Exome Sequencing Implicates Ancestry-Related Mendelian Variation at SYNE1 in Childhood-Onset Essential Hypertension

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date. Here, we identify recessive segregation of rare and putatively damaging missense variation in the spectrin domain of spectrin repeat containing nuclear envelope protein 1 (SYNE1), a cardiovascular candidate gene, in 3 of 16 families with early-onset COEH without an antecedent family history. By leveraging exome sequence data from an additional 48 COEH families, 1,700 in-house trios, and publicly available data sets, we demonstrate that compound heterozygous SYNE1 variation in these COEH individuals occurred more often than expected by chance and that this class of biallelic rare variation was significantly enriched among individuals of African genetic ancestry. Using in vitro shRNA knockdown of SYNE1, we show that reduced SYNE1 expression resulted in a substantial decrease in the elasticity of smooth muscle vascular cells that could be rescued by pharmacological inhibition of the downstream RhoA/Rho-associated protein kinase pathway. These results provide insights into the molecular genetics and underlying pathophysiology of COEH and suggest a role for precision therapeutics in the future

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Using a bioinformatics approach to identify genes that have possible candidacy of association with retinitis pigmentosa: GeneWeaver

Retinitis pigmentosa (RP) is a retinal degenerative disorder that affects about 1 in 3,000 people. The disease is genetic in cause, and currently there is no cure. The genetic cause of the disease may be contributed to one of several different genes, underscoring the complex genetic underpinnings of this disease. The information required to determine which genes are potentially causative for RP may exist, but it is difficult to determine which genes are most suitable for study because of the immense wealth and breadth of available information. In other words, large-scale heterogeneous species-specific data often obfuscates the true causative genetic background of RP. In this study we describe a method of identifying genes that may contribute to RP using the bioinformatics techniques of graph theory and database utilization. We report a potential ranked list of genes in which disruptions are likely causative of RP

A Descriptive Study of Digital Stress among Employees Who Adopt a Hybrid Working System at PT.XYZ

One consequence of pandemic COVID-19 was that most companies implemented a hybrid working system (a mixture of work from home and office). During this period, employees at PT. XYZ who adopted the hybrid working system, experienced stress that caused by the usage of massive information and communication technology, that resulted in psychological detrimental effects. The objective of this study was to investigate the level and the types of digital stresses that faced by those employees. This research took place in March 2022, used a quantitative, online survey-based questionnaire named Digital Stressors Scale (α = 0.865) consisted of 50 questions with seven-points Likert Scale and convenient sampling technique, involving 107 employees of PT. XYZ as the participants. Data were then analyzed using descriptive statistics with the help of SPSS software. Result suggested that overall employees faced a high level of digital stress and the highest mean among the 10 dimensions of digital stress was invasion (M = 4.18, SD = 1.47 - stress about the tendency harming their individual personal data). The result is expected to help the management to think of various solutions to curb the problems as to improve the well-being of the employees working at PT. XYZ

Facial attractiveness ratings from video-clips and static images tell the same story.

Most of what we know about what makes a face attractive and why we have the preferences we do is based on attractiveness ratings of static images of faces, usually photographs. However, several reports that such ratings fail to correlate significantly with ratings made to dynamic video clips, which provide richer samples of appearance, challenge the validity of this literature. Here, we tested the validity of attractiveness ratings made to static images, using a substantial sample of male faces. We found that these ratings agreed very strongly with ratings made to videos of these men, despite the presence of much more information in the videos (multiple views, neutral and smiling expressions and speech-related movements). Not surprisingly, given this high agreement, the components of video-attractiveness were also very similar to those reported previously for static-attractiveness. Specifically, averageness, symmetry and masculinity were all significant components of attractiveness rated from videos. Finally, regression analyses yielded very similar effects of attractiveness on success in obtaining sexual partners, whether attractiveness was rated from videos or static images. These results validate the widespread use of attractiveness ratings made to static images in evolutionary and social psychological research. We speculate that this validity may stem from our tendency to make rapid and robust judgements of attractiveness

Avaliação funcional das fraturas intra-articulares do calcâneo tratadas cirurgicamente Functional evaluation of surgically-treated intra-articular fractures of the calcaneus

OBJETIVO: Realizar uma avaliação clínica e funcional das fraturas intra-articulares do calcâneo tratadas cirurgicamente pelo Grupo de Cirurgia do Pé e Tornozelo do Serviço de Ortopedia e Traumatologia do Hospital Universitário Cajuru no período compreendido entre janeiro de 2001 e dezembro de 2006. MÉTODOS: 107 pacientes, com 113 fraturas, foram submetidos ao tratamento conforme a classificação de Essex-Lopresti: nas fraturas tipo língua ou depressão central com cominuição intraarticular utilizaram-se redução aberta e fixação interna com placa para calcâneo (Synthes®) ou duplo H; nas demais fraturas tipo depressão central realizou-se tratamento minimamente invasivo e nas fraturas tipo língua, tratamento percutâneo. Foram avaliados e acompanhados clinicamente, com pontuação na tabela AOFAS, pelo mesmo grupo de cirurgiões. RESULTADOS: Houve 73% de resultados satisfatórios, média de 75,4 pontos, e 27% de insatisfatórios. CONCLUSÃO: A adequada redução das fraturas representa fator importante para que o paciente não tenha dor e edema residual. As fraturas do tipo depressão central foram as que resultaram em menor pontuação funcional. O não restabelecimento do ângulo de Böhler também levou a importantes alterações funcionais.<br>OBJECTIVE: To perform a clinical and functional evaluation of intra-articular fractures of the calcaneus treated surgically by the Group of Foot and Ankle Surgery at the Cajuru University Hospital from January 2001 to December 2006. METHODS: 107 patients, with 113 fractures, were submitted to treatment according to the Essex-Lopresti classification: in the tongue type fractures or central depression fractures with intra-articular comminution, open reduction and internal fixation with calcaneus plates (Synthes®) or Double H were used; for the other central depression type of fractures, the authors resorted to the minimally invasive treatment, and in tongue type fractures, percutaneous treatment was preferred. The patients were evaluated and clinically followed-up by the same group of surgeons, with evaluation scores according to the AOFAS table. RESULTS: 73% of satisfactory results, with a mean of 75.4 score points, and 27% unsatisfactory results. CONCLUSION: Adequate reduction of the fractures is an important factor to prevent pain and residual edema. Central depression type of fractures were those that had the lowest functional score. Non-reestablishment of the Böhler angle also culminated in relevant functional alterations

Perceived barriers and facilitators to physical activity in childhood cancer survivors and their parents: A large-scale interview study from the International PACCS Study

publishedVersio

The gap between expectations and reality: A qualitative study of psychosocial challenges of young childhood cancer survivors from the PACCS study

Objective In this sub-study from the ‘PACCS’ study, we explored the psychosocial experiences of children and adolescents in everyday life post-cancer treatment and the possible factors that can moderate these experiences. Methods This is a qualitative explorative study using semi-structured interviews with 43 childhood cancer survivors between the ages of nine and 18 from Norway and Denmark. We conducted a secondary thematic analysis using Malterud's systematic text condensation. Results Two main themes were identified: ‘The post-treatment gap between expectations and reality’ comprised two subthemes: (1) lack of mastery and feeling different and (2) lack of understanding and acceptance. The second main theme, ‘Managing the gap’, comprised three subthemes: (1) information and knowledge, (2) adjustments and adaptions and (3) social support and openness. The findings reveal that the psychosocial challenges resulted from the remaining ability gap(s). Measures such as tailored information, school adjustments and social support were potential dynamic factors affecting the gap(s) positively or negatively. Psychosocial challenges post-treatment are experiences of lack of acceptance and understanding from others. Conclusion To safeguard a positive transition back to everyday life, health care providers should support the survivors' psychosocial care, including getting back to school and re-entering social interactions