Mutagenesis
January 2025
The fetal brain is susceptible to programming effects during pregnancy, potentially leading to long-term consequences for offspring's cognitive health. Fructose intake is thought to adversely affect fetal brain development, whereas physical exercise before and during pregnancy may be protective. Therefore, this study aimed to assess biochemical and genotoxic changes in maternal hippocampi and behavioral, genotoxic, and biochemical alterations in offspring hippocampi.
View Article and Find Full Text PDFA century of research established that GABA inhibits proprioceptive inputs presynaptically to sculpt spinal neural inputs into skilled motor output. Recent results in mice challenged this theory by showing that GABA can also facilitate action potential conduction in proprioceptive afferents. Here, we tackle this controversy in monkeys, the most human-relevant animal model, and show that GABA receptors (GABARs) indeed facilitate sensory inputs to spinal motoneurons and interneurons and that this mechanism also influences sensory transmission to supraspinal centers.
View Article and Find Full Text PDFHerpesvirus of turkey (HVT) recombinant vector vaccines are widely used in the poultry industry. However, due to limitations in loading multiple foreign antigens into a single HVT vector, other viral vectors are urgently needed. Since chickens lack maternal immunity to duck enteritis virus (DEV), vector vaccines using DEV as a backbone are currently under study.
View Article and Find Full Text PDFAims: The ideal dosing weight metric for enoxaparin remains elusive. Dosing remains focused on actual body weight, which may inadvertently increase the risk of bleeding in those with obesity, or ideal weight, which may underdose those with obesity. Our aim was to determine the optimal obesity-adjusted enoxaparin dosing weight.
View Article and Find Full Text PDFSeasonal snow in the extratropical Andes is a primary water source for major rivers supplying water for drinking, agriculture, and hydroelectric power in Central Chile. Here, we used estimates from the Moderate Resolution Imaging Spectroradiometer (MODIS) to analyze changes in snow cover extent over the period 2001-2022 in a total of 18 watersheds spanning approximately 1,100 km across the Chilean Andes (27-36°S). We found that the annual snow cover extent is receding in the watersheds analyzed at an average pace of approximately 19% per decade.
View Article and Find Full Text PDFSpeech and swallowing are complex motor acts that depend upon the integrity of input neural signals from motor cortical areas to control muscles of the head and neck. Lesions damaging these neural pathways result in weakness of key muscles causing dysarthria and dysphagia, leading to profound social isolation and risk of aspiration and suffocation. Here we show that Deep Brain Stimulation (DBS) of the motor thalamus improved speech and swallowing functions in two participants with dysarthria and dysphagia.
View Article and Find Full Text PDFPeptide-based drugs are powerful inhibitors of therapeutically relevant protein-protein interactions. Their affinity and selectivity for target proteins are commonly assessed using fluorescence-based assays such as anisotropy/polarization or quantitative microarrays. This study reveals that labeling can perturb peptide/protein binding by more than 1 order of magnitude.
View Article and Find Full Text PDFCerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for therapies aimed at improving volitional muscle activation. Here we hypothesize that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby immediately potentiating motor output.
View Article and Find Full Text PDFIn the recent EULAR recommendations, ultrasound examination is now recommended as a first-line imaging test in all patients with suspected giant cell arteritis (GCA) and the axillary arteries should be included in the standard exam. As an alternative to ultrasound evaluation, cranial and extracranial arteries can be examined using FDG-PET or MRI. The aim of our study was to observe in a retrospective case series whether there is a correlation between biomarkers and imaging activity in a population of patients followed in real life with GCA treated with prednisone (PDN) and tocilizumab (TCZ).
View Article and Find Full Text PDFThe results and details of the clinical studies and research must be securely stored to ensure reliability, accountability, and prevent malicious misuse. To accomplish this, a secure method for storing metadata and study results is crucial. Also, a mechanism to ensure accountability for both data owners and researchers is needed.
View Article and Find Full Text PDFSystemic sclerosis (SSc) is characterised by a heterogeneous clinical expression probably reflecting the different genetic background of each patient. Progress has been made in the definition of the principal pathogenetic events of the disease that can be summarised in endothelial damage and dysfunction, inflammation with activation of immune system and fibrosis. The aetiology of the disease still remains to be clarified and probably the first events are attributable to the repeated action of environmental stimuli in genetically predisposed subjects.
View Article and Find Full Text PDFBackground: According to recent data, the age of patients could represent an important risk factor for MACE (major cardiovascular events), cancer, and VTE (venous thromboembolism) during treatment with JAK inhibitors in rheumatoid arthritis. We decided to analyze the population involved in the ReLiFiRa study by identifying two groups of patients: 65 years or more and less than 65 years of age, evaluating the efficacy and tolerability of 200 mg of Filgotinib daily.
Methods: Of the 120 ReLiFiRa patients, 54 were younger than 65 years old and 66 patients were 65 years old or older.
Objective: To retrospectively evaluate the incidence rate (IR) of elevated echocardiographic estimated systolic pulmonary artery pressure (sPAP), suspected for pulmonary hypertension (PH), in systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers.
Methods: Patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old with a history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months, were included.
Background: Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects.
View Article and Find Full Text PDFBackground: Artificial intelligence (AI) has become a pivotal tool in advancing contemporary personalised medicine, with the goal of tailoring treatments to individual patient conditions. This has heightened the demand for access to diverse data from clinical practice and daily life for research, posing challenges due to the sensitive nature of medical information, including genetics and health conditions. Regulations like the Health Insurance Portability and Accountability Act (HIPAA) in the U.
View Article and Find Full Text PDFLong-term aerosol optical depth (AOD) datasets focused on the Pacific Ocean in the downwind area of China over a 19-year period from 2003 to 2021 were derived from satellite observations, reanalysis datasets, and numerical simulations. Considering the significant year-to-year changes in the amounts of aerosols transported from China to the Pacific Ocean during this period, we proposed a metric named R. This is defined as the AOD over the ocean relative to that near the eastern coast of China within the same latitude band (25-30°N).
View Article and Find Full Text PDFIntroduction: Formulating reliable prognosis for ischemic stroke patients remains a challenging task. We aimed to develop an artificial intelligence model able to formulate in the first 24 h after stroke an individualized prognosis in terms of NIHSS.
Patients And Methods: Seven hundred ninety four acute ischemic stroke patients were divided into a training (597) and testing (197) cohort.
In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally.
View Article and Find Full Text PDFMutat Res Genet Toxicol Environ Mutagen
April 2024
Predictive modelling of cancer outcomes using radiomics faces dimensionality problems and data limitations, as radiomics features often number in the hundreds, and multi-institutional data sharing is ()often unfeasible. Federated learning (FL) and feature selection (FS) techniques combined can help overcome these issues, as one provides the means of training models without exchanging sensitive data, while the other identifies the most informative features, reduces overfitting, and improves model interpretability. Our proposed FS pipeline based on FL principles targets data-driven radiomics FS in a multivariate survival study of non-small cell lung cancer patients.
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