160 kb deletion in ISPD unmasking a recessive mutation in a patient with Walker–Warburg syndrome

Walker–Warburg syndrome (WWS) is a severe muscular dystrophy with eye and brain malformations. On a molecular level, WWS is a disorder of the O-linked glycosylation of α-dystroglycan and therefore referred to as one of the dystroglycanopathies. The disease family of muscular dystrophy–dystroglycanopathy (MDDG) contains a spectrum of severe to mild disorders, designated as MDDG type A to C. WWS, as the most severe manifestation, corresponds to MDDG type A. Defects in the genes POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GTDC2, G3GALNT2, GMPPB, B3GNT1, TMEM5 and COL4A1 and ISPD have been described as causal for several types of MDDG including WWS, but can only be confirmed in about 60–70% of the clinically diagnosed individuals. The proteins encoded by these genes are involved in the posttranslational modification of α-dystroglycan. Mutations in POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, GMPPB, TMEM5 and COL4A1 and ISPD lead to a wide spectrum of phenotypes of congenital muscular dystrophies with or without eye and brain abnormalities. Patients with WWS frequently demonstrate a complete lack of psychomotor development, severe eye malformations, cobblestone lissencephaly and a hypoplastic cerebellum and brainstem, seizures, hydrocephalus and poor prognosis. Here, we present a boy with WWS who showed compound heterozygous changes in ISPD and discuss the clinical and radiological phenotype and the molecular genetic findings, including a novel pathogenic mutation in ISPD.     

Differences Between Autistic and Non-Autistic Adults in the Recognition of Anger from Facial Motion Remain after Controlling for Alexithymia

Journal of Autism and Developmental Disorders - To date, studies have not established whether autistic and non-autistic individuals differ in emotion recognition from facial motion cues when...     

Palliative Care bei über 80-jährigen Patienten mit COVID‑19-Pneumonie auf der Intensivstation – invasive Beatmung zielführend?

Wiener Medizinische Wochenschrift - Mit dem Auftreten des neuartigen SARS-CoV-2-Virus im Februar 2020 und der damit assoziierten COVID‑19-Viruspneumonie kam es zu einer Vielzahl schwer...     

25 Jahre Notfall+Rettungsmedizin – reine Männersache?

Notfall + Rettungsmedizin -     

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post‐transplant CDT monitoring for alcohol relapse assessment – a retrospective study

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post‐LT long‐term observation is challenging, and biomarkers as carbohydrate‐deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow‐up was 73 months (0–213). One‐ and five‐year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post‐transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single‐center analysis showed good post‐transplant long‐term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post‐LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.     

Microbial contamination of embryo cultures in an ART laboratory: sources and management

BACKGROUND: Although rare, microbial contamination of culture dishes occasionally occurs in our IVF/ICSI programme. Despite stringent culture conditions and the use of medium containing penicillin and streptomycin, an increasing number of infections was observed once they were routinely recorded. In this study, 95 cases of contaminated culture dishes were examined, in an attempt to identify possible causes. METHODS: Relevant data of the IVF/ICSI treatment cycles and the micro-organisms isolated from the infected culture dishes were evaluated retrospectively. RESULTS: Infections were observed only in IVF culture dishes and never after applying intra-cytoplasmic sperm injection. Identification of the contaminating micro-organisms showed that infections were mainly caused by Escherichia coli (n = 56; 58.9%) and Candida species (n = 24; 25.3%). Of the E. coli strains isolated, 41 (73.2%) appeared to be resistant to both antibiotics used in the culture medium and 13 (23.2%) appeared to resist either penicillin or streptomycin. Of all bacterial strains isolated, the resistances were 61.4% to both and 30% to one of the antibiotics used. CONCLUSIONS: Applying the ICSI procedure prevents colonization of the culture dishes by micro-organisms. Infections in IVF culture dishes are mainly caused by bacterial strains insensitive to the antibiotics used or due to yeast colonization by Candida species which frequently reside in the vagina.     

SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome

Background

Heterozygous gain‐of‐function mutations in various genes encoding proteins of the Ras‐MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio‐facio‐cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS.

Methods and results

We investigated SOS1 in a large cohort of patients with disorders of the NS–CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene.

Conclusion

We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gain‐of‐function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically.     

Implementing Intervention Research into Public Policy—the “I<Superscript>3</Superscript>-Approach”

Evidence-based intervention programs have become highly important in recent years, especially in educational contexts. However, transferring these programs into practice and into the wider field of public policy often fails. As a consequence, the field of implementation research has emerged, several implementation frameworks have been developed, and implementation studies conducted. However, intervention research and implementation research have not yet been connected systematically and different traditions and research groups are involved. Implementation researchers are mostly given mandates by politicians to take on the implementation of already existing interventions. This might be one of the key reasons why there are still many problems in translating programs into widespread community practice. In this paper, we argue for a systematic integration of intervention and implementation research (“I³-Approach”) and recommend a six-step procedure (PASCIT). This requires researchers to design and develop intervention programs using a field-oriented and participative approach. In particular, the perspective of policymakers has to be included as well as an analysis of which factors support or hinder evidence-based policy in contrast to opinion-based policy. How this systematic connection between intervention and implementation research can be realized, is illustrated by means of the development and implementation of the ViSC school program, which intends to reduce aggressive behavior and bullying and to foster social and intercultural competencies.