The Relation of Patient Dependence to Home Health Aide Use in Alzheimer's Disease

BACKGROUND: Although there has been much research devoted to understanding the predictors of nursing home placement (NHP) in Alzheimer's disease (AD) patients, there is currently a lack of research concerning the predictors of home health care. The objective of this study was to examine whether the Dependence Scale can predict home health aide (HHA) use. METHODS: The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States. Markov analyses (n=75) were used to calculate annual transition probabilities for the "new onset" of HHA use (instances where an HHA was absent at the previous visit, but present at the next visit) as a function of HHA presence at the preceding year's visit and dependence level at that preceding year's visit. RESULTS: The dependence level at the previous year's visit was a significant predictor of HHA use at the next year's visit. Three specific items of the Dependence Scale (needing household chores done for oneself, needing to be watched or kept company when awake, and needing to be escorted when outside) were significant predictors of the presence of an HHA. CONCLUSION: The Dependence Scale is a valuable tool for predicting HHA use in AD patients. Obtaining a better understanding of home health care in AD patients may help delay NHP and have a positive impact on the health and well-being of both the caregiver and the patient

High throughput analysis of lignin by agarose gel electrophoresis

A high-throughput agarose gel electrophoresis (AGE) analytical method has been developed to separate lignin fractions according to their molecular weight (Mw), charge, and shape. Operating conditions to effect separation of species have been evaluated along with imaging parameters. Kraft, soda (Protobind), and Organosolv lignins showed distinct differences in migration. Bands were cut, extracted, and cross-analyzed by gel permeation chromatography (GPC), 1H NMR, and pyrolysis GC/MS to confirm their identity as lignin. The band intensity was correlated with lignin concentration by running serially diluted samples and imaging each lane to produce a precise calibration curve. The AGE technique was used to monitor and compare enzymatic, bacterial, chemical, and hydrothermal lignin digestions. Each method showed changes in lignin migration and band intensities over time. Low Mw species were seen in samples collected from the anode buffer tank. Though requiring further development, the AGE method can provide structural information about the lignin and is accessible to biological and chemistry laboratories

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.Peer reviewe

The global burden of non-typhoidal salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017

Background Non-typhoidal salmonella invasive disease is a major cause of global morbidity and mortality. Malnourished children, those with recent malaria or sickle-cell anaemia, and adults with HIV infection are at particularly high risk of disease. We sought to estimate the burden of disease attributable to non-typhoidal salmonella invasive disease for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We did a systematic review of scientific databases and grey literature, and estimated non-typhoidal salmonella invasive disease incidence and mortality for the years 1990 to 2017, by age, sex, and geographical location using DisMod-MR, a Bayesian meta-regression tool. We estimated case fatality by age, HIV status, and sociodemographic development. We also calculated the HIV-attributable fraction and estimated health gap metrics, including disability-adjusted life-years (DALYs). Findings We estimated that 535 000 (95% uncertainty interval 409 000-705 000) cases of non-typhoidal salmonella invasive disease occurred in 2017, with the highest incidence in sub-Saharan Africa (34.5 [26.6-45.0] cases per 100 000 person-years) and in children younger than 5 years (34.3 [23.2-54.7] cases per 100 000 person-years). 77 500 (46 400-123 000) deaths were estimated in 2017, of which 18 400 (12 000-27 700) were attributable to HIV. The remaining 59 100 (33 300-98 100) deaths not attributable to HIV accounted for 4.26 million (2.38-7.38) DALYs in 2017. Mean all-age case fatality was 14.5% (9.2-21.1), with higher estimates among children younger than 5 years (13.5% [8.4-19.8]) and elderly people (51.2% [30.2-72.9] among those aged >= 70 years), people with HIV infection (41.8% [30.0-54.0]), and in areas of low sociodemographic development (eg, 15.8% [10.0-22.9] in sub-Saharan Africa). Interpretation We present the first global estimates of non-typhoidal salmonella invasive disease that have been produced as part of GBD 2017. Given the high disease burden, particularly in children, elderly people, and people with HIV infection, investigating the sources and transmission pathways of non-typhoidal salmonella invasive disease is crucial to implement effective preventive and control measures. Funding Bill & Melinda Gates Foundation. Copyright (c) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Keywords: 195 COUNTRIES; CLINICAL PRESENTATION; TERRITORIES; RESISTANCE; EPIDEMIOLOGY; INFECTIONS; DISABILITY; INJURIES; OUTCOME

Highly Productive Continuous Flow Synthesis of Di- and Tripeptides in Water

The reaction of amino acid derived N-carboxyanhydrides (NCAs) with unprotected amino acids under carefully controlled aqueous continuous flow conditions realized the formation of range of di- and tripeptide products in 60-85% conversion at productivities of up to 535 g.L-1h-1. This required a fundamental understanding of the physicochemical aspects of the reaction resulting in the design of a bespoke continuous stirred tank reactor (CSTR) with continuous solids addition, high shear mixing, automated pH control to avoid the use of buffer, and efficient heat removal to control the reaction at 1±1 °C

Rationalizing and Adapting Water-Accelerated Reactions for Sustainable Flow Organic Processes

Water-accelerated reactions, wherein at least one organic reactant is not soluble in water, are an important class of organic reactions, with a potentially pivotal impact on sustainability of chemical manufacturing processes. However, mechanistic understanding of the factors controlling the acceleration effect has been limited, due to the complex and varied physical and chemical nature of these processes. In this study, a theoretical framework has been established to calculate the rate acceleration of known water-accelerated reactions, giving computational estimations of the change to ΔG‡ which correlate with experimental data. In-depth study of a Henry reaction between N-methylisatin and nitromethane using our framework led to rationalization of the reaction kinetics, its lack of dependence on mixing, kinetic isotope effect, and different salt effects with NaCl and Na2SO4. Based on these findings, a multiphase flow process which includes continuous phase separation and recycling of the aqueous phase was developed, and its superior green metrics (PMI-reaction = 4 and STY = 0.64 kg L–1 h–1) were demonstrated. These findings form the essential basis for further in silico discovery and development of water-accelerated reactions for sustainable manufacturing

Ruthenacycles and Iridacycles as Catalysts for Asymmetric Transfer Hydrogenation and Racemisation

Ruthenacycles, which are easily prepared in a single step by reaction between enantiopure aromatic amines and [Ru(arene)Cl2]2 in the presence of NaOH and KPF6, are very good asymmetric transfer hydrogenation catalysts. A range of aromatic ketones were reduced using isopropanol in good yields with ee’s up to 98%. Iridacycles, which are prepared in similar fashion from [IrCp*Cl2]2 are excellent catalysts for the racemisation of secondary alcohols and chlorohydrins at room temperature. This allowed the development of a new dynamic kinetic resolution of chlorohydrins to the enantiopure epoxides in up to 90% yield and 98% enantiomeric excess (ee) using a mutant of the enzyme Haloalcohol dehalogenase C and an iridacycle as racemisation catalyst.