Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Defining children's rights to work and care in Sub-Saharan Africa: tensions and challenges in policy and practice

This chapter explores the spatialities of children's rights through a focus on how children's paid and unpaid work in Sub-Saharan Africa intersects with wider debates about child labor, child domestic work and young caregiving. Several tensions surround the universalist and individualistic nature of the rights discourse in the context of Sub-Saharan Africa and policymakers, practitioners, children and community members have emphasized children's responsibilities to their families and communities, as well as their rights. The limitations of ILO definitions of child labor and child domestic work and UNCRC concerns about 'hazardous' and 'harmful' work are highlighted through examining the situation of children providing unpaid domestic and care support to family members in the private space of their own or a relative's home. Differing perspectives towards young caregiving have been adopted to date by policymakers and practitioners in East Africa, ranging from a child labor/ child protection/ abolitionist approach, to a 'young carers'/ child-centered rights perspective. These differing perspectives influence the level and nature of support and resources that children involved in care work may be able to access. A contextual, multi-sectorial approach to young caregiving is needed that seeks to understand children's, family members' and community members' perceptions of what constitutes inappropriate caring responsibilities within particular cultural contexts and how these should best be alleviated.

A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3

Amelogenesis imperfecta (AI) is a collective term used to describe phenotypically diverse forms of defective tooth enamel development. AI has been reported to exhibit a variety of inheritance patterns, and several loci have been identified that are associated with AI. We have performed a genome-wide scan in a large Brazilian family segregating an autosomal dominant form of AI and mapped a novel locus to 8q24.3. A maximum multipoint LOD score of 7.5 was obtained at marker D8S2334 (146,101,309 bp). The disease locus lies in a 1.9 cM (2.1 Mb) region according to the Rutgers Combined Linkage-Physical map, between a VNTR marker (at 143,988,705 bp) and the telomere (146,274,826 bp). Ten candidate genes were identified based on gene ontology and microarray-facilitated gene selection using the expression of murine orthologues in dental tissue, and examined for the presence of a mutation. However, no causative mutation was identified.

Upplevelsen av motivationsarbete – en studie ur klienters och kontaktpersoners perspektiv på Frösö LVM-hem

Studien undersöker hur klienter och kontaktpersoner upplever motivationsarbetet på Frösö LVM-hem. I studien tillämpades både kvalitativ och kvantitativ metod. I ett första skede genomfördes intervjuer med avdelningsföreståndare på samtliga tre avdelningar på institutionen. Detta intervjumaterial användes för utformandet av enkäter som besvarades separat av klienter och kontaktpersoner. Enkäten mäter upplevelsen av motivationsarbete genom skattning av hur viktiga olika insatser och faktorer är för att klienten skall utveckla motivation till fortsatt frivillig vård, hur dessa insatser och faktorer fungerar på Frösö LVM-hem och i vilken omfattning insatserna tillämpas, samt slutligen klientens egen motivation att fortsätta i frivillig vård. Klientenkäten innehöll dessutom instrumentet SOCRATES, som skattar motivation såsom faser i förändringsprocess. Resultatet visar att båda grupperna är mest tillfredsställda med framtidsplanering och aktiviteter, däremot är de mest otillfredsställda på områdena som handlar om kontaktpersonernas utredningsinsatser och klimatet på avdelningen. Detta kan tyda på att kraftfullare insatser efterfrågas på sistnämnda områden. Den generella värderingen av hela arbetet vid institutionen ges också en positiv bedömning. Studien innehåller också fördjupade analyser t.ex. parvis mellan klient och kontaktperson, och i förhållande till utfallet motivation. Kontaktpersonens förhållningssätt och relationen mellan klient och kontaktperson har det största sambandet med utfallet motivation. Resultaten kan användas i ett pågående utvecklingsarbete vid Frösö LVM-hem om motivationsarbetet.