Ethanol upregulates the P2X7 purinergic receptor in human macrophages

Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome and are involved in many ethanol‐related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis, and certain cancers). We hypothesized that ethanol regulates purinergic receptors and thus modulates the NLRP3 inflammasome's activity. In experiments with monocyte‐derived macrophages, we found that interleukin (IL)‐1β secretion was inhibited after 7 h of exposure (but not 48 h of exposure) to ethanol. The disappearance of ethanol's inhibitory effect on IL‐1β secretion after 48 h was not mediated by the upregulated production of IL‐1β, IL‐1α, IL‐6 or the inflammasome components NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain, and caspase 1. P2X7R expression was upregulated by ethanol, whereas expression of the P2X4 and P2X1 receptors was not. Taken as a whole, our results suggest that ethanol induces NLRP3 inflammasome activation by upregulating the P2X7 receptor. This observation might have revealed a new mechanism for inflammation in ethanol‐related diseases.     

The impact of inpatient bed capacity on length of stay

Objective

Large reductions in inpatient length of stay and inpatient bed supply have occurred across health systems in recent years. However, the direction of causation between length of stay and bed supply is often overlooked. This study examines the impact of changes to inpatient bed supply, as a result of recession-induced healthcare expenditure changes, on emergency inpatient length of stay in Ireland between 2010 and 2015.

Study design

We analyse all public hospital emergency inpatient discharges in Ireland from 2010 to 2015 using the administrative Hospital In-Patient Enquiry dataset. We use changes to inpatient bed supply across hospitals over time to examine the impact of bed supply on length of stay. Linear, negative binomial, and hospital–month-level fixed effects models are estimated.

Results

U-shaped trends are observed for both average length of stay and inpatient bed supply between 2010 and 2015. A consistently large positive relationship is found between bed supply and length of stay across all regression analyses. Between 2010 and 2012 while length of stay fell by 6.4%, our analyses estimate that approximately 42% (2.7% points) of this reduction was associated with declines in bed supply.

Conclusion

Changes in emergency inpatient length of stay in Ireland between 2010 and 2015 were closely related to changes in bed supply during those years. The use of length of stay as an efficiency measure should be understood in the contextual basis of other health system changes. Lower length of stay may be indicative of the lack of resources or available bed supply as opposed to reduced demand for care or the shifting of care to other settings.

     

Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial

Graefe's Archive for Clinical and Experimental Ophthalmology - Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases....     

Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D)

AimsSodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D.MethodsPilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period.ResultsForty-five T2D participants on metformin monotherapy (mean age 57 ± 8 years, duration 7 ± 6 years, HbA1c 7.8 ± 1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride.ConclusionsShort term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN.Clinical trial registration: NCT02973477     

Worsening head bleeds in elderly blunt head trauma patients taking antithrombotics: Delayed CT head fails to change management

Background

Most elderly trauma patients suffer blunt head injury and many utilize antithrombotic (AT) medications. The utility of delayed CT-head (D-CTH) in neurologically intact elderly patients using AT who have an intracranial hemorrhage (ICH) on presentation is unknown. We hypothesized that D-CTH would not alter clinical management and aimed to evaluate the role of D-CTH in this population.

Sperm fishing: antigen-antibody complexes for the capture and enrichment of spermatozoa in mixed cell substrates

ABSTRACT

In many sexual assault cases, the most common evidence gathered comes in the form of intimate swabs. These swabs contain cells from both the female and male. In these cases the most common cell present is epithelial cells from the female with relatively few spermatozoa from the male. To produce an STR DNA profile suitable for an investigation, separation of the cell types is required to prevent a mixed profile that may complicate interpretation. While there are methods that can achieve this separation, they are labour intensive and have no guarantee of complete separation of the spermatozoa. Immunomagnetic bead separation techniques are being adapted from other scientific fields to be used in forensic biology to separate spermatozoa from mixed substrates. This study tested the binding of a Hyaluronidase PH-20 (SPAM1) antibody to spermatozoa in mixed cell samples that have been dried and stored for a short period of time. Fluorescently tagged antibodies were incubated with cellular mixtures and visualized using fluorescent microscopy. Successful binding of the antibodies to spermatozoa was observed in all samples. The SPAM1 antibody appears to be suitable for selection of spermatozoa and creates opportunities for linking with magnetic beads facilitate cell separation and DNA profiling.