Certolizumab Pegol in the Treatment of Psoriasis and Psoriatic Arthritis: Preliminary Real-Life Data

Abstract

Introduction

We present the results of real-life tests conducted in adults affected by psoriatic arthritis (PsA) with mild cutaneous involvement to evaluate the efficacy of certolizumab pegol (CZP), an anti-tumor necrosis factor-alpha agent approved in Europe for the treatment of rheumatoid arthritis and PsA.

Methods

Assessments included an evaluation of the Psoriasis Area and Severity Index (PASI) and the Disease Activity Score computed on 44 joints (DAS-44) correlated to the erythrocyte sedimentation rate (ESR) (DAS44-ESR). A total of 41 patients (16 men, 25 women; mean age 59.8 ± 8 years) completed the study. Of these, 36 patients were affected by both PsA and psoriasis, and five patients were affected only by PsA. A total of 32 patients (group A) completed 3 months of treatment (W12), and 12 patients completed 6 months of treatment (W24) (group B).

Results

The clinical efficacy of CZP was consistent on both the cutaneous and rheumatic components of the treatment. The mean PASI score decreased from 4.4 ± 4.7 at baseline (BL) to 2.3 ± 3.7 at W12 (group A), and from 5.1 ± 5.7 at BL to 0.8 ± 1.2 at W24 (group B). The DAS44-ESR decreased from 4.4 ± 0.6 at BL to a mean of 2.2 ± 0.9 at W12 (group A) and from 4.1 ± 0.6 at BL to a mean of 1.9 ± 0.5 at W24 (group B). No adverse events were reported.

Conclusion

Our results demonstrate that CZP can be used safely and effectively to treat both the cutaneous and joint components of PsA. However, long-term data are needed to confirm our preliminary observations.

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Cover Image

The cover image, by Jianjian Qiu et al., is based on the Original Article ¹⁸F-Fluoromisonidazole positron emission tomography/CT-guided volumetric-modulated arc therapy-based dose escalation for hypoxic subvolume in nasopharyngeal carcinomas: A feasibility study, DOI: 10.1002/hed.24925.

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Issue Information - Contents

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Novel topical agent containing superoxide dismutase 100 000 IU and 4% of plant extracts as a mono-therapy for atopic dermatitis

Abstract

Introduction

Corticosteroids are the mainstay of treatment for the acute phase of atopic dermatitis (AD), whereas topical emollients are mainly used for maintenance of remission. A topical agent that combines emollient and anti-inflammatory properties would achieve control of all phases of AD, without the need for chronic corticosteroid use.

Aim

To assess the efficacy of a novel topical agent containing superoxide dismutase (SOD) 100 000 IU and 4% of a combination of plant extracts (blackcurrant seed oil, sunflower oil concentrate, balloon vine extract).

Methods

Twenty patients (age range from 8 months to 72 years old) with mild-to-moderate atopic dermatitis were assessed. The product was used as mono-therapy, applied to the affected skin areas twice daily. Patients were evaluated before and after a 30-day course using the SCORAD and the Visual Analog Scale for assessment of pruritus intensity. Primary endpoint was improvement of AD according to SCORAD and clinical assessment. Secondary endpoint was patient satisfaction and improvement of pruritus.

Results

Mean SCORAD on day 0 was 32.61(range = 16.0-46.9) and decreased to 10.55 (range = 0-17.0) on day 30, reflecting a reduction of 67.6%. On day 30, all patients described significant improvement in pruritus and quality of sleep.

Conclusion

The application of the study product cream resulted in significant improvement of AD, as reflected by the objective SCORAD measurement, and the subjective assessment of pruritus and quality of life. This novel anti-inflammatory emollient product may emerge as a safe and effective therapeutic tool for all phases of AD without the adverse effects of chronic use of corticosteroids.

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Vaccines We Need But Don't Have

Viral Immunology , Vol. 0, No. 0.


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Association of Single-Nucleotide Polymorphisms in Immune-Related Genes with Development of Dengue Hemorrhagic Fever in a Mexican Population

Viral Immunology , Vol. 0, No. 0.


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Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8+ T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A + D

Viral Immunology , Vol. 0, No. 0.


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Correction to: Abstracts

Abstract

In Oral Free Paper Sessions, the first-author name was missing from the authorship group originally listed for Abstract OFP-04-012 (page S14), entitled "Differentiating primary pulmonary squamous cell carcinoma from squamous cell carcinoma of the cervix metastatic to the lung: Histological and immunohistochemistry study".

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Pharmacokinetics and drug-drug interactions of lopinavir/ritonavir administered with first and second-line antituberculosis drugs in HIV-infected children treated for multidrug-resistant tuberculosis [PublishAheadOfPrint]

Background Lopinavir/ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir/ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir/ritonavir and routine drugs used for MDR-TB treatment in HIV-infected children.

Methods A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 on MDR-TB treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin: and 16 without TB), who were established on a lopinavir/ritonavir-containing antiretroviral regimen.

Results One-compartment models with first-order absorption and elimination for both lopinavir and ritonavir were combined into an integrated model. The dynamic inhibitory effect of ritonavir concentration on lopinavir clearance was described using an Imax model. Even after adjusting for the effect of body weight with allometric scaling, large variability in lopinavir and ritonavir exposure was detected, together with strong correlations between the pharmacokinetic parameters of lopinavir and ritonavir. MDR-TB treatment did not have a significant effect on the bioavailability, clearance, or absorption rate constants of lopinavir or ritonavir. Most children (81% of MDR-TB; 88% of controls) achieved therapeutic lopinavir trough concentrations (>1 mg/L).

Conclusions No significant effect was found on key pharmacokinetic parameters of lopinavir or ritonavir when co-administered with routine drugs used for MDR-TB. These findings should be considered in the context of large inter-patient variability and the modest sample size.

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Ritonavir-boosted protease inhibitors but not cobicistat appear safe in HIV-positive patients ingesting dabigatran [PublishAheadOfPrint]

Patients with human immunodeficiency virus (HIV) have a near normal life expectancy and as a result are experiencing common age-related medical conditions (e.g., atrial fibrillation) and polypharmacy.1,2 ...

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Fungal prophylaxis with a gastro-resistant posaconazole tablet for patients with hematological malignancies: final result of the POSANANTES study. [PublishAheadOfPrint]

Posaconazole is an antifungal drug used in both prophylaxis and treatment of invasive fungal infections. Its oral formulation requires therapeutic drug monitoring. To overcome gastric acidity, a gastro-resistant posaconazole tablet has recently been developed. POSANANTES was a prospective non interventional study that aimed to monitor plasma concentration trough level (Cmin) of posaconazole tablets used prophylactically in patients with hematological malignancies. Fifty patients were included. Group A (n= 31) included patients receiving induction chemotherapy for myeloid malignancies and group B (n=19) included patients treated for graft versus host disease after allogeneic hematopoietic stem cells transplantation. In multivariate analysis, female sex, group B and evaluation of Cmin at D8 (versus any other day planned by the analysis) were associated with a higher Cmin, while diarrhea was associated with a lower Cmin (p<0.05). Thirty-four percent (n=17) of all included patients had to prematurely stop treatment, mainly in group A. In conclusion, this real-life prospective study showed good absorption of posaconazole tablets prophylaxis in patients with hematological malignancies even though this strategy was somewhat limited due to the high number of patients in group A who had to stop their treatment in an untimely fashion.

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Mutations in gene fusA1 as a novel mechanism of aminoglycoside resistance in clinical strains of Pseudomonas aeruginosa [PublishAheadOfPrint]

Resistance of clinical strains of Pseudomonas aeruginosa to aminoglycosides can result from production of transferable aminoglycoside-modifying enzymes, of 16S rRNA methylases, and/or mutational derepression of intrinsic multidrug efflux pump MexXY(OprM). The present study reports on characterization of a new type of mutants 4- to 8-fold more resistant to 2-deoxystreptamine derivatives (e.g., gentamicin, amikacin, tobramycin), as compared with wild-type strain PAO1. The genetic alterations of three in vitro mutants were mapped on fusA1, and found to result in single amino acid substitutions in domains II, III and V of elongation factor G (EF-G1A), a key component of translational machinery. Transfer of the mutated fusA1 alleles into PAO1 reproduced the resistance phenotype. Interestingly, fusA1 mutants with other amino acid changes in domains G, IV and V of EF-G1A were identified among clinical strains with decreased susceptibility to aminoglycosides. Allelic exchange experiments confirmed the relevance of these latter mutations and of three other previously reported alterations located in domains G and IV. Pump MexXY(OprM) was found to partly contribute to the resistance conferred by the mutated EF-G1A variants, and to have additive effects on aminoglycosides MICs when mutationally up-regulated. Altogether, our data demonstrate that cystic fibrosis (CF) and non-CF strains of P. aeruginosa can acquire a therapeutically significant resistance to important aminoglycosides, via a new mechanism involving mutations in elongation factor EF-G1A.

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Emergence of chromosome borne colistin resistance gene mcr-1 in clinical isolates of Klebsiella pneumoniae from India [PublishAheadOfPrint]

Transmissible colistin resistance gene, mcr-1 has breached the one of the last line of defense for treatment of infections caused by carbapenem-resistant Enterobacteriaceae....

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A promising anti-prion trimethoxychalcone binds to the globular domain of PrPC and changes its cellular location [PublishAheadOfPrint]

The search for anti-prion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein conversion into protease-resistant forms (PrP^Res or PrP^Sc) is a critical step in the development of TSEs, thus being one of the main targets in the screening for anti-prion compounds. In this work, three trimethoxychalcones (J1, J8, J20) and one oxadiazole (Y17), previously identified in vitro as potential anti-prion compounds, were evaluated through different approaches in order to gain inferences about their mechanism of action. None of them changed PrP^C mRNA levels in N2a cells as shown by RT-qPCR. Among them, J8 and Y17 were effective in RT-QuIC reactions using rodent rPrP^23--231 as substrate and PrP^Sc seeds from hamster and human brain. However, when rPrP^90--231, which lacks the N-terminal domain, was used as substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with PrP^C globular domain. J8 also reduced the fibrillation of mouse rPrP^23--231 seeded with in vitro-produced fibrils. Furthermore, most of the compounds decreased the amount of PrP^C on N2a cell surface by trapping this protein in the endoplasmic reticulum. Based on these results, we hypothesize that J8, a non-toxic promising anti-prion compound as previously shown, may act by different mechanisms, since its efficacy is attributable not only to the PrP conversion inhibition, but also to reduction of PrP^C content on the cell surface.

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Levofloxacin population pharmacokinetics in South African children treated for multidrug-resistant tuberculosis [PublishAheadOfPrint]

Background: Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited paediatric pharmacokinetic data to inform dose selection for children.

Methods: Children routinely receiving levofloxacin (250 mg adult tablets) for MDR-TB prophylaxis or disease in Cape Town, South Africa, underwent pharmacokinetic sampling following a 15 or 20 mg/kg dose, given as whole tablet(s) or crushed, orally, or by nasogastric tube. Pharmacokinetic parameters were estimated using non-linear mixed effects modelling. Model-based simulations were performed to estimate doses across weight bands that would achieve adult exposures with 750mg once-daily dosing.

Results: 109 children were included, median age 2.1 years (range 0.3–8.7); median weight 12 kg (range 6–22). Levofloxacin followed 2-compartment kinetics with 1st-order elimination and absorption with a lag time. After inclusion of allometric scaling, the model characterised age-driven maturation of clearance (CL) with an effect reaching 50% around 2 months after birth and 100% by 2 years of age.. CL in a typical child (12 kg, 2-year-old) was 4.7 L/h. HIV infection reduced CL by 16%. Using the adult 250 mg formulation, Levofloxacin exposures were substantially lower than those reported in adults receiving a similar mg/kg dose. To achieve adult-equivalent exposures at a 750 mg daily dose, higher levofloxacin paediatric doses may be required -from 18 mg/kg/day for younger children with weights 3-4 kg (due to immature clearance) to 40 mg/kg/day for older children.

Conclusions: Currently recommended doses of levofloxacin for MDR-TB in children result in exposures considerably lower than in adults. The effect of different formulations and formulation manipulation require further investigation.

We recommend age- and weight-banded doses of 250 mg tablets adult-formulation most likely to achieve target concentrations for prospective evaluation.

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Outcomes of vancomycin plus a {beta}-lactam versus vancomycin only for the treatment of methicillin-resistant Staphylococcus aureus bacteremia [PublishAheadOfPrint]

The objective of this retrospective study was to compare the rates of treatment failure, which was a composite of clinical and microbiologic failure, of patients receiving vancomycin and a β-lactam to those receiving vancomycin only for MRSA bacteremia. Patients 16 to 89 years of age with MRSA bacteremia admitted to a university-affiliated hospital from January 1^st, 2014 to December 31^st, 2016 were screened for study inclusion. Patients were eligible if they received >48 hours of vancomycin and a β-lactam (combination group) or vancomycin only (standard group) within 48 hours following bacteremia onset. 182 patients were screened: 47 were included in the standard group and 63 in the combination group. The combination group had a higher baseline body mass index (29.2 ± 8.0 kg/m² vs 25.8 ± 7.1 kg/m², p=0.022), acute physiologic assessment and chronic health evaluation-II (APACHE-II) score (median [interquartile range], 21 (15-26) vs 16 (10-22), p=0.003), and incidence of septic shock (31.8% vs 14.9%, p=0.047). Using multivariate analysis, combination therapy was the only variable that decreased treatment failures (odds ratio [95% confidence interval], 0.337 [0.142 to 0.997]), while vancomycin MIC >1 mg/L and male gender increased treatment failures (4.018 [1.297 to 12.444] and 2.971 [1.040 to 8.488], respectively). 30-day mortality rates (15.0% vs 14.9%, p=1.000) and incidence of adverse drug events (19.1% vs 23.4%, p=0.816) were not statistically different between the combination and standard groups. Combination therapy of vancomycin with a β-lactam led to significantly fewer treatment failures than vancomycin monotherapy for MRSA bacteremia.

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A Novel Mechanism of Inactivating Antibacterial Nitro Compounds in the Human Pathogen Staphylococcus aureus by Overexpression of a NADH-dependent Flavin Nitroreductase [PublishAheadOfPrint]

Recently, the nitro substituted bisquaternary bisnaphthalimides were reported to have substantial anti-infective activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Here, we selected resistant S. aureus clones by cultivation in increasing concentrations of the most active compound MT02. Interestingly, MT02 resistant variants induced a diffusible red color of the broth. Chromatographic and spectroscopic investigations revealed a stepwise reduction of the bisquaternary bisnaphthalimide nitro groups to amino groups. The corresponding derivatives were completely inactive against staphylococci. RNAseq experiments revealed a strong overexpression of a novel oxidoreductase in MT02 resistant strains. Deletion mutants of this enzyme did not produce the red color and were not able to develop resistance against bisquaternary bisnaphthalimides. Biochemical reactions confirmed a NADH-dependent deactivation of the nitro-substituted compounds. Thus, this is the first report of a nitroreductase-based antibiotic resistance mechanism in the human pathogen S. aureus.

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Use of Pharmacokinetic and Pharmacodynamic Analyses to Determine the Optimal Fixed Dosing Regimen of Iclaprim for Treatment of Serious Gram-Positive Infections [PublishAheadOfPrint]

Iclaprim is a bacterial dihydrofolate reductase inhibitor that is currently being evaluated in two Phase 3 trials for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Prior animal infection models studies suggest that the pharmacokinetic and pharmacodynamics (PK/PD) drivers for efficacy are area under the curve from 0-24 hours at steady state (AUC_0-24hss), AUC/minimum inhibitory concentration (MIC), and time above the MIC during the dosing interval (T > MIC) while QTc prolongation was associated to maximal concentration at steady state (C_maxss) in a thorough QTc Phase 1 study. Using PK data collected from 470 patients from the previously conducted Phase 3 complicated skin and skin infection (cSSSI) trials, population PK modeling and Monte Carlo simulation were used to identify a fixed iclaprim dosage regimen for its ongoing Phase 3 ABSSSI studies that maximized AUC_0-24hss, AUC/MIC, and T > MIC while minimizing probability of a C_maxss ≥ 800 ng/mL relative to the cSSSI regimen of 0.8 mg/kg intravenously infused over 0.5 hours, every 12 hours. The MCS analyses indicated that administration of 80 mg as a two hour infusion every 12 hours provides a 28%, 28%, and 32% increase in AUC_0-24hss, AUC,/MIC, & T > MIC, respectively, compared to the 0.8 mg/kg cSSSI regimen, while decreasing the probability of C_maxss ≥ 800 ng/mL by 9%. Based on PK/PD analyses, iclaprim 80 mg administered over two hours every 12 hours was selected as the dosing scheme for its subsequent Phase 3 clinical trials.

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CD101, a Novel Echinocandin Possesses Potent Anti-biofilm Activity Against Early and Mature Candida albicans Biofilms [PublishAheadOfPrint]

Currently available echinocandins are generally effective against Candida biofilms, but recent emergence of resistance has underscored the importance of developing new antifungal agents that are effective against biofilms. CD101 is a long-acting, novel echinocandin with distinctive pharmacokinetic properties and improved stability and safety relative to other drugs in the same class. CD101 is currently being evaluated as a once-weekly IV infusion for the treatment of candidemia and invasive candidiasis. In this study, we determined: (1) the effect of CD101 against early and mature phase biofilms formed by C. albicans in vitro, and (2) the temporal effect of CD101 on formation of biofilms using time lapse microscopy (TLM). Early or mature phase biofilms were formed on silicone elastomer discs and exposed to the test compounds for 24 h and quantified by measuring their metabolic activity. Separate batches were observed under confocal microscope or used to capture TLM images from 0 to 16 h. Metabolic activity showed that CD101 (0.25 or 1 μg/ml) significantly prevented adhesion phase cells to develop into mature biofilms (P = 0.0062 or 0.0064, respectively), and eradicated pre-formed mature biofilms (P = 0.04 or 0.01, respectively), compared to untreated controls. Confocal microscopy showed significant reduction in biofilm thickness for both early and mature phases (P < 0.05). TLM showed that CD101 stopped the growth of adhestion and early phase biofilms within minutes. CD101-treated hyphae failed to grow into mature biofilms. These results suggest that CD101 may be effective in prevention and treatment of biofilm-associated nosocomial infections.

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Synthesis of Methyl 4-(7-hydroxy-4,4,8-trimethyl-3-oxabicyclo[3.3.1]nonan-2-yl)benzoate and their evaluation as anti-leishmanial: Synergistic effect with Miltefosine [PublishAheadOfPrint]

In perpetuation of our interest in oxabicyclic compounds as potent anti-leishmanial, the present work deals with the chemical synthesis of new oxabicyclic derivative Methyl 4-(7-hydroxy-4,4,8-trimethyl-3-oxabicyclo[3.3.1]nonan-2-yl)benzoate (PS-207). This oxabicyclic derivative showed good anti-leishmanial effect on the parasite, both on promastigote and amastigote stages. The mode of parasitic death after PS-207 seems to be apoptotic. Interestingly, the combination of PS-207 with low dose of miltefosine showed synergistic effect against the parasite.

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Development of protective immunity in New Zealand White rabbits challenged with Bacillus anthracis spores and treated with antibiotics and obiltoxaximab, a monoclonal antibody against protective antigen [PublishAheadOfPrint]

Recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax Protective Antigen (PA) is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for treatment of inhalational anthrax. Because of spore latency, disease re-emergence after treatment cessation is a concern and there is a need to understand development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens. Here, acquired protective immunity was examined in NZW rabbits challenged with a targeted lethal dose of B. anthracis spores and treated with antibiotics, obiltoxaximab or a combination of both. Survivors of the primary challenge were re-challenged 9 month later, and monitored for survival. Survival rates after primary and re-challenge, for controls and animals treated with obiltoxaximab, levofloxacin or a combination of both were 0, 65, 100, 95% and 0, 100, 95, 89%, respectively. All surviving immune animals had circulating antibodies to PA and serum toxin neutralizing titers prior to re-challenge. Following re-challenge, systemic bacteremia and toxemia were not detected in most animals and levels of circulating anti-PA IgG titers increased starting 5 days post re-challenge. We conclude that treatment with obiltoxaximab, alone or combined with antibiotics, significantly improves survival of rabbits that received a lethal inhalation B. anthracis spore challenge and does not interfere with development of immunity. Survivors of primary challenge are protected against re-exposure, have rare incidents of systemic bacteremia and toxemia, and have evidence of an anamnestic response.

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Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-resistant Enterobacteriaceae in an In Vitro Hollow Fiber Model [PublishAheadOfPrint]

The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains when tested at an inocula of 10⁸ CFU/mL. Thirteen K. pneumoniae isolates, three Enterobacter cloacae isolates, and one Escherichia coli isolate were examined in an in vitro hollow fiber model over 32 hours. Simulated dosage regimens of meropenem 1-2 g with vaborbactam 1-2 g, meropenem administered every 8 hours by 3 hour infusion based on Phase 1 or Phase 3 patient pharmacokinetic data were studied in the model. Meropenem 2 g in combination with vaborbactam 2 g was bactericidal against K. pneumoniae, E. cloacae, and E. coli strains with meropenem-vaborbactam MICs of up to 8 mg/L. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in Phase 3 trials (24 h free AUC ~ 550 vs 320 mg*h/L in the Phase 1 studies), meropenem 2 g with vaborbactam 2 g was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/L. In addition, this level of vaborbactam, also suppressed the development of resistance observed using Phase 1 exposures. In this pharmacodynamic model, exposures similar to meropenem 2 g in combination with vaborbactam 2 g administered every 8 hours by 3 hour infusion in Phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem resistant, KPC producing strains of Enterobacteriaceae.

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The frequency and mechanism of spontaneous resistance to sulbactam combined with the novel {beta}-lactamase inhibitor ETX2514 in clinical isolates of Acinetobacter baumannii [PublishAheadOfPrint]

The novel diazabicyclooctenone ETX2514 is a potent, broad spectrum serine β-lactamase inhibitor that restores sulbactam activity against resistant Acinetobacter baumannii. The frequency of spontaneous resistance to sulbactam-ETX2514 in clinical isolates was found to be 7.6x10^-10 to <9.0x10^-10 at 4x MIC and mapped to residues near the active site of PBP3. Purified mutant PBP3 proteins demonstrated reduced affinity for sulbactam. In a sulbactam-sensitive isolate, resistance also mapped to stringent response genes associated with resistance to PBP2 inhibitors, suggesting that, in addition to β-lactamase inhibition, ETX2514 may also enhance sulbactam activity in A. baumannii via inhibition of PBP2.

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Copper ions and coordination complexes as novel carbapenem adjuvants [PublishAheadOfPrint]

Carbapenem-resistant Enterobacteriaceae are an urgent threat to global human health. These organisms produce β-lactamases with carbapenemase activity, such as the metallo-β-lactamase NDM-1, which is notable due to its association with mobile genetic elements and the lack of a clinically useful inhibitor. Here we examined the ability of copper to inhibit the activity of NDM-1 and explored the potential of a copper coordination complex as a mechanism to efficiently deliver copper as an adjuvant in clinical therapeutics. An NDM-positive Escherichia coli isolate, MS6192, was cultured from the urine of a patient with urinary tract infection. MS6192 was resistant to antibiotics from multiple classes, including diverse β-lactams (penicillins, cephalosporins, and carbapenems), aminoglycosides and fluoroquinolones. However, in the presence of copper (range 0-2 mM), the susceptibility of MS6192 to the carbapenems ertapenem and meropenem increased significantly. In standard checkerboard assays, copper decreased the MIC of ertapenem and meropenem against MS6192 in a dose-dependent manner, suggesting a synergistic mode of action. To examine the inhibitory effect of copper in the absence of other β-lactamases, the bla_NDM-1 gene from MS6192 was cloned and expressed in a recombinant E. coli K-12 strain. Analysis of cell-free extracts prepared from this strain revealed copper directly inhibits NDM-1 activity, and this was further confirmed using purified recombinant NDM-1. Finally, delivery of copper at a low concentration of 10 μM using the FDA-approved coordination complex copper-pyrithione sensitised MS6192 to ertapenem and meropenem in a synergistic manner. Overall, this work demonstrates the potential use of copper-coordination complexes as novel carbapenemase adjuvants.

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What is resistance? Impact of phenotypic versus molecular drug resistance testing on multi- and extensively drug-resistant tuberculosis therapy [PublishAheadOfPrint]

Rapid and accurate drug-susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using BACTEC 960 MGIT or Löwenstein-Jensen to construct M/XDR-TB treatment regimens for a cohort of 25 consecutive M/XDR-TB patients and 15 possible anti-TB drugs.

Genotypic DST results from Cepheid GeneXpert MTB/RIF (Xpert) and line probe assays (LPAs: Hain GenoType MTBDRplus 2.0 and MTBDRsl 2.0)] and whole genome sequencing (WGS) were translated into individual algorithm-derived treatment regimens for each patient. We further analysed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results.

Compared with pDST, the average agreement in the number of drugs prescribed in 'genotypic' regimens ranged from just 49% (95% CI 39-59%) for Xpert and 63% (95% CI 56-70%) for LPAs to 93% (95% CI 88-98%) for WGS. Only the WGS regimens did not comprise any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampicin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high.

WGS can be used to rule-in resistance even in M/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be re-examined to avoid systematic false-susceptible results in low-level resistant isolates.

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Interspecies transmission of the blaOXA-48 gene from Klebsiella pneumoniae high-risk clone ST147 to different Escherichia coli clones in the gut microbiota [PublishAheadOfPrint]

OXA-48—producing K. pneumoniae (OXA-Kpn) have quickly spread in Spain and other European countries (1)....

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Efficacy of Tilorone Dihydrochloride against Ebola Virus Infection [PublishAheadOfPrint]

Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug that is used clinically as an antiviral outside of the US. A machine learning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone as a potent in vitro EBOV inhibitor, making it a candidate for the treatment of Ebola virus disease (EVD). In the present study, a series of in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated the drug has excellent solubility, high Caco-2 permeability, was not a P-glycoprotein substrate and had no inhibitory activity against five human CYP450 enzymes (3A4, 2D6, 2C19, 2C9 and 1A2). Tilorone was shown to have 52% human plasma protein binding with excellent plasma stability and a mouse liver microsome half-life of 48 minutes. Dose range-finding studies in mice demonstrated a maximum tolerated single dose of 100 mg/kg. A pharmacokinetics study in mice at 2 and 10 mg/kg dose levels showed that the drug is rapidly absorbed, has dose-dependent increases in C_max and AUC values with a half-life of approximately 18 hours in both males and females, although the exposure was ~2.5-fold higher in male mice. Tilorone doses of 25 and 50 mg/kg proved efficacious in protecting 90% of mice from a lethal challenge with mouse-adapted EBOV (maEBOV) with once daily intraperitoneal (ip) dosing for 8 days. A subsequent study showed that 30 mg/kg/day of tilorone given ip starting 2 or 24 hours post-challenge and continuing through Day 7 post infection was fully protective, indicating promising activity for the treatment of EVD.

http://ift.tt/2hp6hob

Discovery of new inhibitors of Toxoplasma gondii thanks to the Pathogen Box [PublishAheadOfPrint]

Toxoplasma gondii is a cosmopolitan protozoan parasite which affects approximately 30% of the population worldwide. The drugs currently used against toxoplasmosis are few in number and show several limitations, such as a drug intolerance, poor bioavailability or drug resistance mechanism developed by the parasite. Thus it is important to find new compounds able to inhibit parasite invasion or proliferation. In this study, the 400 compounds of the open access Pathogen Box provided by the Medicines for Malaria Venture (MMV) foundation were screened for their anti-Toxoplasma gondii activity. A preliminary in vitro screening performed over 72 hours by an enzyme-linked immunosorbent assay (ELISA) revealed fifteen interesting compounds that were effective against T. gondii at 1 μM. Their cytotoxicity was estimated on Vero cells and their 50% inhibitory concentration (IC₅₀) values were further calculated. As a result, eight anti-Toxoplasma gondii compounds with an IC₅₀ value lesser than 2 μM and a selectivity index (SI) value greater than 4 were identified. The most active was MMV675968, showing an IC₅₀ of 0.02 μM and a selectivity index value equal to 275. Two other compounds, MMV689480 and MMV687807, also showed a good activity against T. gondii with IC₅₀ values of 0.10 μM (SI = 86.6) and 0.15 μM (SI = 11.3), respectively. Structure-activity relationships for the eight selected compounds were also discussed on the basis of fingerprinting similarity measurements using the Tanimoto method. The anti-Toxoplasma gondii compounds highlighted here represent potential candidates for the development of new drugs that could be used against toxoplasmosis.

http://ift.tt/2zFZPDk

Interaction of zearalenone with bovine serum albumin as determined by fluorescence quenching

Abstract

The major aim of this study was to examine the binding of zearalenone (ZEN) to bovine serum albumin (BSA) by measuring the quenching of the intrinsic fluorescence of the protein under aqueous conditions. The results suggest that ZEN has a strong ability to quench the intrinsic fluorescence of BSA through a static mechanism. The hydrophobicity of the microenvironment around the tyrosine (Tyr) residues in BSA was increased in the presence of ZEN. The quenching constants, ratio of protein with ZEN, and thermodynamic parameters were determined. The collaborative action of hydrophobic and electrostatic interactions was involved in the binding process and the formation of the complex was mainly enthalpy-driven. The average binding distance between ZEN and BSA was calculated to be 2.20 nm. This is much closer in magnitude than the distance reported for the binding of most toxins to HSA and most pharmaceuticals to BSA, indicating a strong affinity.

http://ift.tt/2yxOrX5

ACS NSQIP risk calculator reliability in head and neck oncology: The effect of prior chemoradiation on NSQIP risk estimates following laryngectomy

To determine whether inclusion of chemoradiation history increases estimated risk for complications following total laryngectomy using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator.

http://ift.tt/2AH5aZe

Ohrmuschelplastik der Dysplasie Grad I

Laryngo-Rhino-Otol 2017; 96: 797-807
DOI: 10.1055/s-0043-119044

Die Korrektur der Ohrmuscheldysplasie Grad I gehört zu den häufigsten ästhetischen Eingriffen im HNO-Gebiet. In den allermeisten Fällen liegt eine komplexe Pathologie von Anthelix, Cavum conchae und/oder Lobulus vor. Der Operateur muss deshalb nach einer genauen Analyse der Pathologie aus den verschiedenen Korrekturmöglichkeiten nach dem „Baukastenprinzip" die für das spezielle Problem geeignetsten Operationstechniken auswählen können.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2AF59oR

Nasenmuscheloperation: Welche olfaktorischen Leistungen werden eingeschränkt

Laryngo-Rhino-Otol 2017; 96: 753-754
DOI: 10.1055/s-0043-119601

Konstantinidis I et al. Intranasal trigeminal function in patients with empty nose syndrome. Laryngoscope 2017;127: 1263–1267 Das trigeminale System vermittelt die Wahrnehmung des nasalen Luftflusses. Eine griechische Arbeitsgruppe hat nun in einer Studie untersucht, inwieweit bei „Syndrom der leeren Nase"-Patienten (Empty Nose Syndrome, ENS) die geschädigte intranasale Trigeminusfunktion Teil einer paradoxen Nasenatmungsbehinderung ist.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Ungewöhnlicher Verlauf eines stumpfen Traumas der Halsregion im Rahmen eines Sportunfalles

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-119757

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

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Narrow Band Imaging (NBI) zur Früherkennung von Zweitkarzinomen

Laryngo-Rhino-Otol 2017; 96: 754-755
DOI: 10.1055/s-0043-119566

Tirelli G et al. Follow-up of oral and oropharyngeal cancer using narrow-band imaging and high-definition television with rigid endoscope to obtain an early diagnosis of second primary tumors: a prospective study. Eur Arch Otorhinolaryngol 2017; 274: 2529–2536 Italienische Wissenschaftler testeten, inwieweit nach einer Behandlung von oralen Karzinomen und Tumoren des Oropharynx mit einer starren Endoskopie mit NBI-Licht Zweittumore oder lokale Rezidive besser detektierbar sind als mit Weißlicht-Endoskopie (WLE). Darüber hinaus untersuchten sie inwieweit vorherige Radiotherapie, Läsionsseite und Lernkurve die NBI-Leistung zur Detektion mukosaler Gefäßveränderungen tangiert.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Rhinoplastik

Laryngo-Rhino-Otol 2017; 96: 810-813
DOI: 10.1055/s-0043-119386

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

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Idiopathische subglottische Stenose: Rezidivwahrscheinlichkeit unverändert

Laryngo-Rhino-Otol 2017; 96: 755-756
DOI: 10.1055/s-0043-119935

Aarnæs MT et al. Idiopathic subglottic stenosis: an epidemiological single-center study. Eur Arch Otorhinolaryngol 2017; 274: 2225–2228 Wissenschaftler der HNO-Klinik der Universität Oslo untersuchten Inzidenz, Management und Behandlungsergebnisse der idiopathischen subglottischen Stenose.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Aus der Gutachtenpraxis: Die Begutachtung der Facialisparese in der österreichischen privaten Unfallversicherung

Laryngo-Rhino-Otol 2017; 96: 792-796
DOI: 10.1055/s-0043-119592

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Koniotomie

Laryngo-Rhino-Otol 2017; 96: 757-758
DOI: 10.1055/s-0043-119561

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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http://ift.tt/2yybVeG

Fragen für die Facharztprüfung

Laryngo-Rhino-Otol 2017; 96: 808-809
DOI: 10.1055/s-0043-119804

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2AGXpCv

Hörverlust und Sprachverstehen im Alter

Laryngo-Rhino-Otol 2017; 96: 759-764
DOI: 10.1055/s-0043-119388

Das Verstehen von Sprache bei Hintergrundgeräuschen bereitet vielen älteren Menschen Probleme. In der klinischen Praxis wird diese Qualität des Hörvermögens durch Sprachtests im Störgeräusch untersucht. Die Studie HÖRSTAT setzte den Göttinger Satztest (GÖSA) im Störgeräusch zusätzlich zur Tonaudiometrie und einer Befragung bei einer Zufallsstichprobe aus der Allgemeinbevölkerung ein. Wie erwartet nahm der Anteil Schwerhörender ab ca. 60 Jahren stark zu. Bei Ausschluss sehr hoher Hörverluste waren im Alter von 60–85 Jahren jedoch 68 % von 553 Probanden nach dem WHO-Kriterium als normalhörend einzustufen. Von diesen erreichte im GÖSA allerdings nur jeder Dritte annähernd das Sprachverstehen im Störgeräusch junger Normalhörender. Die Selbsteinschätzung des Hörvermögens folgte dabei nur eingeschränkt der messbaren Verschlechterung. Ab einem Alter von ca. 70 Jahren wurden die eigenen Hör-Fähigkeiten eher über- und die Defizite unterschätzt.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Kommentar der Schriftleitung

Laryngo-Rhino-Otol 2017; 96: 750-751
DOI: 10.1055/s-0043-122090

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

http://ift.tt/2AE5NTn

Tablet-based sublingual immunotherapy for respiratory allergy

Publication date: Available online 13 November 2017
Source:Allergologia et Immunopathologia
Author(s): L. Prieto
Allergic respiratory disease represents a significant and expanding health problem worldwide. The gold standard of therapeutic intervention is still grucocorticosteroids, although they are not effective in all patients and may cause side effects. Allergen Immunotherapy has been administrated as subcutaneous injections for treatment of allergic rhinoconjunctivitis and asthma and has been practiced for the past century. Sublingual immunotherapy (SLIT) tablets are now available for grass- or ragweed-induced rhinoconjunctivitis and will be available in Spain for house dust mite (HDM)-induced rhinoconjunctivitis and asthma in the next months. In this review, new developments in the field of tablet-based SLIT for respiratory allergy are summarized, with special emphasis on HDM-induced allergic rhinitis and asthma. SLIT tablets are the best-documented immunotherapy products on the market and represent a more patient-friendly concept because they can be self-administrated at home.



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Und sie bewegt sich doch!

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Combined use of high doses of vasopressin and corticosteroids in a patient with Crohn’s disease with refractory septic shock after intestinal perforation: a case report

In this article, we present a clinical case of refractory septic shock resulting from intestinal perforation treated with high doses of vasopressin and hydrocortisone during emergency surgery.

http://ift.tt/2yYJHhe

Change over time in the rates of adverse events in patients receiving systemic therapy for psoriasis: a cohort study

http://ift.tt/2zDZSj2

Validity and Accuracy of a Mobile Phone Application for the Assessment of Wounds in Recessive Dystrophic Epidermolysis Bullosa

http://ift.tt/2yYaIkY

The role of T helper 25 (Th25) cells in the immune response to M. leprae

http://ift.tt/2yXb9vT

Rituximab as first line adjuvant in pemphigus: retrospective analysis of the long-term outcomes in a single center

http://ift.tt/2mksIQs

All cause mortality in patients with basal and squamous cell carcinoma: A systematic review and meta-analysis

There are varying reports of the association of basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (SCC) with all-cause mortality.Patients with a history of SCC have an approximately 25% increased risk of all-cause mortality compared to the general population CC may be a clinical marker of a decline in health

http://ift.tt/2mrdxFx

Soft palate reconstruction after radionecrosis: Combined anterolateral thigh adipofascial and nasoseptal flaps

Although radiation-based treatment for nasopharyngeal cancer may achieve excellent long term oncologic results, late effects of therapy may lead to soft tissue radionecrosis and velopharyngeal insufficiency (VPI). Repair of these oro- and nasopharyngeal defects presents a complex reconstructive challenge. We present a case of a long-term survivor treated with chemoradiotherapy for nasopharyngeal cancer who developed progressive dysphagia, velopharyngeal insufficiency, and radionecrosis of the nasopharynx and soft palate, leading to tracheostomy and gastrostomy tube dependence.

http://ift.tt/2mns70y

Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms

Abstract

In 1983, a monoclonal antibody, Ki67, was generated, that labeled the nuclei of proliferating non-neoplastic and neoplastic cells. The name Ki67 derived from the city of Kiel (Ki) where the antibody was produced in the university department of pathology and refers to the number of the original clone (67). Systematic assessment of the proliferative activity of tumors using Ki67 started in the 1990s, when Ki67, which only worked on frozen tissue, was complemented by the antibody MIB-1 that also worked in formalin-fixed tissues. Pancreatic neuroendocrine neoplasms (PanNENs) were the first endocrine tumors whose proliferative activity was assessed with Ki67. This approach was so successful that Ki67 was included as prognostic marker in the 2000 and 2004 WHO classifications of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In 2010, the WHO classification of GEP-NENs introduced a three-tiered grading, originally proposed by ENETS in 2006 that was mainly based on the Ki67 index. As it has subsequently been shown that the Ki67 index is the most reliable factor in the prognostic evaluation of GEP-NENs, especially of PanNENs, the 2017 WHO classification of PanNENs requires its use and strongly recommends exact assessment of the proportion Ki67-labeled cells as basis for the calculation of the Ki67 index. Problems in assessing the Ki67 index include intertumoral and intratumoral staining heterogeneity and counting methods. Despite such problems, the Ki67 index has emerged as indispensable for the prognostic and therapeutic stratification of the majority of GEP-NENs and can barely be replaced by counting mitoses. In future, however, it can be anticipated that the Ki67 cut-offs experience refinement in relation to the type of tumor, its location, and its response to therapy. It is also possible that the prognostic risk of an individual tumor is calculated for each Ki67 unit and not for an "a priori" fixed Ki67 class.

http://ift.tt/2mqpMCe

Selected Literature Watch

Violence and Gender , Vol. 0, No. 0.


http://ift.tt/2mnQpaz

Trump Picks Ex-Pharma Exec Alex Azar to Head HHS

Azar, who served in HHS before, will be Trump's point person for reducing the cost of prescription drugs.
Medscape Medical News

http://ift.tt/2zTugHp

How Trump's Tax Plan Could Affect Doctors

The impending tax overhaul may still change, but here's how the elements of the proposed plans could affect physicians.
Medscape Business of Medicine

http://ift.tt/2zG1XsQ

Synchronized Spontaneous Otoacoustic Emissions Provide a Signal-to-Noise Ratio Advantage in Medial-Olivocochlear Reflex Assays

Abstract

Detection of medial olivocochlear-induced (MOC) changes to transient-evoked otoacoustic emissions (TEOAE) requires high signal-to-noise ratios (SNR). TEOAEs associated with synchronized spontaneous (SS) OAEs exhibit higher SNRs than TEOAEs in the absence of SSOAEs, potentially making the former well suited for MOC assays. Although SSOAEs may complicate interpretation of MOC-induced changes to TEOAE latency, recent work suggests SSOAEs are not a problem in non-latency-dependent MOC assays. The current work examined the potential benefit of SSOAEs in TEOAE-based assays of the MOC efferents. It was hypothesized that the higher SNR afforded by SSOAEs would permit detection of smaller changes to the TEOAE upon activation of the MOC reflex. TEOAEs were measured in 24 female subjects in the presence and absence of contralateral broadband noise. Frequency bands with and without SSOAEs were identified for each subject. The prevalence of TEOAEs and statistically significant MOC effects were highest in frequency bands that also contained SSOAEs. The median TEOAE SNR in frequency bands with SSOAEs was approximately 8 dB higher than the SNR in frequency bands lacking SSOAEs. After normalizing by TEOAE amplitude, MOC-induced changes to the TEOAE were similar between frequency bands with and without SSOAEs. Smaller MOC effects were detectable across a subset of the frequency bands with SSOAEs, presumably due to a higher TEOAE SNR. These findings demonstrate that SSOAEs are advantageous in assays of the MOC reflex.

http://ift.tt/2ic6wDA

Aminoglycoside Damage and Hair Cell Regeneration in the Chicken Utricle

Abstract

In this study, we present a systematic characterization of hair cell loss and regeneration in the chicken utricle in vivo. A single unilateral surgical delivery of streptomycin caused robust decline of hair cell numbers in striolar as well as extrastriolar regions, which in the striola was detected very early, 6 h post-insult. During the initial 12 h of damage response, we observed global repression of DNA replication, in contrast to the natural, mitotic hair cell production in undamaged control utricles. Regeneration of hair cells in striolar and extrastriolar regions occurred via high rates of asymmetric supporting cell divisions, accompanied by delayed replenishment by symmetric division. While asymmetric division of supporting cells is the main regenerative response to aminoglycoside damage, the detection of symmetric divisions supports the concept of direct transdifferentiation where supporting cells need to be replenished after their phenotypic conversion into new hair cells. Supporting cell divisions appear to be well coordinated because total supporting cell numbers throughout the regenerative process were invariant, despite the initial large-scale loss of hair cells. We conclude that a single ototoxic drug application provides an experimental framework to study the precise onset and timing of utricle hair cell regeneration in vivo. Our findings indicate that initial triggers and signaling events occur already within a few hours after aminoglycoside exposure. Direct transdifferentiation and asymmetric division of supporting cells to generate new hair cells subsequently happen largely in parallel and persist for several days.

http://ift.tt/2zVZEVA

Safety Outcomes Following Spine and Cranial Neurosurgery: Evidence From the National Surgical Quality Improvement Program.

Background: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was used to establish predictors for 30-day postoperative complications following spine and cranial neurosurgery. Materials and Methods: The ACS-NSQIP participant use files were queried for neurosurgical cases between 2005 and 2015. Prevalence of postoperative complications following neurosurgery was determined. Nested multivariable logistic regression analysis was used to identify demographic, comorbidity, and perioperative characteristics associated with any complication and mortality for spine and cranial surgery. Results: There were 175,313 neurosurgical cases (137,029 spine, 38,284 cranial) identified. A total of 23,723 (13.5%) patients developed a complication and 2588 (1.5%) patients died. Compared with spine surgery, cranial surgery had higher likelihood of any complication (22.2% vs. 11.1%; P

http://ift.tt/2zHYKJw

Phenytoin-induced Excessive Sedation During Awake Craniotomy: An Unusual Observation.

No abstract available

http://ift.tt/2iRKvtD

Complement in the pathogenesis of Alzheimer’s disease

Abstract

The emergence of complement as an important player in normal brain development and pathological remodelling has come as a major surprise to most scientists working in neuroscience and almost all those working in complement. That a system, evolved to protect the host against infection, should have these unanticipated roles has forced a rethink about what complement might be doing in the brain in health and disease, where it is coming from, and whether we can, or indeed should, manipulate complement in the brain to improve function or restore homeostasis. Complement has been implicated in diverse neurological and neuropsychiatric diseases well reviewed elsewhere, from depression through epilepsy to demyelination and dementia, in most complement drives inflammation to exacerbate the disease. Here, I will focus on just one disease, the most common cause of dementia, Alzheimer's disease. I will briefly review the current understanding of what complement does in the normal brain, noting, in particular, the many gaps in understanding, then describe how complement may influence the genesis and progression of pathology in Alzheimer's disease. Finally, I will discuss the problems and pitfalls of therapeutic inhibition of complement in the Alzheimer brain.

http://ift.tt/2zDU75g

Synchronized Spontaneous Otoacoustic Emissions Provide a Signal-to-Noise Ratio Advantage in Medial-Olivocochlear Reflex Assays

Abstract

Detection of medial olivocochlear-induced (MOC) changes to transient-evoked otoacoustic emissions (TEOAE) requires high signal-to-noise ratios (SNR). TEOAEs associated with synchronized spontaneous (SS) OAEs exhibit higher SNRs than TEOAEs in the absence of SSOAEs, potentially making the former well suited for MOC assays. Although SSOAEs may complicate interpretation of MOC-induced changes to TEOAE latency, recent work suggests SSOAEs are not a problem in non-latency-dependent MOC assays. The current work examined the potential benefit of SSOAEs in TEOAE-based assays of the MOC efferents. It was hypothesized that the higher SNR afforded by SSOAEs would permit detection of smaller changes to the TEOAE upon activation of the MOC reflex. TEOAEs were measured in 24 female subjects in the presence and absence of contralateral broadband noise. Frequency bands with and without SSOAEs were identified for each subject. The prevalence of TEOAEs and statistically significant MOC effects were highest in frequency bands that also contained SSOAEs. The median TEOAE SNR in frequency bands with SSOAEs was approximately 8 dB higher than the SNR in frequency bands lacking SSOAEs. After normalizing by TEOAE amplitude, MOC-induced changes to the TEOAE were similar between frequency bands with and without SSOAEs. Smaller MOC effects were detectable across a subset of the frequency bands with SSOAEs, presumably due to a higher TEOAE SNR. These findings demonstrate that SSOAEs are advantageous in assays of the MOC reflex.

http://ift.tt/2ic6wDA

Aminoglycoside Damage and Hair Cell Regeneration in the Chicken Utricle

Abstract

In this study, we present a systematic characterization of hair cell loss and regeneration in the chicken utricle in vivo. A single unilateral surgical delivery of streptomycin caused robust decline of hair cell numbers in striolar as well as extrastriolar regions, which in the striola was detected very early, 6 h post-insult. During the initial 12 h of damage response, we observed global repression of DNA replication, in contrast to the natural, mitotic hair cell production in undamaged control utricles. Regeneration of hair cells in striolar and extrastriolar regions occurred via high rates of asymmetric supporting cell divisions, accompanied by delayed replenishment by symmetric division. While asymmetric division of supporting cells is the main regenerative response to aminoglycoside damage, the detection of symmetric divisions supports the concept of direct transdifferentiation where supporting cells need to be replenished after their phenotypic conversion into new hair cells. Supporting cell divisions appear to be well coordinated because total supporting cell numbers throughout the regenerative process were invariant, despite the initial large-scale loss of hair cells. We conclude that a single ototoxic drug application provides an experimental framework to study the precise onset and timing of utricle hair cell regeneration in vivo. Our findings indicate that initial triggers and signaling events occur already within a few hours after aminoglycoside exposure. Direct transdifferentiation and asymmetric division of supporting cells to generate new hair cells subsequently happen largely in parallel and persist for several days.

http://ift.tt/2zVZEVA

Rhumatisme psoriasique en France, du nourrisson à la personne âgée : données de deux études transversales multicentriques

Publication date: Available online 13 November 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Galezowski, F. Maccari, S. Hadj-Rabia, M.-L. Sigal, A. Phan, M. Lahfa, A.-C. Bursztejn, H. Barthélémy, F. Boralévi, Z. Reguiai, C. Chiavérini, E. Estève, E. Bourrat, M. Ruer-Mulard, A. Beauchet, E. Mahé
IntroductionLe rhumatisme psoriasique touche 20 à 30 % des patients atteints de psoriasis cutané. Peu de données épidémiologiques sont disponibles en France sur sa prévalence, ses associations avec l'atteinte dermatologique et ses comorbidités.ObjectifsÉvaluer les aspects épidémiologiques et associations cliniques et épidémiologiques du rhumatisme psoriasique chez les enfants et les adultes, en France.MéthodesDeux études transversales, multicentriques ont été menées en France chez les enfants (χ-Psocar, 23 centres de dermatologie pédiatrique membres du GR SFDP, 1 an) et les adultes (Resopsocar, 29 centres de dermatologie membres du GEM RESOPSO, 4 mois) pour étudier les comorbidités cardiovasculaires et métaboliques du psoriasis.RésultatsParmi les 313 enfants (garçons : 47,6 % ; âge moyen, 9,4 ans) et 1954 adultes (hommes : 56,0 % ; âge moyen : 48,5 ans) atteints de psoriasis, 4,2 % des enfants et 21,0 % des adultes souffraient de rhumatisme psoriasique. La prévalence augmentait avec l'âge : 2,2 % des enfants, 14,2 % des adolescents et plus de 20 % après 40 ans. Elle diminuait après 70 ans (19,4 %). Quel que soit l'âge, le sexe n'était pas associé au rhumatisme psoriasique. Chez les enfants, le rhumatisme était associé à l'atteinte unguéale (p=0,04) et à la sévérité de la maladie (p=0,0004). Chez les adultes il était associé au psoriasis en plaques (p=0,002), à la sévérité de la maladie (p<0,0001) et à l'obésité (p<0,0001). Le psoriasis en plaques localisé (cuir chevelu, psoriasis palmo-plantaire par exemple) était moins souvent associé au rhumatisme psoriasique (p<0,05).ConclusionsCes deux études transversales menées en France sur 2267 patients, principalement hospitaliers, donnent une idée de la prévalence du rhumatisme psoriasique tout au long de la vie. La prévalence augmente progressivement avec l'âge, sans différence de genre, avant de diminuer chez les personnes âgées. Nous confirmons l'association avec l'onychopathie psoriasique dès l'enfance et avec l'obésité chez les adultes.BackgroundPsoriatic arthritis affects 20–30% of patients with psoriasis. Few epidemiological data are available in France about its prevalence and its association with skin lesions and comorbidities.ObjectivesTo assess the epidemiological aspects and the risk factors for psoriatic arthritis in children and adults in France.MethodsTwo cross-sectional studies were conducted in France in children (χ-Psocar, 23 pediatric dermatology centers belonging to the SFDP, 1 year) and adults (Resopsocar, 29 dermatology centers belonging to GEM RESOPSO, 4 months) to study the link between psoriasis and cardiovascular and metabolic comorbidities.ResultsThree hundred and thirteen children (males: 47.6%; mean age: 9.4 yrs) and 1,954 adults (males: 56.0%; mean age: 48.5 yrs) with psoriasis were included, with 4.2% of the children and 21.0% of the adults presenting psoriatic arthritis. Prevalence increased with age: 2.2% of children, 14.2% of adolescents, and over 20% after 40 years. It decreased after the age of 70 years (19.4%). Regardless of age, arthritis was not associated with gender. In the children's group, rheumatism was associated with nail involvement (P=0.04) and disease severity (P=0.0004). Adult rheumatism was associated with generalized plaque psoriasis (P=0.002), disease severity (P<0.0001), and obesity (P<0.0001). Localized plaque psoriasis was less often associated with arthritis (P<0.05).ConclusionsThese two cross-sectional studies conducted in 2267 patients in France yielded information on the prevalence of joint involvement from infants to elderly subjects. It is the first study conducted in a single population to provide data for the whole population. Prevalence gradually increases with age, without gender difference, before decreasing in old age. We confirm the association of nail involvement in the first years of life, and of obesity in adults.



http://ift.tt/2ABX7wf

Use of a Non-ICU Specialty Ward For Immediate Post-operative Management of Head and Neck Free Flap

Conditions:   Head and Neck Cancer;   Head and Neck Squamous Cell Carcinoma;   Head and Neck Carcinoma;   Trauma
Intervention:   Other: Non-ICU Specialty ward
Sponsor:   Arnaud Bewley
Recruiting

http://ift.tt/2zEBs9l

Multiorgan Metabolic Imaging Response Assessment of Abemaciclib

Conditions:   Esophageal Adenocarcinoma;   Esophagus SCC;   Cholangiocarcinoma;   Urothelial/Bladder Cancer, Nos;   Endometrial Cancer
Intervention:   Drug: Abemaciclib
Sponsors:   Jules Bordet Institute;   Eli Lilly and Company
Not yet recruiting

http://ift.tt/2hqarfs

Melanoma tumors exhibit a variable but distinct metabolic signature

http://ift.tt/2ic7Ru9

Life cycle assessment of optimised chemical looping air separation systems for electricity production

Tagliaferri, C; Görke, R; Scott, S; Dennis, J; Lettieri, P; (2017) Life cycle assessment of optimised chemical looping air separation systems for electricity production. Chemical Engineering Research and Design (In press).

http://ift.tt/2jne7D5

Spoiling for a fight: B lymphocytes as initiator and effector populations within tertiary lymphoid organs in autoimmunity and transplantation

Alsughayyir, J; Pettigrew, GJ; Motallebzadeh, R; (2018) Spoiling for a fight: B lymphocytes as initiator and effector populations within tertiary lymphoid organs in autoimmunity and transplantation. Frontiers in Immunology (In press).

http://ift.tt/2huseFV

Compulsivity Reveals a Novel Dissociation between Action and Confidence

Vaghi, MM; Luyckx, F; Sule, A; Fineberg, NA; Robbins, TW; De Martino, B; (2017) Compulsivity Reveals a Novel Dissociation between Action and Confidence. Neuron , 96 (2) 348-354.e4. 10.1016/j.neuron.2017.09.006 . Green open access

http://ift.tt/2jne3mP

The role of the ER stress response protein PERK in rhodopsin retinitis pigmentosa

Athanasiou, D; Aguila, M; Bellingham, J; Kanuga, N; Adamson, P; Cheetham, ME; (2017) The role of the ER stress response protein PERK in rhodopsin retinitis pigmentosa. Human Molecular Genetics 10.1093/hmg/ddx370 . (In press). Green open access

http://ift.tt/2hw2toM

Multi-arm Clinical Trials – Teams within Teams

Langley, RE; Mason, MD; (2017) Multi-arm Clinical Trials – Teams within Teams. [Editorial comment]. Clinical Oncology 10.1016/j.clon.2017.10.001 . (In press).

http://ift.tt/2jnuFuo

Autonomous vision-guided bi-manual grasping and manipulation

Rastegarpanah, Alireza; (2017) Autonomous vision-guided bi-manual grasping and manipulation. In: Proceedings of Advanced Robotics and its Social Impacts (ARSO). IEEE Xplore: Austin, TX, USA. Green open access

http://ift.tt/2hwtPeu

miR-200 family controls late steps of postnatal forebrain neurogenesis via Zeb2 inhibition

Beclin, C; Follert, P; Stappers, E; Barral, S; Nathalie, C; de Chevigny, A; Magnone, V; ... Cremer, H; + view all Beclin, C; Follert, P; Stappers, E; Barral, S; Nathalie, C; de Chevigny, A; Magnone, V; Lebrigand, K; Bissels, U; Huylebroeck, D; Bosio, A; Barbry, P; Seuntjens, E; Cremer, H; - view fewer (2016) miR-200 family controls late steps of postnatal forebrain neurogenesis via Zeb2 inhibition. SCIENTIFIC REPORTS , 6 , Article 357. 10.1038/srep35729 . Green open access

http://ift.tt/2jm82Xp

HIV prevention trial design in an era of effective pre-exposure prophylaxis

Cutrell, A; Donnell, D; Dunn, DT; Glidden, DV; Grobler, A; Hanscom, B; Stancil, BS; ... Cuffe, RL; + view all Cutrell, A; Donnell, D; Dunn, DT; Glidden, DV; Grobler, A; Hanscom, B; Stancil, BS; Meyer, RD; Wang, R; Cuffe, RL; - view fewer (2017) HIV prevention trial design in an era of effective pre-exposure prophylaxis. HIV Clinical Trials 10.1080/15284336.2017.1379676 . (In press). Green open access

http://ift.tt/2hw21ac

Variational-based segmentation of bio-pores in tomographic images

Bauer, B; Cai, X; Peth, S; Schladitz, K; Steidl, G; (2017) Variational-based segmentation of bio-pores in tomographic images. Computers & Geosciences , 98 pp. 1-8. 10.1016/j.cageo.2016.09.013 .

http://ift.tt/2jndLwf

running into each other: run! run! run! a festival and a collaboration

Latham, A; Tan, KS; (2017) running into each other: run! run! run! a festival and a collaboration. Cultural Geographies , 24 (4) pp. 625-630. 10.1177/1474474017702511 .

http://ift.tt/2hxapWH

Joint Multimodal Segmentation of Clinical CT and MR from Hip Arthroplasty Patients

Ranzini, MBM; Ebner, M; Cardoso, MJ; Fotiadou, A; Vercauteren, T; Henckel, J; Hart, A; ... Modat, M; + view all Ranzini, MBM; Ebner, M; Cardoso, MJ; Fotiadou, A; Vercauteren, T; Henckel, J; Hart, A; Ourselin, S; Modat, M; - view fewer (2017) Joint Multimodal Segmentation of Clinical CT and MR from Hip Arthroplasty Patients. In: (Proceedings) MICCAI: International Conference on Medical Image Computing and Computer-Assisted Intervention - MICCAI Workshop. Springer: Switzerland, Cham. (In press).

http://ift.tt/2jndFVp

The medical device development landscape in South Africa: Institutions, sectors and collaboration

de Jager, K; Chimhundu, C; Saidi, T; Douglas, TS; (2017) The medical device development landscape in South Africa: Institutions, sectors and collaboration. South African Journal of Science , 113 (5-6) , Article 2016-0259. 10.17159/sajs.2017/20160259 . Green open access

http://ift.tt/2hw1UeM

Magnetic Resonance with Squeezed Microwaves

Bienfait, A; Campagne-Ibarcq, P; Kiilerich, AH; Zhou, X; Probst, S; Pla, JJ; Schenkel, T; ... Bertet, P; + view all Bienfait, A; Campagne-Ibarcq, P; Kiilerich, AH; Zhou, X; Probst, S; Pla, JJ; Schenkel, T; Vion, D; Esteve, D; Morton, JJL; Moelmer, K; Bertet, P; - view fewer (2017) Magnetic Resonance with Squeezed Microwaves. Physical Review X , 7 (4) , Article 041011. 10.1103/PhysRevX.7.041011 . Green open access

http://ift.tt/2jndyJt

Imaging outcome measures for progressive multiple sclerosis trials

Moccia, M; de Stefano, N; Barkhof, F; (2017) Imaging outcome measures for progressive multiple sclerosis trials. Multiple Sclerosis Journal , 23 (12) pp. 1614-1626. 10.1177/1352458517729456 . Green open access

http://ift.tt/2hwczpK

Air Pollution and Seasonality Effects on Mode Choice in China

Li, W; Kamargianni, M; (2017) Air Pollution and Seasonality Effects on Mode Choice in China. Transportation Research Record: Journal of the Transportation Research Board , 2634 pp. 101-109. 10.3141/2634-15 .

http://ift.tt/2jqeHjv

UK Quantitative WB-DWI Technical Workgroup: consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion weighted imaging for cancer

Barnes, A; Alonzi, R; Blackledge, M; Charles-Edwards, G; Collins, D; Cook, G; Coutts, G; ... Punwani, S; + view all Barnes, A; Alonzi, R; Blackledge, M; Charles-Edwards, G; Collins, D; Cook, G; Coutts, G; Goh, V; Martin, G; Kelly, C; Koh, D-M; McCallum, H; Miquel, ME; O'Connor, JP; Padhani, A; Pearson, R; Priest, AN; Rockall, A; Stirling, J; Taylor, SA; Tunariu, N; vanderMeulen, J; Walls, D; Winfield, J; Punwani, S; - view fewer (2017) UK Quantitative WB-DWI Technical Workgroup: consensus meeting recommendations on optimisation, quality control, processing and analysis of quantitative whole-body diffusion weighted imaging for cancer. Br J Radiol 10.1259/bjr.20170577 . (In press). Green open access

http://ift.tt/2hv6B8B

The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates fibroblast activation in systemic sclerosis.

Bergmann, C; Brandt, A; Merlevede, B; Hallenberger, L; Dees, C; Wohlfahrt, T; Pötter, S; ... Distler, JHW; + view all Bergmann, C; Brandt, A; Merlevede, B; Hallenberger, L; Dees, C; Wohlfahrt, T; Pötter, S; Zhang, Y; Chen, C-W; Mallano, T; Liang, R; Kagwiria, R; Kreuter, A; Pantelaki, I; Bozec, A; Abraham, D; Rieker, R; Ramming, A; Distler, O; Schett, G; Distler, JHW; - view fewer (2017) The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates fibroblast activation in systemic sclerosis. Ann Rheum Dis 10.1136/annrheumdis-2017-211501 . (In press).

http://ift.tt/2jnci8S

The patterns of birthmarks suggest a novel population of melanocyte precursors arising around the time of gastrulation

Kinsler, VA; Larue, L; (2017) The patterns of birthmarks suggest a novel population of melanocyte precursors arising around the time of gastrulation. Pigment Cell and Melanoma Research 10.1111/pcmr.12645 . (In press). Green open access

http://ift.tt/2hxany3

PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer

Brasó-Maristany, F; Filosto, S; Catchpole, S; Marlow, R; Quist, J; Francesch-Domenech, E; Plumb, DA; ... Tutt, AN; + view all Brasó-Maristany, F; Filosto, S; Catchpole, S; Marlow, R; Quist, J; Francesch-Domenech, E; Plumb, DA; Zakka, L; Gazinska, P; Liccardi, G; Meier, P; Gris-Oliver, A; Cheang, MCU; Perdrix-Rosell, A; Shafat, M; Noël, E; Patel, N; McEachern, K; Scaltriti, M; Castel, P; Noor, F; Buus, R; Mathew, S; Watkins, J; Serra, V; Marra, P; Grigoriadis, A; Tutt, AN; - view fewer (2016) PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. Nature Medicine , 22 (11) pp. 1303-1313. 10.1038/nm.4198 .

http://ift.tt/2jn3IHk

Can diversity encourage entrepreneurship in transition economies?

Nikolova, E; (2017) Can diversity encourage entrepreneurship in transition economies? IZA World of Labor , 2017 , Article 313. 10.15185/izawol.313 . Green open access

http://ift.tt/2hwYhVD

Molecular photoprotection of human keratinocytes in vitro by the naturally occurring mycosporine-like amino acid (MAA) palythine

Summary

Background

Solar ultraviolet radiation (UVR) induces molecular and genetic changes in the skin, which result in skin cancer, photoageing and photosensitivity disorders. The use of sunscreens is advocated to prevent such photodamage, however most formulations contain synthetic UVR filters that are non-biodegradable and can damage fragile marine ecosystems. Mycosporine-like amino acids (MAA) are natural UVR-absorbing compounds that have evolved in marine species for protection against chronic UVR exposure in shallow-water habitats.

Objectives

To determine if palythine, a photostable model MAA, could offer protection against a range of UVR-induced damage biomarkers that are important in skin cancer and photoageing.

Methods

HaCaT human keratinocytes were used to assess the photoprotective potential of palythine using a number of endpoints including cell viability, DNA damage (non-specific, cyclobutane pyrimidine dimers and oxidatively generated damage), gene expression changes (linked to inflammation, photoageing and oxidative stress) and oxidative stress. The anti-oxidant mechanism was investigated using chemical quenching and Nrf2 pathway activation assays.

Results

Palythine offered statistically significant protection (p<0.005) against all endpoints tested even at extremely low concentrations (0.3% w/v). Additionally, palythine was found to be a potent antioxidant, reducing oxidatively generated stress, even when added post exposure.

Conclusions

Palythine is an extremely effective multifunctional photoprotective molecule in vitro that has potential to be developed as a natural and biocompatible alternative to synthetic UVR filters.

This article is protected by copyright. All rights reserved.

http://ift.tt/2AAYpY6

How to get rid of a nose piercing bump

Even with the best aftercare, a bump may form around a nose piercing. In this article, learn how to treat and prevent a nose piercing bump.

http://ift.tt/2iRdYDL

Gluten sensitivities and the allergist: Threshing the grain from the husks

Abstract

"Gluten sensitivity" has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well-defined entities, but are becoming a fraction of individuals following a gluten-free diet. WA has a prevalence of <0.5%. Wheat, specifically its omega-5 gliadin fraction, is the most common allergen implicated in food-dependent, exercise-induced anaphylaxis. CD is a non-IgE hypersensitivity to certain cereal proteins: gluten in wheat, secalin in rye, hordein in barley, and to a lesser extent avenin in oat. It is a rare disease, with an estimated prevalence that varied widely geographically, being higher in Northern Europe and the African Saharawi region than in Southeast Asia. In addition to suggestive symptoms, serologic testing has high diagnostic reliability and biopsy is a confirmatory procedure. CD patients have extra-intestinal autoimmune comorbid conditions more frequently than expected. A third entity is non-celiac gluten sensitivity, which has been created because of the increasing number of subjects who claim a better quality of life or improvement of their variety of symptoms on switching to a gluten-free diet. The phenomenon is being fueled by the media and exploited by the industry. The lack of a specific objective test has been raising substantial controversy about this entity. Allergists and gastroenterologists need to pay attention to the multitudes of individuals who elect to follow a gluten-free diet. Many such subjects might have WA, CD, or another illness. Providing them with appropriate evaluation and specific management would be of great advantages, medically and economically.

This article is protected by copyright. All rights reserved.

http://ift.tt/2hvzocY

Quality of life is significantly impaired in non-allergic rhinitis patients

Abstract

Background

In contrast to the well-known significant impairment of quality of life (QoL) in allergic rhinitis (AR), the degree of impairment in QoL in non-allergic rhinitis (NAR) remained unknown for a long time, due to a lack of a validated questionnaire to assess QoL in the NAR patient group.

In this study a validation for the mini-RQLQ questionnaire in NAR patients was performed, followed by an assessment of QoL in NAR patients compared to AR and healthy controls.

Secondly, use of medication and treatment satisfaction in AR and NAR was assessed.

Methods

The study was an observational cohort study in 287 AR and 160 NAR patients.

Patients with symptoms of rhinitis were recruited from a tertiary care outpatient clinic of the Otorhinolaryngology Department. AR was defined as one or more positive results on skin prick testing and clinically relevant symptoms of rhinitis related to their sensitization. NAR was defined as clinically relevant symptoms of rhinitis but without positive results on skin prick testing.

The mini-RQLQ was successfully validated in this study for NAR patients.

Results

QoL in NAR patients was equally -and for some aspects even more- impaired compared to AR. More than half of both AR and NAR patients were unsatisfied with treatment.

Conclusion

These results demonstrate a significant impairment in both AR and NAR patients in their QoL combined with a low treatment satisfaction, emphasizing the need for adequate treatment, especially in the NAR patient group.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jndol2

Abdominopelvic Tuberculosis Secondary to a Nontuberculous Mycobacterium in an Immunocompetent Patient

Tuberculosis (TB) remained as one of the top 10 causes of death worldwide despite an overall decline in its incidence rate globally. Extrapulmonary TB is uncommon and only accounts for 10–20% of overall TB disease burden. Abdominopelvic TB is the sixth most common location of extrapulmonary TB. The symptoms and signs are often insidious and nonspecific. Diagnosing abdominopelvic TB can be very challenging at times and poses great difficulties to the clinician. Infection with nontuberculous Mycobacterium (NTM) is even rarer especially in an immunocompetent patient. We report a case of NTM in abdominopelvic TB. A 37-year-old foreign worker, para 3, presented with a one-week history of suprapubic pain associated with fever. An assessment showed presence of a right adnexal mass. She was treated as tuboovarian abscess with intravenous antibiotics. Unfortunately, she did not respond. She underwent exploratory laparotomy. Intraoperatively, features of the mass were suggestive of a right mature cystic teratoma with presence of slough and cheesy materials all over the abdominal cavity as well as presence of ascites. Diagnosis of NTM was confirmed with PCR testing using the peritoneal fluid. This case was a diagnostic dilemma due to the nonspecific clinical presentation. Management of such rare infection was revisited.

http://ift.tt/2AG8ggm

Comparing and Contrasting A Priori and A Posteriori Generalizability Assessment of Clinical Trials on Type 2 Diabetes Mellitus

Zhe, H; Gonzalez-Izquierdo, A; Denaxas, SC; Sura, A; Guo, Y; Hogan, W; Shenkman, E; Zhe, H; Gonzalez-Izquierdo, A; Denaxas, SC; Sura, A; Guo, Y; Hogan, W; Shenkman, E; Bian, J; - view fewer (2017) Comparing and Contrasting A Priori and A Posteriori Generalizability Assessment of Clinical Trials on Type 2 Diabetes Mellitus. In: Sarkar, N, (ed.) American Medical Informatics Association (AMIA) 2017 Annual Symposium. Hanley and Belfus, Inc. (In press).

http://ift.tt/2ADffXc

Hybrid simulations of positively and negatively charged pickup ions and cyclotron wave generation at Europa

Desai, RT; Cowee, MM; Wei, H; Fu, X; Gary, SP; Volwerk, M; Coates, AJ; (2017) Hybrid simulations of positively and negatively charged pickup ions and cyclotron wave generation at Europa. Journal of Geophysical Research: Space Physics 10.1002/2017JA024479 . (In press). Green open access

http://ift.tt/2AEE1X1

Wind Speed and Sea State Dependencies of Air-Sea Gas Transfer: Results From the High Wind Speed Gas Exchange Study (HiWinGS)

Blomquist, BW; Brumer, SE; Fairall, CW; Huebert, BJ; Zappa, CJ; Brooks, IM; Yang, M; ... Pascal, RW; + view all Blomquist, BW; Brumer, SE; Fairall, CW; Huebert, BJ; Zappa, CJ; Brooks, IM; Yang, M; Bariteau, L; Prytherch, J; Hare, JE; Czerski, H; Matei, A; Pascal, RW; - view fewer (2017) Wind Speed and Sea State Dependencies of Air-Sea Gas Transfer: Results From the High Wind Speed Gas Exchange Study (HiWinGS). Journal of Geophysical Research: Oceans 10.1002/2017JC013181 . (In press). Green open access

http://ift.tt/2ywhSIM

Functional connectivity changes following interpersonal reactivity

Krause, A; Colic, L; Borchardt, V; Li, M; Strauss, B; Buchheim, A; Fonagy, P; ... Walter, M; + view all Krause, A; Colic, L; Borchardt, V; Li, M; Strauss, B; Buchheim, A; Fonagy, P; Wildgruber, D; Nolte, T; Walter, M; - view fewer (2018) Functional connectivity changes following interpersonal reactivity. Human Brain Mapping (In press).

http://ift.tt/2AH8iV1

MyTraces: Investigating Correlation and Causation between Users' Emotional States and Mobile Phone Interaction

Mehrotra, A; Tsapeli, F; Hendley, R; Musolesi, M; (2017) MyTraces: Investigating Correlation and Causation between Users' Emotional States and Mobile Phone Interaction. Proceedings of the ACM on Interactive, Mobile, Wearable and Ubiquitous Technologies , 1 (3) , Article 83. 10.1145/3130948 .

http://ift.tt/2ywhNos

Large-scale fluctuations in the cosmic ionizing background: the impact of beamed source emission

Suarez, T; Pontzen, A; (2017) Large-scale fluctuations in the cosmic ionizing background: the impact of beamed source emission. Monthly Notices of the Royal Astronomical Society , 472 (3) pp. 2643-2650. 10.1093/mnras/stx2104 . Green open access

http://ift.tt/2AFCYWL

Structural brain abnormalities in successfully treated HIV infection: associations with disease and cerebrospinal fluid biomarkers

Van Zoest, RA; Underwood, J; De Francesco, D; Sabin, CA; Cole, JH; Wit, FW; Caan, MWA; ... Co-morBidity in Relation to AIDS (COBRA) Collaboration, .; + view all Van Zoest, RA; Underwood, J; De Francesco, D; Sabin, CA; Cole, JH; Wit, FW; Caan, MWA; Kootstra, NA; Fuchs, D; Zetterberg, H; Majoie, CBLM; Portegies, P; Winston, A; Sharp, DJ; Gisslén, M; Reiss, P; Co-morBidity in Relation to AIDS (COBRA) Collaboration, .; - view fewer (2017) Structural brain abnormalities in successfully treated HIV infection: associations with disease and cerebrospinal fluid biomarkers. Journal of Infectious Diseases 10.1093/infdis/jix553 . (In press).

http://ift.tt/2yxjFgG

A 3-way hybrid approach to generate a new high quality chimpanzee reference genome (Pan_tro_3.0)

Kuderna, LFK; Tomlinson, C; Hillier, LW; Tran, A; Fiddes, I; Armstrong, J; Laayouni, H; ... Marques-Bonet, T; + view all Kuderna, LFK; Tomlinson, C; Hillier, LW; Tran, A; Fiddes, I; Armstrong, J; Laayouni, H; Gordon, D; Huddleston, J; Perez, RG; Povolotskaya, I; Armero, AS; Garrido, JG; Ho, D; Ribeca, P; Alioto, T; Green, RE; Paten, B; Navarro, A; Betranpetit, J; Herrero, J; Eichler, EE; Sharp, AJ; Feuk, L; Warren, WC; Marques-Bonet, T; - view fewer (2017) A 3-way hybrid approach to generate a new high quality chimpanzee reference genome (Pan_tro_3.0). GigaScience , 6 (11) pp. 1-6. 10.1093/gigascience/gix098 . Green open access

http://ift.tt/2AFmXQr

A study of the relationship between the migration of image silver and perceived yellowing of silver gelatine photographs

Moon, J; Curran, K; (2017) A study of the relationship between the migration of image silver and perceived yellowing of silver gelatine photographs. Heritage Science , 5 , Article 45. 10.1186/s40494-017-0159-9 . Green open access

http://ift.tt/2yxpV8k

International multicentre randomised controlled trial of improvisational music therapy for children with autism spectrum disorder: TIME-A study

Crawford, MJ; Gold, C; Odell-Miller, H; Thana, L; Faber, S; Assmus, J; Bieleninik, L; ... Hassiotis, A; + view all Crawford, MJ; Gold, C; Odell-Miller, H; Thana, L; Faber, S; Assmus, J; Bieleninik, L; Geretsegger, M; Grant, C; Maratos, A; Sandford, S; Claringbold, A; McConachie, H; Maskey, M; Mossler, KA; Ramchandani, P; Hassiotis, A; - view fewer (2017) International multicentre randomised controlled trial of improvisational music therapy for children with autism spectrum disorder: TIME-A study. Health Technology Assessment , 21 (59) pp. 1-40. 10.3310/hta21590 . Green open access

http://ift.tt/2AFmXzV

Investigating the moral and scientific thinking of 7-8 year olds when taught socio-scientific issues related to energy and genetics

McCrory, A; (2014) Investigating the moral and scientific thinking of 7-8 year olds when taught socio-scientific issues related to energy and genetics. Doctoral thesis (Ph.D), Institute of Education.

http://ift.tt/2yxjemy

Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project

van Maurik, IS; Zwan, MD; Tijms, BM; Bouwman, FH; Teunissen, CE; Scheltens, P; Wattjes, MP; ... Alzheimer's Disease Neuroimaging Initiative, .; + view all van Maurik, IS; Zwan, MD; Tijms, BM; Bouwman, FH; Teunissen, CE; Scheltens, P; Wattjes, MP; Barkhof, F; Berkhof, J; van der Flier, WM; Alzheimer's Disease Neuroimaging Initiative, .; - view fewer (2017) Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project. JAMA Neurology 10.1001/jamaneurol.2017.2712 . (In press).

http://ift.tt/2AGLwgf

Regulation of developing myelin sheath elongation by oligodendrocyte calcium transients in vivo

Krasnow, AM; Ford, MC; Valdivia, LE; Wilson, SW; Attwell, D; (2017) Regulation of developing myelin sheath elongation by oligodendrocyte calcium transients in vivo. Nature Neuroscience (In press).

http://ift.tt/2yxpzi0

Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress

Fanelli, G; Gonzalez-Cordero, A; Gardner, PJ; Peng, Q; Fernando, M; Kloc, M; Farrar, CA; ... Sacks, SH; + view all Fanelli, G; Gonzalez-Cordero, A; Gardner, PJ; Peng, Q; Fernando, M; Kloc, M; Farrar, CA; Naeem, A; Garred, P; Ali, RR; Sacks, SH; - view fewer (2017) Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress. Scientific Reports , 7 , Article 14625. 10.1038/s41598-017-15212-z . Green open access

http://ift.tt/2AFwKWG

Diabetes und Krebs – den Zusammenhängen auf der Spur

http://ift.tt/2zFF6xD

Extragenitale, disseminierte Infektion mit humanen Papillomaviren

Zusammenfassung

Bei einem 50-jährigen Patienten mit seit 5 Jahren bestehender großflächiger Warzenmanifestation und extremem Pruritus kamen wir zur Diagnose einer reaktivierten HPV (humane Papillomaviren)-Infektion durch 3 molekulargenetisch gesicherte Virustypen (6, 16, 18), die im Impfstoff Gardasil® enthalten sind. Nachdem konventionelle Therapieverfahren keinen Erfolg erbrachten, zeigte sich nach Gardasil®-Immunisierung rasch ein signifikanter Rückgang der Hautmanifestation. Inwieweit therapieresistente HPV-Infektionen mittels einer aktiven HPV-Impfung zu beeinflussen sind, sollte in weiteren Studien untersucht werden.

http://ift.tt/2zTV4Hj

Equivalence in outcomes between Draf 2B vs Draf 3 frontal sinusotomy for refractory chronic frontal rhinosinusitis

Background

Endoscopic Draf 2B and Draf 3 frontal sinusotomies are frequently performed for chronic refractory frontal rhinosinusitis. The purpose of this study was to compare outcomes between Draf 2B and Draf 3 procedures.

Methods

A retrospective cohort study was conducted comparing patients undergoing bilateral Draf 2B vs Draf 3 procedures from 2000 to 2016. Patients with neoplasia, dysplasia, mucocele, cystic fibrosis, or ciliary dyskinesia were excluded. Preoperative disease parameters included number of prior surgeries, presence of polyps, preoperative 22-item Sino-Nasal Outcome Test (SNOT-22) score, frontal Lund-Mackay score, anterior-posterior diameter of the frontal ostium, and Global Osteitis Scoring Scale (GOSS). Postoperative outcomes included SNOT-22 score, neo-ostium patency, surgical revision rates, and complications.

Results

A total of 21 patients with bilateral Draf 2B and 17 patients with Draf 3 surgeries were compared. Mean follow-up time was 15.6 months. No significant differences were seen between groups for any preoperative disease parameter. Both cohorts showed statistically significant (p = 0.0001 [Draf 2B]; p = 0.0001 [Draf 3]) and clinically meaningful (Δ = 24.1; Δ = 24.9) improvements in SNOT-22 at last follow-up vs preoperatively. The Draf 2B group had greater improvement in SNOT-22 score than the Draf 3 group at 1 to 3 months (p = 0.003), but the magnitude of improvement equalized at 5 to 9 months (p = 0.66) and last follow-up (p = 0.90). No significant differences were noted between groups regarding patency, revision rates, or complications.

Conclusion

Both Draf 2B and Draf 3 procedures offer durable symptomatic improvement for patients with refractory frontal CRS. The Draf 2B is associated with earlier postoperative symptom improvement and overall shows comparable long-term outcomes to the Draf 3 sinusotomy.

http://ift.tt/2ho4gsg

Behandlungsalgorithmus CUP

http://ift.tt/2huSj82

Treatment-related survival associations of claudin-2 expression in fibroblasts of colorectal cancer

Abstract

Claudin-2 is a trans-membrane protein—component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types. Claudin-2 expression was also analyzed by immunofluorescence in primary cultures of human CRC cancer-associated fibroblasts (CAFs). Initial analyses identified previously unrecognized expression patterns of claudin-2 in CAFs of human CRC. Claudin-2 expression in CAFs of the invasive margin was associated with shorter progression-free survival. Subgroup analyses demonstrated that the survival associations occurred among cases that received 5-FU+oxaliplatin combination treatment, but not in patients receiving 5-FU±irinotecan. The finding was validated by analyses of the independent cohort. In summary, previously unreported stromal expression of claudin-2 in CAFs of human CRC was detected together with significant association between high claudin-2 expression in CAFs and shorter survival in 5-FU+oxaliplatin-treated mCRC patients.

http://ift.tt/2iQvoAD

Development of the UK hereditary spastic paraplegia registry: Analysis of SPAST patients reveals high rate of psychiatric comorbidities

Chelban, V; Tucci, A; Houlden, H; (2016) Development of the UK hereditary spastic paraplegia registry: Analysis of SPAST patients reveals high rate of psychiatric comorbidities. In: (Proceedings) 20th International Congress of Parkinson's Disease and Movement Disorders. (pp. S191-S192). WILEY-BLACKWELL

http://ift.tt/2yyiEVT

PROSPECT: A UK-based longitudinal observational study of PSP, CBD, MSA and atypical Parkinsonism syndromes

Woodside, J; Lamb, R; Chelban, V; Burn, D; Church, A; Gerhard, A; Hu, M; ... Houlden, H; + view all Woodside, J; Lamb, R; Chelban, V; Burn, D; Church, A; Gerhard, A; Hu, M; Leigh, N; Rowe, J; Houlden, H; - view fewer (2016) PROSPECT: A UK-based longitudinal observational study of PSP, CBD, MSA and atypical Parkinsonism syndromes. In: (Proceedings) 20th International Congress of Parkinson's Disease and Movement Disorders. (pp. S87-S88). WILEY-BLACKWELL

http://ift.tt/2AFeEEt

Genetic and clinical analysis of cerebral calcifications

Chelban, V; Kaiyrzhanov, R; Houlden, H; (2017) Genetic and clinical analysis of cerebral calcifications. In: (Proceedings) 21st International Congress of Parkinson's Disease and Movement Disorders. WILEY

http://ift.tt/2yxwEPK

Genotype-Phenotype correlations and expansion of the molecular spectrum of AP4M1-related Hereditary Spastic Paraplegia

Efthymiou, S; Bettencourt, C; Damiano, VS; Houlden, H; (2017) Genotype-Phenotype correlations and expansion of the molecular spectrum of AP4M1-related Hereditary Spastic Paraplegia. In: (Proceedings) 21st International Congress of Parkinson's Disease and Movement Disorders. WILEY

http://ift.tt/2ADULNT

Genetic and clinical analysis of cerebral calcification

Chelban, V; Kaiyrzhanov, R; Houlden, H; (2017) Genetic and clinical analysis of cerebral calcification. In: (Proceedings) 3rd Congress of the European-Academy-of-Neurology. (pp. p. 73). WILEY

http://ift.tt/2yxkJBo

Femoral diaphyseal endoprosthetic reconstruction after segmental resection of primary bone tumours

Hanna, SA; Sewell, MD; Aston, WJS; Pollock, RC; Skinner, JA; Cannon, SR; Briggs, TWR; (2010) Femoral diaphyseal endoprosthetic reconstruction after segmental resection of primary bone tumours. JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME , 92B (6) pp. 867-874. 10.1302/0301-620X.92B6.23449 .

http://ift.tt/2AF7u2U

Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians.

Li, C; Kim, YK; Dorajoo, R; Li, H; Lee, I-T; Cheng, C-Y; He, M; ... Kelly, TN; + view all Li, C; Kim, YK; Dorajoo, R; Li, H; Lee, I-T; Cheng, C-Y; He, M; Sheu, WH-H; Guo, X; Ganesh, SK; He, J; Lee, J; Liu, J; Hu, Y; Rao, DC; Tsai, F-J; Koh, JY; Hu, H; Liang, K-W; Palmas, W; Hixson, JE; Han, S; Teo, Y-Y; Wang, Y; Chen, J; Lu, CH; Zheng, Y; Gui, L; Lee, W-J; Yao, J; Gu, D; Han, B-G; Sim, X; Sun, L; Zhao, J; Chen, C-H; Kumari, N; He, Y; Taylor, KD; Raffel, LJ; Moon, S; Rotter, JI; Ida Chen, Y-D; Wu, T; Wong, TY; Wu, J-Y; Lin, X; Tai, E-S; Kim, B-J; Kelly, TN; - view fewer (2017) Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. Circ Cardiovasc Genet , 10 (2) , Article e001527. 10.1161/CIRCGENETICS.116.001527 .

http://ift.tt/2yxkA0O

Editorial

Freeman, M; Woodin, T; Wright, S; (2017) Editorial. History of Education , 46 (6) pp. 709-710. 10.1080/0046760X.2017.1382973 .

http://ift.tt/2AF7kbO

Continental Currents: Paris and London

Atkinson, J; (2017) Continental Currents: Paris and London. In: Shattock, J, (ed.) Journalism and the Periodical Press in Nineteenth-Century Britain. Cambridge University Press: Cambridge.

http://ift.tt/2ywnVNw

French Novels and the Victorians

Atkinson, J; (2017) French Novels and the Victorians. Oxford University Press, USA

http://ift.tt/2AFeMDX

Vertical implantable collamer lens (ICL) rotation for the management of high vault due to lens oversizing.

Matarazzo, F; Day, AC; Fernandez-Vega Cueto, L; Maurino, V; (2017) Vertical implantable collamer lens (ICL) rotation for the management of high vault due to lens oversizing. Int Ophthalmol 10.1007/s10792-017-0757-2 .

http://ift.tt/2yxwE2c

Evaluation of the rat thyroid cell strain FRTL-5 as an in-vitro bioassay system for thyrotrophin.

Bidey, SP; Chiovato, L; Day, A; Turmaine, M; Gould, RP; Ekins, RP; Marshall, NJ; (1984) Evaluation of the rat thyroid cell strain FRTL-5 as an in-vitro bioassay system for thyrotrophin. J Endocrinol , 101 (3) pp. 269-276.

http://ift.tt/2AFeLzT

Gas transfer model to design a ventilator for neonatal total liquid ventilation.

Bonfanti, M; Cammi, A; Bagnoli, P; (2015) Gas transfer model to design a ventilator for neonatal total liquid ventilation. Med Eng Phys , 37 (12) pp. 1133-1140. 10.1016/j.medengphy.2015.09.003 .

http://ift.tt/2yxkgiC

A method to estimate concrete hydraulic conductivity of underground tunnel to assess lining degradation

Bagnoli, P; Bonfanti, M; Della Vecchia, G; Lualdi, M; Sgambi, L; (2015) A method to estimate concrete hydraulic conductivity of underground tunnel to assess lining degradation. Tunnelling and Underground Space Technology , 50 pp. 415-423. 10.1016/j.tust.2015.08.008 .

http://ift.tt/2AF7cJm

Satisfaction in stages: The academic profession in the United Kingdom and the British commonwealth

Locke, W; Bennion, A; (2013) Satisfaction in stages: The academic profession in the United Kingdom and the British commonwealth. In: Job Satisfaction around the Academic World. (pp. 223-238).

http://ift.tt/2yxkczo

Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure

Sands, SA; Mebrate, Y; Edwards, BA; Nernati, S; Manisty, CH; Desai, AS; Wellman, A; ... Malhotra, A; + view all Sands, SA; Mebrate, Y; Edwards, BA; Nernati, S; Manisty, CH; Desai, AS; Wellman, A; Willson, K; Francis, DP; Butler, JP; Malhotra, A; - view fewer (2017) Resonance as the Mechanism of Daytime Periodic Breathing in Patients with Heart Failure. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE , 195 (2) pp. 237-246. 10.1164/rccm.201604-07610C .

http://ift.tt/2AFeIUJ

Utilization of Indocyanine green to demonstrate lymphatic mapping in colon cancer.

Joshi, HM; Keller, DS; Chand, M; (2017) Utilization of Indocyanine green to demonstrate lymphatic mapping in colon cancer. J Surg Oncol 10.1002/jso.24795 .

http://ift.tt/2yxzHYg

EFNS/MDS-ES recommendations for the diagnosis of Parkinson's disease

Berardelli, A; Wenning, G; Antonini, A; Berg, D; Bloem, BR; Bonifati, V; Brooks, D; ... Vidailhet, M; + view all Berardelli, A; Wenning, G; Antonini, A; Berg, D; Bloem, BR; Bonifati, V; Brooks, D; Burn, D; Colosimo, C; Ferreira, J; Gasser, T; Grandas, F; Kanovsky, P; Kostic, V; Kulisevsky, J; Oertel, W; Poewe, W; Reese, J-P; Relja, M; Ruzicka, E; Schapira, A; Schrag, A; Seppi, K; Taba, P; Vidailhet, M; - view fewer (2012) EFNS/MDS-ES recommendations for the diagnosis of Parkinson's disease. In: (Proceedings) 16th Congress of the European-Federation-of-Neurological-Societies (EFNS). (pp. p. 813). WILEY-BLACKWELL

http://ift.tt/2AF7b8g

Functional neuroimaging of psychogenic dystonia

Schrag, AE; Mehta, AR; Bhatia, KP; Brown, RJ; Frackowiak, RSJ; Trimble, MR; Ward, NS; Schrag, AE; Mehta, AR; Bhatia, KP; Brown, RJ; Frackowiak, RSJ; Trimble, MR; Ward, NS; Rowe, JB; - view fewer (2012) Functional neuroimaging of psychogenic dystonia. In: (Proceedings) 16th International Congress of Parkinson's Disease and Movement Disorders. (pp. S246-S247). WILEY-BLACKWELL

http://ift.tt/2yvIVEd

Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus

Marshall, A; Celentano, A; Cirillo, N; Mirams, M; McCullough, M; Porter, S; (2017) Immune receptors CD40 and CD86 in oral keratinocytes and implications for oral lichen planus. JOURNAL OF ORAL SCIENCE , 59 (3) pp. 373-382. 10.2334/josnusd.16-0334 .

http://ift.tt/2AF7aBe

DFD-01 Reduces Transepidermal Water Loss and Improves Skin Hydration and Flexibility

Abstract

Introduction

In plaque psoriasis, the benefit of topical steroids is well established. The vehicle formulation of topical steroids may also provide benefit in addition to the effects of the steroid itself. DFD-01 (betamethasone dipropionate spray, 0.05%) is a formulation composed of a topical steroid in an emollient-like vehicle that enhances penetration to the target site of inflammation in the skin. The aim of this study was to assess the effect of DFD-01 and its vehicle on skin hydration and barrier function in compromised skin and to evaluate its effect on flexibility in healthy skin.

Methods

Eighteen healthy white volunteers were enrolled in each of two studies. In Study 1, dry shaving of volar forearms created a compromised skin barrier, through which transepidermal water loss (TEWL) was measured using an evaporimeter. Capacitance, a measure of epidermal hydration, was also measured at baseline and at 1, 2 and 4 h after application of DFD-01 or its vehicle formulation. In Study 2, intact skin flexibility was tested with a cutometer before and at 1, 2 and 4 h after application of DFD-01 or vehicle.

Results

In Study 1, both DFD-01 and its vehicle were effective at reducing TEWL through the compromised stratum corneum. Capacitance measurements confirmed this finding; razor-chafed skin treated with either DFD-01 or vehicle exhibited levels of skin hydration similar to unshaved control skin. Study 2 found softening and greater flexibility of normal skin treated with either DFD-01 or vehicle compared with nontreated control skin samples.

Conclusions

These tests suggest that the DFD-01 formulation and its vehicle are each effective at retaining moisture within a damaged skin barrier and for softening and increasing the flexibility of intact skin.

Funding

Dr. Reddy's Laboratories.

http://ift.tt/2ACNFbL

Post-traumatic untreated chronic osteomyelitis: an extreme presentation with severe complications

Description

An 89-year-old man presented to the hospital complaining of several episodes of lipotimia and non-specific malaise. Comorbidities included a right lower limb chronic osteomyelitis, as consequence of a trauma at the age of 12 years, with occasional bleeding, and which has never been medical or surgically treated before. He was haemodynamically stable with normal cardiac and pulmonary auscultation during the physical examination. The right lower limb revealed an extensive extremely putrefied and suppurative wound with bone exposition in which fragments could easily be removed (figure 1A,B). Considering the patient's complaints, a 12-lead ECG was performed and showed normal sinus rhythm with 2:1 atrioventricular block, ST-segment elevation in the inferior leads and V6 and ST-segment depression in V1, V2, aVL and aVR. Patient denied chest pain. The laboratory investigation revealed a microcytic and hypochromic anaemia with an Hb of 4.2 g/dL (reference range 13.5–17.0 g/dL) and...

http://ift.tt/2zwAkFb

Tubular sigmoid duplication in an adult man: an interesting incidental finding

A 61-year-old man attended an outpatient colorectal clinic for a chronic, non-specific abdominal pain, associated with rectal bleeding. He underwent a number of investigations including a CT pneumocolon, which revealed an incidental finding of 20 cm of additional sigmoid colon. This case is interesting because tubular sigmoid duplication is an extremely unusual condition, rarely diagnosed in adults; only a few cases have been reported of this condition in the adult population. Our team chose to treat this patient conservatively, in order to avoid putting the patient at risk of an unnecessary surgery.

http://ift.tt/2zSeVH0

Urachal sinus leading to pyourachus presenting as recurrent periumbilical sepsis in an infant

Description

A 5-month-old female infant presented with an 8 days duration of fever and irritability. In the previous 48 hours, she developed a rash around her umbilicus with reduced feeding and wet nappies (figure 1). She was born at 38+3/40 weeks gestation by caesarean section for breech presentation. At 4 months of age, she had gastro-oesophageal reflux. She initially presented to the general practitioner (GP) at 3 months of age with redness around the umbilicus and dried clots in the centre without any swelling. She had no fever and was otherwise well. Initial treatment given by GP included a 1-week course of oral flucloxacillin for provisional diagnosis of infected umbilical granuloma. This seemed to have resolved her symptoms.

Figure 1

Clinical photograph showing a diffuse periumbilical erythema.

The baby was referred for paediatric assessment by her GP with recurrent symptoms mentioned above. On examination,...

http://ift.tt/2zwAhJv

Successful downstaging of locally recurrent penile squamous cell carcinoma with neoadjuvant nanosomal docetaxel lipid suspension (NDLS) based regimen followed by curative surgery

Penile squamous cell carcinoma (pSCC) is a relatively rare disease in Western world but is a significant health problem in developing countries like India. We report here a case of successful multimodality management of recurrent pSCC with pelvic lymphadenopathy in a 56-year-old male patient with poorly controlled diabetes. The patient presented with ulceroproliferative growth over the residual penile stump clinically involving root of penis and with right pelvic lymphadenopathy. The patient had a history of partial penectomy done elsewhere 20 months ago. In view of the comorbidities, locally recurrent disease and presence of right Iliac lymphadenopathy, the patient was treated with nanosomal docetaxel lipid suspension (NDLS), cisplatin and 5-fluorouracil (TPF regimen) in the neoadjuvant setting followed by staged surgical resection. This is the first case report showing successful treatment of recurrent pSCC with NDLS-based TPF regimen in the neoadjuvant setting followed by staged surgery in a patient with poorly controlled diabetes.

http://ift.tt/2zSeRHg

Single coronary artery with high aortic take-off-a rare coronary anomaly

Description

High take-off of coronary arteries refers to the origin of coronary arteries >1 cm above the sinotubular junction.1 Its prevalence in general population is estimated to be 0.20%.1 Some consider it to be benign, while others have reported it to be associated with ischaemia, myocardial infarction, syncope and sudden cardiac death.1 Similarly, single coronary artery is a rare coronary anomaly, where only one coronary artery originates from the single ostium from the aorta and supplies the entire heart. Its incidence varies between 0.0024% and 0.066% in those undergoing coronary angiography.2 It is extremely rare to find a single coronary artery with a high aortic take-off from the aorta, with only a few case reports available previously.3

A 65-year-old man with diabetes presented with a history of chronic stable angina and a positive exercise stress test at low threshold. During his diagnostic...

http://ift.tt/2zwAEDM

Global aphasia in a case of bilateral frontal lobe infarcts involving both caudate nuclei

Description 

We report a 50-year-old man with history of systemic hypertension, nicotine addiction and a folk singer by profession was brought to the hospital with history of abrupt onset of speech arrest at the peak of a high note during his stage performance. His co-performer friend noticed that he was unable to restart his song performance despite back stage prompting. He appeared clueless and unresponsive with expressionless face all of a sudden. His relatives were certain that there was a dramatic change in patient's personality (from an extrovert to an introvert). The patient seemed disinterested in his surroundings. He seemed to have a 'vacant stare'. On examination, his blood pressure was 170/100 mm Hg. He was conscious, alert, but unresponsive to simple verbal commands. There was no speech output. Fundus examination showed grade 1 hypertensive retinopathy, no papilloedema. Motor functions were preserved. MRI of brain with magnetic resonance angiography (MRA) was done in view...

http://ift.tt/2zTDtzr