Αρχειοθήκη ιστολογίου

Δευτέρα 5 Δεκεμβρίου 2016

N-Acetyl-L-cysteine and Cysteamine: New Strategies Against Mixed Biofilms of Non-encapsulated Streptococcus pneumoniae and Non-typeable Haemophilus influenzae [PublishAheadOfPrint]

Acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. It is most frequently caused by encapsulated Streptococcus pneumoniae and non-typeable Haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently producing an increase in carriage of non-encapsulated S. pneumoniae. Frequently, pneumococci and H. influenzae live together in the human nasopharynx forming a self-produced biofilm. Biofilms represent a global medical challenge since the inherent antibiotic resistance of their producers demands the use of high doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence. Here, we describe the development of an in vitro, non-encapsulated S. pneumoniae–non-typeable H. influenzae biofilm system using polystyrene or glass-bottom plates. Using confocal laser scanning microscopy and specific fluorescent labeling of pneumococcal cells with Helix pomatia agglutinin revealed an even distribution of both species within the biofilm. This simple and robust protocol of mixed biofilms has been used for testing the antimicrobial properties of two well known antioxidants that are widely used in the clinical setting, i.e., N-acetylcysteine and cysteamine. This repurposing approach showed the high potency of N-acetylcysteine and cysteamine against mixed biofilms of non-encapsulated S. pneumoniae and non-typeable H. influenzae. Decades of clinical use mean that these compounds are safe to use, which may accelerate their evaluation in humans.



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Genetic environment of the blaKPC-2 gene in Klebsiella pneumoniae isolate which may have been imported to Russia from Southeast Asia [PublishAheadOfPrint]

The nucleotide sequence of a blaKPC-2-harboring plasmid (pKPCAPSS) from Klebsiella pneumoniae ST273 isolated in Saint Petersburg, Russia from a patient with history of recent travel to Vietnam is presented. This 127,970-bp plasmid possessed both IncFII and IncR replicons. blaKPC-2 was localized on a hypothetical mobile element. This element was flanked by 38bp inverted Tn3 repeats and included a Tn3-specific transposase gene, macrolide resistance operon (mphA, mrx, mphR), and a fragment of blaTEM with unique polymorphisms.



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Pharmacokinetic Evaluation of Darunavir Administered Once or Twice daily in Combination with Ritonavir or the Three Direct Acting Antiviral Regimen of Ombitasvir, Paritaprevir, Ritonavir and Dasabuvir in Adults Co-infected with Hepatitis C and Human Immunodeficiency Virus [PublishAheadOfPrint]

Background: The three-direct acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir and dasabuvir ± ribavirin (RBV) is approved for treatment of HCV GT1/HIV-1 co-infection. Results of a pharmacokinetic substudy of 3D and darunavir are presented.

Methods: HCV/HIV-1 infected subjects were randomized to maintain a darunavir 800 mg once daily (QD) or switch to a darunavir 600 mg twice daily (BID) based antiretroviral regimen. On Study Day 1, subjects received 3D and RBV plus darunavir for 12 weeks. Pharmacokinetic parameters were compared for darunavir with and without 3D. Pharmacokinetic parameters of 3D were compared to historical data.

Results: Ten subjects received darunavir QD and 12 subjects received darunavir BID. The central value ratios (90% confidence interval [CI]) for darunavir Cmax, AUC24 and C24 administered QD with 3D vs. alone were 0.92 (0.72, 1.18), 0.83 (0.71, 0.98) and 0.64 (0.44, 0.93), respectively. The ratios (90% CI) for darunavir Cmax, AUC12 and C12 administered BID with 3D were 0.92 (0.76, 1.12), 0.88 (0.73, 1.05) and 0.73 (0.58, 0.92), respectively. Exposures of 3D were similar or slightly lower compared with historical data. All darunavir trough concentrations (Ctrough) associated with an HIV-1 RNA >40 copies/mL were above the darunavir EC50 of 550 ng/mL for resistant virus.

Conclusions: The 3D regimen with darunavir QD or BID did not affect darunavir Cmax and AUC, whereas darunavir Ctrough decreased. Changes in pharmacokinetic parameters of 3D were not considered clinically significant. Episodes of intermittent HIV-1 viremia were infrequent and not associated with darunavir Ctrough values below 550 ng/mL. (This study has been registered at ClinicalTrials.gov under identifier NCT01939197.)



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Genetic Evidence for Cytochrome b Qi Site Inhibition by 4(1H)-quinolone-3-diarylethers and Antimycin in Toxoplasma gondii [PublishAheadOfPrint]

Toxoplasma gondii is an apicomplexan parasite that causes fatal and debilitating brain and eye disease. Endochin-like-quinolones (ELQs) are preclinical compounds that are efficacious against apicomplexan-caused diseases including toxoplasmosis, malaria and babesiosis. Of the ELQs, ELQ-316 has demonstrated the greatest efficacy against acute and chronic experimental toxoplasmosis. Although genetic analyses in other organisms have highlighted the importance of the cytochrome bc1 complex Qi site for ELQ sensitivity, the mechanism of action of ELQs against T. gondii and the mechanism of ELQ-316 remains unknown. Here we describe the selection and genetic characterization of T. gondii clones resistant to ELQ-316. A T. gondii strain selected under ELQ-316 drug pressure was found to possess a Thr222-Pro amino acid substitution that confers 49-fold resistance to ELQ-316 and 19-fold resistance to antimycin, a well-characterized Qi site inhibitor. These findings provide further evidence for ELQ Qi site inhibition in T. gondii and greater insight into the interaction of Qi site inhibitors with the apicomplexan cytochrome bc1 complex.



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Safety and Pharmacokinetics of CD101 IV, a Novel Echinocandin, in Healthy Adults [PublishAheadOfPrint]

CD101 IV is a novel echinocandin with distinctive pharmacokinetic properties that is being developed as a once-weekly treatment for candidemia and invasive candidiasis. CD101 has potent in vitro activity and in vivo efficacy against a broad range of Candida and Aspergillus species. The primary objective of two randomized, double-blind, placebo-controlled, dose-escalation studies in healthy adults was to determine the safety and tolerability of CD101 IV. Sequential cohorts of 8 subjects (n=6, active; n=2, placebo) were administered single (50, 100, 200, 400 mg) or multiple once-weekly (100 mg x2, 200 mg x2, 400 mg x3) doses of CD101 IV infused over 1 hour. There were no deaths, serious adverse events (SAEs), severe adverse events (AEs), or withdrawals from the study due to an AE. The majority of AEs were mild and all completely resolved. There was a higher incidence of total AEs and mild transient infusion reactions in the 400 mg x3 dose group. There were no clinically meaningful trends in postbaseline laboratory abnormalities and no safety issues related to electrocardiograms, vital signs, or physical exams. CD101 showed dose-proportional plasma exposures, minor accumulation (30%-55%), low apparent clearance (<0.28 L/hour), long half-life (t1/2 >80 h), and minimal urine excretion. CD101 IV was safe and well tolerated at single and multiple doses up to 400 mg once weekly for 3 weeks, exhibited a long t1/2, minimal accumulation over several weeks, negligible renal excretion, and high plasma exposures enabling once-weekly dosing.



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High-throughput screening and prediction models building for novel hemozoin inhibitors using physicochemical properties [PublishAheadOfPrint]

It is essential to continue the search for novel antimalarial drugs due to current spread of resistance against artemisinin by Plasmodium falciparum parasites. In this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. The in vitro colorimetric high throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9600 structurally diverse compounds. Physicochemical properties of positive hits and randomly selected compounds were extracted from ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i.e. traditional multivariate logistic regression, and Bayesian Modeling Average. Our results showed that a total of 224 positive hits exhibited the ability to inhibit the hemozoin formation with IC50 ranging from 3.1 μM to 199.5 μM. The "best" model according to traditional multivariate logistic regression included three variables: octanol-water partition coefficient, number of hydrogen bond donors, and number of atoms of hydrogen. Whereas, the "best" model according to Bayesian Modeling Average was octanol-water partition coefficient, number of hydrogen bond donors, and index of refraction. Both models had a good discriminatory power with the area under curve values were 0.736, and 0.781 for the traditional multivariate model, and the Bayesian Modeling Average model respectively. In conclusion, the prediction models can be a new, useful and cost-effective approach for the first screen of hemozoin inhibition based antimalarial drug discovery.



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Genotyping and prevalence of pyrazinamide- and moxifloxacin-resistant tuberculosis in China, 2000-2010: findings from the national survey data [PublishAheadOfPrint]

We investigated the prevalence, trends and risk factors for pyrazinamide (PZA) and moxifloxacin (MOX) resistance among TB cases in China, and also analyzed the population structure of Mycobacterium tuberculosis strains.All the M. tuberculosis strains enrolled in this study were collected from the national TB prevalence surveys. Each strain was genotyped by analyzing the regions of RD105 and the IS6110 in the NTF region. The BACTEC MGIT 960 system was used to detect the drug susceptibility of M. tuberculosis isolates against PZA and MOX. Based on the genotyping results, 241 (66.4%) strains were classified as Beijing genotype in 2000, which was significantly lower than in 2010 (76.2%, P<0.01). The proportion of the modern Beijing genotype increased significantly from 49.6% in 2000 to 68.1% in 2010 (P<0.01), while no significant difference was observed in the rate of ancient Beijing genotype between 2000 and 2010 (P=0.676). In addition, we found that the proportion of PZA-resistance in 2010 (15.0%) was significantly higher than that in 2000 (9.6%, P=0.04). For MOX, there were more MOX-resistant isolates detected in 2010 (7.7%) than in 2000 (3.0%). In conclusion, our data demonstrate that the Beijing genotype was the predominant M. tuberculosis lineage during the past decade. The proportion of Beijing genotype significantly increased from 2000 to 2010, largely due to an increase in the modern Beijing sublineage. In addition, resistance to PZA and MOX increased significantly in China between 2000 and 2010.



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Study of intracellular Staphylococcus aureus control by virulent bacteriophage within MAC-T bovine mammary epithelial cells [PublishAheadOfPrint]

Bacteriophages (phages) are known to effectively kill extracellular multiplying bacteria. The present study demonstrated that phages penetrated bovine mammary epithelial cells and cleared intracellular Staphylococcus aureus, in a time-dependent manner. In particular, phage vB_SauM_JS25 reached the nucleus within the 3 h post-incubation. The phages had an endocytotic efficiency of 12%. This ability to kill intracellular host bacteria suggests the utility of phage-based therapies, and may protect from recurrent infection and treatment failure.



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Cephalosporin-3 -diazeniumdiolate NO-donor prodrug PYRRO-C3D enhances azithromycin susceptibility of Non-typeable Haemophilus influenzae biofilms [PublishAheadOfPrint]

Objectives: PYRRO-C3D is a cephalosporin-3-diazeniumdiolate nitric oxide (NO)-donor prodrug designed to selectively deliver NO to bacterial infection sites. The objective of this study was to assess the activity of PYRRO-C3D against non-typeable Haemophilus influenzae (NTHi) biofilms and examine the role of NO in reducing biofilm-associated antibiotic tolerance.

Methods: The activity of PYRRO-C3D on in vitro NTHi biofilms was assessed through CFU enumeration and confocal microscopy. NO release measurements were performed using an ISO-NO probe. NTHi biofilms grown on primary ciliated respiratory epithelia at an air-liquid interface were used to investigate the effects of PYRRO-C3D in the presence of host tissue. Label-free LC/MS proteomic analyses were performed to identify differentially expressed proteins following NO treatment.

Results: PYRRO-C3D specifically released NO in the presence of NTHi, while no evidence of spontaneous NO release was observed when the compound was exposed to primary epithelial cells. NTHi lacking β-lactamase activity failed to trigger NO release. Treatment significantly increased the susceptibility of in vitro NTHi biofilms to azithromycin, causing a log-fold reduction in viability (p<0.05) relative to azithromycin alone. The response was more pronounced for biofilms grown on primary respiratory epithelia, where a 2-log reduction was observed (p<0.01). Label-free proteomics showed that NO increased expression of sixteen proteins involved in metabolic and transcriptional/translational functions.

Conclusions: NO release from PYRRO-C3D enhances the efficacy of azithromycin against NTHi biofilms, putatively via modulation of NTHi metabolic activity. Adjunctive therapy with NO mediated through PYRRO-C3D represents a promising approach for reducing biofilm-associated antibiotic tolerance.



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Prevalence of ESBL and/or carbapenemase-producing Escherichia coli isolated from yellow-legged gulls from Barcelona, Spain [PublishAheadOfPrint]

Seventy two (54.5%) out of 132 fecal samples were positive for either extended spectrum beta-lactamases (ESBL) (51.5%), carbapenemase (1.5%) or cephamycinase (1.5%) producing Escherichia coli from a group of yellow–legged gulls in Barcelona, Spain. The isolation of two carbapenemase-producing E. coli strains is a matter of concern.



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Significant Divergence in Sensitivity to Antimalarial Drugs between Neighboring Plasmodium falciparum Populations along the Eastern Border of Myanmar [PublishAheadOfPrint]

Malaria parasites in different endemic areas display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to ten drugs. Despite their close proximity, the Kachin parasites displayed higher IC50 values than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine and dihydroartemisinin. Genotyping of genes associated with drug resistance also showed significant differences in the prevalence of mutant alleles between the two regions. Particularly, major pfdhfr mutations mediating pyrimethamine resistance and the pfdhps A437G mutation had significantly higher frequencies in the Kachin parasites (P<0.005). Moreover, when pfdhfr and pfdhps were considered together, the wild-type allele was found only in the Wa samples (22.6%). In addition, the pfmdr1 Y184F mutation reached 38.7% in the Kachin parasites as compared to 9.7% in the Wa parasites, whereas N86Y was only detected in the Wa parasites at 22.6%. Furthermore, the F446I mutation and all mutations in the propeller domain of PfK13 gene were significantly more frequent in the Kachin parasites. Collectively, this work demonstrated that even in spatially closely separated regions, parasites could exhibit drastic differences in drug sensitivities and genetic make-ups underlying drug resistance, which may reflect regionally different drug histories and genetic drift of these isolated parasite populations.



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Identification of a Novel Lincomycin Resistance Mutation Associated with Activation of Antibiotic Production in Streptomyces coelicolor A3(2) [PublishAheadOfPrint]

Comparative genome sequencing analysis of a lincomycin-resistant strain of Streptomyces coelicolor A3 (2) and the wild type strain identified a novel mutation conferring a high level of lincomycin resistance. Surprisingly, the new mutation was an in-frame DNA deletion in the genes SCO4597-SCO4598, resulting in formation of the hybrid gene linR. SCO4597 and SCO4598 encode two histidine kinases, which, together with SCO4596, encoding a response regulator, constitute a unique two-component system. Sequence analysis indicated that these three genes and their arrangement patterns are ubiquitous among all Streptomyces genomes sequenced to date, suggesting these genes play important regulatory roles. Gene replacement showed that this mutation was responsible for the high level of lincomycin resistance, the overproduction of the antibiotic actinorhodin, and the enhanced morphological differentiation of this strain. Moreover, heterologous expression of the hybrid gene linR in Escherichia coli conferred resistance to lincomycin in this organism. Introduction of the hybrid gene linR in various Streptomyces strains by gene engineering technology may widely activate and/or enhance antibiotic production.



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Structure-Activity Relationships of a Series of Echinocandins and the Discovery of CD101, a Highly Stable and Soluble Echinocandin with Distinctive Pharmacokinetic Properties [PublishAheadOfPrint]

Echinocandins are first-line therapy for candidemia and invasive candidiasis. They are generally safe with few drug interactions, but the stability and pharmacokinetic properties of currently approved echinocandins are such that each was developed for daily intravenous infusion. We sought to discover a novel echinocandin with properties that would enable more flexible dosing regimens, alternate routes of delivery, and expanded utility. Derivatives of known echinocandin scaffolds were generated, and an iterative process of design and screening led to the discovery of CD101, a novel echinocandin that has since demonstrated improved chemical stability and pharmacokinetics. Here, we report the structure-activity relationships (including preclinical efficacy and pharmacokinetic data) for a series of echinocandin analogs from which CD101 was selected. In a mouse model of disseminated candidiasis, the test compounds displayed a clear dose response and were generally associated with lowered fungal burdens than that of anidulafungin. Single-dose pharmacokinetic studies in beagle dogs revealed a wide disparity in half-lives and volumes of distribution, with one compound (now known as CD101) displaying a half-life nearly 5-fold longer than that of anidulafungin itself (53.1 h vs 11.6 h, respectively). In vitro activity data against panels of Candida spp. and Aspergillus spp. demonstrated that CD101 behaved similarly to the approved echinocandins in terms of potency and spectrum of activity, suggesting that the improved efficacy observed in vivo for CD101 is a result of features beyond the antifungal potency inherent to the molecule. Factors potentially contributing to the improved in vivo efficacy of CD101 are discussed.



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Carbapenemase-producing Enterobacteriaceae recovered from the environment of a swine farrow-to-finish operation in the United States [PublishAheadOfPrint]

Carbapenem-resistant Enterobacteriaceae (CRE) present an urgent threat to public health. While carbapenem antimicrobials are restricted in food-producing animals, other β-lactams, such as ceftiofur, are used in livestock. This use may provide selection pressure favoring the amplification of carbapenem resistance but this relationship has not been established. Previously unreported from US livestock, plasmid-mediated CREs have been reported from livestock in Europe and Asia.

Environmental and fecal samples were collected from a 1,500 sow, US farrow-to-finish operation during 4 visits over a 5 month period, 2015. Samples were screened using selective media for the presence of CRE, with resulting carbapenemase-producing isolates further characterized.

Of 30 environmental samples collected from a nursery room on our initial visit, 2 (7%) samples yielded 3 isolates: 2 ST 218 Escherichia coli and 1 Proteus mirabilis, carrying the metallo-β-lactamase gene blaIMP-27 on IncQ1 plasmids. We recovered 15 IMP-27-bearing isolates of multiple Enterobacteriaceae species from 11 of 24 (46%) environmental samples from 2 farrowing rooms collected on our third visit. These isolates each also carried blaIMP-27 on IncQ1 plasmids. No CRE isolates were recovered from fecal swabs or samples in this study.

As is common in US swine production, piglets on this farm receive ceftiofur at birth, with males receiving a second dose at castration (day 6). This selection pressure may favor the dissemination of blaIMP-27-bearing Enterobacteriaceae in this farrowing barn. The absence of this selection pressure in the nursery and finisher barns likely resulted in the loss of the ecological niche needed for maintenance of this carbapenem resistance gene.



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Plazomicin activity against 346 Extended-Spectrum-{beta}-lactamase/AmpC-producing Escherichia coli urinary isolates, related to aminoglycoside-modifying enzymes characterized. [PublishAheadOfPrint]

The activity of plazomicin and clinically relevant aminoglycosides were tested against 346 ESBL/AmpC-producer Escherichia coli urinary isolates and the results were correlated with the presence of aminoglycoside-modifying enzymes (AMEs).

Data showed that plazomicin was very active against all ESBL/AmpC-producing E. coli urinary isolates. Its activity was not related to the AME genes studied.



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Carbapenemase-producing Enterobacteriaceae in swine production in the United States: impact and opportunities [PublishAheadOfPrint]

The discovery of carbapenemase-producing Enterobacteriaceae in U.S. swine production is troubling, and underscores a tumultuous period where the outlook on the battle against superbugs is bleak. However, all is not lost. This commentary highlights both the good and the bad that can come from such findings.



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Examining the Role of Preoperative Positron Emission Tomography/Computerized Tomography in Combination with Ultrasonography in Discriminating Benign from Malignant Cytologically Indeterminate Thyroid Nodules

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Thyroid , Vol. 0, No. 0.


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Effect of Marijuana Use on Thyroid Function and Autoimmunity

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Thyroid , Vol. 0, No. 0.


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Podoplanin Expression in Canine Melanoma

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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Sprachaudiometrie bei der Indikation von Hörhilfen und Hörimplantaten

Zusammenfassung

Die soziale Funktion des menschlichen Gehörs ist das Verstehen von Sprache. Durch die Etablierung der Sprachaudiometrie in der Diagnostik von Hörstörungen wurden Möglichkeiten geschaffen, diese Funktion zu quantifizieren. Hierzu wurden zahlreiche sprachaudiometrische Verfahren im deutschen Sprachraum entwickelt, die für spezifische Fragestellungen eingesetzt werden können. Im Rahmen der Indikationsstellung von apparativen Hörhilfen hat sich v. a. der Freiburger Einsilbertest über viele Jahre hinweg bewährt. Ergänzend dazu sind insbesondere Satztests für den Einsatz zur Hörgeräteindikation und -kontrolle vorgeschlagen worden. Der vorliegende Beitrag stellt die Eigenschaften und Einsatzgebiete unterschiedlicher sprachaudiometrischer Verfahren vor und zeigt die methodischen Limitationen der einzelnen Tests auf.



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Postoperative Bildgebung des inneren Gehörgangs

Zusammenfassung

Hintergrund

Die Beurteilungsfähigkeit des inneren Gehörgangs und der Cochlea ist von zentraler neurootologischer Bedeutung. Bei den verschiedenen Formen aktiver auditorischer Implantate ist aufgrund ihrer ferromagnetischer Komponenten eine auf der Magnetresonanztomographie (MRT) basierende Beurteilung dieser Strukturen typenspezifisch variabel. Die Kenntnis der Ausprägung der typenspezifischen Bildartefakte und die Möglichkeiten, auf diese Einfluss zu nehmen, ist für die auditorische Rehabilitation spezifischer Krankheitsbilder (z. B. Akustikusneurinom) von Bedeutung.

Methodik

Es handelt sich um eine Literaturübersicht.

Ergebnisse

Die postoperative Beurteilung des inneren Gehörgangs und der Cochlea mittels MRT ist nach Versorgung mittels eines aktiven auditorischen Implantats nur bei einer perkutanen Knochenleitungsversorgung („bone-anchored hearing aid", BAHA; Ponto) problemlos möglich. Unter Berücksichtigung spezifischer Maßnahmen (Implantatpositionierung und MRT-Sequenz) ist eine Beurteilung auch mit einem Cochlea Implantat möglich. Komplikationen wie Magnetdislokation und Schmerz sind zu berücksichtigen.

Schlussfolgerung

Die Beurteilbarkeit von innerem Gehörgang/Cochlea mittels MRT ist für die auditorische Rehabilitation von Patienten nach AKN-Extirpation von großer Bedeutung und sollte berücksichtigt werden.



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Druckausgleichende Funktion der Eustachischen Röhre

Zusammenfassung

Hintergrund

Die Eustachische Röhre bildet eine Verbindung zwischen der Paukenhöhle (Cavum tympani) und dem Nasenrachen (Nasopharynx), über die ein Druckausgleich zwischen Mittelohr und Umgebungsdruck möglich ist. Insbesondere beim Tauchen und Fliegen ist ein funktionierender Druckausgleich aufgrund von ungewohnt großen Druckdifferenzen nötig.

Fragestellung

Die Überprüfung der druckausgleichenden Tubenfunktion ist weiterhin eine klinisch-wissenschaftliche Herausforderung. Dieser Übersichtsartikel evaluiert die vorhandene Datenlage.

Methoden

Verschiedene Methoden zur Überprüfung der Tubenfunktion werden nach Literaturrecherche unter besonderer Berücksichtigung der Evaluation der druckausgleichenden Tubenfunktion in einer hypo-/hyperbaren Druckkammer vorgestellt und bewertet.

Ergebnisse

Mit der Druckkammer steht ein Diagnostikum zur Verfügung, das einerseits die Dynamik der Tubenfunktion im aktiven und passiven Druckausgleich provoziert und andererseits eine genaue Messung der Drücke im Millibarbereich ermöglicht.

Schlussfolgerung

Die Untersuchung der Funktion der Eustachischen Röhre in einer Druckkammer scheint aufgrund der vorliegenden Datenlage geeignet, um Therapien der Tubendysfunktion zu beurteilen. Weitere Studien sind notwendig, um den Stellenwert der Druckkammer in Zusammenschau mit anderen Funktionsprüfungen zu evaluieren.



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Guidelines for Contributing Authors



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Editorial Board



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Table of Contents



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Bei HNO-Beschwerden auch an Reflux denken



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Inhaltsverzeichnis



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Fundraising bringt Kliniken zusätzliche Mittel ein



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Kopf- und Halstumoren: Beobachten statt Neck-Dissection

Bei Patienten mit fortgeschrittenem Plattenepithelkarzinom im Kopf- und Halsbereich (SCCHN) sind oft auch die Lymphknoten befallen. Neueren Daten zufolge scheint ein vollständiges Ausräumen der Lymphknoten ohne konkreten Befund aber nicht sinnvoll.



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Ihr liebstes Titelbild 2016



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Glukokortikoidtherapie bei Hörsturz?



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Bereits 500 Gesundheits-App getestet



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Vertuschen, verschleiern, tricksen



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Berufshaftpflichtpolice: Angestellte Ärzte sind für Fiskus tabu



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Haben Sie auch eine fachliche Frage?



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Jede Antibiotikaeinnahme verdoppelt das CRS-Risiko

Bei Patienten mit chronischer Rhinosinusitis (CRS) ist die Diversität des sinunasalen Mikrobioms reduziert. Jede Antibiotikaeinnahme, egal aufgrund welcher Indikation, kann diese Biodiversität empfindlich stören und — so eine Hypothese — die Manifestation einer CRS begünstigen. Untermauern konnten diese Hypothese kürzlich US-amerikanische HNO-Ärzte.



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Wann ist eine Operation indiziert?



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Schwindeldiagnostik: Auch die Funktion der Kopfgelenke testen



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Sonografie ist zentraler Bestandteil der Schilddrüsendiagnostik



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The utility of vacuum-assisted closure therapy for skin necrosis secondary to cervical abscess in the elderly

Publication date: Available online 5 December 2016
Source:Auris Nasus Larynx
Author(s): Tadataka Tsuji, Koichi Satoh, Emi Okuno, Akiko Sobue, Yoshiya Nishide, Susumu Tanaka, Mikihiko Kogo
Vacuum-assisted closure (VAC) systems have been used as negative-pressure dressings in various fields, including decubitus ulcer, trauma, and wound dehiscence. To the best of our knowledge, few reports have examined the utility of VAC therapy for neck abscess in an oldest-old patient. We present here a rare case of neck abscess secondary to parotid abscess, resulting in extensive skin necrosis. Successful management included emergency drainage following epithelial induction through a VAC system without using skin grafting. Two months after surgical intervention, the cervical wound was completely healed without a solid scar. We consider the VAC therapy to be a key factor leading to the complete healing in the elderly under low serum albumin condition.



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Reality Training: Unresponsive teen after intentional asphyxiation

By Tim Nowak

You are dispatched to a residence for an unresponsive 14-year-old male patient after choking. You arrive to find frantic parents leading you to the basement, where the patient is unresponsive on the floor. He has a belt around his neck.

The other teens on scene tell you they were "playing a choking game," where they tried to asphyxiate themselves to the brink of unresponsiveness in an attempt to gain a "head rush" and achieve an euphoric state. The patient did this by wrapping a belt around his neck, securing it to the top of a door as it is closed in the frame to create a hanging-point.

This case presents a number of airway issues. First, the patient has had an hypoxic-asphyxiate event. He also has a strong potential for airway trauma due to the hanging mechanism.

Maintaining the ABCs are crucial for this patient. BVM management, supplemental oxygenation, basic airway adjunct insertion and proper airway positioning are all indicated. Taking into account the patient's potential airway trauma, cervical spine motion restriction is an additional consideration.

Clinical findings
The most immediate treatment is to remove the belt from the patient's neck to end the airway compromise. Next, your partner starts to provide ventilations to the patient while you gather some more information.

  • BP: 116/78
  • Pulse: 110
  • Respirations: 6
  • SpO2: 92 percent, room air
  • ETCO2: 54 mm Hg
  • GCS: 3

Looking at his initial vital signs, his respirations are low so you manage them by assisting ventilations. His ETCO2 is high because he is retaining CO2 due to low respirations.

A normally shaped capnography waveform with a higher amplitude is present and sinus tachycardia is noted on the monitor. You find no evidence of other trauma, his friends are insistent upon no alcohol or drug use and his parents verify that the patient has a clear medical history with no prescriptions.

Transport destination
While transporting him to an appropriate pediatric medical/trauma center is preferred, for the purpose of resuscitation, he is an adult. He has reached the age of puberty. This means he receives adult rescue breathing rates, medication dosing and resuscitation equipment.

Transport time should have some bearing on the upcoming decision to intubate; especially in a rapid sequence intubation (RSI) scenario. For this patient, BLS airway management is working, and physician-level assessment and care is urgently needed. Because of the mechanism of injury, however, the necessity to adequately secure the patient's airway is warranted. Though RSI can be a single-paramedic skill in some places, it's a complicated procedure that really requires extensive airway management and pharmacology experience, so it may not always be the best practice. Since you are a two-paramedic crew, you decide to add a short period of on-scene time to perform RSI.

Complication to care
This case is not just a cut-and-dry "ventilate, package and transport" kind of call. You really need to be concerned about this patient's airway. 

His mechanism is similar to a hanging. You need to consider c-spine injury, larynx and tracheal trauma and the potential for bleeding and swelling in the tissues around the airway structures and into the trachea as strong possibilities. There is also a potential for great vessel damage in his the neck. 

Because of these factors, this patient's airway needs stability and security. When you attempt to insert an oral airway, the patient has an intact gag response. Two nasal airways are inserted to start, but your gut tells you that this patient needs more airway management (and, by the way, your gut is right!).

Endotracheal intubation
Here's why this patient needs an endotracheal tube. Since you are worried about the potential for airway swelling, trauma and bleeding, this patient needs direct tracheal access; not just oropharynx access with a supraglottic device.

The patient has a need for visualized airway insertion and an intact gag reflex so rapid sequence intubation — chemical sedation and paralysis — is indicated for paramedics who are authorized to perform the procedure. 

Recognizing this need, you turn to your partner and you both get the same concerned look. Your  standing orders are for adult RSI, not pediatric RSI. Are you still sure this patient is an adult?

Not taking any chances or wasting any time, your partner starts to prep your airway equipment while you make a quick phone call to the emergency department. This is your report:

"Medic-1 to ED, I need a doc for orders. We're on scene with a 14-year-old male that is unresponsive with agonal respirations from a witnessed hanging event. The patient had a belt around his neck on arrival and was witnessed hanging from a doorway by his friends. This is not a suicide attempt. We removed the belt. He has an intact gag reflex, respirations at 6, we're ventilating at 10, pulse is 110 with sinus tach, SpO2 was initially 92 percent on room air and has increased with ventilations, ETCO2 was in the 50s and is now in the 30s with assisted ventilations. Swelling and redness are noted on his neck. Requesting orders for pediatric RSI."

The doctor gives permission for pediatric RSI.

Patient disposition
Critical thinking plays heavily into this call. Could you have maintained that patient's airway with ventilations after inserting NPAs and placing a cervical collar? Sure.

Could you have tried minimal sedation to help facilitate advanced airway placement? I guess.

Would a supraglottic airway have worked to provide ventilations? Yes, unless swelling displaced the airway.

Would all of these actions provided the best treatment path or at least limit the patient's risks of future immediate complications like airway closure from edema, aspiration, bleeding or allow for direct tracheal access? No.

There's a right time for supraglottic airways. There's a right time for basic airway management. And there's a right time for RSI. This patient fits the right time for RSI.

Share your thoughts about the management of this complex case in the comments and consider these additional questions:

As an EMT, what signs would you look for indicating that ventilations are becoming more difficult and less effective? As a paramedic, what medications can you administer to facilitate intubation, without having access to paralytics?

As a provider, how would you have managed this complicated case?



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Effects of green tea and bisphosphonate association on dental socket repair of rats

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Publication date: March 2017
Source:Archives of Oral Biology, Volume 75
Author(s): Edson Yoshihiro Mada, Alana Claro Cunha Santos, Angelica Cristina Fonseca, Claudia Cristina Biguetti, Fernando Tozze Alves Neves, Patrícia Pinto Saraiva, Mariza Akemi Matsumoto
ObjectivesTo evaluate the effects of green tea intake and zoledronic acid intravenous therapy on teeth socket repair.DesignSixty male albinus Wistar rats were divided into 4 groups: C—Control, intravenous (IV) 0.9% saline solution (SS), GT—1% green tea in drinking water and IV SS, BP—IV zoledronic acid (BP), and BP+GT—IV BP and 1% green tea. 0.035mg/kg of BP was administered every two weeks. After ten weeks, right upper molars were extracted and the green tea started to be offered for GT and BP+GT. After 7, 14, and 28days the animals were euthanized.ResultsHistopathology analysis revealed lack of socket repair in BP and BP+GT groups, which presented significant increased number of polimorphonuclear leukocytes at day 28, in comparison with C (p<0.05). No significant differences were detected between C and the experimental groups at the same period (p<0.05) when considering mononuclear leukocytes. Immunolabeling revealed that the association of BP and GT caused a slight disturbance in OPG/RANKL system and retarded Runx-2 labeling. Although strong TRAP labeling was observed, most of the positive cells in BP and BP+GT groups were not located on bone surface.ConclusionsSocket healing of rats treated with BP and regular drinking green tea presented no relevant differences in comparison to those treated with BP alone.



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Production of endogenous hydrogen sulfide in human gingival tissue

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Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): Jiang Chun-Mei, Chen Wu, Meng Guo-Liang, Gu Yue, Chen Ning, Yong Ji
ObjectiveEndogenous hydrogen sulfide (H2S) has recently been shown to play an important role in inflammation, but the role of endogenous H2S in the human gingival tissue is unknown. The aim of this study was to investigate whether gingiva had enzymes for H2S synthesis, and whether the effect of these enzymes for H2S production changed with periodontal inflammation.DesignGingival tissues were collected from patients undergoing periodontal operation including gingivitis, moderate chronic periodontitis, severe chronic periodontitis and normal controls. RT-PCR and western blotting were performed to measure mRNA and protein levels of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) for H2S production. Immunohistochemistry was carried out to detect the location of the enzymes. H2S levels and synthesis in gingival tissue were evaluated with modified methylene blue method.ResultsThe mRNA and protein of CBS and CSE were both expressed in human gingiva and raised significantly in moderate and severe periodontitis compared of that in healthy control. CBS, but not CSE, increased in gingivitis (p<0.05). However, there was no significant difference of H2S level and synthesis among these groups (p>0.05).ConclusionsBoth CBS and CSE were expressed in human gingival tissue. The mRNA and protein levels of CBS and CSE were up-regulated in periodontitis.



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Calcitonin induces collagen synthesis and osteoblastic differentiation in human periodontal ligament fibroblasts

Publication date: February 2017
Source:Archives of Oral Biology, Volume 74
Author(s): Yibo Wei, Qing Ye, Zhen Tang, Gang Tian, Qiang Zhu, Haocheng Gao, Dalin Wang, Zhizhong Cao
BackgroundExtracellular matrix (ECM) secretion and osteogenic differentiation in periodontal ligament fibroblasts (PDLF) facilitate the neogenesis of alveolar bone, which is the cellular basis for alveolar bone repair. Calcitonin (CT) has been reported to play an important role in promoting ECM expression and inducing osteogenic differentiation in osteoblast, but its effects on PDLFs remain obscure.MethodsThe expression of CT, transforming growth factor-beta 1(TGF-β1) and bone morphogenetic protein (BMP) in gingival crevicular fluid (GCF) was measured by ELISA. The effects of CT on collagen synthesis and osteogenic differentiation in hPDLFs were investigated by using the primarily cultured hPDLFs infected with adenovirus carrying the CT gene. Gene expression was measured by quantitative PCR and western blot.ResultsThe expression of CT in gingival crevicular fluid (GCF) of patients with periodontitis was significantly higher than that of healthy subjects. In addition, CT expression correlated with the clinical indexes including probing pocket depth (PPD), clinical attachment level (CAL), and gingival index (GI). The in vitro study demonstrated that overexpression of CT by adenovirus infection increased the expression of TGF-β1, collagen type I and III, and osteoblastic markers including BMP-2/-4, alkaline phosphatase and osteocalcin in human PDLFs. Moreover, CT-enhanced collagen synthesis was abrogated in hPDLFs transfected with TGF-β1 siRNA, and CT-induced osteoblastic differentiation was blocked in hPDLFs by BMPs inhibitor noggin.ConclusionsThese results suggest that CT promotes collagen synthesis and osteogenic differentiation in hPDLFs via the TGF-β1 and BMPs signaling pathways, respectively.



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Metabolites: deciphering the molecular language between DCs and their environment

Abstract

Dendritic cells (DCs) determine the outcome of the immune response based on signals they receive from the environment. Presentation of antigen under various contexts can lead to activation and differentiation of T cells for immunity or dampening of immune responses by establishing tolerance, primarily through the priming of regulatory T cells. Infections, inflammation and normal cellular interactions shape DC responses through direct contact or via cytokine signaling. Although it is widely accepted that DCs sense microbial components through pattern recognition receptors (PRRs), increasing evidence advocates for the existence of a set of signals that can profoundly shape DC function via PRR-independent pathways. This diverse group of host- or commensal-derived metabolites represents a newly appreciated code from which DCs can interpret environmental cues. In this review, we discuss the existing information on the effect of some of the most studied metabolites on DC function, together with the implications this may have in immune-mediated diseases.



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Computed tomography and magnetic resonance fusion imaging in cholesteatoma preoperative assessment

Abstract

The purpose of this study is to describe a method for developing fusion imaging for the preoperative evaluation of cholesteatoma. In 33 patients diagnosed with cholesteatoma, a high-resolution temporal bone computed tomography (CT) scan without intravenous contrast and propeller diffusion-weighted magnetic resonance imaging (MRI) were performed. Both studies were then sent to the BrainLAB work station, where the images were fused to obtain a morphological and color map. Intraoperative findings coincided with fusion CT–MRI imaging in all but two patients. In addition, one false positive and one false negative case were observed. CT and diffusion-weighted MRI are complementary techniques that should be employed to assess a cholesteatoma prior to surgery in many cases. Hence, to combine the advantages of each technique, we developed a fusion image technique similar to those that are routinely employed for radiotherapy planning and positron emission tomography–CT imaging. Fusion images can prove useful in selected cases.



http://ift.tt/2gJUTEb

The utility of vacuum-assisted closure therapy for skin necrosis secondary to cervical abscess in the elderly

Vacuum-assisted closure (VAC) systems have been used as negative-pressure dressings in various fields, including decubitus ulcer, trauma, and wound dehiscence. To the best of our knowledge, few reports have examined the utility of VAC therapy for neck abscess in an oldest-old patient. We present here a rare case of neck abscess secondary to parotid abscess, resulting in extensive skin necrosis. Successful management included emergency drainage following epithelial induction through a VAC system without using skin grafting.

http://ift.tt/2h0SEwU

Effect of basal insulin dosage on blood glucose concentration in ambulatory surgery patients with type 2 diabetes

Among patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery.

http://ift.tt/2gZUL1j

The effect of tramadol plus paracetamol on consumption of morphine after coronary artery bypass grafting

To compare the effects of oral tramadol+paracetamol combination on morphine consumption following coronary artery bypass grafting (CABG) in the patient-controlled analgesia (PCA) protocol.

http://ift.tt/2g2BhMB

Minimum effective fluid volume of colloid to prevent hypotension during caesarean section under spinal anesthesia using a prophylactic phenylephrine infusion: An up-down sequential allocation study

The aim of this study was to de termine the minimum effective fluid volume (MEFV) of hydroxyethyl starch 130/0.4 (HES) infused in a preload fashion which would prevent hypotension in 50% of parturients undergoing caesarean section. A secondary objective was to measure the hemodynamic effect of fluid loading on the subjects.

http://ift.tt/2gZWROQ

Regularization strategy for an inverse problem for a 1+1 dimensional wave equation

Korpela, J; Lassas, M; Oksanen, L; (2016) Regularization strategy for an inverse problem for a 1+1 dimensional wave equation. Inverse Problems , 32 (6) , Article 065001. 10.1088/0266-5611/32/6/065001 .

http://ift.tt/2ha2XPA

'Can you recommend any good STI apps?' A review of content, accuracy and comprehensiveness of current mobile medical applications for STIs and related genital infections

Gibbs, J; Gkatzidou, V; Tickle, L; Manning, SR; Tilakkumar, T; Hone, K; Ashcroft, RE; Gibbs, J; Gkatzidou, V; Tickle, L; Manning, SR; Tilakkumar, T; Hone, K; Ashcroft, RE; Sonnenberg, P; Sadiq, ST; Estcourt, CS; - view fewer (2016) 'Can you recommend any good STI apps?' A review of content, accuracy and comprehensiveness of current mobile medical applications for STIs and related genital infections. Sexually Transmitted Infections 10.1136/sextrans-2016-052690 . (In press). Green open access

http://ift.tt/2g2vxNY

What are the characteristics of, and clinical outcomes in men who have sex with men prescribed HIV postexposure prophylaxis following sexual exposure (PEPSE) at sexual health clinics in England?

Mitchell, H; Furegato, M; Hughes, G; Field, N; Nardone, A; (2016) What are the characteristics of, and clinical outcomes in men who have sex with men prescribed HIV postexposure prophylaxis following sexual exposure (PEPSE) at sexual health clinics in England? Sexually Transmitted Infections 10.1136/sextrans-2016-052806 . (In press). Green open access

http://ift.tt/2ha6z4e

Informed seller with taste heterogeneity

Koessler, F; Skreta, V; (2016) Informed seller with taste heterogeneity. Journal of Economic Theory , 165 pp. 456-471. 10.1016/j.jet.2016.06.004 .

http://ift.tt/2g2fL5E

Phosphatidylinositol 4-kinase IIβ negatively regulates invadopodia formation and suppresses an invasive cellular phenotype

Alli-Balogun, GO; Gewinner, CA; Jacobs, R; Kriston-Vizi, J; Waugh, MG; Minogue, S; (2016) Phosphatidylinositol 4-kinase IIβ negatively regulates invadopodia formation and suppresses an invasive cellular phenotype. Molecular Biology of the Cell 10.1091/mbc.E16-08-0564 . (In press).

http://ift.tt/2haePRJ

Scleroderma Lung Study II-clarity or obfuscation?

Denton, CP; (2016) Scleroderma Lung Study II-clarity or obfuscation? Lancet Respiratory Medicine , 4 (9) pp. 678-679. 10.1016/S2213-2600(16)30191-6 .

http://ift.tt/2g2rTU2

Tissue Specificity and Sex-Specific Regulatory Variation Permit the Evolution of Sex-Biased Gene Expression

Dean, R; Mank, JE; (2016) Tissue Specificity and Sex-Specific Regulatory Variation Permit the Evolution of Sex-Biased Gene Expression. The American Naturalist , 188 (3) E74-E84. 10.1086/687526 .

http://ift.tt/2ha5lps

Reliable Linear, Sesquilinear, and Bijective Operations on Integer Data Streams Via Numerical Entanglement

Anam, MA; Andreopoulos, Y; (2016) Reliable Linear, Sesquilinear, and Bijective Operations on Integer Data Streams Via Numerical Entanglement. IEEE Transactions on Signal Processing , 64 (17) pp. 4606-4617. 10.1109/TSP.2016.2560134 . Green open access

http://ift.tt/2g2nQY4

‘Shock And Kill’ Strategy For Curing HIV May Endanger Patients’ Brains

Combination drug treatments have become successful at long-term control of HIV infection, but the goal of totally wiping out the virus and curing patients has so far been stymied by HIV's ability to hide out in cells and become dormant for long periods of time. Now a new study on HIV's close cousin, simian immunodeficiency virus (SIV), in macaques finds that a proposed curative strategy could backfire and make things worse if the virus is in fact lurking in the brain.



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A Rare Case of Clavicle Osteomyelitis in a Child and Literature Review

Acute clavicle osteomyelitis in children is rare representing

http://ift.tt/2gH7urV

Validation of the Method "CaptHPV" for the Diagnosis of Human Papillomavirus Associated Infiltrating Carcinomas

Conditions:   Cervical Cancer;   Vulvar Cancer;   Anal Cancer;   Oropharynx Cancer
Intervention:   Other: CaptHPV method
Sponsor:   Institut de Cancérologie de Lorraine
Not yet recruiting - verified November 2016

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Enlargement of Meckel's cave in patients with spontaneous cerebrospinal fluid leaks

Background

Spontaneous cerebrospinal fluid (CSF) leaks have imaging findings consistent with chronically elevated intracranial pressure, such as empty sella. Meckel's cave is a CSF-filled space that houses the trigeminal ganglion at the cranial base. Our objective in this study was to evaluate "dilated" Meckel's cave as a radiologic sign in patients with elevated intracranial pressure spontaneous CSF leaks and compare the dimensions with those from a control cohort.

Methods

Meckel's cave dimensions were measured in patients with spontaneous CSF leaks and documented elevated intracranial pressure. A control group of subjects who underwent magnetic resonance imagine (MRI) scans for unrelated diagnoses were also evaluated. Subjects were included only if suitable MRIs with T2-weighted sequences in the axial plane were available.

Results

Sixty-three patients with spontaneous CSF leaks and 91 normal control patients were included in the study. There was significant (p < 0.05) enlargement in all measured dimensions (length and width) for the spontaneous CSF leak group. When evaluating area, spontaneous CSF leak subjects again showed significant enlargement compared with controls (0.81 ± 0.35 cm2 vs 0.52 ± 0.15 cm2; p < 0.0001). Average intracranial pressure measurements were 25.9 ± 9.0 cmH2O.

Conclusion

Patients with spontaneous CSF leaks have evidence of enlarged Meckel's caves. Evaluation of Meckel's cave dimensions should be included in preoperative imaging assessment as an additional indicator of chronically elevated intracranial pressure.



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The International Classification of the radiological Complexity (ICC) of frontal recess and frontal sinus

Background

The frontal sinus is considered the most challenging sinus to address surgically. There are no current classifications of the degree of surgical complexity of different frontal sinus configurations. The aim of this study is to develop a classification system of the degree of complexity of frontal recess surgery based on preoperative computed tomography (CT) scans.

Methods

Authors were asked to submit a classification system. These were circulated to all authors. Selection of the final 3 classifications was based on a majority consensus. These classifications were compared further for time-taken, ease-of-use, and interrater agreement. These were assessed by the authors on 10 CT scans representing a range of anticipated surgical difficulty.

Results

Out of 3 compared classifications, classification A was the quickest to score (1.44 minutes vs 1.57 minutes and 2.25 minutes), subjectively easiest (3.23 vs 4.07 and 5 on a visual analogue scale [VAS]), and had a moderate interrater agreement (0.52 vs 0.42 and 0.79). In addition, the grading of complexity was as good whether measurements were taken on the CT scans or whether size of the frontal ostium was visually estimated.

Conclusion

We propose a fast, easy classification to anticipate the complexity of surgery in the frontal sinus and recess, for patients undergoing primary surgery.



http://ift.tt/2g20ce6

Pencil beam all-optical ultrasound imaging

Alles, EJ; Noimark, S; Zhang, E; Beard, PC; Desjardins, AE; (2016) Pencil beam all-optical ultrasound imaging. Biomedical Optics Express , 7 (9) pp. 3696-3704. 10.1364/BOE.7.003696 . Green open access

http://ift.tt/2gt1tvD

Osteoporosis in postmenopausal women living with HIV

Finnerty, F; Walker-Bone, K; Tariq, S; (2017) Osteoporosis in postmenopausal women living with HIV. Maturitas , 95 pp. 50-54. 10.1016/j.maturitas.2016.10.015 .

http://ift.tt/2gGTVs6

Property titles and the urban poor: from informality to displacement?

Varley, A; (2016) Property titles and the urban poor: from informality to displacement? Planning Theory & Practice 10.1080/14649357.2016.1235223 . (In press).

http://ift.tt/2gsTYFe

Modeling corporate defaults: Poisson autoregressions with exogenous covariates (PARX)

Agosto, A; Cavaliere, G; Kristensen, D; Rahbek, A; (2016) Modeling corporate defaults: Poisson autoregressions with exogenous covariates (PARX). Journal of Empirical Finance , 38 (Part B) pp. 640-663. 10.1016/j.jempfin.2016.02.007 .

http://ift.tt/2gGNBRq

Claiming the University for Critical Urbanism

Addie, JD; (2017) Claiming the University for Critical Urbanism. City: analysis of urban trends, culture, theory, policy, action 10.1080/13604813.2016.1267331 . (In press).

http://ift.tt/2gsZxU7

Stability criteria for a multi-city epidemic model with travel delays and infection during travel

Knipl, D; (2016) Stability criteria for a multi-city epidemic model with travel delays and infection during travel. Electronic Journal of Qualitative Theory of Differential Equations , 2016 , Article 74. 10.14232/ejqtde.2016.1.74 .

http://ift.tt/2gGPjlT

Combined soft and skeletal tissue modelling of normal and dysmorphic midface postnatal development

Ibrahim, A; Suttie, M; Bulstrode, NW; Britto, JA; Dunaway, D; Hammond, P; Ferretti, P; (2016) Combined soft and skeletal tissue modelling of normal and dysmorphic midface postnatal development. Journal of Cranio-Maxillofacial Surgery , 44 (11) pp. 1777-1785. 10.1016/j.jcms.2016.08.020 .

http://ift.tt/2gsVyHd

Increased DNA methylation variability in type 1 diabetes across three immune effector cell types

Paul, DS; Teschendorff, AE; Dang, MA; Lowe, R; Hawa, MI; Ecker, S; Beyan, H; Paul, DS; Teschendorff, AE; Dang, MA; Lowe, R; Hawa, MI; Ecker, S; Beyan, H; Cunningham, S; Fouts, AR; Ramelius, A; Burden, F; Farrow, S; Rowlston, S; Rehnstrom, K; Frontini, M; Downes, K; Busche, S; Cheung, WA; Ge, B; Simon, MM; Bujold, D; Kwan, T; Bourque, G; Datta, A; Lowy, E; Clarke, L; Flicek, P; Libertini, E; Heath, S; Gut, M; Gut, IG; Ouwehand, WH; Pastinen, T; Soranzo, N; Hofer, SE; Karges, B; Meissner, T; Boehm, BO; Cilio, C; Elding Larsson, H; Lernmark, Å; Steck, AK; Rakyan, VK; Beck, S; Leslie, RD; - view fewer (2016) Increased DNA methylation variability in type 1 diabetes across three immune effector cell types. Nature Communications , 7 , Article 13555. 10.1038/ncomms13555 . Green open access

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Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Chen, L; Ge, B; Casale, FP; Vasquez, L; Kwan, T; Garrido-Martín, D; Watt, S; Chen, L; Ge, B; Casale, FP; Vasquez, L; Kwan, T; Garrido-Martín, D; Watt, S; Yan, Y; Kundu, K; Ecker, S; Datta, A; Richardson, D; Burden, F; Mead, D; Mann, AL; Fernandez, JM; Rowlston, S; Wilder, SP; Farrow, S; Shao, X; Lambourne, JJ; Redensek, A; Albers, CA; Amstislavskiy, V; Ashford, S; Berentsen, K; Bomba, L; Bourque, G; Bujold, D; Busche, S; Caron, M; Chen, SH; Cheung, W; Delaneau, O; Dermitzakis, ET; Elding, H; Colgiu, I; Bagger, FO; Flicek, P; Habibi, E; Iotchkova, V; Janssen-Megens, E; Kim, B; Lehrach, H; Lowy, E; Mandoli, A; Matarese, F; Maurano, MT; Morris, JA; Pancaldi, V; Pourfarzad, F; Rehnstrom, K; Rendon, A; Risch, T; Sharifi, N; Simon, MM; Sultan, M; Valencia, A; Walter, K; Wang, SY; Frontini, M; Antonarakis, SE; Clarke, L; Yaspo, ML; Beck, S; Guigo, R; Rico, D; Martens, JH; Ouwehand, WH; Kuijpers, TW; Paul, DS; Stunnenberg, HG; Stegle, O; Downes, K; Pastinen, T; Soranzo, N; - view fewer (2016) Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells. Cell , 167 (5) 1398-1414.e24. 10.1016/j.cell.2016.10.026 . Green open access

http://ift.tt/2gt1srz

Host allometry influences the evolution of parasite host- generalism: theory and meta-analysis

Walker, JG; Hurford, A; Cable, J; Ellison, AR; Price, SJ; Cressler, C; (2017) Host allometry influences the evolution of parasite host- generalism: theory and meta-analysis. Philosophical Transactions of the Royal Society of London: Biological Sciences (In press).

http://ift.tt/2gGLVaB

Visual Deception and the Beholder in Cinematic Space: the role of imaginative perception in film viewing

Cammack, J; (2010) Visual Deception and the Beholder in Cinematic Space: the role of imaginative perception in film viewing. Doctoral thesis, UCL (University College London).

http://ift.tt/2gt2pAu

Metaphors for 'good' and 'bad' deaths: A health professional view

Demjén, Z; Semino, E; Koller, V; (2016) Metaphors for 'good' and 'bad' deaths: A health professional view. Metaphor and the Social World , 6 (1) pp. 1-19. 10.1075/msw.6.1.01dem . Green open access

http://ift.tt/2gGInFv

Skin Manifestations of Insulin Resistance: From a Biochemical Stance to a Clinical Diagnosis and Management

Abstract

Worldwide, more than 1.9 billion adults are overweight, and around 600 million people suffer from obesity. Similarly, ~382 million individuals live with diabetes, and 40–50% of the global population is labeled at "high risk" (i.e., prediabetes). The impact of these two chronic conditions relies not only on the burden of illnesses per se (i.e., associated increased morbidity and mortality), but also on their increased cost, burden of treatment, and decreased health-related quality of life. For this review a comprehensive search in several databases including PubMed (MEDLINE), Ovid EMBASE, Web of Science, and Scopus was conducted. In both diabetes and obesity, genetic, epigenetic, and environmental factors overlap and are inclusive rather than exclusive. De facto, 70–80% of the patients with obesity and virtually every patient with type 2 diabetes have insulin resistance. Insulin resistance is a well-known pathophysiologic factor in the development of type 2 diabetes, characteristically appearing years before its diagnosis. The gold standard for insulin resistance diagnosis (the euglycemic insulin clamp) is a complex, invasive, costly, and hence unfeasible test to implement in clinical practice. Likewise, laboratory measures and derived indexes [e.g., homeostasis model assessment of insulin resistance (HOMA-IR-)] are indirect, imprecise, and not highly accurate and reproducible tests. However, skin manifestations of insulin resistance (e.g., acrochordons, acanthosis nigricans, androgenetic alopecia, acne, hirsutism) offer a reliable, straightforward, and real-time way to detect insulin resistance. The objective of this review is to aid clinicians in recognizing skin manifestations of insulin resistance. Diagnosing these skin manifestations accurately may cascade positively in the patient's health by triggering an adequate metabolic evaluation, a timely treatment or referral with the ultimate objective of decreasing diabetes and obesity burden, and improving the health and the quality of care for these patients.



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A reddish pulsatile mass beyond tympanic membrane: think before act

We report a case of a 76-year-old man that referred to our hospital because of progressive mixed right hearing loss, aural fullness and pulsatile tinnitus synchronized with heart beats. Otoscopic examination revealed a reddish pulsatile mass beyond tympanic membrane. CT and MRI scans showed a class C glomus tumor. Anamnesis and a complete physical examination, with careful differential diagnosis, should be obtained to rule out highly vascularized middle ear lesion before any invasive procedure.

L'articolo A reddish pulsatile mass beyond tympanic membrane: think before act sembra essere il primo su European Review.



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Repeated failed non-invasive prenatal testing in a woman with immune thrombocytopenia and antiphospholipid syndrome: lessons learnt

We present a case of a 37-year-old Chinese woman (gravida 4 para 0) with a history of immune thrombocytopenia and type IIb antiphospholipid syndrome. She was started on 100 mg of aspirin, 20 mg of prednisolone and 20 mg of subcutaneous low-molecular-weight heparin daily for her fourth pregnancy. She opted for non-invasive prenatal testing for aneuploidy screening but had failed results three times consecutively from insufficient fetal cfDNA initially or high variance in cfDNA counts on redraws. She declined invasive karyotyping. Her pregnancy was complicated by severe pre-eclampsia and fetal growth restriction at 19+6 weeks of gestation and was terminated. Subsequent fetal karyotyping revealed a normal karyotype of 46XY with no apparent abnormalities.



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Venous and arterial air embolism: a rare phenomenon with fatal consequences

Air embolism is often an iatrogenic complication which may occur in venous or arterial circulation depending on the port of entry. We present two cases in which air embolism occurred in venous and arterial circulation after contrast medium injection (CMI) and coronary artery bypass graft (CABG) surgery, respectively. In one case, accumulation of air bubbles was observed in the pulmonary artery after CMI. This was attributed to inadvertent injection of air owing to improper connection of the injector and the catheter. The patient was managed with 100% oxygen in the Trendelenburg and left lateral decubitus position. Repeat imaging demonstrated resorption of the emboli. In another case, air was introduced during CABG in the left atrium and ventricle. Immediate suction of air was attempted however, the patient developed cardiogenic shock requiring vasopressors, and subsequently seizures and coma due to diffuse ischaemic stroke. The patient eventually expired.



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Adult ileocolic intussusception caused by Burkitt lymphoma

Ileocolic intussusception due to Burkitt lymphoma is extremely rare in adults. A man aged 17 years presented with a history of recurrent abdominal pain over the past 3 weeks. The abdomen was distended with diffuse tenderness, and bowel sounds were present. Abdominal ultrasound and CT scans showed evidence of small bowel obstruction with marked wall thickening in the ileocecal region and 'target' signs suggestive for intussusception. At laparoscopy, a mass involving the caecum and the terminal ileum was found, along with multiple locoregional nodes, which was highly suggestive of malignancy. A typical en bloc right colectomy with intracorporeal ileocolic anastomosis was performed. Histopathological examination showed a high-grade B-cell Burkitt lymphoma that was confirmed by immunohistochemistry. The patient was subsequently treated with adjuvant combination chemotherapy and is alive and disease-free at the 3-year follow-up.



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Novel technique for repigmentation of senescence grey hair



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Efficacy and tolerability of a new topical nitric-zinc preparation for “difficult-to-treat” warts

Abstract

Treating plantar, periungual, and external genital warts can be challenging. A prospective study from four centers in Italy evaluated 37 immunocompetent patients with single or multiple warts and treated each lesion with a nitric-zinc topical solution composed of organic and inorganic acids meant to devitalize tissue and destroy HPV DNA in infected keratinocytes. Thirty of the 37 patients had external genital warts, two had plantar warts, two had palm and finger warts, and three had subungual warts for a total of 55 lesions treated. Nitric-zinc aqueous solution was applied over each wart utilizing a 30 µL capillary tube until a whitening response was observed. Additional applications as needed were accomplished at 2-week intervals until the wart was gone. In those with hand, plantar, and subungual warts, there was a 100% clearance after two to three sessions. Three with external genital warts had only a partial response and one no benefit after four applications. Thus, this approach was effective in external genital and other "difficult-to-treat" warts in 90% of patients after one to four applications. It also was easy to use with no adverse events noted.



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Human newborn B cells mount an IFNAR-dependent humoral response to RSV

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Publication date: Available online 5 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Jop Jans, Matthew Pettengill, Dhohyung Kim, Cas van der Made, Ronald de Groot, Stefanie Henriet, Marien I. de Jonge, Gerben Ferwerda, Ofer Levy

Teaser

This study provides evidence of a first line of human humoral defense against RSV infection in early life including the presence of natural neutralizing anti-RSV IgM as well as an IFN-β-mediated newborn B cell activation.


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Effect of probiotics in prevention of atopic dermatitis is dependent on the intrinsic microbiota at early infancy

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Publication date: Available online 5 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Ekaterina Avershina, Raul Cabrera-Rubio, Krister Lundgård, Gaspar Perez-Martinez, Maria Carmen Collado, Ola Storrø, Torbjørn Øien, Christian Kvikne Dotterud, Roar Johnsen, Knut Rudi
Although a link between probiotic intervention and reduction in atopic disease has been documented, no consistent associations with microbiota has yet been established. Here we have conducted an extensive analysis of the microbiota from more than 250 mother child pairs from a probiotic intervention cohort, where we previously have shown 40 % reduction in atopic dermatitis. Within the probiotic intervention group at the age of 10 days we found that the atopic children had a deviating microbiota (p = 0.028, BH-FDR corrected Kruskal Wallis) with high levels (> 10 %) of a bacterium related to Bifidobacterium dentium (p=0.039, BH-FDR corrected Chi-square). Based on these findings, we propose a model with two groups of children where the group responding to probiotic intervention, has gut microbiota related to that of non-atopic children; while the non-responding group has a divergent microbiota at the age of 10 days with overrepresented amounts of B. dentium. In conclusion, our results support the importance of early colonization for prevention of diseases developing later in life, with potential intervention effects being dependent on the intrinsic microbiota.

Teaser

Here we report a study suggesting that effect of probiotic intervention is dependent on intrinsic microbiota. Specifically, children who developed AD regardless of probiotic intake had divergent microbiota and characteristically higher levels of B. dentium at 10 days of age.


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Molecular engineering of a therapeutic antibody for Blo t 5-induced allergic asthma

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Publication date: Available online 5 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): J. H. Sherlynn Chan, Yen Leong Chua, Hong Yong Peh, Vojislav Jovanovic, Nicholas R.J. Gascoigne, W. S. Fred Wong, Fook Tim Chew, Brendon J. Hanson, David M. Kemeny, Paul A. MacAry




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Identification of IL-17F/frequent exacerbator endotype in asthma

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Publication date: Available online 5 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Fabio L.M. Ricciardolo, Valentina Sorbello, Anna Folino, Fabio Gallo, Gian Mario Massaglia, Gabriella Favatà, Salvatore Conticello, Davide Vallese, Federica Gani, Mario Malerba, Gert Folkerts, Giovanni Rolla, Mirella Profita, Thais Mauad, Antonino Di Stefano, Giorgio Ciprandi
BackgroundSevere asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.ObjectiveTo study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics in relation to exacerbation rate.MethodsInflammatory cells and IL-17A+, IL-17F+, IL-21+, IL-22+ and IL-23+ cells were examined by immunohistochemistry (IHC) in cryostat sections of bronchial/nasal biopsies obtained from 33 SA (21 frequent exacerbators (FE)), 31 MA (3 FE) and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by IHC in bronchial tissue obtained from subjects died for fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F co-localization.ResultsHigher number (p<0.05) of neutrophils, IL-17A+, IL-17F+ and IL-21+ cells in bronchial biopsies and higher number (p<0.01) of IL-17F+ and IL-21+ cells in nasal biopsies were observed in SA compared to MA. Bronchial IL-17F+ cells correlated with bronchial neutrophils (r=0.54), exacerbation rate (r=0.41) and FEV1 (r=-0.46). Nasal IL-17F+ cells correlated with bronchial IL-17F (r=0.35), exacerbation rate (r=0.47) and FEV1 (r=-0.61). FE showed increased number of bronchial neutrophils/eosinophils/CD4+/CD8+ cells and bronchial/nasal IL-17F+ cells. ROC curve analysis evidenced predictive cut-off values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MA and SA and between FE and non-FE. IL-17F protein increased in bronchial/nasal lysates of SA and FE and in bronchial tissue of fatal asthma. IL-17F co-localized in CD4+/CD8+ cells.ConclusionsIL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation suggesting a pathogenic role of IL-17F in frequent exacerbators.

Teaser

Overexpression of nasal/bronchial IL-17F is a feature of severe asthma in relation to neutrophils, airway obstruction and exacerbation rate and it is also able to recognize frequent exacerbator phenotype potentially at risk of asthma death.


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Coagulopathy related to hemodilution and acidosis



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A painful leg ulcer



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Recurrent oral ulcers and blisters in a young woman



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A curious case of blinking bottom



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Vulvar basal cell carcinoma with adhesion of the labia majora and minora



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Idiopathic eruptive macular pigmentation with papillomatosis



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