Validation of AD8-Philippines (AD8-P): A brief informant-based questionnaire for dementia screening in the Philippines

Aim: This study was aimed at validating the Filipino version of AD8 (AD8-P). Methods: Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for dementia. Results: A total of 366 community-dwelling Filipino older persons aged ≥60 years, 213 with normal cognition and 153 with dementia, and their informants were included in this study. Majority (90%) were at the mildest stage of dementia. Area under the receiver-operating-characteristic curve (AUROC) for AD8-P was 0.94 (95% CI 0.92 to 0.96), demonstrating excellent overall predictive power to screen for dementia. The optimal AD8-P cut-off score with best balance sensitivity (91.5%) and specificity (77.9%) was ≥3. Conclusion: AD8-P demonstrated good psychometric properties to screen for dementia, even at the earliest stage of cognitive decline

A High Docosahexaenoic Acid Diet Alters the Lung Inflammatory Response to Acute Dust Exposure

Agricultural workers are at risk for the development of acute and chronic lung diseases due to their exposure to organic agricultural dusts. A diet intervention using the omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to be an effective therapeutic approach for alleviating a dust-induced inflammatory response. We thus hypothesized a high-DHA diet would alter the dust-induced inflammatory response through the increased production of specialized pro-resolving mediators (SPMs). Mice were pre-treated with a DHA-rich diet 4 weeks before being intranasally challenged with a single dose of an extract made from dust collected from a concentrated swine feeding operation (HDE). This omega-3-fatty-acid-rich diet led to reduced arachidonic acid levels in the blood, enhanced macrophage recruitment, and increased the production of the DHA-derived SPM Resolvin D1 (RvD1) in the lung following HDE exposure. An assessment of transcript-level changes in the immune response demonstrated significant differences in immune pathway activation and alterations of numerous macrophage-associated genes among HDE-challenged mice fed a high DHA diet. Our data indicate that consuming a DHA-rich diet leads to the enhanced production of SPMs during an acute inflammatory challenge to dust, supporting a role for dietary DHA supplementation as a potential therapeutic strategy for reducing dust-induced lung inflammation

A contemporary comparison of the effect of shunt type in hypoplastic left heart syndrome on the hemodynamics and outcome at stage 2 reconstruction

ObjectiveWe compare the hemodynamics and perioperative course of shunt type in hypoplastic left heart syndrome at the time of stage 2 reconstruction and longer-term survival.MethodsWe retrospectively reviewed the echocardiograms, catheterizations, and hospital records of all patients who had a stage 1 reconstruction between January 2002 and May 2005 and performed a cross-sectional analysis of hospital survivors.ResultsOne hundred seventy-six patients with hypoplastic left heart syndrome and variants underwent a stage 1 reconstruction with either a right ventricle–pulmonary artery conduit (n = 62) or a modified Blalock–Taussig shunt (n = 114). The median duration of follow-up is 29.1 months (range, 0-57 months). By means of Kaplan–Meier analysis, there is no difference in survival at 3 years (right ventricle–pulmonary artery conduit: 73% [95% confidence limit, 59%–83%] vs modified Blalock–Taussig shunt: 69% [95% confidence limit, 59%–77%]; P = .6). One hundred twenty-four patients have undergone stage 2 reconstruction (78 modified Blalock–Taussig shunts and 46 right ventricle–pulmonary artery conduits). At the time of the stage 2 reconstruction, patients with right ventricle–pulmonary artery conduits were younger (153 days [range, 108–340 days]; modified Blalock–Taussig shunt, 176 days [range, 80–318 days]; P = .03), had lower systemic oxygen saturation (73% [range, 58%–85%] vs 77% [range, 57%–89%], P < .01), and had higher preoperative hemoglobin levels (15.8 g/dL [range, 13–21 g/dL] vs 14.8 g/dL [range, 12–19 g/dL], P < .01) compared with those of the modified Blalock–Taussig shunt group. By means of echocardiographic evaluation, there was a higher incidence of qualitative ventricular dysfunction in patients with right ventricle–pulmonary artery conduits (14/46 [31%] vs 9/73 [12%], P = .02). However, no difference was observed in common atrial pressure or the arteriovenous oxygen difference.ConclusionInterim analyses suggest no advantage of one shunt type over another. This report raises concern of late ventricular dysfunction and outcome in patients with a right ventricle–pulmonary artery conduit

Tackling challenges in care of Alzheimer's disease and other dementias amid the COVID-19 pandemic, now and in the future

We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, outpatient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term

Blood amyloid-β oligomerization associated with neurodegeneration of Alzheimers disease

Introduction Oligomeric amyloid-ß is a major toxic species associated with Alzheimers disease pathogenesis. Methods used to measure oligomeric amyloid-β in the blood have increased in number in recent years. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a specific method to measure oligomerization tendencies in the blood. The objective of this study was to determine the association between amyloid-ß oligomerization in the plasma and structural changes of the brain. Methods We studied 162 subjects composed of 92 community-based normal healthy subjects, 17 with subjective cognitive decline, 14 with mild cognitive impairment and 39 with Alzheimers disease dementia. All subjects underwent MDS-OAβ and three-dimensional T1 magnetic resonance imaging. To determine the structural changes of the brain that are statistically correlated with MDS-OAβ level, we used voxel-based morphometry with corrections for age and total intracranial volume covariates. Results We found brain volume reduction in the bilateral temporal, amygdala, parahippocampal and lower parietal lobe and left cingulate and precuneus regions (family-wise error, p < 0.05). Reduction was also found in white matter in proximity to the left temporal and bilateral lower parietal lobes and posterior corpus callosum (family-wise error, p < 0.05). Brain volume increment was not observed in any regions within grey or white matter. Discussion Findings suggest that substantial correlation exists between amyloid ß oligomerization in the blood and brain volume reduction in the form of Alzheimers disease despite of uncertainty in the casual relationship.This work was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C1251)

Lynx Mission Concept Status

Lynx is a concept under study for prioritization in the 2020 Astrophysics Decadal Survey. Providing orders of magnitude increase in sensitivity over Chandra, Lynx will examine the first black holes and their galaxies, map the large-scale structure and galactic halos, and shed new light on the environments of young stars and their planetary systems. In order to meet the Lynx science goals, the telescope consists of a high-angular resolution optical assembly complemented by an instrument suite that may include a High Definition X-ray Imager, X-ray Microcalorimeter and an X-ray Grating Spectrometer. The telescope is integrated onto the spacecraft to form a comprehensive observatory concept. Progress on the formulation of the Lynx telescope and observatory configuration is reported in this paper

Effects of an exercise program on hepatic metabolism, hepatic fat, and cardiovascular health in overweight/obese adolescents from Bogotá, Colombia (the HEPAFIT study): study protocol for a randomized controlled trial

Background: A considerable proportion of contemporary youth have a high risk of obesity-related disorders such as cardiovascular disease, metabolic syndrome, or non-alcoholic fatty liver disease (NAFLD). Although there is consistent evidence for the positive effects of physical activity on several health aspects, most adolescents in Colombia are sedentary. It is, therefore, important to implement strategies that generate changes in lifestyle. The HEPAFIT study aims to examine whether a 6-month exercise program has benefits for hepatic fat content and cardiovascular health outcomes among overweight/obese adolescents from Bogotá, Colombia. Methods/design: Altogether, 100 hundred overweight/obese, sedentary adolescents (aged 11–17 years) attending two public schools in Bogotá, Colombia, will be included in a parallel-group randomized controlled trial. Adolescents will be randomly assigned to an intervention group following one of four curricula: (1) the standard physical education curriculum (60 min per week of physical activity, n = 25) at low-to-moderate intensity; (2) a high-intensity physical education curriculum (HIPE, n = 25), consisting of endurance and resistance games and non-competitive activities, such as running, gymkhanas, lifting, pushing, wrestling, or hauling, for 60-min sessions, three times per week, with an energy expenditure goal of 300 to 500 kcal/session at 75–85% maximum heart rate (HRmax); (3) a low-to-moderate intensity physical education curriculum (LIPE, n = 25) consisting of endurance and resistance games and non-competitive activities (e.g., chasing, sprinting, dribbling, or hopping) for 60-min sessions, three times per week with an energy expenditure goal of 300 kcal/session at 55–75% HRmax; and (4) a combined HIPE and LIPE curriculum (n = 25). The HIPE, LIPE, and combined interventions were performed in addition to the standard physical education curriculum. The primary outcome for effectiveness is liver fat content, as measured by the controlled attenuation parameter 1 week after the end of the intervention program. Discussion: The translational focus may be suitable for collecting new information in a school setting on the possible effects of physical activity interventions to reduce liver fat content and to improve metabolic profiles and the cardiometabolic health of overweight/obese adolescents. This may lead to the more efficient use of school physical education resources.The HEPAFIT study was carried out with the financial support of Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología “Francisco José de Caldas” COLCIENCIAS (code 59700 and no 122277757900). Katherine González-Ruíz receive a scholarship from Universidad del Rosario, Colombia, Escuela de Medicina y Ciencias de la Salud, to do a Doctorate. This article presents independent research commissioned by COLCIENCIAS under its Program Grants for Applied Research funding scheme (Convocatoria 777–2017)

Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCF^Slmb degron

Spinal muscular atrophy (SMA) is caused by homozygous mutations in human SMN1. Expression of a duplicate gene (SMN2) primarily results in skipping of exon 7 and production of an unstable protein isoform, SMNΔ7. Although SMN2 exon skipping is the principal contributor to SMA severity, mechanisms governing stability of survival motor neuron (SMN) isoforms are poorly understood. We used a Drosophila model system and label-free proteomics to identify the SCFSlmb ubiquitin E3 ligase complex as a novel SMN binding partner. SCFSlmb interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box oligomerization domains. Substitution of a conserved serine (S270A) interferes with SCFSlmb binding and stabilizes SMNΔ7. SMA-causing missense mutations that block multimerization of full-length SMN are also stabilized in the degron mutant background. Overexpression of SMNΔ7S270A, but not wild-type (WT) SMNΔ7, provides a protective effect in SMA model mice and human motor neuron cell culture systems. Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered when SMN forms higher-order multimers

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18