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PURPOSE: Since pediatric surgeons aim to follow their patients with anorectal malformations (ARM) into adulthood the aim of this study was to investigate how pediatric surgeons deal with sexual issues related to ARM. METHODS: In 2018, a questionnaire was developed by the working group "Follow-up and sexuality" of the ARM-Net consortium and sent to all consortium-linked pediatric surgeons from 31 European pediatric surgical centers. Obtained data were statistically analyzed. RESULTS: Twenty-eight of 37 pediatric surgeons (18 males/10 females) answered the questionnaire. The majority of pediatric surgeons (82%) think they should talk about sexual issues with their patient. More than 50% of pediatric surgeons do not feel at all or only moderately confident discussing the topic of sexuality. Most pediatric surgeons require more support (96%) and wish to be trained in sexuality and sexual issues (78%) to feel confident towards their ARM-patients/parents. For optimal care, sexual issues with ARM-patients should be managed by a multidisciplinary team. CONCLUSIONS: Pediatric surgeons feel that sexuality is an important issue for their ARM-patients, which they are primarily responsible of but should be managed in concert with a multidisciplinary team. A training in sexuality is wished to feel more confident about this specific issue. ispartof: PEDIATRIC SURGERY INTERNATIONAL vol:35 issue:9 pages:935-943 ispartof: location:Germany status: published

Background: The impact of perioperative care interventions on postreconstructive complications and short-term colorectal outcome in patients with anorectal malformation (ARM) type rectovestibular fistula is unknown.Methods: An ARM-Net consortium multicenter retrospective cohort study was performed including 165 patients with a rectovestibular fistula. Patient characteristics, perioperative care interventions, timing of reconstruction, postreconstructive complications and the colorectal outcome at one year of follow-up were registered.Results: Overall complications were seen in 26.8% of the patients, of which 41% were regarded major. Differences in presence of enterostomy, timing of reconstruction, mechanical bowel preparation, antibiotic prophylaxis and postoperative feeding regimen had no impact on the occurrence of overall complications. However, mechanical bowel preparation, antibiotic prophylaxis >= 48 h and postoperative nil by mouth showed a significant reduction in major complications. The lowest rate of major complications was found in the group having these three interventions combined (5.9%).Multivariate analyses did not show independent significant results of any of the perioperative care interventions owing to center-specific combinations. At one year follow-up, half of the patients experienced constipation and this was significantly higher among those with preoperative mechanical bowel preparation.Conclusions: Differences in perioperative care interventions do not seem to impact the incidence of overall complications in a large cohort of European rectovestibular fistula-patients. Mechanical bowel preparation, antibiotic prophylaxis >= 48 h, and postoperative nil by mouth showed the least major complications. Independency could not be established owing to center-specific combinations of interventions.Type of study: Treatment study. (C) 2019 Elsevier Inc. All rights reserved.

The extracellular matrix comprises a network of macromolecules such as collagens, proteoglycans and glycoproteins. VWA1 (von Willebrand factor A domain containing 1) encodes a component of the extracellular matrix that interacts with perlecan/collagen VI, appears to be involved in stabilizing extracellular matrix structures, and demonstrates high expression levels in tibial nerve. Vwa1-deficient mice manifest with abnormal peripheral nerve structure/function; however, VWA1 variants have not previously been associated with human disease. By interrogating the genome sequences of 74 180 individuals from the 100K Genomes Project in combination with international gene-matching efforts and targeted sequencing, we identified 17 individuals from 15 families with an autosomal-recessive, non-length dependent, hereditary motor neuropathy and rare biallelic variants in VWA1. A single disease-associated allele p.(G25Rfs*74), a 10-bp repeat expansion, was observed in 14/15 families and was homozygous in 10/15. Given an allele frequency in European populations approaching 1/1000, the seven unrelated homozygote individuals ascertained from the 100K Genomes Project represents a substantial enrichment above expected. Haplotype analysis identified a shared 220 kb region suggesting that this founder mutation arose >7000 years ago. A wide age-range of patients (6-83 years) helped delineate the clinical phenotype over time. The commonest disease presentation in the cohort was an early-onset (mean 2.0 ± 1.4 years) non-length-dependent axonal hereditary motor neuropathy, confirmed on electrophysiology, which will have to be differentiated from other predominantly or pure motor neuropathies and neuronopathies. Because of slow disease progression, ambulation was largely preserved. Neurophysiology, muscle histopathology, and muscle MRI findings typically revealed clear neurogenic changes with single isolated cases displaying additional myopathic process. We speculate that a few findings of myopathic changes might be secondary to chronic denervation rather than indicating an additional myopathic disease process. Duplex reverse transcription polymerase chain reaction and immunoblotting using patient fibroblasts revealed that the founder allele results in partial nonsense mediated decay and an absence of detectable protein. CRISPR and morpholino vwa1 modelling in zebrafish demonstrated reductions in motor neuron axonal growth, synaptic formation in the skeletal muscles and locomotive behaviour. In summary, we estimate that biallelic variants in VWA1 may be responsible for up to 1% of unexplained hereditary motor neuropathy cases in Europeans. The detailed clinical characterization provided here will facilitate targeted testing on suitable patient cohorts. This novel disease gene may have previously evaded detection because of high GC content, consequential low coverage and computational difficulties associated with robustly detecting repeat-expansions. Reviewing previously unsolved exomes using lower QC filters may generate further diagnoses.

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article.

Next-generation sequencing is a powerful tool for the discovery of genes related to neurodevelopmental disorders (NDDs). Here, we report the identification of a distinct syndrome due to de novo or inherited heterozygous mutations in Tousled-like kinase 2 (TLK2) in 38 unrelated individuals and two affected mothers, using whole-exome and whole-genome sequencing technologies, matchmaker databases, and international collaborations. Affected individuals had a consistent phenotype, characterized by mild-borderline neurodevelopmental delay (86%), behavioral disorders (68%), severe gastro-intestinal problems (63%), and facial dysmorphism including blepharophimosis (82%), telecanthus (74%), prominent nasal bridge (68%), broad nasal tip (66%), thin vermilion of the upper lip (62%), and upslanting palpebral fissures (55%). Analysis of cell lines from three affected individuals showed that mutations act through a loss-of-function mechanism in at least two case subjects. Genotype-phenotype analysis and comparison of computationally modeled faces showed that phenotypes of these and other individuals with loss-of-function variants significantly overlapped with phenotypes of individuals with other variant types (missense and C-terminal truncating). This suggests that haploinsufficiency of TLK2 is the most likely underlying disease mechanism, leading to a consistent neurodevelopmental phenotype. This work illustrates the power of international data sharing, by the identification of 40 individuals from 26 different centers in 7 different countries, allowing the identification, clinical delineation, and genotype-phenotype evaluation of a distinct NDD caused by mutations in TLK2.

Contains fulltext : 185259.pdf (Publisher’s version ) (Open Access) BACKGROUND: Mutations in EFTUD2 were proven to cause a very distinct mandibulofacial dysostosis type Guion-Almeida (MFDGA, OMIM #610536). Recently, gross deletions and mutations in EFTUD2 were determined to cause syndromic esophageal atresia (EA), as well. We set forth to find further conditions caused by mutations in the EFTUD2 gene (OMIM *603892). METHODS AND RESULTS: We performed exome sequencing in two familial cases with clinical features overlapping with MFDGA and EA, but which were previously assumed to represent distinct entities, a syndrome with esophageal atresia, hypoplasia of zygomatic complex, microcephaly, cup-shaped ears, congenital heart defect, and intellectual disability in a mother and her two children [AJMG 143A(11):1135-1142, 2007] and a supposedly autosomal recessive oto-facial syndrome with midline malformations in two sisters [AJMG 132(4):398-401, 2005]. While the analysis of our exome data was in progress, a recent publication made EFTUD2 mutations highly likely in these families. This hypothesis could be confirmed with exome as well as with Sanger sequencing. Also, in three further sporadic patients, clinically overlapping to these two families, de novo mutations within EFTUD2 were identified by Sanger sequencing. Our clinical and molecular workup of the patients discloses a broad phenotypic spectrum, and describes for the first time an instance of germline mosaicism for an EFTUD2 mutation. CONCLUSIONS: The clinical features of the eight patients described here further broaden the phenotypic spectrum caused by EFTUD2 mutations or deletions. We here show, that it not only includes mandibulofacial dysostosis type Guion-Almeida, which should be reclassified as an acrofacial dysostosis because of thumb anomalies (present in 12/35 or 34% of patients) and syndromic esophageal atresia [JMG 49(12). 737-746, 2012], but also the two new syndromes, namely oto-facial syndrome with midline malformations published by Megarbane et al. [AJMG 132(4): 398-401, 2005] and the syndrome published by Wieczorek et al. [AJMG 143A(11): 1135-1142, 2007] The finding of mild phenotypic features in the mother of one family that could have been overlooked and the possibility of germline mosaicism in apparently healthy parents in the other family should be taken into account when counseling such families.

De kwaliteit van moerplanten heeft direct effect op de kwaliteit van stek en de daaruit groeiende productieplant. Het is mogelijk de gemiddelde kwaliteit en de homogeniteit van uitgangsmateriaal te verbeteren door een aantal simpele principes aan te houden. De kan tot duurder materiaal leiden, maar in meerjagie teelten zoals roos is dat

Item does not contain fulltext Feingold syndrome (FS) is a dominantly inherited combination of microcephaly with or without learning disabilities, hand and foot abnormalities, short palpebral fissures and esophageal/duodenal atresia. The syndrome has autosomal dominant inheritance with full penetrance, and variable expressivity. Digital anomalies are almost always present. The gene for FS is localized to a 2.2 cM region in 2p23-p24. We report on the first Turkish family with Feingold syndrome. The propositus is a male infant with microcephaly, frontal balding, brachymesophalangy of the second and fifth fingers, bilateral syndactyly of toes 2-3, facial anomalies, choanal atresia and focal epilepsy. His father has microcephaly, and more severe hands and feet abnormalities. One of his brothers died because of eosofageal atresia. Clinical presentation of the family was suggestive of Feingold syndrome, and genetic testing of the MYCN gene confirmed the diagnosis. The missense mutation we report here has not been described previously. FS is an autosomal dominant condition, and therefore, the diagnosis has important implications for genetic counseling.

Congenital long QT-syndrome (LQTS) was diagnosed in three patients. The first patient, a 10-year-old girl, presented with recurrent episodes of syncope during swimming and was diagnosed with type 1 LQTS. The second patient, a 36-year-old asymptomatic man, was accidentally diagnosed with type 2 LQTS. His family history revealed syncope and sudden death at a young age after auditory stimuli. Type 3 LQTS was diagnosed post-mortem in a 16-year-old boy who died during his sleep. All clinical diagnoses were confirmed by genetic testing. Congenital LQTS is one of the leading causes of sudden cardiac death at a young age. Mutations in genes encoding for myocardial ion channel proteins lead to a prolonged QT-interval and abnormal ST-T segments in the 12-lead ECG. Patients may present with syncope or sudden cardiac death caused by ventricular tachyarrhythmias. Genotype-specific differences in ECG-abnormalities and triggers for cardiac events may help to distinguish the type of LQTS and make possible the initiation of genotype-specific treatment before the results of genetic testing are known. Identification of the genetic substrate by genetic testing, genotype-specific treatment, and the possibility of treatment with an implantable cardioverter-defibrillator have all led to dramatic improvement in the prognosis of patients with LQTS. Therefore, young patients with unexplained recurrent syncope after specific stimuli and those with atypical forms of epilepsy should be referred for cardiologic evaluation in a specialised centre

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Distillates from crude oil such as diesel and fuel oil may contain significant amounts of dibenzothiophenes and their alkylated derivatives, containing organically bound sulfur. Combustion of those fossil fuels leads to the release of polluting sulfur dioxide into the atmosphere, where it causes 'acid rain'. Due to stricter environmental legislation and depletion of crude oil reserves with low organic sulfur contents, effective desulfurization processes are becoming increasingly important. For instance: beginning in 2005 the maximal allowable sulfur content in gas oil in the European Community will be 0.005 wt.%. Currently, the refining industry applies the energy intensive physico-chemical hydrodesulfurization (HDS) process in order to reduce the sulfur content. Due to the high costs and inherent chemical limitations associated with HDS, biodesulfurization of hydrocarbon streams might represent an attractive complementary method to obtain sufficiently low sulfur levels. Bacteria require relatively mild process conditions (pressure and temperature) and bacterial enzymes are very selective in converting target molecules.The objective of this thesis was to develop an anaerobic biodesulfurization process. The thesis is build up around the reductive desulfurization reaction presented below.Dibenzothiophene (DBT) is converted under anaerobic conditions to biphenyl and sulfide with the concomitant conversion of reduction equivalents. The caloric value of the fuel molecule is retained and the sulfur is removed specifically.Chapter 1 presents a general introduction on physico-chemical and microbiological methods to desulfurize organic sulfur compounds.In Chapter 2 the DBT mass transfer rate within hydrocarbon droplets is compared to aerobic DBT conversion rates. The apolar DBT must diffuse to the hydrocarbon/water interface where bacteria prevail. The calculated values for the DBT mass transfer rate were compared to those found for aerobic DBT conversion rates, as reported in the literature. Temperature dependent data (ranging from 20 up to 60°C) of viscosity, density, and interfacial tension of various hydrocarbon distillates were incorporated in the model. The model simulated the DBT diffusion in hydrocarbon droplets as obtained in a stirred tank reactor. Based on these calculations, we estimated that the mass transfer rate of DBT within the hydrocarbon droplet to the hydrocarbon/water interface is at least a factor 10 to 10 4higher than the specific DBT conversion rates. However, the presence of a high specific surface area is essential to enhance the surface contact between bacteria and the hydrocarbon phase.The availability of a suitable biomass is crucial to develop this new bioprocess. In Chapter 3 a screening method is described to enrich biomass from mixed bacterial populations obtained from oil-polluted environments. The enriched cultures were able to grow in the presence of thiophenes as the sole electron acceptor. A proof of principle was obtained; the formation of sulfide and biphenyl from dibenzothiophene was shown conclusively. Also thiophene and benzothiophene depletion with concomitant sulfide formation was observed. However, apart from sulfide no thiophene nor benzothiophene desulfurization products could be demonstrated. The main problem during consecutive enrichments was the loss of biological activity after transferring the desulfurizing biomass. A mixed population was present and the active desulfurizing biomass was easily overgrown by acetogenic bacteria. Therefore, it was attempted to isolate the desulfurizing bacteria. The isolation procedure resulted in the availability of highly enriched cultures able to desulfurize thiophenes when cultivated using a selective medium with H 2 as electron donor and limiting amounts of bicarbonate and acetate (1 mM each).Based on process considerations H 2 gas is the most suitable electron donor for the reductive desulfurization process. In Chapters 4 and 5 attention is paid to the mass transfer rate of H 2 in a gas/water/hydrocarbon three-phase system using n -dodecane as model solvent. Because vigorous foam formation occurs when H 2 gas is directly added to a n -dodecane in water dispersion, it was proposed to saturate the n -dodecane with H 2 gas prior to disperse it into the water phase. Experiments to determine the H 2 mass transfer coefficients involved using physical methods are described in Chapter 4. The H 2 mass transfer coefficients between the gas and the n -dodecane phase ( k d ) and between the gas and the water phase ( k w ) were determined using a dynamic method by following the pressure decline in time, whilst the overall H 2 mass transfer coefficient between n -dodecane and water ( k dw ) was determined using a steady state method. The value for k dw was assessed using tritium-hydride (T-H instead of H-H) as the tracer. The effects of the temperature (30, 40 and 50 oC) and salt concentrations (0-250 mM) were studied. The value for k w [(9.7 ± 0.2) x 10 -5ms -1at 30ºC] was found to be a factor 3.3 higher than for k d [(2.89 ± 0.12) x 10 -5ms -1at 30ºC] because of the lower viscosity of water. No effect was found for the presence of salts (up to 250 mM NaCl) on the k w -value. The k dw -value determined in the steady state experiments at 30ºC was (5 ± 0.6) x 10 -6ms -1which is 19.4 times smaller than the above-mentioned k w -value. The considerable smaller value for k dw must be attributed to the additional mass transfer resistance introduced by the second liquid phase. Calculations of the maximal attainable H 2 flux revealed values of 0.016 x 10 -3mol/m 2s and 3.9 x 10 -3mol/m 2s for a n -dodecane/water and gas/water system, respectively. Therefore, the specific surface area between n -dodecane and water is the determining parameter for sufficient H 2 mass transfer. In Chapter 5, the H 2 mass transfer is described further using a bioreactor equipped with a nozzle to create very fine n -dodecane droplets. The specific surface area is dependent on the maximum attainable hold-up of n -dodecane and the diameter of the droplets. These parameters were studied in a model system consisting of n -dodecane and water supplemented with NaCl. The use of the nozzle resulted in droplets with a Sauter mean diameter of only 10.3±0.9mm. The droplet size was found to be independent of the applied pressure drop over the nozzle. The hold-up of n -dodecane in the aqueous medium is clearly dependent on the sodium ion concentration. The hold-up decreases rapidly (from 0.14 to 0.04) with increasing sodium ion concentrations due to coagulation; from 94 mM onwards the hold-up becomes 0.04. The application of n -dodecane droplets as carrier phase for H 2 mass transfer was demonstrated in batch tests for biological sulfate reduction. During operation of the bioreactor, biomass attached to the rising n -dodecane droplets and eventually flotated from the system.In addition biological steady state experiments were performed with hydrogenotrophic sulfate reducing bacteria to determine the H 2 mass transfer coefficient for a n -dodecane/water system ( k dw ). A value of (4.0±0.24) x 10 -6ms -1was found, which is close to the values found in the experiments using tritium hydride. Final calculations showed that the volumetric H 2 mass transfer rate (mol/m 3s) from n -dodecane to water can be comparable to values found for gas lift reactors, thus the high specific surface area that can be created by applying a nozzle can overcome the lower value of the H 2 flux (mol/m 2s) to a large extent.Chapter 6 addresses the role of sulfide on anaerobic biodesulfurization. The presence of increased sulfide concentrations is undesirable because it is expected that sulfide will inhibit the DBT conversion. Therefore, insight in the partitioning of gaseous hydrogen sulfide (H 2 S) over a three-phase gas/water/hydrocarbon system is required. The partitioning of H 2 S over a gas/water/ n -dodecane system is described. Experimental results matched well with the model predictions. The effect of the presence of an extra hydrocarbon phase ( n -dodecane) notably decreased the total sulfide in the water phase and the H 2 S fraction in the gas phase. The hydrocarbon phase serves as a sink for H 2 S molecules and by scrubbing the H 2 S in a separate process step ( e.g. during H 2 saturation) the sulfide concentration can be lowered to favor the anaerobic biodesulfurization.