos os sexos, freqüentadores de restaurantes industriais em dois órgãos públicos de Brasília, Distrito Federal. Na primeira e terceira entrevistas foram aplicados um recordatório 24 horas e um questionário de freqüência de consumo alimentar, e na segunda entrevista, um recordatório 24 horas. A duração média do estudo foi de 181 dias. Macronutrientes, vitaminas A e C, cálcio, ferro, zinco, colesterol, fibras e energia total foram analisados utilizando-se os coeficientes de correlação intraclasse e de Pearson, este último na forma bruta e deatenuada. RESULTADOS: Quanto à reprodutibilidade, o questionário de freqüência de consumo alimentar obteve desempenho adequado, apresentando resultados acima de 0,7 para lipídeo, colesterol, energia e proteína. Para a validade, os melhores coeficientes deatenuados foram observados para vitamina C (r=0,66), ferro (r=0,58), proteína (r=0,55) e carboidrato (r=0,55) e os piores, para colesterol (r=0,32) e vitamina A (r=0,37). CONCLUSÃO: A obtenção de coeficientes de correlação expressivos para alguns nutrientes indica que este questionário de freqüência de consumo alimentar constitui-se em um bom instrumento de pesquisa para estudos epidemiológicos em população adulta, podendo fornecer informações importantes para a implementação de ações na área de saúde e nutrição.OBJECTIVE: The aim of the present study was to investigate the validity and reproducibility of a food frequency questionnaire developed for the adult population. METHODS: Sixty-nine individuals from both genders who attended industrial restaurants from two government divisions in Brasília, Federal District, Brazil, were interviewed on three different occasions. In the first and third interviews, a 24h recall and a food frequency questionnaire were applied, and in the second interview only a 24h recall was applied. The study lasted 181 days. Macronutrients, vitamins A and C, calcium, iron, zinc, cholesterol, fibers and total energy were analyzed using the intraclass and Pearson's correlation coefficients, this last one in a crude and deattenuated manner. RESULTS: Regarding reproducibility, the food frequency questionnaire provided adequate results, presenting correlation coefficients above 0.7 for lipid, cholesterol, energy and protein. For validity, the best deattenuated coefficients were observed for vitamin C (r=0.66), iron (r=0.58), protein (r=0.55) and carbohydrate (r=0.55) and the worst for cholesterol (r=0.32) and vitamin A (r=0.37). CONCLUSION: The expressive correlation coefficients obtained for some nutrients indicates that this food frequency questionnaire constitutes a good research instrument for epidemiological studies in the adult population, as it can supply important dietary information allowing the implementation of actions in the health and nutrition areas

Generation of induced pluripotent stem cells (iPSC) from an atrial fibrillation patient carrying a KCNA5 p.D322H mutation

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with several cardiac risk factors, but increasing evidences indicated a genetic component. Indeed, genetic variations of the atrial specific KCNA5 gene have been identified in patients with early-onset lone AF. To investigate the molecular mechanisms underlying AF, we reprogrammed to pluripotency polymorphonucleated leukocytes isolated from the blood of a patient carrying a KCNA5 p.D322H mutation, using a commercially available non-integrating system. The generated iPSCs expressed pluripotency markers and differentiated toward cells belonging to the three embryonic germ layers. Moreover, the cells showed a normal karyotype and retained the p.D322H mutation

Avaliação do almoço servido a participantes do programa de alimentação do trabalhador

OBJECTIVE: In the light of the Workers' Food Program (WFP) growth and its recent review of nutritional parameters regulations, the study aimed at evaluating food intake in WFP through dietary assessment of lunch served in the program and workers' nutritional status. METHODS: A cross-sectional study was carried out in a representative sample of workers in Brasília, Federal District, Brazil. A total of 1,044 subjects who had lunch at 52 food and nutrition units were evaluated. Social-economic and demographic data were collected as well as anthropometric measures for calculating the Body Mass Index. Food intake was assessed by dish weight and direct observation of dish composition. RESULTS: Of all subjects, 43% had excess weight, 33.7% were overweight and 9.3% were obese. Males were most affected. Median lunch energy intake was 515 kcal in women and 736 kcal in men. Median dietary fiber intake was 6.0 g among women and 8.3 g among men, and median cholesterol intake was over 90 mg among subjects with excess weight. CONCLUSIONS: The results indicate that the study population who is often seen as healthy is at nutritional risk. Workers in WFP should be targeted for health promotion strategies using especially nutritionists' skills as educators.OBJETIVO: Face à expansão do Programa de Alimentação do Trabalhador no País e sua atualização na normatização dos aspectos nutricionais, foi avaliado o consumo alimentar de trabalhadores participantes do programa, por meio da análise nutricional do almoço servido e do estado nutricional da população atendida. MÉTODOS: Realizou-se estudo transversal com amostra representativa dos trabalhadores participantes do Programa de Alimentação do Trabalhador no Distrito Federal (n=1.044) que almoçam em 52 Unidades de Alimentação e Nutrição. Foram avaliadas variáveis socioeconômicas e sociodemográficas, medidas antropométricas para o cálculo do Índice de Massa Corporal e o consumo alimentar obtido pelo método da pesagem e pela observação direta da montagem dos pratos. RESULTADOS: Observou-se que 43% da população estudada apresentam excesso de peso, sendo 33,7% com sobrepeso e 9,3% com obesidade, com maiores percentuais no sexo masculino. A mediana do valor energético do almoço foi de 515 Kcal para as mulheres e de 736 Kcal para os homens. O consumo mediano de fibras foi de 6,0 g para o sexo feminino e de 8,3 g para o sexo masculino, e o consumo mediano de colesterol foi acima de 90 mg nos indivíduos com excesso de peso. CONCLUSÕES: Os resultados indicam risco nutricional nessa população, tradicionalmente considerada sadia, devendo a mesma ser alvo de estratégias com foco na promoção da saúde, salientado-se, assim, a atribuição de educador do nutricionista

P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice

Introduction: sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: sepsis was induced in wild-type (WT), P2X7−/− , and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7−/− sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba−1 ) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7−/− sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: the modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsisassociated encephalopathy, being considered an important therapeutic target