Exploring Antipsychotic Prescribing Behaviors for Nursing Home Residents With Dementia: A Qualitative Study

Objectives

Caution is advised when prescribing antipsychotics to people with dementia. This study explored the determinants of appropriate, evidence-based antipsychotic prescribing behaviors for nursing home residents with dementia, with a view to informing future quality improvement efforts and behavior change interventions.

The XS106 cell: a Langerhans’ cell surrogate with a selective type 2 phenotype

Epidermal Langerhans’ cells (LC) play important roles in initiating and regulating cutaneous immune responses. However, LC comprise less than 3% of all epidermal cells and consequently are difficult to study ex vivo. In the current investigations, we have examined the utility of the XS106 cell line, a dendritic cell (DC) line derived from mouse epidermis, as a surrogate for LC. Membrane marker expression, type 1- and type 2-associated chemokine production, and migration patterns have been characterised following treatment of XS106 cells with a range of toll-like receptor (TLR) ligands. Comparisons have been made with mouse bone marrow-derived DC- and LC-derived ex vivo. Like BMDC, XS106 cells expressed generic DC markers, in addition to displaying higher levels of skin DC markers compared with BMDC. XS106 cells and LC-enriched epidermal fractions both displayed higher constitutive expression of type 2-associated chemokines than type 1 chemokines. Furthermore, although treatment with a range of TLR ligands induced cytokine secretion by XS106 cells, only type 2 TLR ligands increased membrane marker expression of major histocompatibility complex class II and co-stimulatory molecules. Moreover, type 1-associated TLR ligands failed to induce selective type 1 chemokine secretion by XS106 cells. XS106 cells also displayed functional similarity to LC, migrating in response to chemokines that are known to induce the migration of LC. On the basis of membrane marker expression and selective type 2 polarisation XS106 cells provide a useful surrogate for LC.     

The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells

Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.     

Gender differences in hypertrophy, insulin resistance and ischemic injury in the aging type 2 diabetic rat heart

Aging and diabetes in women increase their susceptibility to myocardial ischemic injury, but the cellular mechanisms involved are not understood. Consequently, we studied the influence of gender on cardiac insulin resistance and ischemic injury in the aging of Goto-Kakizaki (GK) rat, a model of type 2 diabetes. Male and female GK rats had heart/body weight ratios 29% (P < 0.0001) and 53% (P < 0.0001) higher, respectively, than their sex-matched controls, with the female GK rat hearts significantly more hypertrophied than the male (P < 0.001). Glucose transporter (GLUT) 1 protein levels were the same in all hearts, but GLUT4 protein levels were 28% lower (P < 0.01) in all GK rat hearts compared with their sex-matched controls. In isolated, perfused hearts, insulin-stimulated (3)H-glucose uptake rates were decreased by 23% (P < 0.05) and 40% (P < 0.05) in male and female GK rat hearts, respectively, compared with their controls, with the female significantly more insulin resistant than the male GK rat hearts (P < 0.05). Protein kinase B protein levels and insulin-stimulated phosphorylation were the same in all hearts. During low-flow ischemia, glucose uptake was 59% lower (P < 0.001) in female, but the same as controls in male, GK rat hearts. Consequently, recovery of contractile function during reperfusion was 30% lower (P < 0.05) in female, but the same as controls in male GK rat hearts. We conclude that the aging female type 2 diabetic rat heart has increased insulin resistance and greater susceptibility to ischemic injury, than non-diabetic or male type 2 diabetic rat hearts.     

In vitro batch cultures of gut microbiota from healthy and ulcerative colitis (UC) subjects suggest that sulphate-reducing bacteria levels are raised in UC and by a protein-rich diet

Imbalances in gut microbiota composition during ulcerative colitis (UC) indicate a role for the microbiota in propagating the disorder. Such effects were investigated using in vitro batch cultures (with/without mucin, peptone or starch) inoculated with faecal slurries from healthy or UC patients; the growth of five bacterial groups was monitored along with short-chain fatty acid (SCFA) production. Healthy cultures gave two-fold higher growth and SCFA levels with up to ten-fold higher butyrate production. Starch gave the highest growth and SCFA production (particularly butyrate), indicating starch-enhanced saccharolytic activity. Sulphate-reducing bacteria (SRB) were the predominant bacterial group (of five examined) for UC inocula whereas they were the minority group for the healthy inocula. Furthermore, SRB growth was stimulated by peptone presumably due to the presence of sulphur-rich amino acids. The results suggest raised SRB levels in UC, which could contribute to the condition through release of toxic sulphide.     

Effect of Dapagliflozin in DAPA-HF According to Background Glucose-Lowering Therapy

OBJECTIVETo determine whether the benefits of dapagliflozin in patients with heart failure and reduced ejection fraction (HFrEF) and type 2 diabetes in the Dapagliflozin And Prevention of Adverse-Outcomes in Heart Failure trial (DAPA-HF) varied by background glucose-lowering therapy (GLT).RESEARCH DESIGN AND METHODSWe examined the effect of study treatment by the use or not of GLT and by GLT classes and combinations. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death.RESULTSIn the 2,139 type 2 diabetes patients, the effect of dapagliflozin on the primary outcome was consistent by GLT use or no use (hazard ratio 0.72 [95% CI 0.58–0.88] vs. 0.86 [0.60–1.23]; interaction P = 0.39) and across GLT classes.CONCLUSIONSIn DAPA-HF, dapagliflozin improved outcomes irrespective of use or no use of GLT or by GLT type used in patients with type 2 diabetes and HFrEF.