Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with its molecular etiology still unclear. Here we present a spatial transcriptomic (ST) and single-nucleus transcriptomic survey of late-onset sporadic AD and AD in Down syndrome (DSAD). Studying DSAD provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD.

Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer's Disease.

The pathogenesis of Alzheimer's disease (AD) depends on environmental and heritable factors, with remarkable differences evident between individuals at the molecular level. Here we present a transcriptomic survey of AD using spatial transcriptomics (ST) and single-nucleus RNA-seq in cortical samples from early-stage AD, late-stage AD, and AD in Down Syndrome (AD in DS) donors. Studying AD in DS provides an opportunity to enhance our understanding of the AD transcriptome, potentially bridging the gap between genetic mouse models and sporadic AD.

Comparative effectiveness of glycemic control in patients with type 2 diabetes treated with GLP-1 receptor agonists: a network meta-analysis of placebo-controlled and active-comparator trials.

Background: Clinical studies of patients with type 2 diabetes show that GLP-1 receptor agonists (GLP-1 RAs) improve glycemic control and promote weight loss. We conducted a Bayesian network meta-analysis (NMA) of placebo- and active-controlled randomized trials to assess the comparative effectiveness of liraglutide, albiglutide, dulaglutide, and exenatide twice daily and once weekly, with a focus on glycemic control.

Materials And Methods: We searched Medline, Embase, and the Cochrane Library (up to December 2014) for core registration programs for US-approved GLP-1 RAs.

Analysis of Glycemic Control of a Pharmacist-Led Medication Management Program in Patients with Type 2 Diabetes.

Background: An integrated health care system with its own regional health plan located in Texas implemented a pharmacist-led diabetes medication management program (MMP) to treat type 2 diabetic patients (baseline A1c > 7.5%). The MMP formed collaborative practice agreements with the system's physicians to allow ambulatory care pharmacists to modify and adjust diabetic drug regimens when appropriate.

Psoriasis disease severity affects patient satisfaction with treatment.

Background: Patients with psoriasis are often dissatisfied with available treatments, but contributing factors are not well defined.

Objective: Examine relationships between psoriasis severity, patient characteristics, and treatment satisfaction.

Methods: Patients with psoriasis were classified into mild and moderate-to-severe groups based on self-reported data.

Evaluating the economic burden of psoriasis in the United States.

Background: Psoriasis has significant economic impact on patients. However, its total economic burden has not been fully quantified.

Objectives: To assess the annual economic burden of psoriasis in the United States.

Patterns of medication utilization and costs associated with the use of etanercept, adalimumab, and ustekinumab in the management of moderate-to-severe psoriasis.

Background: Dose escalations of biologic agents may be attempted in the management of moderate-to-severe psoriasis. This has implications for the real-world cost of treatment.

Objective: To examine the utilization patterns and costs associated with the use of etanercept, adalimumab, and ustekinumab among patients with moderate-to-severe psoriasis.

Economic and comorbidity burden among moderate-to-severe psoriasis patients with comorbid psoriatic arthritis.

Objective: To compare the prevalence of comorbidities, health care utilization, and costs between moderate-to-severe psoriasis (PsO) patients with comorbid psoriatic arthritis (PsA) and matched controls.

Methods: Adults ages 18-64 years with concomitant diagnoses of PsO and PsA (PsO+PsA) were identified in the OptumHealth Reporting and Insights claims database between January 2007 and March 2012. Moderate-to-severe PsO was defined based on the use of at least one systemic or phototherapy during the 12-month study period after the index date (randomly selected date after the first PsO diagnosis).

Time- and behavioral state-dependent changes in posterior hypothalamic GABAA receptors contribute to the regulation of sleep.

Sleep-wake behavior is regulated by a circadian rhythm, homeostatically and by additional mechanisms that determine the timing of slow-wave sleep and rapid eye movement sleep (REMS) episodes. The posterior hypothalamus coordinates the neural and humoral signals with the rest-activity cycle. It contains wake-active neurons, and is a site where stimulation of inhibitory GABAA receptors promotes sleep, whereas their antagonism enhances wakefulness.

Electromyographic activity at the base and tip of the tongue across sleep-wake states in rats.

Obstructive sleep apnea (OSA) patients have elevated tonic and phasic inspiratory activity in the genioglossus and other upper airway muscles during wakefulness; this protects their upper airway from collapse. In this group, sleep-related decrements of upper airway motor tone result in sleep-related upper airway obstructions. We previously reported that in the rat, a species widely used to study the neural mechanisms of both sleep and breathing, lingual electromyographic activity (EMG) is minimal or absent during slow-wave sleep (SWS) and then gradually increases after the onset of rapid eye movement sleep (REMS) due to the appearance of large phasic bursts.

Disinhibition of perifornical hypothalamic neurones activates noradrenergic neurones and blocks pontine carbachol-induced REM sleep-like episodes in rats.

Studies in behaving animals suggest that neurones located in the perifornical (PF) region of the posterior hypothalamus promote wakefulness and suppress sleep. Among such cells are those that synthesize the excitatory peptides, orexins (ORX). Lack of ORX, or their receptors, is associated with narcolepsy/cataplexy, a disorder characterized by an increased pressure for rapid eye movement (REM) sleep.

Differential effect of sleep-wake states on lingual and dorsal neck muscle activity in rats.

Postural tone is reduced during slow-wave sleep (SWS) and absent during rapid eye movement sleep (REMS). In obstructive sleep apnea subjects, upper airway dilating muscles, including those of the tongue, show a similar pattern; this contributes to sleep-related airway obstructions. However, in healthy subjects, state-dependent changes in the activity of pharyngeal muscles are variable.