Orbital Exenteration in Rhino-Orbito-Cerebral Mucormycosis: A Prospective Analytical Study with Scoring System

Abstract

Mucormycosis is an uncommon, rapidly progressive, angio-invasive, commonly fatal, opportunistic fungal infection. The most critical decision in the management of rhinoorbital mucormycosis is whether the orbit should be exenterated. (1) To layout the indications of orbital exenteration in patients with rhino-orbito-cerebral mucormycosis. (2) To devise a scoring system that predicts the stage at which the exenteration needs to be carried out. A scoring system was devised by a team of experienced Otorhinolaryngologists and Ophthalmologists from prior experience in managing mucormycosis. All patients of mucormycosis visiting our hospital were admitted and included in the study. A total of 15 patients were included. The scoring system is based on 3 main criteria, namely: (1) clinical signs and symptoms. (2) Direct and Indirect Ophthalmoscopy. (3) Imaging. The Sion Hospital Scoring System is an accurate and promising measure to solve the dilemma that is associated with orbital exenteration in orbito-rhino-cerebral mucormycosis.

http://ift.tt/2IjneMW

Post Earthquake Equilibrium Disturbance: A Study After Nepal–India Earthquake 2015

Abstract

Nepal and adjoining areas of India suffered a series of massive earthquakes in April–May 2015. This was followed by a remarkable increase in the patient presenting with vague dizziness like features which could not be attributed to any defined variant of vestibular disorder. Extensive search of literature revealed only scarce information about ambiguous post-earthquake vestibular symptoms and their management. We performed a detailed epidemiological analysis of these patients to analyse the presentation, underlying mechanism and optimal management. The results were scrutinised in light of existing international literature. We observed that earthquake precipitated a psychological stress like event that provoked features of disequilibrium and the neuroanatomical basis of the proposition was explored. We renounce the hypothesis of Secondary BPPV precipitated by earthquake leading to symptoms. The results were interpreted from the perspective of Indian scenario and its utility in post-earthquake disaster management in our country has been highlighted.

http://ift.tt/2paxKx5

Comparison between the efficacy of microneedling combined with 5-fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo

Summary

Background

Several treatment modalities had been used for the treatment of vitiligo, but the optimal treatment has not yet been identified.

Objectives

To study the efficacy of microneedling with 5-flurouracil vs its efficacy with tacrolimus in the treatment of vitiligo.

Patients and methods

Twenty-five patients with vitiligo were subjected to microneedling of 2 patches of vitiligo with dermapen, then application of 5-fluorouracil to 1 patch and tacrolimus on the other patch. This procedure was repeated every 2 weeks for every patient for maximum 6 months (12 sessions). The patients were followed up for 3 months after the last session.

Results

The overall repigmentation was significantly higher in 5-fluorouracil-treated patches compared with tacrolimus. Excellent improvement occurred in 48% of 5- flurouracil-treated patches while only in 16% of tacrolimus-treated patches. In the acral parts, 40% of the patches treated with 5-fluorouracil achieved excellent improvement (repigmentation >75%), while no patch in the acral parts achieved excellent improvement with tacrolimus. However, there was significant difference between the 2 drugs,regarding inflammation, ulceration, and hyperpigmentation which occurred with 5-fluorouracil.

Conclusion

Microneedling combined with 5-fluorouracil or tacrolimus is safe and effective treatment of vitiligo. However, 5-fluorouracil achieved a greater percentage of repigmentation than tacrolimus particularly in the acral parts.

http://ift.tt/2HvJYYR

Orbital Exenteration in Rhino-Orbito-Cerebral Mucormycosis: A Prospective Analytical Study with Scoring System

Abstract

Mucormycosis is an uncommon, rapidly progressive, angio-invasive, commonly fatal, opportunistic fungal infection. The most critical decision in the management of rhinoorbital mucormycosis is whether the orbit should be exenterated. (1) To layout the indications of orbital exenteration in patients with rhino-orbito-cerebral mucormycosis. (2) To devise a scoring system that predicts the stage at which the exenteration needs to be carried out. A scoring system was devised by a team of experienced Otorhinolaryngologists and Ophthalmologists from prior experience in managing mucormycosis. All patients of mucormycosis visiting our hospital were admitted and included in the study. A total of 15 patients were included. The scoring system is based on 3 main criteria, namely: (1) clinical signs and symptoms. (2) Direct and Indirect Ophthalmoscopy. (3) Imaging. The Sion Hospital Scoring System is an accurate and promising measure to solve the dilemma that is associated with orbital exenteration in orbito-rhino-cerebral mucormycosis.

http://ift.tt/2IjneMW

Post Earthquake Equilibrium Disturbance: A Study After Nepal–India Earthquake 2015

Abstract

Nepal and adjoining areas of India suffered a series of massive earthquakes in April–May 2015. This was followed by a remarkable increase in the patient presenting with vague dizziness like features which could not be attributed to any defined variant of vestibular disorder. Extensive search of literature revealed only scarce information about ambiguous post-earthquake vestibular symptoms and their management. We performed a detailed epidemiological analysis of these patients to analyse the presentation, underlying mechanism and optimal management. The results were scrutinised in light of existing international literature. We observed that earthquake precipitated a psychological stress like event that provoked features of disequilibrium and the neuroanatomical basis of the proposition was explored. We renounce the hypothesis of Secondary BPPV precipitated by earthquake leading to symptoms. The results were interpreted from the perspective of Indian scenario and its utility in post-earthquake disaster management in our country has been highlighted.

http://ift.tt/2paxKx5

Cover Image

The cover image, by Matthias Leonhard et al., is based on the Original Article In vitro biofilm growth on modern voice prostheses, DOI: 10.1002/hed.25053.

http://ift.tt/2Im37hb

Issue Information

http://ift.tt/2pa8Ei6

NKG2D and its ligands in cancer

Payal Dhar | Jennifer D Wu

http://ift.tt/2HvSt6n

Metabolites, genome organization, and cellular differentiation gene programs

Danielle A Chisolm | Amy S Weinmann

http://ift.tt/2FKNX6O

Justifying the principle of indifference

Abstract

This paper presents a new argument for the Principle of Indifference. This argument can be thought of in two ways: as a pragmatic argument, justifying the principle as needing to hold if one is to minimise worst-case expected loss, or as an epistemic argument, justifying the principle as needing to hold in order to minimise worst-case expected inaccuracy. The question arises as to which interpretation is preferable. I show that the epistemic argument contradicts Evidentialism and suggest that the relative plausibility of Evidentialism provides grounds to prefer the pragmatic interpretation. If this is right, it extends to a general preference for pragmatic arguments for the Principle of Indifference, and also to a general preference for pragmatic arguments for other norms of Bayesian epistemology.

http://ift.tt/2HpBtyk

Bacterial adaptation to antibiotics through regulatory RNAs [PublishAheadOfPrint]

The extensive use of antibiotics has resulted in a situation where multidrug-resistant pathogens have become a severe menace to human health worldwide. A deeper understanding of the principles used by pathogens to adapt, respond and resist against antibiotics will pave the road to drugs with novel mechanisms. For bacteria, antibiotics are clinically-relevant stresses that induce protective responses. The recent implication of regulatory RNAs (sRNAs) into antibiotic response and resistance in many bacterial pathogens suggests that they should be considered as innovative drug targets. This review discusses sRNA-mediated mechanisms exploited by bacterial pathogens to fight against antibiotics. A critical discussion of the newest findings in the field is provided, with emphasis on the implication of sRNAs in major mechanisms leading to antibiotic resistance: drug uptake, active drug efflux, drug target modifications, biofilms, cell wall and LPS biosynthesis. Of interest is the lack of knowledge about sRNAs implicated in Gram-positive resistance, compared to Gram-negative bacteria.

http://ift.tt/2FDK6VJ

Mutation in the Squalene epoxidase gene of Trichophyton interdigitale and Trichophyton rubrum associated with allylamine resistance [PublishAheadOfPrint]

Dermatophytosis, the commonest superficial fungal infection, has gained recent attention due to its change of epidemiology and treatment failures. Despite availability of several effective antifungal agents against dermatophytes, the incidence of chronic infection, re-infection and treatment failures are on the rise. Trichophyton rubrum and Trichophyton interdigitale are the two frequent clinical isolates in India. Consecutive patients (n=195) with suspected dermatophytosis during second half of 2014 were included in this study. Patients were categorized into relapse and new cases according to standard definitions. Antifungal susceptibility testing of the isolated Trichophyton species (n=127) was carried out against 12 antifungal agents —fluconazole, voriconazole, itraconazole, ketoconazole, sertaconazole, clotrimazole, terbinafine, naftifine, amorolfine, ciclopirox olamine, griseofulvin and luliconazole. Squalene epoxidase gene was evaluated for mutation (if any) in 15 - T. interdigitale and five - T. rubrum isolates exhibiting high minimum inhibitory concentration to terbinafine. T1189C mutation was observed in four T. interdigitale and two T. rubrum isolates. This transition leads to the substitution of amino acid phenylalanine to leucine in 397^th position of the squalene epoxidase enzyme. In homology modelling the mutant residue was smaller than wild type and positioned in the dominant site of squalene epoxidase during drug interaction, which may lead to failure to block ergosterol biosynthesis pathway by the antifungal drug.

http://ift.tt/2FKBuQh

A Phase 3, Randomized, double-blind, multicenter study to EValuate the safety and efficacy of intravenous Iclaprim versus Vancomycin for the trEatment of acute bacterial skin and skin structure infections suspected or confirmed to be due to Gram-positive pathogens: REVIVE-2 [PublishAheadOfPrint]

Iclaprim is a novel diaminopyrimidine antibiotic that may be an effective and safe treatment for serious skin infections. The safety and effectiveness of iclaprim were assessed in a global Phase 3, double-blind, randomized, active-controlled trial. Six-hundred thirteen adults with acute bacterial skin and skin structure infections (ABSSSI) suspected or confirmed to be due to Gram-positive pathogens were randomized to iclaprim (80 mg) or vancomycin (15mg/kg), both administered intravenously every 12 hours for 5 - 14 days. The primary endpoint was a ≥20% reduction in lesion size, compared with baseline, at 48 to 72 hours after the start of administration of study drug in the intent-to-treat population. Among patients randomized to iclaprim, 78.3% (231 of 295) met this primary endpoint, compared with 76.7% (234 of 305) for those receiving vancomycin (treatment difference: 1.58%, 95% CI: -5.10% to 8.26%). This met the pre-specified 10% non-inferiority margin. Iclaprim was well tolerated, with most adverse events categorized as mild. In conclusion, iclaprim was non-inferior to vancomycin in this Phase 3 clinical trial for the treatment of acute bacterial skin and skin structure infections. Based on these results, iclaprim may be an efficacious and safe treatment for skin infections suspected or confirmed to be due to Gram-positive pathogens.

(This trial has ben registered at ClinicalTrials.gov under identifier NCT02607618.)

http://ift.tt/2FJ7sN3

In Vitro Antifungal Activity of Novel Triazole Efinaconazole and Five Comparators Against Dermatophyte Isolates [PublishAheadOfPrint]

The objective was to assess the in vitro activity of the novel triazole antifungal drug, efinaconazole, and five comparators (luliconazole, lanoconazole, terbinafine, itraconazole and fluconazole) against a large collection of Trichophyton interdigitale and Trichophyton rubrum clinical isolates. The geometric mean MICs were the lowest for luliconazole (0.0005 μg/mL), followed by lanoconazole (0.002 μg/mL), efinaconazole (0.007 μg/mL), terbinafine (0.011 μg/mL), itraconazole (0.095 μg/mL) and fluconazole (12.77 μg/mL). It appears that efinaconazole, lanoconazole and luliconazole are promising candidates for the treatment of dermatophytosis due to T. interdigitale and T. rubrum.

http://ift.tt/2FD2Swv

Elimination of doripenem during dialysis and pharmacokinetic evaluation of post-hemodialytic dosing in intermittent renal replacement therapy [PublishAheadOfPrint]

Objectives: Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa and Enterobacteriaceae. Current dosing regimens recommend the administration of 0.25-0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investigate a 1-g post-hemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem.

Patients: Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode.

Results: The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance in between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average pre-hemodialysis trough concentration was 2.4 ± 1.3 mg/l, while the EUCAST resistance breakpoint for Enterobacteriaceae is set at 2 mg/l. The interpatient variability was considerably higher than the intrapatient variability. Apart from one patient who suffered an allergic reaction, doripenem was tolerated well by all patients.

Conclusion: Our data indicate, that post-hemodialysis administration of 1 g doripenem result in sufficient plasma levels in anuric, but not oliguric patients during the entire dosing interval.

http://ift.tt/2FOF9wM

Selection and Characterization of Rupintrivir-Resistant Norwalk Virus Replicon Cells in vitro [PublishAheadOfPrint]

Human norovirus (HuNoV) is a major cause of nonbacterial gastroenteritis worldwide yet, despite their impact on society, vaccines and antivirals are currently lacking. A HuNoV replicon system has been widely applied to the evaluation of antiviral compounds and has thus accelerated the process of drug discovery against HuNoV infection. Rupintrivir, an irreversible inhibitor of the human rhinovirus 3C protease, has been reported to inhibit the replication of the Norwalk virus replicon via the inhibition of the norovirus protease. Here we report, for the first time, the generation of rupintrivir-resistant human Norwalk virus replicon in vitro. Sequence analysis revealed that these replicon cells contained amino acid substitutions of alanine 105 to valine (A105V) and isoleucine 109 to valine (I109V) in the viral protease NS6. The application of a cell-based fluorescence resonance energy transfer (FRET) assay for protease activity demonstrated that these substitutions were involved in the enhanced resistance to rupintrivir. Furthermore, we validated the effect of these mutations using the reverse genetics in murine norovirus (MNV), demonstrating that a recombinant MNV with a single I109V substitution in the protease also showed reduced susceptibility to rupintrivir. In summary, using a combination of different approaches, we have demonstrated that, under the correct conditions, mutations in the norovirus protease can rapidly occur that lead to the generation of resistant mutants.

http://ift.tt/2FOBmiK

Discovery of a Novel Metallo-ss-Lactamase Inhibitor, which can Potentiate Meropenem Activity against Carbapenem-Resistant Enterobacteriaceae [PublishAheadOfPrint]

Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent and have become a major worldwide threat to human health. Carbapenem resistance is driven primarily by the acquisition of β-lactamase enzymes which are able to degrade carbapenem antibiotics (hence termed carbapenemases) and can result in high levels of resistance and treatment failure. Clinically relevant carbapenemases include both serine-β-lactamases (SBLs, e.g. KPC-2 and OXA-48) and metallo-β-lactamases (MBLs), such as NDM-1. MBL-producing strains are endemic within the community in many Asian countries, have successfully spread worldwide, and account for many significant CRE outbreaks. Recently approved combinations of β-lactam antibiotics with β-lactamase inhibitors are only active against SBL-producing pathogens. Therefore, new drugs that specifically target MBLs and which restore carbapenem efficacy against MBL-producing CRE pathogens are urgently needed. Here, we report the discovery of a novel MBL inhibitor, ANT431, that can potentiate the activity of MEM against a broad range of MBL-producing CRE, and restore its efficacy against an Escherichia coli NDM-1 strain in a murine thigh infection model. This is a strong starting point for a chemistry lead optimization program that could deliver a first-in-class MBL inhibitor/carbapenem combination. This would complement the existing weaponry against CREs and address an important and growing unmet medical need.

http://ift.tt/2FM3naN

Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam [PublishAheadOfPrint]

Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen acquired predominantly by immunosuppressed patients during hospitalization. Relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates the Pseudomonas-Derived Cephalosporinase (PDC-3) with a k₂/K of 41,400 M^-1s^-1 and a k_off of 0.00095 s^-1. Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant (MDR) P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against P. aeruginosa.

http://ift.tt/2FDK68b

Population Pharmacokinetics of Meropenem in Plasma and Subcutis in Patients on Extracorporeal Membrane Oxygenation Treatment [PublishAheadOfPrint]

The objectives of this study were to describe meropenem pharmacokinetics (PK) in plasma and/or subcutaneous adipose tissue (SCT) in critically ill patients receiving ECMO treatment, and to develop a population PK model to simulate alternative dosing regimens and modes of administration. We conducted a prospective observational study. Ten patients on ECMO treatment received meropenem (1 or 2 g) intravenously over 5 min every 8 hours. Serial SCT concentrations were determined using microdialysis and compared with plasma concentrations. A population PK model of SCT and plasma data was developed using NONMEM. Time above clinical breakpoint MIC for Pseudomonas aeruginosa (8 mg/L) was predicted for each patient. The following targets were evaluated: 40% fT>MIC, 100% fT>MIC and 100% fT>4xMIC. For all dosing regimens simulated in both plasma and SCT 40% fT>MIC was attained. However, prolonged meropenem infusion would be needed for 100% fT>MIC and 100% fT>4xMIC to be obtained. Meropenem plasma and SCT concentrations were associated with estimated creatinine-clearance (eCL_Cr). Simulations showed that in patients with increased eCL_Cr, dose increment or continuous infusion may be needed to obtain therapeutic meropenem concentrations. In conclusion, our results show that when using traditional targets of 40% fT>MIC standard meropenem dosing of 1 g intravenously 8-hourly is likely to provide sufficient meropenem concentration to treat the problematic pathogen P. aeruginosa for patients receiving ECMO treatment. However, for patients with an increased eCL_Cr or if more aggressive targets like 100% fT>MIC or 100% fT>4xMIC are adopted, dose increment or continuous infusion may be needed.

http://ift.tt/2FLP71B

Micafungin breakthrough fungemia in patients with hematological disorders [PublishAheadOfPrint]

Limited data are available on micafungin breakthrough fungemia (MBF), fungemia that develops on administration of micafungin, in patients with hematological disorders. We reviewed medical and microbiological records of patients with hematological disorders who developed MBF between January 2008 and June 2015. A total of 39 patients with MBF were identified and Candida (30 strains) and non-Candida (9 strains) fungal species were recognized as causative strains. Among 35 stored strains, C. parapsilosis (14 strains), Trichosporon asahii (7 strains), C. glabrata (5 strains), and other fungal species (9 strains) were identified by sequencing. Neutropenia was identified as an independent predictor of non-Candida fungemia (P = 0.023). T. asahii was the most common causative strain (7/19) during neutropenia. The 14-day crude mortality rate of patients treated with early micafungin change (EMC) to other antifungal agents was lower than that of the patients not treated with EMC (14% vs. 43%, P = 0.044). Most of the stored causative Candida strains were susceptible (80%) or showed wild-type susceptibility (72%) to micafungin. The minimum inhibitory concentrations (MICs) of voriconazole for T. asahii were low (range, 0.015 to 0.12 μg/mL), whereas MICs of amphotericin B for T. asahii were high (range, 2 to 4 μg/mL). MBF caused by non-Candida fungus should be considered, especially in patients with neutropenia. EMC could improve early mortality. Based on epidemiology and drug susceptibility profiling, empiric voriconazole-containing therapy might be suitable for treating MBF during neutropenia to cover for T. asahii.

http://ift.tt/2HtB0eO

Constitutive activation of MexT by amino acid substitutions results in MexEF-OprN overproduction in clinical isolates of Pseudomonas aeruginosa [PublishAheadOfPrint]

When overproduced, the multidrug efflux system MexEF-OprN increases resistance of Pseudomonas aeruginosa to fluoroquinolones, chloramphenicol and trimethoprim. In this work, we demonstrate that gain-of-function mutations in regulatory gene mexT result in oligomerization of LysR regulator MexT, in constitutive upregulation of the efflux pump and increased resistance in clinical isolates.

http://ift.tt/2FODIyb

TLR7 agonists display potent antiviral effects against norovirus infection via innate stimulation [PublishAheadOfPrint]

Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections, and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and as adjuvants for norovirus virus-like particle (VLP) vaccines. However, developing norovirus therapies are largely direct-acting antivirals (DAAs) with fewer compounds that target the host. Our aim was to assess the antiviral potential of TLR7 agonist immunomodulators on norovirus infection using the murine norovirus (MNV) and human Norwalk replicon models. TLR7 agonists R-848, Gardiquimod, GS-9620, R-837 and Loxoribine were screened using a plaque reduction assay and each displayed inhibition of MNV replication (EC₅₀ values: 23.5 nM, 134.4 nM, 0.59 μM, 1.5 μM and 79.4 μM, respectively). RNA-sequencing of TLR7 stimulated cells revealed a predominant upregulation of innate immune response genes and ISGs that are known to drive an antiviral state. Furthermore, the combination of R-848 and the nucleoside analogue (NA) 2' C-methylcytidine elicited a synergistic antiviral effect against MNV demonstrating that combinational therapy of host-modulators and DAA's could be used to reduce drug cytotoxicity. In summary, we have identified that TLR7 agonists display potent inhibition of norovirus replication and are a therapeutic option to combat norovirus infections.

http://ift.tt/2Hv2L6J

Posaconazole-Induced Pseudohyperaldosteronism [PublishAheadOfPrint]

A woman in her late 60s with disseminated histoplasmosis was treated with posaconazole since first-line therapies were not tolerated. She subsequently presented with decompensated heart failure, hypertension, and hypokalemia. Labs revealed low renin and aldosterone levels. A potential mechanism is inhibition of the enzyme 11 beta-hydroxysteroid dehydrogenase 2, with resultant apparent mineralocorticoid excess.

http://ift.tt/2FMcEzy

Association of Vancomycin MIC and Molecular Characteristics With Clinical Outcomes in Methicillin-Susceptible Staphylococcus aureus Acute Hematogenous Osteoarticular Infections in Children [PublishAheadOfPrint]

Background: Methicillin-resistant Staphylococcus aureus (MRSA), particularly those belonging to the USA300 pulsotype, have been well described to cause severe osteoarticular infections (OAI). Vancomycin MIC ≥ 1.5 μg/ml has been demonstrated to contribute to disease severity in adults with MRSA and even MSSA bacteremia. Little data exists describing the outcomes of MSSA OAI in terms of molecular characteristics and vancomycin MIC.

Methods: All patients/isolates were chosen from a surveillance study at Texas Children's Hospital (TCH). S. aureus OAI isolates were identified from 2011-2016 and subjected to vancomycin E-tests, PFGE and PCR for PVL and agr group.

Results: 252 cases of S. aureus OAI were identified; 183 were MSSA (72.6%). During the study period, a decrease in the proportion of cases secondary to MRSA was observed, declining from 37.8% to 15.9% (p=0.02). 26.2% and 23.5% of MSSA isolates were USA300 and PVL-positive, respectively. An increase in the proportion of MSSA isolates with a vancomycin MIC ≥ 1.5 μg/ml occurred in the study period (p=0.004). In MSSA, elevated vancomycin MIC was associated with multiple surgical procedures and and venous thromboses even when adjusting for empiric β-lactam use. An increase in vancomycin MIC was noted among isolates belonging to agr group 4 during the study period.

Conclusion: Methicillin-resistance is declining among S. aureus OAI isolates at TCH. Simultaneously, vancomycin E-test MICs are increasing among MSSA isolates. Vancomycin MIC ≥ 2 μg/ml are associated with adverse clinical outcomes in MSSA irrespective of antibiotic choice suggesting that this may be a surrogate for organism virulence.

http://ift.tt/2HvnXtb

Potent Activity of Luliconazole, Lanoconazole and Eight Comparators against Molecularly Characterized Fusarium species [PublishAheadOfPrint]

A collection of clinical (n=47) and environmental (n=79) Fusarium isolates were tested against 10 antifungal drugs, including two novel imidazoles. Luliconazole and lanoconazole demonstrated very low GM MIC values of 0.005 μg/ml and 0.013 μg/ml, respectively, in comparison with 0.51 μg/ml for micafungin, 0.85 μg/ml for efinaconazole, 1.12 μg/ml for natamycin, 1.18 μg/ml for anidulafungin, 1.31 μg/ml for voriconazole, 1.35 μg/ml for caspofungin, 1.9 μg/ml for amphotericin B and 4.08 μg/ml for itraconazole. Results show that these drugs are potential candidates for (topical) treatment of skin and nail infections due to Fusarium species.

http://ift.tt/2FODzuD

The combination of tedizolid and daptomycin against methicillin-resistant Staphylococcus aureus in an in vitro model of simulated endocardial vegetations [PublishAheadOfPrint]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for healthcare-associated infections, and treatment options are limited. Tedizolid (TZD), is a novel, oxazolidinone antibiotic with activity against MRSA. Previously, daptomycin (DAP), has demonstrated synergy with other antibiotics against MRSA. We sought to determine the efficacy of the combination of TZD + DAP against MRSA in an in vitro model of simulated endocardial vegetations (SEVs).

Methods: TZD simulations of 200 mg once daily and DAP simulations of 6-mg/kg and 10-mg/kg once daily were tested alone and in the combinations of TZD + DAP 6-mg/kg or DAP 10-mg/kg against two clinical strains of MRSA, 494 and 67. These regimens were tested in SEV models over 8 days to determine antibacterial activity of the regimens and whether synergy or antagonism might be present between the agents.

Results: Against both 494 and 67 and at both DAP dose regimens, the combination of TZD and DAP was antagonistic at 192 hours. In all cases, DAP alone was statistically superior to DAP + TZD. When the combination was stopped after 96 hours, transitioning to DAP 6-mg/kg or DAP 10-mg/kg alone resulted in better antibacterial activity than either of the TZD + DAP combinations, further demonstrating antagonistic effects.

Conclusions: Against MRSA, we have demonstrated that TZD and DAP have antagonistic activity that hinders overall antimicrobial efficacy. The exact nature of this antagonistic relationship is as of yet undetermined, but its presence warrants further study into the potentially harmful grouping of these two antibiotics in clinical use.

http://ift.tt/2FD0mGk

Increasing resistance to azithromycin of Neisseria gonorrhoeae in eastern Chinese cities: mechanisms and genetic diversity of resistant Nanjing isolates [PublishAheadOfPrint]

Azithromycin resistance (AZM-R) of Neisseria gonorrhoeae is emerging as a clinical and public health challenge. We determined molecular characteristics of recent AZM-R Nanjing gonococcal isolates and tracked the emergence of AZM-R isolates in eastern Chinese cities in recent years. 384 N. gonorrhoeae isolates from Nanjing collected from 2013 to 2014 were tested for susceptibility to AZM and six additional antibiotics; all AZM-R strains were characterized genetically for resistance determinants by sequencing and were genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST). Among the 384 isolates, 124 (32.3%) were AZM-R. High-level resistance (MIC ≥ 256 mg/L) was present in 10.4% (40/384) of isolates, all of which possessed the A2143G mutation in all four 23S rRNA alleles. Low-to-mid resistance (MIC 1 to 64 mg/L) was present in 21.9% (84/384) of isolates, 59.5% of which possessed the C2599T mutation in all four 23S rRNA alleles. The 124 AZM-R isolates were distributed into 71 different NG-MAST STs. ST1866 was the most prevalent type in high-level AZM-R (HL-AZM-R) isolates (45% [18/40]). This study together with previous reports revealed that the prevalence of AZM-R in N. gonorrhoeae isolates in certain eastern Chinese cities has risen more than 4-fold (7% to 32%) from 2008 to 2014. The principle mechanisms of AZM resistance in recent Nanjing isolates were: A2143G mutations (high-level resistance) and C2599T mutations (low-to-mid resistance) in the 23S rRNA alleles. Characterization of NG-MAST STs and phylogenetic analysis indicated genetic diversity of N. gonorrhoeae in Nanjing; however, ST1866 was the dominant genotype associated with HL-AZM-R isolates.

http://ift.tt/2FOBkr8

Workforce Considerations, Training, and Diseases in the Middle East

Evaluating and providing global health assistance, humanitarian aid, and medical missions to Middle Eastern countries can be rewarding and challenging. A broad spectrum of financial capabilities supports effective health care delivery and infrastructure. Middle East tension can make obtaining a visa difficult. Personal safety considerations may hinder efforts to develop and carry out clinical and educational programs. Several Middle East countries have sophisticated and modern health care systems. Medical education and specialty training compares with that of Western medicine. The Middle East has a proud heritage as the foundation of many fundamental and modern medical and surgical principles.

http://ift.tt/2Iifhrf

Response letter to the editor about the editorial by oppenheimer and greenberger “baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO” (2017;119:474-5)

In our editorial "Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO1 regarding the observational study,2 we stated that "the clinician must consider the great cost associated with these agents " referring to omalizumab. A supporting reference3 didn't include indirect costs (absenteeism from school or work, psychologic harms and economic hardships of uncontrolled asthma) although we did mention them. Luskin et al point out that there are indirect benefits from omalizumab that would improve its value (benefits/costs) also known as cost effectiveness ratio.

http://ift.tt/2FvyxDX

A randomized, double-blind, placebo-controlled study of the use of viscous oral cromolyn sodium for the treatment of eosinophilic esophagitis

There is a need for effective, non-steroid pharmacologic therapies for eosinophilic esophagitis (EoE). Cromolyn sodium offers an option as mast cells have been implicated in the symptomatology of EoE and cromolyn has also been shown to have some anti-eosinophilic properties.

http://ift.tt/2DmP2fy

Bioimpedance measurement as an assessment of margin positivity in Mohs surgical specimens of non-melanoma skin cancer: Management implications

http://ift.tt/2HuS187

High neutrophil-to-lymphocyte ratio before starting anti-PD1 immunotherapy predicts poor outcome in patients with metastatic melanoma

http://ift.tt/2FMDdVu

Increased Topical Generic Prices by Manufacturers: An Isolated Trend or Worrisome Future?

There is limited data regarding generic medication prices. Recent studies have shown price changes at the retail level, but much is not known about the pharmaceutical supply chain or price changes at the manufacturer level.

http://ift.tt/2FDqgKf

Clinical, dermoscopic and trichoscopic analysis of frontal fibrosing alopecia associated with acquired dermal macular hyperpigmentation: A cross sectional observational case-control study

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Relation between globus pharyngeus and OSA in patients examined simultaneously by PSG and pH monitor: A cross sectional study

This was a first cross-sectional single-center study to research the relation between globus pharyngeus, OSA and GERD. Since previous clinical studies have demonstrated a relationship between globus phayrngeus and GERD, however, no reported study on the relation between globus pharyngeus, sleep disorders including OSA, and GERD.

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Clinical Research at the Heart of the Spanish Academy of Dermatology and Venereology

M.A. Descalzo
Actas Dermosifiliogr 2018;109:99

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The Future of Treatment for Capillary Malformations

R. del Río
Actas Dermosifiliogr 2018;109:99

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Allergic Reactions to Tattoo Inks: A New Diagnostic Challenge

D. Muñoz Borrás
Actas Dermosifiliogr 2018;109:100

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Psoriasis-Arthritis Units: Three Years On

A. López-Ferrer, A. Láiz-Alonso
Actas Dermosifiliogr 2018;109:101-3

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Genetic Diagnosis of Epidermolysis Bullosa: Recommendations From an Expert Spanish Research Group

C. Sánchez-Jimeno, M.J. Escámez, C. Ayuso, M.J. Trujillo-Tiebas, M. del Río
Actas Dermosifiliogr 2018;109:104-22

Abstract - Full text - PDF

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Melanoma Arising in a Melanocytic Nevus

A. Martín-Gorgojo, E. Nagore
Actas Dermosifiliogr 2018;109:123-32

Abstract - Full text - PDF

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Empowerment in Dermatology

J.J. Domínguez-Cruz, J.J. Pereyra-Rodríguez, R. Ruiz-Villaverde
Actas Dermosifiliogr 2018;109:133-9

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Clinical and Histopathologic Findings of Cutaneous Leiomyosarcoma: Correlation With Prognosis in 12 Patients

E. Rodríguez-Lomba, I. Molina-López, V. Parra-Blanco, R. Suárez-Fernández, A. Pulido-Pérez
Actas Dermosifiliogr 2018;109:140-7

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Clinical Research at Territorial Section Meetings of the Spanish Academy of Dermatology and Venereology (AEDV)

Á. Iglesias-Puzas, A. Batalla, Á. Flórez
Actas Dermosifiliogr 2018;109:148-54

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Diagnostic Tools to Use When We Suspect an Allergic Reaction to a Tattoo: A Proposal Based on Cases at Our Hospital

I. González-Villanueva, J.F. Silvestre Salvador
Actas Dermosifiliogr 2018;109:162-72

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Confluent and Reticulated Papillomatosis With Linear Pseudo-striae: A Description of 20 Cases

C.A. Morales-Cardona, C. Tejada-Figueroa, D.M. Méndez-Velasco
Actas Dermosifiliogr 2018;109:e7-e11

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Erythematous Lesion on the Nose

D. González Fernández, S. Requena López, F. Valdés Pineda
Actas Dermosifiliogr 2018;109:173-4

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Vasculitis With Lesions on the Scalp as the Only Cutaneous Manifestation

F.C. Benavente Villegas, J.M. Sánchez Motilla, N. Rausell Fontestad
Actas Dermosifiliogr 2018;109:175-6

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Rituximab: Revolutionizing the Treatment of Pemphigus

D. Morgado-Carrasco, P. Giavedoni, X. Fustà-Novell, P. Iranzo
Actas Dermosifiliogr 2018;109:177-8

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Viscerocutaneous Loxoscelism

R. Cullen, P. Hasbún, M.P. Piquer
Actas Dermosifiliogr 2018;109:179

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Síndrome de CLAPO

M.Á. Flores-Terry, P. Zamberk-Majlis, M.P. Cortina-de la Calle, M. García-Arpa
Actas Dermosifiliogr 2018;109:180

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Malignant Blue Nevus: A Challenge for Dermatologists and Dermatopathologists

T. Toledo-Pastrana, I. Rodríguez Pérez, P. Eguino Gorrochategui
Actas Dermosifiliogr 2018;109:181-3

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Cutaneous Solitary Fibrous Tumor: A Spindle Cell Neoplasm With Distinctive Immunohistochemical Features

J. Santos-Juanes, B. García-García, Y. Hidalgo, B. Vivanco
Actas Dermosifiliogr 2018;109:183-5

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Allergic diseases: A collection of interactive immunologic disorders at the crossroads of genetics, environment, and immunity

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Association between urticaria and nematode infections

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Association of alopecia areata with atopic dermatitis and chronic spontaneous urticaria

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Association between psoriasis and asthma risk: A meta-analysis

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Safety of a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in children: A randomized clinical trial

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The age-related characteristics of adults with asthma who visited emergency departments in Korea from 2007 to 2012

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Randomized trial to assess the efficacy and safety of beclomethasone dipropionate breath-actuated inhaler in patients with asthma

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VideoEndocrinology™ High-Impact Videos

VideoEndocrinology™
The Official Journal of: American Thyroid Association

FREE ACCESS through March 12, 2018.
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Delphian Lymph Node Dissection: Surgical Dissection Technique as Illustrated by the Johns Hopkins Head and Neck Endocrine Surgery Division
Vaninder K. Dhillon, Jonathon O. Russell, Ralph P. Tufano 

Postoperative Continuous Pressure Monitoring in Thyroid Surgery: Pathophysiology of Post-Thyroidectomy Hemorrhage
Ulrich Wirth, Thomas von Ahnen, Stefan Schopf, Hans Martin Schardey 

An Elusive Parathyroid: Interesting Case Presentation
Anton F. Engelsman, Robert F. Parkyn, Andrew Carter, James Christie, Leigh W. Delbridge 

Transaxillary Robotic Parathyroidectomy: Huge Parathyroid Adenoma
Patrick Aidan, Maroun Bechara

The post VideoEndocrinology™ High-Impact Videos appeared first on American Thyroid Association.

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Asthma control, lung function, symptoms, and corticosteroid sparing after omalizumab initiation in patients with allergic asthma

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Thyroid® High-Impact Articles

FREE ACCESS through March 9, 2018.
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Latest Impact Factor: 5.515
The Official Journal of: American Thyroid Association^®

Gene Fusions in Thyroid Cancer
Valentina D. Yakushina, Larisa V. Lerner, Alexander V. Lavrov

Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients
Fuya Zhao, Jing Feng, Jun Li, Lei Zhao, Yang Liu, Huinan Chen, Ye Jin, Biqiang Zhu, Yunwei Wei 

Cancer Risk Associated with Nuclear Atypia in Cytologically Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis
Pablo Valderrabano, Laila Khazai, Zachary J. Thompson, Susan C. Sharpe, Valentina D. Tarasova, Kristen J. Otto, Julie E. Hallanger-Johnson, J. Trad Wadsworth, Bruce M. Wenig, Christine H. Chung, Barbara A. Centeno, Bryan McIver 

Maternal Thyrotropin Receptor Antibody Concentration and the Risk of Fetal and Neonatal Thyrotoxicosis: A Systematic Review
Naomi Kiyota, Bruce Robinson, Manisha Shah, Ana O. Hoff, Matthew H. Taylor, Di Li, Corina E. Dutcus, Eun Kyung Lee, Sung-Bae Kim, Makoto Tahara

 

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Clinical Thyroidology®High-Impact Articles

FREE ACCESS through March 6, 2018
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Editorial: What's Ahead for Clinical Thyroidology in 2018
Jerome M. Hershman 

Patient Age Is Associated with Papillary Thyroid Cancer Mortality Only in Patients with BRAF V600E Mutation
Masha J. Livhits, Michael W. Yeh

Current ATA Thyroid Cancer Guidelines Are Poor Predictors of the Extent of Thyroidectomy
Tracy S. Wang

A Low-Iodine Diet During Methimazole Treatment Worsens Graves' Disease Outcomes
Elizabeth N. Pearce

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In vitro induction of T regulatory cells by a methylated CpG DNA sequence in humans: Potential therapeutic applications in allergic and autoimmune diseases

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Clinical Thyroidology®for the Public – Highlighted Article

From Clinical Thyroidology^® for the Public: Many clinicians and laboratories check TSH alone as the initial test for thyroid problems and then only add a Free T4 measurement if the TSH is abnormal, referred to as "reflex" testing. Read More….

We welcome your feedback and suggestions. Let us know what you want to see in this publication.

Feedback & Suggestions

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Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E

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ATA® Thyroid Cancer Patient Survey

DIAGNOSED AND TREATED FOR THYROID CANCER?
ATA^® INVITES YOUR FEEDBACK ON THIS SURVEY:

https://www.surveymonkey.com/r/thyroidcancerpatientsurvey

The American Thyroid Association^® (ATA) is collecting information and opinions from patients about their experience with thyroid cancer to better inform medical providers about how patients experience the challenge of thyroid cancer diagnosis and treatment. ATA^® encourages anyone with a history of thyroid cancer to take this survey, feel free to disseminate this survey link broadly, and encourage others to take the survey. We also encourage all thyroid healthcare professionals to share this survey with their patients. Survey results will be compiled and discussed by thyroid leaders at the American Thyroid Association Satellite Symposium: The Spectrum of Thyroid Cancer, from Surveillance to Systemic Therapy on Friday, March 16, 2018 from 11:15 AM – 5:30 PM at McCormick Place West in Chicago, IL. Subsequently, survey results will be posted online with free access to the public as well as made available through publication. Your responses are anonymous and should only take a few minutes to complete.

For more information regarding the ATA Spring Satellite Symposium, visit the ATA website at www.thyroid.org or  https://www.thyroid.org/2018-ata-spring-satellite/.

We again appreciate your continued support of ATA^® and its initiatives.

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Guidance for compassionate restraint of small children to prevent injuries with epinephrine autoinjectors

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For the Patient

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Clinical Thyroidology®High-Impact Articles

FREE ACCESS through February 13, 2018
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Should a Young Patient in Whom a Multinodular Goiter Develops Be Assessed for DICER1 Mutations?
Stephen W. Spaulding

Levothyroxine Treatment Does Not Reduce Risk for Premature Delivery Among TPO-Negative Pregnant Women with a TSH of 2.5 to 10.0 mIU/L
Elizabeth N. Pearce

Adding the Immunosuppressant Mycophenolate Mofetil to Medium-Dose Infusions of Methylprednisolone Improves the Treatment of Graves' Orbitopathy
Jacques Orgiazzi

Surgery for Hyperthyroidism Lowers Cardiovascular Mortality Compared with Radioactive Iodine
Andrew J. Day, Michael W. Yeh, Masha J. Livhits

 

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Characterization and expression of DEC205 in the cDC1 and cDC2 subsets of porcine dendritic cells from spleen, tonsil, and submaxillary and mesenteric lymph nodes

Publication date: April 2018
Source:Molecular Immunology, Volume 96
Author(s): Héctor Parra-Sánchez, Lucinda Puebla-Clark, Mónica Reséndiz, Olivia Valenzuela, Jesús Hernández
Conventional dendritic cells (cDCs) are divided into the following different subtypes: cDC1, which promotes a Th1 response, and cDC2, which stimulates a Th2 and Th17 response. These cells have not been characterized in porcine lymphoid tissues. DEC205 is a receptor that increases antigen presentation and allows DCs to cross-present antigens. The objectives of this work were to characterize cDCs subsets in the tonsil, submaxillary and mesenteric lymph nodes and spleen lymphoid tissues and to determine their expression of DEC205 by flow cytometry. The cDC1 (MHCII^highCADM1^highCD172a^−/low) and cDC2 (MHCII^highCADM1^highCD172a⁺) phenotypes were confirmed by the expression of characteristic cDC1 and cDC2 transcripts (FLT3, XCR1 and FCER1α). Among all lymphoid tissues, the spleen had the highest frequency of total cDCs. The cDC1:cDC2 ratio showed that all lymph tissues had higher levels of cDC1 than levels of cDC2. DEC205⁺ cDCs were found in all analyzed tissues, albeit with different frequencies. Our research will facilitate the study on the function of these cells and the investigation of the strategies for DEC205 targeting and functional studies.



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Contact allergy to benzalkonium chloride in patients using a steroid nasal spray: A report of 3 cases

Jerome Rene Lechien, MD, PhD, MS; Pedro Costa de Araujo, MD; Lisa G. De Marrez, BSc; Jean-Luc Halloy, MD; Mohamad Khalife, MD; Sven Saussez, MD, PhD

Abstract

Benzalkonium chloride (BAC) is a bactericidal preservative excipient commonly found in steroid nasal sprays used to treat allergic rhinitis and nasal polyposis. In rare cases, BAC can be responsible for type I and type IV hypersensitivity reactions that can manifest as rhinorrhea, which a clinician might misinterpret as a lack of response to nasal spray therapy rather than a complication of it. We report 3 cases of type IV hypersensitivity reactions in patients who were being treated with mometasone nasal spray. We describe the epidemiology, clinical features, diagnosis, and treatment of these reactions.

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Recent advances in the selection and identification of antigen-specific nanobodies

Publication date: April 2018
Source:Molecular Immunology, Volume 96
Author(s): Wenshuai Liu, Haipeng Song, Quan Chen, Jianli Yu, Mo Xian, Rui Nian, Dongxiao Feng
Nanobodies represent the next-generation antibody-derived biologics with significant advances over conventional antibodies. Several rapid and robust techniques for isolating highly specific nanobodies have been developed. Antigen specific nanobodies are selected from constructed nanobody libraries, which can be classified into 3 main types: immune library, naïve library, and semisynthetic/synthetic library. The immune library is the most widely used strategy for nanobody screening. Target specific nanobodies are highly enriched in immune libraries than in non-immune libraries; however, it is largely limited by the natural antigenicity of antigens. The naïve library is thus developed. Despite the lack of somatic maturation, protein engineering can be employed to significantly increase the affinities of selected binders. However, a substantial amount of blood samples collected from a large number of individual animals is a prerequisite to ensure the diversity of the naïve library. With this issue considered, the semisynthetic/synthetic library may be a promising path toward obtaining a limitless source of nanobodies against a variety of antigens without the need of animals. In this review, we summarize the state-of-the-art screening technologies with different libraries. The approaches presented here can further boost the diverse applications of nanobodies in biomedicine and biotechnology.



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A South African first: Congenital absence of the cartilaginous nasal septum

Yahya Atiya, MBBCh, MMed (ORL), FCORL

Abstract

Congenital absence of the cartilaginous nasal septum has been reported just once in the literature. We present a case of a young child, diagnosed by exclusion, with complete agenesis of the cartilaginous septum. We believe it is only the second case worldwide, and the first in South Africa, to be reported.

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miR-330-5p/Tim-3 axis regulates macrophage M2 polarization and insulin resistance in diabetes mice

Publication date: March 2018
Source:Molecular Immunology, Volume 95
Author(s): Jiling Sun, Qiujing Huang, Shufa Li, Fanqing Meng, Xunhua Li, Xiaoyun Gong
Obesity is associated with a state of low-grade inflammatory response in adipose tissue, and contributes to the development of type 2 diabetes.Immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Therefore, adipose tissue promotes macrophage infiltration, resulting in local inflammation and insulin resistance. Tim-3 negatively regulates IFN-γ secretion and influences the ability to induce T cell tolerance in diabetes. MicroRNA contributes to the development of immunological tolerance and involves in macrophage polarization. However, the potential of Tim-3 to regulate macrophage polarization and the related microRNA has not been reported. In this experiment, 8-week-old C57BL/6 mice were fed a high-fat diet for 8 weeks. The adipose tissue macrophages were isolated, miR-330-5p and Tim-3 levels, and M1/M2 polarization were analyzed. In addition, insulin tolerance tests was detected. The results demonstrated that miR-330-5p levels increased but Tim-3 levels decreased, leading to M1 polarization and insulin tolerance in diabetes mice. In addition, inhibition of miR-330-5p enhanced Tim-3 levels, leading to M2 polarization and insulin tolerance attenuation in diabetes mice. Furthermore, we detected the inverse relationship between miR-330-5p and Tim-3. We found that Tim-3 mRNA contained conserved miR-330-5p binding sites in its 3′UTR, and miR-330-5p could directly regulate Tim-3 expression through these 3′UTR sites. Our study demonstrated that miR-330-5p served as a regulator of the M2 polarization and miR-330-5p/Tim-3 axis potentially down-regulated insulin resistance in diabetes, probably through enhancing the M2 polarization of macrophage.



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Use of the microdebrider in the surgical management of rhinophyma

Winsion Chow, MD, MSc; Goran Jeremic, MD, FRCSC; Leigh Sowerby, MD, FRCSC

Abstract

Rhinophyma is a disfiguring end-stage manifestation of acne rosacea. It is characterized by a painless hyperplasia of the sebaceous glands and connective tissues of the nose. Numerous surgical modalities-including scalpel surgery, dermabrasion, CO2 laser ablation, and electrocautery-have been reported with varying results. We describe our experience with using a microdebrider to treat 2 patients-a 65-year-old man and a 74-year-old man-who presented with rhinophyma. The instrument we used was the Medtronic Straightshot M4 Microdebrider. Using a low revolution speed, we easily excised the bulky superficial tissue. At higher revolution speeds with the use of a small shaver tip, we were able to achieve delicate contouring of the nasal tip and ala without causing scarring. Postoperatively, both patients exhibited an excellent cosmetic outcome and expressed a high degree of patient satisfaction. We conclude that the microdebrider is an excellent surgical tool for treating rhinophyma lesions. Its ease of use and its availability at most surgical centers makes it a favorable surgical option.

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Emodin attenuates titanium particle-induced osteolysis and RANKL-mediated osteoclastogenesis through the suppression of IKK phosphorylation

Publication date: April 2018
Source:Molecular Immunology, Volume 96
Author(s): Juehong Li, Yamin Li, Xiaochun Peng, Bin Li, Xiangwei Yuan, Yunsu chen
Aseptic loosening due to wear particles is a serious challenge for orthopedic surgeons, sabotaging the long-term success of total joint arthroplasty. The existing treatments for aseptic loosening are still far from satisfactory, necessitating more aggressive drug exploration. Here, we examined the effect of emodin on titanium particle-induced osteolysis and further investigated its underlying mechanism in vivo and in vitro. Thirty-two C57BL/6 mice were randomly assigned into four groups: the Sham group (sham operation with vehicle injection), Vehicle group (titanium particle treatment with vehicle injections), Low group (titanium particle treatment with injections of 10 mg/kg/day emodin) and High group (titanium particle treatment with injections of 50 mg/kg/day emodin). Micro-CT scanning and histological analysis revealed that after emodin injections, the inflammatory response and bone destruction were markedly ameliorated. TRAP staining showed that osteoclast numbers were also dramatically reduced. Throughout the in vitro culture period, emodin significantly decreased the bone resorption area, number of osteoclasts and formation of F-actin rings. Mechanistic studies suggested that reduced NF-κB signaling might be mediating the inhibitory effects of emodin. Collectively, our findings suggest that emodin, a natural product extracted from Rheum palmatum, may be developed as a promising candidate for the treatment of wear particle-induced osteolysis and subsequent aseptic loosening.



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A case of squamous cell carcinoma of the nasal cavity in a patient with granulomatosis with polyangiitis (Wegener granulomatosis)

Edward C. Kuan, MD, MBA; Kevin A. Peng, MD; Lyndon O. Gonzalez, MD; Joel A. Sercarz, MD

Abstract

We report a rare case of squamous cell carcinoma (SCC) of the nasal cavity arising in a patient with granulomatosis with polyangiitis (GPA). The patient was a 35-year-old man who had been diagnosed 15 years earlier with GPA and treated medically for sinonasal, pulmonary, and renal involvement. He presented to us with left-sided orbital and cheek pain and nasal obstruction. Endoscopy detected a friable, exophytic mass that involved the left lateral nasal wall and septum. Biopsy analysis identified the mass as an SCC. A definitive endoscopic resection was performed, followed by chemoradiation, but the patient exhibited progression of disease 2 months after the cessation of therapy. He then underwent an open craniofacial resection and a second round of chemoradiation. At 7 months of follow-up, he remained disease-free. Sinonasal symptoms in GPA are consistent with those in chronic rhinosinusitis, but the presence of unilateral symptoms may suggest a neoplastic process. Immunosuppressants are implicated in the pathophysiology of this malignancy, but equally plausible is the oncogenic role of chronic inflammation.

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Variations of T and B lymphocytes of flounder (Paralichthys olivaceus) after Hirame novirhabdovirus infection and immunization

Publication date: April 2018
Source:Molecular Immunology, Volume 96
Author(s): Jing Xing, Lei Wang, Mengxiao Zhen, Xiaoqian Tang, Wenbin Zhan
T and B lymphocytes are closely related to immunization and pathogen infection. Our previous study confirmed the CD3⁺, CD4-1⁺, CD4-2⁺, CD8β⁺ T lymphocytes and IgM⁺ B lymphocytes presented in the peripheral blood leukocytes (PBLs) of flounder (Paralichthys olivaceus), in this paper, the variations of T and B lymphocytes of flounder after Hirame novirhabdovirus (HIRRV) infection or immunization were investigated. The flounders were injected with live or inactivated HIRRV, then the percentages of T and B lymphocytes in PBLs were analyzed by Flow cytometry (FCM), total antibodies and HIRRV-specific antibodies in serum were detected by Enzyme-linked immunosorbent assay (ELISA), and expression of twelve immune-related genes in the head kidneys were determined using q-PCR. The results showed that the percentages of CD3⁺, CD4-1⁺, CD4-2⁺, CD8β⁺ T lymphocytes and IgM⁺ B lymphocytes significantly increased in both infection and immunization groups, in infection group they decreased rapidly after the peak and significantly lower than control levels at the end of infection, in immunization group they went down steadily to the control levels at the end of immunization. The total antibodies and HIRRV-specific antibodies increased first and peaked on the 7^th day post infection and on the 14^th day post immunization, respectively, then gradually decreased to the control levels. Additionally, twelve immune-related genes were up-regulated in both groups. These results demonstrated that the HIRRV induced both humoral and cellular immunity of flounder, the lymphocytes varied more sharply in infection group than those in immunization group and CD8⁺ T lymphocytes responded much more than CD4⁺ T lymphocytes to HIRRV antigen.



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Silicone granuloma formation associated with dermal injection

Leo L. Wang, MS; William W. Thomas, MD; Cherie M. Ditre, MD; Oren Friedman, MD

Silicone fillers, for all their advantages, are associated with significant long-term risks.

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Immunological network analysis in HPV associated head and neck squamous cancer and implications for disease prognosis

Publication date: April 2018
Source:Molecular Immunology, Volume 96
Author(s): Xiaohang Chen, Bingqing Yan, Huihuang Lou, Zhenji Shen, Fangjia Tong, Aixia Zhai, Lanlan Wei, Fengmin Zhang
Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV−) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV− HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV− HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings.



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Temporal bone anomalies associated with unbalanced 9;13 chromosome translocation depicted on CT and MRI

Daniel Thomas Ginat, MD, MS

The presence of microtia in conjunction with inner ear anomalies is uncommon.

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Absence of a neutralizing antibody response to humanized cobra venom factor in mice

Publication date: May 2018
Source:Molecular Immunology, Volume 97
Author(s): Mathieu Ing, Brian E. Hew, David C. Fritzinger, Sandrine Delignat, Sébastien Lacroix-Desmazes, Carl-Wilhelm Vogel, Julie Rayes
Cobra venom factor (CVF) is the complement-activating protein in cobra venom. Humanized CVF (hCVF) is a human C3 derivative where the C-terminal 168 amino acid residues were replaced with the homologous sequence from CVF. hCVF has been shown in multiple models of disease with complement pathology to be a promising therapeutic agent, with no observed adverse effects. Here we describe the antibody response to hCVF in two different strains of mice. hCVF was able to repeatedly decomplement the mice after four injections in weekly intervals, demonstrating the absence of a neutralizing antibody response. In contrast, natural CVF caused decomplementation in all mice only after the first administration. After two additional administrations of natural CVF, decomplementation was inconsistent and varied tremendously from mouse to mouse. After the fourth administration, natural CVF was essentially unable to deplete complement, consistent with the known generation of a neutralizing antibody response. We also analyzed the IgG antibody response to hCVF. There was great variation, with approximately one quarter of the mice exhibiting non-detectable levels of anti-hCVF IgG, and another quarter very low levels. The levels of anti-hCVF IgG did not correlate with the levels of remaining C3. The anti-hCVF antibodies cross-reacted with natural CVF, recombinant CVF, and human C3. Whereas overall the level of anti-hCVF IgG cross-reacting with human C3 was lower compared to rCVF or nCVF, mice with higher levels of anti-hCVF IgG exhibited higher binding to CVF and human C3, excluding the possibility that higher antibody levels reflect preferential immunogenicity of CVF-specific or human C3-specific epitopes.



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Langerhans cell histiocytosis presenting as a scalp mass in a child

Omar Hariri, BBA; Seckin Ulualp, MD; Ron B. Mitchell, MD

The clinical presentation and course of Langerhans cell histiocytosis can range from a single benign lesion to life-threatening disseminated disease affecting multiple organs.

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Bacterially activated B-cells drive T cell differentiation towards Tr1 through PD-1/PD-L1 expression

Publication date: April 2018
Source:Molecular Immunology, Volume 96
Author(s): Sawsan Sudqi Said, Guliz Tuba Barut, Nesteren Mansur, Asli Korkmaz, Ayca Sayi-Yazgan
Regulatory B cells (Bregs) play a crucial role in immunological tolerance primarily through the production of IL-10 in many diseases including autoimmune disorders, allergy, infectious diseases, and cancer. To date, various Breg subsets with overlapping phenotypes have been identified. However, the roles of Bregs in Helicobacter infection are largely unknown. In the present study, we investigate the phenotype and function of Helicobacter −stimulated B cells. Our results demonstrate that Helicobacter felis −stimulated IL-10- producing B cells (Hfstim- IL-10⁺ B) are composed of B10 and Transitional 2 Marginal Zone Precursor (T2-MZP) cells with expression of CD9, Tim-1, and programmed death 1 (PD-1). On the other hand, Helicobacter felis −stimulated IL-10- nonproducing B (Hfstim- IL-10⁻ B) cells are mainly marginal zone (MZ) B cells that express PD-L1 and secrete TGF-β, IL-6, and TNF-α, and IgM and IgG2b. Furthermore, we show that both Hfstim- IL-10⁺ B cells and Hfstim- IL-10⁻ B cells induce CD49b⁺LAG-3⁺ Tr1 cells. Here, we describe a novel mechanism for PD-1/PD-L1- driven B cell-dependent Tr1 cell differentiation. Finally, we explore the capability of Hfstim- IL-10⁻ B cells to induce Th17 cell differentiation, which we find to be dependent on TGF-β. Taken together, the current study demonstrates that Hfstim- B cells induce Tr1 cells through the PD-1/PD-L1 axis and Th17 cells by secreting TGF-β.



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Microbial flora and antibiotic resistance in odontogenic abscesses in Upstate New York

Ann W. Plum, MD; Anthony J. Mortelliti, MD; Ronald E. Walsh, NP

Abstract

Abscesses in the head and neck frequently have odontogenic sources. As bacterial pathogens and antibiotic resistance patterns may change over time and based on location, we describe the current common bacteria found in odontogenic abscesses, the prevalence of antibiotic resistance, and differences in each between pediatric and adult patients in Upstate New York. This is a retrospective review of patients who underwent drainage of odontogenic abscesses (n = 131) from 2002 to 2012 at an academic institution. The medical records were reviewed for results of abscess cultures, comorbidities, and drainage procedures. Polymicrobial sources were identified in 60.3% and monomicrobial in 33.6%. Overall, the most common bacteria were alpha hemolytic Streptococci (33.6%), Streptococcus milleri (32.1%), Prevotella (16.8%), and coagulase-negative Staphylococcus (14.5%). Candida and Morganella spp were more common in children than in adults. Overall, antibiotic resistance was observed in seven different pathogens. The most common antibiotic resistances were to clindamycin and erythromycin, which should be considered when deciding initial antibiotic therapy, especially in adult patients, who trended in this study toward having pathogens with higher rates of resistance.

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Endoscopic view of a mucocele obstructing a middle meatal antrostomy

Eiji Yanagisawa, MD, FACS; Dewey A. Christmas, MD; Joseph P. Mirante, MD, MBA, FACS

Mucoceles can occur naturally as mucus retention cysts or after sinus surgery, by ostial obstruction and formation of a lesion lined by low columnar epithelium.

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The head impulse test as a predictor of videonystagmography caloric test lateralization according to the level of examiner experience: A prospective open-label study

Ashraf Awadie, MD; Yehuda Holdstein, MD; Margalit Kaminer, MSc; Avi Shupak, MD

Abstract

We conducted a study to compare how well the head impulse test (HIT), without and with eye-movement recordings, would predict videonystagmographic (VNG) caloric test lateralization when performed by a resident and an experienced otoneurologist. This prospective, open-label, blinded study was conducted in an ambulatory tertiary care referral center. Our study population was made up of 60 patients-29 men and 31 women, aged 20 to 82 years (mean: 56.4 ± 11.4)-with peripheral vestibulopathy who underwent HIT and VNG caloric testing. The HIT was conducted in two protocols: HIT0 and HIT1. The HIT0 was performed with passive brisk movements of the patient's head from the 0° null position to 20° sideways, and the HIT1 was performed toward the center while the null position was a 20° head rotation to the right and to the left. Each protocol was carried out without video eye-movement recordings (HIT0 and HIT1) and with such recordings (rHIT0 and rHIT1). The primary outcome measures were (1) a comparison of the HIT's sensitivity and specificity when performed by the resident and by the experienced otoneurologist and (2) the ability of video-recorded HIT to predict VNG caloric test lateralization. The sensitivity and specificity obtained by the resident were 41 and 81%, respectively, for HIT0 and 41 and 90% for HIT1. The sensitivity and specificity obtained by the experienced otoneurologist were 18 and 89% for HIT0 and 32 and 85% for HIT1. Analysis of the recorded eye-movement clips of the HIT0 and HIT1 obtained by a second experienced otoneurologist found a sensitivity and specificity of 32 and 63% for rHIT0 and 33 and 82% for rHIT1. We conclude that the HIT yields high false-negative rates in predicting significant caloric lateralization. Analysis of the eye-movement recordings was no better than normal testing alone for detecting saccades. The experience of the examining physician had no impact on test performance characteristics.

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Fiberoptic Endoscopic Evaluation of Swallow (FEES) in Intensive Care Unit Patients Post Extubation

Abstract

Intensive care unit patients frequently require prolonged intubation and ventilator support. Swallowing dysfunction often occurs in patients who receive prolonged mechanical ventilation. Intubation can cause transient injury to the larynx with a subsequent reduction in protective mechanism and increased incidence of oropharyngeal secretions once patient is extubated. Aim of this study was to evaluate the anatomical damage caused by intubation and the occurrence of aspiration/silent aspiration in patients following extubation, using fiberoptic endoscopic evaluation of swallow (FEES) as diagnostic and therapeutic tool. Participants in the study included all adult ICU patients who were intubated for ≥ 48 h. Head injury patients, patients with abnormal neurological status, completely disoriented patients were excluded. We performed FEES in 41 patients. Duration of intubation was in the range of 2–9 days. We studied 41 patients, among them 19(44%) patients had laryngeal injury and 6 (14%) had aspiration. we noticed that all patients who had aspiration had some laryngeal injury. All 6 patients who had aspiration initially recovered their swallowing function fully as noticed during repeat FEES done after swallow therapy. There is a significant impact of intubation on occurrence of aspiration (14%) and laryngeal abnormality (44%). We found in our study that there is a significant correlation to duration of intubation and occurrence of laryngeal injury.

http://ift.tt/2FcUqI3

Comparative Study of Management of BPPV (Benign Paroxysmal Positional Vertigo) with only Drugs Versus Drugs Plus Epley Manoeuvre

Abstract

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder, accounting for 20% of all vertigo cases. Idiopathic BPPV is most common between the ages of 50 and 70, although the condition is found in all age groups. The importance of early diagnosis and treatment can lead to a much improved quality of life for patients afflicted by this ailment. It is presently common for physicians to treat these patients mainly with benzodiazepines, antihistamines, and anticholinergic medications, especially if the history and physical is consistent with BPPV. This method of treatment has had questionable success. Several reviews of the management of vertigo have shown that no medication in current use has well established curative or prophylactic value or is suitable for long-term treatment. Epleys manoeuvre is also used in the treatment of BPPV. This manoeuvre relocates free floating particles from the affected semi-circular canals back into utricle, thus relieving the symptoms of vertigo. The purpose of this study is to compare the efficacy of Epleys manoeuvre with conventional drug therapy versus conventional therapy alone in patients who present with vertigo. The purpose of this study to evaluate and examine two methods of treatment.

http://ift.tt/2HYBPwX

Recognizing HPV Awareness Day

On Sunday, March 4, NCI joins organizations around the world, to promote awareness and education about HPV infection and the HPV-associated diseases that can be prevented through vaccination.

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2017 Embassy Science Fellowship: Bangkok, Thailand

The Embassy Science Fellow (ESF) program provides U.S. embassies access to the expertise of U.S. government officers in science and technology fields. U.S. embassies request Fellows to assist on science, technology, environment or health issues and related policy development and collaboration.

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CGH Recognizes World Cancer Day 2018

On Sunday, February 4th, the National Cancer Institute will recognize World Cancer Day, an initiative of the Union for International Cancer Control.

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Prospects for the Intellectualization of State-of-the-Art Aviation Systems

Abstract

This article, based on a paper heard at a meeting of the RAS Presidium, analyzes the main problems of and trends in the intellectualization of state-of-the-art aviation complexes. The obtaining and intelligent processing of heterogeneous information, intelligent management, and aircraft "self-sensing," as well as intelligent interaction within the pilot–aircraft contour, are highlighted as key functional objectives for the foreseeable future. The primary focus is made on the intelligent processing of measuring and video information, including the automatic mutual referencing and uniting of measuring and geospatial information into a visual complex; continuous provision of an accurate, authentic, and holistic image of the surroundings to the crew, regardless of weather and time conditions; recognition and prediction of dangerous combinations of factors considering the flight path; assessment of the crew's psychophysiological condition; changes in the external environment and technical condition of the aircraft; and recommendations for the crew to escape or prevent abnormal situations.

http://ift.tt/2GjJYvv

Interaction between Man and the Natural Environment: A Major Factor of the Existence of Civilization On the Results of the Year of Ecology in Russia

Abstract

The history of humans as a biological species is tightly connected with the geological evolution of the Earth, the development of the biosphere, and the consumption of its resources. Life-supporting resources, which the biosphere produces "free of charge," and the attitude of Homo sapiens to them constitute the main factor of human existence, determining the mode of our society. Modern approaches to the interaction between man and the natural environment, as well as conditions leading to the biosphere's degradation, are discussed. Among the global factors that affect the state of the biosphere, the authors identify the following: the uncontrollable growth of the planet's population, anthropization, climate change and the increased frequency of catastrophic natural and natural–anthropogenic phenomena, and changes in the human gene pool. All these factors are considered in the strategy of the sustainable development of modern society. Alternatives of implementing the sustainable development concept are considered in the article, including the idea of the noosphere, a fundamentally new approach to interaction between man and nature.

http://ift.tt/2Gjm9UM

The Outward Expansion of China As a Result of Its Victorious Modernization

Abstract

The author considers the People's Republic of China of the mid-2010s as a country of accomplished modernization, emphasizing the reorientation of the state and society to find solutions to fundamentally new problems. At the present stage, the attention of the country's leadership is focused on the social and environmental situation, the consumer revolution, and the development of science and technology. The monetary financial and external economic stability allows the fifth generation of Chinese leaders to offer the country and the world a new vector of socioeconomic growth. Right in front of our eyes, China is becoming an exporter of modernization and can exert a significant influence on its partners. In the opinion of the author, the center of global development is shifting to the East, where gigantic and dynamic China is beginning to form global trends.

http://ift.tt/2tCxnRJ

Comparison of Tectonic Phases and Geomagnetic Reversals in the Late Mesozoic and in the Cenozoic

Abstract

The authors consider the chronological relation of two groups of phenomena in the history of the Earth over the last 150 mln years. One of them is relatively short (a few million years) tectonic phases, or orogenic phases, identified by H.W. Stille in 1924 and characterized by an increase in compressive deformation in mobile belts of the Earth. Deformations that occur during such phases are quite explicable by collisional interactions of lithospheric plates. However, these interactions do not explain the synchronous occurrence of phases in different belts and on different continents. The other group is the frequency of magnetic reversals, i.e., changes such that the positions of magnetic north and magnetic south are interchanged. Tectonic phases are more frequent in epochs of frequent geomagnetic reversals. During the last 24 mln years, when geomagnetic reversals were especially numerous, tectonic phases came one after another in short intervals. An emerging trend for them is the lagging of phase peaks by one to two million years relative to the most frequent magnetic reversals. The chronological relations identified show that tectonic phases are determined not only by geodynamic processes in the lithosphere but also by the action of energy pulses that occur in the Earth's core and at the boundary of the core with the mantle, where the Earth's magnetic field is generated. On the geological time scale, this interaction takes place quickly, which excludes energy pulse convection and prompts the search for other mechanisms of this transfer. It is possible that it takes place because the lithosphere is affected by alternating body forces that occur under a change in currents in the core, which is followed by changes in the mode of the Earth's rotation and the adaptation to it of lithospheric masses.

http://ift.tt/2FxOwRV

The Global Competitiveness Index As an Indicator of Sustainable Development

Abstract

The competitiveness of 41 European countries, based on the global competitiveness index, is analyzed for the period 2014–2016, proving that this indicator is primarily determined not by any one factor or by several factors but by all of those included in the index. The author evaluates the contribution of each factor to the value of the global competitiveness index using various statistical methods, as well as additional data from the World Economic Forum's Global Competitiveness Reports 2014–2016. The analysis of the competitiveness of the European countries in line with the global competitiveness index helps reveal the specifics of the existing regional socioeconomic differentiation compared to averaged European data. These characteristics should be considered when building the national competitive strategy of each state of the region. The study reveals a high correlation between a country's rating for the global competitiveness index and the human development index, the gross domestic product per capita, the level of gender inequality, and the competitiveness of the travel and tourism industry.

http://ift.tt/2tH52JO

Constitutional Modernization in the CIS Countries: New Trends

Abstract

New trends resulting from the most considerable changes in the constitutions of the CIS countries and several other states of the former Soviet Union are analyzed. The constitutional model developed in Eurasian states of this region is transitional, incomplete, and hybrid, which predetermines the need for further modernization (novelization) of the constitutions. The common features of the initial period of independent development in this group of countries are undergoing substantial transformations; there have emerged multidirectional vectors of constitutional modernization with account for characteristic traits of the evolution of the political and legal systems of different states. The author's conclusions concern the regimentation of the foundations of constitutional systems, forms of state, and human rights—the main subjects of constitutional–legal regulation in any state and the most important objectives of constitutional reform for constitutions under modernization. Study of the trends in the constitutional development of the post-Soviet countries of Eurasia, which is of significant interest for political sciences, contributes to the elaboration of the theory of postsocialist states and their constitutions.

http://ift.tt/2Gl8r3U

Attitudes to Death As a Scientific Problem

Abstract

The topic of attitudes to death is traditionally taboo in society but penetrates mass culture in the form of simulacra. The evolution of attitudes to death in the history of European civilization and in individual consciousness proceeding from the opinions of philosophers and theologians, as well as the results of empirical studies characterizing the attitude to death in mass consciousness, is shown. How popular is the belief in afterlife? Does religiosity have any effect on the fear of death? What are people afraid of when they think about death? Can one form a positive attitude to death? This article attempts to answer these questions.

http://ift.tt/2tI0Eua

The Logic of Directed Development in Postcolonial India

Abstract

It has been presumed that an increase in economic growth rates automatically intensifies inflation processes, which provoke sensitivity among mass layers of the population. However, manifestations of interdependence between growth and inflation are different in different economic systems. Of importance are the degree of the maturity of the economic organism, its historical experience, and the sociopolitical context. Financial instability is a fundamental qualitative characteristic of the capitalist economy with its complex branched system of institutions. The suppression of inflation implies disciplinary actions from above, regulating the economic behavior of various groups of society. Rigid control over inflationary processes is characteristic of "late start" societies and, even more so, of states of the third wave of modernization, particularly India. Inflation in its acute forms turned out to be a result of the administration's policy intended to form a middle class. The author of this article holds that the approach of India's authorities to inflation problems is based on three strategic principles: measures to normalize circulation, to protect the poorest layers of the population from the consequences of inflation, and to find additional resources of the effectiveness of the country's economic mechanism.

http://ift.tt/2Gl8ooK

Multimodal Interfaces of Human–Computer Interaction

Abstract

An analytical review of state-of-the-art and future intelligent interfaces of human–computer interaction is presented; stages of their evolution are considered from command text to graphic and then to intelligent uni- and multimodal interfaces, based on the transfer of acoustic, visual, textual, and neural information. The principles of organization and the main characteristics and types of multimodal user interfaces, which employ concurrently several tools for automatic processing (recognition and synthesis) of userinputted heterogeneous information, are detailed. The combination of computers with speech and multimodal interfaces, designed for user-friendly information input/output, creates universal information–communicative technologies, man coming to the fore in the interaction between man and computer. Russian and foreign developments in this field are analyzed briefly.

http://ift.tt/2tGbGzZ

Challenges and Opportunities in Forming a Digital Economy in Russia

Abstract

Challenges and risks in forming a digital economy in Russia are discussed. It is shown that they result from the fact that the country lacks companies economically and socially equipped to be leaders in the global semiconductor and radio electronics markets. Half of the global semiconductor market is controlled by US companies, which constitute the basis for the already formed "US digital economy of semiconductors," Russia being a consumer of its products. "The US digital economy" is a project of global semiconductor market leaders, targeted at forming new global markets under the decreasing profitability of semiconductors. In the existing situation, the implementation of most of the National Technology Initiative's projects will be based on borrowed technologies and components, endangering both Russia's prospect to acquire any significant share of new global markets and its information security protection against growing cyberattacks. Russia can parry the challenges and risks of the formation of its digital economy through the creation of economically and socially significant IT companies, oriented at digitizing the country's strategic industries and able to claim leadership in global markets.

http://ift.tt/2Gkiw0W

Urgent Problems of Valuation of Recoverable Oil and Gas Reserves

Abstract

Economic, technical, technological, and organizational problems of subsurface management, primarily oil and gas, are considered. The authors justify the necessity of cardinal restructuring of the valuation system for mineral resources and the assessment of the efficiency of their development projects. Social (economic) efficiency criterion should top the agenda here as in several developed countries. This will help not only consider the requirements of the country's long-term sustainable development but also improve considerably the oil, gas, and condensate recovery factors and reduce the negative environmental consequences. Simultaneously, it is necessary to balance out the interests of the subsurface user, the state, and society, which requires certain changes in the organizational and economic mechanism of implementing subsurface management projects. If oil and gas projects are implemented in conditions of uncertainty and risk, the organizational and economic mechanism of their implementation should envisage the adaptation of projects to the changing conditions and the methods of valuation of reserves should be updated.

http://ift.tt/2tJ10Rs

The Uniform Electronic Knowledge Space Revisited

Abstract

The set of issues associated with the formation of a single Russian electronic knowledge space is considered. This task, first formulated in the Russian Presidential Decree On Approval of the Foundations of a State Cultural Policy, has become particularly urgent in the context of the so-called Big Challenges, preconditioned by the development of scientific knowledge and technologies. To solve this task, it is necessary to develop a tool kit based on the Semantic Web technology, using scientific electronic libraries and other data arrays, as well as classifications, thesauruses, ontologies, and systems of metadata and other tools for subject area representation. The creation of a single Russian electronic knowledge space may be referred to nationwide projects, and the RAS scientific organizations and the country's leading universities should play the leading role in it.

http://ift.tt/2GjwsIt

Mathematical Modeling and the Philosophy of Science

Abstract

Philosophical and methodological aspects of predictive mathematical modeling are considered. Predictive mathematical modeling in the epoch of technological challenges to postindustrial society is becoming a third way of cognition, supplementing and uniting classical theory and natural experiment. The author describes conceptual, architectoral, and technological problems of creating an integrated software environment for high-performance solutions to interdisciplinary direct and reciprocal new-generation problems for multiprocessor petascale computing systems with scalable parallelism. Trends are unfolding in the development of "neoinformatics" with the introduction of cognitive principles into the automation of model and algorithm building and into the creation of decision-making systems for a wide range of users from various production and social spheres. Constructive and infrastructural principles are proposed for the development of an open basic modeling system that supports all basic stages of science-intensive computer experimentation and is oriented at an effective long-life cycle and coordinated development by various design teams.

http://ift.tt/2tJ2Ils

Automated Vehicles and Transportation Justice

Abstract

Despite numerous ethical examinations of automated vehicles, philosophers have neglected to address how these technologies will affect vulnerable people. To account for this lacuna, researchers must analyze how driverless cars could hinder or help social justice. In addition to thinking through these aspects, scholars must also pay attention to the extensive moral dimensions of automated vehicles, including how they will affect the public, nonhumans, future generations, and culturally significant artifacts. If planners and engineers undertake this task, then they will have to prioritize their efforts to avoid additional harm. The author shows how employing an approach called a "complex moral assessment" can help professionals implement these technologies into existing mobility systems in a just and moral fashion.

http://ift.tt/2GjJm9b