Enamel histomorphometry, growth patterns and developmental trajectories of the first deciduous molar in an Italian early medieval skeletal series.

Understanding the growth patterns and developmental trajectories of teeth during early life stages provides valuable insights into the ontogeny of individuals, particularly in archaeological populations where such information is scarce. This study focuses on first deciduous molars, specifically investigating crown formation times and daily secretion rates, through histological analysis. A total of 34 teeth from the Early Medieval necropolises of Casalmoro and Guidizzolo (Mantua, Lombardy, northern Italy) were analysed assessing growth parameters and identifying possible differences between sites and between sexes, which are determined through proteomic analysis.

A familial form of Charcot-Marie-Tooth disease (type 2d) caused by a previously unreported variant in .

Genetic variants in gene, encoding for the glycyl tRNA synthetase 1, cause Charcot-Marie-Tooth disease, type 2D (CMT2D). Here we describe a 14-year-old boy affected by neuropathy with prominent weakness in the upper extremities carrying two missense variants in gene: the c.803C > T, p.

Altered molecular and cellular mechanisms in KIF5A-associated neurodegenerative or neurodevelopmental disorders.

Mutations targeting distinct domains of the neuron-specific kinesin KIF5A associate with different neurodegenerative/neurodevelopmental disorders, but the molecular bases of this clinical heterogeneity are unknown. We characterised five key mutants covering the whole spectrum of KIF5A-related phenotypes: spastic paraplegia (SPG, R17Q and R280C), Charcot-Marie-Tooth disease (CMT, R864*), amyotrophic lateral sclerosis (ALS, N999Vfs*40), and neonatal intractable myoclonus (NEIMY, C975Vfs*73) KIF5A mutants. CMT-R864*-KIF5A and ALS-N999Vfs*40-KIF5A showed impaired autoinhibition and peripheral localisation accompanied by altered mitochondrial distribution, suggesting transport competence disruption.

Next-generation sequencing in pediatric-onset epilepsies: Analysis with target panels and personalized therapeutic approach.

Objective: The objective of this study is to report the results of the genetic analysis in a large and well-characterized population with pediatric-onset epilepsies and to identify those who could benefit from precision medicine treatments.

Methods: In this retrospective observational study, we consecutively recruited patients with pediatric-onset epilepsy observed at a tertiary neurological center over a time span of 7 years, collecting clinical and laboratory findings. Following in-depth diagnostic process to exclude possible structural and metabolic causes of the disease, patients with a suspected genetically determined etiology underwent next-generation sequencing (NGS) screening with panels for the analysis of target genes causative of epilepsy.

Phenotypic Spectrum and Natural History of Gillespie Syndrome. An Updated Literature Review with 2 New Cases.

Background: Gillespie syndrome is a rare disorder caused by pathogenic variants in ITPR1 gene and characterized by the typical association of cerebellar ataxia, bilateral aniridia and intellectual disability. Since its first description in 1965, less than 100 patients have been reported and only 30 with a molecular confirmation.

Methods: We present two additional cases, both carrying a loss-of-function variant in the Gly2539 amino acid residue.

Phenotypic spectrum of myelin protein zero-related neuropathies: a large cohort study from five mutation clusters across Italy.

Background: We aimed to investigate the clinical features of a large cohort of patients with myelin protein zero ()-related neuropathy, focusing on the five main mutation clusters across Italy.

Methods: We retrospectively gathered a minimal data set of clinical information in a series of patients with these frequent mutations recruited among Italian Charcot-Marie-Tooth (CMT) registry centres, including disease onset/severity (CMTES-CMT Examination Score), motor/sensory symptoms and use of orthotics/aids.

Results: We collected data from 186 patients: 60 had the p.

Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.

Objectives: The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina.

Methods: A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed.

Distribution of the hexanucleotide repeat expansion in healthy subjects: a multicenter study promoted by the Italian IRCCS network of neuroscience and neurorehabilitation.

Introduction: High repeat expansion (HRE) alleles in have been linked to both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); ranges for intermediate allelic expansions have not been defined yet, and clinical interpretation of molecular data lacks a defined genotype-phenotype association. In this study, we provide results from a large multicenter epidemiological study reporting the distribution of repeats in healthy elderly from the Italian population.

Methods: A total of 967 samples were collected from neurologically evaluated healthy individuals over 70 years of age in the 13 institutes participating in the RIN (IRCCS Network of Neuroscience and Neurorehabilitation) based in Italy.

Pan American League of Associations for Rheumatology Guidelines for the treatment of ANCA-associated vasculitis.

Considerable variability exists in the way health-care providers treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Latin America. The most frequently used treatments for ANCA-associated vasculitis are cyclophosphamide and prolonged glucocorticoid tapers; however, randomised controlled trials conducted over the past 30 years have led to the development of several evidence-based treatment alternatives for these patients. Latin America faces socioeconomic challenges that affect access to care, and the use of certain costly medications with proven efficacy ANCA-associated vasculitis is often restricted.

Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review.

A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome.

Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.

Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34).

Difficult to treat rheumatoid arthritis in a comprehensive evaluation program: frequency according to different objective evaluations.

Difficult-to-treat Rheumatoid Arthritis (RA-D2T) is a condition in which patients do not achieve the treatment target despite multiple advanced therapies, more others features. Aims: to estimate the frequency of RA-D2T in a cohort comprehensively evaluated (clinical, serology, imaging), and to analyze the associated characteristics. In a second part, the frequency of RA-D2T after 1 year of follow-up, analyzing the predictive variables at baseline and therapeutic behavior.

Adult-onset leukodystrophy with vanishing white matter: a case series of 19 patients.

Background: Leukodystrophy with vanishing white matter (LVWM) is an autosomal recessive disease with typical pediatric-onset caused by mutations in one of the five EIF2B genes. Adult-onset (AO) cases are rare.

Methods: In this observational study, we reviewed clinical and laboratory information of the patients with AO-LVWM assessed at two referral centers in Italy and Portugal from Jan-2007 to Dec-2019.

AA16 Oxidoreductases Boost Cellulose-Active AA9 Lytic Polysaccharide Monooxygenases from .

Copper-dependent lytic polysaccharide monooxygenases (LPMOs) classified in Auxiliary Activity (AA) families are considered indispensable as synergistic partners for cellulolytic enzymes to saccharify recalcitrant lignocellulosic plant biomass. In this study, we characterized two fungal oxidoreductases from the new AA16 family. We found that AA16A from and AA16A from did not catalyze the oxidative cleavage of oligo- and polysaccharides.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Complex Ataxia-Dementia Phenotype in Patients with Digenic TBP/STUB1 Spinocerebellar Ataxia.

Background And Objectives: Spinocerebellar ataxias (SCAs) are autosomal dominant disorders with extensive clinical and genetic heterogeneity. We recently identified a form of SCA transmitted with a digenic pattern of inheritance caused by the concomitant presence of an intermediate-length expansion in TATA-box binding protein gene (TBP ) and a heterozygous pathogenic variant in the Stip1-homologous and U-Box containing protein 1 gene (STUB1). This SCA represents the first example of a cerebellar disorder in which digenic inheritance has been identified.

Ultrasound tenosynovitis: A differential feature of patients with seronegative rheumatoid arthritis.

Objective: To identify differential features between patients with seropositive and seronegative rheumatoid arthritis (RA).

Method: Prospective cohort study, including patients who were admitted for polyarthralgia. At baseline was performed: laboratory studies, X-rays of hands and feet, ultrasound of both hands with power Doppler technique, clinical data and clinimetry.