drug-induced-sleep-endoscopy-dise-with-target-controlled-infusion-tci

Drug-Induced Sleep Endoscopy (DISE) with Target Controlled Infusion (TCI) and Bispectral Analysis in Obstructive Sleep Apnea

The aim of this study was to establish a standardized protocol for drug-induced sleep endoscopy (DISE) to differentiate obstruction patterns in ...

Friedrich-Alexander University Erlangen-Nürnberg (FAU)

Francisella tularensis, the causative agent of tularemia, has been recognized as a human and zoonotic pathogen for almost 100 years. The increasing number of tularemia outbreaks in regions of Europe outside the classic endemic areas in recent years has prompted renewed interest in this rare infectious disease. We report on a case of oropharyngeal tularemia in an 18-year-old girl from Bavaria (Germany) who presented with tonsillopharyngitis and cervical lymphadenitis. Strongly positive serological tests and PCR detection of F. tularensis subsp. holarctica in lymph node tissue led to the diagnosis of tularemia. After long-term treatment with doxycycline, partly in combination with ciprofloxacin, the patient recovered completely. Clinical presentation, diagnostics, treatment and recent epidemiological aspects of tularemia in Europe are discussed in this case report and review of the literature.

Oropharyngeal tularemia--a differential diagnosis of tonsillopharyngitis and cervical lymphadenitis.

Expression levels of membrane transporters may affect the disposition, and thereby treatment efficacy, of anticancer drugs in human head and neck squamous cell carcinoma (HNSCC). Herein, we analyzed the gene expression profile of membrane transporters in HNSCC. In addition, we evaluated the mechanisms of transporter regulation in HNSCC and focused on the role of the nuclear pregnane X receptor (or NR1I2) and epigenetic mechanisms. Real-time RT-PCR revealed a significantly increased mRNA expression of membrane transporters SLCO1A2 and SLCO1B3 and a significantly decreased expression of transporters SLCO2B1, SLCO2A1, and ABCC3 in human HNSCC tumors compared with adjacent normal mucosa. An association between SLCO2B1 mRNA levels in tumors and 5-year survival of patients with HNSCC was observed (χ2 = 6.59, P = 0.010). Bisulfite sequencing revealed that promoter CpG islands of ABCC3 and SLCO2A1 were not hypermethylated, indicating that these genes were not epigenetically silenced in HNSCC tumors. In HNSCC-derived cell lines, transcript expression of transporters (e.g., ABCC3 or SLCO2A1; P < 0.001 for both) and NR1I2 (P < 0.001) was markedly induced by the DNA methyltransferase inhibitor, decitabine. Cotreatment with the prototypical pregnane X receptor activator, rifampicin, significantly reversed decitabine-induced ABCC3 and SLCO2A1 expression. In summary, the expression of drug transporters (i) is markedly changed in HNSCC tumor tissues compared with normal mucosa, (ii) might be predictive of the outcome of patients with HNSCC, and (iii) is affected by novel epigenetic therapies and is further modulated by nuclear receptor-mediated mechanisms.

Transporter gene expression in human head and neck squamous cell carcinoma and associated epigenetic regulatory mechanisms.

The lung constantly interacts with numerous pathogens. Thus, complex local immune defence mechanisms are essential to recognise and dispose of these intruders. This work describes the detection, characterisation and three-dimensional structure of a novel protein of the lung (surfactant-associated protein 3 (SFTA3/SP-H)) with putative immunological features. Bioinformatics, biochemical and immunological methods were combined to elucidate the structure and function of SFTA3. The tissue-specific detection and characterisation was performed by using electron microscopy as well as fluorescence imaging. Three-dimensional structure generation and analysis led to the development of specific antibodies and, as a consequence, to the localisation of a novel protein in human lung under consideration of cystic fibrosis, asthma and sepsis. In vitro experiments revealed that lipopolysaccharide induces expression of SFTA3 in the human lung alveolar type II cell line A549. By contrast, the inflammatory cytokines interleukin (IL)-1β and IL-23 inhibit expression of SFTA3 in A549. Sequence- and structure-based prediction analysis indicated that the novel protein is likely to belong to the family of lung surfactant proteins. The results suggest that SFTA3 is an immunoregulatory protein of the lung with relevant protective functions during inflammation at the mucosal sites.

SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation.

[Not Available].

The objective of the study was to investigate the first-night treatment success of a nasopharyngeal stent compared to standard nCPAP-titration. This is a case series and a single-center study. Eight participants (n = 8) were selected with untreated obstructive sleep apnea with a prestudy AHI ≥ 10. A newly developed nasopharyngeal stent was tested individually versus standard nCPAP-titration. Cardiorespiratory polysomnography was performed on two consecutive nights (random order: stent, nCPAP). The AHI, the number of obstructive apneas and hypopneas, the mean oxygen saturation, and the minimum oxygen saturation were compared before and after using the nasopharyngeal stent or standard nCPAP. The AHI value before treatment (AHIpre) was 31.1 ± 12.0 (mean ± standard deviation). After inserting the AlaxoStent, the mean AHIstent was 19 ± 12.0 compared to mean AHInCPAP 8.2 ± 11.9 with standard nCPAP-titration. Both nasopharyngeal stenting and nCPAP-titration could reduce the mean number of obstructive apneas by >94 %. Compared to responder rates of classic surgical interventions like uvulopalatopharyngoplasty or multi-level surgery, the nasopharyngeal stent seems to give a comparable responder rate of 50 %. There were no complications associated with the use of the stent and it was well tolerated by all subjects. Nasopharyngeal stenting widens the range of non-invasive mechanical treatment and seems to be an effective mechanical therapeutic alternative to surgery in nCPAP non-compliant patients with OSA. Careful selection of the patient population is a prerequisite of treatment and therefore it should be reserved for individual cases only.

A novel nasopharyngeal stent for the treatment of obstructive sleep apnea: a case series of nasopharyngeal stenting versus continuous positive airway pressure.

The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (L-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag.

The sound spectra obtained in a synthetic larynx exhibited subharmonic tones that are characteristic for diplophonia. Although the generation of subharmonics is commonly associated with asymmetrically oscillating vocal folds, the synthetic elastic vocal folds showed symmetrical oscillations. The amplitudes of the subharmonics decreased with an increasing lateral diameter of the supraglottal channel, which indicates a strong dependence of the supraglottal boundary conditions. Investigations of the supraglottal flow field revealed small cycle-to-cycle variations of the static pressure in the region of the pulsatile glottal jet as the origin of the first subharmonic tone. It is located at half the fundamental frequency of the vocal fold oscillation. A principle component analysis of the supraglottal flow field with the fully developed glottal jet revealed a large recirculation area in the second spatial eigenvector which deflected the glottal jet slightly in a perpendicular direction of the jet axis. The rotation direction of the recirculation area changed with different oscillation cycles between clockwise and counterclockwise. As both directions were uniformly distributed across all acquired oscillation cycles, a cycle-wise change can be assumed. It is concluded that acoustic subharmonics are generated by small fluctuations of the glottal jet location favored by small lateral diameters of the supraglottal channel.

The mechanisms of subharmonic tone generation in a synthetic larynx model.

To compare efficacy, in terms of disease control/survival in advanced hypopharyngeal and laryngeal lesions, according to treatment strategy (primary surgery, PS or primary chemoradiotherapy, CRT) and invasion pattern (cartilage, CAI or soft tissue involvement, STI).

Article	Year
Oropharyngeal tularemia--a differential diagnosis of tonsillopharyngitis and cervical lymphadenitis. Wiener klinische Wochenschrift\| PubMed ID: 20213378	2010
Transporter gene expression in human head and neck squamous cell carcinoma and associated epigenetic regulatory mechanisms. The American journal of pathology\| PubMed ID: 23137910	2013
SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation. The European respiratory journal\| PubMed ID: 24743970	2014
[Not Available]. Laryngo- rhino- otologie\| PubMed ID: 26465022	2015
A novel nasopharyngeal stent for the treatment of obstructive sleep apnea: a case series of nasopharyngeal stenting versus continuous positive airway pressure. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery\| PubMed ID: 26525882	2016
Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag. Viruses\| PubMed ID: 27120610	2016
The mechanisms of subharmonic tone generation in a synthetic larynx model. The Journal of the Acoustical Society of America\| PubMed ID: 27369142	2016
Management of advanced hypopharyngeal and laryngeal cancer with and without cartilage invasion. Auris, nasus, larynx\| PubMed ID: 27569289	2016

Maximilian Traxdorf

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