The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals

J. Kaprio, S. Ripatti ja M.-L. Lokki työryhmien jäseniä.Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Secrets, shame and guilt: HIV disclosure in rural Chinese families from the perspective of caregivers

This in-depth ethnographic study examines the processes, barriers and impacts experienced by Mainland Chinese caregivers residing in rural Yunnan for disclosing HIV status to their adolescents born with the infection and other community members. In particular, highlighted are their associated personal, social, relational and cultural vulnerabilities. A purposeful sample of 13 pairs of HIV-born adolescents between the ages of 11–19 years and their primary caregivers were recruited in December 2014. The Conceptual Model Sexual Health Disclosure (CMSHD) was modified with Chinese culturally specific adaptation to guide the exploration of the complex aspects of the adolescents and caregiver’s relationships. All interviews were audiotaped, transcribed verbatim and then translated into English. Complex sociocultural interactions emerging in these dyadic interviews included guilt, shame, unintended disclosure, the need for secrecy, perceived stigma, ‘loss of face’, protection of parents, inability to support their families and deep concerns over lineage and future marriage prospects amongst the parents, which had significant psychosocial and even physical impacts for these adolescents born with HIV and their families. Frontline health-care workers and HIV peer support programs are recommended to counteract China’s current top-down biomedical disease-related approach to health services. It is crucial to provide instrumental avenues of confidential psychosocial support including disclosure approaches for caregivers of HIV positive adolescents within a uniquely Chinese cultural context

The safe use of dating applications among men who have sex with men:A study protocol for a randomised controlled trial to evaluate an interactive web-based intervention to reduce risky sexual behaviours

BACKGROUND: Notably, both international and local studies have found a high prevalence of sexually transmitted infections (STIs) and risky sexual behaviours, such as condomless anal sex, substance misuse in conjunction with sex ('chemsex') and group sex, among men who have sex with men (MSM) dating application (app) users. Although the use of dating apps is an emerging sexual risk factor, little effort has been expended on the promotion of safe sex and good sexual health among the users of those apps. Therefore, the aim of the proposed study is to develop and evaluate the effectiveness of an interactive web-based intervention in improving the sexual health of MSM dating app users in Hong Kong. METHODS: A two-armed randomised controlled trial will be conducted. Chinese MSM dating app users will be recruited and randomly allocated into either the intervention (n = 200) or control group (n = 200). Subjects in the intervention group will receive the web-based intervention containing interactive content that (1) encourages a positive attitude towards consistent condom use and HIV/STI testing and negative attitude towards chemsex and group sex; (2) positions condom use and regular HIV/STI testing as normative; and (3) targets improved perceived self-efficacy concerning condom use and negotiation and HIV/STI testing. The control group will receive only web-based information without sexual health components. Subjects in both groups will be evaluated at baseline and three and 6 months after baseline. The primary outcome will be the frequency of condomless anal sex in the past 3 months. DISCUSSION: The proposed study will aid development of culturally relevant health promotion programmes aimed at minimising the potential harm of dating app use and promoting the sexual health of MSM dating app users. The web-based intervention, if found successful, will have important clinical and policy implications, as it can be adopted by the government and non-governmental organisations targeting MSM. Moreover, the proposed intervention can reach many MSM at relatively low cost, and thus has the potential to check the burgeoning HIV/STI epidemic among MSM in Hong Kong in a cost-effective manner. TRIAL REGISTRATION: International standard randomized controlled trial number (ISRCTN) registry: ISRCTN16681863 registered on 28 April 2020