Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance

ObjectivesThis study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.BackgroundExperimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.MethodsThe study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.ResultsMedian plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m² vs. 82 ± 15 ml/m²; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.ConclusionsOnly primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).     

Mid‐term results of bariatric surgery in morbidly obese Japanese patients with slow progressive autoimmune diabetes

Introduction

Bariatric surgery is recognized as an effective treatment for type 2 diabetes mellitus, but data on its efficacy for type 1 diabetes mellitus, especially slowly progressive insulin‐dependent diabetes mellitus, are limited.

Methods

We investigated five Japanese patients with slowly progressive insulin‐dependent diabetes mellitus who underwent bariatric surgery at our center.

Results

Five morbidly obese glutamic acid decarboxylase antibody‐positive diabetic patients underwent two different types of bariatric surgery. The mean titer of anti‐glutamic acid decarboxylase antibody was 4.6 U/mL, and the mean preoperative bodyweight and BMI were 113 kg and 39.6 kg/m², respectively. The mean hemoglobin A1c was 8.4%. The mean fasting serum C‐peptide was 5.0 ng/mL. Laparoscopic sleeve gastrectomy was performed in two patients, while laparoscopic sleeve gastrectomy with duodenojejunal bypass was performed in three patients. At one year after surgery, the mean bodyweight and BMI significantly dropped, and the mean percentage of excess weight loss was 96.4%. The mean hemoglobin A1c was 5.7%. This favorable trend was maintained at mid‐term.

Conclusion

Bariatric surgery for morbidly obese patients with anti‐glutamic acid decarboxylase antibody–positive type 1 diabetes mellitus, especially slow progressive autoimmune diabetes, seemed effective in achieving mid‐term glycemic control. Longer follow‐up with a larger number of patients, as well as validation with more advanced patients with slowly progressive insulin‐dependent diabetes mellitus, will be needed.

     

Utility of ultrasound for body fat assessment: validity and reliability compared to a multicompartment criterion

Measurement of body composition to assess health risk and prevention is expanding. Accurate portable techniques are needed to facilitate use in clinical settings. This study evaluated the accuracy and repeatability of a portable ultrasound (US) in comparison with a four‐compartment criterion for per cent body fat (%Fat) in overweight/obese adults. Fifty‐one participants (mean ± SD; age: 37·2 ± 11·3 years; BMI: 31·6 ± 5·2 kg m^?2) were measured for %Fat using US (GE Logiq‐e) and skinfolds. A subset of 36 participants completed a second day of the same measurements, to determine reliability. US and skinfold %Fat were calculated using the seven‐site Jackson–Pollock equation. The Wang 4C model was used as the criterion method for %Fat. Compared to a gold standard criterion, US %Fat (36·4 ± 11·8%; P = 0·001; standard error of estimate [SEE] = 3·5%) was significantly higher than the criterion (33·0 ± 8·0%), but not different than skinfolds (35·3 ± 5·9%; P = 0·836; SEE = 4·5%). US resulted in good reliability, with no significant differences from Day 1 (39·95 ± 15·37%) to Day 2 (40·01 ± 15·42%). Relative consistency was 0·96, and standard error of measure was 0·94%. Although US overpredicted %Fat compared to the criterion, a moderate SEE for US is suggestive of a practical assessment tool in overweight individuals. %Fat differences reported from these field‐based techniques are less than reported by other single‐measurement laboratory methods and therefore may have utility in a clinical setting. This technique may also accurately track changes.     

Endogenous Pain Modulation Induced by Extrinsic and Intrinsic Psychological Threat in Healthy Individuals

Many factors interact to influence threat perception and the subsequent experience of pain. This study investigated the effect of observing pain (extrinsic threat) and intrinsic threat of pain to oneself on pressure pain threshold (PPT). Forty socially connected pairs of healthy volunteers were threat-primed and randomly allocated to experimental or control roles. An experimental pain modulation paradigm was applied, with non-nociceptive threat cues used as conditioning stimuli. In substudy 1, the extrinsic threat to the experimental participant was observation of the control partner in pain. The control participant underwent hand immersion in noxious and non-noxious water baths in randomized order. Change in the observing participant's PPT from baseline to mid- and postimmersion was calculated. A significant interaction was found for PPT between conditions and test time (F_2,78?=?24.9, P?<?.005). PPT increased by 23.6%?±?19.3% between baseline and during hand immersion (F_1,39?=?43.7, P?<?.005). Substudy 2 investigated threat of imminent pain to self. After a 15-minute break, the experimental participant's PPT was retested (“baseline 2”). Threat was primed by suggestion of whole arm immersion in an icier, larger water bath. PPT was tested immediately before anticipated arm immersion, after which the experiment ended. A significant increase in PPT between “baseline 2” and “pre-immersion” was seen (t?=??7.6, P?=?.005), a pain modulatory effect of 25.8?±?20.7%. Extrinsic and intrinsic threat of pain, in the absence of any afferent input therefore influences pain modulation. This may need to be considered in studies that use noxious afferent input with populations who show dysfunctional pain modulation.

强化健康教育干预对妊娠期糖尿病患者血糖及妊娠结局的影响评价

目的:探讨强化健康教育干预对妊娠期糖尿病(GDM)患者血糖及妊娠结局的影响.方法:选取2013年1月～2014年1月该院收治的GDM孕妇98例,随机分为实验组和对照组,每组各49例.对照组孕妇给予常规健康教育干预,实验组孕妇给予强化健康教育干预,通过分析两组血糖及分娩后母婴的结局情况对干预结果进行评估.结果:两组孕妇在经过为期3个月的健康教育干预后,均取得相应的效果,实验组孕妇所取得干预效果更为显著,其对GDM知识的认识、生活方式改善程度、早产、产褥感染、分娩后婴儿的结局以及血糖达标程度均优于对照组,两组比较,差异有统计学意义(P＜0.05).结论:对于GDM孕妇给予强化健康教育干预可以有效降低孕妇的血糖、改善妊娠后母婴结局,值得在临床中推广应用.     

Stopped hearts,amputated toes and NASA: contemporary legends among healthy volunteers in US phase I clinical trials

The first stage of testing new pharmaceuticals in humans is referred to as a phase I clinical trial. The purpose of these studies is to test the safety of the drugs and to establish appropriate doses that can later be given to patients. Most of these studies are conducted under controlled, in‐patient conditions using healthy volunteers who are paid for their participation. To explore healthy volunteers’ experiences in clinical trials, an ethnographic study was conducted at six in‐patient phase I clinics in the USA. In addition to the observation of clinic activities (from informed consent procedures to dosing to blood draws), 268 semi‐structured interviews were conducted, 33 with clinic staff and 235 with healthy volunteers. Drawing on this dataset, this article explores healthy volunteers’ exchange of contemporary legends about phase I clinical trials. In addition to potentially scaring the listener and communicating distrust in the medical community, these incredible stories help participants cope with perceived stigma and establish a gradient of risk of trial participation, creating potential boundaries to their participation in medical research. The article argues that contemporary legends play a productive role in society, shaping how people view themselves and others and influencing their decisions about risky activities.     

Characteristics of Youth Food Preparation in Low-Income,African American Homes: Associations with Healthy Eating Index Scores

This study explores food preparation behaviors, including types of food prepared, methods of preparation, and frequency of preparation of low-income urban African American youth ages 9–15 in Baltimore City (n = 289) and analyzes a potential association to diet quality as measured through Healthy Eating Index 2010 (HEI) scores. Overall, the youth prepared their own food 6.7 ± 0.33 times per week without significant differences between age groups or genders as measured through pairwise comparison of means. Cereal, noodles, and sandwiches were amongst the foods prepared most frequently. Linear regression analysis found youth food preparation frequency was not significantly associated with total HEI (p = 0.59), sodium (p = 0.58), empty calories (p = 0.96), or dairy scores (p = 0.12). Younger age was associated with higher total HEI scores (p = 0.012) and higher dairy scores (p = 0.01) and female gender was associated with higher total HEI scores (p = 0.03), higher sodium scores (p = 0.03), and lower dairy scores (p = 0.008).     

Safety,Tolerability, and Pharmacokinetics of Single and Repeat Doses of Nemiralisib Administered via the Ellipta Dry Powder Inhaler to Healthy Subjects

Purpose

Novel therapies to treat chronic obstructive pulmonary disease are highly desirable. The safety, tolerability, and pharmacokinetic (PK) parameters of nemiralisib, a phosphoinositide 3-kinase δ inhibitor, administered via the Ellipta dry powder inhaler (GlaxoSmithKline, Research Triangle Park, North Carolina) was evaluated, including an assessment of oral bioavailability.

Inhibitory effects of Doenjang,Korean traditional fermented soybean paste,on oxidative stress and inflammation in adipose tissue of mice fed a high-fat diet

BACKGROUND/OBJECTIVES

Doenjang, Korean traditional fermented soybean paste has been reported to have an anti-obesity effect. Because adipose tissue is considered a major source of inflammatory signals, we investigated the protective effects of Doenjang and steamed soybean on oxidative stress and inflammation in adipose tissue of diet-induced obese mice.

MATERIALS/METHODS

Male C57BL/6J mice were fed a low fat diet (LF), a high-fat diet (HF), or a high-fat containing Doenjang diet (DJ) or a high-fat containing steamed soybean diet (SS) for 11 weeks.

RESULTS

Mice fed a DJ diet showed significantly lower body and adipose tissue weights than those in the HF group. Although no significant differences in adipocyte size and number were observed among the HF diet-fed groups, consumption of Doenjang alleviated the incidence of crown-like structures in adipose tissue. Consistently, we observed significantly reduced mRNA levels of oxidative stress markers (heme oxygenase-1 and p40^phox), pro-inflammatory adipokines (tumor necrosis factor alpha and macrophage chemoattractant protein-1), macrophage markers (CD68 and CD11c), and a fibrosis marker (transforming growth factor beta 1) by Doenjang consumption. Gene expression of anti-inflammatory adipokine, adiponectin was significantly induced in the DJ group and the SS group compared to the HF group. The anti-oxidative stress and anti-inflammatory effects observed in mice fed an SS diet were not as effective as those in mice fed a DJ diet, suggesting that the bioactive compounds produced during fermentation and aging may be involved in the observed health-beneficial effects of Doenjang.

CONCLUSIONS

Doenjang alleviated oxidative stress and restored the dysregulated expression of adipokine genes caused by excess adiposity. Therefore, Doenjang may ameliorate systemic inflammation and oxidative stress in obesity via inhibition of inflammatory signals of adipose tissue.