Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

QUADAS评价:一种用于诊断性研究的质量评价工具(修订版)

背景 QUADAS是一种新近发展起来的诊断性研究的质量评价工具。虽然已有系统评价采用了QUADAS,但尚未得以正式确证。本研究的目的是评价QUADAS的有效性和实用性。方法3位评价者采用QUADAS独立评价30项研究的质量。比较每位评价者的评分与最终结论之间的意见一致度。这主要是通过比较所有QUADAS条目的总分和每个单项的得分来实现的。20位曾在其系统评价中使用过QUADAS的评价者就其使用经验完成一份简短的问卷。结果就所有条目而言,每位评价者的评分与最终结论之间的意见一致度分别达到了91%、90%和85%。就单项QUADAS条目而言,一致度在50%至100%之间,中位值是90%。与难以解释的试验结果和退出病例相关的条目,评分结果差异最大。有关QUADAS内容的反馈意见普遍较好,仅少数评价者提出了有关QUADAS涵盖面、使用便利性、评分说明的清晰度及有效性方面的问题。结论QUADAS内容本身无需作大的修改。评价过程的主要困难出现在难以解释的试验结果和退出病例这2个条目的评分上。对这些条目的评分指南提出了修改意见。评价者必需根据其系统评价制定相应的评分指南,并确保所有评价者都清楚如何评分。评价者还应考虑是否所有的QUADAS条目都与其系统评价相关,以及其他质量条目是否应作为其系统评价的评价部分。     

Potential therapeutic effect of Allium cepa L. and quercetin in a murine model of Blomia tropicalis induced asthma

Background

Asthma is an inflammatory condition characterized by airway hyperresponsiveness and chronic inflammation. The resolution of inflammation is an essential process to treat this condition. In this study we investigated the effect of Allium cepa L. extract (AcE) and quercetin (Qt) on cytokine and on smooth muscle contraction in vitro and its therapeutic potential in a murine model of asthma.

Methods

AcE was obtained by maceration of Allium cepa L. and it was standardized in terms of quercetin concentration using high performance liquid chromatography (HPLC). In vitro, using AcE 10, 100 or 1000 μg/ml or Qt 3.5, 7.5, 15 μg/ml, we measured the concentration of cytokines in spleen cell culture supernatants, and the ability to relax tracheal smooth muscle from A/J mice. In vivo, Blomia tropicalis (BT)-sensitized A/J mice were treated with AcE 100, 1000 mg/kg or 30 mg/kg Qt. We measured cell influx in bronchoalveolar lavage (BAL), eosinophil peroxidase (EPO) in lungs, serum levels of Bt-specific IgE, cytokines levels in BAL, and lung histology.

Results

We observed a reduction in the production of inflammatory cytokines, a relaxation of tracheal rings, and a reduction in total number of cells in BAL and EPO in lungs by treatment with AcE or Qt.

Conclusion

AcE and Qt have potential as antiasthmatic drugs, as they possess both immunomodulatory and bronchodilatory properties.     

A case of dengue‐related osteonecrosis of the maxillary dentoalveolar bone

Dengue is a mosquito transmitted flaviviral infection which can give rise to severe haemorrhage (dengue haemorrhagic fever) and with capillary leakage induces hypovolaemic shock (dengue shock syndrome). Although dengue symptoms and complications have been known for many decades, there has only been one documented case of osteonecrosis of the maxilla which was treated by excision of the necrotic bone. In this case of dengue infection, extensive maxillary osteonecrosis and minimal root resorption appeared to follow factitious injury with a toothpick but resolved with non‐surgical management.     

Sexual Function and Quality of Life for Women with Mild‐to‐Moderate Stress Urinary Incontinence

Introduction: Sexual function is affected by stress urinary incontinence with or without pelvic organ prolapse. The aim of the study was to describe the sexual function of women with mild‐to‐moderate stress urinary incontinence, with or without pelvic organ prolapse (up to stage 2) and examine correlations with symptoms and quality of life. This investigation was part of a large, randomized, clinical trial of women with stress urinary incontinence who participated in an exercise intervention. Methods: Women included in the study suffered from stress urinary incontinence as measured by a pad test and were interested in an exercise intervention. All participants underwent assessment for prolapse staging. Instruments included: the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ‐12), Incontinence Quality of Life Questionnaire (I‐QOL), and a health and urinary leakage questionnaire. Results: One hundred and eighty‐seven ambulatory women, aged 20 to 65 years, had a mean sexual function score of 36.9 (standard deviation [SD] 5.9). No significant correlation was found between the sexual function scores and quantity of urinary leakage. A significant correlation existed between the sexual function and I‐QOL scores (P < .001). An additional finding was that women with urgency symptoms were older (P= .04) and had significantly lower sexual function scores (mean 35.7; SD 6.4) than those who did not report urgency (mean 38.7; SD 4.6; P < .001). Discussion: Women with mild‐to‐moderate stress urinary incontinence, without or with lower stages of pelvic organ prolapse, demonstrated good sexual function, which correlated with physical and psychosocial factors. Health professionals need to perform multifaceted intake assessments on women with urinary leakage to customize their health promotion regimen.     

Systematic analysis of research underfunding in maternal and perinatal health

Background  Little published evidence supports the widely held contention that research in pregnancy is underfunded compared with other disease areas.
Objectives  To assess absolute and relative government and charitable funding for maternal and perinatal research in the UK and internationally.
Search strategy, selection criteria, data collection, and analysis  Major research funding bodies and alliances were identified from an Internet search and discussions with opinion leaders/senior investigators. Websites and annual reports were reviewed for details of strategy, research spend, grants awarded, and allocation to maternal and/or perinatal disease using generic and disease-specific search terms.
Main results  Within the imprecision in the data sets, ≤1% of health research spend in the UK was on maternal/perinatal health. Other countries fared better with 1–4% investment, although nonexclusive categorisation may render this an overestimate. In low-resource settings, government funders focused on infectious disease but not maternal and perinatal health despite high relative disease burden, while global philanthropy concentrated on service provision rather than research. Although research expenditure has been deemed as appropriate for 'reproductive health' disease burden in the UK, there are no data on the equity of maternal/perinatal research spend against disease burden, which globally may justify a manyfold increase.
Author's conclusions  This systematic review of research expenditure and priorities from national and international funding bodies suggests relative underinvestment in maternal/perinatal health. Contributing factors include the low political priority given to women's health, the challenging nature of clinical research in pregnancy, and research capacity dearth as a consequence of chronic underinvestment.