Explore the vast range of titles available.

Concern of a correlation between disease relapse in patients with acquired demyelinating disorders of central nervous system (CNS) and SARS-CoV2 vaccines has been raised. In this single center study, we retrospectively evaluated safety of SARS-CoV2 vaccination and COVID-19 short-term outcome in pediatric acquired demyelinating disorders of CNS. Patients with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD) with disease onset before 18 years of age were included. Demographic and clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. We included nine patients with MOGAD. Six patients received SARS-CoV2 vaccination and complained pain at injection site while only one had fever and fatigue. Median follow-up was 28 weeks (range 20-48). Seven patients had COVID-19 occurring with mild flu-like symptoms and median follow-up was 28 weeks (range 24-34). Nobody had disease relapse. Five patients with NMOSD were included. All patients received SARS-CoV2 vaccination (BNT162b2-Pfizer-BioNTech). The median follow-up was 20 weeks (range 14-24) and only two patients complained pain at injection site, fever and fatigue. Three patients had also COVID-19 with mild flu-like symptoms, despite two of them being under immunosuppressive treatment. Lastly, forty-three patients with MS were included. 35 out of 43 received SARS-CoV2 vaccination with a median follow-up of 24 weeks (range 8-36). Fourteen patients had no side effects, while 21 complained mild side effects (mainly pain at injection site) and one experienced a disease relapse with complete recovery after steroid therapy. At vaccination, all but one were under treatment. Sixteen patients had COVID-19 occurring with mild symptoms. COVID-19 outcome was good although many patients were under immunosuppressive treatment. Vaccine-related side effects were frequent but were mild and self-limited. Only one MS patient had a post-vaccination relapse with complete recovery after steroid therapy. In conclusion, our data support the safety of SARS-CoV-2 vaccines in pediatric MS, MOGAD and NMOSD.

Obesity has been suggested as an environmental risk factor for multiple sclerosis (MS) and may negatively effect the progression of the disease. The aim of this study is to determine any correlation between overweight/obesity and the clinical and neuroradiological features at the onset of pediatric onset multiple sclerosis (POMS). Were included patients referred to the POMS Unit of the Bambino Gesù Children’s Hospital between June 2012 and June 2021. The diagnosis of MS with an onset of less than 18 years was required. For all included subjects, we considered for the analysis the following data at the onset of symptoms: general data (age, sex, functional system compromised by neurological signs, weight and height), brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid exams. We identified 55 pediatric cases of POMS and divided them into two groups according to the body mass index (BMI): 60% were healthy weight (HW) and 40% were overweight/obese (OW/O). OW/O patients experienced a two-year age difference in disease onset compared to the HW patients (12.7 ± 3.8 years vs. 14.6 ± 4.1 years; p < 0.05). Onset of polyfocal symptoms was seen more frequently in OW/O patients than in HW (72.7% vs. 21.2%; p < 0.05). The pyramidal functions were involved more frequently in the OW/O group than in the HW group (50% vs. 25%; p < 0.005). Black holes were detected more frequently in OW/O patients in onset MRI scans compared to the HW group (50% vs. 15.5%; p < 0.05). Our findings suggest that being overweight/obese affects the risk of developing MS at an earlier age and is associated with an unfavorable clinical–radiological features at onset. Weight control can be considered as a preventive/therapeutic treatment.

Background/Objectives: Sleep disorders (SDs) and Restless Legs Syndrome (RLS) have been reported with high prevalence in Multiple Sclerosis (MS), but data on Pediatric-Onset MS (POMS) are scarce. This study aims to assess the prevalence of SDs, particularly RLS, in a POMS cohort and examine associated clinical features. Methods: We recruited POMS patients who attended the POMS Center of the Bambino Gesù Children’s Hospital between September 2021 and February 2023; they were evaluated for SDs using the Pittsburgh Sleep Quality Index (PSQI) or the Sleep Disturbance Scale for Children (SDSC) and screened for RLS. Correlations with demographical, clinical, neuroradiological, and laboratory findings were analyzed. Results: We recruited 44 POMS patients, of whom 39% were classified as “good sleepers” and 61% were identified as “poor sleepers.” RLS was diagnosed in 10 patients (22.7%). Those with RLS were older and had higher Expanded Disability Status Scale (EDSS) scores compared to non-RLS patients (p = 0.028; p = 0.03). The presence of RLS did not show any significant correlation with MRI lesion load or laboratory data. Conclusions: Our findings suggest an increased rate of SDs and RLS in pediatric MS patients compared to the general pediatric population. Clinical data could support a secondary form of RLS in this population, but results need further confirmation.

PurposeMultiple sclerosis (MS) is a chronic neurological condition that affects approximately 150 000 people in the UK and presents a significant healthcare burden, including the high costs of disease-modifying treatments (DMTs). DMTs have substantially reduced the risk of relapse and moderately reduced disability progression. Patients exhibit a wide range of responses to available DMTs. The Predicting Optimal INdividualised Treatment response in MS (POINT-MS) cohort was established to predict the individual treatment response by integrating comprehensive clinical phenotyping with imaging, serum and genetic biomarkers of disease activity and progression. Here, we present the baseline characteristics of the cohort and provide an overview of the study design, laying the groundwork for future analyses.ParticipantsPOINT-MS is a prospective, observational research cohort and biobank of 781 adult participants with a diagnosis of MS who consented to study enrolment on initiation of a DMT at the Queen Square MS Centre (National Hospital of Neurology and Neurosurgery, University College London Hospital NHS Trust, London) between 01/07/2019 and 31/07/2024. All patients were invited for clinical assessments, including the expanded disability status scale (EDSS) score, brief international cognitive assessment for MS and various patient-reported outcome measures (PROMs). They additionally underwent MRI at 3T, optical coherence tomography and blood tests (for genotyping and serum biomarkers quantification), at baseline (i.e., within 3 months from commencing a DMT), and between 6–12 (re-baseline), 18–24, 30–36, 42–48 and 54–60 months after DMT initiation.Findings to date748 participants provided baseline data. They were mostly female (68%) and White (75%) participants, with relapsing–remitting MS (94.3%), and with an average age of 40.8 (±10.9) years and a mean disease duration of 7.9 (±7.4) years since symptom onset. Despite low disability (median EDSS 2.0), cognitive impairment was observed in 40% of participants. Most patients (98.4%) had at least one comorbidity. At study entry, 59.2% were treatment naïve, and 83.2% initiated a high-efficacy DMT. Most patients (76.4%) were in either full- or part-time employment. PROMs indicated heterogeneous impairments in physical and mental health, with a greater psychological than physical impact and with low levels of fatigue. When baseline MRI scans were compared with previous scans (available in 668 (89%) patients; mean time since last scan 9±8 months), 26% and 8.5% of patients had at least one new brain or spinal cord lesion at study entry, respectively. Patients showed a median volume of brain lesions of 6.14 cm3, with significant variability among patients (CI 1.1 to 34.1). When brain tissue volumes z-scores were obtained using healthy subjects (N=113, (mean age 42.3 (± 11.8) years, 61.9% female)) from a local MRI database, patients showed a slight reduction in the volumes of the whole grey matter (−0.16 (−0.22 to –0.09)), driven by the deep grey matter (−0.47 (−0.55 to –0.40)), and of the whole white matter (−0.18 (−0.28 to –0.09)), but normal cortical grey matter volumes (0.10 (0.05 to 0.15)). The mean upper cervical spinal cord cross-sectional area (CSA), as measured from volumetric brain scans, was 62.3 (SD 7.5) mm2. When CSA z-scores were obtained from the same healthy subjects used for brain measures, patients showed a slight reduction in CSA (−0.15 (−0.24 to –0.10)).Future plansModelling with both standard statistics and machine learning approaches is currently planned to predict individualised treatment response by integrating all the demographic, socioeconomic, clinical data with imaging, genetic and serum biomarkers. The long-term output of this research is a stratification tool that will guide the selection of DMTs in clinical practice on the basis of the individual prognostic profile. We will complete long-term follow-up data in 4 years (January 2029). The biobank and MRI repository will be used for collaborative research on the mechanisms of disability in MS.

: Sleep disorders (SDs) and Restless Legs Syndrome (RLS) have been reported with high prevalence in Multiple Sclerosis (MS), but data on Pediatric-Onset MS (POMS) are scarce. This study aims to assess the prevalence of SDs, particularly RLS, in a POMS cohort and examine associated clinical features. : We recruited POMS patients who attended the POMS Center of the Bambino Gesù Children's Hospital between September 2021 and February 2023; they were evaluated for SDs using the Pittsburgh Sleep Quality Index (PSQI) or the Sleep Disturbance Scale for Children (SDSC) and screened for RLS. Correlations with demographical, clinical, neuroradiological, and laboratory findings were analyzed. We recruited 44 POMS patients, of whom 39% were classified as \"good sleepers\" and 61% were identified as \"poor sleepers.\" RLS was diagnosed in 10 patients (22.7%). Those with RLS were older and had higher Expanded Disability Status Scale (EDSS) scores compared to non-RLS patients ( = 0.028; = 0.03). The presence of RLS did not show any significant correlation with MRI lesion load or laboratory data. : Our findings suggest an increased rate of SDs and RLS in pediatric MS patients compared to the general pediatric population. Clinical data could support a secondary form of RLS in this population, but results need further confirmation.

Rhizoctonia solani, causing Rhizoctonia crown and root rot, is a major risk to sugar beet (Beta vulgaris L.) cultivation. The development of resistant varieties accelerated by marker-assisted selection is a priority of breeding programs. We report the identification of a single-nucleotide polymorphism (SNP) marker linked to Rhizoctonia resistance using restriction site-associated DNA (RAD) sequencing of two geographically discrete sets of plant materials with different degrees of resistance/susceptibility to enable a wider selection of superior genotypes. The variant calling pipeline utilized SAMtools for variant calling and the resulting raw SNPs from RAD sequencing (15,988 and 22,439 SNPs) were able to explain 13.40% and 25.45% of the phenotypic variation in the two sets of material from different sources of origin, respectively. An association analysis was carried out independently on both the datasets and mutually occurring significant SNPs were filtered depending on their contribution to the phenotype using principal component analysis (PCA) biplots. To provide a ready-to-use marker for the breeding community, a systematic molecular validation of significant SNPs distributed across the genome was undertaken to combine high-resolution melting, Sanger sequencing, and rhAmp SNP genotyping. We report that RsBv1 located on Chromosome 6 (9,000,093 bp) is significantly associated with Rhizoctonia resistance (p < 0.01) and able to explain 10% of the phenotypic disease variance. The related SNP assay is thus ready for marker-assisted selection in sugar beet breeding for Rhizoctonia resistance.

The fatty acids profile has been playing a decisive role in recent years, thanks to technological, sensory and health demands from producers and consumers. The application of NIRS technique on fat tissues, could lead to more efficient, practical, and economical in the quality control. The study aim was to assess the accuracy of Fourier Transformed Near Infrared Spectroscopy technique to determine fatty acids composition in fat of 12 European local pig breeds. A total of 439 spectra of backfat were collected both in intact and minced tissue and then were analyzed using gas chromatographic analysis. Predictive equations were developed using the 80% of samples for the calibration, followed by full cross validation, and the remaining 20% for the external validation test. NIRS analysis of minced samples allowed a better response for fatty acid families, n6 PUFA, it is promising both for n3 PUFA quantification and for the screening (high, low value) of the major fatty acids. Intact fat prediction, although with a lower predictive ability, seems suitable for PUFA and n6 PUFA while for other families allows only a discrimination between high and low values. The proportions of fatty acids in pork fat took on a decisive role over the years, both due to the degree of fat unsaturation representing a key factor in the technological quality of processed meat and to the significant influence on qualitative parameters linked to sensory and nutritional profile 1. High quality meat demand of consumers and processing industry is increasing, in particular meat and meat-products derived from local breeds has been growing interest due to the positive perception of their quality products in terms of health and animal welfare 2 .

Active surveillance of cervical intraepithelial neoplasia grade 2 (CIN2) is increasingly adopted to reduce the risk of overtreatment, particularly in young women. However, the appropriateness of this approach remains debated, especially in light of evidence suggesting an increased long-term risk of cervical cancer in certain subpopulations. A retrospective cohort study was conducted on HPV-positive women with histologically confirmed p16-positive CIN2 managed with active surveillance. Medium-term clinical outcomes included regression, persistence, and progression to CIN3 or higher during follow-up. Survival analyses (Kaplan-Meier), Cox regression models, and Modified Poisson regression models with robust standard errors were performed to identify independent factors associated with progression. The mean follow-up was 27 months, with a maximum follow-up of 48 months. During the observation period, spontaneous regression was observed in 61% of cases, while 25.5% of patients showed progression and 13.8% persistence of the lesion. Regression occurred predominantly within the first 24-36 months, followed by a plateau in the curves. Progression was significantly associated with high-grade cytology (ASC-H/HSIL) and HPV16/18 positivity. In multivariable models, both factors remained independent factors associated with progression, whereas non-16/18 HPV genotypes and low-grade cytology were associated with a higher likelihood of regression. Although this study does not allow for a direct assessment of long-term cancer risk, the identification of early factors associated with persistence and progression provides clinically relevant insights into CIN2 profiles associated with an increased risk of progression within the observed follow-up period. These findings suggest that active surveillance of CIN2 may not be equally appropriate across all patient subgroups and requires careful risk stratification based on virological and cytological factors to support selective and clinically sound management.

microRNA-22 (miR-22) is a key regulator of lipid and energy homeostasis and represents a promising therapeutic target for NAFLD and obesity. We have previously identified a locked nucleic acid (LNA)-modified antisense oligonucleotide compound complementary to miR-22, designated as RES-010 that mediated robust inhibition of miR-22 function in cultured cells and in vivo . In this study we investigated the immune potential of RES-010 in human peripheral blood mononuclear cells (PBMCs). We treated fresh human peripheral blood mononuclear cells isolated from six healthy volunteers with different concentrations of the RES-010 compound and assessed its proinflammatory effects by quantifying IL-1β, IL-6, IFN-γ, TNF-α, IFN-α2a, IFN-β, IL-10, and IL-17A in the supernatants collected 24 h of treatment with RES-010. The T-cell activation markers, CD69, HLA-DR, and CD25 were evaluated by flow cytometry after 24 and 144 h of treatment, respectively, whereas cell viability was assessed after 24 h of treatment with RES-010. Our results show that RES-010 compound does not induce any significant immunostimulatory responses in human PBMCs in vitro compared to controls, implying that the proinflammatory potential of RES-010 is low.

MicroRNA-125a-5p (miR-125a) is a vertebrate homolog of lin-4, the first discovered microRNA, and plays a fundamental role in embryo development by downregulating Lin-28 protein. MiR-125a is also expressed in differentiated cells where it generally acts as an antiproliferative factor by targeting membrane receptors or intracellular transductors of mitogenic signals. MiR-125a expression is downregulated in several tumors, including hepatocellular carcinoma (HCC) where it targets sirtuin-7, matrix metalloproteinase-11, VEGF-A, Zbtb7a, and c-Raf. In this study, we have isolated the transcription promoter of human miR-125a and characterized its activity in HCC cells. It is a TATA-less Pol II promoter provided with an initiator element and a downstream promoter element, located 3939 bp upstream the genomic sequence of the miRNA. The activity of the promoter is increased by the transcription factor NF-kB, a master regulator of inflammatory response, and miR-125a itself was found to strengthen this activation through inhibition of TNFAIP3, a negative regulator of NF-kB. This finding contributes to explain the increased levels of miR-125a observed in the liver of patients with chronic hepatitis B.