Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D)

AimsSodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D.MethodsPilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period.ResultsForty-five T2D participants on metformin monotherapy (mean age 57 ± 8 years, duration 7 ± 6 years, HbA1c 7.8 ± 1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride.ConclusionsShort term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN.Clinical trial registration: NCT02973477     

HLA-B27: What is its role in the development of ankylosing spondylitis?

Although the association between HLA-B27 and ankylosing spondylitis (AS) is well established, the mechanism governing this association remains unknown. Although ∼90% of affected individuals possess the HLA-B27 antigen, HLA-B27 is also present in ∼8% of the normal population. This article examines the association by reviewing recent literature. Theories proposed have ranged from HLA-B27's possible role as a marker for an AS susceptibility gene to the possibility of HLA-B27 being a direct contributor to disease. Theories suggest the presence of pathogenic and benign forms of the antigen, as well as interaction with genetic and environmental factors in disease development. Recent investigations have focused on a link with Klebsiella and its role in a “cross-reactive” mechanism with HLA-B27 in AS development. Studies to date have not provided conclusive evidence on the exact mechanism by which HLA-B27 predisposes individuals to the development of disease. The importance of isolating a specific causative agent for AS is discussed.     

兔转化生长因子-β2基因的克隆及其表达的检测

目的　克隆兔转化生长因子 β2 (TGF β2 )基因 ,并获得其在兔重要脏器及角膜中的表达。方法　利用不同物种的相似序列设计相关引物 ,制备兔肝组织的RNA并逆转录 ,RT PCR技术获得TGF β2 基因蛋白编码区序列后克隆 ,RT PCR半定量及荧光定量PCR检测TGF β2 在兔重要脏器及角膜中的表达。结果　成功地克隆了兔TGF β2 的蛋白编码区序列 ,测序证实和人、大鼠及小鼠具有高度的同源性 ,含有TGF β2 的保守结构域 ,TGF β2 基因在兔心脏、肝脏、脾脏、肺脏、肾脏、肾上腺和角膜组织中均有不同程度表达。结论　利用同源序列克隆进化上保守的基因是简捷快速的方法。获得兔TGF β2 的基因有助于进一步研究其在机体重要脏器纤维化、肿瘤以及角膜疾病中的作用     

Ability and willingness to pay for family planning services in low resource settings: evidence from an operational research

ObjectiveThis paper establishes levels and patterns of ability and willingness to pay (AWTP) for contraceptives, and associated factors.Study designA three-stage cluster and stratified sampling was applied in selection of enumeration areas, households and individuals in a baseline survey for a 5-year Family planning programme. Multivariable linear and modified Poisson regressions are used to establish factors associated with AWTP.ResultsAbility to pay was higher among men (84%) than women (52%). A high proportion of women (96%) and men (82%) were able to pay at least Ug Shs 1000 ($0.27) for FP services while 93% of women and 83% of men who had never used FP services will in future be able to pay for FP services costed at least Shs 2000 ($0.55). The factors independently associated with AWTP were lower age group (<25 years), residence in urban areas, attainment of higher education level, and higher wealth quintiles.ConclusionAWTP for FP services varied by different measures. Setting the cost of FP services at Shs 1000 ($0.27) will attract almost all women (96%) and most of men (82%). Key determinants of low AWTP include residence in poor regions, being from rural areas and lack of/low education.Implications statement: Private providers should institute price discrimination for FP services by region, gender and socioeconomic levels. More economic empowerment for disadvantaged populations is needed if the country is to realise higher contraceptive uptake. More support for total market approach for FP services needed.     

Executive dysfunction and attention contribute to gait interference in ‘off’ state Parkinson's Disease

Motor and cognitive processes are required for successful ‘real world’ walking. We explored the specific contribution of motor function, executive function, and attention to functional gait performance in people with Parkinson's Disease (PD) when ‘off’ medication. Twenty-nine people with PD wearing an accelerometer were tested in their home whilst walking under four task conditions. Explanatory characteristics included age, motor function, executive function, sustained attention and divided attention. Repeated measures ANOVA compared gait speed under different task conditions. Multiple regression analysis explored the effect of characteristics on gait speed and gait interference (difference between dual and single task). Gait performance deteriorated under complex conditions (F = 51.0, P < .001). Motor function and attention explained up to 65% variance in gait speed. Motor function, attention and executive function explained up to 66% variance in gait interference. Sustained attention explained up to 10% variance in gait speed; executive function explained up to 21% variance in gait interference and divided attention explained up to 22% variance in gait interference. Motor function, executive function and attention contribute to gait speed and gait interference in PD during a functional walking task whilst ‘off’ medication. When both executive function and attention are included as explanatory variables, attention discriminates gait performance more effectively. Whilst both contribute to functional gait, they are used selectively to optimise performance for different conditions and to meet complex task requirements.     

Investigation into the multidimensional genetic basis of drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe blistering skin diseases, which are mainly caused by drugs. The two idiosyncratic conditions are distinguished on the basis of the degree of blistering, possibly representing diseases at different ends of the same spectrum. A genetic predisposition has been postulated. METHOD: We have retrospectively identified a heterogeneous group of patients with SJS and TEN (n = 73 cases, 141 matched controls) induced by a number of marketed drugs and evaluated effector candidate genetic predisposition. We have used a multivariate genetic analysis method for the first time to handle the heterogeneity of clinical presentation, drug etiology, ethnicity and gender in these adverse events. RESULTS: Our results show that predisposition varied according to ethnicity. There was a correlation for SJS with HLA-B*44, DRB1*07 and with the MHC ancestral 57.1 haplotype (and its constituents) in subjects who self-reported as Caucasians, which did not differ with gender. The HLA-DRB and -DRQ genetic predisposition to SJS seemed to be distinct from that of TEN, but further work is needed for both conditions to identify the causal variants. No conclusion concerning correlations with different drugs could be made because of small numbers in each drug group. CONCLUSION: This study stresses the importance of accurate clinical phenotyping, exemplifies a novel analysis method to dissect complicated samples and calls for collaborative prospective studies.