Newborn morbidities and care procedures at the special newborn care units of Gandaki Province, Nepal: a retrospective study.

Background: Despite recent improvements in the overall health status of Nepal's population, newborn morbidities and mortalities have remained a challenge. This study explores the situation and care strategies for newborn health problems in the Gandaki Province of Nepal.

Methods: This is a retrospective hospital records analysis.

Characteristics of and Risk Factors for Depressive Symptoms Preceding Dementia: A Study of 82-Year-Old Men From the Uppsala Longitudinal Study of Adult Men.

Background: Depression and dementia are known to be associated. The identification of characteristics distinguishing depression prodromal to dementia from other depressive symptoms would be of value for early identification of dementia. The study of risk factors for depressive symptoms prodromal to dementia could improve preventive care and provide clues to the causes of dementia.

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.

Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.

Design, Setting, And Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age.

Altered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion.

Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer's disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation properties of Aβ. We recently identified the Uppsala APP mutation (APPUpp), which causes Aβ pathology by a triple mechanism: increased β-secretase and altered α-secretase APP cleavage, leading to increased formation of a unique Aβ conformer that rapidly aggregates and deposits in the brain.

Prediction of conversion to dementia disorders based on timed up and go dual-task test verbal and motor outcomes: a five-year prospective memory-clinic-based study.

Background: While assessment tools can increase the detection of cognitive impairment, there is currently insufficient evidence regarding clinical outcomes based on screening for cognitive impairment in older adults.

Methods: The study purpose was to investigate whether Timed Up and Go dual-task test (TUGdt) results, based on TUG combined with two different verbal tasks (name different animals, TUGdt-NA, and recite months in reverse order, TUGdt-MB), predicted dementia incidence over a period of five years among patients (N = 186, mean = 70.7 years; 45.

Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases.

Dual-Task Interference of Gait Parameters During Different Conditions of the Timed Up-and-Go Test Performed by Community-Dwelling Older Adults.

The Timed Up-and-Go (TUG) test has been combined with different verbal/cognitive tasks (i.e., TUG dual task [TUGdt]) as a form of motor-cognitive testing.

Mixed Pathologies in a Subject with a Novel PSEN1 G206R Mutation.

Background: There are more than 300 presenilin-1 (PSEN1) mutations identified but a thorough postmortem neuropathological assessment of the mutation carriers is seldom performed.

Objective: To assess neuropathological changes (NC) in a 73-year-old subject with the novel PSEN1 G206R mutation suffering from cognitive decline in over 20 years. To compare these findings with an age- and gender-matched subject with sporadic Alzheimer's disease (sAD).

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10), which were delineated to 338 distinct association signals.

CRISPR-Cas9 treatment partially restores amyloid-β 42/40 in human fibroblasts with the Alzheimer's disease M146L mutation.

Presenilin 1 (PS1) is a central component of γ-secretase, an enzymatic complex involved in the generation of the amyloid-β (Aβ) peptide that deposits as plaques in the Alzheimer's disease (AD) brain. The M146L mutation in the PS1 gene () leads to an autosomal dominant form of early-onset AD by promoting a relative increase in the generation of the more aggregation-prone Aβ42. This change is evident not only in the brain but also in peripheral cells of mutation carriers.

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

Mutation analysis of disease causing genes in patients with early onset or familial forms of Alzheimer's disease and frontotemporal dementia.

Background: Most dementia disorders have a clear genetic background and a number of disease genes have been identified. Mutations in the tau gene (MAPT) lead to frontotemporal dementia (FTD), whereas mutations in the genes for the amyloid-β precursor protein (APP) and the presenilins (PSEN1, PSEN2) cause early-onset, dominantly inherited forms of Alzheimer's disease (AD). Even if mutations causing Mendelian forms of these diseases are uncommon, elucidation of the pathogenic effects of such mutations have proven important for understanding the pathogenic processes.

Extraction of gait parameters from marker-free video recordings of Timed Up-and-Go tests: Validity, inter- and intra-rater reliability.

Background: We study dual-task performance with marker-free video recordings of Timed Up-and-Go tests (TUG) and TUG combined with a cognitive/verbal task (TUG dual-task, TUGdt).

Research Question: Can gait parameters be accurately estimated from video-recorded TUG tests by a new semi-automatic method aided by a technique for human 2D pose estimation based on deep learning?

Methods: Thirty persons aged 60-85 years participated in the study, conducted in a laboratory environment. Data were collected by two synchronous video-cameras and a marker-based optoelectronic motion capture system as gold standard, to evaluate the gait parameters step length (SL), step width (SW), step duration (SD), single-stance duration (SSD) and double-stance duration (DSD).