Exocrine Proteins Including Trypsin(ogen) as a Key Biomarker in Type 1 Diabetes

   Objective Proteomic profiling can identify useful biomarkers. Monozygotic(MZ) twins, discordant for a condition represent an ideal test population. We aimed to investigate and validate proteomic profiling in twins with type 1 diabetes and in other well characterised cohorts. Research Design and Methods A broad, multiplex analysis of 4068 proteins in sera from MZ twins concordant (n=43) and discordant for type 1 diabetes (n=27) identified major differences which were subsequently validated by a trypsin(ogen) assay in MZ pairs concordant (n=39) and discordant (n=42) for type 1 diabetes, individuals at-risk (n=195) and with type 1 diabetes (n=990), as well as with non-insulin requiring adult-onset diabetes diagnosed as either autoimmune (n=96) or type 2 (n=291). Results Proteomic analysis identified major differences between exocrine enzyme levels in discordant MZ twin pairs despite strong correlation between twins, whether concordant or discordant for type 1 diabetes (p Conclusions Type 1 diabetes is associated with altered exocrine function, even before onset. Twin data suggest roles for genetic and non-genetically determined factors. Exocrine/endocrine interactions are important under-investigated factors in type 1 diabetes.</p

Southern Ocean phytoplankton dynamics and carbon export: insights from a seasonal cycle approach

Quantifying the strength and efficiency of the Southern Ocean biological carbon pump (BCP) and its response to predicted changes in the Earth's climate is fundamental to our ability to predict long-term changes in the global carbon cycle and, by extension, the impact of continued anthropogenic perturbation of atmospheric CO2. There is little agreement, however, in climate model projections of the sensitivity of the Southern Ocean BCP to climate change, with a lack of consensus in even the direction of predicted change, highlighting a gap in our understanding of a major planetary carbon flux. In this review, we summarize relevant research that highlights the important role of fine-scale dynamics (both temporal and spatial) that link physical forcing mechanisms to biogeochemical responses that impact the characteristics of the seasonal cycle of phytoplankton and by extension the BCP. This approach highlights the potential for integrating autonomous and remote sensing observations of fine scale dynamics to derive regionally optimized biogeochemical parameterizations for Southern Ocean models. Ongoing development in both the observational and modelling fields will generate new insights into Southern Ocean ecosystem function for improved predictions of the sensitivity of the Southern Ocean BCP to climate change. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'

Coital Experience Among Adolescents in Three Social-Educational Groups in Urban Chiang Mai, Thailand

This article compares coital experience of Chiang Mai 17–20-year-olds who were: (1) out-of-school; (2) studying at vocational schools; and (3) studying at general schools or university. Four-fifths, two-thirds and one-third, respectively, of males in these groups had had intercourse, compared to 53, 62 and 15 per cent of females. The gender difference for general school/university students, but not vocational school students, probably reflects HIV/AIDS refocusing male sexual initiation away from commercial sex workers. Vocational school females may have been disproportionately affected. Loss of virginity was associated, for both sexes, with social-educational background and lifestyle, and was less likely in certain minority ethnic groups. Among males, it was also associated with age and parental marital dissolution, and among females, with independent living and parental disharmony. Within social-educational groups, lifestyle variables dominated, but among general school/university students, parental marital dissolution (for males) and disharmony (for females) were also important, and Chinese ethnicity deterred male sexual experimentation

Designing an implementation science clinical trial to integrate hypertension and cardiovascular diseases care into existing HIV services package in Botswana (InterCARE)

Background: Despite success in HIV treatment, diagnosis and management of hypertension (HTN) and cardiovascular disease (CVD) remains suboptimal among people living with HIV (PLWH) in Botswana, with an overall HTN control of only 19% compared to 98% HIV viral suppressed. These gaps persist despite CVD primary care national guidelines and availability of free healthcare including antihypertensive medications. Our study aims to develop and test strategies to close the HTN care gap in PLWH, through integration into HIV care, leveraging the successful national HIV care and treatment program and strategies. Methods: The InterCARE trial is a cluster randomized controlled hybrid type 2 effectiveness-implementation trial at 14 sites designed to enroll 4652 adults living with HIV and HTN plus up to 2326 treatment partners. Primary outcomes included effectiveness (HTN control) and implementation outcomes using the Reach Effectiveness Adoption Implementation and Maintenance framework, with explanatory mixed methods used to understand variability in outcomes. InterCARE trial’s main strategies include healthcare worker HTN and CVD care training plus long-term practice facilitation, electronic health record (EHR) documentation of key indicators and use of reminders, and use of treatment partners to provide social support to people living with HIV and HTN. InterCARE started with formative research to identify contextual factors influencing care gaps using the Consolidated Framework for Implementation Research. Results were used to adapt initial and develop additional implementation strategies to address barriers and leverage facilitators. The package was pilot tested in two clinics, with findings used to further adapt or add strategies for the clinical trial. Discussion: If successful, the InterCARE model can be scaled up to HIV clinics nationwide to improve diagnosis, management, and support in Botswana. The trial will provide insights for scale-up of HTN integration into HIV care in the region. Trial registration: ClinicalTrials.gov reference NCT05414526. Registered 18 May 2022, https://clinicaltrials.gov/study/NCT05414526?term=NCT05414526.&rank=1