EDENT1FI Master Protocol for screening of presymptomatic early-stage type 1 diabetes in children and adolescents.

Introduction: The identification of type 1 diabetes at an early presymptomatic stage has clinical benefits. These include a reduced risk of diabetic ketoacidosis (DKA) at the clinical manifestation of the disease and a significant reduction in clinical symptoms. The European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception (EDENT1FI) represents a pioneering effort to advance early detection of type 1 diabetes through public health screening.

IL-10 predicts incident neuroinflammatory disease and proviral load dynamics in a large Brazilian cohort of people living with human T-lymphotropic virus type 1.

Human T-Lymphotropic Virus type-1 (HTLV-1) is a unique retrovirus associated with both leukemogenesis and a specific neuroinflammatory condition known as HTLV-1-Associated Myelopathy (HAM). Currently, most proposed HAM biomarkers require invasive CSF sampling, which is not suitable for large cohorts or repeated prospective screening. To identify non-invasive biomarkers for incident HAM in a large Brazilian cohort of PLwHTLV-1 (n=615 with 6,673 person-years of clinical follow-up), we selected all plasma samples available at the time of entry in the cohort (between 1997-2019), in which up to 43 cytokines/chemokines and immune mediators were measured.

Design of a flow modulation device to facilitate individualized ventilation in a shared ventilator setup.

This study aims to resolve the unmet need for ventilator surge capacity by developing a prototype device that can alter patient-specific flow in a shared ventilator setup. The device is designed to deliver a predictable tidal volume (VT), requiring minimal additional monitoring and workload. The prototyped device was tested in an in vitro bench setup for its performance against the intended use and design criteria.

High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam.

To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam.

Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation.

Background: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors.

Noninvasive integrative approach applied to children in the context of recent air pollution exposure demonstrates association between fractional exhaled nitric oxide (FeNO) and urinary CC16.

Exposure to the air pollutant particulate matter (PM) is associated with increased risks of respiratory diseases and enhancement of airway inflammation in children. In the context of large scale air pollution studies, it can be challenging to measure fractional exhaled nitric oxide (FeNO) as indicator of lung inflammation. Urinary CC16 (U-CC16) is a potential biomarker of increased lung permeability and toxicity, increasing following short-term PM exposure.

Assessment of the Feasibility of a Future Integrated Larger-Scale Epidemiological Study to Evaluate Health Risks of Air Pollution Episodes in Children.

Air pollution exposure can lead to exacerbation of respiratory disorders in children. Using sensitive biomarkers helps to assess the impact of air pollution on children's respiratory health and combining protein, genetic and epigenetic biomarkers gives insights on their interrelatedness. Most studies do not contain such an integrated approach and investigate these biomarkers individually in blood, although its collection in children is challenging.

Phytoprostanes from Date Palm Fruit and Byproducts: Five Different Varieties Grown in Two Different Locations As Potential sources.

Date palm fruit has been considered for centuries as an ancient nutritional constituent in the human diet. Recently, global trade in dates increased at an average that, simultaneously, will be accompanied by an increase in date palm byproducts. Supported by date phytochemicals and their health benefits, the aim of this work is to evaluate for the first time the presence of special metabolites of plant called phytoprostanes (PhytoPs) in five different varieties of the L.

Age-related changes in the fractal dimension of the retinal microvasculature, effects of cardiovascular risk factors and smoking behaviour.

Purpose: This cross-sectional study investigates the association between retinal vessel complexity and age and studies the effects of cardiovascular health determinants.

Methods: Retinal vessel complexity was assessed by calculating the box-counting fractal dimension (D ) from digital fundus photographs of 850 subjects (3-97 years). All photographs were labelled as 'non-pathological' by the treating ophthalmologist.

Shared Care and Virtual Clinics for Glaucoma in a Hospital Setting.

Glaucoma patients require lifelong management, and the prevalence of glaucoma is expected to increase, resulting in capacity problems in many hospital eye departments. New models of care delivery are needed to offer requisite capacity. This review evaluates two alternative schemes for glaucoma care within a hospital, i.

Road to Metastasis: The TWEAK Pathway as a Discriminant between Metastasizing and Non-Metastasizing Thick Melanomas.

Cutaneous melanoma (CM) is the most aggressive form of skin cancer, and its worldwide incidence is rapidly increasing. Early stages can be successfully treated by surgery, but once metastasis has occurred, the prognosis is poor. However, some 5-10% of thick (≥2 mm) melanomas do not follow this scenario and run an unpredictable course.

Behavioral changes before lockdown and decreased retail and recreation mobility during lockdown contributed most to controlling COVID-19 in Western countries.

Background: The COVID-19 pandemic has prompted a lockdown in many countries to control the exponential spread of the SARS-CoV-2 virus, hereby reducing the time-varying basic reproduction number (R) to below one. Governments are looking for evidence to balance the demand of their citizens to ease some of the restriction, against the fear of a new peak in infections. In this study, we wanted to quantify the relative contribution of mobility restrictions, and that of behavioral changes that occurred already before the lockdowns, on the reduction of transmission during lockdowns in Western countries in early 2020.

Phenotypical and Functional Characterization of Neutrophils in Two Pyrin-Associated Auto-inflammatory Diseases.

Purpose: Familial Mediterranean Fever (FMF) and Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis (PAAND) are clinically distinct autoinflammatory disorders caused by mutations in the pyrin-encoding gene MEFV. We investigated the transcriptional, phenotypical, and functional characteristics of patient neutrophils to explore their potential role in FMF and PAAND pathophysiology.

Methods: RNA sequencing was performed to discover transcriptional aberrancies.

New lipophenols prevent carbonyl and oxidative stresses involved in macular degeneration.

Dry age-related macular degeneration and Stargardt disease undergo a known toxic mechanism caused by carbonyl and oxidative stresses (COS). This is responsible for accumulation in the retinal pigment epithelium (RPE) of A2E, a main toxic pyridinium bis-retinoid lipofuscin component. Previous studies have shown that carbonyl stress in retinal cells could be reduced by an alkyl-phloroglucinol-DHA conjugate (lipophenol).

Using Large-Scale NO Data from Citizen Science for Air-Quality Compliance and Policy Support.

Citizen science projects that monitor air quality have recently drastically expanded in scale. Projects involving thousands of citizens generate spatially dense data sets using low-cost passive samplers for nitrogen dioxide (NO), which complement data from the sparse reference network operated by environmental agencies. However, there is a critical bottleneck in using these citizen-derived data sets for air-quality policy.

Isoprostanoid Profiling of Marine Microalgae.

Algae result from a complex evolutionary history that shapes their metabolic network. For example, these organisms can synthesize different polyunsaturated fatty acids, such as those found in land plants and oily fish. Due to the presence of numerous double-bonds, such molecules can be oxidized nonenzymatically, and this results in the biosynthesis of high-value bioactive metabolites named isoprostanoids.

Preclinical pharmacology of a lipophenol in a mouse model of light-induced retinopathy.

Environmental light has deleterious effects on the outer retina in human retinopathies, such as ABCA4-related Stargardt's disease and dry age-related macular degeneration. These effects involve carbonyl and oxidative stress, which contribute to retinal cell death and vision loss. Here, we used an albino Abca4 mouse model, the outer retina of which shows susceptibility to acute photodamage, to test the protective efficacy of a new polyunsaturated fatty acid lipophenol derivative.

Characterization and modulation of brain lipids content of rainbow trout fed with 100% plant based diet rich in omega-3 long chain polyunsaturated fatty acids DHA and EPA.

Brain functions are known to be mainly modulated by adequate dietary intake. Inadequate intake as can be an excess or significant deficiency affect cognitive processes, behavior, neuroendocrine functions and synaptic plasticity with protective or harmful effects on neuronal physiology. Lipids, in particular, ω-6 and ω-3 long chain polyunsaturated fatty acids (LC-PUFAs) play structural roles and govern the different functions of the brain.

Isopropyl-phloroglucinol-DHA protects outer retinal cells against lethal dose of all-trans-retinal.

All-trans-retinal (atRAL) is a highly reactive carbonyl specie, known for its reactivity on cellular phosphatidylethanolamine in photoreceptor. It is generated by photoisomerization of 11-cis-retinal chromophore linked to opsin by the Schiff's base reaction. In ABCA4-associated autosomal recessive Stargardt macular dystrophy, atRAL results in carbonyl and oxidative stress, which leads to bisretinoid A2E, accumulation in the retinal pigment epithelium (RPE).

Identification and quantification of phytoprostanes and phytofurans of coffee and cocoa by- and co-products.

Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are isoprostanoids that result from the peroxidation of α-linolenic acid and are biomarkers of oxidative stress in plants and humans. These compounds exhibit several interesting biological activities (e.g.

Bis-allylic Deuterated DHA Alleviates Oxidative Stress in Retinal Epithelial Cells.

Oxidative stress plays a crucial role in developing and accelerating retinal diseases including age-related macular degeneration (AMD). Docosahexaenoic acid (DHA, C22:6, n-3), the main lipid constituent of retinal epithelial cell membranes, is highly prone to radical and enzymatic oxidation leading to deleterious or beneficial metabolites for retinal tissue. To inhibit radical oxidation while preserving enzymatic metabolism, deuterium was incorporated at specific positions of DHA, resulting in D-DHA when incorporated at position 6 and D-DHA when incorporated at the 6,9 -allylic positions.

New Lipophenol Antioxidants Reduce Oxidative Damage in Retina Pigment Epithelial Cells.

Age-related macular degeneration (AMD) is a multifactorial pathology and its progression is exacerbated by oxidative stress. Oxidation and photo-oxidation reactions modify lipids in retinal cells, contribute to tissue injury, and lead to the formation of toxic adducts. In particular, autofluorescent pigments such as -retinylidene--retinylethanolamine (A2E) accumulate as lipofuscin in retinal pigment epithelial cells, contribute to the production of additional reactive oxygen species (ROS), and lead to cell degeneration.

Non-Enzymatic Synthesis of Bioactive Isoprostanoids in the Diatom following Oxidative Stress.

The ecological success of diatoms requires a remarkable ability to survive many types of stress, including variations in temperature, light, salinity, and nutrient availability. On exposure to these stresses, diatoms exhibit common responses, including growth arrest, impairment of photosynthesis, production of reactive oxygen species, and accumulation of triacylglycerol (TAG). We studied the production of cyclopentane oxylipins derived from fatty acids in the diatom in response to oxidative stress.

Predictors of non adherence to antiretroviral therapy at an urban HIV care and treatment center in Tanzania.

Background: Measurement of adherence to antiretroviral therapy (ART) can serve as a proxy for virologic failure in resource-limited settings. The aim of this study was to determine the factors underlying nonadherence measured by three methods.

Patients And Methods: This is a prospective longitudinal cohort of 220 patients on ART at Amana Hospital in Dar es Salaam, Tanzania.