An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease.

Sleep apnoea is a highly prevalent disease that often goes undetected and is associated with poor clinical prognosis, especially as it exacerbates many different disease states. However, most animal models of sleep apnoea (e.g., intermittent hypoxia) have recently been dispelled as physiologically unrealistic and are often unduly severe. Owing to a lack of appropriate models, little is known about the causative link between sleep apnoea and its comorbidities. To overcome these problems, we have created a more realistic animal model of moderate sleep apnoea by reducing the excitability of the respiratory network. This has been achieved through controlled genetically mediated lesions of the preBötzinger complex (preBötC), the inspiratory oscillator. This novel model shows increases in sleep disordered breathing with alterations in breathing during wakefulness (decreased frequency and increased tidal volume) as observed clinically. The increase in dyspnoeic episodes leads to reduction in REM sleep, with all lost active sleep being spent in the awake state. The increase in hypoxic and hypercapnic insults induces both systemic and neural inflammation. Alterations in neurophysiology, an inhibition of hippocampal long-term potentiation (LTP), is reflected in deficits in both long- and short-term spatial memory. This improved model of moderate sleep apnoea may be the key to understanding why this disorder has such far-reaching and often fatal effects on end-organ function.

The Epidemiology of Traumatic Brain Injury Due to Traffic Accidents in Latin America: A Narrative Review.

Objective Traumatic brain injuries (TBIs) are devastating injuries and represent a major cause of morbidity and mortality worldwide. Traffic accidents are one of the main causes, especially in low- and middle-income countries. The epidemiology of TBI due to road traffic in Latin America is not clearly documented. Methods A narrative review was conducted using PubMed, SCOPUS, and Google Scholar, looking for TBI studies in Latin America published between 2000 and 2018. Seventeen studies were found that met the inclusion and exclusion criteria. Results It was found that TBI due to road traffic accidents (RTAs) is more frequent in males between the ages of 15 and 35 years, and patients in motor vehicles accounted for most cases, followed by pedestrians, motorcyclists, and cyclists. Conclusion Road traffic accidents is a common cause of TBI in Latin America. More studies and registries are needed to properly document the epidemiological profiles of TBI related to RTAs.

Reduction in self-monitoring of blood glucose in type 2 diabetes: an observational controlled study in east London.

BACKGROUND: Self-monitoring of blood glucose (SMBG) confers no benefit for many people with type 2 diabetes not being treated with insulin. It accounts for 21% of diabetes prescribing costs. AIM: To improve care quality at reduced cost for type 2 diabetes by reducing unnecessary SMBG. DESIGN AND SETTING: Non-randomised, observational controlled study in two intervention clinical commissioning groups (CCGs) and one control CCG in east London. METHOD: In total, 19,602 people with type 2 diabetes not being treated with insulin were recruited from two intervention CCGs; 16,033 were recruited from a control CCG. The intervention (from 2010 to 2013) comprised implementation of a locally developed guideline, including IT support and peer feedback of performance. Data on practice prescribing SMBG testing strips were gathered using GP electronic health records. Information on costs were obtained via the ePACT electronic database. RESULTS: Over 4 years, in all non-insulin type 2 diabetes treatment groups, use of SMBG was reduced in the two intervention CCGs from 42.8% to 16.5%, and in the control CCG from 56.4% to 47.2%. In people on metformin alone or no treatment, intervention CCGs reduced SMBG use from 29.6% to 6.0%, and in the control CCG use dropped from 47.1% to 38.7% (P<0.001). From 2009 to 2012 the total cost of all SMBG prescribing (type 1 and type 2 diabetes, including users of insulin) was reduced by 4.9% (£62,476) in the two intervention CCGs and increased in the control CCG by 5.0% (£42,607); in England, the total cost increased by 13.5% (£19.4 million). In total, 20% (3865 of 19 602) fewer patients used SMBG in the intervention CCGs. CONCLUSION: This low-cost programme demonstrated a major reduction in unnecessary prescribing of SMBG, along with cost savings. If replicated nationally, this would avoid unnecessary testing in 340 000 people and prescribing costs that total £21.8 million.

Identification of compounds that enhance the anti-lymphoma activity of rituximab using flow cytometric high-content screening.

In this report, we describe a new flow cytometry technique termed flow cytometric high-content screening (FC-HCS) which involves semi-automated processing and analysis of multiparameter flow cytometry samples. As a first test of the FC-HCS technique, we used it to screen a 2000-compound library, called the National Cancer Institute (NCI) Diversity Set, to identify agents that would enhance the anti-lymphoma activity of the therapeutic monoclonal antibody rituximab. FC-HCS identified 15 compounds from the Diversity Set that significantly enhanced the ability of rituximab to inhibit cell cycle progression and induce apoptosis in lymphoma cells. The validity of the screening results was confirmed for several compounds using additional assays of cell proliferation, apoptosis and cell growth. The FC-HCS technique was relatively simple and reliable and could process up to 1000 samples/day on a single flow cytometer. The FC-HCS technique may be useful for a variety of applications including drug discovery, immunologic monitoring of patients, functional genomics studies and tissue engineering efforts.