Explore the vast range of titles available.

Background The diagnostic journey for many rare disease patients remains challenging despite use of latest genetic technological advancements. We hypothesize that some patients remain undiagnosed due to more complex diagnostic scenarios that are currently not considered in genome analysis pipelines. To better understand this, we characterized the rare disorder (RD) spectrum using various bioinformatics resources (e.g., Orphanet/Orphadata, Human Phenotype Ontology, Reactome pathways) combined with custom-made R scripts. Results Our in silico characterization led to identification of 145 borderline-common, 412 rare and 2967 ultra-rare disorders. Based on these findings and point prevalence, we would expect that approximately 6.53%, 0.34%, and 0.30% of individuals in a randomly selected population have a borderline-common, rare, and ultra-rare disorder, respectively (equaling to 1 RD patient in 14 people). Importantly, our analyses revealed that (1) a higher proportion of borderline-common disorders were caused by multiple gene defects and/or other factors compared with the rare and ultra-rare disorders, (2) the phenotypic expressivity was more variable for the borderline-common disorders than for the rarer disorders, and (3) unique clinical characteristics were observed across the disorder categories forming the spectrum. Conclusions Recognizing that RD patients who remain unsolved even after genome sequencing might belong to the more common end of the RD spectrum support the usage of computational pipelines that account for more complex genetic and phenotypic scenarios.

The palatability of a plant refers to the degree of attraction or preference that animals show toward that particular plant. Various factors can influence palatability, including the plant’s chemical composition, texture, taste, aromas, and the circumstances under which herbivorous animals consume it. The study aims to assess the plant species composition in grasslands and pastures within the Danube Delta, Romania. Both old or new references on palatability were considered. The evaluation of plant composition and degree of plant palatability was carried out in 12 grazing areas in the Danube Delta and the surrounding region. The study revealed 121 plant species identified in some pastures. Of these, 31 were “Non-Palatable”, 16 were “Highly Palatable”, 32 were “Mostly Palatable”, 16 were “Less Palatable”, and 26 were “Rarely Palatable”. Animals preferred 60 plant species in their fresh condition, with 29 preferred in fresh and dry. Most animals consumed whole plants (48 species), followed by leaves (43 species), fruits (three species), and inflorescences (two species). By analysing the feeding preferences of animals, it was found that cows exhibited a preference for the broadest range of plants (75 species), followed by sheep (67 species), goats (59 species), and horses (34 species).  Domestic animals like goats, sheep, cows, and horses may prefer certain plants based on nutritional content or digestibility while avoiding toxic plants. The study showed that the investigated areas have a diverse flora with a varied supply of plants, including palatable species. The palatability index is essential in assessing the quality of pastures, especially in obtaining average daily gains based on the species of animals living on the pastures. Considering the dynamic climatic conditions and poor pasture quality in the Danube Delta, more detailed and interdisciplinary studies are needed to understand the deltaic biocenoses comprehensively.

Pulmonary ultrasound has become a fundamental tool for the early detection and management of major neonatal lung diseases in neonatal intensive care units (NICUs). The advantages of this imaging investigation include its rapid execution and information acquisition, non-invasive nature, early diagnosis establishment, dynamic monitoring, and usefulness in therapeutic management. Regarding therapeutic management, the lung ultrasound (LUS) score is used as a basic tool for indicating surfactant administration. Performing and interpreting pulmonary ultrasounds requires an experienced clinician capable of recognizing anatomical structures, understanding the limitations of the technique, and correlating the obtained data with the patient's clinical picture. A series of diagnostic characteristics of pulmonary ultrasonography for neonatal lung pathologies have been described, making pulmonary ultrasound a useful tool in establishing differential diagnoses. This study evaluates the effectiveness of ultrasonography in determining the severity of lung pathologies in newborns and its impact on therapeutic decision-making, including surfactant administration and continuous positive airway pressure (CPAP) support. Newborns admitted to the NICU with various respiratory conditions underwent LUS scoring. The study analyzed the relationship between LUS scoring and the severity of conditions such as pneumonia, respiratory distress syndrome, meconium aspiration syndrome, transient tachypnea of the newborn, and pneumothorax. The correlation between LUS scoring, surfactant administration, and CPAP requirements was also examined.

Objectives: To report a case series of children presenting with episodes of abrupt onset psychotic symptoms presumably linked to pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS). Methods: Children/adolescents were selected among the group of individuals affected by clinical diagnosis of PANDAS/PANS. One group was selected by affected individuals coming from the Center UMDNJ—New Jersey Medical School, New Jersey, USA and the other from the Department of Pediatrics Catania University, Italy. Child health Questionnaire Parent form 50 was given to parents to describe children's quality of life. Results: Among the group of individuals with PANDAS/PANS disorders, eight children/adolescents were selected, six coming from the UMDNJ—New Jersey and two from Catania, University centers showing among the other typical manifestations severe episodes of abrupt onset of psychotic symptoms. Conclusions: Severe psychotic symptoms may be considered one among the other neuropsychiatric clinical manifestations presenting in individuals with PANDAS/PANS syndromes.

Background This case series reports the performance of a next‐generation sequencing (NGS) panel of 176 retinal genes (NGS 176) in patients with inherited retinal disease (IRD). Methods Subjects are patients who underwent genetic testing between 1 August 2016 and 1 January 2018 at Moorfields Eye Hospital, London, UK. Panel‐based genetic testing was performed unless a specific gene (e.g., RS1) or small group of genes (e.g., ABCA4, PRPH2) were suspected. If a novel variant was identified, a further comment on their predicted pathogenicity and evolutionary conservation was offered and segregation studies performed. The main outcome measure is the likelihood of obtaining a genetic diagnosis using NGS 176. Results 488 patients were included. A molecular diagnosis was obtained for 59.4% of patients. Younger patients were more likely to receive a molecular diagnosis; with 92% of children under the age of 6 years receiving a conclusive result. There was a change in their initially assigned inheritance pattern in 8.4% of patients following genetic testing. Selected IRD diagnoses (e.g., achromatopsia, congenital stationary night blindness) were associated with high diagnostic yields. Conclusion This study confirms that NGS 176 is a useful first‐tier genetic test for most IRD patients. Age and initial clinical diagnosis were strongly associated with diagnostic yield. A retrospective study of 488 patients with inherited retinal dystrophy confirms that NGS 176 is a useful first tier genetic test, achieving a molecular diagnosis in 59.4% of those tested. Age and initial clinical diagnosis were strongly associated with diagnostic yield.

Background Migraine and Cluster Headache (CH) are two primary headaches with severe disease burden. The disease expression and the mechanisms involved are poorly known. In some attacks of migraine and in most attacks of CH, there is a release of vasoactive intestinal peptide (VIP) originating from parasympathetic cranial ganglia such as the sphenopalatine ganglion (SPG). Patients suffering from these diseases are often deprived of effective drugs. The aim of the study was to examine the localization of the botulinum toxin receptor element synaptic vesicle glycoprotein 2A (SV-2A) and the vesicular docking protein synaptosomal-associated protein 25 (SNAP25) in human and rat SPG. Additionally the expression of the neurotransmitters pituitary adenylate cyclase activating polypeptide (PACAP-38), nitric oxide synthase (nNOS), VIP and 5-hydroxttryptamine subtype receptors (5-HT 1B,1D,1F ) were examined. Methods SPG from adult male rats and from humans, the later removed at autopsy, were prepared for immunohistochemistry using specific antibodies against neurotransmitters, 5-HT 1B,1D,1F receptors, and botulinum toxin receptor elements. Results We found that the selected neurotransmitters and 5-HT receptors were expressed in rat and human SPG. In addition, we found SV2-A and SNAP25 expression in both rat and human SPG. We report that all three 5-HT receptors studied occur in neurons and satellite glial cells (SGCs) of the SPG. 5-HT 1B receptors were in addition found in the walls of intraganglionic blood vessels. Conclusions Recent focus on the SPG has emphasized the role of parasympathetic mechanisms in the pathophysiology of mainly CH. The development of next generation’s drugs and treatment of cranial parasympathetic symptoms, mediated through the SPG, can be modulated by treatment with BoNT-A and 5-HT receptor agonists.

We have established a pig resource population specifically designed to elucidate the genetics involved in development of obesity and obesity related co-morbidities by crossing the obesity prone Göttingen Minipig breed with two lean production pig breeds. In this study we have performed genome wide association (GWA) to identify loci with effect on blood lipid levels. The most significantly associated single nucleotide polymorphisms (SNPs) were used for linkage disequilibrium (LD) and haplotype analyses. Three separate haploblocks which influence the ratio between high density lipoprotein cholesterol and total cholesterol (HDL-C/CT), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) levels respectively were identified on Sus Scrofa chromosome 3 (SSC3). Large additive genetic effects were found for the HDL-C/CT and LDL-C haplotypes. Haplotypes segregating from Göttingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Göttingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.

The aim of this case report is to present a rare case of epidural Ewing sarcoma with spinal cord compression, which is an uncommon presentation of this tumor. Ewing's sarcoma is a primary malignant tumor predominantly affecting individuals in their second decade of life, primarily impacting those aged 10 to 25, with the average age of onset being around 20 years. Epidemiological studies reveal that this cancer most commonly arises in the diaphyses of the long tubular bones in the lower extremities. Spinal involvement, however, is exceedingly uncommon. A case of sacral type of Ewing's sarcoma, with the most common localization of the primary spinal sarcomas and an extremely aggressive course, has been described in the literature. Other localizations of Ewing's sarcoma located in other areas of the spine are also presented. Even rarer are cases in which the tumor formation is located epidurally and exhibits marked medullary compression and absent neurological symptoms. We present the case of a 20-year-old patient who was admitted to the neurology department with symptoms of lower flaccid paraparesis and pelvic-reservoir dysfunction, specifically urinary retention for 16-17 hours, after which a catheter was added. MRI revealed an epidural tumor spanning TH5-TH7 vertebral levels, causing significant spinal cord compression. A CT scan of the chest identified a tumor on the left side at the level of the sixth rib, featuring soft tissue involvement, rib destruction, lung invasion, and a small pleural effusion. Due to the critical neurological symptoms, the patient underwent emergency surgery in the neurosurgical department, which included thoracic laminectomies, maximal possible tumor resection, and effective spinal cord decompression. Postoperative period was uneventful. Histopathological examination confirmed the diagnosis of Ewing's epidural sarcoma. The patient subsequently received adjuvant chemotherapy and radiotherapy. Six months post-treatment, the patient demonstrated a satisfactory overall condition with significant improvement in gait and continues to undergo chemotherapy courses.

The ever-expanding availability and evolution of microscopy tools has enabled ground-breaking discoveries in neurobiology, particularly with respect to the analysis of cell-type density and distribution. Widespread implementation of many of the elegant image processing tools available continues to be impeded by the lack of complete workflows that span from experimental design, labeling techniques, and analysis workflows, to statistical methods and data presentation. Additionally, it is important to consider open science principles (e.g., open-source software and tools, user-friendliness, simplicity, and accessibility). In the present methodological article, we provide a compendium of resources and a FIJI-ImageJ-based workflow aimed at improving the quantification of cell density in mouse brain samples using semi-automated open-science-based methods. Our proposed framework spans from principles and best practices of experimental design, histological and immunofluorescence staining, and microscopy imaging to recommendations for statistical analysis and data presentation. To validate our approach, we quantified neuronal density in the mouse barrel cortex using antibodies against pan-neuronal and interneuron markers. This framework is intended to be simple and yet flexible, such that it can be adapted to suit distinct project needs. The guidelines, tips, and proposed methodology outlined here, will support researchers of wide-ranging experience levels and areas of focus in neuroscience research.

Background Mutations in GABRB3 have been identified in subjects with different types of epilepsy and epileptic syndromes, including West syndrome (WS), Dravet syndrome (DS), Lennox‐Gastaut syndrome (LGS), myoclonic‐atonic epilepsy (MAE), and others. Methods and results We herewith report on a girl affected by DS, who has been followed from infancy to the current age of 18 years. Next‐generation sequencing (NGS)‐based genetic testing for multigene analysis of neurodevelopmental disorders identified two likely de novo pathogenic mutations, a missense variant in GABRB3 gene (c.842 C>T; p.Thr281IIe) and a nonsense variant found in BBS4 gene (c.883 C>T; p.Arg295Ter). Conclusion A likely relationship between the novel GABRB3 gene variant and the clinical manifestations presented by the girl is proposed. Previously, one case of DS and two of DS‐like linked with GABRB3 mutations have been reported. To the best of our knowledge, this is the first report of DS associated with this novel variant. A literature review of clinical cases with various types of epileptic encephalopathies (EEs) related to GABRB3 mutations is reported. Our study explores a likely new gene‐phenotype relationship between a novel GABRB3 gene variant and the clinical manifestations of Dravet syndrome (DS). We, herewith, report on a long‐term follow‐up of a girl affected by DS, who harbors a novel likely pathogenic variant of GABRB3. A literature review of cases with various types of epileptic encephalopathy related to GABRB3 mutations is discussed.