Experimental and theoretical study on the impact of a nitrate group on the chemistry of alkoxy radicals.

The chemistry of nitrated alkoxy radicals, and its impact on RO2 measurements using the laser induced fluorescence (LIF) technique, is examined by a combined theoretical and experimental study. Quantum chemical and theoretical kinetic calculations show that the decomposition of β-nitrate-alkoxy radicals is much slower than β-OH-substituted alkoxy radicals, and that the spontaneous fragmentation of the α-nitrate-alkyl radical product to a carbonyl product + NO2 prevents other β-substituents from efficiently reducing the energy barrier. The systematic series of calculations is summarized as an update to the structure-activity relationship (SAR) by Vereecken and Peeters (2009), and shows increasing decomposition rates with higher degrees of substitution, as in the series ethene to 2,3-dimethyl-butene, and dominant H-migration for sufficiently large alkoxy radicals such as those formed from 1-pentene or longer alkenes.

Theoretical and experimental study of peroxy and alkoxy radicals in the NO-initiated oxidation of isoprene.

The initial stages of the nitrate radical (NO3) initiated oxidation of isoprene, in particular the fate of the peroxy (RO2) and alkoxy (RO) radicals, are examined by an extensive set of quantum chemical and theoretical kinetic calculations. It is shown that the oxidation mechanism is highly complex, and bears similarities to its OH-initiated oxidation mechanism as studied intensively over the last decade. The nascent nitrated RO2 radicals can interconvert by successive O2 addition/elimination reactions, and potentially have access to a wide range of unimolecular reactions with rate coefficients as high as 35 s-1; the contribution of this chemistry could not be ascertained experimentally.

Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy.

Objective: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features.

Design: Retrospective analysis of the Italian data set of patients with TNDM.

Biallelic hypomorphic variants in ALDH1A2 cause a novel lethal human multiple congenital anomaly syndrome encompassing diaphragmatic, pulmonary, and cardiovascular defects.

This study shows a causal association between ALDH1A2 variants and a novel, severe multiple congenital anomaly syndrome in humans that is neonatally lethal due to associated pulmonary hypoplasia and respiratory failure. In two families, exome sequencing identified compound heterozygous missense variants in ALDH1A2. ALDH1A2 is involved in the conversion of retinol (vitamin A) into retinoic acid (RA), which is an essential regulator of diaphragm and cardiovascular formation during embryogenesis.

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome.

Kabuki syndrome (KS) is a rare genetic condition with multiple congenital abnormalities and developmental delay. The cardinal manifestations of KS include characteristic facial features, intellectual disability, skeletal defects, dermatoglyphic abnormalities, and postnatal growth deficiencies. Cardiac and urological malformations are commonly present in patient with KS, as well as language deficits and immunological abnormalities.

Correlation of mesolevel characteristics of the healthcare system and socioeconomic inequality in healthcare use: a scoping review protocol.

Introduction: Although the impact of macrolevel characteristics of health systems on socioeconomic inequity in health has been studied extensively, the impact of access characteristics on a smaller scale of health systems has received less attention. These mesolevel characteristics can influence access to healthcare and might have the potential to moderate or aggravate socioeconomic inequity in healthcare use. This scoping review aims to map the existing evidence of the association of socioeconomic inequity in healthcare use and mesolevel access characteristics of the health system.

Fetal early motor neuron disruption and prenatal molecular diagnosis in a severe BICD2-opathy.

BICD2 (BICD Cargo Adaptor 2, MIM*609797) mutations are associated with severe prenatal-onset forms of spinal muscular atrophy, lower extremity-predominant 2B (SMALED2B MIM 618291) or milder forms with childhood-onset (SMALED2A MIM 615290). Etiopathogenesis is not fully clarified and a wide spectrum of phenotypic presentations is reported, ranging from extreme prenatal forms with adverse outcome, to slow progressive late-onset forms. We report a fetus at 22 gestational weeks with evidence of Arthrogryposis Multiplex Congenita on ultrasound, presenting with fixed extended lower limbs and flexed upper limbs, bilateral clubfoot and absent fetal movements.

Autism and severe clinical phenotype in a patient with 8p21.2p11.21 deletion: Case report and literature review.

Interstitial 8p deletions were previously described, in literature and databases, in approximately 30 patients with neurodevelopmental disorders. We report on a novel patient with a 8p21.2p11.

Cytogenetics and Molecular Investigations detect a Mosaic Variant of Turner Syndrome only Suspected by Non-Invasive Prenatal Testing: Two Case Reports with Negative Ultrasound Examinations.

Prenatal testing has been moving towards non-invasive methods to determine fetal risk for genetic disorders. Numerous studies have focused the attention on common trisomies; although the detection rate (DR) for trisomy 21 is high (over 95%), the accuracy regarding the DR for trisomies 13 and 18 has come under scrutiny. The testing has been applied to sex chromosome aneuploidies, but many studies have shown that it is not as effective as it is for common trisomies.

Homozygous and Gene Variants in a Boy with Growth Hormone Deficiency and Early Onset Osteoporosis.

We report on a patient born to consanguineous parents, presenting with Growth Hormone Deficiency (GHD) and osteoporosis. SNP-array analysis and exome sequencing disclosed long contiguous stretches of homozygosity and two distinct homozygous variants in (Q6H) and (E1361K) genes. The variant was described as causative in a few subjects with an incompletely penetrant dominant form of combined pituitary hormone deficiency (CPHD).

Clinical and molecular characterizations of 11 new patients with type 1 Feingold syndrome: Proposal for selecting diagnostic criteria and further genetic testing in patients with severe phenotype.

Feingold Syndrome type 1 (FS1) is an autosomal dominant disorder due to a loss of function mutations in the MYCN gene. FS1 is generally clinically characterized by mild learning disability, microcephaly, short palpebral fissures, short stature, brachymesophalangy, hypoplastic thumbs, as well as syndactyly of toes, variably associated with organ abnormalities, the most common being gastrointestinal atresia. In current literature, more than 120 FS1 patients have been described, but diagnostic criteria are not well agreed upon, likewise the genotype-phenotype correlations are not well understood.

A new and short protocol to achieve the early diagnosis of mild cognitive impairment.

Purpose: The mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected for the age and education of the subject but are not significant enough to interfere with instrumental activities of daily living. The identification of individuals with MCI is particularly important for those who might benefit from new therapies. The aim of this work is to propose a comprehensive neuropsychological protocol to achieve early diagnosis of MCI.

Clinical Application of Easychip 8x15K Platform in 4106 Pregnancies Without Ultrasound Anomalies.

Clinical utility of Array-CGH Easychip 8x15K platform can be assessed by testing its ability to detect the occurrence of pathogenic copy number variants (CNVs), and occurrence of variants of uncertain significance (VoUS) in pregnancies without structural fetal malformations. The demand of chromosomal microarray analysis in prenatal diagnosis is progressively increasing in uneventful pregnancies. However, depending on such platform resolution, a genome-wide approach also provides a high risk of detecting VoUS and incidental finding (IF) also defined as "toxic findings.

Biallelic variants in cause a severe neurodevelopmental disorder with microcephaly, bilateral cataract, epilepsy and simplified gyration.

Background: Next-generation sequencing, combined with international pooling of cases, has impressively enhanced the discovery of genes responsible for Mendelian neurodevelopmental disorders, particularly in individuals affected by clinically undiagnosed diseases. To date, biallelic missense variants in gene, encoding a Krüppel-type zinc-finger protein, have been reported in three families with non-syndromic intellectual disability.

Methods: Here, we describe five individuals from four unrelated families with an undiagnosed neurodevelopmental disorder in which we performed exome sequencing, on a combination of trio-based (4 subjects) or single probands (1 subject).

Clinical presentation and molecular characterization of a novel patient with variant POC1A-related syndrome.

Biallelic pathogenic variants in POC1A result in SOFT (Short-stature, Onychodysplasia, Facial-dysmorphism, and hypoTrichosis) and variant POC1A-related (vPOC1A) syndromes. The latter, nowadays described in only two unrelated subjects, is associated with a restricted spectrum of variants falling in exon 10, which is naturally skipped in a specific POC1A mRNA. The synthesis of an amount of a POC1A isoform from this transcript in individuals with vPOC1A syndrome has been believed as the likely explanation for such a genotype-phenotype correlation.

Role of contextual and compositional characteristics of schools for health inequalities in childhood and adolescence: protocol for a scoping review.

Introduction: Childhood and adolescence are crucial life stages for health trajectories and the development of health inequalities in later life. The relevance of schools for health and well-being of children and adolescents has long been recognised, and there is some research regarding the association of contextual and compositional characteristics of schools and classes with health, health behaviour and well-being in this population. Little is known about the role of meso-level characteristics in relation to health inequalities.

Levodopa-carbidopa intrajejunal infusion in Parkinson's disease: untangling the role of age.

Objectives: Levodopa-Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson's disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG.

Exon-Trapping Assay Improves Clinical Interpretation of and Intronic Variants in Stickler Syndrome Type 2 and Otospondylomegaepiphyseal Dysplasia.

Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in and , respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation.

Immunofluorescence mapping, electron microscopy and genetics in the diagnosis and sub-classification of inherited epidermolysis bullosa: a single-centre retrospective comparative study of 87 cases with long-term follow-up.

Background: Epidermolysis bullosa (EB) comprises a heterogeneous group of skin fragility disorders, classified in four major types based on skin cleavage level, i.e. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, and in more than 30 subtypes defined by the combination of laboratory and clinical data, including disease course.

When embryology meets genetics: the definition of developmentally incompetent preimplantation embryos (DIPE)-the consensus of two Italian scientific societies.

A clear definition of developmentally incompetent preimplantation embryo (DIPE) in literature is still missing, while several scientific societies are discussing this challenging topic. From both a clinical and scientific perspective, the identification of embryos unfit for reproductive purpose is crucial. This aim should be pursued in light of all diagnostic technologies for embryo evaluation, encompassing also genetic analyses, of recent implementation in IVF.

Heterozygous Variants in KDM4B Lead to Global Developmental Delay and Neuroanatomical Defects.

KDM4B is a lysine-specific demethylase with a preferential activity on H3K9 tri/di-methylation (H3K9me3/2)-modified histones. H3K9 tri/di-demethylation is an important epigenetic mechanism responsible for silencing of gene expression in animal development and cancer. However, the role of KDM4B on human development is still poorly characterized.

Recurrent prenatal PIEZO1-related lymphatic dysplasia: Expanding molecular and ultrasound findings.

Generalized lymphatic dysplasia (GLD), characterized by lymphedema, lymphangiectasias, chylothorax, effusions, represents a recognized cause of fetal hydrops. We describe for the first time recurrent pregnancies showing different ultrasound presentations of lymphatic dysplasia. The first fetus displayed diffuse subcutaneous cysts and septations while the second one presented fetal hydrops.

Prorocentroic Acid, a Neuroactive Super-Carbon-Chain Compound from the Dinoflagellate .

Prorocentroic acid (PA) was isolated from the dinoflagellate Relative configurations for its 35 asymmetric centers were determined by analysis of NMR data including heteronuclear couplings and quantum mechanical calculations. PA was tested by using murine cortical neurons grown on microelectrode arrays. Long-term exposure to subtoxic concentrations induced a significant reorganization of neuronal signaling, mainly by changes in the bursting activity.

Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis.

We describe a 2 year old boy with two previously undescribed frameshift mutations in the interferon (IFN)α/β receptor 2 () gene presenting with hemophagocytic lymphohistiocytosis (HLH) following measles-mumps-rubella vaccination. Functional analyses show the absence of response to type I IFN in the patient's cells, as revealed by the lack of phosphorylation of STAT1 and the lack of induction of interferon-stimulated genes upon stimulation with IFNα. HLH has been reported in patients with inborn errors of type I IFN-mediated immune responses following vaccination with live-attenuated viruses.

7q11.23 Microduplication Syndrome: Clinical and Neurobehavioral Profiling.

7q11.23 Microduplication (dup7q11.23) syndrome is a rare autosomal dominant disorder due to a recurring 1.