Using psychological theory to understand the clinical management of type 2 diabetes in Primary Care: a comparison across two European countries

Background  

Long term management of patients with Type 2 diabetes is well established within Primary Care. However, despite extensive efforts to implement high quality care both service provision and patient health outcomes remain sub-optimal. Several recent studies suggest that psychological theories about individuals' behaviour can provide a valuable framework for understanding generalisable factors underlying health professionals' clinical behaviour. In the context of the team management of chronic disease such as diabetes, however, the application of such models is less well established. The aim of this study was to identify motivational factors underlying health professional teams' clinical management of diabetes using a psychological model of human behaviour.     

C2orf37 mutational spectrum in Woodhouse–Sakati syndrome patients

Alazami AM, Schneider SA, Bonneau D, Pasquier L, Carecchio M, Kojovic M, Steindl K, de Kerdanet M, Nezarati MM, Bhatia KP, Degos B, Goh E, Alkuraya FS. C2orf37 mutational spectrum in Woodhouse–Sakati syndrome patients. Woodhouse–Sakati syndrome (WSS) is a rare autosomal recessive disorder that encompasses hypogonadism, deafness, alopecia, mental retardation, diabetes mellitus and progressive extrapyramidal defects. The syndrome is caused by mutation of the C2orf37 gene. Here we studied a cohort of seven new cases from three ethnic backgrounds, presenting with the hallmarks of WSS, in an effort to extend the mutational spectrum of this disorder. Genetic analysis revealed a novel mutation in each of the four families investigated, of which three were nonsense mutations and the fourth was a splice site ablation. We also examined a separate collection of 11 cases presenting with deafness and dystonia, two constituents of WSS, but found no pathogenic changes. This study doubles the number of known mutations for this disorder, confirms that truncating mutations in C2orf37 are the only known cause of WSS, and suggests that mutations in this gene do not contribute significantly to cases presenting with isolated elements of WSS such as deafness and dystonia. The lack of correlation between clinically expressivity of WSS and the site of the eight truncating mutations strongly supports that they are equally null, while the intrafamilial variability argues for an important role of modifiers in this disease.     

Positron emission tomography imaging of tissue P-glycoprotein activity during pregnancy in the non-human primate

Background and purpose:

Changes in tissue P-glycoprotein (P-gp) activity during pregnancy could affect the pharmacokinetics and thus the efficacy and toxicity of many drugs. Therefore, using positron emission tomography (PET) imaging, we tested whether gestational age affects tissue P-gp activity in the pregnant non-human primate, Macaca nemestrina.

Experimental approach:

Mid-gestational (day 75 ± 13, n= 7) and late-gestational (day 150 ± 10, n= 5) age macaques were imaged after administration of a prototypic P-gp substrate, ¹¹C-verapamil (13.7–75.4 MBq·kg⁻¹), before and during intravenous infusion of a P-gp inhibitor, cyclosporin A (CsA) (12 or 24 mg·kg⁻¹·h⁻¹). Accumulation of radioactivity in the fetal liver served as a reporter of placental P-gp activity. P-gp activity was expressed as CsA-induced percent change in the ratio of the area (0–9 min) under the ¹¹C-radioactivity concentration–time curve in the tissue (AUC_tissue) to that in the maternal plasma (AUC_plasma).

Key results:

The CsA-induced change in AUC_{fetal liver}/AUC_{maternalplasma} of ¹¹C-radioactivity significantly increased from mid- (35 ± 25%) to late gestation (125 ± 66%). Likewise, the CsA-induced change in AUC_{maternal brain}/AUC_plasma increased from mid- (172 ± 80%) to late gestation (337 ± 148%). The AUC ratio for the other maternal tissues was not significantly affected. Neither the CsA blood concentrations nor the level of circulating ¹¹C-verapamil metabolites were significantly affected by gestational age.

Conclusions and implications:

P-gp activity at the blood–brain barrier and the placental barrier in the macaque increased with gestational age. If replicated in humans, the exposure of the fetus and maternal brain to P-gp substrate drugs, and therefore their efficacy and toxicity, will change during pregnancy.     

三维肛管直肠超声在肛管直肠疾病中的应用

肛管直肠超声可用来诊断多种肛管直肠良、恶性疾病。近几年来．该技术取得了长足进步．其应用360度旋转高频（6．16MHZ）探头（焦距2．8～6．2cm）,无需转动探头便可获得高清晰的肛管直肠三维结构图。位于探头远端的换能晶片向近端边旋转边移动,持续55S．可获得长约6cm的图像。这个图像是将连续的0．2mm层厚轴向切面通过容积再现技术合成的高清晰的三维数字立体图像。其拥有多个视角（同时4～6个视野）．可同时观察多个解剖平面．进行低亮度、高对比度调整,可形成半透明暗腔。     

Identification of three novel ECEL1 mutations in three families with distal arthrogryposis type 5D

Arthrogryposis refers to congenital contracture in at least two different body parts. When distal joints are primarily involved, the term distal arthrogryposis (DA) is used. The recognition of clinically distinct subtypes of DA has proven very useful in mapping the disease genes for this genetically heterogeneous condition. DA5D is characterized by ocular involvement usually in the form of ptosis and incomitant strabismus, but extraocular manifestations have also been reported. In a multiplex consanguineous family with DA5D, we combined autozygosity mapping and exome sequencing to identify a novel mutation in ECEL1. This was followed by targeted sequencing of this gene in another two extended consanguineous family with the same phenotype, which revealed two additional novel homozygous mutations. Our results support the recent identification of mutations in ECEL1 as a disease gene in DA5D and expand the clinical and allelic spectrum of this condition.     

The M694V mutation in Armenian‐Americans: a 10‐year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA

Familial Mediterranean fever (FMF), inherited in an autosomal recessive manner, is a systemic auto‐inflammatory disorder characterized by recurrent attacks of fever with peritonitis, pleuritis, synovitis and erysipeloid rash. The marenostrin‐encoding fever (MEFV) gene, located on chromosome 16p13.3, is the only gene in which mutations are currently known to cause FMF. To correlate specific genotypes with adverse phenotypes of affected populations residing in the Western United States, a retrospective case series review was conducted of all MEFV gene mutation testing completed at UCLA Clinical Molecular Diagnostic Laboratory between February 2002 and February 2012, followed by clinical chart review of all subjects who either have a single or double mutation. All 12 common mutations in the MEFV gene were analyzed and the M694V variant was found to be associated with an adverse FMF clinical outcome in the Armenian‐American population, manifested by earlier onset of disease, increased severity of disease, and renal amyloidosis.     

Mutations in ALDH1A3 cause microphthalmia

Microphthalmia is an important inborn error of eye development that can be associated with multisystem involvement. Anophthalmia is more severe and rarer. Single mutations in an expanding list of genes are known to cause this spectrum of anomaly. In one branch of a multiplex family with microphthalmia and anophthalmia, autozygome analysis excluded all known microphthalmia genes at the time of doing this study. Exome sequencing and autozygome filtration identified a novel homozygous variant in ALDH1A3. Subsequently, we identified another homozygous variant in 2 of the 10 probands with microphthalmia we specifically screened for mutations in ALDH1A3. Interestingly, the other branch of the original family was found to segregate anophthalmia/syndactyly with a novel homozygous SMOC1 variant. Our data support the very recent and independent identification of ALDH1A3 as a disease gene in microphthalmia. Locus heterogeneity should be considered in consanguineous families even for extremely rare phenotypes.