Submicron Dispersions of Phytosterols Reverse Liver Steatosis with Higher Efficacy than Phytosterol Esters in a Diet Induced-Fatty Liver Murine Model.

Consumption of phytosterols is a nutritional strategy employed to reduce cholesterol absorption, but recent research shows that their biological activity might go beyond cholesterol reduction for the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD), and novel phytosterol formulations, such as submicron dispersions, could improve these effects. We explored the therapeutic activity of phytosterols, either formulated as submicron dispersions of phytosterols (SDPs) or conventional phytosterol esters (PEs), in a mouse model of MAFLD. MAFLD was induced in mice by atherogenic diet (AD) feeding.

Preclinical activity of resazurin in acute myeloid leukaemia.

Resazurin, a phenoxazine used in cell viability assays, acts in vitro as an anti-leukaemic compound through the production of cellular reactive oxygen species (ROS) resulting in mitochondrial dysfunction and cell death. However, the in vivo tolerance and efficacy of resazurin in cancer are unknown. In this study, we investigated the in vitro and in vivo effects of resazurin in acute myeloid leukaemia (AML).

Hospital-Level Variation in COVID-19 Treatment Among Hospitalized Adults in the United States: A Retrospective Cohort Study.

Study Design: Retrospective cohort study.

Objective: To characterize variation in dexamethasone and remdesivir use over time among hospitals.

Background: Little is known about hospital-level variation in COVID-19 drug treatments in a large and diverse network in the United States.

The effectiveness of coronary computed tomography angiography and functional testing for the diagnosis of obstructive coronary artery disease: results from the individual patient data Collaborative Meta-Analysis of Cardiac CT (COME-CCT).

Aim: To determine the effectiveness of functional stress testing and computed tomography angiography (CTA) for diagnosis of obstructive coronary artery disease (CAD).

Methods And Results: Two-thousand nine-hundred twenty symptomatic stable chest pain patients were included in the international Collaborative Meta-Analysis of Cardiac CT consortium to compare CTA with exercise electrocardiography (exercise-ECG) and single-photon emission computed tomography (SPECT) for diagnosis of CAD defined as ≥ 50% diameter stenosis by invasive coronary angiography (ICA) as reference standard. Generalised linear mixed models were used for calculating the diagnostic accuracy of each diagnostic test including non-diagnostic results as dependent variables in a logistic regression model with random intercepts and slopes.

Timut Pepper Extract Slows Age-Dependent Decline of Mobility and Collagen Loss and Promotes Longevity.

Investigations into human longevity are increasingly focusing on healthspan enhancement, not just lifespan extension. Lifestyle modifications and nutritional choices, including food supplements, can significantly affect aging and general health. Phytochemicals in centenarians' diets, such as those found in Timut pepper, a Nepalese spice with various medicinal properties, may contribute to their longevity.

Epistemological Flexibility in Person-Centered Care: The Cynefin Framework for (Re)Integrating Indigenous Body Representations in Manual Therapy.

Background: Chiropractic, osteopathy, and physiotherapy (COP) professionals regulated outside the United States traditionally incorporate hands-on procedures aligned with their historical principles to guide patient care. However, some authors in COP research advocate a pan-professional, evidence-informed, patient-centered approach to musculoskeletal care, emphasizing hands-off management of patients through education and exercise therapy. The extent to which non-Western sociocultural beliefs about body representations in health and disease, including Indigenous beliefs, could influence the patient-practitioner dyad and affect the interpretation of pillars of evidence-informed practice, such as patient-centered care and patient expectations, remains unknown.

Haploinsufficiency underlies the neurodevelopmental consequences of SLC6A1 variants.

Heterozygous variants in SLC6A1, encoding the GAT-1 GABA transporter, are associated with seizures, developmental delay, and autism. The majority of affected individuals carry missense variants, many of which are recurrent germline de novo mutations, raising the possibility of gain-of-function or dominant-negative effects. To understand the functional consequences, we performed an in vitro GABA uptake assay for 213 unique variants, including 24 control variants.

Monosomy 7/del(7q) cause sensitivity to inhibitors of nicotinamide phosphoribosyltransferase in acute myeloid leukemia.

Monosomy 7 and del(7q) (-7/-7q) are frequent chromosomal abnormalities detected in up to 10% of patients with acute myeloid leukemia (AML). Despite unfavorable treatment outcomes, no approved targeted therapies exist for patients with -7/-7q. Therefore, we aimed to identify novel vulnerabilities.

Oncogenic context shapes the fitness landscape of tumor suppression.

Tumors acquire alterations in oncogenes and tumor suppressor genes in an adaptive walk through the fitness landscape of tumorigenesis. However, the interactions between oncogenes and tumor suppressor genes that shape this landscape remain poorly resolved and cannot be revealed by human cancer genomics alone. Here, we use a multiplexed, autochthonous mouse platform to model and quantify the initiation and growth of more than one hundred genotypes of lung tumors across four oncogenic contexts: KRAS G12D, KRAS G12C, BRAF V600E, and EGFR L858R.

Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia.

Background: Increasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the pathogenesis of ePVS remains unknown. Here, we tested the possibility that baseline cerebrovascular dysfunction, as measured by a magnetic resonance imaging measure of cerebrovascular reactivity, contributes to the later development of ePVS.

Safety of Switching From a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients With Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.

Background: There is ambiguity whether frail patients with atrial fibrillation managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC).

Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older patients with atrial fibrillation living with frailty (≥75 years of age plus a Groningen Frailty Indicator score ≥3) were randomly assigned to switch from international normalized ratio-guided VKA treatment to an NOAC or to continued VKA treatment.

Structure of the HIV immature lattice allows for essential lattice remodeling within budded virions.

For HIV virions to become infectious, the immature lattice of Gag polyproteins attached to the virion membrane must be cleaved. Cleavage cannot initiate without the protease formed by the homo-dimerization of domains linked to Gag. However, only 5% of the Gag polyproteins, termed Gag-Pol, carry this protease domain, and they are embedded within the structured lattice.

Demonstration of quantum-digital payments.

Digital payments have replaced physical banknotes in many aspects of our daily lives. Similarly to banknotes, they should be easy to use, unique, tamper-resistant and untraceable, but additionally withstand digital attackers and data breaches. Current technology substitutes customers' sensitive data by randomized tokens, and secures the payment's uniqueness with a cryptographic function, called a cryptogram.

Effects of OsomeFood Clean Label plant-based meals on the gut microbiome.

Background: Plant-based diets offer more beneficial microbes and can modulate gut microbiomes to improve human health. We evaluated the effects of the plant-based OsomeFood Clean Label meal range ('AWE' diet), on the human gut microbiome.

Methods: Over 21 days, ten healthy participants consumed OsomeFood meals for five consecutive weekday lunches and dinners and resumed their regular diets for other days/meals.

Assessment of Pertussis Underreporting in Italy.

A study was conducted to assess the degree of pertussis underreporting in Italy. An analysis was performed to compare the frequency of pertussis infections estimated using seroprevalence data with the pertussis incidence based on reported cases among the Italian population. For this purpose, the proportion of subjects who had an anti-PT ≥ 100 IU/mL (indicative of infection within the last 12 months) was compared with the reported incidence rate among the Italian population ≥5 years old, divided into two age groups (6-14 and ≥15 years old), obtained from the European Centre for Disease Prevention and Control (ECDC) database.

Automated Good Manufacturing Practice-Compatible CRISPR-Cas9 Editing of Hematopoietic Stem and Progenitor Cells for Clinical Treatment of β-Hemoglobinopathies.

Cellular therapies hold enormous potential for the cure of severe hematological and oncological disorders. The forefront of innovative gene therapy approaches including therapeutic gene editing and hematopoietic stem cell transplantation needs to be processed by good manufacturing practice to ensure safe application in patients. In the present study, an effective transfection protocol for automated clinical-scale production of genetically modified hematopoietic stem and progenitor cells (HSPCs) using the CliniMACS Prodigy system including the CliniMACS Electroporator (Miltenyi Biotec) was established.

Detectability of Medication Errors With a STOPP/START-Based Medication Review in Older People Prior to a Potentially Preventable Drug-Related Hospital Admission.

Introduction: Multimorbidity and polypharmacy are risk factors for drug-related hospital admissions (DRAs) in the ageing population. DRAs caused by medication errors (MEs) are considered potentially preventable. The STOPP/START criteria were developed to detect potential MEs in older people.

Epidemiology of Progressive Supranuclear Palsy: Real World Data from the Second Largest Health Plan in Israel.

Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative movement disorder and no disease modifying therapy (DMT) is currently available. This study aims to assess the epidemiology of PSP in Israel and to describe its clinical features. This retrospective analysis identified patients with PSP between 2000 and 2018 over the age of 40 years at first diagnosis (index date).

Preference of grade and lymphovascular invasion over invasive size measurement in stage I lung adenocarcinoma.

Aims: Although it is necessary to measure the invasive size of lung adenocarcinoma with a lepidic component, it is not uncommon to have trouble in measuring the invasive size of lung adenocarcinoma. This study examined whether there were other stronger prognostic factors than invasive size.

Methods: We characterised the clinicopathological features associated with recurrence-free survival (RFS) of 686 patients with the pathological stage (p-Stage) I lung adenocarcinoma.

Frequency and Acceptance of Clinical Decision Support System-Generated STOPP/START Signals for Hospitalised Older Patients with Polypharmacy and Multimorbidity.

Background: The Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) instrument is used to evaluate the appropriateness of medication in older people. STOPP/START criteria have been converted into software algorithms and implemented in a clinical decision support system (CDSS) to facilitate their use in clinical practice.

Objective: Our objective was to determine the frequency of CDSS-generated STOPP/START signals and their subsequent acceptance by a pharmacotherapy team in a hospital setting.

Preventing and Mitigating Radiology System Failures: A Guide to Disaster Planning.

Disaster planning is a core facet of modern health care practice. Owing to complex infrastructure requirements, radiology departments are vulnerable to system failures that may occur in isolation or during a disaster event when the urgency for and volume of imaging examinations increases. Planning for systems failures helps ensure continuity of service provision and patient care during an adverse event.