Congenital Diaphragmatic Hernia: A Case Report and Literature Review

Background: Congenital Diaphragmatic Hernia (CDH) is a rare developmental abnormality of the diaphragm with an incidence of approximately 2.5 cases per 10,000 births. Despite advances in treatment, mortality and long-term morbidity among survivors remain high. Case Presentation: A newborn was delivered by planned caesarean section due to prenatal diagnosis of CDH, diagnosed at 18 weeks and 5 days (Correction 3.1) during routine ultrasound. The Observed-to-Expected (O/E) Lung area-to-Head circumference Ratio (LHR) was 52%. After birth, the newborn was in respiratory distress and required mechanical invasive ventilation. Surgical repair was planned after stabilisation for the second day of life. A subcostal laparotomy was performed, and an anteromedial hernia with mostly small intestine, the left colon flexure and the spleen as content was found. The abdominal contents were reduced, and the hernia was repaired with a suture. Due to the development of a severe pulmonary hypertension, extubation was only possible on the fifth postoperative day, but reintubation was needed. The patient remained in the intensive care unit for a total of 25 days and could be discharged 46 days after birth in a good condition. Discussion: When treating patients with CDH, the most feared complication is pulmonary hypertension, which can be life-threatening and refractory to treatment. Surgical repair should be postponed until the newborn is medically stable. Conclusion: CDH presents a diagnostic and therapeutic challenge. When diagnosed prenatally, patients should be referred to a tertiary centre for a multidisciplinary approach

R91W mutation in Rpe65 leads to milder early-onset retinal dystrophy due to the generation of low levels of 11-cis-retinal

RPE65 is a retinal pigment epithelial protein essential for the regeneration of 11-cis-retinal, the chromophore of cone and rod visual pigments. Mutations in RPE65 lead to a spectrum of retinal dystrophies ranging from Leber's congenital amaurosis to autosomal recessive retinitis pigmentosa. One of the most frequent missense mutations is an amino acid substitution at position 91 (R91W). Affected patients have useful cone vision in the first decade of life, but progressively lose sight during adolescence. We generated R91W knock-in mice to understand the mechanism of retinal degeneration caused by this aberrant Rpe65 variant. We found that in contrast to Rpe65 null mice, low but substantial levels of both RPE65 and 11-cis-retinal were present. Whereas rod function was impaired already in young animals, cone function was less affected. Rhodopsin metabolism and photoreceptor morphology were disturbed, leading to a progressive loss of photoreceptor cells and retinal function. Thus, the consequences of the R91W mutation are clearly distinguishable from an Rpe65 null mutation as evidenced by the production of 11-cis-retinal and rhodopsin as well as by less severe morphological and functional disturbances at early age. Taken together, the pathology in R91W knock-in mice mimics many aspects of the corresponding human blinding disease. Therefore, this mouse mutant provides a valuable animal model to test therapeutic concepts for patients affected by RPE65 missense mutation

In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rod

Sachliche Erschliessung und die neue Suchmaschine des Österreichischen Bibliothekenverbundes

Recently, the Austrian Library Network implemented its new search engine, Primo. Hence, a reappraisal and realignment was needed for the display, indexing and – for the first time – faceted navigation of all data elements relevant for subject access. After a short overview of the software and the status of subject indexing and classification in the union catalogue of the consortium, the article deals in detail with the intended implementation in the new search engine. The main emphasis is on subject headings (according to the German subject cataloguing rules) as the most important means of intellectual indexing. In the second part, the actual implementation in Primo is outlined. Finally, future developments and improvements are discussed

Characterization of the intrinsic strength between epoxy and silica using a multiscale approach

Organic–inorganic interfaces exist in many natural or synthetic materials, such as mineral–protein interfaces found in bone and epoxy–silica interfaces found in concrete construction. Here, we report a model to predict the intrinsic strength between organic and inorganic materials, based on a molecular dynamics simulation approach combined with the metadynamics method, used to reconstruct the free energy surface between attached and detached states of the bonded system and scaled up to incorporate it into a continuum model. We apply this technique to model an epoxy–silica system that primarily features nonbonded and nondirectional van der Waals and Coulombic chemical interactions. The intrinsic strength between epoxy and silica derived from the molecular level is used to predict the structural behavior of epoxy–silica interface at the macroscopic length scale by invoking a finite element approach using a cohesive zone model which shows a good agreement with existing experimental results.National Science Foundation (U.S.). Division of Civil and Mechanical Systems (Grant 0856325

First microwave-assisted synthesis of an electron-rich phosphane and its coordination chemistry with platinum(II) and palladium(II)

The P–O ligand 3-(di(2-methoxyphenyl)phosphanyl)propionic acid (HL) was synthesized by a microwave-assisted reaction of a secondary phosphane. The coordination of HL to PtII yielded the neutral mononuclear complex trans-[PtCl(κ2-P,O-L)(κ-P-HL)] (1), while the reaction of PdClMe(η4-COD) (COD = 1,4-cyclooctadiene) with HL in the presence of NEt3 gave the anionic PdII compound of the formula (HNEt3)[PdClMe(κ2-P,O-L)] (2). Upon crystallization of the latter compound the neutral chloride-bridged dimetallic compound cis-[Pd(μ-Cl)Me(HL)]2 (3) was obtained. HL, 1 and 3·CH2Cl2 have been characterized by single crystal X-ray structure analyses

The lectin OS-9 delivers mutant neuroserpin to endoplasmic reticulum associated degradation in familial encephalopathy with neuroserpin inclusion bodies

A feature of neurodegenerative diseases is the intraneuronal accumulation of misfolded proteins. In familial encephalopathy with neuroserpin inclusion bodies (FENIB), mutations in neuroserpin lead to accumulation of neuroserpin polymers within the endoplasmic reticulum (ER) of neurons. Cell culture based studies have shown that ER-associated degradation (ERAD) is involved in clearance of mutant neuroserpin. Here, we investigate how mutant neuroserpin is delivered to ERAD using cell culture and a murine model of FENIB. We show that the ER-lectin OS-9 but not XTP3-B is involved in ERAD of mutant neuroserpin. OS-9 binds mutant neuroserpin and the removal of glycosylation sites leads to increased neuroserpin protein load whereas overexpression of OS-9 decreases mutant neuroserpin. In FENIB mice, OS-9 but not XTP3-B is differently expressed and impairment of ERAD by partial inhibition of the ubiquitin proteasome system leads to increased neuroserpin protein load. These findings show that OS-9 delivers mutant neuroserpin to ERAD by recognition of glycan side chains and provide the first in vivo proof of involvement of ERAD in degradation of mutant neuroserpin

Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls.

Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer's disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results. We included several quality controls that identified and reduced technical variation to increase the reliability of our data. We showed that the expression levels of circulating miRNAs measured in CSF did not correlate with levels in serum. Using cluster analysis we found expression pattern in serum that, in part, reflects the genomic organization and affiliation to a specific miRNA family and that were specifically altered in bvFTD, AD, and control groups. Applying factor analysis we identified a 3-factor model characterized by a miRNA signature that explained 80% of the variance classifying healthy controls with 97%, bvFTD with 77% and AD with 72% accuracy. MANOVA confirmed signals like miR-320a and miR-26b-5p at BH corrected significance that contributed most to discriminate bvFTD cases with 96% sensitivity and 90% specificity and AD cases with 89% sensitivity and specificity compared to healthy controls, respectively. Correlation analysis revealed that miRNAs from the 3-factor model also correlated with levels of protein biomarker amyloid-beta1-42 and phosphorylated neurofilament heavy chain, indicating their potential role in the monitoring of progressive neuronal degeneration. Our data show that miRNAs can be reproducibly measured in serum and CSF without pre-amplification and that serum includes higher expressed signals that demonstrate an overall better ability to classify bvFTD, AD and healthy controls compared to signals detected in CSF