Laryngopharyngeal Reflux: Current Concepts on Etiology and Pathophysiology and Its Role in Dysphagia

Abstract

Purpose of Review

Laryngopharyngeal reflux (LPR) is one of the most commonly encountered chronic inflammatory conditions of the larynx. The lack of a unifying consensus regarding diagnosis and management makes it difficult to relate laryngeal disorders and dysphagia to this disease entity, particularly for an otolaryngologist. This article reviews diagnosis and management of LPR from an otolaryngological and gastroenterological perspective by reconciling current trends in the literature.

Recent Findings

More sophisticated testing via multichannel pH probes as well as the implementation of pepsin assays has potential in diagnosing LPR. This will hopefully more clearly delineate this disease entity, in the setting of dysphagia.

Summary

Dysphagia and LPR both have significant overlap with numerous disease entities. Though there is little literature to address outcomes in treatment and management of dysphagia in the setting of LPR, few studies show that managing LPR-related dysphagia may improve with surgical intervention if there is no improvement with conservative management.

https://ift.tt/2HH8qHd

Book review—Diagnostic Pathology: Cytopathology, 2nd edition

https://ift.tt/2HFq12b

CD14+ monocytes contribute to inflammation in chronic nonbacterial osteomyelitis (CNO) through increased NLRP3 inflammasome expression

Publication date: Available online 30 April 2018
Source:Clinical Immunology
Author(s): D. Brandt, E. Sohr, J. Pablik, A. Schnabel, F. Kapplusch, K. Mäbert, J.H. Girschick, H. Morbach, F. Thielemann, S.R. Hofmann, C.M. Hedrich
The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1β release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for "drivers" of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.



https://ift.tt/2HDdQqW

Commonly used oncology drugs decrease antifungal effectiveness against Candida and Aspergillus species [PublishAheadOfPrint]

The incidence of invasive fungal infections has risen significantly in recent decades as medical interventions have become increasingly aggressive. These infections are extremely difficult to treat due to the extremely limited repertoire of systemic antifungals, the development of drug resistance, and the extent of to which the patient's immune function is compromised. Even when the appropriate antifungal therapies are administered in a timely fashion, treatment failure is common, frequently even in the absence of in vitro microbial resistance. In this study, we screened a small collection of FDA approved oncolytic agents for compounds that impact the efficacy of the two most widely used classes of system antifungals against Candida albicans, Candida glabrata, and Aspergillus fumigatus. We have identified several drugs that enhance fungal growth in the presence of the azole antifungals and examine the potential that these drugs directly affect fungal fitness, specifically antifungal susceptibility, and may be contributing to clinical treatment failure.

https://ift.tt/2rc7uDQ

Emergence of high-level colistin resistance in an Acinetobacter baumannii clinical isolate mediated by inactivation of the global regulator H-NS. [PublishAheadOfPrint]

Colistin is a crucial last-line drug used for the treatment of life-threatening infections caused by multi-drug resistant strains of the Gram-negative bacteria, Acinetobacter baumannii. However, colistin-resistant A. baumannii isolates can be isolated following failed colistin therapy. Resistance is most often mediated by the addition of phosphoethanolamine (pEtN) to lipid A by PmrC, following missense mutations in the pmrCAB operon encoding PmrC and the two-component signal transduction system PmrA/PmrB. We recovered a pair of A. baumannii isolates from a single patient before (6009-1) and after (6009-2) failed colistin treatment. These strains displayed low and very high levels of colistin resistance, (MICs 8-16 μg/mL and 128 μg/mL) respectively. To understand how increased colistin resistance arose, we genome sequenced each isolate which revealed that 6009-2 had an extra copy of the insertion sequence element ISAba125 within a gene encoding an H-NS-family transcriptional regulator. To confirm the role of H-NS in colistin resistance we generated an hns deletion mutant in 6009-1 and showed that colistin resistance increased upon deletion of hns. We also provided 6009-2 with an intact copy of hns and showed that the strain was no longer resistant to high concentrations of colistin. Transcriptomic analysis of the clinical isolates identified more than 150 genes as differentially expressed in the colistin-resistant, hns mutant, 6009-2. Importantly, expression of eptA, encoding a second lipid A-specific pEtN transferase, but not pmrC, was increased in the hns mutant. This is the first time an H-NS-family transcriptional regulator has been associated with a pEtN transferase and colistin resistance.

https://ift.tt/2HDBy6h

Determination of MIC Distribution and Mechanisms of Decreased Susceptibility to Bedaquiline Among Clinical Isolates of Mycobacterium abscessus [PublishAheadOfPrint]

Chemotherapeutic options are very limited against Mycobacterium abscessus infections. Bedaquiline, a new anti-tuberculosis drug, is effective for the treatment of multidrug-resistant TB. However, little data is available on bedaquiline in treating M. abscessus infections. In this study, we reported the in vitro susceptibility profile of M. abscessus clinical isolates to bedaquiline and investigated the potential molecular mechanisms of decreased susceptibility. A total of 197 M. abscessus clinical isolates were collected from sputum and bronchoalveolar fluid of patients with lung infections. Standard broth microdilution test revealed that bedaquiline exhibited high in vitro killing activity against M. abscessus isolates, with MIC50 of 0.062 and MIC90 of 0.125 mg/L. Whole genome sequencing data showed that no nonsynonymous mutation occurred in atpE, the gene encoding the bedaquiline targeted protein. However, of 6 strains with decreased susceptibility of bedaquiline (MIC=0.5-1 mg/L), 3 strains had nonsynonymous mutations in mab_4384, the gene encoding the repressor of efflux pump MmpS5/MmpL5. qRT-PCR analysis showed that the expression of MmpS5/MmpL5 in the group with decreased susceptibility to bedaquiline were significantly higher than those with medium MIC (MIC=0.125-0.5 mg/L) or low MIC group (MIC≤ 0.062 mg/L). Two isolates with increased MIC didn't show overexpression of MmpS5/MmpL5, which couldn't be explained by known molecular mechanisms. This is the first report showing the association of MmpS5/MmpL5 with decreased bedaquiline susceptibility in M. abscessus clinical isolates, and suggesting the presence of other yet-to-be identified mechanisms for decreased bedaquiline susceptibility in M. abscessus.

https://ift.tt/2rc7io6

Genetic and functional characterization of an MCR-3-like producing Escherichia coli recovered from swine, Brazil [PublishAheadOfPrint]

A collection of 126 pigs were screened for carriage of colistin-resistant Enterobacteriaceae in a farm in Minas Gerais, Brazil. Out of this collection, eigth colistin-resistant Escherichia coli isolates were recovered, including one from Minas Gerais State, producing a new MCR-3 variant (MCR-3.12). Analysis of the lipopolysaccharide revealed that MCR-3.12 had a similar function as MCR-1 and MCR-2 by adding a phosphoethanolamine group to the lipid A. Genetic analysis showed that the mcr-3.12 gene was carried by an IncA/C₂ plasmid and was embedded in an original genetic environment. This study reports the occurrence of the MCR-3-like determinant in South America and firstly demonstrates the functionality of this group of enzymes as a phosphoethanolamine transferase.

https://ift.tt/2HDXNJt

Novel Mutations Associated with Clofazimine Resistance in Mycobacterium abscessus [PublishAheadOfPrint]

Mycobacterium abscessus (Mab) is a major non-tuberculous mycobacterial (NTM) pathogen responsible for about 80% of all pulmonary infections caused by rapidly growing mycobacteria. Clofazimine is an effective drug active against Mab, but the mechanism of resistance to clofazimine in Mab is unknown. To investigate the molecular basis of clofazimine resistance in Mab. We isolated 29 Mab mutants resistant to clofazimine, and subjected them to whole genome sequencing to identify possible mutations associated with clofazimine resistance. We found that mutations in MAB_2299c gene which encodes possible transcriptional regulatory protein, MAB_1483 and MAB_0540 are most commonly associated with clofazimine resistance. In addition, mutations in MAB_0416c, MAB_4099c, MAB_2613, MAB_0409, and MAB_1426 were also associated with clofazimine resistance but in less frequency. Two identical mutations which are likely to be polymorphisms unrelated to clofazimine resistance were found in MAB_4605c and MAB_4323 in 13 mutants. We conclude that mutations in MAB_2299c, MAB_1483, and MAB_0540 are the major mechanisms of clofazimine resistance in Mab. Future studies are needed to address the role of the identified mutations in clofazimine resistance in Mab. Our findings have implications for understanding mechanisms of resistance of clofazimine and for rapid detection of clofazimine resistance in this organism.

https://ift.tt/2raTeuZ

The Artemisinin Derivative Artemisone Is a Potent Inhibitor of Human Cytomegalovirus Replication [PublishAheadOfPrint]

Human cytomegalovirus (HCMV) is a major cause of disease in immunocompromised individuals and the most common cause of congenital infection and neuro-sensorial disease. The expanding target populations for HCMV antiviral treatment along with the limitations of the currently available HCMV DNA polymerase inhibitors underscore the need for new antiviral agents with alternative modes of action. The anti-malarial artemisinin derivative artesunate was shown to inhibit HCMV in vitro, yet has demonstrated limited antiviral efficacy in vivo, prompting our search for more potent anti-HCMV artemisinin derivatives. Here we show that the innovative artemisinin derivative artemisone, which has been screened against malaria in human clinical studies, is a potent and non-cytotoxic inhibitor of HCMV. Artemisone exhibited an antiviral efficacy comparable to ganciclovir (EC₅₀ 1.20 ± 0.46 μM) in human foreskin fibroblasts, with enhanced relative potency in lung fibroblasts and epithelial cells. Significantly, the antiviral efficacy of artemisone was consistently ≥10-fold superior to that of artesunate in all cells. Artemisone effectively inhibited both laboratory-adapted and low-passage clinical strains, as well as drug-resistant HCMV strains. By using quantitative viral kinetics and gene expression studies, we showed that artemisone is a reversible inhibitor, targeting an earlier phase of the viral replication cycle than ganciclovir. Importantly, artemisone most effectively inhibited HCMV infection ex vivo in a clinically-relevant multicellular model of integral human placental tissues maintained in organ culture. Our promising findings encourage preclinical and clinical studies of artemisone as a new inhibitor against HCMV.

https://ift.tt/2HBc7Ce

Incidence of Acute Kidney Injury among Patients Treated with Piperacillin-Tazobactam or Meropenem in combination with Vancomycin [PublishAheadOfPrint]

Acute kidney injury increases during empiric antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) when compared to monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM+VAN or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease, who received MEM+VAN or TZP+VAN for at least 2 days were included. AKI was assessed using RIFLE criteria. Inverse probability of treatment weighting was utilized to control for differences between groups. In total, 10,236 patients met inclusion criteria, with 9,898 receiving TZP+VAN and 338 receiving MEM+VAN. AKI occurred in 15.4% of MEM+VAN patients compared to 27.4% of TZP+VAN patients (p<0.001). TZP+VAN was associated with increased AKI compared to MEM+VAN (OR=2.53; 95%CI 1.82-3.52), after controlling for confounders. MEM+VAN should be considered an appropriate alternative therapy to TZP+VAN if nephrotoxicity is a major concern. The results of this study demonstrate that judicial use of TZP+VAN for empiric coverage of infection is needed.

https://ift.tt/2rakY2Q

Carbapenem-resistant hypervirulent Klebsiella pneumoniae of sequence type 36 [PublishAheadOfPrint]

ST36 Klebsiella pneumoniae distributes worldwide. We found that a ST36 K. pneumoniae clinical isolate was carbapenem resistant, carried bla_KPC-2, had mucoid regulator gene rmpA and exhibited high virulence. The findings suggest the emergence of carbapenem-resistant hypervirulent K. pneumoniae of ST36 and surveillance on carbapenem-resistant hypervirulent K. pneumoniae is required.

https://ift.tt/2HFcagi

Activity of combinations of antistaphylococcal antibiotics with fusidic acid against staphylococcal biofilms in in vitro static and dynamic models [PublishAheadOfPrint]

Staphylococcal biofilms are a major cause of therapeutic failure, especially when caused by multiresistant strains. Oral fusidic acid is currently being re-developed in the US for skin and skin structure and orthopedic infections, in which biofilms play a major role. The aim of this study was to examine the activity of fusidic acid alone or combined with other anti-staphylococcal drugs against biofilms made by a reference strain and five clinical isolates of Staphylococcus aureus or Staphylococcus epidermidis in in vitro static or dynamic models (microtiter plates and CDC reactor) exposed to clinically-relevant concentrations. In microtiter plates, antibiotics alone were poorly active, with marked differences among strains. At concentrations mimicking free-drug human C_max, combination of fusidic acid with linezolid, daptomycin or vancomycin resulted in increased activity against 4-5 strains and combination with doxycycline, rifampin, or moxifloxacin, increased activity against 1-3 strains only. In the CDC reactor, biofilms were grown under constant flow and antibiotic concentrations decreased over time according to human elimination rates. A bactericidal effect was obtained when fusidic acid was combined with daptomycin or linezolid, but not with vancomycin. The higher tolerance of biofilms to antibiotics in the CDC reactor is probably attributable to the more complex architecture they adopt when growing under constant flow. Because biofilms grown in the CDC reactor are considered more similar to those developing in vivo, the data support further testing of combinations of fusidic acid with daptomycin or linezolid in models pertinent to chronic skin and skin structure or orthopedic infections.

https://ift.tt/2rbcU1L

First penicillin-binding protein occupancy patterns of {beta}-lactams and {beta}-lactamase inhibitors in Klebsiella pneumoniae [PublishAheadOfPrint]

Penicillin-binding proteins (PBPs) are the high affinity target sites of all β-lactam antibiotics in bacteria. It is well known that each β-lactam covalently binds to and thereby inactivates different PBPs with varying affinity. Despite β-lactams serving as cornerstone of our therapeutic armamentarium against Klebsiella pneumoniae, PBP binding data are missing for this pathogen. We aimed to generate the first PBP binding data on 13 chemically diverse and clinically relevant β-lactams and β-lactamase inhibitors in K. pneumoniae. PBP binding was determined using isolated membrane fractions from K. pneumoniae strains ATCC 43816 and ATCC 13883. Binding reactions were conducted using β-lactam concentrations from 0.0075 to 256 mg/liter (or 128 mg/liter). After β-lactam exposure, unbound PBPs were labelled by Bocillin FL. Binding affinities (IC50s) were reported as the β-lactam concentrations that half-maximally inhibited Bocillin FL binding. PBP occupancy patterns by β-lactams were consistent across both strains. Carbapenems bound to all PBPs with PBP2 and PBP4 as highest affinity targets (IC50s <0.0075 mg/liter). Preferential PBP2 binding was observed by mecillinam (IC50: <0.0075 mg/liter) and avibactam (2 mg/liter). Aztreonam showed high affinity for PBP3 (IC50: 0.06 to 0.12 mg/liter). Ceftazidime bound PBP3 at low (IC50: 0.06 to 0.25 mg/liter) and PBP1a/b at higher concentrations (4 mg/liter), whereas cefepime bound PBPs 1-4 more evenly (IC50s: 0.015 to 2 mg/liter). These PBP binding data on a comprehensive set of 13 clinically relevant β-lactams and β-lactamase inhibitors in K. pneumoniae enable, for the first time, rational design and optimization of double β-lactam and β-lactam/β-lactamase inhibitor combinations.

https://ift.tt/2HGQ6BW

A Population Pharmacokinetic Model for a Solid Oral Tablet Formulation of Posaconazole [PublishAheadOfPrint]

A delayed-release solid tablet formulation that releases posaconazole in the small intestine was developed to maximize systemic absorption. This study aimed to characterize the pharmacokinetics of the posaconazole solid tablet formulation in adult subjects and to investigate the potential impact of demographic and clinical factors on posaconazole exposure through a population pharmacokinetic approach. Nonlinear mixed-effects modeling was performed using data from several studies conducted in healthy volunteers and patients. The influence of demographic and clinical factors on pharmacokinetic parameters was evaluated using a stepwise forward inclusion/backward exclusion procedure. The final pharmacokinetic model was used to simulate posaconazole exposure in patients at high risk for invasive fungal diseases treated with the proposed posaconazole dose of 300 mg twice daily on day 1, followed by 300 mg daily for 27 days. A one-compartment pharmacokinetic model with sequential zero-order and first-order absorption and a first-order disposition from the central compartment adequately described the pharmacokinetic profile of the posaconazole solid tablet formulation. Significant covariates included disease state (acute myeloid leukemia/myelodysplasia vs allogeneic hematopoietic stem cell transplantation), body weight, and formulation on bioavailability; food status on first-order absorption rate; and dosing regimen (single dose vs multiple doses) on clearance. Except for body weight, the impact of these covariates on posaconazole exposure was considered clinically irrelevant. This population pharmacokinetic analysis confirmed that the proposed dose of the posaconazole solid tablet formulation provides adequate target therapeutic exposure (>0.5 mg/l) to a broad range of patients at high risk for invasive fungal disease.

https://ift.tt/2rdqAJL

Resistance to echinocandins in Candida can be detected by performing the Etest directly on blood culture samples [PublishAheadOfPrint]

Background: We examined the rapid evaluation of susceptibility to echinocandins in Candida spp. using the Etest performed directly on positive blood cultures and anidulafungin-containing agar plates.

Methods: We prospectively collected 80 positive blood cultures (Bactec™-FX system, Becton-Dickinson, Cockeysville, Maryland, USA) with echinocandin-susceptible Candida spp (n=60) and echinocandin-intermediate C. parapsilosis (n=20) from patients with candidemia. Additionally, blood culture bottles of nonfungemic/bacteremic patients were spiked with 35 echinocandin-resistant Candida spp. isolates. A total of 2-4 drops of medium from each bottle was stroked directly both onto RPMI 1640 agar plates with micafungin and anidulafungin Etest strips (ET_DIR) and on Sabouraud agar plates containing 2 mg/L of anidulafungin. Isolates were tested according to the EUCAST method and Etest standard (ET_SD). Essential and categorical agreement between methods was calculated.

Results: Essential agreement and categorical agreement between EUCAST and ET_DIR and ET_SD were both >97.4%. The essential agreement between ET_DIR and EUCAST for both echinocandins was >97%. The categorical agreement between the FKS sequence (gold standard) and ET_DIR was 97.4%. The ET_DIR MIC of anidulafungin and micafungin (≥ 0.19 mg/L and ≥ 0.064 mg/L, respectively) effectively separated all susceptible/FKS wild-type isolates from the resistant/FKS mutant isolates. The categorical agreement (62.6%) between EUCAST and growth on anidulafungin-containing plates was poor, with the best agreement observed for C. glabrata (94.2%).

Conclusions: When performed directly on positive blood cultures from patients with candidemia, the Etest with micafungin and anidulafungin is a reliable procedure for a rapid testing of susceptibility to echinocandins in Candida spp. isolates.

https://ift.tt/2HDXCxN

Pharmacokinetics, pharmacodynamics, and tolerability of single-dose oral LCB01-0371, a novel oxazolidinone with broad-spectrum activity, in healthy volunteers [PublishAheadOfPrint]

LCB01-0371 is a novel oxazolidinone with broad-spectrum activity against Gram-positive pathogens in both in vitro studies and animal infection models. The objectives of this study were to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics following single ascending doses (NCT01554995). Single oral doses of 600 mg Linezolid, a placebo, or LCB01-0371 between 50 mg and 3200 mg were tested in 69 healthy male subjects. Blood and urine were sampled, and LCB01-0371 concentrations were measured, and the serum inhibitory and bactericidal titers of LCB01-0371 and Linezolid were determined. LCB01-0371 was well tolerated up to 2400 mg. The most common drug-related clinical and laboratory adverse events were nausea with or without vomiting, decreased neutrophil count, and increased total bilirubin. The frequency of adverse events and drug-related adverse events was similar among the treatment groups. The systemic exposure was approximately dose-proportional over the range of 50mg--800 mg, which includes the anticipated clinical dose. The mean clearance, renal clearance, and volume of distribution were significantly decreased at higher doses (above 800 mg). LCB01-0371 exhibited early bacteriostatic activity against all tested strains except for S. pneumonia, and the potency of LCB01-0371 at 800 mg was similar to that of Linezolid at the therapeutic dose (600 mg). However, LCB01-0371 had less bactericidal activity than Linezolid. Taken together, LCB01-0371 was well tolerated and exhibited approximate dose proportionality within the anticipated clinically relevant dose range, and showed bacteriostatic and bactericidal activity comparable to that of Linezolid. These results support the further clinical development of LCB01-0371.

https://ift.tt/2rdqC4l

Direct Activation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) by PF-06409577 Inhibits Flavivirus Infection through Modification of Host-Cell Lipid Metabolism [PublishAheadOfPrint]

Mosquito-borne flaviviruses are a group of RNA viruses that constitute global threats for human and animal health. Replication of these pathogens is strictly dependent on cellular lipid metabolism. We have evaluated the effect of the pharmacological activation of Adenosine Monophosphate-activated Protein Kinase (AMPK), a master regulator of lipid metabolism, on the infection of three medically relevant flaviviruses: West Nile virus (WNV), Zika virus (ZIKV) and dengue virus (DENV). WNV is responsible for recurrent outbreaks of meningitis and encephalitis affecting humans and horses worldwide. ZIKV has caused a recent pandemic associated with birth defects (microcephaly), reproductive disorders, and severe neurological complications (Guillain-Barré syndrome). DENV is the etiological agent of the most prevalent mosquito-borne viral disease that can induce a potentially lethal complication called severe dengue. Our results showed, for the first time, that activation of AMPK using the specific small molecule activator PF-06409577 reduced both WNV, ZIKV, and DENV infection. This antiviral effect was associated to an impairment of viral replication due to the modulation of host cell lipid metabolism exerted by the compound. These results support that the pharmacological activation of AMPK, which currently constitutes an important pharmacological target for human diseases, could also provide a feasible approach for broad-spectrum host-directed antiviral discovery.

https://ift.tt/2HHOhor

Pharmacokinetics of anidulafungin in obese and normal-weight adults [PublishAheadOfPrint]

In 2025, approximately one out of five adults will be obese. Physiological changes associated with obesity have shown to influence the pharmacokinetics of drugs. Anidulafungin is frequently used in critically ill patients and to achieve optimal efficacy it is essential that its dose is appropriate for each patients' characteristics. We combined data from obese subjects with data from normal-weight subjects and determined an optimal dosing regimen for obese patients by population-PK modeling.

Twenty adults, of which twelve were normal-weight healthy subjects (median weight 67.7 kg; range: 61.5-93.6 kg) and eight morbidly obese subjects (median weight 149.7 kg; range: 124.1-166.5 kg) were included in the analysis. Subjects received a single dose of 100 mg anidulafungin IV in 90 minutes upon which blood samples were obtained. Monte Carlo simulations were performed to optimize dosing in obesity.

A three-compartment model and equal volumes of distribution described the data best. Total body weight was identified as descriptor for both clearance and volume of distribution but the effect of weight on these parameters was limited. Simulations showed that with the licensed 100 mg dose more than 97% of subjects with a weight above 140 kg will have an AUC_0-24 lower than 99 mg*h/L (reference of normal weight individuals).

We found that anidulafungin pharmacokinetics in obese and normal-weight subjects, weight influenced both clearance and volume of distribution implying a lower exposure to anidulafungin in (morbidly) obese individuals. Consequently, a 25% increase in loading and maintenance dose could be considered in patients weighing more than 140 kg.

https://ift.tt/2r73g06

Use of Neodymium magnetic discs as pressure earrings for ear lobe keloid post-excision

https://ift.tt/2JBiGBp

2 to Z flap for reconstruction of adjacent skin defects

https://ift.tt/2ra1Brg

Effect of Petrolatum Coating on Fast-Absorbing Gut Suture

https://ift.tt/2JIShlj

Split Ear Lobe Repair with Piercing Preservation and Optimal Ear Lobe Aesthetics

https://ift.tt/2FtYdMx

First-Time Detection of Porcine Reproductive and Respiratory Syndrome Virus and Porcine Circovirus 2 in an Albanian Farrow-to-Finish Herd

Viral Immunology, Ahead of Print.


https://ift.tt/2JE8OXt

The Characterization of Monoclonal Antibodies to Mouse TLT-1 Suggests That TLT-1 Plays a Role in Wound Healing

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Volume 37, Issue 2, Page 78-86, April 2018.


https://ift.tt/2KqqeIv

Development of Monoclonal Antibodies Specifically Recognizing the Nonstructural Protein 12 of Type 2 Porcine Reproductive and Respiratory Syndrome Virus

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Volume 37, Issue 2, Page 73-77, April 2018.


https://ift.tt/2FvdigK

Multiple Tolerization Reduces Antibody Binding Against Tolerogen Cells: Implications for the Production of Monoclonal Antibodies

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Volume 37, Issue 2, Page 100-104, April 2018.


https://ift.tt/2KphzpD

Evidence That Graves' Ophthalmopathy Immunoglobulins Do Not Directly Activate IGF-1 Receptors

Thyroid, Ahead of Print.


https://ift.tt/2HCZ9UF

Thyroid Dysfunction and Anemia: A Prospective Cohort Study and a Systematic Review

Thyroid, Ahead of Print.


https://ift.tt/2raCdRG

PAs Less Accurate Than Dermatologists at Diagnosing Melanoma

Compared with dermatologists, physician assistants (PAs) are less likely to diagnose melanoma and more likely to perform more biopsies for each case of diagnosed skin cancer, researchers say.
Reuters Health Information

https://ift.tt/2HCR6TW

Pathologic significance of AKT, mTOR, and GSK3β proteins in oral squamous cell carcinoma-affected patients

Abstract

Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3β activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3β proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1^Thr308, pAKT^Ser473, GSK3β, pGSK3β^Ser9, and pmTOR^Ser2448 was analyzed by immunohistochemistry. The mean expression of GSK3β, pGSK3β^Ser9, total AKT, and pmTOR²⁴⁴⁸ was always higher in the OSCC tissues than that in the controls. A positive correlation was also found among these proteins. Total AKT, pmTOR^Ser2448, and pGSK3β^Ser9 expression was significantly higher in the PNM and PM groups than that in the control group. However, only GSK3β expression was significantly higher in the PM group compared with the PNM group. High expression levels of GSK3β and pGSK3β^Ser9 were significantly associated with CLN metastasis, but only GSK3β remained an independent predictor of CLN metastasis. pGSK3β^Ser9 and CLN metastasis were associated with a poor prognosis, but only the latter remained an independent prognostic parameter. Kaplan-Meier survival curves showed that pGSK3β^Ser9 and CLN metastasis were significantly related to reduced survival rates. These results suggest that AKT and mTOR proteins are involved in OSCC biology and that GSK3β itself may drive CLN metastatic spread of OSCC cells.

https://ift.tt/2HC3lE0

Intestinal paracoccidioidomycosis resembling Crohn’s disease in a teenager: a case report

Differential diagnosis of inflammatory bowel disease is often very challenging. Paracoccidioidomycosis is a fungal disease that can mimic manifestations of Crohn's disease.

https://ift.tt/2r9ruaL

De novo subgaleal abscess – a rare presentation of melioidosis: a case report

Melioidosis is an emerging infection in the tropics caused by the bacterium Burkholderia pseudomallei. Poorly controlled diabetes is a known risk factor. Melioidosis has a broad spectrum of clinical manifestation...

https://ift.tt/2JH5s6n

Experiencia clínica en pacientes con síndrome de Meige primario y disfonía espasmódica

Publication date: Available online 30 April 2018
Source:Acta Otorrinolaringológica Española
Author(s): María Fernanda Pedrero-Escalas, Isabel García-López, Susana Santiago-Pérez, Francisco Vivancos, Javier Gavilán
IntroducciónEl síndrome de Meige (SM) es considerado una distonía craneal segmentaria que afecta a dos o más músculos craneales. Específicamente, asocia blefaroespasmo a otra distonía craneal (oromandibular, cervical o laríngea). El objetivo de este artículo es presentar nuestra experiencia clínica en pacientes con disfonía espasmódica (DE) asociada a SM primario.Material y métodosEstudio retrospectivo realizado entre mayo de 2010 y junio de 2015. Incluyó 8 pacientes. Las variables recogidas fueron: sexo, edad, distonías asociadas, electromiografía laríngea y tratamiento. Los resultados clínicos objetivados fueron realizados, siempre por el mismo investigador, con la escala GRBAS(i) y el cuestionario VHI-30.ResultadosCincuenta y seis pacientes fueron tratados de SM por el servicio de Neurología. Ocho pacientes asociaron DE (prevalencia 14%). El 100% de nuestros pacientes tenían DE aductora. La mediana de edad para la aparición de DE fue de 71años. Todos los pacientes fueron tratados con infiltración intralaríngea de toxina botulínica bajo control electromiográfico. Se objetivó mejoría clínica tanto en la escala GRBAS(i) como en los cuestionarios VHI-30.ConclusiónEn el estudio de la DE siempre debe tenerse presente su posible asociación con el SM. Desde el punto de vista otorrinolaringológico, el uso conjunto de la escala GRBAS(i) y los cuestionarios VHI-30 es útil, fiable y eficiente como método para evaluar evolución y respuesta a tratamiento. La infiltración laríngea de toxina botulínica bajo control electromiográfico es la alternativa terapéutica que provee mejores resultados clínicos. El manejo de la DE asociada al SM no difiere del de la DE aislada.IntroductionMeige syndrome (MS) is part of the group of segmental cranial dystonias, which affect more than two cranial muscle groups. Specifically, blepharospasm is associated with another cranial dystonia (oromandibular, cervical or laryngeal). The aim of this paper was to report our experience in patients with spasmodic dysphonia (SD) associated with primary MS.Material and methodsA retrospective study involving 8 patients between May 2010 and June 2015. Variables recorded were: age, sex, associated dystonia, electromyographic pattern in laryngeal muscles and treatment given. Outcomes after treatment were assessed using GRBAS(i) scale and VHI-30 questionnaire, always provided by the same examiner.ResultsFifty-six patients with MS were treated in the Neurology Department. Eight patients of 56 were diagnosed with SD (prevalence of 14%). All of our patients had adductor SD. The median age was 71years. All the patients were treated with intralaryngeal botulinum toxin under electromyographic control. Clinically relevant improvements were found after treatment on both the GRBAS(i) scale and the VHI-30 questionnaire.ConclusionIn the study of SD, we should always rule out an association with MS. From the point of view of otorhinolaryngology, the joint use of the GRBAS(i) scale and the VHI-30 questionnaire are useful, reliable and efficient methods for assessing progress and response to treatment. Laryngeal infiltration under electromyographic control with botulinum toxin is the therapeutic alternative that provides better results. The management of SD associated with MS does not differ from isolated SD.



https://ift.tt/2FtlAWr

"There is a World out There We Can Step Into”: The University of Reading (UK) and the World Rankings

Locke, W; (2016) "There is a World out There We Can Step Into": The University of Reading (UK) and the World Rankings. In: Yudkevich, M and Altbach, PG and Rumbley, LE, (eds.) The Global Academic Rankings Game: Changing Institutional Policy, Practice, and Academic Life. Routledge: New York, New York. Green open access

https://ift.tt/2HC1GhU

In-vivo human sock-mapping validation of a simple model that explains unipolar electrogram morphology in relation to conduction-repolarization dynamics

Orini, M; Taggart, P; Lambiase, PD; (2018) In-vivo human sock-mapping validation of a simple model that explains unipolar electrogram morphology in relation to conduction-repolarization dynamics. Journal of Cardiovascular Electrophysiology 10.1111/jce.13606 . (In press).

https://ift.tt/2raJhhc

Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds

Wagner, T; Page, J; Burniston, M; Skillen, A; Ross, JC; Manwani, R; McCool, D; ... Wechalekar, AD; + view all Wagner, T; Page, J; Burniston, M; Skillen, A; Ross, JC; Manwani, R; McCool, D; Hawkins, PN; Wechalekar, AD; - view fewer (2018) Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds. European Journal of Nuclear Medicine and Molecular Imaging 10.1007/s00259-018-3995-2 . (In press). Green open access

https://ift.tt/2HC1tLE

The intracellular component of VERDICT (Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors) MRI distinguishes Gleason 4 pattern better than Apparent Diffusion Coefficient

Brizmohun, M; Johnston, E; Latifoltojar, A; O'Callaghan, J; Bonet-Carne, E; Ferizi, U; Yvernault, B; ... Punwani, S; + view all Brizmohun, M; Johnston, E; Latifoltojar, A; O'Callaghan, J; Bonet-Carne, E; Ferizi, U; Yvernault, B; Pye, H; Patel, D; Clemente, J; Piga, W; Heavey, S; Grey, A; Saborowska, A; Ourselin, S; Hawkes, D; Moore, C; Emberton, M; Ahmed, H; Whitaker, H; Rodriguez-Justo, M; Freeman, A; Atkinson, D; Alexander, D; Panagiotaki, E; Punwani, S; - view fewer (2018) The intracellular component of VERDICT (Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors) MRI distinguishes Gleason 4 pattern better than Apparent Diffusion Coefficient. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris Expo Porte de Versailles, Paris, France.

https://ift.tt/2rakJoh

Full blood count values as a predictor of poor outcome of pneumonia among HIV-infected patients

Camon, S; Quiros, C; Saubi, N; Moreno, A; Marcos, MA; Eto, Y; Rofael, S; ... Perello, R; + view all Camon, S; Quiros, C; Saubi, N; Moreno, A; Marcos, MA; Eto, Y; Rofael, S; Monclus, E; Brown, J; McHugh, TD; Mallolas, J; Perello, R; - view fewer (2018) Full blood count values as a predictor of poor outcome of pneumonia among HIV-infected patients. BMC Infectious Diseases , 18 , Article 189. 10.1186/s12879-018-3090-0 . Green open access

https://ift.tt/2HC1i2W

APT-CEST post Gadolinium. Should it be avoided? Comparison of pre- & post- Gadolinium CEST on glioma at 3T

Torrealdea, F; Hearle, J; Evans, V; Zaiss, M; Carvalho, A; Shankar, A; Hyare, H; ... Rega, M; + view all Torrealdea, F; Hearle, J; Evans, V; Zaiss, M; Carvalho, A; Shankar, A; Hyare, H; Atkinson, D; Golay, X; Barnes, A; Rega, M; - view fewer (2018) APT-CEST post Gadolinium. Should it be avoided? Comparison of pre- & post- Gadolinium CEST on glioma at 3T. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France.

https://ift.tt/2rakyJD

Is arterial stiffening associated with adiposity, severity of obesity and other contemporary cardiometabolic markers in a community sample of adolescents with obesity in the UK?

Hudson, L; Kinra, S; Wong, I; Cole, TJ; Deanfield, J; Viner, R; (2017) Is arterial stiffening associated with adiposity, severity of obesity and other contemporary cardiometabolic markers in a community sample of adolescents with obesity in the UK? BMJ Paediatrics Open , 1 (1) , Article e000061. 10.1136/bmjpo-2017-000061 . Green open access

https://ift.tt/2HBqZR3

Spatial Vascular Heterogeneity in the Normal Placenta Assessed with Multicompartment Placental MRI

Pratt, R; Melbourne, A; Owen, D; Sokolska, M; Bainbridge, A; Atkinson, D; Deprest, J; ... David, A; + view all Pratt, R; Melbourne, A; Owen, D; Sokolska, M; Bainbridge, A; Atkinson, D; Deprest, J; Kendall, G; Vercauteren, T; Ourselin, S; David, A; - view fewer (2018) Spatial Vascular Heterogeneity in the Normal Placenta Assessed with Multicompartment Placental MRI. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France. (In press).

https://ift.tt/2r9r2Zm

Hi-C as a tool for precise detection and characterisation of chromosomal rearrangements and copy number variation in human tumours

Harewood, L; Kishore, K; Eldridge, MD; Wingett, S; Pearson, D; Schoenfelder, S; Collins, VP; Harewood, L; Kishore, K; Eldridge, MD; Wingett, S; Pearson, D; Schoenfelder, S; Collins, VP; Fraser, P; - view fewer (2017) Hi-C as a tool for precise detection and characterisation of chromosomal rearrangements and copy number variation in human tumours. Genome Biology , 18 , Article 125. 10.1186/s13059-017-1253-8 . Green open access

https://ift.tt/2HCBO5l

Chemical Exchange Saturation Transfer imaging of prostate cancer at 3T: Repeatability, and initial results of an acquisition and multi-pool analysis protocol

Evans, V; Torrealdea, F; Rega, M; Kim, M; Brizmohun, M; Latifoltojar, A; Punwani, S; ... Atkinson, D; + view all Evans, V; Torrealdea, F; Rega, M; Kim, M; Brizmohun, M; Latifoltojar, A; Punwani, S; Golay, X; Atkinson, D; - view fewer (2018) Chemical Exchange Saturation Transfer imaging of prostate cancer at 3T: Repeatability, and initial results of an acquisition and multi-pool analysis protocol. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France. (In press).

https://ift.tt/2rakLwp

MRI assessed small bowel dysmotility and its relationship with patient reported symptoms: An exploration of automated vs subjective assessment techniques

Gollifer, R; Menys, A; Plumb, A; Vos, F; Stoker, J; Taylor, S; Atkinson, D; (2018) MRI assessed small bowel dysmotility and its relationship with patient reported symptoms: An exploration of automated vs subjective assessment techniques. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France. (In press).

https://ift.tt/2HCkhub

Multi-echo T2 modelling to predict PIRADS 2.0 score

Devine, W; Giganti, F; Johnston, E; Panagiotaki, E; Punwani, S; Alexander, D; Atkinson, D; (2018) Multi-echo T2 modelling to predict PIRADS 2.0 score. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France. (In press).

https://ift.tt/2rbAMCk

An identity transformation? Social class, language prejudice and the erasure of multilingual capital in higher education

Preece, S; (2016) An identity transformation? Social class, language prejudice and the erasure of multilingual capital in higher education. In: Preece, S, (ed.) The Routledge Handbook of Language and Identity. (pp. 366-381). Routledge: London, United Kindom. Green open access

https://ift.tt/2HCYliJ

Vascular-derived Vegfa promotes cortical interneuron migration and proximity to the vasculature in the developing forebrain

Barber, M; Andrews, WD; Memi, F; Gardner, P; Ciantar, D; Tata, M; Ruhrberg, C; Barber, M; Andrews, WD; Memi, F; Gardner, P; Ciantar, D; Tata, M; Ruhrberg, C; Parnavelas, JG; - view fewer (2018) Vascular-derived Vegfa promotes cortical interneuron migration and proximity to the vasculature in the developing forebrain. Cerebral Cortex 10.1093/cercor/bhy082 . (In press).

https://ift.tt/2r8YQG4

Two compartment fitting for Luminal Water Imaging: multi-echo T2 in Prostate Cancer

Devine, W; Giganti, F; Johnston, E; Panagiotaki, E; Punwani, S; Alexander, DC; Atkinson, D; (2018) Two compartment fitting for Luminal Water Imaging: multi-echo T2 in Prostate Cancer. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France. (In press).

https://ift.tt/2HGjloz

Physical computing with plug-and-play toolkits:Key recommendations for collaborative learning implementations

Katterfeldt, ES; Cukurova, M; Spikol, D; Cuartielles, D; (2018) Physical computing with plug-and-play toolkits:Key recommendations for collaborative learning implementations. International Journal of Child-Computer Interaction 10.1016/j.ijcci.2018.03.002 . (In press).

https://ift.tt/2r8YAXC

Placental Insufficiency Investigated with Multi-compartment Placental MRI

Melbourne, A; Pratt, R; Owen, D; Sokolska, M; Bainbridge, A; Atkinson, D; Deprest, J; ... Ourselin, S; + view all Melbourne, A; Pratt, R; Owen, D; Sokolska, M; Bainbridge, A; Atkinson, D; Deprest, J; Kendall, G; Vercauteren, T; David, A; Ourselin, S; - view fewer (2018) Placental Insufficiency Investigated with Multi-compartment Placental MRI. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France. (In press).

https://ift.tt/2HDS5Hu

Reduction in tuberculosis incidence in the UK from 2011 to 2015: a population-based study

Harris, RJ; Muzyamba, MC; Davidson, JA; Lalor, MK; Campbell, CNJ; Anderson, SR; Zenner, D; (2018) Reduction in tuberculosis incidence in the UK from 2011 to 2015: a population-based study. Thorax 10.1136/thoraxjnl-2017-211074 . (In press). Green open access

https://ift.tt/2rbBD5Y

Pre-treatment intra- and inter- voxel magnetic resonance diffusion heterogeneity correlates with chemoradiotherapy treatment outcome of patients with head and neck squamous cell carcinoma

Papoutsaki, M; Sidhu, H; Dikaios, N; Atkinson, D; Beale, T; Morley, S; Forster, M; ... Punwani, S; + view all Papoutsaki, M; Sidhu, H; Dikaios, N; Atkinson, D; Beale, T; Morley, S; Forster, M; Carnell, D; Mendes, R; Punwani, S; - view fewer (2018) Pre-treatment intra- and inter- voxel magnetic resonance diffusion heterogeneity correlates with chemoradiotherapy treatment outcome of patients with head and neck squamous cell carcinoma. Presented at: Joint Annual Meeting ISMRM-ESMRMB 2018, Paris, France. (In press).

https://ift.tt/2HCYiU5

Uncertain association between depression and stroke risk in Chinese mega-study

Brunner, EJ; Weinreb, IR; (2017) Uncertain association between depression and stroke risk in Chinese mega-study. Evidence-Based Mental Health , 20 , Article e8. 10.1136/eb-2016-102572 . Green open access

https://ift.tt/2rak0n3

Safety and efficacy of HCV eradication during etanercept treatment for severe psoriasis

Dermatologic Therapy, EarlyView.


https://ift.tt/2Ftloq4

Few Patients Maximize Opioid-Sparing Medications after Orthopaedic Surgery, Study Finds

A new study led by Johns Hopkins researchers adds to growing evidence that patients underuse nonopioid pain relievers to supplement opioid pain management after spine and joint surgery.

https://ift.tt/2HDGFTW

A Comprehensive Analysis of Benign Vocal Fold Lesions Causing Hoarseness of Voice and Our Experience with Cold Knife Endolaryngeal Surgery in a Tertiary Healthcare Centre

Abstract

Benign vocal fold lesions (BVFL) frequently affect the general population and cause significant hoarseness by interfering with daily communication. Healthcare for low income groups in India is all about affordability and availability without giving up on quality and providing maximum satisfaction. (1) To analyse over a period of 4 years, the demographics, clinical profile, diagnostics and management options of BVFL. (2) To assess the diagnostic potential of rigid laryngoscopy in diagnosing these lesions. (3) Cold knife endolaryngeal surgery as a cost effective, satisfactory and efficient treatment modality to tackle majority of these BVFL. A prospective cross sectional study over a period of 4 years from 2013 to 2017. 114 patients presenting with hoarseness of voice were evaluated by indirect laryngoscopy followed by video laryngoscopy and stroboscopy in the department of ENT, MYH Hospital Indore (M.P.). Male:female ratio of 1.59:1 with male predominance (61.4%) and maximum incidence in the third decade (32%). All cases presented with hoarseness (100%) while vocal fatigue (63%) was the most common associated complaint followed by foreign body sensation (60%). Housewives (32%) were most commonly involved non professional group while teachers (13%) constituted the most common group of professionals. Laryngitis (26%) involving bilateral vocal folds diffusely was the most common finding followed by vocal fold sulcus (18%) and vocal fold cysts (14%). The duration of symptom was 6 months to 1 year in 52% patients. The positive predictive value for rigid laryngoscopy was 100% for vocal nodules, arytenoid granulomas and anterior glottis web. Out of 114 patients, 66 patients improved on conservative management while 48 patients underwent cold knife endolaryngeal surgery. As per the GRBAS scale to assess the post therapeutic prognosis, all had good outcome of voice with only two recurrences due to patient non compliance. In this rapidly evolving era of sophisticated lasers which is a costly affair that requires skilled personnel and safety precautions, the prime goal in a government run setup has always been to provide affordable and quality healthcare to the common man. Cold knife endolaryngeal surgery is a simple, cost effective and efficient way to tackle most of these lesions and hence helps in achieving this goal.

https://ift.tt/2HFtbmB

Skin neurogenic inflammation

Abstract

The epidermis closely interacts with nerve endings, and both epidermis and nerves produce substances for mutual sustenance. Neuropeptides, like substance P (SP) and calcitonin gene-related protein (CGRP), are produced by sensory nerves in the dermis; they induce mast cells to release vasoactive amines that facilitate infiltration of neutrophils and T cells. Some receptors are more important than others in the generation of itch. The Mas-related G protein-coupled receptors (Mrgpr) family as well as transient receptor potential ankyrin 1 (TRPA1) and protease activated receptor 2(Par2) have important roles in itch and inflammation. The activation of MrgprX1 degranulates mast cells to communicate with sensory nerve and cutaneous cells for developing neurogenic inflammation. Mrgprs and transient receptor potential vanilloid 4 (TRPV4) are crucial for the generation of skin diseases like rosacea, while SP, CGRP, somatostatin, β-endorphin, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating polypeptide (PACAP) can modulate the immune system during psoriasis development. The increased level of SP, in atopic dermatitis, induces the release of interferon (IFN)-γ, interleukin (IL)-4, tumor necrosis factor (TNF)-α, and IL-10 from the peripheral blood mononuclear leukocytes. We are finally starting to understand the intricate connections between the skin neurons and resident skin cells and how their interaction can be key to controlling inflammation and from there the pathogenesis of diseases like atopic dermatitis, psoriasis, and rosacea.

https://ift.tt/2vWfKNV

Boobs and Barbie: Feminist Posthuman and new materialism perspectives on gender, bodies and practice

Ringrose, JL; Coffey, J; (2016) Boobs and Barbie: Feminist Posthuman and new materialism perspectives on gender, bodies and practice. In: Practice Theory and Education Diffractive readings in professional practice. Routledge

https://ift.tt/2r8fRA0

Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study

Vallejo-Torres, L; Pujol, M; Shaw, E; Wiegand, I; Vigo, JM; Stoddart, M; Grier, S; ... RESCUING Study Group and Study Sites, ; + view all Vallejo-Torres, L; Pujol, M; Shaw, E; Wiegand, I; Vigo, JM; Stoddart, M; Grier, S; Gibbs, J; Vank, C; Cuperus, N; van den Heuvel, L; Eliakim-Raz, N; Carratala, J; Vuong, C; MacGowan, A; Babich, T; Leibovici, L; Addy, I; Morris, S; RESCUING Study Group and Study Sites, ; - view fewer (2018) Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study. BMJ Open , 8 (4) , Article e020251. 10.1136/bmjopen-2017-020251 . Green open access

https://ift.tt/2HGAsa4

Statistical Modeling for Health Economic Evaluations

Baio, G; (2018) Statistical Modeling for Health Economic Evaluations. ANNUAL REVIEW OF STATISTICS AND ITS APPLICATION, VOL 5 , 5 pp. 289-309. 10.1146/annurev-statistics-031017-100404 .

https://ift.tt/2r974xS

Competition, accountability and performativity: Exploring schizoid neo-liberal ‘equality objectives’ in a UK primary school

Harvey, J; Ringrose, J; (2016) Competition, accountability and performativity: Exploring schizoid neo-liberal 'equality objectives' in a UK primary school. In: Education and Political Subjectivities in Neoliberal Times and Places: Emergences of Norms and Possibilities. (pp. 50-67). Green open access

https://ift.tt/2HEAuPL

Cutaneous vasculitis and recurrent infection caused by deficiency in complement factor I

Nanthapisal, S; Eleftheriou, D; Gilmour, K; Leone, V; Ramnath, R; Omoyinmi, E; Hong, Y; ... Brogan, PA; + view all Nanthapisal, S; Eleftheriou, D; Gilmour, K; Leone, V; Ramnath, R; Omoyinmi, E; Hong, Y; Klein, N; Brogan, PA; - view fewer (2018) Cutaneous vasculitis and recurrent infection caused by deficiency in complement factor I. Frontiers in Immunology , 9 , Article 735. 10.3389/fimmu.2018.00735 . Green open access

https://ift.tt/2r9seMl

Development of the human placenta and fetal heart: Synergic or independent?

Burton, GJ; Jauniaux, E; (2018) Development of the human placenta and fetal heart: Synergic or independent? Frontiers in Physiology , 9 , Article 373. 10.3389/fphys.2018.00373 . Green open access

https://ift.tt/2HCIosO

Autumn MIST 2017

Sandhu, JK; Graham, GA; Bentley, SN; Coxon, J; (2018) Autumn MIST 2017. Astronomy & Geophysics , 59 (2) pp. 26-29. 10.1093/astrogeo/aty083 . Green open access

https://ift.tt/2rasaMn

Diagnosing cancer in patients with ‘non-alarm’ symptoms: Learning from diagnostic care innovations in Denmark

Forster, AS; Renzi, C; Lyratzopoulos, G; (2018) Diagnosing cancer in patients with 'non-alarm' symptoms: Learning from diagnostic care innovations in Denmark. [Editorial comment]. Cancer Epidemiology , 54 pp. 101-103. 10.1016/j.canep.2018.03.011 . Green open access

https://ift.tt/2HFU2TB

The redshift evolution of rest-UV spectroscopic properties in Lyman Break Galaxies at z ~ 2-4

Du, X; Shapley, AE; Reddy, NA; Jones, T; Stark, DP; Steidel, CC; Strom, AL; ... Pettini, M; + view all Du, X; Shapley, AE; Reddy, NA; Jones, T; Stark, DP; Steidel, CC; Strom, AL; Rudie, GC; Erb, DK; Ellis, R; Pettini, M; - view fewer (2018) The redshift evolution of rest-UV spectroscopic properties in Lyman Break Galaxies at z ~ 2-4. The Astrophysical Journal (In press).

https://ift.tt/2r8Fktp

Accessibility, affordability and equity: Assessing ‘pro-poor’ public transport subsidies in Bogotá

Oviedo Hernandez, DR; Guzman, LA; (2018) Accessibility, affordability and equity: Assessing 'pro-poor' public transport subsidies in Bogotá. Journal of Transport Geography , 68 pp. 37-51. 10.1016/j.tranpol.2018.04.012 .

https://ift.tt/2HBgxZW

Digital Mediation, Connectivity and Affective Materialities

Ringrose, JL; Harvey, L; (2017) Digital Mediation, Connectivity and Affective Materialities. In: Routledge Handbook of Physical Cultural Studies. Routledge

https://ift.tt/2rfc6cr

Risk Factors for Prognosis in Patients With Severely Decreased GFR

Evans, M; Grams, ME; Sang, Y; Astor, BC; Blankestijn, PJ; Brunskill, NJ; Collins, JF; ... Wheeler, DC; + view all Evans, M; Grams, ME; Sang, Y; Astor, BC; Blankestijn, PJ; Brunskill, NJ; Collins, JF; Kalra, PA; Kovesdy, CP; Levin, A; Mark, PB; Moranne, O; Rao, P; Rios, PG; Schneider, MP; Shalev, V; Zhang, H; Chang, AR; Gansevoort, RT; Matsushita, K; Zhang, L; Eckardt, KU; Hemmelgarn, B; Wheeler, DC; - view fewer (2018) Risk Factors for Prognosis in Patients With Severely Decreased GFR. Kidney International Reports 10.1016/j.ekir.2018.01.002 . (In press). Green open access

https://ift.tt/2HBgkpC

Effectiveness of Universal Self-regulation–Based Interventions in Children and Adolescents: A Systematic Review and Meta-analysis

Pandey, A; Hale, D; Das, S; Goddings, AM; Blakemore, S; Viner, RM; (2018) Effectiveness of Universal Self-regulation–Based Interventions in Children and Adolescents: A Systematic Review and Meta-analysis. JAMA Pediatrics 10.1001/jamapediatrics.2018.0232 . (In press).

https://ift.tt/2r8ELzN

Towards the development of Helpful Aspects of Morenian Psychodrama Content Analysis System (HAMPCAS)

Cruz, AS; Sales, CMD; Moita, G; Gomes Alves, PC; (2016) Towards the development of Helpful Aspects of Morenian Psychodrama Content Analysis System (HAMPCAS). In: Psychodrama. Empirical Research and Science 2. (pp. 57-67). Springer: Wiesbaden.

https://ift.tt/2HB3Qy8

Hyperacusis: major research questions

Abstract

Background

Hyperacusis is a troublesome symptom that can have a marked negative impact on quality of life.

Objectives

To identify major research questions in hyperacusis.

Materials and methods

Review of gaps in knowledge regarding hyperacusis, and where opportunities may lie to address these.

Results

Eight major research questions were identified as priorities for future research. These were: What is the prevalence of hyperacusis in adults and children? What are the risk factors associated with hyperacusis? What is the natural history of hyperacusis? How is 'pain hyperacusis' perceived? What mechanisms are involved in hyperacusis? What is the relationship between hyperacusis and tinnitus? Can a questionnaire be developed that accurately measures the impact of hyperacusis and can be used as a treatment outcome measure? What treatments, alone or in combination, are effective for hyperacusis?

Conclusion

This clinical/researcher-led project identified major research questions in hyperacusis. A further development to identify patient-prioritized research will follow.

https://ift.tt/2KnwVeg

Update HNO

https://ift.tt/2FtFLUa

Smartphone-App-gestützte Ansätze in der Tinnitusbehandlung

Zusammenfassung

In den letzten Jahren werden vermehrt Anwendungen für medizinische Zwecke entwickelt und vorgestellt, so auch Applikationen („Apps"), mit denen sich in Verbindung mit Mobiltelefonen (Smartphones) eine Diagnostik und Dokumentation von Hörproblemen wie Schwerhörigkeit und Tinnitus durchführen lässt. Auch Smartphone-Apps zur Therapie, besonders für Tinnitus, wurden auf den Markt gebracht. In dieser Übersichtsarbeit wird die bislang vorliegende wissenschaftliche Literatur zu diesen Smartphone-Applikationen erörtert. Für die Tinnitustherapie wurden internetbasierte und evaluierte Angebote der Verhaltenstherapie entwickelt. Zur Behandlung von Tinnitus vorgestellte Apps verbinden akustische Stimulation und Musik oder dienen der akustischen Stimulation kortikaler Regionen im Bereich der Tinnitusfrequenz. Sie gelten zwar als sehr innovativ, jedoch wurde bislang der wissenschaftliche Nutzen ihrer Wirksamkeit noch nicht erbracht. Ein generelles Problem bezüglich der Anwendung von Smartphone-Applikationen liegt in ihrer tatsächlichen Sicherheit in Bezug auf mögliche Nebenwirkungen wie auch bezüglich des persönlichen Datenschutzes. Dennoch können Internetangebote und Apps eine sinnvolle Ergänzung multimodaler Therapieformen bilden.

https://ift.tt/2r5fZQW

Bothersome tinnitus

Abstract

Tinnitus is not traceable to a single disease or pathology, but merely a symptom, which is distressing to some but not all individuals able to perceive it. The experience of tinnitus does not equate to tinnitus distress. Tinnitus suffering might be understood as a function of tinnitus-related distress in that bothersome tinnitus is an illness rather than a disease. In bothersome (distressing) tinnitus, the perception of the characteristic sound is a very disturbing and bothersome experience because of maladaptive psychological responses. Several cognitive and behavioral theoretical frameworks attempting to explain the nature and cause of tinnitus suffering have been introduced in and will be summarized here. Current treatment approaches are generally based on models that aim to: alleviate the perceptional experience by focusing on the tinnitus perception for habituation or even soothing purposes; decrease awareness of the sound by attentional training and cognitive interventions; decrease the maladaptive responses and the resulting distress by behavioral methods (i. e., exposure). The cognitive behavioral fear-avoidance model may offer an integrative cognitive behavioral approach that can lead to a new set of paradigms for studying the underlying mechanisms explaining chronic tinnitus suffering as well for developing innovative strategies to treat bothersome tinnitus.

https://ift.tt/2HFQbWD

A Comprehensive Analysis of Benign Vocal Fold Lesions Causing Hoarseness of Voice and Our Experience with Cold Knife Endolaryngeal Surgery in a Tertiary Healthcare Centre

Abstract

Benign vocal fold lesions (BVFL) frequently affect the general population and cause significant hoarseness by interfering with daily communication. Healthcare for low income groups in India is all about affordability and availability without giving up on quality and providing maximum satisfaction. (1) To analyse over a period of 4 years, the demographics, clinical profile, diagnostics and management options of BVFL. (2) To assess the diagnostic potential of rigid laryngoscopy in diagnosing these lesions. (3) Cold knife endolaryngeal surgery as a cost effective, satisfactory and efficient treatment modality to tackle majority of these BVFL. A prospective cross sectional study over a period of 4 years from 2013 to 2017. 114 patients presenting with hoarseness of voice were evaluated by indirect laryngoscopy followed by video laryngoscopy and stroboscopy in the department of ENT, MYH Hospital Indore (M.P.). Male:female ratio of 1.59:1 with male predominance (61.4%) and maximum incidence in the third decade (32%). All cases presented with hoarseness (100%) while vocal fatigue (63%) was the most common associated complaint followed by foreign body sensation (60%). Housewives (32%) were most commonly involved non professional group while teachers (13%) constituted the most common group of professionals. Laryngitis (26%) involving bilateral vocal folds diffusely was the most common finding followed by vocal fold sulcus (18%) and vocal fold cysts (14%). The duration of symptom was 6 months to 1 year in 52% patients. The positive predictive value for rigid laryngoscopy was 100% for vocal nodules, arytenoid granulomas and anterior glottis web. Out of 114 patients, 66 patients improved on conservative management while 48 patients underwent cold knife endolaryngeal surgery. As per the GRBAS scale to assess the post therapeutic prognosis, all had good outcome of voice with only two recurrences due to patient non compliance. In this rapidly evolving era of sophisticated lasers which is a costly affair that requires skilled personnel and safety precautions, the prime goal in a government run setup has always been to provide affordable and quality healthcare to the common man. Cold knife endolaryngeal surgery is a simple, cost effective and efficient way to tackle most of these lesions and hence helps in achieving this goal.

https://ift.tt/2HFtbmB

Evaluation of selected skin parameters following the application of 5% vitamin C concentrate

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2rasudV

Analysis of the changes in scalp hair angles: In vivo and in vitro comparison before and after tumescence

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2rbOwwO

Association between clinical characteristics, quality of life, and sleep quality in patients with periorbital hyperchromia

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2HD16QO

Evidence‐based treatment for gynoid lipodystrophy: A review of the recent literature

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2HD0XNg

Platelet‐rich plasma on female androgenetic alopecia: Tested on 10 patients

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2rask6j

Combination of fractional carbon dioxide laser with narrow band ultraviolet B to induce repigmentation in stable vitiligo: A comparative study

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2HD0SJs

Correlation between serum IL‐17A level and SALT score in patients with alopecia areata before and after NB‐UVB therapy

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2ras7A3

Serum Adenosine Deaminase Levels and Human Papillomavirus as Prognostic and Predictive Factors for Laryngeal and Pharyngeal Carcinomas

Abstract

Head and neck cancer is one of the most common cancers in the world, accounting for up to 30–40% malignancies in India. Research is always on the lookout for parameters that help in early diagnosis of such disease and to explore the possibility of discovering such parameters that would assist in management of the disease by its potential to predict and prognosticate the disease. To estimate serum ADA levels and to correlate with response to therapy and also to correlate between different clinical stages and serum ADA levels and to correlate HPV status to response to therapy. A prospective cohort study. 30 patients who were diagnosed with squamous cell carcinoma of the oropharynx, hypopharynx and larynx were considered in this study. The pre and post treatment values of serum ADA was estimated in these patients and the tumour was assessed for HPV status. The difference in the in the serum ADA levels before and after treatment was 9.982 which was statistically significant with a p value of < 0.001. HPV positive status and response to therapy in the form of recurrence shows a p value of 0.485 which is not statistically significant. Serum ADA level can be used as a parameter to assess the severity of the disease and the response to treatment in cases of carcinoma of the oropharynx, hypopharynx and larynx. HPV status of the disease has its limitation in prediction and prognosis of the disease.

https://ift.tt/2FsFYXD

Serum Adenosine Deaminase Levels and Human Papillomavirus as Prognostic and Predictive Factors for Laryngeal and Pharyngeal Carcinomas

Abstract

Head and neck cancer is one of the most common cancers in the world, accounting for up to 30–40% malignancies in India. Research is always on the lookout for parameters that help in early diagnosis of such disease and to explore the possibility of discovering such parameters that would assist in management of the disease by its potential to predict and prognosticate the disease. To estimate serum ADA levels and to correlate with response to therapy and also to correlate between different clinical stages and serum ADA levels and to correlate HPV status to response to therapy. A prospective cohort study. 30 patients who were diagnosed with squamous cell carcinoma of the oropharynx, hypopharynx and larynx were considered in this study. The pre and post treatment values of serum ADA was estimated in these patients and the tumour was assessed for HPV status. The difference in the in the serum ADA levels before and after treatment was 9.982 which was statistically significant with a p value of < 0.001. HPV positive status and response to therapy in the form of recurrence shows a p value of 0.485 which is not statistically significant. Serum ADA level can be used as a parameter to assess the severity of the disease and the response to treatment in cases of carcinoma of the oropharynx, hypopharynx and larynx. HPV status of the disease has its limitation in prediction and prognosis of the disease.

https://ift.tt/2FsFYXD