Αρχειοθήκη ιστολογίου

Δευτέρα 24 Απριλίου 2017

Allocation of organs should be based on the current status of medical science.

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No abstract available

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Dynamics of B cell recovery following kidney/bone marrow transplant recipients.

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Background: Previous studies identified B cell gene signatures and predominance of specific B cell subsets as a marker of operational tolerance following kidney transplantation. These findings suggested a role for B cells in the establishment or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of whom achieved tolerance after combined kidney/bone marrow transplantation. Methods: Peripheral B cell subsets were examined longitudinally by flow cytometry. Immunoglobulin heavy chain repertoire analysis was performed using next generation sequencing. Lastly, the patients' serum reactivity to HLA was assessed by Luminex. Results: B cell counts recovered approximately 1 year posttransplant except for 1 subject who experienced delayed reconstitution. This subject resumed immunosuppression for acute rejection at 10 months posttransplant and underwent preemptive retransplantation at 3 years for chronic rejection. B cell recovery was accompanied by a high frequency of CD20+CD24highCD38high transitional B cells and a diversified clonal repertoire. However, all 4 subjects showed prevalence of CD20+CD27+ memory B cells around 6 months posttransplant when B cell counts were still low and the clonal B cell repertoire very limited. The predominance of memory B cells was also associated with high levels of somatically mutated IGHV sequences and transient serum reactivity to HLA. Conclusions: Our observations reveal the presence of memory B cells early posttransplant that likely escaped the preparative regimen at a time consistent with the establishment of tolerance. Further studies are warranted to characterize the functional properties of these persisting memory cells and evaluate their potential contribution to tolerance induction. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Cut the "Gordian Knot".

No abstract available

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Keratoacanthoma, palmoplantar keratoderma developing in an advanced melanoma patient treated with vemurafenib regressed by blockade of mitogen-activated protein kinase kinase signaling



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Novel nonsense mutation in SERPINB7 and the treatment of foot odor in a patient with Nagashima-type palmoplantar keratosis



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Angioleiomyoma mimicking pes anserinus bursitis: A case report



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Biologic treatments for elderly patients with psoriasis

Abstract

The number of elderly patients with psoriasis is increasing in Japan. However, biologic treatment is generally considered to be challenging in elderly patients, due to their increased risk of complications compared with younger patients. Our retrospective study aimed to evaluate the safety profile and efficacy of biologics in senior elderly patients (≥75 years old) with psoriasis. The study involved a cohort of 27 patients aged 75–88 years who were being treated with biologics over a period of more than 1 year. Initial biologics administrated to were adalimumab (five cases) and ustekinumab (22 cases). Eight patients discontinued treatment: two developed cancer; one was transferred to hospital; and five others experienced either bone fracture, interstitial pneumonia, cerebral hemorrhage resulting in death, decrepitude or developed hepatopathy following prophylactic tuberculosis treatment. Efficacy, evaluated by the percentage of patients achieving 75% reduction of Psoriasis Area and Severity Index score, was 76.9% at week 16 (n = 26), 88.0% at week 24 (n = 25) and 90.5% at week 52 (n = 21). Biologic treatments thus show clear efficacy in elderly patients with psoriasis, however, the increased frequency of adverse events requires rigorous patient observation.



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Dengue fever rash: white islands in a sea of red



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Emergence of plasmid-mediated mcr-1 gene in clinical KPC-2-producing Klebsiella pneumoniae ST392 in Brazil [PublishAheadOfPrint]

Since the first report of the plasmid-mediated colistin resistance mcr-1 gene in Escherichia coli and Klebsiella pneumoniae isolates from China (1), mcr-1 had already spread to most continents, being detected in different species from several sources, including in carbapenemase-producing clinical isolates (2)....



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Susceptibility of imipenem-susceptible but meropenem-resistant Enterobacteriaceae carrying blaIMP-6 to various antibacterials including siderophore cephalosporin, cefiderocol. [PublishAheadOfPrint]

Carbapenemase-producing Enterobacteriaceae (CPE) have been spreading worldwide and are a great concern among healthcare settings (1)....



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Pyrazinoic Acid Inhibits a Bifunctional Enzyme in Mycobacterium tuberculosis [PublishAheadOfPrint]

Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug by Mycobacterium tuberculosis into pyrazinoic acid (POA) has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report a new PZA resistance determinant: Asp67Asn substitution in Rv2783 confers M. tuberculosis resistance to PZA. Expression of the mutant but not the wild-type allele in M. tuberculosis recapitulates PZA resistance observed in clinical isolates. In addition to catalyzing metabolism of RNA and single-stranded DNA, Rv2783 also metabolized ppGpp, an important signal transducer involved in the stringent response in bacteria. All catalytic activities of the wild-type Rv2783 but not themutant were significantly inhibited by POA. These results, which indicate that Rv2783 is a target of PZA, provide new insight into the molecular mechanism of the sterilizing activity of this drug and a basis for improving molecular diagnosis of PZA resistance and developing evolved PZA derivatives to enhance its anti-tuberculosis activity.



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Treatment with Entinostat heals experimental cholera by affecting physical and chemical barrier functions of intestinal epithelia [PublishAheadOfPrint]

We have previously shown that oral treatment of an experimental model of shigellosis with sodium butyrate or phenylbutyrate improves clinical outcome and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we have found that Entinostat, an aroylated phenylenediamine compound has similar therapeutic potential against shigellosis. Here, we aim to evaluate Entinostat as a potential candidate for host-directed therapy against cholera in an experimental model. Vibrio cholerae-infected rabbits were treated with two different dose regimen of Entinostat i.e. 0.5 mg twice daily for 2 days and 1 mg once daily for 2 days. Treatment effect on clinical outcomes and shedding of V. cholerae (CFU count in stool) was observed. Immunohistochemical analysis was carried out to assess CAP-18 expression in ileal and jejunal mucosa. Serum zonulin level was measured by ELISA to evaluate gut permeability. Infection of rabbits with V. cholerae down-regulated CAP-18 expression in the ileal epithelium; the expression was replenished by oral treatment with Entinostat at both dose regimens. Level of serum zonulin, a marker of gut permeability was up-regulated after infection, which was counteracted after treatment with Entinostat. Entinostat treatment also led to recovery from cholera and decline in V. cholerae count in stool. In conclusion, improved clinical outcome of treatment with Entinostat in cholera is associated with induction of CAP-18 and reduction of gut epithelial permeability.



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Demonstrating the protective efficacy of the novel fluoroquinolone finafloxacin against an inhalational exposure to Burkholderia pseudomallei [PublishAheadOfPrint]

Burkholderia pseudomallei is the causative agent of melioidosis, a serious disease endemic in South East Asia and Northern Australia. Antibiotic treatment is lengthy and relapse often occurs. Finafloxacin is a novel fluoroquinolone with increased antibacterial activity in acidic conditions in contrast to other fluoroquinolones which demonstrate reduced activity at lower pH. Therefore finafloxacin may have improved efficacy against B. pseudomallei, which can survive within host cells where the local pH is acidic. In vitro analysis was performed using MICs, MBCs, time kill assays, persister cell assays and macrophage assays. Finafloxacin showed increased bactericidal activity at pH 5 in comparison to pH 7 and ciprofloxacin at pH 5. In vivo studies in BALB/c mice included pharmacokinetic studies to inform an appropriate dosing regimen. Finafloxacin efficacy was evaluated in an inhalational murine model of melioidosis where antibiotic treatment was initiated at 6 or 24 hours post challenge and continued for 14 days, and mice were observed for 63 days. Survival of infected mice following 14 days of treatment was 80%, 60% or 0% for treatment initiated at 6 hours and 60%, 30% or 0 % for treatment initiated at 24 hours for finafloxacin, co-trimoxazole or ciprofloxacin, respectively. In summary, finafloxacin has increased bactericidal activity for B. pseudomallei under acidic conditions in vitro and improves survival in a murine model of melioidosis when compared to ciprofloxacin. Furthermore, finafloxacin improves bacteriological clearance when compared to co-trimoxazole, suggesting it may offer effective post exposure prophylaxis against B. pseudomallei.



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Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in Chromosome [PublishAheadOfPrint]

The extended-spectrum β-lactamase (ESBL)- and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14 and NY9, carrying both blaCTX-M and blaKPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, blaCTX-M and blaKPC were carried on two different plasmids. In contrast, CN1 had one blaKPC-2 and three copies of blaCTX-M-15 integrated in the chromosome, for which the blaCTX-M-15 genes were linked to an insertion sequence ISEcp1, whereas blaKPC-2 gene was in the context of a Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn4401a-blaKPC-2-prophage genomic island, CN1 also carried a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of Type I-E CRISPR-cas in K. pneumoniae strains; and suggested that the evolving CRISPR-cas with its acquired novel spacer might have induced the mobilization of antimicrobial resistance genes from plasmids into chromosome. The integration and dissemination of multiple copies of blaCTX-M and blaKPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae. Additionally, the implications from this study also raise concern for the application of a CRISPR-cas strategy against antimicrobial resistance.



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Genomic insights into mcr-1-positive plasmids carried by the colistin-resistant Escherichia coli from the inpatients [PublishAheadOfPrint]

Colistin, a family of cationic polypeptide antibiotics, acts as a final resort against infections by the multidrug-resistant Gram-negative pathogens....



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Potassium iodide potentiates antimicrobial photodynamic inactivation mediated by Rose Bengal: in vitro and in vivo studies. [PublishAheadOfPrint]

Rose Bengal (RB) is a halogenated xanthene dye that has been used to mediate antimicrobial photodynamic inactivation for several years. While highly active against Gram-positive bacteria, RB is largely inactive in killing Gram-negative bacteria. We have discovered that addition of the non-toxic salt potassium iodide (100mM) potentiates green light (540nm)-mediated killing by up to six extra logs with Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, Gram-positive methicillin resistant Staphylococcus aureus, and fungal yeast Candida albicans. The mechanism is proposed to be singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes into radicals, and finally forms hydrogen peroxide and molecular iodine. The effects of these different bactericidal species can be teased apart by comparing killing in three different scenarios: (1) cells+RB+KI are mixed together then illuminated with green light; (2) cells+RB are centrifuged then KI added then green light; (3) RB+KI+green light then cells added after light. We also showed that KI could potentiate RB-PDT in a mouse model of skin abrasions infected with bioluminescent P. aeruginosa.



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IncX2 and IncX1-X2 hybrid plasmids coexisting in FosA6-producing Escherichia coli [PublishAheadOfPrint]

IncX plasmids are receiving much attention as vehicles of carbapenem and colistin resistance genes, such as blaNDM, blaKPC and mcr-1. Among them, IncX2 subgroup plasmids remain rare. Here we characterized IncX2 and IncX1-X2 hybrid plasmids coexisting in a FosA6-producing Escherichia coli strain, which were possibly generated as a consequence of recombination events between an R6K-like IncX2 plasmid and a pLN126_33-like IncX1 plasmid. Variable multidrug resistance mosaic regions were observed in these plasmids indicating their potential to serve as flexible carriers of resistance genes. The diversity of IncX group plasmid backbones and accessory genes and the evolution of hybrid IncX plasmids pose a challenge in detecting and classifying them.



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Multi-hospital occurrence of pan-resistant Klebsiella pneumoniae ST147 with an ISEcp1-directed blaOXA-181 insertion into the mgrB gene in the United Arab Emirates [PublishAheadOfPrint]

The emergence of pan-resistant Klebsiella pneumoniae strains is an increasing concern. In the current study we describe a cluster of 9 pan-resistant K. pneumoniae ST147 isolates encountered in 4 patients over nearly one year in 3 hospitals of the United Arab Emirates. The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181 and the majority also produced the NDM-5 carbapenemase. Similarly to the previously described single isolate from the UAE, MS6671, the mgrB was disrupted by a functional, ISEcp1-driven blaOXA-181 insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact mgrB gene indicating that it was responsible for colistin resistance. blaNDM-5 was located within a resistance island of an approximately 100 kb IncFII plasmid carrying ermB, mph(A), blaTEM-1B, rmtB, blaNDM-5, sul1, aadA2 and dfrA12 resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including blaNDM-5, had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the blaNDM-5 carrying IncFII plasmids of two K. pneumoniae ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time, and even likely to be transmitted internationally.



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The Correlation between gyrA and CmeR-Box Polymorphism and Fluoroquinolones Resistance in Campylobacter jejuni Isolates in China [PublishAheadOfPrint]

Sequence analysis of 79 ciprofloxacin-resistant Campylobacter jejuni isolates collected in China showed resistance-related sequence variations in gyrA and CmeR-Box. All the isolates contain an identical Thr-86-Ile substitution in GyrA. Several novel CmeR-Box variations were identified, including point substitutions, deletion and insertion. The point insertion or deletion led to dramatically reduced binding of CmeR to the cmeABC promoter, which significantly increase the expression of cmeABC and contribute to the high fluoroquinolone resistance.



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New macrolide-lincosamide-streptogramin B resistance gene erm(48) on the novel plasmid pJW2311 in Staphylococcus xylosus [PublishAheadOfPrint]

Whole-genome sequencing of Staphylococcus xylosus strain JW2311 from bovine mastitis milk identified the novel 49.3 kb macrolide-lincosamide-streptogramin B (MLSB) resistance plasmid pJW2311. It contained the macrolide resistance gene mph(C), the macrolide-streptogramin B resistance gene msr(A), and the new MLSB resistance gene erm (48) and could be transformed into S. aureus by electroporation. Functionality of erm (48) was demonstrated by cloning and expression in S. aureus.



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A tick antivirulence protein potentiates antibiotics against Staphylococcus aureus [PublishAheadOfPrint]

New strategies are needed to combat antibiotic resistance, especially against pathogens such as methicillin-resistant Staphylococcus aureus. A tick antifreeze glycoprotein, IAFGP, possess potent anti-biofilm properties against a variety of clinical pathogens including S. aureus. Synergy between IAFGP, or a peptide (P1) representative of a repeat region of the protein, with different antibiotics was assessed in vitro. Antibiotics that synergized with either IAFPG or P1 were further evaluated in vivo using vertebrate and invertebrate infection models. IAFGP readily enhanced the efficacy of antibiotics against S. aureus. Synergy with daptomycin - an antibiotic used to treat methicillin-resistant S. aureus - was observed in vitro and in vivo using iafgp-transgenic mice and flies. Furthermore, synergy with ciprofloxacin or gentamicin, antibiotics not generally used to treat S. aureus, was also perceived. The combined effect of the antibiotic and IAFGP was associated with improved permeation of the antibiotic into the cell. Our results highlight that synergy of IAFGP with antibiotics traditionally used to treat this pathogen, and enhancement of the potency of antibiotics not commonly used against this microbe, can provide novel alternative therapeutic strategies to combat bacterial infections.



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Presence of VIM positive Pseudomonas species in chickens and their surrounding environment [PublishAheadOfPrint]

Metallo-β-lactamase gene blaVIM was identified on the chromosome of four Pseudomonas spp. isolates from a chicken farm, including one P. aeruginosa from swallow (Yanornis martini), one P. putida from fly, and two P. putida from chickens. The four isolates shared two variants of blaVIM-carrying genomic contexts, which resemble the corresponding regions of clinical MBL-producing Pseudomonas species. Our study suggests the surveillance of carbapenemase-producing bacteria in livestock and their surrounding environment is urgently needed.



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Candida guilliermondii complex is characterized by high antifungal resistance but low mortality: a report on 22 cases of candidemia [PublishAheadOfPrint]

Objectives: The objectives of our study were to describe the characteristics of patients infected with C. guilliermondii candidemia and to perform an in-depth microbiological characterization of isolates and compare them with those of patients with C. albicans candidemia.

Methods: We described the risk factors and outcome of 22 patients with candidemia caused by C. guilliermondii complex. Incident isolates were identified using molecular techniques, and susceptibility to fluconazole, anidulafungin and micafungin was studied. Biofilm formation was measured using the crystal violet assay (biomass production) and the XTT reduction assay (metabolic activity), and virulence was studied using the Galleria mellonella model. Biofilm formation was compared with that observed for C. albicans.

Results: The main conditions predisposing to infection were malignancy (68%), immunosuppressive therapy (59%), and neutropenia (18%). Clinical presentation of candidemia was less severe in patients infected by C. guilliermondii complex than in patients infected by C. albicans, and 30-day mortality was lower in C. guilliermondii patients (13.6% vs 33.9%, P=0.049). Isolates were identified as C. guilliermondii sensu stricto (n=17) and Candida fermentati (n=5). The isolates produced biofilms with low metabolic activity and moderate biomass. The G. mellonella model showed that C. guilliermondii was less virulent than C. albicans (mean of 6 vs 1 days of survival, respectively; P<0.001).

Conclusions: Patients with candidemia caused by C. guilliermondii complex had severe and debilitating underlying conditions. Overall, the isolates showed diminished susceptibility to fluconazole and echinocandins, although poor biofilm formation and the low virulence were associated with favorable outcome.



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Psoriasis Symposium



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Plenary Session 3



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What's New in Journals



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Plenary Session 2



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Genital Dermatology



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Contact Dermatitis



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Global Dermatology Symposium



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Non-Melanoma Skin Cancer Symposium



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Free Papers



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Medical Dermatology Update



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Posters



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Registrars’ Forum



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Acne



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Plenary Session 4



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Surgery Update for General Dermatologists Session 2



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Art of Dermatology and Other Surprises



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Registrars and Fellows Update Session 3



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Registrars and Fellows Update Session 2



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Surgery Update for General Dermatologists Session 1



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Dermatology Hospitalists



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Prediabetes Exhibits Decreased Disposition Index Correlated with Deterioration of Glycemic Parameters in Nonobese Japanese Subjects: A Cross-Sectional Study from Medical Examination

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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Identification of mycobacterial genes involved in antibiotic sensitivity - Implications in the treatment of tuberculosis with {beta}-lactam containing regimens [PublishAheadOfPrint]

In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA, dprE2, rpsT and parA, displayed hypersusceptibility to antibiotics including the β-lactams meropenem, ampicillin, amoxicillin and cefotaxime. Sub MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the parA insertion and enhanced the bactericidal activity of meropenem against Mycobacterium tuberculosis in combination with clavulanate. Our study identifies novel factors associated with antibiotic resistance, with implications in repurposing β-lactams for tuberculosis treatment.



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Evaluation of the Ability of a Novel Miconazole Formulation to Penetrate Nail Using Three Nail In Vitro Models [PublishAheadOfPrint]

In an effort to increase the efficacy of topical medications to treat onychomycosis, several new nail penetration enhancers have recently been developed. In this study, the ability of 10% w/w miconazole nitrate, combined with a penetration enhancer formulation to permeate the nail, is demonstrated by the use of a selection of in vitro nail penetration assays. These assays include bovine hoof, TurChub® zone of inhibition, and infected nail models.



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Molecular profile of malaria drug resistance markers of Plasmodium falciparum in Suriname [PublishAheadOfPrint]

In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum. We genotyped the PfK13 propeller domain of P. falciparum in forty samples as well as other mutations proposed to be associated with artemisinin resistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia but we found fixed resistance mutations for chloroquine and sulfadoxine-pyrimethamine. Additionally, the Pfcrt C350R mutation, associated with reversal of CQ resistance and piperaquine selective pressure was present in 62% of the samples. Our results from neutral microsatellite data also confirmed a high parasite gene flow in the Guiana Shield. Although recruiting participants for therapeutic efficacy studies in very low malaria endemic areas is challenging due to the low number of malaria cases reported, conducting these studies along with molecular surveillance remains essential to monitor artemisinin resistant alleles and to characterize the population structure P. falciparum in areas targeting malaria elimination.



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Analysis of the effects on the QT interval of a gatifloxacin-containing regimen versus standard treatment of pulmonary tuberculosis [PublishAheadOfPrint]

Background: The effects on ventricular repolarisation — recorded on the ECG as lengthening of the QT interval — of acute tuberculosis and those of standard and alternative anti-tuberculosis regimens are under-documented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero.

Methods: ECGs were performed pre- and 1-5 hours post-dosing (month 1, 2, end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampicin and isoniazid for 6 months, pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampicin and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady-state (month 1) in a subset of patients. We compared treatment effects on the QTc and modelled the effect of individual drugs' Cmax on the Fredericia-corrected QT interval.

Results: 1686 patients were eligible for the correction-factor analysis of QT at baseline (mean age 30.7 years, 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature from 37.2 to 36.5 C. Pre-treatment, the non-linear model estimated the best correction factor at 0.4081 in-between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor.

1602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480ms for 21 patients (7 and 14 in the test and control arm) and >500ms for 9 (5 and 4, respectively), corresponding to a risk difference of -0.9% (95% CI: -2.0% to 2.3%, p=0.12) and 0.1% (95% CI: -0.6% to 0.9%, p=0.75), respectively between the test and control arms. 106 (6.6%) patients had a peak measurement change from baseline >60ms (adjusted between-arm difference 0.8%, 95% CI -1.4% to 3.1%, p=0.47). No evidence was found of an association between Cmax of the anti-tuberculosis drugs 1 month into treatment and the length QTcF.

Conclusions: Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appear to carry a sizeable risk of QT prolongation in patients with newly-diagnosed pulmonary tuberculosis. This is to-date the largest dataset studying the effects of anti-tuberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen.



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Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media [PublishAheadOfPrint]

Amoxicillin/clavulanate (A/C), is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but standard dosage of 90/6.4 mg/kg/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea, while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and achieve clinical success. We conducted an open-label study in children aged 6 to 23 months with AOM. In Phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90/3.2 mg/kg/day for 10 days. In Phase 2, we treated 72 children with the same formulation at a dosage of 80/2.85 mg/kg/day for 10 days. We compared these children's rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical response with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in Phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving Phase 2 and standard regimens were 17% and 26%, respectively (P=0.10). Corresponding rates of diaper dermatitis were 22% and 34% (P=0.04), and of AOM treatment failure were 12% and 16% (P=0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit β-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side-effects without reducing clinical efficacy.



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A pseudotumour of the thigh: tensor fasciae latae muscle hypertrophy due to an underlying abductor tendon tear

We present a patient with an asymptomatic unilateral swelling of the anterolateral thigh. MRI showed hypertrophy of the tensor fasciae latae muscle due to an underlying gluteus minimus tendon tear.

Abductor tendon tears can present with swelling of the thigh due to secondary tensor fasciae latae muscle hypertrophy.



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Major Immunodominant Region of Hepatitis B Virus Core Antigen as a Delivery Vector to Improve the Immunogenicity of the Fusion Antigen ROP2-SAG1 Multiepitope from Toxoplasma gondii in Mice

Viral Immunology , Vol. 0, No. 0.


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Modes of Action for Mucosal Vaccine Adjuvants

Viral Immunology , Vol. 0, No. 0.


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Exostosin 1 is expressed in human odontoblasts

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Publication date: August 2017
Source:Archives of Oral Biology, Volume 80
Author(s): Virve Pääkkönen, Stina Saraniemi, Françoise Bleicher, Zvi Nevo, Leo Tjäderhane
ObjectiveDental pulp is soft connective tissue maintaining the vitality of the tooth, while odontoblasts form the dentin. Our earlier DNA microarray analysis revealed expression of putative tumour suppressor exostosin 1 (EXT-1) in odontoblasts. EXT-1 is essential for heparan sulphate synthesis, which may play a role in the dentin mineralization. Since the absence of the functional EXT-1 causes bone tumours, expression in odontoblasts is interesting. Our aim was to analyse further the EXT-1 expression in human tooth.DesignsDNA microarray and PCR techniques were used to study the EXT-1 expression in mature native human odontoblasts and pulp tissue as well as in newly-differentiated cultured odontoblast-like cells. Immunohistochemistry was performed to study EXT-1 protein in mature human teeth, teeth with incomplete root and developing teeth.ResultsMarkedly higher EXT-1 was observed in mature odontoblasts than in pulp at mRNA level with DNA microarray and PCR techniques. Immunohistochemistry of mature tooth revealed EXT-1 both in odontoblasts and the predentin but not in the dentin. EXT-1 was also observed in the odontoblasts of incomplete root, but the localization of the staining was different. In developing foetal tooth, staining was detected in ameloblasts and the basal lamina.ConclusionsThe detection of EXT-1 in both mature and newly-differentiated cells indicates a role in the odontoblast function, and EXT-1 staining in the predentin indicates a function in the dentin formation. Detection of EXT-1 in developing teeth indicates a role in tooth development.



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Alternative sweeteners influence the biomass of oral biofilm

Publication date: August 2017
Source:Archives of Oral Biology, Volume 80
Author(s): Fathilah Abdul Razak, Baizatul Amirah Baharuddin, Elisya Farha Mohd. Akbar, Amira Hanim Norizan, Nur Fazilah Ibrahim, Md. Yusoff Musa
ObjectiveCompact-structured oral biofilm accumulates acids that upon prolonged exposure to tooth surface, causes demineralisation of enamel. This study aimed to assess the effect of alternative sweeteners Equal Stevia®, Tropicana Slim®, Pal Sweet® and xylitol on the matrix-forming activity of plaque biofilm at both the early and established stages of formation.MethodsSaliva-coated glass beads (sGB) were used as substratum for the adhesion of a mixed-bacterial suspension of Streptococcus mutans, Streptococcus sanguinis and Streptococcus mitis. Biofilms formed on sGB at 3h and 24h represented the early and established-plaque models. The biofilms were exposed to three doses of the sweeteners (10%), introduced at three intervals to simulate the exposure of dental plaque to sugar during three consecutive food intakes. The treated sGB were (i) examined under the SEM and (ii) collected for turbidity reading. The absorbance indicated the amount of plaque mass produced. Analysis was performed comparative to sucrose as control.ResultsHigher rate of bacterial adherence was determined during the early compared to established phases of formation. Comparative to the sweeteners, sucrose showed a 40% increase in bacterial adherence and produced 70% more plaque-mass. Bacterial counts and SEM micrographs exhibited absence of matrix in all the sweetener-treated biofilms at the early phase of formation. At the established phase, presence of matrix was detected but at significantly lower degree compared to sucrose (p<0.05).ConclusionAlternatives sweeteners promoted the formation of oral biofilm with lighter mass and lower bacterial adherence. Hence, suggesting alternative sweeteners as potential antiplaque agents.



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Heterogeneous Prognoses for pT3 Papillary Thyroid Carcinomas and Impact of Delayed Risk Stratification

Thyroid , Vol. 0, No. 0.


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Comparison of the efficacy between conventional moxibustion and smoke-free moxibustion on knee osteoarthritis: study protocol of a randomized controlled trial

Conventional moxibustion is a representative non-drug intervention in traditional Chinese medicine, and it has been reported to produce encouraging results and benefits in relieving symptoms and improving the ...

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Forced fluid removal versus usual care in intensive care patients with high-risk acute kidney injury and severe fluid overload (FFAKI): study protocol for a randomised controlled pilot trial

Intravenous administration of fluids is an essential part of critical care. While some fluid administration is likely beneficial, there is increasing observational evidence that the development of fluid overlo...

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Adjacent regenerative peripheral nerve interfaces produce phase-antagonist signals during voluntary walking in rats

Regenerative Peripheral Nerve Interfaces (RPNIs) are neurotized muscle grafts intended to produce electromyographic signals suitable for motorized prosthesis control. Two RPNIs producing independent agonist/an...

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Relationships between potentially traumatic events, sleep disturbances, and symptoms of PTSD and alcohol use disorder in a young adult sample

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Publication date: June 2017
Source:Sleep Medicine, Volume 34
Author(s): Mackenzie J. Lind, Allison Baylor, Cassie M. Overstreet, Sage E. Hawn, Bruce D. Rybarczyk, Kenneth S. Kendler, Danielle M. Dick, Ananda B. Amstadter
ObjectiveTraumatic events, particularly those that are interpersonal in nature, are associated with increased risk for co-occurring sequelae, including sleep disturbances, posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD). However, the associations between these phenotypes have not been explored among college students.MethodsWe examined relationships between type of potentially traumatic event (PTE) exposure (pre-college) and sleep disturbances, as well as mediating effects of lifetime PTSD and AUD symptoms on these relationships, in a large undergraduate sample (N = 1599, 64.7% female). Hierarchical linear regressions were conducted, beginning with demographics and then adding interpersonal and accidental PTEs in a stepwise regression; mediation analyses were run.ResultsWithin the sample, 33.7% endorsed at least one interpersonal PTE, while 64.4% endorsed at least one accidental PTE. Hierarchical regressions demonstrated that interpersonal (β = 0.202, p = 0.000), but not accidental PTE exposure significantly predicted disturbed sleep. Both PTSD and AUD symptoms significantly mediated (p values < 0.001) the relationship between interpersonal PTE exposure and sleep, with indirect effects accounting for 61% and 17% of total effects, respectively. In the correlated mediation model, both disorders remained significant mediators (p < 0.001), with indirect effects accounting for 56% (PTSD symptoms) and 14% (AUD symptoms) of total effects on sleep.ConclusionsResults suggest that interpersonal PTEs are more potent predictors of sleep problems than accidental PTEs. Further, trauma exposure psychiatric symptom sequelae (PTSD, AUD) account for part of the relationship between interpersonal PTE exposure and disturbed sleep, which both independently and jointly suggests that treating PTSD and AUD symptoms in college students may also improve sleep.



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Editorial Board

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Publication date: May 2017
Source:Sleep Medicine, Volume 33





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What can we learn from eye movements distribution during sleep?

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Publication date: May 2017
Source:Sleep Medicine, Volume 33
Author(s): Fabio Pizza, Sudhansu Chokroverty




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The comparative study of resonance disorders for Vietnamese and Korean cleft palate speakers using nasometer

Abstract

Background

Nasalance is used to evaluate the velopharyngeal incompetence in clinical diagnoses using a nasometer. The aim of this study is to find the nasalance differences between Vietnamese cleft palate children and Korean cleft palate children by measuring the nasalance of five oral vowels.

Methods

Ten Vietnamese cleft palate children after surgery, three Vietnamese children for the control group, and ten Korean cleft palate children after surgery with the same age participated in this experimentation. Instead of Korean control, the standard value of Korean version of the simplified nasometric assessment procedures (kSNAP) was used.

Result

The results are as follows: (1) the highest nasalance score among the Vietnamese normal vowels is the low vowel /a/; however, that of Korean normal vowels is the high vowel /i/. (2) The average nasalance score of Korean cleft palate vowels is 18% higher than that of Vietnamese cleft palate vowels. There was a nasalance score of over 45% among the vowels /e/ and /i/ in Vietnamese cleft palate patients and /i/, /o/, and /u/ in Korean cleft palate patients.

Conclusion

These different nasalance scores of the same vowels seem to cause an ethnic difference between Vietnamese and Korean cleft palate children.



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CKS1BP7, a Pseudogene of CKS1B, is Co-Amplified with IGF1R in Breast Cancers

Abstract

Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes. Amplification of CKS1BP7 (dot-like pattern) was found in 28.8% of all cases, while amplified IGF1R (cluster pattern) was identified in 24.2% of all patients. The two events often co-existed (p = 0.01). Within the same tumors, identical CNAs of CKS1BP7 and IGF1R were found in DCIS and invasive carcinoma. Moreover, amplification of both genes was more frequent in aneuploidy tumors and the tumors with high ki67, but wasn't associated with patients' outcome. In summary, CKS1BP7 amplification is a frequent event in breast cancer and often co-occurs with amplified IGF1R, which provides evidence supporting the interactions between CKS1BP7 and IGF1R during mammary carcinogenesis. Our findings suggest that CKS1BP7 as well as IGF1R may serve as potential biomarkers for early detection and predict prognosis in breast cancer.



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Assessment and spontaneous healing outcomes of traumatic eardrum perforation with bleeding

This study investigated the influence of the degree of bleeding from the remnant eardrum on the spontaneous healing of human traumatic tympanic membrane perforations (TMPs).

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Assessment and spontaneous healing outcomes of traumatic eardrum perforation with bleeding

This study investigated the influence of the degree of bleeding from the remnant eardrum on the spontaneous healing of human traumatic tympanic membrane perforations (TMPs).

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The performing animal: causes and consequences of body remodelling and metabolic adjustments in red knots facing contrasting thermal environments

Using red knots (Calidris canutus) as a model, we determined how changes in mass and metabolic activity of organs relate to temperature-induced variation in metabolic performance. In cold-acclimated birds, we expected large muscles and heart, improved oxidative capacity and lipid transport, and we predicted that this would explain variation in maximal thermogenic capacity (Msum). We also expected larger digestive and excretory organs in these birds and predicted that this would explain variation in basal metabolic rate (BMR). Knots kept at 5°C were 20% heavier and maintained 1.5 times more body fat than individuals kept at thermoneutrality (25°C). Cold-acclimated birds also had a BMR up to 32% higher and a Msum 16% higher than birds at 25°C. Organs were larger in the cold, with muscles and heart being 9-20% heavier and digestive and excretory organs being 21-36% larger than at thermoneutrality. Rather than the predicted digestive and excretory organs, the cold-induced increase in BMR correlated with changes in mass of the heart, pectoralis and carcass. Msum varied positively with the mass of the pectoralis, supracoracoideus and heart, highlighting the importance of muscles and cardiac function in cold endurance. Cold-acclimated knots also expressed upregulated capacity for lipid transport across mitochondrial membranes in their pectoralis and leg muscles, higher lipid catabolism capacity in their pectoralis muscles and elevated oxidative capacity in their liver and kidney. These adjustments may have contributed to BMR through changes in metabolic intensity. Our results also suggest indirect constraints on thermogenic capacity through limited cardiac capacity.



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ETB Receptor Contribution to Vascular Dysfunction in Postmenopausal Women

Endothelin-1 (ET-1) contributes to age-related endothelial dysfunction in men via the ETA receptor. However, there are sex differences in the ET-1 system, and ETB receptors are modulated by sex hormones. The purpose of this study was to test the hypothesis that ETB receptors contribute to impaired vasodilatory function in postmenopausal women (PMW). We measured flow-mediated dilation (FMD) using ultrasound, and cutaneous nitric oxide-mediated vasodilation during local heating (42°C) via laser Doppler flowmetry in 18 young (YW; 22±1 years) and 16 PMW (56±1 years). Cutaneous microdialysis perfusions of lactated Ringer's (control), an ETB receptor antagonist (BQ-788, 300nM), and an ETA receptor antagonist (BQ-123, 500 nM), were done through separate fibers, followed by perfusions of sodium nitroprusside (28mM) and local heating to 43°C (max). Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flow/MAP, and expressed as a percent of maximal dilation. FMD (YW: 7.5±0.5 vs. PMW: 5.6±0.6 %) and cutaneous vasodilation (YW: 93±2 vs. PMW: 83±4 CVC % max) were lower in PMW (both P<0.05). Blockade of ETB receptors decreased cutaneous vasodilation in YW (87±2 CVC % max; P<0.05 vs. control), but increased vasodilation in PMW (93±1 CVC % max; P<0.05 vs. control). ETA receptor blockade had minimal effect in YW (92±1 CVC % max), but increased cutaneous vasodilation in PMW (91±2 CVC % max; P<0.05 vs. control). In conclusion, ETB receptors mediate vasodilation in YW, but this effect is lost after menopause. Impaired vasodilatory function in PMW is due in part to a loss of ETB mediated dilation.



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Use of the hyperinsulinemic euglycemic clamp to assess insulin sensitivity in guinea pigs: dose response, partitioned glucose metabolism and species comparisons

The guinea pig is an alternate small animal model for the study of metabolism, including insulin sensitivity. However, only one study to date has reported the use of the hyperinsulinemic-euglycemic clamp (HEC) in anaesthetized animals in this species, and the dose-response has not been reported. We therefore characterized the dose-response curve for whole-body glucose uptake using recombinant human insulin in the adult guinea pig. Inter-species comparisons with published data showed species differences in maximal whole body responses (guinea pig human < rat < mouse), and the insulin concentrations at which half-maximal insulin responses occurred (guinea pig > human rat > mouse). In subsequent studies, we used concomitant D-[3-3H]-glucose infusion to characterize insulin sensitivities of whole body glucose uptake, utilization, production, storage and glycolysis in young adult guinea pigs at human insulin doses that produced ~half (7.5 mU.min-1.kg-1) and near-maximal whole body responses (30 mU.min-1.kg-1). Although human insulin infusion increased rates of glucose utilization (up to 68%) and storage, and at high concentrations increased rates of glycolysis in females, glucose production was only partially suppressed (~23%), even at high insulin doses. Fasting glucose, metabolic clearance of insulin and rates of glucose utilization, storage and production during insulin stimulation were higher in female than male guinea pigs (P<0.05), but insulin sensitivity of these and whole body glucose uptake did not differ between sexes. This study establishes a method for measuring partitioned glucose metabolism in chronically catheterized conscious guinea pigs, allowing studies of regulation of insulin sensitivity in this species.



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Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n=15), gestational hypertension (GH) (n=14), and normotensive controls (NC) (n=44). Urinary markers of tubular injury, alpha-1 microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups, as an A1M/creatinine ratio >13 (66.7%, 8.3%, and 35%, respectively; p=0.01). Concentrations of C5b-9 were higher in the PE group than in GH and NC groups (medians 9.85 ng/mg, 0.05 ng/mg, and 0.28 ng/mg, respectively; p=0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7 and TIMP-2).



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Improved skeletal muscle Ca2+ regulation in vivo following contractions in mice overexpressing PGC-1{alpha}

In skeletal muscle, resting intracellular Ca2+ concentration ([Ca2+]i) homeostasis is exquisitely regulated by Ca2+ transport across the sarcolemmal, mitochondrial and sarcoplasmic reticulum (SR) membranes. Of these three systems, the relative importance of the mitochondria in [Ca2+]i regulation remains poorly understood in in vivo skeletal muscle. We tested the hypothesis that the capacity for Ca2+ uptake by mitochondria is a primary factor in determining [Ca2+]i regulation in muscle at rest and following contractions. Tibialis anterior muscle of anesthetized PGC-1α overexpressing (PGC-1α OE, increased mitochondria model) and wild-type littermates (WT) mice were exteriorized in vivo and loaded with Fura-2 AM and Rhod-2 AM. Ca2+ buffering and mitochondrial [Ca2+] were evaluated at rest and during recovery from fatiguing tetanic contractions. In addition, the effects of pharmacological inhibition of SR (thapsigargin) and mitochondrial (FCCP) function were examined at rest. [Ca2+]i in WT remained elevated for the entire post-contraction recovery period but in PGC-1α OE [Ca2+]i returned to resting baseline. Thapsigargin immediately and substantially increased resting [Ca2+]i in WT whereas in PGC-1α OE this effect was delayed and markedly diminished. FCCP abolished this improvement of [Ca2+]i regulation in PGC-1α OE. Mitochondrial [Ca2+] accumulation was observed in PGC-1α OE following contractions and thapsigargin treatment. In the SR PGC-1α OE down-regulated SERCA1 (Ca2+ uptake) and PV (Ca2+ buffering) protein levels whilst mitochondrial Ca2+ uptake-related proteins (Mfn1, Mfn2 and MCU) were up-regulated. These data demonstrate a heretofore unappreciated role for skeletal muscle mitochondria in [Ca2+]i regulation in vivo following fatiguing tetanic contractions and at rest.



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Neurogenic Hypertension and the Secret of Respiration

In spite of recent advances on the knowledgement of the neural control of cardiovascular function, the cause of sympathetic overactivity in neurogenic hypertension remains unknown. Studies from our laboratory point out that rats submitted to chronic intermittent hypoxia (CIH), an experimental model of neurogenic hypertension, present changes in the central respiratory network that impact the pattern of sympathetic discharge and the levels of arterial pressure. In addition to the fine coordination of respiratory muscle contraction and relaxation, essential for O2 and CO2 pulmonary exchanges, neurons of the respiratory network are precisely connected to the neurons controlling the sympathetic activity in the brainstem. This respiratory-sympathetic neuronal interaction provides adjustments in the sympathetic outflow to the heart and vasculature during each respiratory phase, according to the metabolic demands. Herein we report that CIH-induced sympathetic overactivity and mild hypertension are associated with increased frequency discharge of ventral medullary pre-sympathetic neurons. We also describe that their increased frequency discharge is dependent on synaptic inputs, mostly from neurons of the brainstem respiratory network, rather than to changes in their intrinsic electrophysiological properties. In perspective, we are taking into consideration the possibility that changes in the central respiratory rhythm/pattern generator contribute to increased sympathetic outflow and the development of neurogenic hypertension. Our experimental evidence provides support to the hypothesis that changes in the coupling of respiratory and sympathetic networks might be one of the unrevealed secrets of neurogenic hypertension in rats.



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The effect of submandibular gland preservation during level 1B neck dissection on postoperative xerostomia

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Publication date: Available online 24 April 2017
Source:Auris Nasus Larynx
Author(s): Jeff D. Markey, William G. Morrel, Steven J. Wang, William R. Ryan
ObjectiveCompare the presence and degree of postoperative xerostomia following preservation or excision of the submandibular gland (SMG) during level IB neck dissection (ND) without adjuvant radiation.MethodsRetrospective review with patient questionnaire administered to patients with pT1-2N0 oral squamous cell carcinoma (SCC) who underwent resection and ND with SMG preservation or SMG excision without postoperative radiation from 2011 to 2015. We analyzed an additional control group that was age and gender-matched and had not undergone oral resection or SMG excision. We compared the scores reported by the three groups from three questionnaires: University of Michigan Xerostomia Quality of Life (XeQoL), Short Form-8 (SF-8), and a xerostomia severity scale (XSS). Dry mouth severity (DMS) was calculated based on XSS scores among those complaining of any xerostomia.ResultsEleven SMG preservation group, 14 SMG excision group and 15 control group patients completed the survey. Complication and recurrence rates were comparable among experimental groups. No differences were identified between the two experimental groups for the XeQoL, SF-8, and XSS questionnaires (p=0.96, 0.87, 0.7). Control patients reported less xerostomia on XeQoL (p=0.046) and XSS (p=0.01) compared to the experimental groups combined with no statistical difference in SF-8 scores (p=0.25). No patients in either group developed regional recurrence in level IB.ConclusionSMG preservation, though technically and oncologically sound, does not appear in this study to reduce xerostomia. Oral resection with ND may result in some degree of xerostomia perception.



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The effect of submandibular gland preservation during level 1B neck dissection on postoperative xerostomia

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Publication date: Available online 24 April 2017
Source:Auris Nasus Larynx
Author(s): Jeff D. Markey, William G. Morrel, Steven J. Wang, William R. Ryan
ObjectiveCompare the presence and degree of postoperative xerostomia following preservation or excision of the submandibular gland (SMG) during level IB neck dissection (ND) without adjuvant radiation.MethodsRetrospective review with patient questionnaire administered to patients with pT1-2N0 oral squamous cell carcinoma (SCC) who underwent resection and ND with SMG preservation or SMG excision without postoperative radiation from 2011 to 2015. We analyzed an additional control group that was age and gender-matched and had not undergone oral resection or SMG excision. We compared the scores reported by the three groups from three questionnaires: University of Michigan Xerostomia Quality of Life (XeQoL), Short Form-8 (SF-8), and a xerostomia severity scale (XSS). Dry mouth severity (DMS) was calculated based on XSS scores among those complaining of any xerostomia.ResultsEleven SMG preservation group, 14 SMG excision group and 15 control group patients completed the survey. Complication and recurrence rates were comparable among experimental groups. No differences were identified between the two experimental groups for the XeQoL, SF-8, and XSS questionnaires (p=0.96, 0.87, 0.7). Control patients reported less xerostomia on XeQoL (p=0.046) and XSS (p=0.01) compared to the experimental groups combined with no statistical difference in SF-8 scores (p=0.25). No patients in either group developed regional recurrence in level IB.ConclusionSMG preservation, though technically and oncologically sound, does not appear in this study to reduce xerostomia. Oral resection with ND may result in some degree of xerostomia perception.



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Einseitige supraklavikuläre Schwellung in der Schwangerschaft

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-105795


[...]

© Georg Thieme Verlag KG Stuttgart · New York

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



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What chickens might tell us about the MHC class II system

Aimée Parker | Jim Kaufman

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The effect of submandibular gland preservation during level 1B neck dissection on postoperative xerostomia

Compare the presence and degree of postoperative xerostomia following preservation or excision of the submandibular gland (SMG) during level IB neck dissection (ND) without adjuvant radiation.

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The effect of submandibular gland preservation during level 1B neck dissection on postoperative xerostomia

Compare the presence and degree of postoperative xerostomia following preservation or excision of the submandibular gland (SMG) during level IB neck dissection (ND) without adjuvant radiation.

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Assessment and spontaneous healing outcomes of traumatic eardrum perforation with bleeding

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Publication date: Available online 24 April 2017
Source:American Journal of Otolaryngology
Author(s): Zhong-hai Jin, Zi-Han Lou, Zheng-Cai Lou
ObjectiveThis study investigated the influence of the degree of bleeding from the remnant eardrum on the spontaneous healing of human traumatic tympanic membrane perforations (TMPs).Study designA case series with chart review.SettingA tertiary university hospital.Materials and methodsThe clinical records of traumatic TMP patients who met the case selection criteria were retrieved and categorized into two groups based on the documented degree of bleeding from the remnant eardrum: with and without bleeding. The demographic data and spontaneous healing outcomes (i.e., healing rate and duration) of these two TMP types were analyzed using the chi-squared test or t-test.ResultsOne-hundred and eighty-eight cases met the inclusion criteria and were analyzed. Of these, 58.5% had perforations without bleeding and the remaining 41.5% had perforations with bleeding. The overall closure rate at the end of the 3-month follow-up period was 90.9% for perforations without bleeding and 96.2% for perforations with bleeding; the difference was not statistically significant (P>0.05). However, the average closure time differed significantly between the two groups (P<0.05): 29.4±3.7days for perforations without bleeding and 20.6±9.2days for perforations with bleeding. The closure rate was significantly different between the groups (62 vs. 15.6%, P<0.01) within 2weeks for medium-sized perforations. In total, 11 (39.3%) large-sized perforations achieved complete closure in the group with bleeding, while none of the large-sized perforations closed in the group without bleeding within 2weeks. The closure rate of medium-sized perforations was not significantly different (79.2 vs. 92%, P>0.05) between the groups without and with bleeding within 4weeks, while the closure rate of large-sized perforations was significantly different between the groups without and with bleeding (27.2 vs. 75%, P=0.0).ConclusionThis study shows that traumatic TMPs with bleeding significantly shortened the closure time compared to TMPs without bleeding. This finding indicates a significant correlation between the prognosis of traumatic TMPs and the degree of eardrum bleeding: severe bleeding from and a hematoma in the remnant eardrum appear to be good signs.



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Automated Quantitative Enzyme Biosensing in 24-Well Microplates

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.6b04694
ancham?d=yIl2AUoC8zA


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In Situ Underwater Laser-Induced Breakdown Spectroscopy Analysis for Trace Cr(VI) in Aqueous Solution Supported by Electrosorption Enrichment and a Gas-Assisted Localized Liquid Discharge Apparatus

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Analytical Chemistry
DOI: 10.1021/acs.analchem.7b00629
ancham?d=yIl2AUoC8zA


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Influences of Normalization Method on Biomarker Discovery in Gas Chromatography–Mass Spectrometry-Based Untargeted Metabolomics: What Should Be Considered?

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Analytical Chemistry
DOI: 10.1021/acs.analchem.6b05152
ancham?d=yIl2AUoC8zA


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Assessment and spontaneous healing outcomes of traumatic eardrum perforation with bleeding

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Publication date: Available online 24 April 2017
Source:American Journal of Otolaryngology
Author(s): Zhong-hai Jin, Zi-Han Lou, Zheng-Cai Lou
ObjectiveThis study investigated the influence of the degree of bleeding from the remnant eardrum on the spontaneous healing of human traumatic tympanic membrane perforations (TMPs).Study designA case series with chart review.SettingA tertiary university hospital.Materials and methodsThe clinical records of traumatic TMP patients who met the case selection criteria were retrieved and categorized into two groups based on the documented degree of bleeding from the remnant eardrum: with and without bleeding. The demographic data and spontaneous healing outcomes (i.e., healing rate and duration) of these two TMP types were analyzed using the chi-squared test or t-test.ResultsOne-hundred and eighty-eight cases met the inclusion criteria and were analyzed. Of these, 58.5% had perforations without bleeding and the remaining 41.5% had perforations with bleeding. The overall closure rate at the end of the 3-month follow-up period was 90.9% for perforations without bleeding and 96.2% for perforations with bleeding; the difference was not statistically significant (P>0.05). However, the average closure time differed significantly between the two groups (P<0.05): 29.4±3.7days for perforations without bleeding and 20.6±9.2days for perforations with bleeding. The closure rate was significantly different between the groups (62 vs. 15.6%, P<0.01) within 2weeks for medium-sized perforations. In total, 11 (39.3%) large-sized perforations achieved complete closure in the group with bleeding, while none of the large-sized perforations closed in the group without bleeding within 2weeks. The closure rate of medium-sized perforations was not significantly different (79.2 vs. 92%, P>0.05) between the groups without and with bleeding within 4weeks, while the closure rate of large-sized perforations was significantly different between the groups without and with bleeding (27.2 vs. 75%, P=0.0).ConclusionThis study shows that traumatic TMPs with bleeding significantly shortened the closure time compared to TMPs without bleeding. This finding indicates a significant correlation between the prognosis of traumatic TMPs and the degree of eardrum bleeding: severe bleeding from and a hematoma in the remnant eardrum appear to be good signs.



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Neurological outcomes of antidiabetic therapy: What the neurologist should know

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Publication date: Available online 24 April 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Olaf Eberhardt Md, Helge Topka Md
Considering the causative or contributory effects of diabetes mellitus on common neurological diseases such as polyneuropathy, stroke and dementia, modern antidiabetic drugs may be expected to reduce incidence or progression of these conditions. Nevertheless, most observed benefits have been small, except in the context of therapy for diabetes mellitus type I and new-onset polyneuropathy. Recently, semaglutide, a GLP-1 analogue, has been shown to significantly reduce stroke incidence in a randomized controlled trial. Beneficial effects of antidiabetic drugs on stroke severity or outcome have been controversial, though. The level of risk conferred by diabetes mellitus, the complex pathophysiology of neurological diseases, issues of trial design, side-effects of antidiabetic drugs as well as co-medication might be interacting factors that determine the performance of antidiabetic therapy with respect to neurological outcomes. It might be speculated that early treatment of prediabetes might prevent cerebral arteriosclerosis, cognitive decline or polyneuropathy more effectively, but this remains to be demonstrated.



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Anti-depressant and anxiolytic potential of Acacia hydaspica R. Parker aerial parts extract: Modulation of brain antioxidant enzyme status

Oxidative stress may link to psychiatric disorders, and is being regarded as a plausible mechanism that can affect the regulation of these illnesses. The present study was undertaken to investigate the antidep...

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Improved pressure contour analysis for estimating cardiac stroke volume using pulse wave velocity measurement

Pressure contour analysis is commonly used to estimate cardiac performance for patients suffering from cardiovascular dysfunction in the intensive care unit. However, the existing techniques for continuous est...

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Dependency criterion based brain pathological age estimation of Alzheimer’s disease patients with MR scans

Traditional brain age estimation methods are based on the idea that uses the real age as the training label. However, these methods ignore that there is a deviation between the real age and the brain age due t...

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Primary follicular dendritic cell sarcoma of the urinary bladder: the first case report and potential diagnostic pitfalls

Extranodal follicular dendritic cell sarcoma (FDCS) is a very rare malignancy with a variable clinical course. It is often not considered and has the potential to result in a misdiagnosis of other common sarco...

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The safety and efficacy of percutaneous intraductal radiofrequency ablation in unresectable malignant biliary obstruction: A single-institution experience

Abstract

Background

Patients with unresectable malignant biliary obstruction have limited life expectancy because of limited stent patency and tumor progression. The aim of our study was to retrospectively evaluate the safety and efficacy of combining intraductal RFA with biliary metal stent placement for patients with malignant biliary obstruction.

Methods

Patients who received percutaneous intraductal RFA and biliary stent placement for malignant biliary obstruction between 2013 and 2015 were identified. Outcomes were stent patency, technique and clinical success rate, overall survival (OS) and complication rates. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with stent patency and OS. Complications and laboratory abnormalities were recorded.

Results

Fifty patients were treated with percutaneous RFA and stent placement. The rates of technical success and clinical success were 98% and 92%, respectively. The median stent patency was 7.0 (95% confidence interval [CI]: 5.3, 8.7) months and OS was 5.0 (95% CI: 4.0, 6.0) months. On univariable analysis, previously cholangitis was an independent poor prognosis factor for recurrent biliary obstruction. OS was improved in patients who received more than one intervention compared to those who received only one intervention (log-rank P = 0.007), and in those treated without versus those treated with sequential chemotherapy (log-rank P = 0.017). On multivariable analysis, the occurrence of more than one intervention (P = 0.019) had independent prognostic significance for OS.

Conclusion

Percutaneous RFA and stent placement is a technically safe and feasible therapeutic option for the palliative treatment of malignant biliary obstruction. The long-term efficacy and safety of the procedure is promising, but further study is required via randomized and prospective trials.



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The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds

Abstract

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses.



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Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome

Mastocytosis are rare diseases characterized by an accumulation of clonal mast cells (MCs) in one or multiple organs or tissues. Patients with systemic mastocytosis (SM), whose MCs frequently arbor the activat...

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Therapeutic efficacy of α-radioimmunotherapy with different activity levels of the 213 Bi-labeled monoclonal antibody MX35 in an ovarian cancer model

Abstract

Background

The aim of this study was to compare the therapeutic efficacy of two different activity levels of the 213Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of 213Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy. Body weight and white blood cell counts were monitored after treatment for possible signs of toxicity.

Results

The tumor-free fraction of the animals treated with 3 MBq/mL of 213Bi-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of 213Bi-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor-free fraction of 0.15. No significant reduction in white blood cell counts or weight loss was observed.

Conclusions

Tumor growth after i.p. treatment with 213Bi-MX35 was significantly reduced compared to treatment with unlabeled MX35. Treatment with 9 MBq/mL of 213Bi-MX35 resulted in higher tumor-free fraction compared with 3 MBq/mL of 213Bi-MX35, but this difference was not statistically significant. No signs of toxicity were observed in the treated animals.



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Effective dose estimation for oncological and neurological PET/CT procedures

Abstract

Background

The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds.

PET/CT studies of 210 patients were reviewed including Torso (n = 123), Whole body (WB) (n = 36), Head and Neck Tumor (HNT) (n = 10), and Brain (n = 41) protocols with 18FDG (n = 170), 11C-CHOL (n = 10), 18FDOPA (n = 10), 11C-MET (n = 10), and 18F-florbetapir (n = 10). ED was calculated using conversion factors applied to the radiotracer activity and to the CT dose-length product.

Results

Total ED (mean ± SD) for Torso-11C-CHOL, Torso-18FDG, WB-18FDG, and HNT-18FDG protocols were 13.5 ± 2.2, 16.5 ± 4.5, 20.0 ± 5.6, and 15.4 ± 2.8 mSv, respectively, where CT represented 77, 62, 69, and 63% of the protocol ED, respectively. For 18FDG, 18FDOPA, 11C-MET, and 18F-florbetapir brain PET/CT studies, ED values (mean ± SD) were 6.4 ± 0.6, 4.6 ± 0.4, 5.2 ± 0.5, and 9.1 ± 0.4 mSv, respectively, and the corresponding CT contributions were 11, 14, 23, and 26%, respectively. In 18FDG PET/CT, variations in scan length and arm position produced significant differences in CT ED (p < 0.01). For dual-time-point imaging, the CT ED (mean ± SD) for the delayed scan was 3.8 ± 1.5 mSv.

Conclusions

The mean ED for body and brain PET/CT protocols with different radiopharmaceuticals ranged between 4.6 and 20.0 mSv. The major contributor to total ED for body protocols is CT, whereas for brain studies, it is the PET radiopharmaceutical.



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The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds

Abstract

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses.



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What is a Fetal Heart Echo?

 

See what's behind that heartbeat you love hearing at every appointment! Abby is joined by Dr. Lee and Dr. Warner to discuss the Fetal Care Center, the Fetal Heart Center and fetal echocardiograms.

The post What is a Fetal Heart Echo? appeared first on ChildrensMD.



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Proteomic profiling of human intraschisis cavity fluid

Abstract

Background

X-linked retinoschisis (XLRS) is a vitreoretinal degenerative disorder causing vision deterioration, due to structural defects in retina. The hallmark of this disease includes radial streaks arising from the fovea and splitting of inner retinal layers (schisis). Although these retinal changes are attributed to mutations in the retinoschisin gene, schisis is also observed in patients who do not carry mutations. In addition, the origin of intraschisis fluid, the triggering point of schisis formation and its progression are largely unknown still. So far, there is no report on the complete proteomic analysis of this fluid. Schisis fluid proteome could reflect biochemical changes in the disease condition, helping in better understanding and management of retinoschisis. Therefore it was of interest to investigate the intraschisis fluid proteome using high-resolution mass spectrometry.

Methods

Two male XLRS patients (aged 4 and 40 years) underwent clinical and genetic evaluation followed by surgical extraction of intraschisis fluids. The two fluid samples were resolved on a SDS-PAGE and the processed peptides were analyzed by Q-Exactive plus hybrid quadrupole-Orbitrap mass spectrometry. Functional annotation of the identified proteins was performed using Ingenuity pathway analysis software.

Results

Mass spectrometry analysis detected 770 nonredundant proteins in the intraschisis fluid. Retinol dehydrogenase 14 was found to be abundant in the schisis fluid. Gene ontology based analysis indicated that 19% of the intraschisis fluid proteins were localized to the extracellular matrix and 15% of the proteins were involved in signal transduction. Functional annotation identified three primary canonical pathways to be associated with the schisis fluid proteome viz., LXR/RXR activation, complement system and acute phase response signalling, which are involved in immune and inflammatory responses. Collectively, our results show that intraschisis fluid comprises specific inflammatory proteins which highly reflect the disease environment.

Conclusion

Based on our study, it is suggested that inflammation might play a key role in the pathogenesis of XLRS. To our knowledge, this is the first report describing the complete proteome of intraschisis fluid, which could serve as a template for future research and facilitate the development of therapeutic modalities for XLRS.



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An efficient and compact row buffer architecture on FPGA for real-time neighbourhood image processing

Abstract

This work presents a compact and efficient row buffer (RB) architecture on field-programmable gate array (FPGA). The design confines multiple RBs within the full capacity of Xilinx Block RAM (BRAM) in contrast to the conventional approach which partially utilizes a full BRAM per RB. The configuration of BRAM with different port aspect ratio and its data accessing via an efficient pattern generator circuitry allows the design to buffer pixelwise image data and retrieve multiple pixels per clock in a predefined pattern to achieve the functionality of multiple RBs. The design uses smallest BRAM18 primitive to be scaled in small steps for any larger kernel and image size for providing the best economical solution. The proposed architecture retains the bandwidth requirement to 1 pixel/clock at an ideal efficiency of 1 clock/pixel along with the saving of up to 87.5% BRAMs as compared to the conventional RBs and at the same time sustains high frame rates ( \(1920\times 1080\)  @ 217 fps) to support real-time image processing. Therefore, it is feasible to replace conventional high-cost RBs with our proposed RBs on latest FPGA devices especially for high performance yet area constraint neighbourhood image processing applications.



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The Impact of Oral Promethazine on Human Whole-Body Motion Perceptual Thresholds

Abstract

Despite the widespread treatment of motion sickness symptoms using drugs and the involvement of the vestibular system in motion sickness, little is known about the effects of anti-motion sickness drugs on vestibular perception. In particular, the impact of oral promethazine, widely used for treating motion sickness, on vestibular perceptual thresholds has not previously been quantified. We examined whether promethazine (25 mg) alters vestibular perceptual thresholds in a counterbalanced, double-blind, within-subject study. Thresholds were determined using a direction recognition task (left vs. right) for whole-body yaw rotation, y-translation (interaural), and roll tilt passive, self-motions. Roll tilt thresholds were 31 % higher after ingestion of promethazine (P = 0.005). There were no statistically significant changes in yaw rotation and y-translation thresholds. This worsening of precision could have functional implications, e.g., during driving, bicycling, and piloting tasks. Differing results from some past studies of promethazine on the vestibulo-ocular reflex emphasize the need to study motion perception in addition to motor responses.



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What is a Fetal Heart Echo?

 

See what's behind that heartbeat you love hearing at every appointment! Abby is joined by Dr. Lee and Dr. Warner to discuss the Fetal Care Center, the Fetal Heart Center and fetal echocardiograms.

The post What is a Fetal Heart Echo? appeared first on ChildrensMD.



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Neurodevelopmental Reflex Testing in Neonatal Rat Pups

55261fig1.jpg

Behavioral testing is the gold standard for determining outcomes following brain injury, and can identify the presence of developmental disabilities in infants and children. Neurodevelopmental reflexes are an early indicator of these abnormalities. A host of easily accomplished developmental reflex tests in the neonatal rodent were developed and described here.

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Automatic construction of statistical shape models using deformable simplex meshes with vector field convolution energy

In the active shape model framework, principal component analysis (PCA) based statistical shape models (SSMs) are widely employed to incorporate high-level a priori shape knowledge of the structure to be segm...

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Mercy Named Top Five Health Care System in the U.S.

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Associations between persistent organic pollutants, type 2 diabetes, diabetic nephropathy and mortality

Objective

Relationships were examined between persistent organic pollutants (POPs) and incident type 2 diabetes, end-stage renal disease (ESRD) and mortality.

Methods

In a nested case–control study, 300 persons without diabetes had baseline examinations between 1969 and 1974; 149 developed diabetes (cases) and 151 remained non-diabetic (controls) during 8.0 and 23.1 years of follow-up, respectively. POPs were measured at baseline. ORs for diabetes were computed by logistic regression analysis. The cases were followed from diabetes onset to ESRD, death or 2013. HRs for ESRD and mortality were computed by cause-specific hazard models. Patterns of association were explored using principal components analysis.

Results

PCB151 increased the odds for incident diabetes, whereas hexachlorobenzene (HCB) was protective after adjusting for age, sex, body mass index, sample storage characteristics, glucose and lipid levels. Associations between incident diabetes and polychlorinatedbiphenyl (PCB) or persistent pesticide (PST) components were mostly positive but non-significant. Among the cases, 29 developed ESRD and 48 died without ESRD. PCB28, PCB49 and PCB44 increased the risk of ESRD after adjusting for baseline demographic and clinical characteristics. Several PCBs and PSTs increased the risk of death without ESRD. The principal components analysis identified PCBs with low-chlorine load positively associated with ESRD and death without ESRD, and several PSTs associated with death without ESRD.

Conclusions

Most POPs were positively but not significantly associated with incident diabetes. PCB151 was significantly predictive and HCB was significantly protective for diabetes. Among participants with diabetes, low-chlorine PCBs increase the risk of ESRD and death without ESRD, whereas several PSTs predict death without ESRD.



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Mortality from cancer and other causes among Italian chrysotile asbestos miners

Objective

To investigate the long-term mortality of a cohort of Italian asbestos miners.

Methods

The cohort included 1056 men employed in a chrysotile mine between 1930 and 1990, who were followed up during 1946–2014, for a total of 37 471 person-years of observation. Expected deaths and SMRs were computed using national and local (after 1980, when available) reference.

Results

A total of 294 (27.8%) subjects were alive and at the end of follow-up, 722 (68.4%) were dead and 40 (3.8%) were lost to follow-up. The SMR for overall mortality was 1.35 (95%CI 1.25 to 1.45). The SMR for pleural cancer, based on seven observed deaths, was 5.54 (95% CI 2.22 to 11.4) and related to time since first exposure, but not to duration of employment, cumulative exposure or time since last exposure. The SMR for lung cancer was 1.16 (95% CI 0.87 to 1.52; 53 observed deaths), with no excess among workers with cumulative exposure below 100 fibre/mL-years (SMR 0.82; 95% CI 0.44 to 1.40).

Conclusions

The update of the follow-up of this cohort confirmed an increased mortality from pleural cancer mortality in miners exposed to chrysotile and a lack of significant increase in lung cancer mortality.



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Six Johns Hopkins Doctors Elected to Association of American Physicians

Six Johns Hopkins physicians were elected to the Association of American Physicians at the annual meeting of the organization April 21-23 in Chicago.
 



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Six Johns Hopkins Doctors Elected to Association of American Physicians

Six Johns Hopkins physicians were elected to the Association of American Physicians at the annual meeting of the organization April 21-23 in Chicago.
 



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Human β-defensin-3 Induces IL-8 Release and Apoptosis in Airway Smooth Muscle Cells

Abstract

Background

Human airway smooth muscle cells (ASMCs) may have a pro-inflammatory role through the release of inflammatory mediators. Increasing evidence indicates that human β-defensins (HBDs) are related to pathogenesis of asthma.

Objectives

To examine the plasma level of HBD-1, -2 and -3 in asthmatic patients and the expression of their mouse orthologs in the lung tissue of a mouse model of chronic severe asthma. Further to investigate the effect of HBD-3 on the release of the pro-inflammatory cytokine IL-8 and to explore the mechanisms.

Methods

The plasma levels of HBD-1, -2 and -3 from 34 healthy controls and 25 asthmatic patients were determined by ELISA. The expression of mouse β-defensins MBD-1, -3 and -14 in the lung tissue of asthmatic mice was detected by Western blot. The ASMCs were cultured with HBD-3 for 24h, and then the supernatant level of IL-8 was evaluated by ELISA and the cell viability was examined by WST-1 assay. The signaling pathway was investigated with blocking antibodies or pharmacological inhibitors.

Results

The plasma levels of HBD-1 and -3 were elevated in asthmatic patients, and the expression of MBD-14, the mouse ortholog for HBD-3, was increased in asthmatic mice. HBD-3 induced IL-8 production in a CCR6 receptor-specific manner and was dependent on multiple signaling pathways. Moreover, HBD-3 induced cell apoptosis concurrently, which was dependent on the ERK1/2 MAPK pathway. Mitochondrial ROS regulated both HBD-3-induced IL-8 production and cell apoptosis.

Conclusions & Clinical Relevance

These observations provide clear evidence of an important new mechanism for the promotion of airway inflammation and tissue remodeling with potential relevance for the treatment of asthma.

This article is protected by copyright. All rights reserved.



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Human β-defensin-3 Induces IL-8 Release and Apoptosis in Airway Smooth Muscle Cells

Abstract

Background

Human airway smooth muscle cells (ASMCs) may have a pro-inflammatory role through the release of inflammatory mediators. Increasing evidence indicates that human β-defensins (HBDs) are related to pathogenesis of asthma.

Objectives

To examine the plasma level of HBD-1, -2 and -3 in asthmatic patients and the expression of their mouse orthologs in the lung tissue of a mouse model of chronic severe asthma. Further to investigate the effect of HBD-3 on the release of the pro-inflammatory cytokine IL-8 and to explore the mechanisms.

Methods

The plasma levels of HBD-1, -2 and -3 from 34 healthy controls and 25 asthmatic patients were determined by ELISA. The expression of mouse β-defensins MBD-1, -3 and -14 in the lung tissue of asthmatic mice was detected by Western blot. The ASMCs were cultured with HBD-3 for 24h, and then the supernatant level of IL-8 was evaluated by ELISA and the cell viability was examined by WST-1 assay. The signaling pathway was investigated with blocking antibodies or pharmacological inhibitors.

Results

The plasma levels of HBD-1 and -3 were elevated in asthmatic patients, and the expression of MBD-14, the mouse ortholog for HBD-3, was increased in asthmatic mice. HBD-3 induced IL-8 production in a CCR6 receptor-specific manner and was dependent on multiple signaling pathways. Moreover, HBD-3 induced cell apoptosis concurrently, which was dependent on the ERK1/2 MAPK pathway. Mitochondrial ROS regulated both HBD-3-induced IL-8 production and cell apoptosis.

Conclusions & Clinical Relevance

These observations provide clear evidence of an important new mechanism for the promotion of airway inflammation and tissue remodeling with potential relevance for the treatment of asthma.

This article is protected by copyright. All rights reserved.



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Adipose-derived stem cell (ASC)-enriched fat grafting: experiments using White rabbits and an automated cell processing apparatus

Abstract

The grafting of fat mixed with adipose-derived stem cells (ASCs) is being increasingly applied to compensate for the disadvantages of previous fat grafting methods. Devices that automatically isolate fat stem cells also have recently been developed. ASCs were isolated from the inguinal region of White rabbits using Icellator®, and the number of cells and their viability were measured. The cell count per fat graft (mL) was adjusted to the following concentrations and subcutaneously transplanted into the back: Control group, Fat + PBS; Fat + ASCs (×0.5) group, 1.6 × 105 cells/mL; and Fat + ASCs (×1) group, 3.2 × 105 cells/mL. Grafted fat weight was measured after 8 weeks, and histological, immunohistological, and specifically stained sections were prepared. Fat absorption was reduced in Fat + ASCs (×0.5) and Fat + ASCs (×1) groups. The number of blood vessels was higher in Fat + ASCs (×1) than in the control group, and blood vessel areas were higher in Fat + ASCs (×0.5) and Fat + ASCs (×1) groups than in the control group. The usefulness of the automated cell processing apparatus, Icellator®, was confirmed, and the results obtained suggest that grafted ASCs promote the vascularization and engraftment of fat grafts.



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Age-based disparities in the use of total thyroidectomy for papillary thyroid carcinoma

Abstract

Background

Elderly patients may be less likely than younger patients to receive indicated therapy. We hypothesized that older patients with papillary thyroid carcinoma (PTC) would be less likely to receive total thyroidectomy (TT) than their younger counterparts.

Materials and methods

The Surveillance, Epidemiology, and End Results database were queried for adult patients diagnosed with PTC from 2000 through 2009. Patients were categorized according to whether they received a TT or less than a total thyroidectomy (<TT). We used multivariate logistic regression to predict the use of <TT. The likelihood of undergoing <TT was reported as odds ratios (OR) with 95% confidence intervals (CI).

Results

Of the 67,961 patients identified with PTC, 51,276 (75%) received TT, 14,750 (22%) <TT and 1935 (3%) no surgery. On multivariate analysis, advancing age increased the likelihood of receiving <TT (age 45–54 OR 1.15, CI [1.09–1.20]; age 55–64 OR 1.20, CI [1.14–1.26]; age 65–74 OR 1.40, CI [1.32–1.49]; 75–84 OR 1.80, CI [1.65–1.95]; ≥85 OR 3.01, CI [2.51–3.62], all p < 0.001).

Conclusions

Older patients with PTC are less likely to receive TT. Further research is needed to assess if older patients are negatively impacted by less complete surgery.



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Relational responding: testing, training and sequencing effects among children with autism and typically-developing children



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Relational responding: testing, training and sequencing effects among children with autism and typically-developing children



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Visualizing Visual Adaptation

54038fig1.jpg

This article describes a novel method for simulating and studying adaptation in the visual system.

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EMT and Paramedic full time positions - A-1 Ambulance Inc.

EMT and Paramedics will be responsible for caring for and transporting both ALS and BLS patients along with out of town transfers. The EMT and Paramedic will work together with the medical director to provide top notch care that is in his/her scope of practice and adhere to the protocols already in place.

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Spatiotemporal reorganization of the reading network in adult dyslexia

S00109452.gif

Publication date: Available online 24 April 2017
Source:Cortex
Author(s): Eddy Cavalli, Pascale Colé, Chotiga Pattamadilok, Jean-Michel Badier, Christelle Zielinski, Valérie Chanoine, Johannes C. Ziegler
Developmental dyslexia is characterized by impairments in reading fluency and spelling that persist into adulthood. Here, we hypothesized that high-achieving adult dyslexics (i.e., university students with a history of dyslexia) manage to cope with these deficits by relying to a greater extent on morphological information than do non-impaired adult readers. We used magnetoencephalography (MEG) in a primed lexical decision task, in which we contrasted orthographic, morphological and semantic processing. Behavioral results confirmed that adult dyslexics did indeed rely to a greater extent on the semantic properties of morphemes than controls. In line with this, MEG results showed early morphological effects (100-200ms) in a frontal network, which reflected the contribution of semantic processing. The same effects occurred much later in controls (∼400ms). In contrast, controls showed early orthographic priming effects in posterior left inferior temporal gyrus at around 130ms, which were not seen in dyslexics. In the left inferior temporal gyrus, dyslexics showed only late activation of semantic and orthographic information. The present results suggest a spatiotemporal reorganization of the reading network, in which morphological information located in frontal regions is activated earlier in high-achieving adults dyslexics than controls.



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The Dynamic Invertible Intramolecular Charge-transfer Fluorescence Probe: Real-time Monitoring of Mitochondrial ATPase Activity

Chem. Commun., 2017, Accepted Manuscript
DOI: 10.1039/C7CC02450A, Communication
Hua Zhang, Yafu Wang, Xiaopeng Xuan, Ge Wang, Haiming Guo, Jiangli Fan
The dynamic invertible intramolecular charge-transfer (ICT) process could provide abundant response signals for the real-time monitoring in living organism. Herein, based on the dynamic invertible ICT, we reported a cancer...
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Psychiatric associations of adult-onset focal dystonia phenotypes

Background

Depression and anxiety frequently accompany the motor manifestations of isolated adult-onset focal dystonias. Whether the body region affected when this type of dystonia first presents is associated with the severity of these neuropsychiatric symptoms is unknown.

Objectives

The aim of this study was to determine whether depression, anxiety and social anxiety vary by dystonia onset site and evaluate whether pain and dystonia severity account for any differences.

Methods

Patients with isolated focal dystonia evaluated within 5 years from symptom onset, enrolled in the Natural History Project of the Dystonia Coalition, were included in the analysis. Individual onset sites were grouped into five body regions: cervical, laryngeal, limb, lower cranial and upper cranial. Neuropsychiatric symptoms were rated using the Beck Depression Inventory, Hospital Anxiety and Depression Scale and Liebowitz Social Anxiety Scale. Pain was estimated using the 36-Item Short Form Survey.

Results

Four hundred and seventy-eight subjects met our inclusion criteria. High levels of depression, anxiety and social anxiety occurred in all groups; however, the severity of anxiety and social anxiety symptoms varied by onset site group. The most pronounced differences were higher anxiety in cervical and laryngeal, lower anxiety in upper cranial and higher social anxiety in laryngeal. Increases in pain were associated with worse neuropsychiatric symptom scores within all groups. Higher anxiety and social anxiety in laryngeal and lower anxiety in upper cranial persisted after correcting for pain and dystonia severity.

Conclusion

Anxiety and social anxiety severity vary by onset site of focal dystonia, and this variation is not explained by differences in pain and dystonia severity.



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