Expanding the natural history of CASK-related disorders to the prenatal period

Aim To assess whether microcephaly with pontine and cerebellar hypoplasia (MICPCH) could manifest in the prenatal period in patients with calcium/calmodulin-dependent serine protein kinase (CASK) gene disorders. Method In this international multicentre retrospective study, we contacted a CASK parents' social media group and colleagues with expertise in cerebellar malformations and asked them to supply clinical and imaging information. Centiles and standard deviations (SD) were calculated according to age by nomograms. Results The study consisted of 49 patients (44 females and 5 males). Information regarding prenatal head circumference was available in 19 patients; 11 out of 19 had a fetal head circumference below -2SD (range -4.1SD to -2.02SD, mean gestational age at diagnosis 20 weeks). Progressive prenatal deceleration of head circumference growth rate was observed in 15 out of 19. At birth, 20 out of 42 had a head circumference below -2SD. A total of 6 out of 15 fetuses had a TCD z-score below -2 (range -5.88 to -2.02). Interpretation This study expands the natural history of CASK-related disorders to the prenatal period, showing evidence of progressive deceleration of head circumference growth rate, head circumference below -2SD, or small TCD. Most cases will not be diagnosed according to current recommendations for fetal central nervous system routine assessment. Consecutive measurements and genetic studies are advised in the presence of progressive deceleration of head circumference growth rates or small TCD

Second-generation antipsychotic and diabetes mellitus in children and adolescents

Second generation antipsychotics (SGA) are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before), clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation. Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months. Blood sugar and HbA1c levels remained stable for about a year and then increased again, requiring the introduction of metformin that improved glycemia. In children and adolescents assuming SGA serum glucose and lipid profile should always be assessed before therapy and then frequently monitored. Drug selection must consider family history and the individual risk. Molecule final choice remains equilibrium between efficacy and safety

Clinical variability at the mild end of BRAT1‐related spectrum: Evidence from two families with genotype–phenotype discordance

Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal to neurodevelopmental disorder, and cerebellar atrophy with or without seizures, without obvious genotype-phenotype associations. We describe two families at the mildest end of the spectrum, differing in clinical presentation despite a common genotype at the BRAT1 locus. Two siblings displayed nonprogressive congenital ataxia and shrunken cerebellum on magnetic resonance imaging. A third unrelated patient showed normal neurodevelopment, adolescence-onset seizures, and ataxia, shrunken cerebellum, and ultrastructural abnormalities on skin biopsy, representing the mildest form of NEDCAS hitherto described. Exome sequencing identified the c.638dup and the novel c.1395G>A BRAT1 variants, the latter causing exon 10 skippings. The p53-MCL test revealed normal ATM kinase activity. Our findings broaden the allelic and clinical spectrum of BRAT1-related disease, which should be suspected in presence of nonprogressive cerebellar signs, even without a neurodevelopmental disorder

A regional audit system for stillbirth: A way to better understand the phenomenon

Background: Implementation of high-quality national audits for perinatal mortality are needed to improve the registration of all perinatal deaths and the identification of the causes of death. This study aims to evaluate the implementation of a Regional Audit System for Stillbirth in Emilia-Romagna Region, Italy. Methods: For each stillbirth ( 65 22 weeks of gestation, 65 500 g) occurred between January 1, 2014 to December 1, 2016 (n = 332), the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death (ReCoDe classification) and the quality of care. Data were reviewed by the Regional Audit Group. Stillbirth rates, causes of death and the quality of care were established for each case. Results: Total stillbirth rate was 3.09 per 1000 births (332/107,528). Late stillbirth rate was 2.3 per 1000 (251/107,087). Sixteen stillbirths were not registered by the Regional Birth Register. The most prevalent cause of death was placental disorder (33.3%), followed by fetal (17.6%), cord (14.2%) and maternal disorders (7.6%). Unexplained cases were 14%. Compared to local audits, the regional group attributed different causes of death in 17% of cases. At multivariate analysis, infections were associated with early stillbirths (OR 3.38, CI95% 1.62-7.03) and intrapartum cases (OR 6.64, CI95% 2.61-17.02). Placental disorders were related to growth restriction (OR 1.89, CI95% 1.06-3.36) and were more frequent before term (OR 1.86, CI95% 1.11-3.15). Stillbirths judged possibly/probably preventable with a different management (10.9%) occurred more frequently in non-Italian women and were mainly related to maternal disorders (OR 6.64, CI95% 2.61-17.02). Conclusions: Regional Audit System for Stillbirth improves the registration of stillbirth and allows to define the causes of death. Moreover, sub-optimal care was recognized, allowing to identify populations which could benefit from preventive measures

A combination of three engineering tools for identifying and evaluating the possible failures of a process

This paper presents a combination of three engineering tools, i.e. Dysfunctional Mode and Effects Critical Analysis (DMECA), Fault Tree Analysis (FTA) and House of Reliability (HoR), for identifying and evaluating the possible failures of a process. This tools are well known in the academic and industrial world. The methodology presented joined the strengths of them to analyze at the same time both the effects and causes of failures. Working for preventing or reducing them lead sometimes to avoid the failures of some activities of the process. This combination enables users to: • analyze each activity of a process • evaluate each potential failure and his causes • evaluate a Risk Priority Number (RPN) for each cause considering the degree of importance of each effect • study the relationship between causes and between causes and effects • support the definition and evaluation of the possible improvement actions First there is a briefly description of the strengths of these tools. Then, in order to illustrate the methodology there is an industrial application, i.e. for the delivery process of a famous company in the media-entertainment sector

AlmaDL Journals: servizi di qualità per l’editoria scientifica ad accesso aperto dell’Università di Bologna

The article illustrates AlmaDL Journals, the open access e-publishing service supporting scientific peer reviewed journals edited by Departments and research groups of the University of Bologna. Digital technologies and the Internet have deeply changed the way researchers and scholars access and share information. Moreover new technologies challenge professionals involved in the publishing value chain and publication life cycle at various levels. The traditional scholarly communication model fails to meet researchers’ needs and expectations. Initiatives such as the AlmaDL Journals seeks to provide alternative models that take full advantage of the digital environment and new media while ensuring quality requirements and the traditional functions of scientific serial publications.RiassuntoL’articolo illustra AlmaDL Journals, il servizio di editoria ad accesso aperto che offre supporto alle redazioni di riviste scientifiche referate pubblicate dai Dipartimenti e dai gruppi di ricerca dell’Università di Bologna. Le tecnologie del digitale e Internet hanno modificato profondamente il modo in cui studiosi e ricercatori accedono e condividono le informazioni. Inoltre le nuove tecnologie rappresentano una sfida difficile da affrontare per i professionisti coinvolti a vari livelli nella catena del valore e nel ciclo di vita delle pubblicazioni scientifiche digitali. Il modello di comunicazione scientifica tradizionale non riesce più a soddisfare in modo soddisfacente i bisogni e le aspettative dei ricercatori, Iniziative come quella di AlmaDL Journals cercano di fornire dei modelli alternativi che possano sfruttare a pieno le possibilità offerte dal digitale e dai nuovi media reti pur continuando ad assicurare i requisiti di qualità e le funzioni tradizionali di una pubblicazione scientifica periodica.Résumé L’article illustre AlmaDLJournals, le service d’édition à accès ouvert qui offre support aux rédactions de revues scientifiques publiées par les Départements et par les groupes de recherche de l’Université de Bologne. Les technologies du numérique et Internet ont profondément modifié la façon dont les savants et les rechercheurs accèdent et partagent les informations. En outre, les nouvelles technologies représentent un défi difficile à affronter pour les professions impliquées à différents niveaux dans la chaîne de la valeur et dans le cycle de vie des publications scientifiques numériques. Le modèle de communication scientifique traditionnelle ne réussit plus à satisfaire de façon satisfaisante les besoins et les attentes des rechercheurs. Des initiatives comme celle de AlmaDLJournals cherchent à fournir des modèles alternatifs qui puissent exploiter à fond les possibilités offertes par le numérique et par les nouveaux médias tout en continuant à assurer les conditions requises de qualité et les fonctions traditionnelles d’une publication scientifique périodique.Zusammenfassung Der Artikel erläutert AlmaDL Journals, einen frei zugänglichen Verlagsservice zur Unterstützung der Redaktionen wissenschaftlicher Zeitschriften, die von den Ministerien und Forschungsgruppen der Universität Bologna referiert und veröffentlicht werden. Digitale Technologien und das Internet haben die Art des Informationszugangs und der Teilung von Informationen von Studenten und Forschern tief greifend verändert. Darüber hinaus stellen neue Technologien eine für auf verschiedenen Ebenen in der Wertkette und im Lebenszyklus wissenschaftlicher digitaler Veröffentlichungen eingebundene Professoren äußerst schwierige Herausforderung dar. Das traditionelle wissenschaftliche Kommunikationsmodell ist nicht länger in der Lage, die Anforderungen und Erwartungen von Forschern zufriedenstellend zu erfüllen. Initiativen wie AlmaDLJournals versuchen, Alternativmodelle zu liefern, anhand derer sich die von der digitalen Welt und den neuen Medien gebotenen Möglichkeiten vollends ausschöpfen lassen, ohne dabei den Qualitätsanspruch und die traditionellen Funktionen einer regelmäßig erscheinenden wissenschaftlichen Veröffentlichung zu kompromittieren.Resumen El artículo ilustra AlmaDLJournals, el servicio editorial de acceso libre que brinda apoyo a las redacciones de revistas científicas referenciadas publicadas por Departamentos y grupos de investigación de la Universidad de Bologna. Las tecnologías del digital e Internet han modificado profundamente la manera con la cual estudiosos e investigadores acceden y comparten las informaciones. Además las nuevas tecnologías plantean un reto difícil para los profesionales involucrados a varios niveles en la cadena del valor y en el ciclo de vida de las publicaciones científicas digitales. El modelo de comunicación científica tradicional ya no consigue cumplir de manera satisfactoria las necesidades y las expectativas de los investigadores. Iniciativas como la de AlmaDLJournals intentan sugerir modelos alternativos capaces de explotar al máximo las posibilidades ofrecidas por el digital y los nuevos medios garantizando a la vez los requisitos de calidad y manteniendo las funciones tradicionales de las publicaciones científicas periódicas.РезюмеСтатья рассказывает о AlmaDLJournals, издательской службе открытого до­ступа, которая обеспечивает поддержку редакциям реферируемых научных жур­налов, опубликованных Отделами и исследовательскими группами Болонского университета. Цифровые технологии и Интернет глубоко изменили методы, кото­рыми пользуются ученые и исследователи для получения информации и обмена ею. Кроме этого, новые технологии являются серьезным вызовом для профессо­ров, которые участвуют на разных уровнях в оценке и жизненном цикле цифро­вых научных публикаций. Традициональная модель научной коммуникации уже не в состоянии удовлетворить должным образом нужды и ожидания исследова­телей. Такие инициативы как AlmaDLJournals, пытаются предложить альтерна­тивные модели, которые способны полностью воспользоваться возможностями, предлагаемыми цифровыми технологиями и новыми медия, и в то же время про­должают гарантировать реквизиты качества и традициональную функциональ­ность научной переодики.ԱմփոփումՀոդվածը նկարագրում է Բոլոնյայի համալսարանի AlmaDL ամսագրերը, որոնք առաջարկում են հրատարակչության բաց հասանելիութուն, աջակցություն հետազոտական խմբերի կողմից հրատարակված refereed գիտական ամսագրերի: Թվային (digital) տեխնոլոգիաները և ինտերնետը արդեն խորապես փոխել են այն եղանակը, որով գիտնականները և հետազոտողները ունեն հասանելիության և 213 CONSERVATION SCIENCE IN CULTURAL HERITAGE տեղեկատվություն: Ավելին, նոր տեխնոլոգիաները ներկայացնում են մի դժվարին մարտահրավեր տարբեր մասնագիտությունների միջև որ ներգրավված են տարբեր մակարդակներում և կյանքի փուլի թվային գիտական հրապարակումներում: Ավանդական մոդելը, գիտական կապը այլևս ի վիճակի չեն բավարարել, հետազոտողների, երիտասարդերի նախաձեռնությունները, կարիքներն ու ակնկալիքները, դրա համար AlmaDL ամսագրերը ձգտում են ապահովել այլընտրանքային մոդելներ, որոնք կարող են լիովին օգտագործել թվային և նոր լրատվամիջոցների ցանցերի կողմից առաջարկվող հնարավորությունները, շարունակելով ապահովել պահանջները և ավանդական գիտական պարբերականի դիմագիծը

Age and sex prevalence estimate of Joubert syndrome in Italy

OBJECTIVE: To estimate the prevalence of Joubert syndrome (JS) in Italy applying standards of descriptive epidemiology and to provide a molecular characterization of the described patient cohort. METHODS: We enrolled all patients with a neuroradiologically confirmed diagnosis of JS who resided in Italy in 2018 and calculated age and sex prevalence, assuming a Poisson distribution. We also investigated the correlation between proband chronological age and age at diagnosis and performed next-generation sequencing (NGS) analysis on probands' DNA when available. RESULTS: We identified 284 patients with JS: the overall, female- and male-specific population-based prevalence rates were 0.47 (95% confidence interval [CI] 0.41-0.53), 0.41 (95% CI 0.32-0.49), and 0.53 (95% CI 0.45-0.61) per 100,000 population, respectively. When we considered only patients in the age range from 0 to 19 years, the corresponding population-based prevalence rates rose to 1.7 (95% CI 1.49-1.97), 1.62 (95% CI 1.31-1.99), and 1.80 (95% CI 1.49-2.18) per 100,000 population. NGS analysis allowed identifying the genetic cause in 131 of 219 screened probands. Age at diagnosis was available for 223 probands, with a mean of 6.67 ± 8.10 years, and showed a statistically significant linear relationship with chronological age (r2 = 0.79; p < 0.001). CONCLUSIONS: We estimated for the first time the age and sex prevalence of JS in Italy and investigated the patients' genetic profile. The obtained population-based prevalence rate was ≈10 times higher than that available in literature for children population

Genetic Variability among Swine Influenza Viruses in Italy: Data Analysis of the Period 2017–2020

Swine play an important role in the ecology of influenza A viruses (IAVs), acting as mixing vessels. Swine (sw) IAVs of H1N1 (including H1N1pdm09), H3N2, and H1N2 subtypes are enzootic in pigs globally, with different geographic distributions. This study investigated the genetic diversity of swIAVs detected during passive surveillance of pig farms in Northern Italy between 2017 and 2020. A total of 672 samples, IAV-positive according to RT-PCR, were subtyped by multiplex RT-PCR. A selection of strains was fully sequenced. High genotypic diversity was detected among the H1N1 and H1N2 strains, while the H3N2 strains showed a stable genetic pattern. The hemagglutinin of the H1Nx swIAVs belonged to HA-1A, HA-1B, and HA-1C lineages. Increasing variability was found in HA-1C strains with the circulation of HA-1C.2, HA-1C.2.1 and HA-1C.2.2 sublineages. Amino acid deletions in the HA-1C receptor binding site were observed and antigenic drift was confirmed. HA-1B strains were mostly represented by the Δ146-147 Italian lineage HA-1B.1.2.2, in combination with the 1990s human-derived NA gene. One antigenic variant cluster in HA-1A strains was identified in 2020. SwIAV circulation in pigs must be monitored continuously since the IAVs’ evolution could generate strains with zoonotic potential

Impaired urinary concentration ability is a sensitive predictor of renal disease progression in Joubert syndrome

Joubert syndrome (JS) is an inherited ciliopathy characterized by a complex midbrain-hindbrain malformation and multiorgan involvement. Renal disease, mainly juvenile nephronophthisis (NPH), was reported in 25-30% patients although only ∼18% had a confirmed diagnosis of chronic kidney disease (CKD). NPH often remains asymptomatic for many years, resulting in delayed diagnosis. The aim of the study was to identify a biomarker able to quantify the risk of progressive CKD in young children with JS

Current evidence in the field of the management with TNF-α inhibitors in psoriatic arthritis and concomitant hepatitis C virus infection

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory condition involving the spine, enthesis and peripheral joints, which is associated with psoriasis. PsA therapy varies from use of NSAIDs to disease-modifying anti-rheumatic agents (DMARDs). However, their use can represent a limitation in patients with concomitant hepatitis C virus (HCV) infection. In the last few decades, anti-TNF-α therapy has opened new horizons in the treatment of PsA. Hence, the purpose of this review is to explore the efficacy and safety of anti-TNF-α agents in PsA and concomitant HCV infection. Areas covered: We reviewed the available medical literature to find all cases of PsA and concomitant HCV infection treated with TNF-α inhibitors. We found a total of 38 cases of patients with PsA and concomitant HCV infection in therapy with anti-TNF-α agents. Expert opinion: The available literature, summarized in this review, still remains very limited. Data suggest that therapy with the anti-TNF-α agents, mainly etanercept and adalimumab, at least with short-term use, would appear efficacious and reasonably safe in the management of PsA patients with concomitant HCV infection. With regard to infliximab, efficacy and safety have been scarcely explored, whereas in the case of golimumab and certolizumab no report was found, may be due to their recent introduction on the market