Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study.

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches.

Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Magnetic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission.

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia.

Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations.

Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer's Disease.

Objective: Identifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR-tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes. We examined the cerebrospinal fluid (CSF) MTBR-tau species in dominantly inherited Alzheimer's disease (DIAD) mutation carriers to assess the association with Alzheimer's disease (AD) biomarkers and clinical symptoms.

Methods: Cross-sectional and longitudinal CSF from 229 DIAD mutation carriers and 130 mutation non-carriers had sequential characterization of N-terminal/mid-domain phosphorylated tau (p-tau) followed by MTBR-tau species and tau positron emission tomography (tau PET), other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy.

The effect of a roving nurse mentor on household coverage and quality of care provided by community health worker teams in South Africa: a longitudinal study with a before, after and 6 months post design.

Objective: Community health workers (CHW) are undertaking more complex tasks as part of the move towards universal health coverage in many low- and middle-income settings. They are expected to provide promotive and preventative care, make referrals to the local clinic, and follow up on non-attendees for a range of health conditions. CHW programmes can improve access to care for vulnerable communities, but many such programmes struggle due to inadequate supervision, low levels of CHW literacy, and the marginalized status of CHW in the health system.

The Benson Complex Figure Test detects deficits in visuoconstruction and visual memory in symptomatic familial frontotemporal dementia: A GENFI study.

Objective: Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, and to explore its cognitive and neuroimaging correlates.

The political polarization of COVID-19 treatments among physicians and laypeople in the United States.

In the United States, liberals and conservatives disagree about facts. To what extent does expertise attenuate these disagreements? To study this question, we compare the polarization of beliefs about COVID-19 treatments among laypeople and critical care physicians. We find that political ideology predicts both groups' beliefs about a range of COVID-19 treatments.

A unified classification approach rating clinical utility of protein biomarkers across neurologic diseases.

A major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers.

Effective engagement of a stakeholder advisory board in severe mental illness (SMI) research: A case study of a clinical trial to improve adherence among people with SMI and hypertension.

Objective: Poor adherence to antihypertensive medication occurs in 50-80% of patients. An ongoing randomized controlled trial (RCT) is evaluating a personalized mobile-health intervention in poorly adherent hypertensive persons with bipolar disorder. To enhance efficacy, the ongoing trial elicited guidance from a Stakeholder Advisory Board (SAB) comprised of patients, family members, clinicians, and health system administrators.

Sleep Deprivation, Burnout, and Acute Care Surgery.

Purpose Of Review: To define what sleep deprivation is, how it relates to the growing problem of burnout within surgeons, and what can be done to mitigate its effects.

Recent Findings: There is a growing awareness that sleep deprivation, in both its acute and chronic manifestations, plays an immense role in burnout. The physical and mental manifestations of sleep deprivation are manifold, effecting nearly every physiologic system.

Anti-amyloid antibody therapies in Alzheimer's disease.

After years of failed attempts to develop a disease-modifying therapy for Alzheimer's disease, consistent evidence in support of clinical efficacy was finally presented for a monoclonal antibody targeting the amyloid-β protofibrils. In addition to meeting the primary outcome of slowing clinical disease progression over 18 months, secondary clinical outcomes and amyloid-β lowering on PET also underpin the positive results of the trial. In this opinion piece, we highlight the key characteristics of the previous unsuccessful trials and analyse the potential reasons why those attempts to develop a treatment for early Alzheimer's disease failed.

Nothingness, Oneness, and Infinity: Transcendent Experience as a Promising Frontier for Religion and Health Research.

This paper advocates for a renewed focus into the experiential domain of religious and spiritual expression in research on physical and mental health. Most studies, up to now, have investigated risk or protection associated with behavioral measures of religiousness, whether public behaviors such as religious attendance or private behaviors such as personal prayer. Religious attitudes, beliefs, and identity have been studied, as well, as have religious self-rating scales of various types, but, relatively less emphasized have been subjective experiences, such as feelings of transcendence or unitive connection with the divine.

Cross-sectional and longitudinal comparisons of biomarkers and cognition among asymptomatic middle-aged individuals with a parental history of either autosomal dominant or late-onset Alzheimer's disease.

Background: Comparisons of late-onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD) are confounded by age.

Methods: We compared biomarkers from cerebrospinal fluid (CSF), magnetic resonance imaging, and amyloid imaging with Pittsburgh Compound-B (PiB) across four groups of 387 cognitively normal participants, 42 to 65 years of age, in the Dominantly Inherited Alzheimer Network (DIAN) and the Adult Children Study (ACS) of LOAD: DIAN mutation carriers (MCs) and non-carriers (NON-MCs), and ACS participants with a positive (FH+) and negative (FH-) family history of LOAD.

Results: At baseline, MCs had the lowest age-adjusted level of CSF Aβ42 and the highest levels of total and phosphorylated tau-181, and PiB uptake.

Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales.

Background: Current clinical rating scales in frontotemporal dementia (FTD) often do not incorporate neuropsychiatric features and may therefore inadequately measure disease stage.

Methods: 832 participants from the Genetic FTD Initiative (GENFI) were recruited: 522 mutation carriers and 310 mutation-negative controls. The standardised GENFI clinical questionnaire assessed the frequency and severity of 14 neuropsychiatric symptoms: visual, auditory, and tactile hallucinations, delusions, depression, anxiety, irritability/lability, agitation/aggression, euphoria/elation, aberrant motor behaviour, hypersexuality, hyperreligiosity, impaired sleep, and altered sense of humour.

Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer's disease.

Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and CSF and is predictive of cognitive function in individuals with Alzheimer's disease. There has been limited prior work linking neurofilament light and functional connectivity, and no prior work has investigated neurofilament light associations with functional connectivity in autosomal dominant Alzheimer's disease. Here, we assessed relationships between blood neurofilament light, cognition, and functional connectivity in a cross-sectional sample of 106 autosomal dominant Alzheimer's disease mutation carriers and 76 non-carriers.

Prediction of extubation failure among low birthweight neonates using machine learning.

Objective: To develop machine learning models predicting extubation failure in low birthweight neonates using large amounts of clinical data.

Study Design: Retrospective cohort study using MIMIC-III, a large single-center, open-source clinical dataset. Logistic regression and boosted-tree (XGBoost) models using demographics, medications, and vital sign and ventilatory data were developed to predict extubation failure, defined as reintubation within 7 days.

Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study.

Unlabelled: A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation.

The Impact of COVID-19 on Surgical Volume and Productivity at an Academic Orthopaedic Surgery Department.

COVID-19 pandemic rapidly progressed, resulting in temporary cessation of elective surgery in the U.S. The goal of this study was to evaluate the impact of COVID-19 on surgical volume, charges, work relative value units (WRVUs), and net receipts at an academic orthopaedic surgery department.

Transitioning to Outpatient Shoulder Arthroplasty: Safety, Efficiency, and Cost in a Diverse Payer Mix.

Outpatient shoulder arthroplasty presents potential clinical benefits but also risk without perioperative optimization. Length of stay depends largely on surgeon preferences, and a large single-surgeon cohort may provide insight into optimal strategies and costs for outpatient shoulder arthroplasty. A single-surgeon cohort of 472 anatomic and reverse shoulder arthroplasties performed between 2017 and 2020 was retrospectively reviewed.

Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer's disease: Associations with Aβ-PET, neurodegeneration, and cognition.

Background: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility.

Methods: We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease.

Assessment of perfusion deficit with early phases of [F]PI-2620 tau-PET versus [F]flutemetamol-amyloid-PET recordings.

Purpose: Characteristic features of amyloid-PET (A), tau-PET (T), and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of amyloid- or tau-PET recordings serve to detect cerebrometabolic deficits equally to FDG-PET, therefore providing a surrogate of neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan.

Outcomes after bilateral shoulder arthroplasty: a systematic review.

The purpose of this systematic review was to report outcomes after bilateral shoulder arthroplasty including bilateral total shoulder arthroplasty (TSA), bilateral reverse shoulder arthroplasty (RSA), and ipsilateral TSA with contralateral RSA (TSA/RSA). Two reviewers independently performed a PRISMA-guided systematic search using MEDLINE/PubMed, Embase, and Cochrane Database of Systematic Reviews up to May 11, 2021. The databases were queried using the following search terms: (["bilateral" OR "contralateral"] AND "shoulder" AND ["arthroplast∗" OR "replacement"]).