Dietary control of peripheral adipose storage capacity through membrane lipid remodelling.

Genetic and dietary cues are known drivers of obesity, yet how they converge at the molecular level is incompletely understood. Here we show that PPARγ supports hypertrophic expansion of adipose tissue via transcriptional control of LPCAT3, an endoplasmic reticulum (ER)-resident O-acyltransferase that selectively enriches diet-derived omega-6 polyunsaturated fatty acids (n-6 PUFAs) in the membrane lipidome. In mice fed a high-fat diet, lowering membrane n-6 PUFA levels through genetic or dietary interventions results in aberrant adipose triglyceride (TG) turnover, ectopic fat deposition and insulin resistance.

The Importance of Instigating Automated Insulin Delivery Systems at Onset of Type 1 Diabetes: 1-Year Follow-Up of Children and Adolescents from Two Tertiary Pediatric Diabetes Centers.

To evaluate differences in glucometrics in children and adolescents assigned to automated insulin delivery (AID), predictive low-glucose suspend (PLGS), or multiple daily injections (MDI) in the first month of diabetes management. In this real-world prospective cohort study, all subjects aged 0-18 years with diabetes onset between January 1, 2020, and June 30, 2023, were assigned to MDI ( = 24), PLGS ( = 28), or AID ( = 32) but were allowed to switch after the first 3 months. The primary outcome was HbA1c after 12 months.

Nonvesicular cholesterol transport in physiology.

In mammalian cells cholesterol can be synthesized endogenously or obtained exogenously through lipoprotein uptake. Plasma membrane (PM) is the primary intracellular destination for both sources of cholesterol, and maintaining appropriate membrane cholesterol levels is critical for cellular viability. The endoplasmic reticulum (ER) acts as a cellular cholesterol sensor, regulating synthesis in response to cellular needs and determining the metabolic fates of cholesterol.

From Paper to Digital: Evaluating Electronic Medical Records and their Compliance with EMA Guidelines in European Clinical Trials.

Background: Over the past decade, there has been a significant shift from paper-based to digital medical record management, driven largely by advances in digital technology. This transition has led to widespread adoption of Electronic Medical Records (EMRs), with the expectation that paper documentation will soon be fully replaced. In response, the European Medicines Agency's "Guideline on Computerised Systems in Clinical Trials" outlines essential criteria for validated EMR systems to ensure data integrity and security, and sets standards for electronic source documents in clinical trials.

Electroencephalogram monitoring during anesthesia and critical care: a guide for the clinician.

Perioperative anesthetic, surgical and critical careinterventions can affect brain physiology and overall brain health. The clinical utility of electroencephalogram (EEG) monitoring in anesthesia and intensive care settings is multifaceted, offering critical insights into the level of consciousness and depth of anesthesia, facilitating the titration of anesthetic doses, and enabling the detection of ischemic events and epileptic activity. Additionally, EEG monitoring can aid in predicting perioperative neurocognitive disorders, assessing the impact of systemic insults on cerebral function, and informing neuroprognostication.

Dietary control of peripheral adipose storage capacity through membrane lipid remodelling.

Complex genetic and dietary cues contribute to the development of obesity, but how these are integrated on a molecular level is incompletely understood. Here, we show that PPARγ supports hypertrophic expansion of adipose tissue via transcriptional control of LPCAT3, a membrane-bound O-acyltransferase that enriches diet-derived omega-6 ( -6) polyunsaturated fatty acids (PUFAs) in the phospholipidome. In high-fat diet-fed mice, lowering membrane -6 PUFA levels by adipocyte-specific knockout ( ) or by dietary lipid manipulation leads to dysfunctional triglyceride (TG) storage, ectopic fat deposition and insulin resistance.

Cholesterol binding to VCAM-1 promotes vascular inflammation.

Hypercholesterolemia has long been implicated in endothelial cell (EC) dysfunction, but the mechanisms by which excess cholesterol causes vascular pathology are incompletely understood. Here we used a cholesterol-mimetic probe to map cholesterol-protein interactions in primary human ECs and discovered that cholesterol binds to and stabilizes the adhesion molecule VCAM-1. We show that accessible plasma membrane (PM) cholesterol in ECs is acutely responsive to inflammatory stimuli and that the nonvesicular cholesterol transporter Aster-A regulates VCAM-1 stability in activated ECs by controlling the size of this pool.

Damaging mutations in liver X receptor-α are hepatotoxic and implicate cholesterol sensing in liver health.

Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis.

The role of EEG and neuroimaging in the diagnosis of non-convulsive status epilepticus in Subacute Encephalopathy with Seizures in Alcoholics (SESA syndrome): a case report and overview of the literature.

Epileptic seizures are frequently associated with liver dysfunction and alcoholism. Subacute encephalopathy with seizures in chronic alcoholics (SESA) is an underrecognized condition with peculiar clinical, EEG and neuroradiological features.We report the case of a 58-year-old man with previous alcohol use disorder (AUD) and acute-on chronic liver failure on alcohol-related cirrhosis, referred for urgent Orthotopic Liver Transplantation evaluation.

Conversion to Brivaracetam Monotherapy in Clinical Practice: A Retrospective Study.

Introduction: The study aimed to evaluate the effectiveness and safety of brivaracetam (BRV) as conversion monotherapy in adults with focal epilepsy treated in the context of real-world clinical practice.

Methods: This was a retrospective, observational, non-interventional study in adults with focal epilepsy who converted to BRV monotherapy following the withdrawal of background antiseizure medications (ASMs). Primary effectiveness outcome was the retention rate of BRV as single ASM at 6 and 12 months.

The risk of hospitalisation from RSV is not increased by co-infection in children under 24-months-of-age.

The recent pandemic prompted renewed interest in paediatric respiratory infections, including whether co-infections - particularly with RSV - have an adverse prognostic impact. We evaluated the charts of all children presenting with respiratory symptoms to our unit between October 2022 and April 2023, each of whom was subjected to a multiplex PCR assay to detect eight viral targets and one bacterial target and examine the relationships between mono- and co-infections and hospitalization outcomes. We observed that younger age and RSV infection were both associated with the need for hospitalisation and the duration of hospitalisation after adjusting for confounders.

Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake.

Intestinal absorption is an important contributor to systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1) assists in the initial step of dietary cholesterol uptake, but how cholesterol moves downstream of NPC1L1 is unknown. We show that Aster-B and Aster-C are critical for nonvesicular cholesterol movement in enterocytes.

Tagging EEG features within exam reports to quickly generate databases for research purposes.

Objective: assess the effectiveness of a new method for classifying EEG recording features through the use of tags within reports. We present feature prevalence in a sample of patients with toxic-metabolic encephalopathy and discuss the advantages of this approach over existing classification systems.

Methods: during EEG report creation, tags reflecting background activity, epileptiform features and periodic discharges were selected according to the findings of each recording.

Multicentric, observational, longitudinal study for the evaluation of nutritional management implications in newly diagnosed Italian cancer patients: the Italian Registry of Malnutrition in Oncology (IRMO).

Background: Malnutrition is a frequent problem in oncology and is associated with reduced response to cancer treatments, increased drug-related toxicity, higher rates of clinical complications, reduced quality of life (QoL) and worse prognosis. Guidelines on clinical nutrition in oncology emphasise the usefulness of early assessment of nutritional status for a prompt identification of malnutrition and the implementation of effective interventions, but no real-world clinical data are available on the adequate management of nutritional support in patients with cancer in Italy.

Methods And Analysis: This is an observational, longitudinal, multicentre registry of patients with a new diagnosis of cancer or metastatic disease, candidates for active treatment.

Rationale and Design of a Single-Arm, Phase 2, Multi-Center Study of Chemo-Immunotherapy Followed by Hypo-Fractionated RT and Maintenance Immunotherapy in Patients With Unresectable Stage III NSCLC: The DEDALUS Trial.

Introduction/background: This single-arm, phase 2, multi-center, study aims to assess the safety and efficacy of a regimen of induction chemo-immunotherapy followed by de-intensified, hypo-fractionated thoracic radiotherapy (RT) given concurrently with durvalumab and maintenance durvalumab in patients with unresectable, stage III NSCLC.

Material And Methods: we will enroll 45 patients with unresectable stage III NSCLC, any PD-L1, deemed ineligible for concurrent CRT by a thoracic oncology multidisciplinary team, and candidate to sequential chemoradiation followed by durvalumab.

Results: Primary endpoint is safety, defined by the incidence of grade 3 and 4 possibly related adverse events (PRAEs) within 6 months from the initiation of treatment.

The Bio-Diversity and the Role of Gut Microbiota in Postmenopausal Women with Luminal Breast Cancer Treated with Aromatase Inhibitors: An Observational Cohort Study.

The interactions between aromatase inhibitors (AI) in breast cancer (BC) and gut microbiota (GM) have not been completely established yet. The aim of the study is to evaluate the bio-diversity of GM and the relationship between GM, inflammation and tumor-infiltrating lymphocytes (TILs) in postmenopausal women with BC during adjuvant AI treatment compared to women with disease relapse during or after one year of AI therapy ("endocrine-resistant"). We conducted a monocenter observational case-control study.

Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs.

GATA4 is a transcription factor known for its crucial role in the development of many tissues, including the liver; however, its role in adult liver metabolism is unknown. Here, using high-throughput sequencing technologies, we identified GATA4 as a transcriptional regulator of metabolism in the liver. GATA4 expression is elevated in response to refeeding, and its occupancy is increased at enhancers of genes linked to fatty acid and lipoprotein metabolism.

Multicentre, randomised, open-label, parallel-group, clinical phase II study to evaluate immunonutrition in improving efficacy of immunotherapy in patients with metastatic non-small cell lung cancer, undergoing systematic nutritional counseling.

Background: Nutritional support, including nutritional counseling and oral nutritional supplements (ONS), has been recommended as a first-line strategy in patients with non-small cell lung cancer (NSCLC). Evidence on the efficacy of immunonutrition during immunotherapy in these patients is positive, but still limited some secondary endpoints, such as treatment toxicity and tolerance. We hypothesize that early systematic provision of ONS with a high-protein-high calorie mixture containing immunonutrients (Impact®) in addition to nutritional counseling, compared to nutritional counseling alone, is beneficial to patients with NSCLC receiving immunotherapy with or without chemotherapy.

Effectiveness of the available early therapies in reducing severe COVID-19 in non-hospitalized patients with solid tumors on active treatment.

Emergency use authorization of drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by regulatory authorities has provided new options to treat high-risk outpatients with mild-to-moderate Coronavirus disease 2019 (COVID-19). We conducted an ambispective cohort study of patients with solid tumors on active treatment to examine the effectiveness of these drugs in preventing the progression to severe COVID-19. Sixty-nine patients with solid tumors (43 women, 26 men; median age 61, range 26-80) reported a laboratory-confirmed diagnosis of SARS-CoV-2 infection.

The value of EEG attenuation in the prediction of outcome in COVID-19 patients.

Introduction: During the COVID-19 pandemic, electroencephalography (EEG) proved to be a useful tool to demonstrate brain involvement. Many studies reported non-reactive generalized slowing as the most frequent pattern and epileptiform activity in a minority of patients.

Objective: To investigate the prevalence of diffuse unreactive background attenuation or suppression and its correlation with outcome in a cohort of COVID-19 patients.