Brain effects of 5:2 intermittent fasting and the healthy living diet in a randomized controlled trial.

Background: Insulin Resistance (IR) is implicated in brain aging and Alzheimer’s disease (AD) pathogenesis. Dietary changes may promote brain health in older adults with metabolic abnormalities. An extensive animal literature suggests pro‐cognitive and beneficial systemic and brain effects of intermittent fasting (IF) that may mitigate AD risk.

Critical assessment of anti-amyloid-β monoclonal antibodies effects in Alzheimer's disease: a systematic review and meta-analysis highlighting target engagement and clinical meaningfulness.

Despite most monoclonal antibodies against Aβ in Alzheimer's failed to demonstrate efficacy, the newest antibodies showed statistically significant clinical effects. We conducted a systematic review and meta-analysis to assess the efficacy, target engagement, and safety of anti-Aβ antibodies in sporadic AD including phase III RCTs published up to November 28, 2023. Antibodies as a drug class, attenuated worsening on the clinical scales CDR-SB and ADAS-Cog by very small effect sizes and reduced amyloid on PET by a very large effect size.

Brain responses to intermittent fasting and the healthy living diet in older adults.

Diet may promote brain health in metabolically impaired older individuals. In an 8-week randomized clinical trial involving 40 cognitively intact older adults with insulin resistance, we examined the effects of 5:2 intermittent fasting and the healthy living diet on brain health. Although intermittent fasting induced greater weight loss, the two diets had comparable effects in improving insulin signaling biomarkers in neuron-derived extracellular vesicles, decreasing the brain-age-gap estimate (reflecting the pace of biological aging of the brain) on magnetic resonance imaging, reducing brain glucose on magnetic resonance spectroscopy, and improving blood biomarkers of carbohydrate and lipid metabolism, with minimal changes in cerebrospinal fluid biomarkers for Alzheimer's disease.

Brain Iron Dysregulation in Iron Deficiency Anemia-Related Restless Leg Syndrome Revealed by Neuron-Derived Extracellular Vesicles: A Case-Control Study.

Brain iron deficiency (ID) and, to a degree, systemic ID have been implicated in restless leg syndrome (RLS) pathogenesis. Previously, we found increased ferritin in neuron-derived extracellular vesicles (NDEVs) in RLS, suggesting a mechanism for depleting intracellular iron by secreting ferritin-loaded NDEVs. In this study, we hypothesized that increased NDEV ferritin occurs even in RLS accompanied by systemic ID and that neuronal intracellular iron depletion in RLS also manifests as NDEV abnormalities in other iron regulatory proteins, specifically, decreased transferrin receptor (TfR) and increased ferroportin.

Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

Background And Aims: Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F).

Approach And Results: A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed.

Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

Background And Aims: Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease.

Approach And Results: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022.

Open-Label Sulforaphane Trial in FMR1 Premutation Carriers with Fragile-X-Associated Tremor and Ataxia Syndrome (FXTAS).

Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60-88 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane.

Comparative assessment of Alzheimer's disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study.

Alzheimer's disease (AD) is currently defined according to biomarkers reflecting the core underlying neuropathological processes: Aβ deposition, Tau, and neurodegeneration (ATN). The soluble phase of plasma and plasma neuron-derived extracellular vesicles (NDEVs) are increasingly being investigated as sources of biomarkers. The aim of this study was to examine the comparative biomarker potential of these two biofluids, as well as the association between respective biomarkers.

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 () gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death.

Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta-analysis of 92 studies.

Aims: Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs.

Methods: Medline and Embase were systematically searched until April 2021.

Isolated Abducens Nerve Palsy in a Patient With COVID-19: A Case Report and Literature Review.

Introduction: The pandemic of coronavirus disease 2019 (COVID-19) stands as a major global health and social burden. As cases are growing, several other symptoms, besides the typical respiratory ones, are emerging. The involvement of the nervous system is increasingly recognized with manifestations ranging from hyposmia to meningoencephalitis and cranial neuropathies.

Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta-analysis.

Aim: To compare the effects of glucose-lowering drugs on body weight and blood pressure in adults with type 2 diabetes.

Methods: We searched Medline, Embase, the Cochrane Library, and grey literature sources until 29 September 2020 for randomized controlled trials of at least 24 weeks' duration assessing the effects of glucose-lowering drugs on body weight and blood pressure in adults with type 2 diabetes. We performed frequentist network meta-analyses and calculated weighted mean differences and 95% confidence intervals combining trial arms of different approved doses of a given intervention into a single group.

Dabigatran, rivaroxaban, and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation: An updated meta-analysis.

Background: Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation (AF) originated from western countries.

Aim: To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.

Methods: Medline, Cochrane, and ClinicalTrial.

Comparative efficacy and safety of glucose-lowering drugs as adjunctive therapy for adults with type 1 diabetes: A systematic review and network meta-analysis.

Aim: To assess the efficacy and safety of glucose-lowering drugs used as an adjunct to insulin therapy in adults with type 1 diabetes.

Methods: We searched Medline, Embase and the Cochrane Central Register of Controlled Trials up to 24 January 2020 for randomized controlled trials. Our primary outcome was change in HbA1c.

Targeted Therapy- and Chemotherapy-Associated Skin Toxicities: Systematic Review and Meta-Analysis.

Problem Identification: Preventing and managing skin toxicities can minimize treatment disruptions and improve well-being. This systematic review aimed to evaluate the effectiveness of interventions for the prevention and management of cancer treatment-related skin toxicities.

Literature Search: The authors systematically searched for comparative studies published before April 1, 2019.

Prospective Surveillance and Risk Reduction of Cancer Treatment-Related Lymphedema: Systematic Review and Meta-Analysis.

Problem Identification: Secondary lymphedema is a chronic condition that may result from cancer-related treatments. Evidence is emerging on prospective surveillance and risk reduction.

Literature Search: Databases were systematically searched through April 1, 2019, for comparative studies evaluating interventions aiming to prevent lymphedema in patients with cancer.

Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

Background: Several pharmacologic options for type 2 diabetes are available.

Purpose: To compare benefits and harms of glucose-lowering drugs in adults with type 2 diabetes.

Data Sources: Several databases from inception through 18 December 2019 and ClinicalTrials.

Carvedilol for prevention of variceal bleeding: a systematic review and meta-analysis.

Background: Beta-blockers are used for prophylaxis of variceal bleeding. Our aim was to assess the efficacy and safety of carvedilol for primary or secondary prevention of variceal bleeding in patients with cirrhosis.

Methods: We searched Medline, Embase, CENTRAL and gray literature sources for randomized controlled trials (RCTs) comparing carvedilol with placebo or any active intervention.

Intravenous Immunoglobulin for Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Aim: To assess the efficacy and safety of intravenous immunoglobulin (IVIg) for patients with Alzheimer's disease (AD).

Materials And Methods: We searched electronic databases and other sources for randomized controlled trials comparing IVIg with placebo or other treatment for adults with AD. Primary outcome was change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog).

Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.

Aims: To assess the efficacy and safety of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes.

Materials And Methods: We searched major electronic databases and grey literature sources for randomized controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA1c.