Delayed Reconstruction after Major Head and Neck Cancer Resection: An Interdisciplinary Feasibility Study.

A single immediate reconstruction with free tissue transfer is the method of choice after major head and neck cancer (HNC) resection, but this is frequently associated with long operating hours. Considering regulatory working hour constraints, we investigated whether a two-staged reconstructive approach with temporary defect coverage by an artificial tissue substitute would be feasible. HNC patients underwent either immediate or delayed reconstruction after tumor resection. Patients with delayed reconstruction received preliminary reconstruction with an artificial tissue substitute followed by definitive microvascular reconstruction in a separate, second procedure. Of the 33 HNC patients, 13 received delayed reconstruction and 20 received immediate reconstruction. Total anesthesia time (714 vs. 1011 min; p < 0.002) and the total duration of hospital stay (34 ± 13 vs. 25 ± 6 days; p = 0.03) were longer in the delayed reconstruction group. Perioperative morbidity (p = 0.58), functional outcome (p > 0.1) and 5-year postoperative survival rank (p = 0.28) were comparable in both groups. Delayed reconstruction after HNC resection was feasible. Perioperative morbidity, functional outcome and overall survival were comparable to immediate reconstruction.

The Endo-Lysosomal System of Brain Endothelial Cells Is Influenced by Astrocytes In Vitro.

Receptor- and adsorptive-mediated transport through brain endothelial cells (BEC) of the blood-brain barrier (BBB) involves a complex array of subcellular vesicular structures, the endo-lysosomal system. It consists of several types of vesicles, such as early, recycling, and late endosomes, retromer-positive structures, and lysosomes. Since this system is important for receptor-mediated transcytosis of drugs across brain capillaries, our aim was to characterise the endo-lysosomal system in BEC with emphasis on their interactions with astrocytes. We used primary porcine BEC in monoculture and in co-culture with primary rat astrocytes. The presence of astrocytes changed the intraendothelial vesicular network and significantly impacted vesicular number, morphology, and distribution. Additionally, gene set enrichment analysis revealed that 60 genes associated with vesicular trafficking showed altered expression in co-cultured BEC. Cytosolic proteins involved in subcellular trafficking were investigated to mark transport routes, such as RAB25 for transcytosis. Strikingly, the adaptor protein called AP1-µ1B, important for basolateral sorting in epithelial cells, was not expressed in BEC. Altogether, our data pin-point unique features of BEC trafficking network, essentially mapping the endo-lysosomal system of in vitro BBB models. Consequently, our findings constitute a valuable basis for planning the optimal route across the BBB when advancing drug delivery to the brain.

A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy.

Progressive retinal atrophy is a common cause of blindness in the dog and affects >100 breeds. It is characterized by gradual vision loss that occurs due to the degeneration of photoreceptor cells in the retina. Similar to the human counterpart retinitis pigmentosa, the canine disorder is clinically and genetically heterogeneous and the underlying cause remains unknown for many cases. We use a positional candidate gene approach to identify putative variants in the Hungarian Puli breed using genotyping data of 14 family-based samples (CanineHD BeadChip array, Illumina) and whole-genome sequencing data of two proband and two parental samples (Illumina HiSeq 2000). A single nonsense SNP in exon 2 of BBS4 (c.58A > T, p.Lys20*) was identified following filtering of high quality variants. This allele is highly associated (PCHISQ = 3.425e-14, n = 103) and segregates perfectly with progressive retinal atrophy in the Hungarian Puli. In humans, BBS4 is known to cause Bardet-Biedl syndrome which includes a retinitis pigmentosa phenotype. From the observed coding change we expect that no functional BBS4 can be produced in the affected dogs. We identified canine phenotypes comparable with Bbs4-null mice including obesity and spermatozoa flagella defects. Knockout mice fail to form spermatozoa flagella. In the affected Hungarian Puli spermatozoa flagella are present, however a large proportion of sperm are morphologically abnormal and <5% are motile. This suggests that BBS4 contributes to flagella motility but not formation in the dog. Our results suggest a promising opportunity for studying Bardet-Biedl syndrome in a large animal model.

Minimum Information about a Cardiac Electrophysiology Experiment (MICEE): standardised reporting for model reproducibility, interoperability, and data sharing.

Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information about a Cardiac Electrophysiology Experiment (MICEE). The ultimate goal is to develop a useful tool for cardiac electrophysiologists which facilitates and improves dissemination of the minimum information necessary for reproduction of cardiac electrophysiology research, allowing for easier comparison and utilisation of findings by others. It is hoped that this will enhance the integration of individual results into experimental, computational, and conceptual models. In its present form, this draft is intended for assessment and development by the research community. We invite the reader to join this effort, and, if deemed productive, implement the Minimum Information about a Cardiac Electrophysiology Experiment standard in their own work.

Transcatheter closure of symptomatic aortopulmonary window in an infant.

An aortopulmonary window is a rare congenital cardiac defect. In the majority of symptomatic neonates and infants, primary surgical repair is the treatment of choice. In selected infants, catheter closure of the defect with a device may be feasible. We report on the successful closure of an AP window in a 12 month old infant, using a 6mm Amplatzer septal occluder. The procedure and follow-up were uneventful.