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.     

The patellar ligament: A comprehensive review

The patellar ligament (PL) is an epiphyseal ligament and is part of the extensor complex of the knee. The ligament has gained attention due to its clinical relevance to autograft and tendinopathy. A variety of anatomical variations of the PL such as aplasia, numerical variations, and vascularity are being reported recently by clinicians and anatomists. The aim of this literature was to review the available literature to provide a consensus regarding anatomic variations of the PL, neurovasculature surrounding the PL, histology of the PL, and various aspects of PL measurements with relevance to the surgical considerations and sex and age-related differences. A narrative review of the patellar ligament was performed by conducting a detailed literature search and review of relevant articles. A total of 90 articles on the patellar ligament were included and were categorized into studies based on anatomical variations, neurovasculature, morphometrics, microanatomy, sex and age-related difference, and ACL reconstruction. The anatomical variations and morphometrics of the PL were found to correlate with the frequency of strain injuries, tendinopathy, and efficacy of the PL autograft in anterior cruciate ligament reconstruction. The sex differences in PL measurements and the effect of estrogen on collagen synthesis explained a higher incidence of patellar tendinopathy in women. An awareness of its variations enables careful selection of surgical incisions, thereby avoiding complications related to nerve injury. Accurate knowledge of the PL microanatomy assists in understanding the mechanism of ligament degeneration, rupture, autograft harvesting, and ligamentization results.     

How Do Students Source and Supply Drugs? Characteristics of the University Illegal Drug Trade

Background: It is widely known that a proportion of university students use drugs. However, much less is known about how they source and supply their drugs. Objectives: In this article, we investigate student drug trading activity, including how they obtained their drugs, whether they sold drugs, and the extent to which their drug trading might be described as a form of “social supply”. Methods: A survey was conducted of all students across seven of the nine universities of Wales. In total, 7855 students submitted a questionnaire and 1877 of these reported drug use in the current academic year. All students who reported using one or more illegal drugs in the current academic year were asked how they obtained their drugs, how they funded their drug use, whether they had sold, traded or given away illegal drugs, along with their motives for drug trading. Results: The results showed that about half of users obtained drugs solely from friends and associates and one-fifth obtained them solely from external dealers. One-quarter used friends and associates as well as external markets. In many cases, supplying drugs amounted to sharing them or giving them away. However, over one-third of students said that they had sold drugs. Conclusions: Overall, the methods of sourcing and supplying drug among university students shares features of both “social supply” and “traditional” drug markets. We conclude that the student drug market investigated is best described as a “hybrid” combination of both.     

Issues regarding data on race and ethnicity: the Census Bureau experience.

In this paper, the authors describe some of the complexities of collecting and presenting data on race and ethnicity based on the experiences of the Bureau of the Census. Different methods of data collection, different content and format of questions, and different definitions make it difficult to collect consistent race and ethnic data across data systems. The Bureau of the Census experiences have shown that changing ethnic self-identity and concepts, intent of the question, consistency of reporting, and the classification of persons of mixed racial parentage affect the quality of the data. These are some of the issues that must be addressed as statistical agencies and researchers seek to provide comparable race and ethnic data.     

Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.     

Endogenous vasopressin and baroreflex mechanisms

This article reviews the anatomical and functional evidence for ascending pathways from specific brain regions to the PVN and SON which could influence AVP release. The majority of evidence favours the main projection being from a region in the caudal VLM which may coincide with the noradrenergic neurons of the A₁ cell group. However, the transmitter(s) involved have yet to be identified, and whether the pathway is excitatory and/or inhibitory remains to be fully resolved.Anatomical and functional evidence is reviewed for descending projections from the SON and PVN to specific brain regions involved in cardiovascular control, and their possible involvement in baroreflex mechanisms is discussed. However, there is little unequivocal evidence that AVP is the main neurotransmitter utilized by descending projections from PVN to NTS and DMX. While, in some situations, circulating endogenous AVP exerts cardiovascular effects, details of its putative influences on baroreflex mechanisms are lacking.     

Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.