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.     

Does a high Mandard score really define a poor response to chemotherapy in oesophageal adenocarcinoma?

Background A high Mandard score implies a non-response to chemotherapy in oesophageal adenocarcinoma. However, some patients exhibit tumour volume reduction and a nodal response despite a high score. This study examines survival and recurrence patterns in these patients.Methods Clinicopathological factors were analysed using multivariable Cox regression assessing time to death and recurrence. Computed tomography-estimated tumour volume change was examined in a subgroup of consecutive patients.Results Five hundred and fifty-five patients were included. Median survival was 55 months (Mandard 1–3) and 21 months (Mandard 4 and 5). In the Mandard 4 and 5 group (332 patients), comparison between complete nodal responders and persistent nodal disease showed improved survival (90 vs 18 months), recurrence rates (locoregional 14.75 vs 28.74%, systemic 24.59 vs 48.42%) and circumferential resection margin positivity (22.95 vs 68.11%). Complete nodal response independently predicted improved survival (hazard ratio 0.34 (0.16–0.74). Post-chemotherapy tumour volume reduction was greater in patients with a complete nodal response (−16.3 vs −7.7 cm³, p = 0.033) with no significant difference between Mandard groups.Conclusion Patients with a complete nodal response to chemotherapy have significantly improved outcomes despite a poor Mandard score. High Mandard score does not correspond with a non-response to chemotherapy in all cases and patients with nodal downstaging may still benefit from adjuvant chemotherapy.Subject terms: Oesophageal cancer, Surgical oncology     

Outreach to older adults: matching programs to specific needs.

Mental health services for older adults benefit from an outreach approach that makes both clients and providers aware of the availability and usefulness of a range of programs to address various problems. Coordination of multiple systems of care is usually required to provide the necessary complement of services needed by older adults.     

Pericardial effusion complicating breast cancer.

Thirty-five patients with metastatic breast cancer and pericardial effusions are described. They were treated with specific endocrine or chemotherapy. Twenty-two (63%) had presented in cardiac tamponade and were rapidly relieved by pericardiocentesis. Eighteen (82%) of these required no further local treatment, 2 obtained relief from a second aspiration and 2 needed additional treatment (intrapericardial bleomycin instillation and surgical pleuropericardial window). The median survival was 13.2 months. No patient relapsed again in the pericardium, suggesting that their prognosis was that of the underlying disease. Cardiac tamponade should be considered in any breathless patient with malignancy. In breast cancer, periocardiocentesis is lifesaving and systemic treatment can usefully prolong life.     

An Unexplained Death: Hannah Greener and Chloroform

Background: Reports of major and minor sequelae following lidocaine spinal anesthesia have generated interest in an alternative short-acting intrathecal agent. Of the available anesthetics suitable for short-duration spinal anesthesia, prilocaine is perhaps the most promising agent. However, data comparing the neurotoxicity of these agents are lacking. Accordingly, the present experiments investigate whether prilocaine and lidocaine differ with respect to sensory impairment and histologic damage when administered intrathecally in the rat.

Methods: Ninety rats were divided into three groups to receive an intrathecal infusion of 2.5% prilocaine in saline, 2.5% lidocaine in saline, or normal saline. The animals were assessed for persistent sensory impairment 4 days after anesthetic administration using the tail-flick test. Three days later, the animals were killed, and specimens of the spinal cord and nerve roots were obtained for histopathologic examination.

Results: Prilocaine and lidocaine produced equivalent elevations in tail-flick latency that differed significantly from saline. Histologic injury scores with prilocaine were greater than with lidocaine, but this difference did not reach statistical significance.     

The role of Self-Defined Race/Ethnicity in Population Structure Control

Population-based association studies are powerful tools for the genetic mapping of complex diseases. However, this method is sensitive to potential confounding by population structure. While statistical methods that use genetic markers to detect and control for population structure have been the focus of current literature, the utility of self-defined race/ethnicity in controlling for population structure has been controversial. In this study of 1334 individuals, who self-identified as either African American, European American or Hispanic, we demonstrated that when the true underlying genetic structure and the self-defined racial/ethnic groups were roughly in agreement with each other, the self-defined race/ethnicity information was useful in the control of population structure.