Synaptic oligomeric tau in Alzheimer's disease - A potential culprit in the spread of tau pathology through the brain.

In Alzheimer's disease, fibrillar tau pathology accumulates and spreads through the brain and synapses are lost. Evidence from mouse models indicates that tau spreads trans-synaptically from pre- to postsynapses and that oligomeric tau is synaptotoxic, but data on synaptic tau in human brain are scarce. Here we used sub-diffraction-limit microscopy to study synaptic tau accumulation in postmortem temporal and occipital cortices of human Alzheimer's and control donors.

The role of tyrosine hydroxylase-dopamine pathway in Parkinson's disease pathogenesis.

Background: Parkinson's disease (PD) is characterized by selective and progressive dopamine (DA) neuron loss in the substantia nigra and other brain regions, with the presence of Lewy body formation. Most PD cases are sporadic, whereas monogenic forms of PD have been linked to multiple genes, including Leucine kinase repeat 2 (LRRK2) and PTEN-induced kinase 1 (PINK1), two protein kinase genes involved in multiple signaling pathways. There is increasing evidence to suggest that endogenous DA and DA-dependent neurodegeneration have a pathophysiologic role in sporadic and familial PD.

Current dichotomous metrics obscure trends in severe and extreme child growth failure.

Historically, the prevalence of child growth failure (CGF) has been tracked dichotomously as the proportion of children more than 2 SDs below the median of the World Health Organization growth standards. However, this conventional "thresholding" approach fails to recognize child growth as a spectrum and obscures trends in populations with the highest rates of CGF. Our analysis presents the first ever estimates of entire distributions of HAZ, WHZ, and WAZ for each of 204 countries and territories from 1990 to 2020 for children less than 5 years old by age group and sex.

Lewy Body-like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α-Synuclein Mutations.

Objective: We utilized human midbrain-like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α-synuclein (α-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating α-syn- and Lewy body-related pathologies and the process of neurodegeneration in the hMLO model.

Methods: We generated and characterized hMLOs from GBA1 and SNCA overexpressing isogenic embryonic stem cells and also generated Lewy body-like inclusions in GBA1/SNCA dual perturbation hMLOs and conduritol-b-epoxide-treated SNCA triplication hMLOs.

Results: We identified for the first time that the loss of glucocerebrosidase, coupled with wild-type α-syn overexpression, results in a substantial accumulation of detergent-resistant, β-sheet-rich α-syn aggregates and Lewy body-like inclusions in hMLOs.

Potassium channel dysfunction in human neuronal models of Angelman syndrome.

Disruptions in the ubiquitin protein ligase E3A () gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability via ubiquitin-mediated degradation of calcium- and voltage-dependent big potassium (BK) channels.

Association of sugar-sweetened beverage intake at 18 months and 5 years of age with adiposity outcomes at 6 years of age: the Singapore GUSTO mother-offspring cohort.

Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767).

Hemodynamic Changes Are Predictive of Coagulopathic Hemorrhage After Living Donor Liver Transplant.

Objectives: Our goal was to evaluate the predictors of coagulopathic hemorrhage after living-donor liver transplant.

Materials And Methods: We retrospectively evaluated 161 patients who had undergone living-donor liver transplant from July 2005 to April 2014 at a single medical institution. Of these patients, 32 developed hemorrhage after transplant.