Collapse of late endosomal pH elicits a rapid Rab7 response via the V-ATPase and RILP.

Endosomal-lysosomal trafficking is accompanied by the acidification of endosomal compartments by the H+-V-ATPase to reach low lysosomal pH. Disruption of the correct pH impairs lysosomal function and the balance of protein synthesis and degradation (proteostasis). Here, we treated mammalian cells with the small dipeptide LLOMe, which is known to permeabilize lysosomal membranes, and find that LLOMe also impacts late endosomes (LEs) by neutralizing their pH without causing membrane permeabilization.

Use of perceptual memory as a performance validity indicator: initial validation with simulated mild traumatic brain injury.

Introduction: Many commonly employed performance validity tests (PVTs) are several decades old and vulnerable to compromise, leading to a need for novel instruments. Because implicit/non-declarative memory may be robust to brain damage, tasks that rely upon such memory may serve as an effective PVT. Using a simulation design, this experiment evaluated whether novel tasks that rely upon perceptual memory hold promise as PVTs.

Brain 11β-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem™ Assessed by PET in Alzheimer's Disease and Cognitively Normal Individuals.

Background: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates intracellular cortisol and its inhibition by the small molecule inhibitor, Xanamem™, may provide a disease-modifying strategy for Alzheimer's disease (AD). Animal models suggest a range of 30-60% enzyme inhibition may suffice to provide neuroprotection.

Objective: To determine the regional brain occupancy of 11β-HSD1 by Xanamem™ in cognitively normal participants (CN) and mild cognitive impairment (MCI)/mild AD patients to investigate potential dosing ranges for future efficacy studies.

Morphodynamics of a composite sand-cobble beach in response to extratropical cyclone Fiona and seasonal wave variability.

Climate change is driving higher coastal water levels, and models project accelerated future sea-level rise and coastal storm intensification. These dynamics paired with anthropogenic coastal alterations will drive drastic coastal change worldwide. Composite beaches with mixed sediment sizes warrant detailed study as these exhibit complex morphodynamics in response to changing hydrodynamics due to the distinct transport thresholds of different sediment types.

Collapse of late endosomal pH elicits a rapid Rab7 response via V-ATPase and RILP.

Endosomal-lysosomal trafficking is accompanied by the acidification of endosomal compartments by the H-V-ATPase to reach low lysosomal pH. Disruption of proper pH impairs lysosomal function and the balance of protein synthesis and degradation (proteostasis). We used the small dipeptide LLOMe, which is known to permeabilize lysosomal membranes, and find that LLOMe also impacts late endosomes (LEs) by neutralizing their pH without causing membrane permeabilization.

Regulation of Endosomal Trafficking by Rab7 and Its Effectors in Neurons: Clues from Charcot-Marie-Tooth 2B Disease.

Intracellular endosomal trafficking controls the balance between protein degradation and synthesis, i.e., proteostasis, but also many of the cellular signaling pathways that emanate from activated growth factor receptors after endocytosis.

Geriatric Phenotypes and Their Impact on Oral Health.

Older adults have multiple morbidities that can impact oral, systemic, and psychological health. Although each disorder requires consideration from the provider before treatment, by assessing the common phenotypic presentations of older adults, we can better understand, select, and coordinate treatment modifications that would need to be considered and implemented for dental care.

Cross-Sectional and Longitudinal Comparison of Tau Imaging with 18F-MK6240 and 18F-Flortaucipir in Populations Matched for Age, MMSE and Brain Beta-Amyloid Burden.

Objectives: Longitudinal tau quantification may provide a useful marker of drug efficacy in clinical trials. Different tau PET tracers may have different sensitivity to longitudinal changes, but without a head-to-head dataset or a carefully designed case-matching procedure, comparing results in different cohorts can be biased. In this study, we compared the tau PET tracers, 18F-MK6240 and 18F-flortaucipir (FTP), both cross-sectionally and longitudinally by case-matching subjects in the AIBL and ADNI longitudinal cohort studies.

Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer's Disease.

Background: Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD.

Oral health for baby boomers: Past, present, and future.

Aims: This paper reviews the oral health services which were available for early (1945-1955) and late (1956-1964) baby boomers, as well as predicts their future oral healthcare needs.

Methods And Results: The knowledge, beliefs, and attitudes of the parents of the baby boomers toward dental hygiene and oral healthcare, are reviewed. The introduction of dental health screenings occurred from 1910 to early 1970s, the creation of the first dental hygiene school and the introduction of water fluoridation influenced oral healthcare.

Endosomal Transport to Lysosomes and the Trans-Golgi Network in Neurons and Other Cells: Visualizing Maturational Flux.

High-level microscopy enables the comprehensive study of dynamic intracellular processes. Here we describe a toolkit of combinatorial approaches for fixed cell imaging and live cell imaging to investigate the interactions along the trans-Golgi network (TGN)-endosome-lysosome transport axis, which underlie the maturation of endosomal compartments and degradative flux. For fixed cell approaches, we specifically highlight how choices of permeabilization conditions, antibody selection, and antibody multiplexing affect interpretation of results.

Opioids and older adults: Increasing trends in opioid usage in a dental population compared to a National Database (NHANES).

Aim: To examine self-reported opioid prevalence at a dental school clinic for patients ≥65 years old as compared to national data, comparing gender, ethnicity/race and older adult age groupings.

Methods And Results: Self-reported prescription opioid medication use was extracted from the medical record for dental patients ≥65 years old who visited the school's general dental clinic (GDC) in 2012 or 2017. This data was compared to the National Health and Nutrition Examination Survey (NHANES) data for 2011-2012 and 2017-18.

First-in-Humans Evaluation of F-SMBT-1, a Novel F-Labeled Monoamine Oxidase-B PET Tracer for Imaging Reactive Astrogliosis.

Reactive gliosis, characterized by reactive astrocytes and activated microglia, contributes greatly to neurodegeneration throughout the course of Alzheimer disease (AD). Reactive astrocytes overexpress monoamine oxidase B (MAO-B). We characterized the clinical performance of F-()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline (F-SMBT-1), a novel MAO-B PET tracer as a potential surrogate marker of reactive astrogliosis.

Assessing Reactive Astrogliosis with F-SMBT-1 Across the Alzheimer Disease Spectrum.

A neuroinflammatory reaction in Alzheimer disease (AD) brains involves reactive astrocytes that overexpress monoamine oxidase-B (MAO-B). F-()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline (F-SMBT-1) is a novel F PET tracer highly selective for MAO-B. We characterized the clinical performance of F-SMBT-1 PET across the AD continuum as a potential surrogate marker of reactive astrogliosis.

Classification accuracy of the word memory test genuine memory impairment index.

Objective: The Word Memory Test (WMT) assesses non-credible performance in neuropsychological assessment. To mitigate risk of false positives among patients with severe cognitive dysfunction, the Genuine Memory Impairment Profile was derived. Only a modest number of investigations has evaluated classification accuracy among clinical samples, leaving the GMIP's accuracy largely uncertain.

PET Imaging of brain muscarinic receptors with F-Fluorobenzyl-Dexetimide: A first in human study.

M1 and M4 muscarinic receptor (mAChR) agonists are under development for the treatment of schizophrenia, Alzheimer's and Parkinson's disease. We performed first-in-human PET imaging of mAChR with F-Fluorobenzyl-Dexetimide (FDEX) in 10 healthy participants (29.4±4.

Association of Oral Health and Mini Nutritional Assessment in Older Adults: A Systematic Review with Meta-analyses.

Purpose: To evaluate whether poor oral health is associated with a higher risk of malnutrition based on the Mini Nutritional Assessment (MNA) or MNA-SF (short form) in older adults.

Study Selection: For this meta-analysis, cohort and cross-sectional studies with adults 65 years and older, reporting oral health outcomes (i.e.

Computed Tomography and Magnetic Resonance Imaging are Similarly Reliable in the Assessment of Glenohumeral Arthritis and Glenoid Version.

Background: The purpose of this study was to compare the intraobserver and interobserver reliability of CT and T2-weighted MRI for evaluation of the severity of glenoid wear, glenohumeral subluxation, and glenoid version.

Methods: Sixty-one shoulders with primary osteoarthritis had CT and MRI scans before shoulder arthroplasty. All slices were blinded and randomized before evaluation.

Memory in multiple sclerosis: A reappraisal using the item specific deficit approach.

Objective: As many as 65% of people with multiple sclerosis (MS) have clinically significant memory impairment, but the nature of this deficit is controversial. Some investigations suggest that an inability to retrieve newly learned information from memory is prominent, whereas others imply that compromised acquisition accounts for impairment. Prior research has not simultaneously evaluated acquisition and retrieval processes in MS, and fewer have attempted to account for initial acquisition when studying retrieval.

A RanBP2-type zinc finger protein functions in intron splicing in Arabidopsis mitochondria and is involved in the biogenesis of respiratory complex I.

The RanBP2 zinc finger (Znf) domain is a prevalent domain that mediates protein interaction and RNA binding. In Arabidopsis, a clade of four RanBP2 Znf-containing proteins, named the Organelle Zinc (OZ) finger family, are known or predicted to be targeted to either the mitochondria or the plastids. Previously we reported that OZ1 is absolutely required for the editing of 14 sites in chloroplasts.

Geriatric Phenotypes and Their Impact on Oral Health.

Older adults have multiple morbidities that can impact oral, systemic, and psychological health. Although each disorder requires consideration from the provider before treatment, by assessing the common phenotypic presentations of older adults, we can better understand, select, and coordinate treatment modifications that would need to be considered and implemented for dental care.

Effects of diminished positive mood and depressed mood upon verbal learning and memory among people with multiple sclerosis.

: Cognitive impairment affects as many as 65% of people with multiple sclerosis (PWMS), and memory impairment confers greater severity of disability and functional impairment. Depression is also common among PWMS, and lifetime prevalence rates are as high as 50%. Research has yet to clearly define the relationship between memory dysfunction and depression among PWMS, and may reflect incomplete assessment of depressive symptoms.

Efficacy of denture adhesives in complete denture wearers compared to denture wearers not using denture adhesives. A systematic review.

Aim: The objective of this systematic review was to evaluate the efficacy of denture adhesives (DAs) in completely edentulous denture wearers compared to not using DAs.

Methods And Results: PubMed, Web of Science, Cochrane Library, and EMBASE were searched from the database inception up to 6 February 2020 for Randomized Controlled Trials (RCTs) involving patients with complete dentures in both arches where the use of DAs was compared to no use of DAs. A total of 497 abstracts were reviewed, resulting in inclusion of 10 RCTs.

Case Report: F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player.

It remains unclear if tau imaging may assist diagnosis of chronic traumatic encephalopathy (CTE). Flortaucipir PET has shown superior frontal with medial temporal tau binding consistent with the provisional neuropathological criteria for mid-stage CTE in group-level analyses of retired symptomatic NFL players and in one individual with pathologically confirmed CTE. F-MK6240 is a new PET ligand that has high affinity for tau.