Conservation of core gene expression in vertebrate tissues

Abstract Background Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates. Results We measured expression of all known and predicted genes across twenty tissues in chicken, frog and pufferfish. By combining the results with human and mouse data and considering only ten common tissues, we have found evidence of conserved expression for more than a third of unique orthologous genes. We find that, on average, transcription factor gene expression is neither more nor less conserved than that of other genes. Strikingly, conservation of expression correlates poorly with the amount of conserved nonexonic sequence, even using a sequence alignment technique that accounts for non-collinearity in conserved elements. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence. Conclusions There are clearly strong evolutionary constraints on tissue-specific gene expression. A major challenge will be to understand the precise mechanisms by which many gene expression patterns remain similar despite extensive cis-regulatory restructuring

Adverse events of special interest following the use of BNT162b2 in adolescents: a population-based retrospective cohort study

Accruing evidence suggests an increased risk of myocarditis in adolescents from messenger RNA COVID-19 vaccines. However, other potential adverse events remain under-researched. We conducted a retrospective cohort study of adolescents aged 12–18 with a territory-wide electronic healthcare database of the Hong Kong population linked with population-based vaccination records and supplemented with age- and sex-specific population numbers. Two age- and sex-matched retrospective cohorts were formed to observe 28 days following the first and second doses of BNT162b2 and estimate the age- and sex-adjusted incidence rate ratios between the vaccinated and unvaccinated. Thirty AESIs adapted from the World Health Organization’s Global Advisory Committee on Vaccine Safety were examined. Eventually, the first-dose cohort comprised 274,881 adolescents (50.25% received the first dose) and the second-dose cohort 237,964 (50.29% received the second dose). Ninety-four (34.2 per 100,000 persons) adolescents in the first-dose cohort and 130 (54.6 per 100,000 persons) in the second-dose cohort experienced ≥1 AESIs. There were no statistically significant differences in the risk of any AESI associated with BNT162b2 except myocarditis [first-dose cohort: incidence rate ratio (IRR) = 9.15, 95% confidence interval (CI) 1.14–73.16; second-dose cohort: IRR = 29.61, 95% CI 4.04–217.07] and sleeping disturbances/disorders after the second dose (IRR = 2.06, 95% CI 1.01–4.24). Sensitivity analysis showed that, with myocarditis excluded as AESIs, no significantly elevated risk of AESIs as a composite outcome associated with vaccination was observed (P = 0.195). To conclude, the overall absolute risk of AESIs was low with no evidence of an increased risk of AESIs except myocarditis and sleeping disturbances/disorders

Treatment with Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) and the Risk of All-Cause Poisoning in Children and Adolescents:A Self-Controlled Case Series Study

BACKGROUND: Children and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning. METHODS: Patients aged 5–18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods). RESULTS: 42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33–5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06–4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males. CONCLUSIONS: The risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40263-021-00824-x

Quantification of injury burden using multiple data sources: a longitudinal study

Quantification of injury burden is vital for injury prevention, as it provides a guide for setting policies and priorities. This study generated a set of Hong Kong specific disability weights (DWs) derived from patient experiences and hospital records. Patients were recruited from the Accident and Emergency Department (AED) of three major trauma centers in Hong Kong between September 2014 and December 2015 and subsequently interviewed with a focus on health-related quality of life at most three times over a 12-month period. These patient-reported data were then used for estimation of DWs. The burden of injury was determined using the mortality and inpatient data from 2001 to 2012 and then compared with those reported in the UK Burden of Injury (UKBOI) and global burden of diseases (GBD) studies. There were 22,856 mortality cases and 817,953 morbidity cases caused by injuries, in total contributing to 1,027,641 disability-adjusted life years (DALYs) in the 12-year study timeframe. Estimates for DALYs per 100,000 in Hong Kong amounted to 1192, compared with 2924 in UKBOI and 3459 in GBD. Our findings support the use of multiple data sources including patient-reported data and hospital records for estimation of injury burden

Reply to: Association Between Alendronate and All-Cause Mortality and Cardiovascular Mortality Among Hip Fracture: An Alternative Explanation.

To the Editor: We are thankful to Prof. Nguyen and Dr. Tran for their interest in our study and we appreciate the opportunity to respond to their comments. As Prof. Nguyen and Dr. Tran suggested that censoring patients at the time of switching medications might have inflated the effect size, we investigated this potential bias by excluding patients with switching of medications. Of the 3,081 alendronate-treated patients, 281 patients (9.1%) switched the therapy during the study period. After excluding these patients, we observed similar findings (Table), suggesting that bias due to treatment of censoring data should be minimal in our study

Nonapeptide influences on social behaviour: effects of vasotocin and isotocin on shoaling and interaction in zebrafish

Nonapeptides are important regulators of social behaviour across vertebrate taxa. While their role in simple grouping behaviour has been explored in estrildid finches, other taxa are understudied, prompting us to investigate nonapeptide influences on shoaling behaviour in zebrafish. Subjects received injections of isotocin, an isotocin antagonist, vasotocin, a vasotocin antagonist, or saline, followed by a test of grouping behaviour. Vasotocin decreased social interaction with the shoal. Unexpectedly, the vasotocin antagonist also reduced social interaction with the shoal, as well as general shoaling behaviour. Isotocin and its antagonist had minimal effects on grouping behaviours. These results suggest social interaction and shoaling are discrete aspects of sociality differentially influenced by vasotocin, although we cannot discount possible anxiogenic effects of vasotocin. Contrasting these results with studies in other systems demonstrates that each nonapeptide’s role in social behaviour varies across taxa, and cautions against a simplistic characterisation of nonapeptides as prosocial regulators of behaviour

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.</p

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.</p

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.</p

Stress ocupacional e alteração do Estatuto da Carreira Docente português

Este estudo foi realizado com 1162 professores, tendo como objetivo analisar a experiência de stress e a síndrome de “burnout”, antes a após a alteração do Estatuto da Carreira Docente em Portugal. Assim, foram efetuadas duas avaliações em momentos temporais distintos, assumindo-se um plano transversal de recolha de dados (2004/2005, n=689 e 2008/2009, n=473). O protocolo de avaliação incluiu medidas de fontes de stress (Questionário de Stress nos Professores, Gomes, Silva, Mourisco, Mota, & Montenegro, 2006) e de “burnout” (Inventário de “Burnout” de Maslach – Versão para Professores, Maslach, Jackson, & Leiter, 1996; Maslach, Jackson, & Schwab, 1996, Adaptação de Gomes et al., 2006). Os resultados indicaram que a experiência de stress e de “burnout” aumentou entre as duas avaliações, verificando-se em 2008/2009 aumentos em áreas relacionadas com as pressões de tempo/excesso de trabalho e com o trabalho burocrático/administrativo e, inversamente, diminuições em áreas relacionadas com as diferentes capacidades e motivações dos alunos. Quanto à predição da síndrome de “burnout”, não se verificaram alterações substanciais nas variáveis preditoras nos dois momentos. Em síntese, os resultados indicaram aumentos nas exigências profissionais dos professores, mas não se pode afirmar que tal se deva às alterações do Estatuto da Carreira Docente uma vez que não observámos alterações no stress associado à carreira docente.(undefined