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Contains fulltext : 245024.pdf (Publisher’s version ) (Open Access), Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10-12.

Contains fulltext : 218274.pdf (Publisher’s version ) (Closed access), Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called "episignatures"). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders.

Contains fulltext : 220453.pdf (publisher's version ) (Open Access)

Contains fulltext : 206572.pdf (publisher's version ) (Open Access), We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.

Item does not contain fulltext, BACKGROUND: Double-lumen tubes (DLTs) or bronchial blockers are commonly used for one-lung ventilation. DLTs are sometimes difficult or even impossible to introduce, and the incidence of postoperative hoarseness and airway injuries is higher. Bronchial blockers are more difficult to position and need more frequent intraoperative repositioning. The design of a Y-shaped bronchial blocker, the EZ-Blocker (Teleflex Life Sciences Ltd., Athlone, Ireland) (EZB), combines some advantages of both techniques. The objective of this study was to assess whether EZB performs clinically better than left-sided DLTs (Broncho-cath; Mallinckrodt, Athlone, Ireland) without causing more injury. Primary outcome was the frequency of initial malpositions. METHODS: Eligible patients were adults scheduled for surgery requiring one-lung ventilation who met criteria for placement of both devices. In this parallel trial, 100 consecutive and blinded patients were assigned randomly using a computer-generated list to two groups. The incidence of malposition and ease and time of placement were recorded. Blinded assessors investigated quality of lung deflation, postoperative complaints, and damage to the airway. RESULTS: Placement of a DLT was unsuccessful twice. The incidence of initial malposition was high and comparable between EZBs (37 of 50) and DLTs (42 of 49) (P = 0.212). Placing single-lumen tubes and EZBs took more time but was rated easier. Quality of lung deflation was comparable. Fewer patients in the EZB group complained of sore throat at day 1. There was a higher incidence of tracheal hematoma and redness and bronchial hematoma in the DLT group. CONCLUSIONS: The EZB is an efficient and effective device for one-lung ventilation and causes less injury and sore throat than a DLT.

Item does not contain fulltext, BACKGROUND: When analyzing the effect of environmental exposure reduction measures on asthma in high-risk children, one must know how far asthmatic families already have applied such measures, because this would affect the effectiveness and efficiency of interventions aimed at reducing environmental exposure. OBJECTIVE: To describe the room for improvement by asthmatic families in mite, pet, and food allergen reducing measures and in parental passive smoking and to determine the resulting levels of mite and pet allergens by the applied sanitation measures. METHODS: Data were sampled by observation, weekly diary entries, and questionnaire when the infant was 6 months old and 1 year old. Dust samples were collected by vacuuming the living room floor and the parental and infant mattresses. Multiple logistic regression analyses were applied with the use of mattress encasing, having a smooth floor covering, having pets, exclusive breast-feeding and/or hypoallergenic formula during the infant's first 6 months, and passive smoking as the dependent variables. RESULTS: Frequencies of applied measures were as follows: having a smooth floor covering, 36%; daily house cleaning, 27%; use of parental and infant antimite mattress encasings, 13% and 9%, respectively; keeping no pets, 66%; no cow's milk-based regular formula, 13%; no solid foods in the first 6 months of life, 28%; and abstinence of smoking by the mother prenatally, 89%; by the mother postnatally, 85%; and by her partner, 76%. Having a smooth floor covering and daily cleaning but not use of antimite mattress encasings resulted in significantly lower mite and pet allergen levels. CONCLUSIONS: There is (still) enough room for improvement to reduce exposure to inhalant and food allergens, especially by application of mattress encasings, exclusive breast-feeding and/or hypoallergenic formula feeding, and postponing the time until first solids are given.

Contains fulltext : 26121___.PDF (publisher's version ) (Open Access)

Contains fulltext : 23594___.PDF (publisher's version ) (Open Access)

Die Molluskenfauna des Dollart-Ems-Gebietes, besonders des eigentlichen Dollart-Gebietes, ist artenarm. Eine Anreicherung der Molluskenfauna in der „Oude Westereems“ deutet auf örtliche Vermischung mit Eemfossilien hin. Im allgemeinen ist Hydrobia stärker vertreten an den Rändern der Priele. Sie hat ihr maximales Auftreten im höchstgelegenen Teil des Watts. Die Besiedelung der Platen besteht hauptsächlich aus Macoma balthica (Linné), Mya arenaria (Linné), und in bedeutend geringerem Masse Scrobicularia plana (Da Costa). Abgesehen von zwei örtlichen Ausnahmen wurden in den Prielen nur tote Exemplare vorgefunden. Eine dieser Ausnahmen wäre vielleicht durch anfangende seitliche Erosion des Prieles zu erklären. Übrigens weist das nur sehr örtliche Vorkommen von Eemfossilien, sowie die Verbreitung der Hydrobia-Formen, auf einen im allgemeinen geringen Transport im ganzen Dollart-Ems-Gebiet hin. Die Mollusken sind aufbewahrt im Zoologischen Museum in Amsterdam.

Het onderzochte gebied ligt in het westelijk gedeelte der Noord-Apennijnen, die zich van de omstreken van Genua in het W tot de Monte Falterona in Toscane in het E uitstrekken. De naam van Ligurische Apennijnen, die vooral door niet-Italianen aan dit gebergte wordt gegeven, is minder verkieselijk, aangezien tot de Ligurische Apennijnen vaak ook het gebergte ten W van Genua wordt gerekend, dat volgens Stille, Kober, e. a. reeds tot de Alpen behoort, volgens Staub e.a. daarentegen een overgangszone vertegenwoordigt tusschen Alpen en Apennijnen, maar dat in ieder geval in bouw zoo sterk afwijkt van de overige Apennijnenketen, dat het juister is de westgrens der Apennijnen ten N van Genua te trekken (fig. 1). Zooals in de titel aangegeven, worden west- en oostgrens van het gebied respectievelijk gevormd door de dalen van de Scrivia en de Stáffora; noord- en zuidgrens zijn onregelmatig, respectievelijk volgen zij ongeveer volgende lijnen: Cassano — Avolasca — Ponte Nizza en Isola del Cantone—Monte Giarolo — S. Margherita di Bobbio.

Cet aperçu sur les Spirorbes du Carbonifère néerlandais présente après une courte description de l’espèce Spirorbis pusillus, quelques remarques sur l’écologie de cette espèce et le commensalisme supposé par certains étudiants, mais encore douteux d’après l’opinion de l’auteur.

L’histoire géologique de Monferrato est marquée par une série de transgressions et de régressions de la mer, qui se manifestent généralement d’une manière très distincte dans la partie orientale de ces collines. Nous avons résumé cette histoire schématiquement dans la fig. 3 1). Dans les règles qui suivent nous décrirons à grands traits le développement de la partie orientale du bassin de Monferrato à partir du Jurassique jusqu’à la fin du Pliocène. Pendant le Jurassique et le Crétacé un grand bassin assez profond (mais certainement pas abyssal) s’étendait des Alpes occidentales (schistes lustrés) jusqu’au SE de Bologna. Ce bassin était entouré de terre ayant peu ou point de relief, de sorte qu’il y avait peu de transport de matériaux terrigènes. Des dépôts argileux se formaient. A la fin du Crétacé une grande régression s’est manifesté (déposition de conglomérats dans les collines occidentales, voir Beets p. 224). Après cette régression le bassin de Monferrato était peu profond et plus ou moins barré. Des argiles bitumineuses et des calcaires marneux se déposaient. Au commencement de l’Eocène supérieur la régression s’est poursuivie: il s’est formé un sédiment de marnes friables alternant avec des couches sableuses, parfois même caillouteuses. A la fin de l’Eocène un plissement s’est manifesté. Les „noyaux” éocènes de Casale et de Brusaschetto se sont formés. L’Oligocène a commencé par une transgression, pendant laquelle il y avait des côtes ou bien des hauts-fonds dans le sud et dans le NE de la région. La quantité de matériel caillouteux amené par les rivières des régions récemment soulevées (Alpes occidentales, Apennins septentrionaux) était grande et a donné naissance aux zones conglomératiques. A la fin du Rupélien le relief des régions soulevées avait beaucoup diminué, de sorte qu’il y avait peu de transport pendant le Chattien („Oligocène supérieur” de Beets). Le bassin chattien était d’