Hairy polyps: A new case presentation and a pathogenetic hypothesis

The Laryngoscope, EarlyView.


https://ift.tt/2PpiITF

Endoscopic Transcanal Autologous Cartilage Ossiculoplasty

Abstract

This was a randomized clinical trial, of thirty-two patients undergoing endoscopic ossiculoplasty, as a second look surgery, at 6 months after primary endoscopic cholesteatoma surgery, in a duration of 9 years. All patients underwent trans-canal endoscopic ossiculoplasty under local anesthesia. Prosthesis used were (1) Titanium partial ossicular replacement prosthesis (PORP) in fourteen, (2) Titanium total ossicular replacement prosthesis (TORP) in six and (3) Autologous cartilage in twelve cases. Puretone audiometry (PTA) were done preoperatively and postoperatively at 2 months and 3 years. Out of twenty-four cases, which presented only with stapes superstructure; fourteen underwent PORP ossiculoplasty and twelve had cartilage short columella ossiculoplasty (SCC). Out of eight cases, which had only mobile stapes footplate, six underwent TORP ossiculoplasty and only two underwent long columella cartilage ossiculoplasty (LCC). Pre-operative average air conduction threshold (AC) of pure tone audiometry were 45.47 dB (PORP), 66.10 dB (TORP), 49.15 dB (SCC) and 59.15 dB (LCC) groups. The post-operative AC at 2 months were respectively 27.37 dB (PORP), 45.83 dB (TORP), 29.99 dB (SCC) and 39.15 dB (LCC) groups. The gap of air and bone conduction (ABG) at 2 months post-operative stage were 19.05 dB (PORP), 20 dB (TORP), 20.32 dB (SCC) and 39.15 dB (LCC) groups and not much changed after 3 years. Extrusion occurred in three PORPs and four TORPs at 4–8 years after surgery. Four cases were lost to follow up. No extrusion occurred in cartilage ossiculoplasty. Trans-canal endoscopic autologous cartilage ossiculoplasty shows encouraging results comparable to titanium prosthesis in repairing ossicles in cholesteatoma disease.

https://ift.tt/2SuJM2j

Submental Ectopic Thyroid Cyst: An Atypical Presentation

Abstract

It is very unusual of an ectopic thyroid to be presented as a submental swelling, clinically mimicking a submental cyst. Suspicious of the disease with complete clinical, biochemical and radiological correlation is the mainstay of diagnosis as the first FNAC is not confirmatory of the ectopic thyroid especially in cases of dysgenesis of thyroid tissue in an unusual location. Here we have presented a rare case of an ectopic thyroid gland presented with a submental swelling successfully managed with the conservative treatment.

https://ift.tt/2zfZ3Ls

Endoscopic Transcanal Autologous Cartilage Ossiculoplasty

Abstract

This was a randomized clinical trial, of thirty-two patients undergoing endoscopic ossiculoplasty, as a second look surgery, at 6 months after primary endoscopic cholesteatoma surgery, in a duration of 9 years. All patients underwent trans-canal endoscopic ossiculoplasty under local anesthesia. Prosthesis used were (1) Titanium partial ossicular replacement prosthesis (PORP) in fourteen, (2) Titanium total ossicular replacement prosthesis (TORP) in six and (3) Autologous cartilage in twelve cases. Puretone audiometry (PTA) were done preoperatively and postoperatively at 2 months and 3 years. Out of twenty-four cases, which presented only with stapes superstructure; fourteen underwent PORP ossiculoplasty and twelve had cartilage short columella ossiculoplasty (SCC). Out of eight cases, which had only mobile stapes footplate, six underwent TORP ossiculoplasty and only two underwent long columella cartilage ossiculoplasty (LCC). Pre-operative average air conduction threshold (AC) of pure tone audiometry were 45.47 dB (PORP), 66.10 dB (TORP), 49.15 dB (SCC) and 59.15 dB (LCC) groups. The post-operative AC at 2 months were respectively 27.37 dB (PORP), 45.83 dB (TORP), 29.99 dB (SCC) and 39.15 dB (LCC) groups. The gap of air and bone conduction (ABG) at 2 months post-operative stage were 19.05 dB (PORP), 20 dB (TORP), 20.32 dB (SCC) and 39.15 dB (LCC) groups and not much changed after 3 years. Extrusion occurred in three PORPs and four TORPs at 4–8 years after surgery. Four cases were lost to follow up. No extrusion occurred in cartilage ossiculoplasty. Trans-canal endoscopic autologous cartilage ossiculoplasty shows encouraging results comparable to titanium prosthesis in repairing ossicles in cholesteatoma disease.

https://ift.tt/2SuJM2j

Submental Ectopic Thyroid Cyst: An Atypical Presentation

Abstract

It is very unusual of an ectopic thyroid to be presented as a submental swelling, clinically mimicking a submental cyst. Suspicious of the disease with complete clinical, biochemical and radiological correlation is the mainstay of diagnosis as the first FNAC is not confirmatory of the ectopic thyroid especially in cases of dysgenesis of thyroid tissue in an unusual location. Here we have presented a rare case of an ectopic thyroid gland presented with a submental swelling successfully managed with the conservative treatment.

https://ift.tt/2zfZ3Ls

The role of long‐wavelength ultraviolet A1 (UVA1) in acral vitiligo

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2PuefPv

Combinatorial application of dissolving microneedle patch and cream for improvement of skin wrinkles, dermal density, elasticity, and hydration

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2RmsHGw

Differin® and depilation, a word of warning

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2PsEc1W

The Association Between Metabolic Syndrome and Serum Concentrations of Micronutrients, Inflammation, and Oxidative Stress Outside of the Clinical Reference Ranges: A Cross-Sectional Study

Metabolic Syndrome and Related Disorders, Ahead of Print.


https://ift.tt/2SuIiFm

MicroRNA-146b-3p Promotes Cell Metastasis by Directly Targeting NF2 in Human Papillary Thyroid Cancer

Thyroid, Ahead of Print.


https://ift.tt/2AAtiiq

Influence of ambient air pressure changes on vestibular symptoms after stapes surgery

To examine if vestibular irritation after stapes surgery may be provoked by pressure changes across the tympanic membrane, which consecutively results in displacements of the ossicular chain and the piston prosthesis suspended to it.

https://ift.tt/2COVoYs

Vaginal gel component hydroxyethyl cellulose significantly enhances the infectivity of Chlamydia trachomatis serovars D and E [Mechanisms of Action]

The transmission of the urogenital serovars of Chlamydia trachomatis can be significantly influenced by vaginal gels. Hydroxyethyl cellulose is a commonly used gelling agent which can be found in vaginal gels. Hydroxyethyl cellulose showed a concentration dependent growth enhancing effect on Chlamydia trachomatis serovars D and E with a 26.1 fold maximal increase in vitro and a 2.57 fold increase in vivo.

https://ift.tt/2CQtDz2

Ceftobiprole Activity against Gram-Positive and -Negative Pathogens Collected from the United States Across a Decade: 2006 and 2016 [Susceptibility]

Ceftobiprole is an advanced cephalosporin with potent activity against Gram-positive and Gram-negative bacteria that is approved in many European and non-European countries to treat community- and hospital-acquired pneumonia (excluding ventilator-associated pneumonia). This study reports on the activity of ceftobiprole against a large set of clinical isolates from hospitalized patients in the United States in 2016 that caused serious infections including pneumonia, bacteremia, and skin and skin structure infections. To assess any potential temporal changes in ceftobiprole activity, the 2016 results were compared to corresponding MIC data from a 2006 U.S. survey that included key target pathogens. Ceftobiprole exhibited potent activity against Staphylococcus aureus (including methicillin-resistant S. aureus isolates that were 99.3% susceptible), coagulase-negative staphylococci (100% susceptible), Enterococcus faecalis (100% susceptible), Streptococcus pneumoniae (99.7% susceptible), and other tested streptococci. Similarly, ceftobiprole was highly active against Enterobacteriaceae isolates that did not exhibit an ESBL phenotype, including Escherichia coli (99.8% susceptible) and Klebsiella pneumoniae (99.6% susceptible). Against Haemophilus influenzae and Moraxella catarrhalis, 99.6% of all isolates were inhibited at ≤1 mg/L of ceftobiprole, and 72.7% of the Pseudomonas aeruginosa isolates were susceptible to ceftobiprole. With the exception of decreased cephalosporin susceptibility among the Enterobacteriaceae, which correlates with an increased prevalence of ESBL-producing isolates, ceftobiprole had similar activity against the isolate sets collected in 2006 and 2016. Therefore, ceftobiprole remains highly active when tested in vitro against a large number of current Gram-positive and Gram-negative pathogens that cause serious infections.

https://ift.tt/2qe8WWa

In Vitro Activity of Plazomicin against Gram-negative and Gram-positive Bacterial Pathogens Isolated from Patients in Canadian Hospitals from 2013 to 2017: CANWARD Surveillance Study [Susceptibility]

The Clinical and Laboratory Standards Institute (CLSI) broth microdilution method was used to evaluate the in vitro activities of plazomicin and comparator antimicrobial agents against 7,712 Gram-negative and 4,481 Gram-positive bacterial pathogens obtained from patients in Canadian hospitals (CANWARD, 2013 to 2017). Plazomicin demonstrated potent in vitro activity against Enterobacteriaceae (MIC₉₀ ≤1 µg/ml for all species tested except Proteus mirabilis and Morganella morganii), including aminoglycoside non-susceptible, extended-spectrum β-lactamase (ESBL)-positive, and multidrug-resistant (MDR) isolates. Plazomicin was equally active against methicillin-susceptible and methicillin-resistant isolates of Staphylococcus aureus.

https://ift.tt/2CQtzPO

In Vivo Efficacy of Humanized WCK 5222 (Cefepime-Zidebactam) Exposures Against Carbapenem-Resistant Acinetobacter baumannii in the Neutropenic Thigh Model [Experimental Therapeutics]

Herein we describe the in vivo efficacy of human-simulated WCK 5222 (cefepime-zidebactam) exposure against carbapenem-resistant Acinetobacter baumannii in a neutropenic murine thigh infection model. Five of six isolates examined expressed OXA-23 or OXA-24. WCK 5222, despite showing MICs 16 – 64 mg/L, produced remarkable in vivo activity; human-simulated exposure showed a decline in bacterial burden for all isolates [mean reduction -2.09 ± 1.01 log₁₀ CFU/thigh], while lack of activity was observed with cefepime and zidebactam monotherapies.

https://ift.tt/2qpGqB7

Applying Rapid Whole Genome Sequencing to Predict Phenotypic Antimicrobial Susceptibility Testing Results Among Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates [Mechanisms of Resistance]

Objective: Standard antimicrobial susceptibility testing (AST) approaches lead to delays in the selection of optimal antimicrobial therapy. We sought to determine the accuracy of antimicrobial resistance (AMR) determinants identified by Nanopore whole genome sequencing in predicting AST results.

Methods: Using a cohort of 40 clinical isolates (21 carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae, 10 non-carbapenemase-producing carbapenem resistant K. pneumoniae, and 9 carbapenem-susceptible K. pneumoniae), three separate sequencing and analysis pipelines were performed: (1) a real-time Nanopore analysis approach identifying acquired AMR genes, (2) an assembly-based Nanopore approach identifying acquired AMR genes and chromosomal mutations, and (3) an approach using short read correction of Nanopore assemblies. The short read correction of Nanopore assemblies served as the reference standard to determine the accuracy of Nanopore sequencing results.

Results: With the real-time analysis approach, full annotation of acquired AMR genes occurred within 8 hours of subcultured isolates. Assemblies sufficient for full resistance gene and single nucleotide polymorphism annotation were available within 14 hours from subcultured isolates. The overall agreement of genotypic results and anticipated AST results for the 40 K. pneumoniae isolates was 77% (range 30-100%) and 92% (range 80-100%) for the real-time approach and the assembly approach, respectively. Evaluating the patients contributing the 40 isolates, the real-time approach and assembly approach could shorten the median time to effective antibiotic therapy by 20 hours and 26 hours, respectively, compared to standard AST.

Conclusions: Nanopore sequencing offers a rapid approach to both accurately identify resistance mechanisms as well as predict AST results for K. pneumoniae isolates. Bioinformatics improvements enabling real-time alignment coupled with rapid extraction and library preparation will further enhance the accuracy and workflow of the Nanopore real-time approach.

https://ift.tt/2CQtxaE

Single-dose Pharmacokinetics, Excretion, and Metabolism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic, in Healthy Volunteers [Pharmacology]

Zoliflodacin is a novel spiropyrimidinetrione with activity against bacterial Type II topoisomerases that inhibits DNA biosynthesis and results in accumulation of double strand cleavages in bacteria. We report results from two Phase 1 studies that investigated the safety, tolerability, and pharmacokinetics (PK) of zoliflodacin, and the absorption, distribution, metabolism, and excretion (ADME) after single doses in healthy volunteers. In the single ascending dose study, zoliflodacin was rapidly absorbed with a T_max between 1.5 and 2.3 h. Exposure increased dose proportionally up to 800 mg, and less than dose proportionally between 800 and 4000 mg. Urinary excretion of unchanged zoliflodacin was >5.0% of the total dose. In the fed state, absorption was delayed (T_max 4 h), accompanied by an increase in the AUC at 1500 and 3000 mg doses. In the ADME study (3000 mg PO), the PK profile of zoliflodacin had similar exposure (AUC and C_max) to the ascending dose study and a median T_max of 2.5 hours. A total of 97.8% of the administered radioactivity was recovered in excreta, with urine and fecal elimination accounting for approximately 18.2% and 79.6% of the dose, respectively. The major clearance pathway was via metabolism and elimination in feces with low urinary recovery of unchanged drug (approximately 2.5%) and metabolites accounting for 56% of the dose excreted in the feces. Zoliflodacin represented 72.3% and metabolite M3 accounted for 16.4% of total circulating radioactivity in human plasma. Along with the results from these studies and based upon the safety, PK, and the PK/PD targets, a dosage regimen was selected for evaluation in a Phase 2 study in urogenital gonorrhea.

https://ift.tt/2qgLx6v

Successfull treatment of Saksenaea sp. osteomyelitis by conservative surgery and intra-diaphysal incorporation of amphotericin B cement beads. [Clinical Therapeutics]

Osteoarticular mucormycosis are quite rare and challenging infections mostly due to direct inoculation during traumatic injury in immunocompetent patients. Their classical management includes a combination of aggressive surgical debridement that may lead to amputation and long-term systemic liposomal amphotericin B therapy. This article describes successful treatment of a Saksenaea sp. osteomyelitis in a patient with diabetes mellitus with a combination of systemic antifungal agents and a conservative surgery with insertion of amphotericin-impregnated cement beads.

https://ift.tt/2COxL2m

Zidovudine-mediated autophagy inhibition enhances mitochondrial toxicity in muscle cells [Antiviral Agents]

Nucleoside reverse transcriptase inhibitors (NRTI) such as zidovudine (AZT) are constituents of HIV-1 therapy and prevention of mother to child transmission. Prolonged thymidine analogues exposure has been associated with mitochondrial toxicities to heart, liver, and skeletal muscle. We hypothesized that the thymidine analogue AZT might interfere with autophagy in myocytes, a lysosomal degradation pathway implicated in regulation of mitochondrial recycling, cell survival and the pathogenesis of myodegenerative diseases. The impact of AZT and lamivudine (3TC) on C2C12 myocyte autophagy was studied using various methods based on LC3-GFP overexpression or LC3 staining in combination with western blotting, flow cytometry and confocal and electron microscopy. Lysosomal and mitochondrial functions were studied using appropriate staining for lysosomal mass, acidity, cathepsin activity as well as mitochondrial mass and membrane potential in combination with flow cytometry and confocal microscopy. AZT, but not 3TC, exerted a significant dose and time-dependent inhibitory effect on late stages of autophagosome maturation, which was reversible upon mTOR inhibition. Inhibition of late autophagy at therapeutic drug concentrations led to dysfunctional mitochondria accumulation with membrane hyperpolarization and increased ROS generation, and ultimately compromised cell viability. These AZT effects could be readily replicated by pharmacological and genetic inhibition of myocyte autophagy and most importantly rescued by pharmacological stimulation of autophago-lysosomal biogenesis. Our data suggest that the thymidine analogue AZT inhibits autophagy in myocytes, which in turn leads to accumulation of dysfunctional mitochondria with increased ROS generation and compromised cell viability. This novel mechanism could contribute to our understanding of the long-term side effects of antiviral agents.

https://ift.tt/2qe8KWW

Azidothymidine produces synergistic activity in combination with colistin against antibiotic-resistant Enterobacteriaceae [Experimental Therapeutics]

Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, antibiotic-resistant Enterobacteriaceae is prevalent and extremely difficult to treat. Reusing existing drugs and rejuvenating the therapeutic potential of existing antibiotics represent an attractive novel strategy. Azidothymidine (AZT) is an antiretroviral drug which is used in combination with other antivirals to prevent and to treat HIV/AIDS. AZT is also active against Gram-negative bacteria but has not been developed for that purpose. Here we investigated in vitro and in vivo efficacy of AZT in combination with colistin against antibiotic-resistant Enterobacteriaceae including extended-spectrum beta-lactamase (ESBL), New Delhi metallo-beta-lactamase 1 (NDM) or the mobilized colistin resistance (mcr-1) producing strains. Minimum inhibitory concentration was determined using the broth microdilution method. The combinatory effect of AZT and colistin was examined using the checkerboard method and time-kill analysis. A murine peritoneal infection model was used to test the therapeutic effect of the combination of AZT and colistin. Fractional inhibitory concentration index from checkerboard assay demonstrated that AZT synergized with colistin against 61% and 87% of ESBL-producing Escherichia coli and Klebsiella pneumoniae, respectively, 100% of NDM-1-producing strains and 92% of mcr-1 producing E. coli. Time-kill analysis demonstrated significant synergistic activities when AZT was combined with colistin. In the murine peritoneal infection model, AZT in combination with colistin showed augmented activities of both drugs in the treatment of NDM-1 K. pneumoniae and mcr-1 E. coli infections. AZT and colistin combination poses a potential to be used coherently to treat antibiotic-resistant Enterobacteriaceae infections.

https://ift.tt/2CMgpDj

Inhibition of Cytomegalovirus Replication with Extended Half-Life Synthetic Ozonides [Antiviral Agents]

Artesunate (AS), a semisynthetic artemisinin approved for malaria therapy, inhibits human cytomegalovirus (HCMV) replication in vitro, but therapeutic success in humans has been variable. We hypothesized that the short in vivo half-life of AS may contribute to the different treatment outcomes. We tested novel synthetic ozonides with longer half-lives against HCMV in vitro and mouse CMV (MCMV) in vivo. Screening of four ozonides against HCMV Towne pp28-luciferase recombinant identified OZ418 to have the best selectivity; its effective concentration inhibiting 50% viral growth (EC₅₀) was 9.8±0.2 µM, and cytotoxicity in non-infected human fibroblasts (CC₅₀) was 128.1±8.0 µM. In plaque reduction assays, OZ418 inhibited HCMV TB40 in a concentration-dependent manner as well as a ganciclovir (GCV)-resistant HCMV. The combination of OZ418 and ganciclovir (GCV) was synergistic in HCMV inhibition in vitro. Virus inhibition by OZ418 occurred at early stage and was dependent on cell density at the time of infection. OZ418 treatment reversed HCMV-mediated cell cycle progression and correlated with reduction of HCMV-induced expression of pRb, E2F1 and CDKs 1, 2, 4, and 6. In a MCMV model, once daily oral administration of OZ418 had significantly improved efficacy against MCMV as compared to twice daily oral AS. A parallel pharmacokinetic study with a single oral dose of OZ418 or AS showed a prolonged plasma half-life and higher unbound concentrations of OZ418 compared to AS. In summary, ozonides are proposed as potential therapeutics, alone or in combination with GCV, for HCMV infection in humans.

https://ift.tt/2qe8Gqa

Preclinical Characterization of NVR 3-778, a First-in-Class Capsid Assembly Modulator Against the Hepatitis B Virus [Antiviral Agents]

NVR 3-778 is the first Capsid Assembly Modulator (CAM) that has demonstrated antiviral activity in HBV infected patients. NVR 3-778 inhibited the generation of infectious HBV DNA containing virus particles with a mean antiviral EC₅₀ of 0.40 µM in HepG2.2.15 cells. The antiviral profile of NVR 3-778 indicates pan-genotypic antiviral activity and lack of cross-resistance with nucleos(t)ide inhibitors of HBV replication. The combination of NVR 3-778 with nucleos(t)ide analogs in vitro resulted in additive or synergistic antiviral activity. Mutations within the hydrophobic pocket at the dimer-dimer interface of the core protein could confer resistance to NVR 3-778, which is consistent with the ability of the compound to bind to core and to induce capsid assembly. By targeting core, NVR 3-778 inhibits pgRNA encapsidation, viral replication and the production of HBV DNA- and HBV RNA-containing particles. NVR 3-778 also inhibited de novo infection and viral replication in primary human hepatocytes with EC₅₀ values of 0.81 µM against HBV DNA and between 3.7 to 4.8 µM against the production of HBV antigens and intracellular HBV RNA. NVR 3-778 showed favorable pharmacokinetics and safety in animal species, allowing serum levels in excess of 100 µM to be achievable in mice and thus enabling efficacy studies in vivo. The overall preclinical profile of NVR 3-778 predicted antiviral activity in vivo and supported further evaluation for safety, pharmacokinetics, and antiviral activity in HBV infected patients.

https://ift.tt/2CMgpTP

Miltefosine reduces the cytolytic activity and virulence of Acinetobacter baumannii [Experimental Therapeutics]

Stagnation in antimicrobial development has led to a serious threat to public health in which some Acinetobacter baumannii infections have become untreatable. New therapeutics with alternative mechanisms of action to combat A. baumannii are therefore necessary to treat these infections. To this end, the virulence of A. baumannii isolates with varying antimicrobial susceptibilities was assessed when treated with miltefosine, a phospholipase C inhibitor. Phospholipase C activity is a contributor to A. baumannii virulence associated with hemolysis, cytolysis of A549 human alveolar epithelial cells and increased mortality in the Galleria mellonella experimental infection model. While the effects on bacterial growth were variable amongst strains, miltefosine treatment significantly reduced both the hemolytic and cytolytic activity of all treated A. baumannii strains. Additionally, scanning electron microscopy of polarized A549 cells infected with bacteria of the A. baumannii ATCC 19606^T strain or the AB5075 multidrug resistant isolate showed decrease in A549 cell damage with a concomitant increase in the presence of A549 surfactant upon administration of miltefosine. The therapeutic ability of miltefosine is further supported by the results of G. mellonella infections wherein miltefosine treatment of animals infected with ATCC 19606^T significantly decreased mortality. These data demonstrate that inhibition of phospholipase C activity results in the overall reduction of A. baumannii virulence in both in vitro and in vivo models making miltefosine a viable option for treatment of A. baumannii infections, particularly those caused by multidrug resistant isolates.

https://ift.tt/2qe8CGW

Emergence of resistance to macrolides and rifampicin in clinical isolates of Rhodococcus equi from foals in central Kentucky, USA: 1995 to 2017 [Epidemiology and Surveillance]

Objective: To determine the prevalence of R. equi strains resistant to macrolides and rifampicin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky.

Methods: Retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostics laboratories in Kentucky between January 1995 and December 2017. Samples were included if R. equi was cultured and tested for in vitro susceptibility to erythromycin or rifampicin.

Results: In vitro susceptibility to erythromycin was available for 2169 isolates of R. equi while susceptibility to both erythromycin and rifampicin was available for 1681 isolates. Rifampicin resistance was first detected in 2000 and erythromycin resistance was first detected in 2004. Between 1995 and 2006, the proportion of resistant isolates of R. equi was 0.7% for erythromycin and 2.3% for rifampicin. There was a significant (P <0.001) increase in the proportion of resistant R. equi between 2007 and 2017, with 13.6% of isolates being resistant to erythromycin and 16.1% being resistant to rifampicin. Between 2007 and 2017, isolates of R. equi resistant to erythromycin or rifampicin were significantly less likely to be isolated from feces than from the respiratory tract, other soft tissues, or musculoskeletal infections.

Conclusions: The considerable increase in the prevalence of isolates of R. equi resistant to macrolides and rifampicin since 2007 is of concern for both human and animal health.

https://ift.tt/2CNS4x0

Spontaneous mutational frequency and FKS mutation rates vary by echinocandin agent against Candida glabrata [Mechanisms of Resistance]

Echinocandins are front-line agents for treatment of invasive candidiasis. There are no reported agent-specific differences in Candida mutational frequency of resistance or propensity to develop FKS mutations. The objective of this study was to measure spontaneous and FKS mutation rates among Candida glabrata. Twenty bloodstream isolates from patients with or without prior echinocandin exposure were included. Minimum inhibitory (MIC), minimum fungicidal (MFC) and mutation prevention concentrations were higher for caspofungin than anidulafungin (P<0.0001) and micafungin (P<0.0001). Mutational frequencies of resistance at 3x baseline MIC were highest for caspofungin and lowest for micafungin. Two-hundred and forty-seven isolates were recovered at or above the MFC for caspofungin (n=159), anidulafungin (n=74), or micafungin (n=14). Agent-specific MIC increases were noted for anidulafungin and caspofungin, but not micafungin. Thirty-three percent of isolates harbored hot spot mutations in FKS1 (n=6) or FKS2 (n=76). Mutations at the Ser629 (Fks1) or Ser663 (Fks2) loci were more common following selection with anidulafungin or micafungin than with caspofungin (P = 0.003). Four isolates demonstrated >4-fold increases in MICs without FKS hot spot mutations; 3 of these harbored Fks2 mutations upstream of hot spot 1. The final isolate was FKS1 and FKS2 wild-type, but IC₅₀s of caspofungin and micafungin were increased 2.7-fold and 8-fold, respectively. In conclusion, micafungin may be superior in vitro to the other agents in limiting the emergence of resistance among C. glabrata. On the other hand, caspofungin exposure may be most likely to promote resistance development. These data provide a foundation for future investigations of newly-developed echinocandin agents.

https://ift.tt/2qiWIeL

Population pharmacokinetic model and limited sampling strategies for personalized dosing of levofloxacin in tuberculosis patients [Clinical Therapeutics]

Levofloxacin is an anti-tuberculosis drug with substantial interindividual pharmacokinetic variability; therapeutic drug monitoring (TDM) could therefore be helpful to improve treatment results. TDM would be more feasible with limited sampling strategies (LSSs), a method to estimate area under the concentration curve for the 24 h dosing interval (AUC_0-24) by using a limited number of samples. This study aimed to develop a population pharmacokinetic (popPK) model of levofloxacin in tuberculosis patients, along with LSSs using a Bayesian and multiple linear regression approach.

The popPK model and Bayesian LSS were developed using data of 30 patients and externally validated with 20 patients. The LSS based on multiple linear regression was internally validated using jackknife analysis. Only clinically suitable LSSs (maximum timespan 8 h, minimum interval 1 h, 1 to 3 samples) were tested. Performance criteria were root mean squared error (RMSE) <15%, mean prediction error (MPE) <5%, and r² > 0.95.

A one compartment model with lag time best described the data while only slightly underestimating the AUC_0-24 (mean –7.9%, SE 1.7%). The Bayesian LSS using 0 and 5 h post-dose samples (RMSE 8.8%, MPE 0.42%, r² 0.957) adequately estimated the AUC_0-24 with a mean underestimation of –4.4% (SE 2.7%). The multiple linear regression LSS using 0 and 4 h post-dose samples (RMSE 7.0%, MPE 5.5%, r² 0.977) was internally validated with a mean underestimation of -0.46% (SE 2.0%).

In this study, we successfully developed a popPK model and two LSSs that could be implemented in clinical practice to assist TDM of levofloxacin.

https://ift.tt/2CMrp3o

Outcomes by Minimum Inhibitory Concentrations for Patients Treated with Isavuconazole or Voriconazole for Invasive Aspergillosis in the Phase 3 SECURE and VITAL Trials [Susceptibility]

This pooled analysis evaluated the relationship of isavuconazole and voriconazole minimum inhibitory concentrations (MICs) of Aspergillus pathogens at baseline with all-cause mortality and clinical outcomes following treatment with either drug in the SECURE and VITAL trials. Isavuconazole and voriconazole may have had reduced efficacy against pathogens with MICs ≥16 µg/mL, but there was no relationship in cases where the MIC was <16 µg/mL with clinical outcomes for either drug.

https://ift.tt/2qe8xmC

Use of Translational PK/PD Infection Models to Understand Impact of Neutropenia on Efficacy of Tedizolid Phosphate [Pharmacology]

Tedizolid phosphate, the prodrug of the active antibiotic tedizolid, is an oxazolidinone for the treatment of acute bacterial skin and skin structure infections. Studies in a mouse thigh infection model demonstrated improved potency and pharmacokinetics-pharmacodynamics (PK/PD) vs linezolid. Subsequent studies showed that the efficacy of tedizolid was enhanced in immune competent (IC) compared with neutropenic (IS) mice, with stasis at clinically relevant doses being achieved only in the presence of granulocytes. The tedizolid label therefore contains a warning about use in neutropenic patients. This study reevaluated the PK/PD of tedizolid and linezolid in the mouse thigh infection model in IC and IS mice using a methicillin-resistant Staphylococcus aureus (MRSA) strain (ATCC 33591) and a methicillin-susceptible S. aureus (MSSA) strain (ATCC 29213). The antistaphylococcal effect of doses ranging from 1–150 mg/kg of tedizolid (once daily) or linezolid (twice daily) was determined at 24, 48, and 72 hours after initiating treatment. In IC mice, stasis was achieved in the absence of antibiotics, and both tedizolid and linezolid reduced the burden further beyond a static effect. In IS mice, tedizolid achieved stasis at 72 hours at a human clinical dose of 200 mg against MRSA ATCC 33591 and MSSA ATCC 29213, several-fold lower than in earlier studies. Linezolid achieved a static effect against MRSA ATCC 33591 in IS mice at a dose lower than that used clinically. This study demonstrates that with time both tedizolid and linezolid at clinically relevant exposures achieve stasis in neutropenic mice with MRSA or MSSA thigh infection.

https://ift.tt/2CNfjXW

Efficacy of azithromycin and miltefosine in experimental systemic pythiosis in immunosuppressed mice [Experimental Therapeutics]

We evaluated the efficacy of azithromycin (50 mg/kg q12h orally) and miltefosine (25 mg/kg q24h orally) treatment in an experimental model of vascular/disseminated pythiosis in immunosuppressed mice. Azithromycin was the only treatment able to reduce mortality. Histopathological findings showed acute vascular inflammation, pathogen dissemination, necrotizing myositis, neuritis, and arteritis. The results suggest that azithromycin, but not miltefosine, may have clinical relevance in the treatment of vascular/disseminated pythiosis.

https://ift.tt/2qhTyYE

Impact of community respiratory viral infections in urban children with asthma

Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on asthmatic children in the community, particularly in the high-risk urban environment, is less well-defined.

https://ift.tt/2Q8TJ49

Introduction: Special Issue—The Origins of Macrophages and Their Roles Beyond Immunology

In the context of ontogeny and phylogeny, macrophages emerge much earlier than other hematopoietic cells, including monocytes, implying that their roles extend beyond immunology. Phagocytosis, a representative function of macrophages, has been examined since the late 19th century and such studies were the basis of characterizing innate immunity. Macrophages also make a range of cytokines important in both innate and adaptive immunity. Recently, their non-immunological homeostatic roles in organ development, angiogenesis, tissue repair/regeneration and metabolism have also become clear. This involvement in so many responses in virtually all tissues requires them to be enormously flexible but their phenotypic and functional heterogeneity have made it difficult to delineate the origins of macrophages in specific sites under different circumstances.

https://ift.tt/2yHFSe8

Myositis ossificans traumatica of the masticatory muscles: etiology, diagnosis and treatment

Abstract

Background

Myositis ossificans describes a heterotopic bone formation within a muscle. Thereby myositis ossificans is classified in two different groups: myositis ossificans progressiva (MOP) which describes a genetic autosomal dominant rare disease and myositis ossificans traumatica (MOT). The exact pathogenesis of MOT is unclear. The aim of this article was to analyse and interpret the existing literature reporting MOT of masticatory muscles and compare the results with our own clinical experience with MOT. Risk-factors, etiology, clinical features, diagnostic imaging, as well as different treatment options were evaluated and recommendations for the prevention, diagnosis, and therapy of MOT of the masticatory muscles were given.

Methods

Following the PRISMA-Guidelines, a systematic search within the PubMed/Medline database with a view to record literature of MOT of the masticatory muscles was performed. Furthermore, the database of our own clinic was screened for cases of MOT.

Results

In total, 63 cases of MOT of the masticatory muscles which were reported in English-based literature were included in this study. Overall, 25 female and 37 male patients could be analysed whereas one patient's gender was unknown. Complication of wisdom-tooth infection (n = 3) as well as the results of dental procedures like dental extraction (n = 7), mandibular nerve block (n = 4), periodontitis therapy (n = 1) were reported as MOT cases. From the 15 reported cases that appeared after dental treatment like extraction or local anesthesia the medial pterygoid (n = 10) was the most affected muscle. Hereof, females were more affected (n = 9) than males (n = 6). The most reported clinical symptom of MOT was trismus (n = 54), followed by swelling (n = 17) and pain (n = 13). One clinical case provided by the authors was detected.

Conclusions

Dental procedures, such as local anesthesia or extractions, may cause MOT of the masticatory musculature. Demographical analyses demonstrate that females have a higher risk of developing MOT with respect to dental treatment. The most important treatment option is surgical excision. Subsequent physical therapy can have beneficial effects. Nevertheless, a benefit of interpositional materials and drugs as therapy of MOT of the masticatory muscles has not yet been proven. Myositis ossificans progressiva has to be excluded.

https://ift.tt/2JpMyla

Tape stripping alters the microbe‐host correlations in mouse skin

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2ETviGv

Developing combination strategies using PD-1 checkpoint inhibitors to treat cancer

Abstract

More than 3000 clinical trials are evaluating the clinical activity of the PD-1 checkpoint inhibitors as monotherapies and in combinations with other cancer therapies [1]. The PD-1 checkpoint inhibitors are remarkable for their clinical activities in shrinking tumors across a wide range of tumor types, in causing durable responses, and in their tolerability. These attributes position them as favorable agents in clinical combinations. Historically, approaches to cancer therapy combinations focused on agents with orthogonal activities to avoid shared resistance mechanisms and shared toxicities. Although CTLA-4/PD-1 combinations have progressed based on possible immune interactions, additional approaches have used more orthogonal treatments such as standard of care chemotherapies and anti-angiogenesis inhibitors. Using the concept of independent activity pioneered by Bliss [2], examples of these approaches were compared. Both standard of care chemotherapy and anti-angiogenesis combinations show promising clinical activity above that predicted by the independent contributions of the agents tested on their own. In contrast, the combinations of CTLA4/PD-1 checkpoint inhibitors in renal cancer and melanoma show no more activity than that predicted by the independent contributions of the monotherapies. This update on approaches to the development of clinical combination therapies highlights the potential importance of combining PD-1 checkpoint inhibitors with a broad range of clinically active partners.

https://ift.tt/2PZ3gu9

Rising to the challenges of precision medicine: nasal inflammation research in China

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2Oec0v4

SMART Infrastructure: Benefits and Pitfalls

Collins, B; Ramchurn, SD; Zhao, D; Bahaj, AB; Richards, D; Jennings, NR; Beckford, J; (2018) SMART Infrastructure: Benefits and Pitfalls. (ICIF White Paper Collection ). International Centre for Infrastructure Futures (ICIF): London, UK. Green open access

https://ift.tt/2Jo7WaH

Enabling trade-offs between accuracy and computational cost: Adaptive algorithms to reduce time to clinical insight

Dakka, J; Farkas-Pall, K; Balasubramanian, V; Turilli, M; Wan, S; Wright, DW; Zasada, S; ... Jha, S; + view all Dakka, J; Farkas-Pall, K; Balasubramanian, V; Turilli, M; Wan, S; Wright, DW; Zasada, S; Coveney, PV; Jha, S; - view fewer (2018) Enabling trade-offs between accuracy and computational cost: Adaptive algorithms to reduce time to clinical insight. In: (Proceedings) 2018 18th IEEE/ACM International Symposium on Cluster, Cloud and Grid Computing (CCGRID). (pp. pp. 572-577). IEEE: Washington DC, USA. Green open access

https://ift.tt/2D9bmOn

Evidence for the Value of a Systems Approach to Infrastructure Planning, Delivery and Operation

Carhart, N; Ersoy, A; Taylor, C; Beigi, S; (2018) Evidence for the Value of a Systems Approach to Infrastructure Planning, Delivery and Operation. (ICIF White Paper Collection ). International Centre for Infrastructure Futures (ICIF): London, UK. Green open access

https://ift.tt/2Jo7KIv

Monocular 3D Reconstruction of the Colon Using CNNs Trained on Synthetic Data

Rau, A; Chadebecq, F; Stoyanov, D; Riordan, P; (2018) Monocular 3D Reconstruction of the Colon Using CNNs Trained on Synthetic Data. In: Proceedings of the 8th joint workshop on New Technologies for Computer/Robot Assisted Surgery:CRAS 2018. CRAS: London, UK. (In press).

https://ift.tt/2DaNgTe

Evaluating retrofit options in a historical city center: Relevance of bio-based insulation and the need to consider complex urban form in decision-making

Claude, S; Ginestet, S; Bonhomme, M; Taylor, JG; Marincioni, V; Korolija, I; Altamirano, H; (2018) Evaluating retrofit options in a historical city center: Relevance of bio-based insulation and the need to consider complex urban form in decision-making. Energy and Buildings 10.1016/j.enbuild.2018.10.026 .

https://ift.tt/2JpCqJa

Multistatic adaptive CFAR detection in non-Gaussian clutter

Palama, R; Greco, M; Gini, F; (2016) Multistatic adaptive CFAR detection in non-Gaussian clutter. EURASIP Journal on Advances in Signal Processing , 2016 , Article 107. 10.1186/s13634-016-0408-1 . Green open access

https://ift.tt/2DbYtDb

The Use of Condition Score to Determine Glycerol Concentration in the Treatment of Waterlogged Leather: an Empirical Solution

Sully, DM; Suenson-Taylor, K; (1996) The Use of Condition Score to Determine Glycerol Concentration in the Treatment of Waterlogged Leather: an Empirical Solution. In: Proceedings of the 6th ICOM-CC Group on Wet Archaeological Organic Materials Conference, York. (pp. pp. 157-172). ICOM-CC Group: Germany: Bremerhaven.

https://ift.tt/2JlLIpT

Emerging Approaches and Issues in Regulation and Governance of Infrastructure Based Services

Hiteva, R; Lovell, K; McArthur, JM; Smith, H; Zerjav, V; (2018) Emerging Approaches and Issues in Regulation and Governance of Infrastructure Based Services. (ICIF White Paper Collection ). International Centre for Infrastructure Futures (ICIF): London, UK. Green open access

https://ift.tt/2D9tw2f

Novel preparation of monodisperse microbubbles by integrating oscillating electric fields with microfluidics

Kothandaraman, A; Harker, A; Ventikos, Y; Edirisinghe, M; (2018) Novel preparation of monodisperse microbubbles by integrating oscillating electric fields with microfluidics. Micromachines , 9 (10) , Article 497. 10.3390/mi9100497 . Green open access

https://ift.tt/2JpkfUa

Precision and False Perceptual Inference

Parr, T; Benrimoh, DA; Vincent, P; Friston, KJ; (2018) Precision and False Perceptual Inference. Frontiers in Integrative Neuroscience , 12 , Article 39. 10.3389/fnint.2018.00039 . Green open access

https://ift.tt/2DbldTO

Enhanced climate instability in the North Atlantic and southern Europe during the Last Interglacial

Tzedakis, PC; Drysdale, RN; Margari, V; Skinner, LC; Menviel, L; Rhodes, RH; Taschetto, AS; ... Zanchetta, G; + view all Tzedakis, PC; Drysdale, RN; Margari, V; Skinner, LC; Menviel, L; Rhodes, RH; Taschetto, AS; Hodell, DA; Crowhurst, SJ; Hellstrom, JC; Fallick, AE; Grimalt, JO; McManus, JF; Martrat, B; Mokeddem, Z; Parrenin, F; Regattieri, E; Roe, K; Zanchetta, G; - view fewer (2018) Enhanced climate instability in the North Atlantic and southern Europe during the Last Interglacial. Nature Communications , 9 , Article 4235. 10.1038/s41467-018-06683-3 . Green open access

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Achieving Low Carbon Thinking Everywhere in Infrastructure Delivery

Bahaj, AS; Richards, DJ; Ruangpattana, S; (2018) Achieving Low Carbon Thinking Everywhere in Infrastructure Delivery. (ICIF White Paper Collection ). International Centre for Infrastructure Futures (ICIF): London, UK. Green open access

https://ift.tt/2DcKL31

Letter to the Editor

Abeysiri, MS; Richards, PT; (2018) Letter to the Editor. Journal of Perioperative Practice , 28 (6) p. 137. 10.1177/2396939318778494 . Green open access

https://ift.tt/2JmNRBF

A Model of Sea Ice Formation in Leads and Polynyas

Heorton, HDBS; Radia, N; Feltham, DL; (2017) A Model of Sea Ice Formation in Leads and Polynyas. Journal of Physical Oceanography , 47 (7) pp. 1701-1718. 10.1175/JPO-D-16-0224.1 . Green open access

https://ift.tt/2D85FAh

Smoking Status and Oral Health-related Quality of Life Among Adults in the United Kingdom

Bakri, NN; Tsakos, G; Masood, M; (2018) Smoking Status and Oral Health-related Quality of Life Among Adults in the United Kingdom. British Dental Journal , 225 (2) pp. 153-158. 10.1038/sj.bdj.2018.529 .

https://ift.tt/2JmbqKD

Precipitation as an Enabling Technology for the Intensification of Biopharmaceutical Manufacture

Martinez, M; Spitali, M; Norrant, EL; Bracewell, DG; (2018) Precipitation as an Enabling Technology for the Intensification of Biopharmaceutical Manufacture. Trends in Biotechnology 10.1016/j.tibtech.2018.09.001 . (In press). Green open access

https://ift.tt/2DbsItR

The treatment of refractory angle-closure glaucoma in a patient with X-linked juvenile retinoschisis

Low, S; Mohamed, R; Ting, M; Webster, AR; Garway-Heath, DF; (2018) The treatment of refractory angle-closure glaucoma in a patient with X-linked juvenile retinoschisis. Ophthalmic Genetics , 39 (5) pp. 625-627. 10.1080/13816810.2018.1490961 .

https://ift.tt/2JnXCiP

Quiet Eye Facilitates Sensorimotor Preprograming and Online Control of Precision Aiming in Golf Putting

Causer, J; Hayes, SJ; Hooper, JM; Bennett, SJ; (2017) Quiet Eye Facilitates Sensorimotor Preprograming and Online Control of Precision Aiming in Golf Putting. Cognitive Processing , 18 (1) pp. 47-54. 10.1007/s10339-016-0783-4 . Green open access

https://ift.tt/2DbbQDI

Statistical study of ULF waves in the magnetotail by THEMIS observations

Zhang, S; Tian, A; Shi, Q; Li, H; Degeling, AW; Jonathan Rae, I; Forsyth, C; ... Pu, Z; + view all Zhang, S; Tian, A; Shi, Q; Li, H; Degeling, AW; Jonathan Rae, I; Forsyth, C; Wang, M; Shen, X; Sun, W; Bai, S; Guo, R; Wang, H; Fazakerley, A; Fu, S; Pu, Z; - view fewer (2018) Statistical study of ULF waves in the magnetotail by THEMIS observations. Annales Geophysicae , 36 (5) pp. 1335-1346. 10.5194/angeo-36-1335-2018 . Green open access

https://ift.tt/2JmbpGz

Search for Standard-model Z and Higgs Bosons Decaying Into a Bottom-antibottom Quark Pair in Proton-antiproton Collisions at 1.96 TeV

Aaltonen, T; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; ... Zucchelli, S; + view all Aaltonen, T; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, JA; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, VE; Barnett, BA; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Bland, KR; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, HS; Burkett, K; Busetto, G; Bussey, P; Butti, P; Buzatu, A; Calamba, A; Camarda, S; Campanelli, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cerri, A; Cerrito, L; Chen, YC; Chertok, M; Chiarelli, G; Chlachidze, G; Cho, K; Chokheli, D; Clark, A; Clarke, C; Convery, ME; Conway, J; Corbo, M; Cordelli, M; Cox, CA; Cox, DJ; Cremonesi, M; Cruz, D; Cuevas, J; Culbertson, R; d'Ascenzo, N; Datta, M; de Barbaro, P; Demortier, L; Deninno, M; D'Errico, M; Devoto, F; Di Canto, A; Di Ruzza, B; Dittmann, JR; Donati, S; D'Onofrio, M; Dorigo, M; Driutti, A; Ebina, K; Edgar, R; Elagin, A; Erbacher, R; Errede, S; Esham, B; Farrington, S; Fernandez Ramos, JP; Field, R; Flanagan, G; Forrest, R; Franklin, M; Freeman, JC; Frisch, H; Funakoshi, Y; Galloni, C; Garfinkel, AF; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Gibson, K; Ginsburg, CM; Giokaris, N; Giromini, P; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; Gonzalez Lopez, O; Gorelov, I; Goshaw, AT; Goulianos, K; Gramellini, E; Grosso-Pilcher, C; da Costa, JG; Hahn, SR; Han, JY; Happacher, F; Hara, K; Hare, M; Harr, RF; Harrington-Taber, T; Hatakeyama, K; Hays, C; Heinrich, J; Herndon, M; Hocker, A; Hong, Z; Hopkins, W; Hou, S; Hughes, RE; Husemann, U; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, EJ; Jindariani, S; Jones, M; Joo, KK; Jun, SY; Junk, TR; Kambeitz, M; Kamon, T; Karchin, PE; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Kilminster, B; Kim, DH; Kim, HS; Kim, JE; Kim, MJ; Kim, SH; Kim, SB; Kim, YJ; Kim, YK; Kimura, N; Kirby, M; Kondo, K; Kong, DJ; Konigsberg, J; Kotwal, A; Kreps, M; Kroll, J; Kruse, M; Kuhr, T; Kurata, M; Laasanen, AT; Lammel, S; Lancaster, M; Lannon, K; Latino, G; Lee, HS; Lee, JS; Leo, S; Leone, S; Lewis, JD; Limosani, A; Lipeles, E; Lister, A; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Luca, A; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Marchese, L; Margaroli, F; Marino, P; Matera, K; Mattson, ME; Mazzacane, A; Mazzanti, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Michielin, E; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Moon, CS; Moore, R; Morello, MJ; Mukherjee, A; Muller, T; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Nigmanov, T; Nodulman, L; Noh, SY; Norniella, O; Oakes, L; Oh, SH; Oh, YD; Okusawa, T; Orava, R; Ortolan, L; Pagliarone, C; Palencia, E; Palni, P; Papadimitriou, V; Parker, W; Pauletta, G; Paulini, M; Paus, C; Phillips, TJ; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Pranko, A; Prokoshin, F; Ptohos, F; Punzi, G; Redondo Fernandez, I; Renton, P; Rescigno, M; Rimondi, F; Ristori, L; Robson, A; Rodriguez, T; Rolli, S; Ronzani, M; Roser, R; Rosner, JL; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Sakumoto, WK; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, EE; Schwarz, T; Scodellaro, L; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, SZ; Shears, T; Shepard, PF; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sliwa, K; Smith, JR; Snider, FD; Song, H; Sorin, V; St Denis, R; Stancari, M; Stentz, D; Strologas, J; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, PK; Thom, J; Thomson, E; Thukral, V; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Vazquez, F; Velev, G; Vellidis, C; Vernieri, C; Vidal, M; Vilar, R; Vizan, J; Vogel, M; Volpi, G; Wagner, P; Wallny, R; Wang, SM; Waters, D; Wester, WC; Whiteson, D; Wicklund, AB; Wilbur, S; Williams, HH; Wilson, JS; Wilson, P; Winer, BL; Wittich, P; Wolbers, S; Wolfmeister, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, UK; Yang, YC; Yao, W-M; Yeh, GP; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, GB; Yu, I; Zanetti, AM; Zeng, Y; Zhou, C; Zucchelli, S; - view fewer (2018) Search for Standard-model Z and Higgs Bosons Decaying Into a Bottom-antibottom Quark Pair in Proton-antiproton Collisions at 1.96 TeV. Physical Review D , 98 , Article 072002. 10.1103/PhysRevD.98.072002 . Green open access

https://ift.tt/2DbsG5d

Seventeen New Cases of Chronic Ulcerative Stomatitis with Literature Review

Abstract

Chronic ulcerative stomatitis (CUS) is a poorly understood disease with clinical and histologic overlap with lichen planus (LP). Unlike classic LP, direct immunofluorescence (DIF) studies in cases of CUS exhibit a granular pattern of IgG in nuclei of basal and parabasal cells. This study assesses the demographic, clinical, histologic, and DIF features of CUS. It is important to differentiate CUS from LP and other vesiculobullous diseases (VBD) because lesions of CUS are resistant to steroid therapy, which is typically used to control LP and VBD. A literature review and IRB-approved retrospective search of CUS was performed within the archives of the University of Florida (UF) Oral Pathology Biopsy Service from 2007 to 2017. Fifty-two cases were identified from the literature and seventeen new cases were identified in our series. All UF patients were female and the median age was 64-years. The majority of patients were Caucasian and the most common location was buccal mucosa. Frequent clinical presentations were pain, erythema, leukoplakia, and ulcerations. Histologic features included epithelial separation, atrophic epithelium, and a chronic inflammatory infiltrate. All cases were confirmed with DIF testing that showed a speckled pattern of IgG staining in basal and parabasal cell nuclei. Fibrinogen was present in eleven cases and two cases were positive for C3. The results of our series are in accordance with the literature. Since CUS has overlapping features with LP and VBD, clinicians and pathologists should consider this entity and confirm diagnosis with DIF testing when recalcitrant oral ulcerative diseases are encountered.

https://ift.tt/2qgN5gR

Seventeen New Cases of Chronic Ulcerative Stomatitis with Literature Review

Abstract

Chronic ulcerative stomatitis (CUS) is a poorly understood disease with clinical and histologic overlap with lichen planus (LP). Unlike classic LP, direct immunofluorescence (DIF) studies in cases of CUS exhibit a granular pattern of IgG in nuclei of basal and parabasal cells. This study assesses the demographic, clinical, histologic, and DIF features of CUS. It is important to differentiate CUS from LP and other vesiculobullous diseases (VBD) because lesions of CUS are resistant to steroid therapy, which is typically used to control LP and VBD. A literature review and IRB-approved retrospective search of CUS was performed within the archives of the University of Florida (UF) Oral Pathology Biopsy Service from 2007 to 2017. Fifty-two cases were identified from the literature and seventeen new cases were identified in our series. All UF patients were female and the median age was 64-years. The majority of patients were Caucasian and the most common location was buccal mucosa. Frequent clinical presentations were pain, erythema, leukoplakia, and ulcerations. Histologic features included epithelial separation, atrophic epithelium, and a chronic inflammatory infiltrate. All cases were confirmed with DIF testing that showed a speckled pattern of IgG staining in basal and parabasal cell nuclei. Fibrinogen was present in eleven cases and two cases were positive for C3. The results of our series are in accordance with the literature. Since CUS has overlapping features with LP and VBD, clinicians and pathologists should consider this entity and confirm diagnosis with DIF testing when recalcitrant oral ulcerative diseases are encountered.

https://ift.tt/2qgN5gR

TERT promoter mutational screening as a tool to predict malignant behaviour in follicular thyroid tumours—three examples from the clinical routine

Abstract

Follicular thyroid adenomas (FTAs) and carcinomas (FTCs), collectively the most common thyroid neoplasms, constitute a significant clinical challenge since histological evidence of invasive behaviour is required for a malignant diagnosis. Small subsets of FTAs relapse as manifest malignant FTCs, indicating that histology is not always adequate to predict malignant potential. Lately, recurrent mutations in the promoter of the Telomerase reverse transcriptase (TERT) gene have been coupled to FTCs, whereas FTAs usually lack this aberrancy. We describe three patients with follicular thyroid tumours in which TERT promoter mutational screening was employed as part of the clinical work-up to pinpoint malignant potential. In two retrospective analyses of seemingly benign lesions, the detected mutations predicted future skeletal metastases, and in one prospective case, the mutational screening led to a different clinical management of the afflicted patient. We therefore consider TERT promoter mutational screening an adjunct tool of value in equivocal cases.

https://ift.tt/2qfBdvh

Carbonic anhydrases II, IX, and XII in Barrett’s esophagus and adenocarcinoma

Abstract

The aim of our retrospective study was to investigate the expression and clinical significance of the cancer-associated carbonic anhydrases (CAs) II, IX, and XII in Barrett's esophagus and esophageal adenocarcinoma (EAC). We evaluated 101 archival specimens from patients with EAC as well as seven and 26 samples from patients with high-and low-grade dysplasia, respectively. In addition, normal esophageal squamous epithelium, gastric, and intestinal metaplasia were analyzed when present. The expression patterns of isozymes were detected by immunohistochemistry. CAII and CIX expression levels were lower in the squamous epithelium than in the columnar cells while CAXII showed an opposite pattern and was present mainly in squamous epithelium. Expression patterns in benign, dysplastic, or malignant esophageal columnar lesions were not significantly different. The assessment of clinicopathological associations showed that CAII was significantly downregulated in metastatic disease (p = 0.026). CAIX showed no association with prognosis, although there appeared to be an association (p = 0.056) between high expression and nodal spread. In conclusion, CAII, CAIX, and CAXII do not serve as biomarkers for different phases in the development of EAC.

https://ift.tt/2Q3WJyD

Anspruch auf Versorgung mit einem Cochleaimplantat

https://ift.tt/2JpkkXV

Targeting cytokines to treat autoinflammatory diseases

Publication date: Available online 28 October 2018

Source: Clinical Immunology

Author(s): Jonathan S. Hausmann

Abstract

Autoinflammatory diseases are rare group conditions manifested by recurrent fevers, systemic inflammation, and dysfunctions of the innate immune system. These conditions are characterized by overproduction or lack of inhibition of various cytokines, and the advent of biologic drugs that block specific cytokines involved in these conditions have revolutionized their treatment. In this review, I will discuss the most common autoinflammatory conditions of adulthood including Familial Mediterranean Fever, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency/hyperimmunoglobulinemia D Syndrome, TNF receptor-associated autoinflammatory syndrome, and systemic juvenile idiopathic arthritis/adult-onset Still's disease. I will discuss how IL-1, IL-6, IL-18, and TNF play pathogenic roles in these conditions and will review the evidence behind cytokine blockade for these diseases. Throughout the paper, I will reflect on gaps in knowledge of autoinflammatory diseases and will highlight the latest advances and newest drugs in development.

https://ift.tt/2CMTt6S

Gastric outlet obstruction secondary to orbera intragastric balloon

Abstract

Intragastric balloons are used as a temporary restrictive method in obesity to induce weight loss. They are typically recommended when patients have mild obesity and have failed traditional first line treatments of diet, exercise and behaviour modification. We report a case of a 45-year-old female who presented with nausea, vomiting and abdominal pain two weeks following an uncomplicated insertion of an intragastric balloon. Following investigation, she was found to have a gastric outlet obstruction which required endoscopic removal of the balloon. While a rare occurrence, gastric outlet obstruction as seen in this case, highlights the importance of early recognition in order to proceed with swift diagnosis and intervention in order to prevent significant morbidity such as ischaemia and perforation.

https://ift.tt/2zbLpt0

Oesophageal adenocarcinoma following gastric band surgery in two patients

Abstract

Oesophageal adenocarcinoma following gastric band surgery has only been reported three times previously. The incidence is higher in morbidly obese patients, and its pathogenesis is correlated to reflux-induced microenvironmental changes. Bariatric surgery is transformative and its potential benefit for a substantial population is huge. Although no causal relationship with bariatric procedures has been evidenced to date, symptoms of adenocarcinoma—particularly anorexia, weight loss and dysphagia—can easily be overshadowed by alterations in eating patterns associated with weight-loss procedures. We report two cases of oesophageal adenocarcinoma in patients who had undergone a gastric banding procedure, and invite readers to consider the role that pre- and post-operative acid reflux dynamics may have precipitating neoplastic disease, and how endoscopic surveillance may play a role in prevention.

https://ift.tt/2StlJkc

Surgical management of a giant right atrial myxoma

Abstract

Cardiac tumours represent around 0.2% of tumours overall, and primary cardiac tumours are even more uncommon. We report the case of a 72-year-old female with a 7 cm × 4 cm right atrial mass which was prolapsing through the tricuspid valve. The mass was resected and histological analysis confirmed a myxoma. This report describes a rare finding of a giant right atrial mxyoma and subsequent surgical management.

https://ift.tt/2zaE5xG

Tulip piercing the aorta: a rare case of IVC filter aortic perforation and obstruction

ABSTRACT

Prolonged implantation of inferior vena cava (IVC) filters can lead to significant morbidity. We present a 25-year-old man with antiphospholipid syndrome, lower extremity deep vein thrombosis, and subsequent Gunther-Tulip IVC filter placement. More than 10 years following IVC filter placement he developed progressive abdominal and back pains. Cross-sectional angiography revealed that he had a chronic IVC occlusion, and IVC filter limb extensions into the infrarenal aorta, lumbar spine, and right psoas muscle. The IVC filter limb protruding into the aorta had also pierced through the backwall to lead to partial lumen thrombosis and obstruction. The patient underwent a transabdominal exposure of the infrarenal IVC and aorta, filter explantation and aortic patch angioplasty repair. This case highlights the severity of aortic injury from a protruding IVC filter limb that necessitated open aortic repair. Improved selection, monitoring and retrieval stewardship of IVC filters can help reduce the risk of unintended aortic complications.

https://ift.tt/2SsXRxd

Hemothorax after emphysematous bullectomy using a linear staple device with bioabsorbable polyglycolic acid felt

Abstract

A linear stapler with bioabsorbable polyglycolic acid felt is widely used during the resection of emphysematous lung. Currently, an improved staple device with polyglycolic acid felt is being used owing to a history of complications, such as bleeding, that was associated with the previous model. Here, we report a case of a 69-year-old man who presented to our department for treatment of left lower lobe lung cancer using the new staple device. A left lower lobectomy and emphysematous bullectomy were performed. Reoperation was performed following the diagnosis of a postoperative hemothorax. During that operation, a staple with reinforcing material was found to be in contact with the proliferating vessels on the lung surface, resulting in an active bleed. The vessel was cauterized, and the bleeding stopped. This is the first case study to report bleeding associated with the improved staple device.

https://ift.tt/2zdbwzT

A left ventricular assist device for a patient with peripartum cardiomyopathy

Abstract

Since its introduction in Japan in 1980, the extracorporeal left ventricular assist device has been used as a bridge to the recovery of cardiac function or to heart transplantation by many institutions. In this case report, we describe a 23-year-old female with peripartum cardiomyopathy. She had a persistently low cardiac index despite intensive care with intravenous inotropes, intra-aortic balloon pumping and extracorporeal membrane oxygenation; thus, we implanted an extracorporeal left ventricular assist device. Thereafter, her cardiac function gradually improved; the device was removed 2 months after the implantation. She currently has good heart function.

https://ift.tt/2Svxab4

Endo GIA stapler malfunction in a small bowel loop resection

Abstract

Endovascular gastrointestinal anastomosis (Endo-GIA) staplers are widely used in various surgical procedures despite difficulties in operating them and associated mechanical failures. We present a case of a patient whose post-operative recovery was complicated by intraoperative Endo-GIA stapler failure, which is rarely reported in literature. Our report describes the behavior and consequences of surgical stapler failure so surgeons can anticipate challenges of newer surgical devices while maintaining optimal patient outcomes.

https://ift.tt/2zbLbCa

Primitive synovial sarcoma of suboccipital region in child

Abstract

Synovial sarcoma (SS) most commonly affects the lower limbs of males in the third to fifth decades of life, with masses of the head and neck accounting for 3–10% of all cases, mainly as a metastatic lesion. The lack of specific symptoms and radiological features in addition to the diversity of their microscopic aspects may cause confusion in the diagnosis; hence, knowledge of the unusual locations of SSs is very important. The immunohistochemistry, and more recently the cytogenetic studies, contribute to the differential diagnosis. We report the case of a 12-year-old girl with a rare primary SS in the suboccipital region, which underwent complete surgical resection.

https://ift.tt/2SqGnBD

Segmental intestinal dilatation associated with ileal gastric heterotopia in a young woman

Abstract

Segmental intestinal dilatation (SID) is a rare gastrointestinal disorder characterized by marked bowel dilatation and can result in signs of intestinal obstruction, abdominal pain and gastrointestinal bleeding. SID is seen most commonly in pediatric patients, with most cases being reported in neonates and infants. Definitive treatment is resection of the dilated segment of bowel with primary anastomosis. This article describes a rare case of SID in an adult patient—a 26-year-old female who presented with chronic abdominal pain. The patient experienced complete resolution of symptoms following surgical resection.

https://ift.tt/2z9AUWX

The impact factor in peril?

Publication date: Available online 28 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): O. Laccourreye, H. Maisonneuve

https://ift.tt/2Pvwx2A

Ethmoid labyrinth: A true sinus? Phylogenetic data

Publication date: Available online 28 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): J.M. Prades, N. Laroche, M. Gavid

https://ift.tt/2RjhAy3

High-dose intraoperative remifentanil infusion increases early postoperative analgesic consumption: a prospective, randomized, double-blind controlled study

Abstract

Purpose

The purpose of this study was to determine whether intraoperative infusion of remifentanil induces acute tolerance to opioids, and compare the postoperative pain and opioid consumption by the effect site concentrations of remifentanil.

Methods

One hundred and ninety-eight patients undergoing gastrectomy were randomly assigned to maintain target effect site concentrations of remifentanil at 0 (Group 1, n = 39), 2 (Group 2, n = 40), 4 (Group 3, n = 39), 8 (Group 4, n = 40), or 12 ng/ml (Group 5, n = 40) during operation. Postoperative pain intensities and fentanyl requirement were recorded at postoperative 2, 6, 24, and 48 h.

Results

Fentanyl requirement for postoperative 2 h was significantly greater in Group 5 compared to Group 1 (376 ± 116 vs. 283 ± 129 µg, P = 0.03). However, there were no differences in fentanyl requirements among the groups after postoperative 2 h. Also, total fentanyl consumption for 48 h was similar in all groups (Group 1; 3106 ± 629, Group 2; 2970 ± 705, Group 3; 3017 ± 555, Group 4; 3151 ± 606, and Group 5; 2984 ± 443 µg, P = 0.717). Pain scores at rest and during deep breathing were comparable in all groups at the time of each examination.

Conclusion

Intraoperative infusion of remifentanil with 12 ng/ml of effect site concentration in patients undergoing gastrectomy increases early postoperative fentanyl requirement. Acute opioid tolerance would be developed by higher concentration of remifentanil than dosage of common anesthetic practice.

https://ift.tt/2Q3Vr6w

An Analysis of Perioperative Outcomes Following Cervical Abscess Drainage in Children Under 2 Years

Publication date: Available online 28 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jonathan A. Harounian, Vijay A. Patel, Michele M. Carr

Abstract

Objective

To identify risk factors and determine perioperative morbidity of children under 2 years of age undergoing cervical abscess drainage.

Methods

Patients who underwent cervical abscess drainage 1-18 years of age were queried via the ACS- National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database (2012-2015). Analyzed outcomes include length of stay, operative time, readmission/reoperation rate, and postoperative complications.

Results

A total of 2181 children were identified, 858 were <2 (51.5% male) and 1323 were > 2 years (57.1% male) (p=0.011). The younger cohort was found to undergo more lateral approaches for cervical abscess drainage whereas the older cohort was found to undergo more intraoral approaches for pharyngeal abscess drainage (p<0.001), suggesting a difference in abscess location related to age at clinical presentation. The younger cohort was also found to have a higher preoperative white blood cell count (20.7 vs. 17.5, p<0.001) but no significant difference in preoperative fulminant sepsis was observed. Younger children were found to have both a longer wait-time until surgery (1.4 vs. 1.1 days, p=0.003) and a prolonged length of stay (LOS) (4.3 vs. 3.4 days, p<0.001). Operative time was found to be lower in the younger cohort (18.4 vs. 21.5 minutes, p=0.003), Finally, the younger cohort was found to have an increased incidence and duration of postoperative mechanical ventilation (63 vs. 41, and 0.4 vs. 0.1 days, p<0.001.).There were no differences in post-op complications (wound infection, dehiscence, pneumonia, reintubation, and reoperation/readmission). Linear regression for LOS showed that major contributors were operative time, days of postop ventilation, and days from admission to surgery with R=0.700.

Conclusion

Children under 2 years of age have longer LOS that may in part be due to a greater likelihood of postoperative ventilation and a delay in operative intervention, despite having surgical approaches associated with a shorter LOS. They are no more prone to complications than are older children. Recognition of these critical factors plays a role in optimizing perioperative risk assessment and procedural planning within this patient population.

https://ift.tt/2Q302pP

PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients

Condition:   Head and Neck Fibrosis
Interventions:   Combination Product: Arm B: A combination of pentoxifylline and tocopherol acetate in addition to best standard care [a structured programme of rehabilitation exercises] for 6 months;   Procedure: • Arm A: Best standard of care only [a structured programme of rehabilitation exercises] for 6 months
Sponsors:   University College, London;   National Institute for Health Research, United Kingdom
Not yet recruiting

https://ift.tt/2OSuMx0

GP-induced Chemotherapy Combined With IMRT and TPF-induced Chemotherapy Combined With IMRT in the Treatment of Distant Metastatic Nasopharyngeal Carcinoma

Condition:   Advanced Nasopharyngeal Carcinoma
Interventions:   Drug: GP+IMRT;   Drug: TPF+IMRT
Sponsor:   Guiyang Medical University
Not yet recruiting

https://ift.tt/2COSAuH

Seventeen New Cases of Chronic Ulcerative Stomatitis with Literature Review

Abstract

Chronic ulcerative stomatitis (CUS) is a poorly understood disease with clinical and histologic overlap with lichen planus (LP). Unlike classic LP, direct immunofluorescence (DIF) studies in cases of CUS exhibit a granular pattern of IgG in nuclei of basal and parabasal cells. This study assesses the demographic, clinical, histologic, and DIF features of CUS. It is important to differentiate CUS from LP and other vesiculobullous diseases (VBD) because lesions of CUS are resistant to steroid therapy, which is typically used to control LP and VBD. A literature review and IRB-approved retrospective search of CUS was performed within the archives of the University of Florida (UF) Oral Pathology Biopsy Service from 2007 to 2017. Fifty-two cases were identified from the literature and seventeen new cases were identified in our series. All UF patients were female and the median age was 64-years. The majority of patients were Caucasian and the most common location was buccal mucosa. Frequent clinical presentations were pain, erythema, leukoplakia, and ulcerations. Histologic features included epithelial separation, atrophic epithelium, and a chronic inflammatory infiltrate. All cases were confirmed with DIF testing that showed a speckled pattern of IgG staining in basal and parabasal cell nuclei. Fibrinogen was present in eleven cases and two cases were positive for C3. The results of our series are in accordance with the literature. Since CUS has overlapping features with LP and VBD, clinicians and pathologists should consider this entity and confirm diagnosis with DIF testing when recalcitrant oral ulcerative diseases are encountered.

https://ift.tt/2qgN5gR

A shadow function model based on perspective projection and atmospheric effect for satellites in eclipse

Li, Z; Ziebart, M; Bhattarai, S; Harrison, D; (2018) A shadow function model based on perspective projection and atmospheric effect for satellites in eclipse. Advances in Space Research 10.1016/j.asr.2018.10.027 . (In press).

https://ift.tt/2CP7QaZ

Do Cognitive Deficits Persist Into Adolescence in Autism

Cantio, C; White, S; Madsen, GF; Bilenberg, N; Jepsen, JRM; (2018) Do Cognitive Deficits Persist Into Adolescence in Autism. Autism Research , 11 (9) pp. 1229-1238. 10.1002/aur.1976 .

https://ift.tt/2qfoTLx

ATTIRE: Albumin to Prevent Infection in Chronic Liver Failure: Study Protocol for an Interventional Randomised Controlled Trial

China, L; Skene, SS; Bennett, K; Shabir, Z; Hamilton, R; Bevan, S; Chandler, T; ... O'Brien, A; + view all China, L; Skene, SS; Bennett, K; Shabir, Z; Hamilton, R; Bevan, S; Chandler, T; Maini, AA; Becares, N; Gilroy, D; Forrest, EH; O'Brien, A; - view fewer (2018) ATTIRE: Albumin to Prevent Infection in Chronic Liver Failure: Study Protocol for an Interventional Randomised Controlled Trial. BMJ Open , 8 (10) , Article e023754. 10.1136/bmjopen-2018-023754 . Green open access

https://ift.tt/2CP7zEZ

The current illusion of educational inclusion

Pellicano, L; Bolte, S; Stahmer, A; (2018) The current illusion of educational inclusion. [Editorial comment]. Autism , 22 (4) pp. 386-387. 10.1177/1362361318766166 . Green open access

https://ift.tt/2qjpWu9

Fixed-Cost Pooling Strategies Based on IR Evaluation Measures

Lipani, A; Palotti, J; Lupu, M; Piroi, F; Zuccon, G; Hanbury, A; (2017) Fixed-Cost Pooling Strategies Based on IR Evaluation Measures. In: Jose, JM and Hauff, C and Altingovde, IS and Song, D and Albakour, D and Watt, S and Tait, J, (eds.) Advances in Information Retrieval. (pp. pp. 357-368). Springer: Cham, Switzerland. Green open access

https://ift.tt/2CNuq3t

A Re-examination of D-H-M in the Meṣad Ḥashavyahu Ostracon (KAI 200)

Noll, S; (2019) A Re-examination of D-H-M in the Meṣad Ḥashavyahu Ostracon (KAI 200). Journal of Semitic Studies (In press).

https://ift.tt/2qeP9G0

Use of Prophylactic Antibiotics in Fat Grafting and Their Effect on Graft Site Infection

Smith, OJ; Esmaeili, A; Mosahebi, A; (2018) Use of Prophylactic Antibiotics in Fat Grafting and Their Effect on Graft Site Infection. [Letter]. Aesthetic Surgery Journal , 38 (8) NP118-NP119. 10.1093/asj/sjy123 .

https://ift.tt/2CNuekL

Introduction: Geographies of Debt and Indebtedness

Harker, CG; Kirwan, S; (2018) Introduction: Geographies of Debt and Indebtedness. Geoforum (In press).

https://ift.tt/2qgi78r

The Use of Historical Data in Rule-Based Modelling for Scenarios to Improve Resilience within the Building Stock

Roumpani, F; Hudson, P; Hudson-Smith, AP; (2018) The Use of Historical Data in Rule-Based Modelling for Scenarios to Improve Resilience within the Building Stock. The Historic Environment: Policy & Practice 10.1080/17567505.2018.1517142 .

https://ift.tt/2CKtgWB

Evaluation of the Effect of an Innovative Automated Text Messaging Service on Patient Experience in Day-case Hand Trauma Surgery

Smith, OJ; Stewart, CJ; Rastogi, N; Abdaal, A; Hachach-Haram, N; Kerstein, R; Mosahebi, A; (2018) Evaluation of the Effect of an Innovative Automated Text Messaging Service on Patient Experience in Day-case Hand Trauma Surgery. [Letter]. Journal of Plastic, Reconstructive & Aesthetic Surgery , 71 (3) pp. 450-451. 10.1016/j.bjps.2017.09.018 . Green open access

https://ift.tt/2qeP7Oo

Metal-on-metal Hips and Heart Failure - Can We Relax

Manisty, C; Skinner, J; Moon, JC; (2018) Metal-on-metal Hips and Heart Failure - Can We Relax. [Editorial comment]. International Journal of Cardiology 10.1016/j.ijcard.2018.09.009 . (In press).

https://ift.tt/2CNtT1t

Boosting photocurrent of GaInP top-cell for current-matched III-V monolithic multiple junction solar cells via plasmonic decahedral-shaped Au nanoparticles

Bai, Y; Yan, L; Wang, F; Yang, Y; Liu, H; Yin, Z; Chen, N; ... Tan, Z; + view all Bai, Y; Yan, L; Wang, F; Yang, Y; Liu, H; Yin, Z; Chen, N; Hayat, T; Alsaedi, A; Tan, Z; - view fewer (2018) Boosting photocurrent of GaInP top-cell for current-matched III-V monolithic multiple junction solar cells via plasmonic decahedral-shaped Au nanoparticles. Solar Energy , 166 pp. 181-186. 10.1016/j.solener.2018.03.024 .

https://ift.tt/2qd3PWe

Photonic Sampling of Broadband Qam Microwave Signals Exploiting Interleaved Optical Nyquist Pulses

Vercesi, V; Onori, D; Davies, J; Seeds, A; Liu, CP; (2018) Photonic Sampling of Broadband Qam Microwave Signals Exploiting Interleaved Optical Nyquist Pulses. In: Proceedings of theOptical Fiber Communications Conference and Exposition (OFC) 2018. IEEE: San Diego, CA, USA. Green open access

https://ift.tt/2CMAN7c

Photonic Sampling of Broadband Qam Microwave Signals Exploiting Interleaved Optical Nyquist Pulses

Vercesi, V; Onori, D; Davies, J; Seeds, A; Liu, C-P; (2018) Photonic Sampling of Broadband Qam Microwave Signals Exploiting Interleaved Optical Nyquist Pulses. In: Proceedings of theOptical Fiber Communications Conference and Exposition (OFC) 2018. OSA Publishing: San Diego, CA, USA.

https://ift.tt/2qouO1f

Human-machine Collaboration: Bringing Artificial Intelligence Into Colonoscopy

Ahmad, OF; Stoyanov, D; Lovat, LB; (2018) Human-machine Collaboration: Bringing Artificial Intelligence Into Colonoscopy. Frontline Gastroenterology 10.1136/flgastro-2018-101047 . (In press). Green open access

https://ift.tt/2CNtvQz

Facilitating Knowledge Sharing Environment Within Bureaucracies by Cultivating Communities of Practice: a Case Study

Duryan, M; Smyth, H; (2017) Facilitating Knowledge Sharing Environment Within Bureaucracies by Cultivating Communities of Practice: a Case Study. In: Proceedings of the 18th European Conference on Knowledge Management:ECKM 2017. (pp. pp. 283-292). ACPI: Barcelona, Spain.

https://ift.tt/2qjCnWB

Anaesthetic Management of a Patient With Critical Respiratory Compromise Resulting From Procedure-induced Broncho-oesophageal Fistulation (BOF)

Oliver, CM; Phillips, S; Saibaba, RJ; (2017) Anaesthetic Management of a Patient With Critical Respiratory Compromise Resulting From Procedure-induced Broncho-oesophageal Fistulation (BOF). Journal of Clinical Anesthesia , 42 pp. 10-11. 10.1016/j.jclinane.2017.07.010 . Green open access

https://ift.tt/2CMIevc

Grit in engineering education – a systematic review

Direito, I; Mitchell, J; (2018) Grit in engineering education – a systematic review. In: Clark, R and Munkebo Hussmann, P and Jarvinen, HM and Murphy, M and Etchells Vigild, M, (eds.) Proceedings of the 46th SEFI Annual Conference 2018: Creativity, Innovation and Entrepreneurship for Engineering Education Excellence. (pp. pp. 740-747). Societe Europeenne pour la Formation des Ingenieurs (SEFI): Brussels, Belgium. Green open access

https://ift.tt/2qjCj9j

Comparing the student experience during a major educational curriculum reform in engineering: findings of a mixed-method study

Direito, I; Tilley, E; Mitchell, J; Marie, J; Davies, J; (2018) Comparing the student experience during a major educational curriculum reform in engineering: findings of a mixed-method study. In: Clark, R and Munkebo Hussmann, P and Jarvinen, HM and Murphy, M and Etchells Vigild, M, (eds.) Proceedings of the 46th SEFI Annual Conference 2018: Creativity, Innovation and Entrepreneurship for Engineering Education Excellence. (pp. pp. 166-173). Societe Europeenne pour la Formation des Ingenieurs (SEFI): Brussels, Belgium. Green open access

https://ift.tt/2CNqSy9

Initial impact of Brexit on European students and academic staff in UK's engineering higher education

Fowler, S; Direito, I; Mitchell, J; Rich, J; (2018) Initial impact of Brexit on European students and academic staff in UK's engineering higher education. In: Clark, R and Munkebo Hussmann, P and Jarvinen, HM and Murphy, M and Etchells Vigild, M, (eds.) Proceedings of the 46th SEFI Annual Conference 2018: Creativity, Innovation and Entrepreneurship for Engineering Education Excellence. (pp. pp. 190-197). Societe Europeenne pour la Formation des Ingenieurs (SEFI): Brussels, Belgium. Green open access

https://ift.tt/2qjC8Lb

59/w mit Erosionen an Mund- und Nasenschleimhaut

https://ift.tt/2Pr5fKU

Die AG JuDerm des BVDD

https://ift.tt/2RozKyB

20/w mit plötzlich auftretendem, ausgeprägtem Haarausfall

https://ift.tt/2PrR0Fx

40/m mit Fluor urethralis

https://ift.tt/2RkD6T6

85/m mit Blasen am gesamten Integument

https://ift.tt/2PtQnLR

77/w mit persistierenden rötlichen und schuppenden Plaques an den Extremitäten und am oberen Stamm

https://ift.tt/2RmYozv

Panorama Dermatologische Praxis

https://ift.tt/2Ax4qIe

46/w mit juckenden Hautveränderungen in den seborrhoischen Arealen

https://ift.tt/2Pp4m5H

Mein Facharzttraining – ein Sonderheft nicht nur für Ärzte vor der Facharztprüfung

https://ift.tt/2RjFkC8

54/m mit rezidivierender Gesichtsdermatitis mit Papeln und Vesikeln an den Extremitäten

https://ift.tt/2PvDHE8

4/m mit Fieber, generalisierter Rötung und Blasen

https://ift.tt/2Rp0DT1

57/m mit hyperkeratotischen Knoten am rechten Unterarm

https://ift.tt/2PqHnah

67/w mit erythematös-schuppenden Plaques am Abdomen mit zentrifugaler Ausbreitung

https://ift.tt/2RgeeM4

46/m mit Pusteln an Hand- und Fußsohlen

https://ift.tt/2PrQRlt

31/w mit livid-erythematösen Papeln und Knoten

https://ift.tt/2Rgvtx0

26/w mit beidseits tibialen druckempfindlichen und hochroten Knoten sowie bihilärer Lymphadenopathie

https://ift.tt/2PvDEYY

37/m mit konfluierenden Papeln und bogenförmig begrenzten erythematosquamösen Plaques am oberen Rumpf und an den Armen

https://ift.tt/2RnvAae

Commentary on letter to editor titled “surgical management of patients with Eagle syndrome”

Publication date: Available online 28 October 2018

Source: American Journal of Otolaryngology

Author(s): Frances Mei Hardin, Roy Xiao, Brian B. Burkey

https://ift.tt/2EQu3Yz

Defining Pollen Seasons: Background and Recommendations

Abstract

Purpose of Review

The definition of a pollen season determines the start and the end of the time period with a certain amount of pollen in the ambient air. Different pollen season definitions were used for a long time including the use of different terms for data and methods used to define a pollen season. Recently suggested pollen season definitions for clinical trials were tested and applied for the first time to more aeroallergens.

Recent Findings

This is a review on pollen season definitions and the latest recommendations. Recently, proposed terminology in aerobiology is promoted here in order to support reproducibility and repeatability in research. Two pollen season definitions, one based on percentages and one based on pollen concentrations, were tested.

Summary

Percentage definitions can be recommended for standard aerobiological routines and for retrospective applications, whereas pollen concentrations definitions can be recommended for prospective applications such as clinical trials.

https://ift.tt/2z6FtBi

Impact of community respiratory viral infections in urban children with asthma

Publication date: Available online 29 October 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Toby C. Lewis, Ediri E. Metitiri, Graciela B. Mentz, Xiaodan Ren, Adam M. Goldsmith, Breanna N. Eder, Kyra E. Wicklund, Megan P. Walsh, Adam T. Comstock, Jeannette M. Ricci, Sean R. Brennan, Ginger L. Washington, Kendall B. Owens, Bhramar Mukherjee, Thomas G. Robins, Stuart A. Batterman, Marc B. Hershenson, the Community Action Against Asthma Steering Committee

Abstract

Background

Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on asthmatic children in the community, particularly in the high-risk urban environment, is less well-defined.

Objective

We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms.

Methods

We studied 53 asthmatic children from Detroit, Michigan during scheduled surveillance periods and self-reported respiratory illnesses for one year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO) and nasal aspirate biomarkers, viral nucleic acid and rhinovirus (RV) copy number were assessed.

Results

Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared to the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75), higher nasal mRNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20 and CCL24. Children with mild (symptom score 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation and normal airflow. RV copy number was associated with nasal chemokine levels but not symptom score.

Conclusion

Urban asthmatic children with high-symptom respiratory viral infections have reduced FEF25-75 and more elevations of nasal biomarkers than children with mild or asymptomatic infections, or virus-negative illnesses.

https://ift.tt/2OcPD9i

Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis–a pilot study

Publication date: Available online 28 October 2018

Source: Archives of Oral Biology

Author(s): Philip Bender, Andreas Egger, Martin Westermann, Nadine Taudte, Anton Sculean, Jan Potempa, Burkhard Möller, Mirko Buchholz, Sigrun Eick

Abstract

Objectives

Human glutaminyl cyclases (QC and isoQC) play an important role in maintaining inflammatory conditions. Meanwhile a glutaminyl cyclase synthesized by Porphyromonas gingivalis (PgQC), a key pathogen in developing periodontitis and a potential link of periodontitis with rheumatoid arthritis (RA), was discovered. This study was aimed to determine the expression of QC, isoQC and PgQC in patients with chronic periodontitis (CP) and RA.

Design

Thirty volunteers were enrolled in a pilot study and divided into 3 groups (healthy, CP and RA individuals). Blood samples, biofilm and gingival crevicular fluid (GCF) were analysed for mRNA expression of QC, isoQC and P. gingivalis QC. Major bacteria being associated with periodontal disease were quantified in subgingival biofilm and protein levels for monocyte chemoattractant protein (MCP)-1, MCP-3 and interleukin (IL)-1β) were determined in the GCF. Expression of PgQC on the mRNA and protein levels was assessed in two P. gingivalis strains.

Results

PgQC is expressed in P. gingivalis strains and the protein seems to be located mainly in peri-plasmatic space. mRNA expression of QC was significantly increased in the peripheral blood from RA patients vs. healthy subjects and CP patients (p = 0.013 and p = 0.003, respectively). In GCF of RA patients, QC mRNA was detected more frequently than in healthy controls (p = 0.043). In these samples IL-1β levels were also elevated compared to GCF from periodontally healthy individuals (p = 0.003). PgQC was detected in eight out of the 13 P. gingivalis positive biofilm samples.

Conclusion

Activity of QC may play a supportive role in maintaining chronic periodontal inflammation and destruction in RA. PgQC is expressed in vivo but further research is needed to evaluate biological importance of this enzyme and if it constitutes a potential target in periodontal antimicrobial therapy.

https://ift.tt/2ET0CVR

Comparative analysis of blood parameters of the erythrocyte lineage between patients with chronic periodontitis and healthy patients: Results obtained from a meta-analysis

Publication date: Available online 28 October 2018

Source: Archives of Oral Biology

Author(s): Luiz Felipe de Carvalho França, Felipe Rodolfo Pereira da Silva, David di Lenardo, Even Herlany Pereira Alves, Hélio Mateus Silva Nascimento, Isabela Aparecida Tito da Silva, Any Carolina Cardoso Guimarães Vasconcelos, Daniel Fernando Pereira Vasconcelos

Abstract

Objective

Quantitatively evaluate blood parameters of the erythrocyte lineage in patients with chronic periodontitis and healthy controls by means of a meta-analysis.

Material and methods

A review of literature was performed in the scientific databases for studies published before September, 2016. The abstracts were evaluated and the extraction of data performed by two examiners. The parameters assessed were: hemoglobin levels, number of circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with chronic periodontitis and healthy controls. The calculations were obtained through the statistical software Review Manager version 5.3, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05.

Results

Nine case/control studies composed the results with 342 patients with chronic periodontitis and 359 healthy controls. There was a significant decrease in hemoglobin levels (MD = -1.60, 95% CI: -2.72, -0.48, P = 0.005) and number of circulating red blood cells (MD = -0.51, 95% CI: -0.78, -0.24, P = 0.0002), hematocrit (MD = -4.41, IC 95%: -7.13, -1.68, P = 0.002), mean corpuscular hemoglobin (MD = -0.80; IC 95%: -1.38, -0,22, P = 0.007) and mean corpuscular hemoglobin concentration (MD = -0.93, IC 95%: -1.63, -0.23, P = 0.009) in patients with chronic periodontitis when compared to healthy controls. No publication bias was found through the funnel plot asymmetry.

Conclusion

There is an associated of the reduction of hematological parameters (such as levels of hemoglobin and circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) to patients with chronic periodontitis.

https://ift.tt/2AyB6B7

Defining Pollen Seasons: Background and Recommendations

Abstract

Purpose of Review

The definition of a pollen season determines the start and the end of the time period with a certain amount of pollen in the ambient air. Different pollen season definitions were used for a long time including the use of different terms for data and methods used to define a pollen season. Recently suggested pollen season definitions for clinical trials were tested and applied for the first time to more aeroallergens.

Recent Findings

This is a review on pollen season definitions and the latest recommendations. Recently, proposed terminology in aerobiology is promoted here in order to support reproducibility and repeatability in research. Two pollen season definitions, one based on percentages and one based on pollen concentrations, were tested.

Summary

Percentage definitions can be recommended for standard aerobiological routines and for retrospective applications, whereas pollen concentrations definitions can be recommended for prospective applications such as clinical trials.

https://ift.tt/2z6FtBi

Hip Mobilization at Preterm Age May Accelerate Developmental Dysplasia Recovery

Purpose. Few studies have described mobilization approaches in developmental dysplasia of the hip (DDH). The present study describes the hip mobilization of a preterm infant (born at 33 6/7 weeks of gestational age) diagnosed with DDH. Design and Methods. During the 43-day hospital stay, the infant was seen twice a week (ten sessions, 20 minutes each). All sessions included hip approximation maneuvers, with the hip positioned in abduction, lateral rotation and flexion, and lower limbs passive mobilization, which were taught to the mother. Early intervention with auditory, tactile, visual, and vestibular stimulations was also performed. The infant was assessed with hip ultrasound before and after treatment. Results. At 34 2/7 weeks of gestational age, she was classified as Graf IIa (left: alpha: 55°, beta: 68°; right: alpha: 59°, beta: 64°). At 40 5/7 weeks, she was classified as Graf I for left (alpha: 67°; beta: 42°) and right (alpha: 66°; beta: 42°) hips. Practical Implications. The intervention seemed to accelerate the acquisition of stability of dysplasic hips in a preterm infant. The outcome supports further investigation of hip approximation maneuvers as part of early stimulation in preterm infants with DDH during hospital stay.

https://ift.tt/2yBHq9C

Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy

Abstract

It has been for long conceived that hallmarks of cancer were intrinsic genetic features driving tumor development, proliferation, and progression, and that targeting such cell-autonomous pathways could be sufficient to achieve therapeutic cancer control. Clinical ex vivo data demonstrated that treatment efficacy often relied on the contribution of host immune responses, hence introducing the concept of tumor microenvironment (TME), namely the existence, along with tumor cells, of non-tumor components that could significantly influence tumor growth and survival. Among the complex network of TME-driving forces, immunity plays a key role and the balance between antitumor and protumor immune responses is a major driver in contrasting or promoting cancer spreading. TME is usually a very immunosuppressed milieu because of a vast array of local alterations contrasting antitumor adaptive immunity, where metabolic changes contribute to cancer dissemination by impairing T cell infiltration and favoring the accrual and activation of regulatory cells. Subcellular structures known as extracellular vesicles then help spreading immunosuppression at systemic levels by distributing genetic and protein tumor repertoire in distant tissues. A major improvement in the knowledge of TME is now pointing the attention back to tumor cells; indeed, recent findings are showing how oncogenic pathways and specific mutations in tumor cells can actually dictate the nature and the function of immune infiltrate. As our information on the reciprocal interactions regulating TME increases, finding a strategy to interfere with TME crosstalk becomes more complex and challenging. Nevertheless, TME interactions represent a promising field for the discovery of novel biomarkers and therapeutic targets for improving treatment efficacy in cancer.

https://ift.tt/2zbcAUR

Spectral imaging of thermal damage induced during microwave ablation in the liver

Clancy, NT; Gurusamy, K; Jones, G; Davidson, B; Clarkson, M; Hawkes, D; Stoyanov, D; (2018) Spectral imaging of thermal damage induced during microwave ablation in the liver. In: (Proceedings) 40th International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 17-21 July 2018, Honolulu, Hawaii, USA. IEEE (In press). Green open access

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Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model

Abstract

Purpose

Heatstroke causes systemic inflammation, followed by vascular endothelial damage. The normal vascular endothelium is coated by endothelial glycocalyx (EGCX). Dexmedetomidine (DEX) has an anti-inflammatory effect, but there has been little investigation on the influence of heatstroke on EGCX and the effect of DEX on this condition. Therefore, we examined whether EGCX was disrupted in heatstroke and if DEX improved survival and preserves EGCX.

Methods

Anesthetized Wistar rats were randomly assigned to three groups: a DEX group treated with DEX (5 µg/kg/h) and 0.9% saline infused continuously at 10 ml/kg/h during heat exposure; a NSS group given 0.9% saline during heat exposure; and a SHAM group given 0.9% saline alone without heat exposure. Heatstroke was induced by exposure to an ambient temperature of 40 °C with relative humidity of 60%. The survival rate was assessed up to 2 h after the start of heat exposure. Plasma levels of syndecan-1 and the thickness of EGCX using electron microscopy were measured when the systolic blood pressure fell to less than 80 mmHg.

Results

The survival rate after 2 h of heat exposure was significantly higher in the DEX group compared to the NSS group (89% vs. 22%, P = 0.004). Plasma levels of syndecan-1 were 0.6 ± 1.3, 9.7 ± 5.9, and 2.1 ± 3.4 ng/ml in the SHAM, NSS and DEX groups, respectively (P = 0.013). The thickness of EGCX was significantly higher in the DEX group compared with the NSS group (P = 0.001).

Conclusions

EGCX was disrupted in heatstroke, and DEX improved survival and preserved EGCX.

https://ift.tt/2Pxdcy2