Silastic sheeting in staged ear surgery: Is there still a role for this procedure?

Objective: To review long-term outcomes for chronic otitis media with and without cholesteatoma in staged canal-wall-up tympanoplasty with temporary silastic sheeting and to compare hearing and recurrence results with the literature.

Methods: Retrospective data analysis of all patients suffering from chronic otitis media with or without cholesteatoma (COMC/COM) and treated by staged canal-wall-up (CWU) technique with silastic insertion between 1992 and 2012. Literature analysis in PubMed 1990-2017.

Simultaneous analysis of large-scale RNAi screens for pathogen entry.

Background: Large-scale RNAi screening has become an important technology for identifying genes involved in biological processes of interest. However, the quality of large-scale RNAi screening is often deteriorated by off-targets effects. In order to find statistically significant effector genes for pathogen entry, we systematically analyzed entry pathways in human host cells for eight pathogens using image-based kinome-wide siRNA screens with siRNAs from three vendors.

Paediatric otogenic lateral sinus thrombosis: therapeutic management, outcome and thrombophilic evaluation.

Objective: Otogenic lateral sinus thrombosis (LST) in children represents a serious condition with potential long-lasting morbidity. The role of adjunct anticoagulation therapy and the benefit of an analysis of prothrombotic factors are unclear. The aim of the study was to report therapeutic management and outcome, analyze prothrombotic factors in children with otogenic LST treated with mastoidectomy/antibiotics/anticoagulation and to evaluate the results with a review of the literature.

iBRAIN2: automated analysis and data handling for RNAi screens.

We report on the implementation of a software suite dedicated to the management and analysis of large scale RNAi High Content Screening (HCS). We describe the requirements identified amongst our different users, the supported data flow, and the implemented software. Our system is already supporting productively three different laboratories operating in distinct IT infrastructures.

Novel inhibitors of dengue virus methyltransferase: discovery by in vitro-driven virtual screening on a desktop computer grid.

Dengue fever is a viral disease that affects 50-100 million people annually and is one of the most important emerging infectious diseases in many areas of the world. Currently, neither specific drugs nor vaccines are available. Here, we report on the discovery of new inhibitors of the viral NS5 RNA methyltransferase, a promising flavivirus drug target.

The Protein Model Portal.

Structural Genomics has been successful in determining the structures of many unique proteins in a high throughput manner. Still, the number of known protein sequences is much larger than the number of experimentally solved protein structures. Homology (or comparative) modeling methods make use of experimental protein structures to build models for evolutionary related proteins.

The protein structure initiative structural genomics knowledgebase.

The Protein Structure Initiative Structural Genomics Knowledgebase (PSI SGKB, http://kb.psi-structuralgenomics.org) has been created to turn the products of the PSI structural genomics effort into knowledge that can be used by the biological research community to understand living systems and disease.

[Rare complication after Le Fort I osteotomy].

Malfunctions of the eustachian tube after Le Fort I osteotomies are rare. A 22-year-old woman was treated by Le Fort I osteotomy for maxillary retrognathism. Postoperatively she developed recurrent tubal malfunction and middle ear effusions on the left side, with no improvement after adenotomy, tonsillectomy, and grommet insertion.

Hearing loss and fluctuating hearing levels in X-linked hypophosphataemic osteomalacia.

Background And Objective: X-linked hypophosphataemic osteomalacia is the most common of the genetically determined forms of osteomalacia. The occurrence of hearing loss in X-linked hypophosphataemic osteomalacia has been known since 1984. However, observations on the progression of such hearing loss, and suggestions regarding possible therapy, have not previously been published.

Identification of androgen-selective androgen-response elements in the human aquaporin-5 and Rad9 genes.

The AR (androgen receptor) is known to influence the expression of its target genes by binding to different sets of AREs (androgen-response elements) in the DNA. One set consists of the classical steroid-response elements which are partial palindromic repeats of the 5'-TGTTCT-3' steroid-receptor monomer-binding element. The second set contains motifs that are AR-specific and that are proposed to be partial direct repeats of the same motif.

Mastoiditis in children: a prospective, observational study comparing clinical presentation, microbiology, computed tomography, surgical findings and histology.

Unlabelled: The aim of this study was to obtain comprehensive data on clinical presentation, microbiology, computed tomography, surgical findings and histology in acute, sub-acute and chronic mastoiditis. We performed a prospective, observational study in children under 16 years of age presenting to our institution during the 2-year period beginning in April 2000. The children were examined and their condition treated in accordance with a standardized protocol elaborated by the paediatric, otolaryngology (ORL) and radiology departments.

Tandem mass spectrometry protein identification on a PC grid.

We present a method to grid-enable tandem mass spectrometry protein identification. The implemented parallelization strategy embeds the open-source x!tandem tool in a grid-enabled workflow. This allows rapid analysis of large-scale mass spectrometry experiments on existing heterogeneous hardware.

Sulfonylureas and glinides exhibit peroxisome proliferator-activated receptor gamma activity: a combined virtual screening and biological assay approach.

Most drugs currently employed in the treatment of type 2 diabetes either target the sulfonylurea receptor stimulating insulin release (sulfonylureas, glinides), or target the peroxisome proliferator-activated receptor (PPARgamma) improving insulin resistance (thiazolidinediones). Our work shows that sulfonylureas and glinides additionally bind to PPARgamma and exhibit PPARgamma agonistic activity. This activity was predicted in silico by virtual screening and confirmed in vitro in a binding assay, a transactivation assay, and by measuring the expression of PPARgamma target genes.

Prediction of cis-regulatory elements for drug-activated transcription factors in the regulation of drug-metabolising enzymes and drug transporters.

The expression of drug-metabolising enzymes is affected by many endogenous and exogenous factors, including sex, age, diet and exposure to xenobiotics and drugs. To understand fully how the organism metabolises a drug, these alterations in gene expression must be taken into account. The central process, the definition of likely regulatory elements in the genes coding for enzymes and transporters involved in drug disposition, can be vastly accelerated using existing and emerging bioinformatics methods to unravel the regulatory networks causing drug-mediated induction of genes.

[Hearing loss after lumbar myelography].

Hearing loss is a possible sequel of myelography. We describe a case of bilateral hearing loss of -60 dB, which recovered completely after an epidural blood patch. In hearing loss or tinnitus in association with a possible cerebrospinal fluid loss after a diagnostic or therapeutic puncture of the lumbar dural sack, an epidural blood patch is a viable and recommended therapeutic option.

A de novo PABPN1 germline mutation in a patient with oculopharyngeal muscular dystrophy.

Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominantly inherited disorder characterized by dysphagia, ptosis, and proximal limb weakness and is caused by germline mutations (triplet repeat expansions) in the polyadenylate binding protein nuclear 1 (PABPN1) gene.

Objective: To describe a 70-year-old female patient with OPMD on the clinical and molecular genetic level and to develop a rapid and efficient molecular genetic screening method to study large patient groups.

Methods: Detailed family history and clinical assessment of the OPMD patient were followed by mutation analysis of the PABPN1 gene by direct DNA sequencing and by our newly developed method, fluorescent PABPN1 polymerase chain reaction (PCR) product (flPPP) method.

LXR deficiency and cholesterol feeding affect the expression and phenobarbital-mediated induction of cytochromes P450 in mouse liver.

Metabolic transformation by the superfamily of cytochromes P450 (CYPs) plays an important role in the detoxification of xenobiotics such as drugs, environmental pollutants, and food additives. Endogenous substrates of CYPs include fatty acids, sterols, steroids, and bile acids. Induction of CYPs via transcriptional activation by substrates and other xenobiotics is an important adaptive mechanism that increases the organism's defense capability against toxicity.

Rapid, accurate and non-invasive detection of cerebrospinal fluid leakage using combined determination of beta-trace protein in secretion and serum.

Background: beta-Trace protein (Btp) has been proposed as a valuable marker of cerebrospinal fluid (CSF) leakage overcoming the drawbacks of beta-2-transferrin (B-2Tr) determination. However, there is still controversy about the appropriate cut-offs to be used (range 0.35-6 mg/L).

The evolution of drug-activated nuclear receptors: one ancestral gene diverged into two xenosensor genes in mammals.

BACKGROUND: Drugs and other xenobiotics alter gene expression of cytochromes P450 (CYP) by activating the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in mammals. In non-mammalian species, only one xenosensor gene has been found. Using chicken as a model organism, the aim of our study was to elucidate whether non-mammalian species only have one or two xenosensors like mammals.

[Highligts from the interdisciplinary consultation for diseases of the mouth in Basel].

A number of medical specialties traditionally face changes and lesions in the mouth, specific for diseases seen routinely in their everyday practice: gastroenterologists, paediatricians, orthodontists, to name just a few, will easily identify the typical aspect of the tongue, the Koplik spots or a dysgnathia respectively, and the treatment of the underlying diseases in question will resolve the local problem. However, more unusual lesions with chronic or recurrent course may cause a much longer patient career, which may last for months or even years and is interspersed with more or less ineffective local antiseptic or steroid treatment regimens before underlying diseases like pemphigus, lichen, diseases of haematopoetic organs, paraneoplastic lesions or even simple mechanical consequences of parafunctions like bruxismus, are identified as the underlying cause. The otorhinolaryngologist, the dermatologist and the dentist-oral-maxillofacial surgeon offer an interdisciplinary consultation at the Center for Dental Medicine at the University of Basel, in which the advantages of an advanced diagnostic armamentarium and a combined pool of experience proves to be a gain for both the patients and involved medical persons.

Identification of the xenosensors regulating human 5-aminolevulinate synthase.

Heme is an essential component of numerous hemoproteins with functions including oxygen transport, energy metabolism, and drug biotransformation. In nonerythropoietic cells, 5-aminolevulinate synthase (ALAS1) is the rate-limiting enzyme in heme biosynthesis. Upon exposure to drugs that induce cytochromes P450 and other drug-metabolizing enzymes, ALAS1 is transcriptionally up-regulated, increasing the rate of heme biosynthesis to provide heme for cytochrome P450 hemoproteins.

The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis.

Estrogen-related receptor alpha (ERRalpha) is one of the first orphan nuclear receptors to be identified, yet its physiological functions are still unclear. We show here that ERRalpha is an effector of the transcriptional coactivator PGC-1alpha [peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha], and that it regulates the expression of genes involved in oxidative phosphorylation and mitochondrial biogenesis. Inhibition of ERRalpha compromises the ability of PGC-1alpha to induce the expression of genes encoding mitochondrial proteins and to increase mitochondrial DNA content.

In silico approaches, and in vitro and in vivo experiments to predict induction of drug metabolism.

Despite being described more than 40 years ago, the molecular mechanism that regulates hepatic induction of cytochromes P450 and other drug-metabolizing enzymes and drug transporters by xenobiotics has remained enigmatic until recently. A major breakthrough was the discovery of the orphan nuclear receptors pregnane X receptor and constitutive androstane receptor playing key roles as species-specific xenosensors in this induction response. Using this newly acquired knowledge, the human induction response can now be more accurately predicted.

Human prion diseases: epidemiology and integrated risk assessment.

Human prion diseases are devastating and incurable, but are very rare. Fears that the bovine spongiform encephalopathy epizootic would lead to a large epidemic of its presumed human counterpart, variant Creutzfeldt-Jakob disease (vCJD), have not been realised. Yet a feeling of uncertainty prevails in the general public and in the biomedical world.