Social connections as determinants of cognitive health and as targets for social interventions in persons with or at risk of Alzheimer's disease and related disorders: a scoping review.

BACKGROUND: Social connections have a significant impact on health across age groups, including older adults. Loneliness and social isolation are known risk factors for Alzheimer's disease and related dementias (ADRD). Yet, we did not find a review focused on meta-analyses and systematic reviews of studies that had examined associations of social connections with cognitive decline and trials of technology-based and other social interventions to enhance social connections in people with ADRD. STUDY DESIGN: We conducted a scoping review of 11 meta-analyses and systematic reviews of social connections as possible determinants of cognitive decline in older adults with or at risk of developing ADRD. We also examined eight systematic reviews of technology-based and other social interventions in persons with ADRD. STUDY RESULTS: The strongest evidence for an association of social connections with lower risk of cognitive decline was related to social engagement and social activities. There was also evidence linking social network size to cognitive function or cognitive decline, but it was not consistently significant. A number of, though not all, studies reported a significant association of marital status with risk of ADRD. Surprisingly, evidence showing that social support reduces the risk of ADRD was weak. To varying degrees, technology-based and other social interventions designed to reduce loneliness in people with ADRD improved social connections and activities as well as quality of life but had no significant impact on cognition. We discuss strengths and limitations of the studies included. CONCLUSIONS: Social engagement and social activities seem to be the most consistent components of social connections for improving cognitive health among individuals with or at risk for ADRD. Socially focused technology-based and other social interventions aid in improving social activities and connections and deserve more research.

Inhibition of IRAK4 kinase activity improves ethanol-induced liver injury in mice.

BACKGROUNDS & AIMS: Alcohol-related liver disease (ALD) is a major cause of chronic liver disease worldwide with limited therapeutic options. Interleukin-1 receptor associated kinase 4 (IRAK4), the master kinase of Toll-like receptor (TLR)/IL-1R-mediated signalling activation, is considered a novel therapeutic target in inflammatory diseases, but has not been investigated in the context of ALD. METHODS: IRAK4 phosphorylation and IRAK1 protein were analysed in liver from alcohol-related hepatitis patients and healthy controls. IRAK4 kinase activity-inactive knock-in (Irak4 KI) mice and bone marrow chimeric mice were exposed to chronic ethanol-induced liver injury. IL-1ß-induced IRAK4-mediated signalling and acute phase response were investigated in cultured hepatocytes. IRAK1/4 inhibitor was used to test the therapeutic potential for ethanol-induced liver injury in mice. RESULTS: Increased IRAK4 phosphorylation and reduced IRAK1 protein were found in livers of patients with alcoholic hepatitis. In the chronic ethanol-induced liver injury mouse model, hepatic inflammation and hepatocellular damage were attenuated in Irak4 KI mice. IRAK4 kinase activity promotes expression of acute phase proteins in response to ethanol exposure, including C-reactive protein and serum amyloid A1 (SAA1). SAA1 and IL-1ß synergistically exacerbate ethanol-induced cell death ex vivo. Pharmacological blockage of IRAK4 kinase abrogated ethanol-induced liver injury, inflammation, steatosis, as well as acute phase gene expression and protein production in mice. CONCLUSIONS: Our data elucidate the critical role of IRAK4 kinase activity in the pathogenesis of ethanol-induced liver injury in mice and provide preclinical validation for use of an IRAK1/4 inhibitor as a new potential therapeutic strategy for the treatment of ALD. LAY SUMMARY: Herein, we have identified the role of IRAK4 kinase activity in the development of alcohol-induced liver injury in mice. Hepatocyte-specific IRAK4 is associated with an acute phase response and release of proinflammatory cytokines/chemokines, which synergistically exacerbate alcohol-induced hepatocyte cell death ex vivo. Pharmacological inhibition of IRAK4 kinase activity effectively attenuates alcohol-induced liver injury in mice and could have therapeutic implications.

A novel foam based separation strategy for extracting minute target impurities.

The purpose of this study was to extract impurities from compounds using a simple separatory bottle to purify target compounds with a foam column and allow for the further characterization of impurities. Charged dyes were used as target compounds due to the ease of detection of dyes and isolated impurities. Foaming agents were used in a glass bottle with a modified cap to separate a target impurity using an appropriately charged ligand. By passing N2 gas through the solution, the surfactants sodium dodecyl sulfate and cetylpyridinium chloride generated foams that separated the dyes, Methylene blue and Orange G, respectively, from a solution containing both dyes. Sodium dodecyl sulfate condensed Methylene blue from the solution with high purity while cetylpyridinium chloride condensed Orange G with less purity. A range of concentrations (0.01-0.5 mmol/L) of dyes were used for separation. The condensability (volume and/or concentration) of the target compound increased as its concentration decreased. This novel separation method is a simple, rapid, inexpensive, and effective way to prepare samples and allows for the characterization of these impurities using sensitive analytical detection techniques.

Ethical, Legal and Forensic Issues in Geriatric Psychiatry.

PURPOSE OF THE REVIEW: To evaluate the ethical, legal and forensic issues that is faced by the older adult population. RECENT FINDINGS: Many older individuals will face a host of ethical, medical and legal issues associated with their care. Most prominent among these issues are the maintenance of autonomy while ensuring their safety and the safety of individuals who care for them. Decisions regarding end of life including the formulation of advance directives add to the complexity of care for these older adults. A significant portion of individuals in the criminal justice system are aging and many of these individuals have psychiatric disorders. Their care is compromised due to the lack of appropriate services within criminal justice system for providing care for these individuals. CONCLUSIONS: Ethical, legal and forensic issues among older are not uncommon and complicate the care of these vulnerable individuals.

Acute blood loss anemia in hospitalized patients is associated with adverse outcomes: An analysis of the Nationwide Inpatient Sample.

BACKGROUND: Acute blood loss anemia is the most common form of anemia and often results from traumatic injuries or gastrointestinal bleeding. There are limited studies analyzing outcomes associated with acute blood loss anemia in hospitalized patients. METHODS: The Nationwide Inpatient Sample (NIS) was analyzed from 2010 to 2014 (n = 133,809). The impact of acute blood loss anemia on in-hospital mortality, length of stay (LOS), healthcare cost, and disposition was determined using regression modeling adjusted for age, gender, race, and comorbidities. RESULTS: Hospitalized patients with acute blood loss anemia had significantly higher healthcare cost (adj OR 1.04; 95% CI: 1.04-1.05), greater lengths of stay (adj OR 1.18; 95% CI: 1.17-1.18), and were less likely to be discharged home compared to the general medical population (adj OR 0.27; 95% CI: 0.26-0.28). Acute blood loss anemia was associated with increased risk for mortality in unadjusted models (unadj 1.16; 95% CI: 1.12-1.20) but not in adjusted models (adj OR 0.91; 95% CI: 0.88-0.94). When analyzing comorbidities, a "muscle loss phenotype" had the strongest association with mortality in patients with acute blood loss anemia (adj OR 4.48; 95% CI: 4.35-4.61). The top five primary diagnostic codes associated with acute blood loss anemia were long bone fractures, GI bleeds, cardiac repair, sepsis, and OB/Gyn related causes. Sepsis had the highest association with mortality (18%, adj OR 2.59; 95% CI: 2.34-2.86) in those with acute blood loss anemia. CONCLUSIONS: Acute blood loss anemia is associated with adverse outcomes in hospitalized patients.

Optimizing ambulatory reflux monitoring: current findings and future directions.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is the most common diagnosis seen in outpatient gastroenterology clinics. The diagnosis is made by a variable combination of symptoms, response to acid suppressive therapy, endoscopic evaluation, and pH testing. In this review, we evaluate how to utilize various reflux testing in clinical practice based on current evidence. AREAS COVERED: Ambulatory reflux monitoring is a recognized diagnostic tool for clinical decision making in patients with/without established GERD, persistent reflux symptoms, and lack of response to proton pump inhibitor (PPI) therapy. Standard evaluation approaches include 24-hour pH or impedance monitoring via transnasal catheter, prolonged (48 to 96 hour) wireless pH monitoring, and the recently developed mucosal integrity testing. Testing using one of these methods allows for measurement of acid exposure, frequency of reflux, and to phenotype patients to personalize treatment recommendations. EXPERT OPINION: The primary goal of future studies should be to simplify ambulatory reflux monitoring, reduce diagnostic latency, improve patient tolerance, and to obtain clinical outcomes-based studies. The current paradigm of reflux testing is vastly complex with multiple modalities and shifting cutoffs of pH abnormality that lead to high economic burden on the society.

Prazosin for the management of behavioural and psychological symptoms of dementia.

Prazosin, a centrally acting α1 adrenoceptor antagonist, has been included in two published algorithms amongst the list of medications that may be used in the management of behavioural and psychological symptoms of dementia (BPSD). However, a review of PubMed, Ovid and Cochrane Collaboration found that there was only one small published randomized controlled trial (RCT) that evaluated the use of prazosin amongst individuals with BPSD. Evidence from this good quality RCT indicates that prazosin appears to benefit individuals with agitation and aggression amongst individuals with BPSD and this medication is well tolerated. When compared to other treatments for BPSD, including atypical antipsychotics, antidepressants, acetylcholinesterase inhibitors, memantine, repetitive transcranial magnetic stimulation and electroconvulsive therapy, where there are multiple studies for each of these treatment modalities, the data for the use of prazosin for BPSD are limited to just one good quality RCT. Given the limitations in available data, the routine use of prazosin for the treatment of BPSD cannot be recommended at this time. However, prazosin may be used for the management of agitation and aggression amongst individuals with dementia when other medication classes, like acetylcholinesterase inhibitors, memantine, antidepressants and/or atypical antipsychotics, have been ineffective or not tolerated.

Acute skeletal muscle loss in SARS-CoV-2 infection contributes to poor clinical outcomes in COVID-19 patients.

BACKGROUND: Chronic disease causes skeletal muscle loss that contributes to morbidity and mortality. There are limited data on the impact of dynamic muscle loss on clinical outcomes in COVID-19. We hypothesized that acute COVID-19-related muscle loss (acute sarcopenia) is associated with adverse outcomes. METHODS: A retrospective analysis of a prospective clinical registry of COVID-19 patients was performed in consecutive hospitalized patients with acute COVID-19 (n = 95) and compared with non-COVID-19 controls (n = 19) with two temporally unique CT scans. Pectoralis muscle (PM), erector spinae muscle (ESM) and 30 day standardized per cent change in cross sectional muscle area were quantified. Primary outcomes included mortality and need for intensive care unit (ICU) admission. Multivariate linear and logistic regression were performed. Cox proportional hazard ratios were generated for ICU admission or mortality for the per cent muscle loss standardized to 30 days. RESULTS: The COVID-19 CT scan cohort (n = 95) had an average age of 63.3 ± 14.3 years, comorbidities including COPD (28.4%) and diabetes mellitus (42.1%), and was predominantly Caucasian (64.9%). The proportion of those admitted to the ICU was 54.7%, with 10.5% requiring tracheostomy and overall mortality 16.8%. Median duration between CT scans was 32 days (IQR: 16-63 days). Significant reductions in median per cent loss was noted for PM (-2.64% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.01, -0.28] in non-COVID-19 CT controls, P < 0.001) and ESM (-1.86% loss [IQR: -0.28, -5.47] in COVID-19 vs. -0.06 loss [IQR: -0.02, -0.11]) in non-COVID-19 CT controls, P < 0.001). Multivariate linear regression analysis of per cent loss in PM was significantly associated with mortality (-10.8% loss [95% CI: -21.5 to -0.19]) and ICU admission (-11.1% loss [95% CI: -19.4 to -2.67]), and not significant for ESM. Cox proportional hazard ratios demonstrated greater association with ICU admission (adj HR 2.01 [95% CI: 1.14-3.55]) and mortality (adj HR 5.30 [95% CI: 1.19-23.6]) for those with significant per cent loss in PM, and greater association with ICU admission (adj HR 8.22 [95% CI: 1.11-61.04]) but not mortality (adj HR 2.20 [95% CI: 0.70-6.97]) for those with significant per cent loss in ESM. CONCLUSIONS: In a well-characterized cohort of 95 hospitalized patients with acute COVID-19 and two temporally distinct CT scans, acute sarcopenia, determined by standardized reductions in PM and ESM, was associated with worse clinical outcomes. These data lay the foundation for evaluating dynamic muscle loss as a predictor of clinical outcomes and targeting acute sarcopenia to improve clinical outcomes for COVID-19.

Aging With Mental Disorders in the Criminal Justice System: A Content Analysis of the Empirical Literature.

To fill a current gap in the literature on aging, mental health, and the criminal justice system, a content analysis of international peer-reviewed research studies was conducted. A comprehensive literature search was conducted to identify English language research studies published in 2018-19. Forty-four articles were located using keyword search terms, such as aging, mental health, and criminal justice. The methods and major findings were analyzed using deductive and inductive approaches. It was found that the majority of the research studies were conducted in the United States and England. The results of the inductive analyses revealed major themes related to mental health detection and access to services, comorbid conditions, and the relationship of age, mental health, criminal behavior, and the social determinants of mental health. Findings from this review have significant implications for advancing epidemiological research, practice, and policy, especially as it relates to the influence of the social determinants of health of aging on life course mental health and criminal justice involvement. Research findings about the correlates and consequences of the social determinants of health, especially as it relates to aging, mental health, and criminal justice involvement, can be used to inform prevention and intervention efforts that target the social determinants of life course health and criminal justice involvement. It also provides a comprehensive assessment of the m methods used in prior studies to help improve future studies in this important area of investigation.

Foam separation of Rhodamine-G and Evans Blue using a simple separatory bottle system.

A simple separatory glass bottle was used to improve separation effectiveness and cost efficiency while simultaneously creating a simpler system for separating biological compounds. Additionally, it was important to develop a scalable separation method so this would be applicable to both analytical and preparative separations. Compared to conventional foam separation methods, this method easily forms stable dry foam which ensures high purity of yielded fractions. A negatively charged surfactant, sodium dodecyl sulfate (SDS), was used as the ligand to carry a positively charged Rhodamine-G, leaving a negatively charged Evans Blue in the bottle. The performance of the separatory bottle was tested for separating Rhodamine-G from Evans Blue with sample sizes ranged from 1 to 12mg in preparative separations and 1-20µg in analytical separations under optimum conditions. These conditions including N2 gas pressure, spinning speed of contents with a magnetic stirrer, concentration of the ligand, volume of the solvent, and concentration of the sample, were all modified and optimized. Based on the calculations at their peak absorbances, Rhodamine-G and Evans Blue were efficiently separated in times ranging from 1h to 3h, depending on sample volume. Optimal conditions were found to be 60psi N2 pressure and 2mM SDS for the affinity ligand. This novel separation method will allow for rapid separation of biological compounds while simultaneously being scalable and cost effective.

An improved design of spiral tube assembly for separation of proteins by high-speed counter-current chromatography.

A new spiral tube assembly was designed to improve the column capacity and partition efficiency for protein separation. This spiral tube assembly has greater column capacity than the original tubing because of an increase in radial grooves from 4 to 12 to accommodate more spiral layers and 12 narrow spots instead of 4 in each circular loop to interrupt the laminar flow that causes sample band broadening. Standard PTFE tubing (1.6mm ID) and the modified flat-twisted tubing were used as the separation column. The performances of both assemblies were compared for separating three stable test proteins including cytochrome c, myoglobin, and lysozyme using a two phase aqueous-aqueous solvent system composed of polyethylene glycol 1000 (12.5% w/w) and dibasic potassium phosphate (12.5% w/w). All samples were run at 1, 2, 3, and 5mL/min at both 800rpm and 1000rpm. The separation of these three protein samples produced high stationary phase retentions at 1, 2, and 3mL/min, yet separated efficiently at 5mL/min in 40min. After comparing the separation efficiency in terms of the peak resolutions, theoretical plate numbers, and separation times, it was determined that the flat-twisted tubing was more effective in separating these protein samples. In order to validate the efficacy of this novel assembly, a mixture of five protein samples (cytochrome c, myoglobin, ovalbumin, lysozyme, and hemoglobin) were separated, under the optimal conditions established with these three protein samples, at 1mL/min with a revolution speed of 1000rpm. There were high stationary phase retentions of around 60%, with effective separations, demonstrating the efficiency of the flat-twisted spiral tube assembly. The separation time of 6h was a limitation but can potentially be shortened by improving the strength of the column that will permit an increase in revolution speed and flow rate. This novel spiral separation column will allow rapid and efficient separation of mixtures with high yield of the constituent components.