Abnormal distance of the extralaryngeal bifurcation point of the recurrent laryngeal nerve from the cricothyroid joint

Abstract

The extralaryngeal bifurcation point of the recurrent laryngeal nerve (RLN) is typically located in a mean distance of 0–2 cm from the cricothyroid joint (CTJ). In the presented case though, the left RLN was unexpectedly identified bifurcating in a mean distance of 7 cm from the left CTJ in a young woman with multinodular goiter during total thyroidectomy. The RLN was carefully exposed throughout its course for the avoidance of iatrogenic injury of the nerval structure. The operation was uneventful. The present manuscript aims to highlight a scarce anatomic variation and its implications for thyroidectomy. Rare anatomic variations of the RLN such as the presented one encumber thyroid surgery and represent a severe risk factor of RLN injury. Meticulous operative technique combined with surgeons' perpetual awareness concerning this peculiar anatomical aberration leads to an injury-free thyroid surgery.

http://ift.tt/2DhrKN3

Intrabilary obstruction by colorectal metastases

Abstract

Intrabiliary colorectal metastases are rare. We present a case of an 84-year-old man who developed obstructive jaundice secondary to intrabiliary growth of colorectal metastases. The patient presented with three weeks of jaundice and significant weight loss in the preceding months. The patient's background included metastatic colorectal carcinoma, with a previous right hemicolectomy and left hepatectomy for liver metastases. A MRCP showed an obstruction of the biliary tract transitioning at the ampulla. Histology confirmed a malignant adenocarcinoma. When compared to the patient's previous resected colorectal liver metastases, morphology and immunohistochemistry was consistent with colorectal metastases. This case highlights the importance of differentiating a new intraductal papillary neoplasm from a colorectal metastasis. Correctly identifying these lesions requires the use of MRCP and ERCP, as well as immunohistochemistry. This is a priority for clinicians to ensure appropriate therapy.

http://ift.tt/2DhgxMu

Metastatic squamous cell cancer of the lung presenting as a perforated cecal cancer

Abstract

Lung cancer is the leading cause of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of diagnoses. Metastasis occurs in ~50% of cases but clinically evident isolated gastrointestinal (GI) metastasis is rare. We present a 78-year-old female who underwent an urgent right hemi-colectomy after cross-sectional imaging revealed a perforated cecal mass. Final pathology demonstrated squamous cell cancer of lung origin. We review the literature on NSCLC with clinically evident metastases to the GI tract, as well as important diagnostic considerations.

http://ift.tt/2Dho129

A Generalized Blaschko Linear Congenital Eruption

Abstract

Blaschko's lines are trace of the migration of primordial cells to the ectoderm during embryogenesis. We report an intriguing, complex and very rare case of a patient with congenital rash on Blaschko's lines. A 30-year-old female patient presented at birth with erythroderma and generalized desquamation that progressively acquired a linear distribution, under Blaschko's lines, associated with pruritus and fissures in the hands.

This article is protected by copyright. All rights reserved.

http://ift.tt/2Db3ate

Medically Unexplained Dermatologic Symptoms (MUDS): Hiding in plain sight?

Abstract

Illness is not the same as disease. Illness refers to "the innately human experience of symptoms and suffering." ¹ Disease "is what the practitioner creates in recasting illness in terms of theories of disorder." ¹ A person's subjective experience of how she feels may not assume an underlying pathology. Illness can be organic, psychological or spiritual. A person can feel ill, but not have a disease.

This article is protected by copyright. All rights reserved.

http://ift.tt/2DFJApP

CHILD Syndrome Mimicking Verrucous Nevus in a Chinese Patient Responded Well to The Topical Therapy of Compound of Simvastatin and Cholesterol

Abstract

Background

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disorder characterized by peculiar cutaneous presentations and ipsilateral skeletal abnormalities. CHILD syndrome is caused by mutations in NSDHL gene, which involves in cholesterol synthesis.

Objectives

To verify the diagnosis of CHILD syndrome and seek effective pathogenesis-based therapy with little side effects.

Method

We comprehensively evaluated the patient's conditions. Pathological biopsy was performed in the lesion location. Genetic tests and real-time quantitative PCR were conducted to further confirm the diagnosis. The topical application of a mixed lotion containing 2% simvastatin and 2% cholesterol to lesion areas based on the pathogenesis as well as the literature review.

Results

We diagnosed a rare and typical case of CHILD syndrome cooccurring with multiple VX -like lesions. The gene mutation is a large deletion of exon 3 and 4 of the NSDHL gene, which was discovered and reported for the first time in CHILD syndrome. The skin lesions, including the verruciform plaques and VX-like lesions, improved obviously after treatment.

Conclusions

Multiple exons deletions or microdeletion were not rare in CHILD syndrome. Classical Sanger sequencing may not be useful enough to find all kinds of mutations. Next Generation Sequencing may be more effective. It is important to conduct genetic counseling to prevent more serious defects in descendants. The excellent therapeutic effect on CHILD syndrome resulted from the topical treatment with simvastatin /cholesterol provides a proof-of-concept for other topical pathogenesis-based therapies for skin disease.

This article is protected by copyright. All rights reserved.

http://ift.tt/2Db319a

Genetic and functional analysis of the RYR1 mutation p.Thr84Met revealed a susceptibility to malignant hyperthermia

Abstract

Purpose

The aim of this study was to analyze the genetic and functional role of a novel RYR1 variant c.251 C > T (p.Thr84Met) identified in a patient with muscle weakness demonstrating MH susceptibility.

Methods

DNA testing of family members was conducted for assessment of pathogenicity of the genetic variant. For functional analysis, Ca²⁺ measurement using patient-derived myotubes and p.Thr84Met RYR1-transfected human embryonic kidney (HEK)-293 cells was performed to evaluate reactivity to RYR1 activators. The half-maximal effective concentration (EC₅₀) values of two RYR1 activators, caffeine and 4-chloro-m-cresol (4CmC), were calculated from the acquired dose–response curves. The EC₅₀ was compared between two groups: for myotubes, the control group and the patient, and for HEK-293 cells, WT and p.Thr84Met.

Results

Dose–response curves for caffeine and 4CmC were shifted to the left in both myotubes and HEK-293 cells compared to controls. The 50% effective concentration values for caffeine and 4CmC were significantly lower in both myotubes and HEK-293 cells compared to controls (P < 0.001 for all comparisons).

Conclusions

Our results of functional testing indicated RYR1 hypersensitivity to caffeine and 4CmC. We conclude that the genetic variant was associated with MH susceptibility.

http://ift.tt/2DhkrVI

Onset of action for loratadine tablets for the symptomatic control of seasonal allergic rhinitis in adults challenged with ragweed pollen in the Environmental Exposure Unit: a post hoc analysis of total symptom score

Loratadine is a second-generation, non-sedating antihistamine used for the relief of allergic rhinitis symptoms. Previous studies reported that when loratadine was encapsulated, the onset of action for symptom...

http://ift.tt/2rezF8j

Exophytic sinonasal papillomas and nasal florid papillomatosis: A retrospective study

Abstract

Background

Sinonasal exophytic papillomas are rare. The multifocal form, florid papillomatosis, has not been yet described in literature. We report on the clinical features and the management of the different forms of exophytic papilloma.

Methods

A retrospective study was conducted that included all patients with exophytic papilloma treated in our center over the past 12 years. We recorded clinical presentation, treatments, recurrences, pathology (p16 expression and human papillomavirus [HPV] status).

Results

We included 13 patients with a mean follow-up of 5 years. The main location of exophytic papilloma was the anterior part of the septum. Lesions were multifocal in 3 patients corresponding to florid papillomatosis. The main treatment was surgery. Cases of HPV-11 or HPV-6 were present in all forms of exophytic papilloma (dysplasia in 4 cases). Late recurrences occurred in 3 patients (2 patients with florid papillomatosis) over a period of 3 years.

Conclusion

Exophytic papilloma has 2 clinical presentations: localized and diffuse. Patients with florid papillomatosis should be monitored closely as recurrence seems to be frequent.

http://ift.tt/2DlwjFw

Endoscopic endonasal approach for sinonasal and anterior skull base malignancies in the elderly

Abstract

Background

The purpose of this study was to report the outcomes of endoscopic transnasal resection for sinonasal and anterior skull-base cancers in elderly patients.

Methods

A retrospective review was performed. The patients were divided into 2 groups, <70 years old and ≥70 years old and compared by univariate analysis. Prognostic factors were evaluated with a multivariate analysis. Survival rates were also calculated.

Results

Two hundred three elderly patients and 397 younger patients were enrolled in this study. The elderly patients reported lower survival rates than the younger patients. When melanoma and esthesioneuroblastoma were censored, the disease-specific survival (DSS) and recurrence-free survival (RFS) were similar. Complication rates were 17.5% without any statistical significance between the groups. Multivariate analysis revealed that histology, stage, surgical margins, and surgical approaches were independent predictors of survival in elderly patients.

Conclusion

The endoscopic transnasal approach reported low mortality and morbidity rates also in geriatric patients, and age itself is not to be considered as a contraindication.

http://ift.tt/2DlAmlW

Fungal kerion of the vulva

http://ift.tt/2FIkC9Y

Establishing Correlates of Protection for Vaccine Development: Considerations for the Respiratory Syncytial Virus Vaccine Field

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2DFFeiK

Association between circulating 25-hydroxyvitamin D levels and psoriasis, and correlation with disease severity: a meta-analysis

Summary

Background

Psoriasis is a chronic, autoimmune, inflammatory skin disorder. 25-hydroxy vitamin D [25(OH)D] deficiency may contribute to the pathogenesis of psoriasis through reduction in antiproliferative, anti-inflammatory and antiangiogenic activities.

Aim

To evaluate the relationship between circulating 25(OH)D levels and psoriasis, and to determine the correlation between serum/plasma 25(OH)D levels and psoriasis severity.

Methods

We performed a meta-analysis to compare serum/plasma 25(OH)D levels between patients with psoriasis and healthy controls (HCs), and to determine the correlation coefficients between circulating 25(OH)D levels and psoriasis severity as assessed by Psoriasis Area and Severity Index (PASI).

Results

Ten articles with a total of 571 patients with psoriasis and 496 HCs were included. The 25(OH)D level was significantly lower in the psoriasis group than in the HC group. Subgroup analysis by sample size revealed a significantly lower level of 25(OH)D in the psoriasis group for large (N > 80) but not for small (N < 80) sample sizes. Stratification by adjustment for age and/or sex or sample type revealed a significantly lower 25(OH)D level in the psoriasis group after adjustment for serum but not after nonadjustment for plasma. Meta-analysis of the correlation coefficients revealed a small but statistically significant positive correlation between circulating 25(OH)D levels and PASI.

Conclusions

This meta-analysis demonstrated that circulating 25(OH)D levels are lower in patients with psoriasis, and that a small but statistically significant negative correlation exists between 25(OH)D levels and psoriasis severity.

http://ift.tt/2mFElhR

Pediatric penile porokeratosis: A case report

Abstract

We present what we believe to be the second case of pediatric penile porokeratosis and the youngest case reported. A 6-year-old boy presented with a pruritic, verrucous growth at the urethral meatus that recurred after two meatotomies. The diagnosis of porokeratosis was confirmed by biopsy. Porokeratosis should be added to the differential diagnosis of chronic hyperkeratotic penile lesions in children.

http://ift.tt/2rdGPtk

Utility of ultrasonography in hair-thread tourniquet syndrome

Abstract

A 2-year-old girl presented with a 2-month history of an erythematous, indurated plaque with well-defined borders on the third toe of the right foot. Bedside high-resolution ultrasonography demonstrated a thickened epidermis overlying a hyperechoic focus within the dermis. Her clinical and sonographic presentation was in keeping with a foreign body causing hair-thread tourniquet syndrome. The foreign body was surgically extirpated without neurovascular sequelae. Ultrasonography expedited accurate diagnosis and is a promising adjunct to clinical evaluation for radiolucent foreign bodies.

http://ift.tt/2DiKkV7

Recurrent terbinafine resistant Trichophyton rubrum infection in a child with congenital ichthyosis

Abstract

Dermatophytosis in children caused by Trichophyton rubrum is preferably treated with topical or systemic terbinafine. We report the first case of terbinafine resistance in a child with recurrent T. rubrum dermatophytosis and congenital ichthyosiform erythroderma.

http://ift.tt/2B94lHz

Case of classic Kaposi sarcoma of the penis successfully treated with radiotherapy

http://ift.tt/2DficSG

Metastatic Crohn's disease in childhood: A case report

http://ift.tt/2B9AlLY

Primary scarring alopecia: A retrospective study of 89 patients in Taiwan

Abstract

Primary scarring alopecia (PSA) is caused by irreversible damage to the hair epithelial stem cells that reside in hair follicles. There is limited published work regarding PSA amongst the Asian population. The aim of this study was to evaluate the clinical features and to characterize the subtypes of PSA in southern Taiwan. In this retrospective case series, we reviewed 89 patients with pathology-confirmed PSA. The data was collected from National Cheng Kung University Hospital between 1988 through 2016. The clinical and histological data were reviewed, and the patients were characterized into different subtypes of PSA based on the clinical features and histological findings. We noted seven different subtypes of PSA. The most common type was dissecting cellulitis (DC) (30.3%), followed by lichen planopilaris (LPP) (23.5%), central centrifugal cicatricial alopecia (CCCA) (12.4%) and acne keloidalis nuchae (AKN) (12.4%). The other subtypes include folliculitis decalvans (FD), discoid lupus erythematosus (DLE) and pseudopelade of Brocq (PPB). Interestingly, FD, DC and AKN were more common in males, while CCCA, LPP, DLE and PPB had a female predominance. The mean age of patients with DLE, DC and AKN were younger, while patients with CCCA, LPP, PPB and FD tend to be older. The pattern of hair loss was more likely to be unifocal-ragged border in CCCA and DLE, multifocal-interconnected in LPP and FD, and multifocal-separated in DC. The pathogenesis of PSA may be influenced by sex, age and genetic background. It is important to identify the hair loss pattern to differentiate the subtypes of PSA.

http://ift.tt/2Dh53bX

Dermoscopic features of Bednar tumor: Report of a case

http://ift.tt/2B7k5Lm

Intrapulmonary Pharmacokinetics of Lascufloxacin in Healthy Adult Volunteers [PublishAheadOfPrint]

This study was performed to investigate the intrapulmonary penetration of lascufloxacin in humans. Thirty healthy adult male Japanese subjects, allocated into five groups, received lascufloxacin in single oral dose of 75 mg. Bronchoalveolar lavage and blood sampling were performed simultaneously in each subject at 1, 2, 4, 6, or 24 hours after administration, and lascufloxacin concentrations in plasma, epithelial lining fluid, and alveolar macrophages were determined. Lascufloxacin was rapidly distributed to the epithelial lining fluid with T_max of 1 hour, which was identical to that in plasma. The C_max values in plasma, epithelial lining fluid, and alveolar macrophages were 0.576, 12.3, and 21.8 μg/mL, respectively. The corresponding AUC_0-24 values were 7.67, 123, and 325 μg⋅h/mL. The mean drug concentrations in the epithelial lining fluid and alveolar macrophages were much higher than those in plasma at all time points examined, and the average site-to-free plasma concentration ratios fell within the ranges of 57.5 -- 86.4 and 71.0 -- 217, respectively. Drug levels in epithelial lining fluid and alveolar macrophages exceeded the MIC₉₀ values for common respiratory pathogens. (This study was registered at JAPIC under registration number JapicCTI- 142547.)

http://ift.tt/2ritDUg

A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for Malaria Venture Open Access Malaria Box [PublishAheadOfPrint]

Cryptosporidiosis causes life-threatening diarrhea in children under age five, and prolonged diarrhea in immunodeficient people, especially AIDS patients. The standard of care, nitazoxanide, is modestly effective in children and ineffective in immunocompromised individuals. In addition to a need for new drugs, better knowledge of drug properties that drive in vivo efficacy is needed to facilitate drug development. We report identification of a piperazine-based lead compound for Cryptosporidium drug development, MMV665917, and a new pharmacodynamic method used for its characterization. MMV665917 was identified from the Medicines for Malaria Venture Malaria Box, followed by dose response studies, in vitro toxicity studies, and structure activity relationship studies using commercial analogues. Potency against C. parvum Iowa and field isolates, and C. hominis was comparable. Furthermore, unlike nitazoxanide, clofazimine, and paromomycin, MMV665917 appeared to be curative in a chronic NOD SCID gamma mouse model of cryptosporidiosis. MMV665917 was also efficacious in an acute interferon- knockout mouse model. To determine if efficacy in this chronic mouse model might relate to whether compounds are cidal or static for C. parvum, we developed a novel in vitro parasite persistence assay. This assay suggested that MMV665917 was cidal, unlike nitazoxanide, clofazimine, and paromomycin. It also enabled determination of the compound concentration required to maximize the rate of parasite elimination. This time-kill assay can be used to prioritize early-stage Cryptosporidium drug leads, and may aide in planning in vivo efficacy experiments. Collectively, these results identify MMV665917 as a promising lead, and establish a new method for characterizing potential anticryptosporidial agents.

http://ift.tt/2mNMNN3

Early clinical assessment of the antimicrobial activity of finafloxacin compared to ciprofloxacin in sub-sets of microbiologically characterized isolates [PublishAheadOfPrint]

Introduction

Two phase II studies were performed in patients with uncomplicated (uUTI) and complicated urinary tract infections or acute pyelonephritis (cUTI/PN) to compare finafloxacin (300 mg b.i.d, p.o. for uUTI 800 mg q.d., i.v. for cUTI/PN) and ciprofloxacin (250 mg b.i.d, p.o. for uUTI and 400 mg b.i.d., i.v. for cUTI/PN). The early response to the study medications was evaluated in the microbiological-intent-to treat population (mITT) at day 3.

Results

21% of the isolates were ciprofloxacin-resistant, 13.7 % were primed pathogens carrying mutation(s) potentially fostering fluoroquinolone-resistance development, and 7.1 % produced ESBLs. Finafloxacin demonstrated very good early clinical activity with microbiological eradication rates of 88.6% (n=132) compared to 78.7% (n=61) for ciprofloxacin, and 69.6% (n=23) compared to 35.7% (n=14) for ciprofloxacin in patients with ciprofloxacin-resistant, and 94.1% (n=17) compared to 80.0% (n=10) for ciprofloxacin in patients infected with uropathogens primed for fluoroquinolone-resistance uropathogens, and 91.7% (n=11) for finafloxacin compared to 0% for ciprofloxacin in patients infected with ESBL-producers.

Conclusions

Finafloxacin demonstrated an early and rapid activity against uropathogens including fluoroquinolone- and/or multi-resistant or ESBL-producers while ciprofloxacin was less active against this subset of resistant pathogens.

Methods

Susceptibilities of pathogens were quantitated by broth microdilution. Isolates were subgrouped according to their susceptibility-patterns, in particular first-step-quinolone-resistance, quinolone-resistance, and ESBL-production. Eradication was defined as elimination or reduction of study entry pathogens to <10³ CFU/ml in urine culture.

http://ift.tt/2rf7RRg

Identification of Hsp90 inhibitors with anti-Plasmodium activity [PublishAheadOfPrint]

Malaria remains a global health burden partly due to Plasmodium parasite resistance to first-line therapeutics. The molecular chaperone heat shock protein 90 (Hsp90) has emerged as an essential protein for blood stage Plasmodium parasites, but details about its function during malaria's elusive liver stage are unclear. We used target-based screens to identify compounds that bind to Plasmodium falciparum and human Hsp90, which revealed insights into chemotypes with species selective binding. Using cell-based malaria assays, we demonstrate that all identified Hsp90-binding compounds are liver and blood stage Plasmodium inhibitors. Additionally, the Hsp90 inhibitor SNX-0723 synergistically reduces liver stage parasite load in combination with the phosphatidylinositol 3-kinase inhibitor PIK-75. Time course inhibition studies with the Hsp90 inhibitors and expression analysis support a role for Plasmodium Hsp90 in late liver stage parasite development. Our results suggest that Plasmodium Hsp90 is essential to liver and blood stage parasite infections and highlight an attractive route to develop species selective PfHsp90 inhibitors that could act synergistically in combination therapies to prevent and treat malaria.

http://ift.tt/2mLDvBa

Population pharmacokinetics of finafloxacin in healthy volunteers and patients with complicated urinary tract infections [PublishAheadOfPrint]

Background: Finafloxacin is a novel fluoroquinolone with increased antibacterial activity at acidic pH and reduced susceptibility to several resistance mechanisms. A phase II study revealed a good efficacy/safety profile in patients with complicated urinary tract infections (cUTI) while pharmacokinetics was characterized by highly variable concentration vs. time profiles, suggesting the need for an elaborated pharmacokinetic model.

Methods: Data from three clinical trials were evaluated; 127 healthy volunteers were dosed orally (N=77) or intravenously (N=50) and 139 patients with cUTI received finafloxacin intravenously. Plasma (2824 samples in volunteers, 414 in patients) and urine (496 samples in volunteers, 135 in patients) concentrations were quantified by LC/MS-MS. NONMEM was used to build a population pharmacokinetic model and pharmacokinetic/pharmacodynamic relationships were investigated via simulations and logistic regression.

Results: A two-compartment model with first-order elimination described the data best (central [Vc] and peripheral [Vp] volumes: 47L [20%] and 43L [67%]; elimination clearance and inter-compartmental clearance: 21L/h [54%] and 2.8L/h [57%]) (median bootstrap estimates, coefficients of variation). Vc increased with body surface area and clearance was reduced in patients (-29%). Oral absorption was described best by parallel first- and zero-order processes (bioavailability 75%). No pharmacodynamic surrogate parameter of clinical/microbiological outcome could be identified, which depended exclusively on the MIC of the causative pathogens.

Conclusions: Despite the inter-individual variability, the present dataset does not support covariate-based dose adjustments. Based on the favorable safety and efficacy data, the clinical relevance of the observed variability appears to be limited.

http://ift.tt/2rhgevo

Efficacy and Safety of Finafloxacin versus Ciprofloxacin in the Treatment of Complicated Urinary Tract Infections: An Explorative Randomized Phase II Clinical Study. [PublishAheadOfPrint]

Introduction

The broad spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity at acidic conditions. This phase II clinical study compared efficacy and safety of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis.

Results

A 5-day regimen with finafloxacin 800 mg q.d. (FINA05) had similar results as a 10-day regimen with finafloxacin 800 mg q.d. (FINA10). Combined microbiological and clinical responses at test of cure visit (TOC) were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 (64 for FINA05, 68 for FINA10 and 61 for CIPRO10) patients of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin in patients with an acidic urine pH (80% of patients) were reduced whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall 43.4% of the patients in FINA05, 42.7% in FINA10 and 54.2% in the CIPRO10 group experienced mostly mild and treatment emergent, but unrelated adverse events.

Conclusion

A short course regimen of five days with finafloxacin resulted in higher eradication and improved clinical outcome rates than treatment with ciprofloxacin for 10 days. In contrast to ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic urine pH.

Methods

Hospitalized adults were randomized 1:1:1 to finafloxacin (800 mg q.d.) either for 5 or 10 days or ciprofloxacin (400 mg/500 mg b.i.d.) for 10 days with an optional switch from i.v. to oral administration at day 3. The primary endpoint was the combined microbiological and clinical response at TOC in the microbiological intent-to-treat population.

http://ift.tt/2mLL3UA

In vitro antibiotic susceptibility pattern of Non-diphtheriae Corynebacterium in Ontario, 2011-2016. [PublishAheadOfPrint]

Non-diphtheriae Corynebacterium-associated disease has been increasingly observed and often presents a conundrum to the treating physician. Analysis of antibiotic susceptibility test data for 1,970 clinical Corynebacterium isolates received between 2011 and 2016 revealed that empiric drug treatment options are limited to vancomycin and linezolid. Corynebacterium striatum was the most frequently observed species during this study period along with C. amycolatum and C. pseudodiphtheriticum/propinquum. Low levels of susceptibility to penicillin (14.5%), erythromycin (15.1%) and clindamycin (8.7%) were observed for non-diphtheriae Corynebacterium species, while 3.0% of isolates were not susceptible to daptomycin. Similarly, 26.9% and 38.1% of Corynebacterium isolates were susceptible to ciprofloxacin and trimethoprim-sulfamethoxazole, respectively. Our data shows much lower susceptibility to penicillin than previously reported in literature and an increasing number of isolates resistant to daptomycin highlighting the need for continued antibiotic surveillance studies for appropriate patient management and treatment success.

http://ift.tt/2rejHLw

Combating carbapenem-resistant Acinetobacter baumannii by an optimized imipenem plus tobramycin dosage regimen - prospective validation via hollow fiber infection and mathematical modeling [PublishAheadOfPrint]

We aimed to prospectively validate an optimized combination dosage regimen against a clinical carbapenem-resistant Acinetobacter baumannii (CRAB; MIC_Imipenem: 32mg/liter, MIC_Tobramycin: 2mg/liter). Imipenem at constant concentrations (7.6, 13.4 and 23.3mg/liter, reflecting a range of clearances) was simulated in a 7-day hollow fiber infection model (inoculum ~10^7.2 CFU/mL) with and without tobramycin (7mg/kg q24h, 0.5h infusions). While monotherapies achieved no killing or failed by 24h, this rationally optimized combination achieved >5 log₁₀ bacterial killing and suppressed resistance.

http://ift.tt/2mMayF9

Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the Murine Neutropenic Thigh Model [PublishAheadOfPrint]

Apramycin, an aminocyclitol aminoglycoside, was rapidly bactericidal against Acinetobacter baumannii. In a neutropenic murine thigh infection model, treatment-associated A. baumannii CFU reduction of greater than 4-log₁₀ per thigh was observed for all exposures for which AUC/MIC was greater than 50 and C_max/MIC was 10 or higher. Based on these findings, we suggest that apramycin deserves further pre-clinical exploration as a repurposed therapeutic for the treatment of multidrug-resistant, Gram-negative pathogens including A. baumannii.

http://ift.tt/2rk0BUn

Pterostilbene, a potential MCR-1 inhibitor that enhances the efficacy of polymyxin B [PublishAheadOfPrint]

We characterized pterostilbene produced a synergistic effect with polymyxin B (FIC index=0.156 or 0.188) against MCR-producing Escherichia coli strains of both human and animal origin. The time-killing assays showed that either pterostilbene or polymyxin B failed to eradicate a mcr-1- and NDM-positive E. coli strain ZJ487, but the combination eliminated by 1-hour post-inoculation. The survival rate of mouse following the intraperitoneal infection significantly promoted from 0% to 60% in the group of combination therapy applied.

http://ift.tt/2mNptyQ

The genetic basis of emerging vancomycin, linezolid, and daptomycin heteroresistance in a case of persistent Enterococcus faecium bacteremia [PublishAheadOfPrint]

Whole-genome sequencing was used to examine a persistent E. faecium bacteremia that acquired heteroresistance to three antibiotics in response to prolonged multidrug therapy. Comparison of complete genomes before and after each change revealed the emergence of known resistance determinants for vancomycin and linezolid, and suggested that a novel mutation in fabF, encoding a fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid recombination contributed to progressive loss of vancomycin resistance after withdrawal of the drug.

http://ift.tt/2rf7LZU

In vitro susceptibility of Neisseria gonorrhoeae strains to mupirocin. An antibiotic reformulated to parenteral nano-liposomal antibiotic [PublishAheadOfPrint]

Neisseria gonorrhoeae is an urgent antibiotic-resistant threat. This study determined the minimum inhibitory concentrations (MIC) of mupirocin to be 0.0039-0.0625 μg/ml for 94 N. gonorrhoeae strains. Cross-resistance with other antibiotics was not detected.

Mupirocin, currently limited to topical administration, demonstrated activity by injection when delivered in nano-liposomes. The nano-liposomal formulation of mupirocin is a potential treatment for drug-resistant N. gonorrhoeae.

http://ift.tt/2mNRvdx

New shuttle vectors for gene cloning and expression in multidrug-resistant Acinetobacter species [PublishAheadOfPrint]

Understanding bacterial pathogenesis requires adequate genetic tools to assess the role of individual virulence determinants by mutagenesis and complementation assays, as well as for homologous and heterologous expression of cloned genes. Our knowledge of Acinetobacter baumannii pathogenesis has so far been limited by the scarcity of genetic tools to manipulate multi drug resistant (MDR) epidemic strains which are responsible for most of infections. Here, we report the construction of new multi-purpose shuttle plasmids, namely pVRL1 and pVRL2, which can efficiently replicate in Acinetobacter sp. and in Escherichia coli. The pVRL1 plasmid has been constructed by combining: i) the cryptic plasmid pWH1277 from Acinetobacter calcoaceticus, which provides an origin of replication for Acinetobacter sp.; ii) a ColE1-like origin of replication; iii) the gentamicin or zeocin resistance cassette for antibiotic selection; iv) a multilinker containing several unique restriction sites. Modification of pVRL1 led to the generation of the pVRL2 plasmid, which allows arabinose-inducible gene transcription, with undetectable basal expression level of cloned genes under un-induced conditions and high-dynamic range of responsiveness to the inducer. Both pVRL1 and pVRL2 can easily be selected in MDR A. baumannii, have narrow host range and high copy number, are stably maintained in Acinetobacter sp., and appear compatible with indigenous plasmids carried by epidemic strains. Plasmid maintenance is guaranteed by the presence of a toxin-antitoxin system, providing more insights into the mechanism of plasmids stability in Acinetobacter sp.

http://ift.tt/2rf7LJo

A novel inhibitor of the LolCDE ABC transporter essential for lipoprotein trafficking in Gram-negative bacteria [PublishAheadOfPrint]

The outer membrane is an essential structural component of Gram-negative bacteria that is composed of lipoproteins, lipopolysaccharides, phospholipids, and integral β-barrel membrane proteins. A dedicated machinery, called the Lol system, ensures proper trafficking of lipoproteins from the inner to the outer membrane. The LolCDE ABC transporter is the inner membrane component, which is essential for bacterial viability. Here, we report a novel pyrrolopyrimidinedione compound, G0507, which was identified in a phenotypic screen for inhibitors of E. coli growth followed by selection of compounds that induced the extracytoplasmic ^E stress response. Mutations in lolC, lolD, and lolE conferred resistance to G0507 suggesting LolCDE as its molecular target. Treatment of E. coli cells with G0507 resulted in accumulation of fully processed Lpp, an outer membrane lipoprotein, in the inner membrane. Using purified protein complexes, we found that G0507 binds to LolCDE and stimulates its ATPase activity. G0507 still binds to LolCDE harboring a LolC_Q258K mutation, which confers high-level resistance to G0507 in vivo, but no longer stimulates ATPase activity. Our work demonstrates that G0507 has significant promise as chemical probe to dissect lipoprotein trafficking in Gram-negative bacteria.

http://ift.tt/2mM8YDe

Effectiveness of an Antimicrobial Stewardship Program in Critical Care: A Before-and-After Study [PublishAheadOfPrint]

We evaluated the use of antimicrobials expressed as defined daily doses (DDDs) per 1,000 patient days and days of therapy (DOT) per 100 occupied bed-days in a intensive care unit (UCI) of a general hospital in Barcelona, Spain, before and after implementation of an antimicrobial stewardship (AMS) program (2007-2010 versus 2011-2015). The quarterly costs of antimicrobials used in the ICU and its weight in the overall hospital costs of antimicrobials were calculated. The effect of the applied AMS program on DDDs and DOT time series data was analyzed by means of intervention time series analysis. A total of 5,002 patients were included (1,971 for the first [before] period and 3,031 for the second [after] period). The percentage of patients treated with one or more antimicrobials decreased from 88.6% to 77.2% (P< 0.001). DDDs decreased from 246.8 to 192.3 (mean difference -54.5, P = 0.001) and DOT from 66.7 to 54.6 (mean difference -12.1, P = 0.066). The mean cost per trimester decreased from 115,543 to 73,477 (mean difference -42,065.4, P< 0.001) and the percentage of ICU antimicrobials cost with respect to the total cost of hospital antimicrobials decreased from 28.5% to 22.8% (mean difference -5.59, P = 0.023). Implementation of an AMS program in the ICU was associated with a marked reduction of the use of antimicrobials, with cost savings close to one million euros since its implementation. An AMS program can have a significant impact on optimizing antimicrobial use in critical care practice.

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Neuroimaging Findings in Patients with Medication Overuse Headache

Abstract

Medication overuse headache (MOH) is a secondary headache syndrome defined as the deterioration of the headache associated with the overuse of analgesics. The prevalence of MOH is 1–2% in the general population and even up to 50% in special clinics. Overuse of abortive medications is highly associated with chronic daily headaches and also a known risk factor for headache evolution. Possible mechanisms include neural plasticity changes such as sensitization and defective endogenous pain inhibition. Psychological studies have suggested dependence, even addiction, in patients with MOH. Neuroimaging studies have provided valuable information concerning MOH pathophysiology. Magnetic resonance imaging analyzed by voxel-based morphometry showed gray matter volume changes in brain areas participating the pain modulations. Changes of brain function at similar areas have been revealed by positron emission tomography and functional magnetic resonance imaging studies. Many of these changes were correlated with either headache and/or analgesics parameters such as frequency and duration. These changes are typically reversible after successful treatment. Though the cause or consequence debate remains unsettled, we are more in favor of these findings as maladaptive changes to the frequent headaches or medication overuse. Of these brain areas involved in MOH, orbitofrontal cortex is of interest in several ways. In an early positron emission tomography study, the hypometabolism persists after successful treatment which implied a causal role. The following morphological studies showed the orbitofrontal cortex volume could predict treatment responses. Functional magnetic resonance imaging studies, task positive and also resting-state ones, also reported changes within the mesocorticolimbic dopamine system, also known as reward system. Important brain areas of this system include ventral tegmental area, striatum, and orbitofrontal cortex. The system plays an important role in decision-making, dependence, and addiction, as implicated in psychological studies of MOH. Further studies on neuromodulation of this system may be considered in the treatment of MOH.

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Acute intestinal obstruction due to extrinsic compression by previa myoma and ectopic pregnancy: a case report

Acute intestinal obstruction during pregnancy is a rare digestive surgical emergency with significant maternal and fetal mortality. Diagnosis is difficult, often delaying the management. Here, we report an exc...

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Epidermal melanocytes of segmental vitiligo show altered expression of E-cadherin, but not P-cadherin

Abstract

Vitiligo is the most common pigmentation disorder, with a worldwide prevalence of 1%. The loss of melanocytes from the skin is the main clinical feature of patients with vitiligo, resulting in depigmentation macules. Vitiligo has been classified into two major forms: non-segmental vitiligo (NSV) and segmental vitiligo (SV). NSV lesions are generally bilateral or symmetrically scattered over the entire body. Onset may occur at any age, but most patients develop vitiligo before 40 years of age, and the depigmentation evolves over time.

This article is protected by copyright. All rights reserved.

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Reflectance Confocal Microscopy for the Diagnosis of Langerhans Cell Histiocytosis

Abstract

Langerhans cell histiocytosis (LCH) is a rare proliferative disease occurring in young children. The most affected organs are the bones and the skin (1). The diagnosis of LCH relies on histopathology. Reflectance confocal microscopy (RCM) is a non-invasive imaging technique used to diagnose skin cancer (2). We report that in three children RCM examination of cutaneous lesions of LCH showed specific signs correlated to histopathology.

This article is protected by copyright. All rights reserved.

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Do Cutibacterium acnes and Staphylococcus aureus define two different types of folliculitis?

Abstract

Scalp folliculitis is a common disorder in dermatology. Its clinical spectrum includes three main forms: "simple" folliculitis with an ad integrum evolution without sequellar alopecia, Quinquaud's folliculitis decalvans, and acne keloidalis nuchae. The pathophysiology of scalp folliculitis remains poorly understood. The assumptions would be infectious and/or inflammatory causes possibly involving Staphylococcus aureus and Propionibacterium acnes (now referred to as Cutibacterium acnes according to a new taxonomic classification).

This article is protected by copyright. All rights reserved.

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Merkel cell carcinoma in France: A registries-based, comprehensive epidemiological survey

Abstract

Background

Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are scarce and have never been analysed in France to identify the main epidemiological trends.

Methods

Data from MCC patients diagnosed between 1998 and 2010 were obtained from 11 French cancer registries in the FRANCIM network. The main epidemiological characteristics of MCC were investigated between 2006 and 2010 because comprehensive data were only available for this period. The main focus was tumour incidence and mortality over time.

Results

Between 1998 and 2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290 cases), European- and world-standardized incidence rates were 0.26 and 0.43 per 100,000 person-years in men; and 0.24 and 0.38 per 100,000 person-years in women. MCC is more frequent in females in France (56.9%) with male/female ratio1.1. Relative survival rates were 84%, 56% and 42% at one, three and five years, respectively.

Conclusions

The incidence of MCC clearly increased over time in all areas under focus. The standardized incidence in France was comparable to the incidence observed in other countries for the same period but French data are too recent to conclude on an increase in MCC incidence. Prognosis remains poor in all countries in which data are available.

This article is protected by copyright. All rights reserved.

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Mogamulizumab-induced phosensitivity in patients with mycosis fungoides and other T cell neoplasms

Abstract

Background

Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4, and was first approved in Japan for the treatment of adult T cell leukaemia/lymphoma (ATLL), followed by cutaneous T cell lymphoma and peripheral T cell lymphoma.

Objective

To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T cell neoplasms after treatment with Mog.

Methods

We treated 7 cutaneous lymphoma patients with Mog. Upon combination treatment with narrow-band UVB, we noticed that 4 patients developed photosensitivity dermatitis following Mog therapy, including 2 cases of mycosis fungoides, one case of adult T-cell leukemia/lymphoma, and one case of EB virus-associated T-cell lymphoproliferative disorder. Phototest was performed with UVA and UVB, and immunohistochemical staining for CD4, CD8 and Foxp3 were conducted in both photosensitivity and lymphoma lesions.

Results

Phototest revealed that the action spectrum of the photosensitivity was UVB in 3 cases and both UVB and UVA in one case. Histopathologically, the photosensitive lesions were characterized by a lichenoid tissue reaction with a CD8⁺ T cell-dominant infiltrate, sharing the feature with chronic actinic dermatitis, an autoreactive photodermatosis with a cytotoxic T-cell response. Foxp3⁺ regulatory T cells (Tregs) were decreased in the photosensitivity lesions compared with the lymphoma lesions.

Conclusion

Increased incidence of photosensitivity reaction was observed during Mog treatment. Decreased number of Tregs in the lesional skin suggests that this reaction is possibly induced by autoreactive cytotoxic T cells.

This article is protected by copyright. All rights reserved.

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Histiocytosis - cutaneous manifestations of hematopoietic neoplasm and non-neoplastic histiocytic proliferations

Abstract

Histiocytoses are rare disorders characterized by the accumulation of cells derived from macrophages, dendritic cells, or monocytes in various tissues. There is a broad spectrum of disease manifestations with some subtypes commonly showing skin lesions while in others the skin is rarely involved. Here we describe cutaneous manifestations of histiocytoses belonging to the Langerhans group (L group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the group of Rosai-Dorfman disease and related histiocytoses (R group) according to the current classification. Charcteristic clinical presentations noted were a rust-brown color or xanthomatous aspect in many cases of histicytoses. Histological criteria for differentiation are described. Immunohistochemistry shows positivity for S100 and CD1a in Langerhans-cell histiocytoses of the L group while CD68 positivity with S100 and CD1a negativity is typical in histiocytoses of the C-group of cutaneous and mucocutaneous histiocytoses. Rosai-Dorfman disease in the R group shows positivity for S100 and CD68 while CD1a is negative. We further review the pathogenesis of Langerhans-cell histiocytoses based on insights on the central role of the MAPK kinase pathway. Common mutations in various histiocytic populations of diverse ontogeny and at different stages of differentiation may be responsible for the diverse clinical picture of this neoplastic entity. For histiocytoses of the C group and R group a reactive origin is discussed with the exception of the disseminated form of juvenile xanthogranuloma. We suggest exploring the role of an origin from skin residing histiocytes for the isolated cutaneous manifestation in some types. With regard to therapeutic options, skin directed therapies are the first choice in limited disease while systemic chemotherapy has traditionally been used in extensive disease. In Langerhans-cell histiocytoses and related entities therapy by BRAF inhibition has led to a breakthrough especially in patients with an activation of the MAPK pathway.

This article is protected by copyright. All rights reserved.

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Reflectance confocal microscopy and optical coherence tomography for the diagnosis of bullous pemphigoid and pemphigus and surrounding sub-clinical lesions

Abstract

Background

Diagnosis of bullous pemphigoid (BP) and pemphigus is based on clinical features, histology, immunofluorescence and laboratory data.

Objectives

To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in order to provide a rapid non-invasive bed-side diagnosis. Secondary objective was to evaluate the detectability of clinically non-visible lesions.

Methods

This was an observational, retrospective, multicentre study in which patients with suspicious lesions for BP or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy for histological and direct immunofluorescence examinations from January 2014 to December 2015. A total of 72 lesions in 24 selected patients were evaluated. Additionally, apparently unaffected skin at two different distances [near (1-2 cm) and far (2-3 cm)] from each lesion was examined in order to test sub-clinical lesion detectability.

Results

RCM was able to detect sub-epidermal and intra-epidermal blisters respectively in 75% and 50% of the patients affected by BP and pemphigus. At OCT the exact blister level was identified in all patients. Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin deposition inside the blisters was only found in BP, evidenced both at RCM and OCT. Among patients with BP, subclinical blisters were detected in 9 (9.4%) clinically healthy skin, while among patients with pemphigus were observed in 10 (20.8%) apparently unaffected skin.

Conclusion

RCM and/or OCT provide useful information for a rapid diagnosis of BP and pemphigus and for the identification of biopsy site. Combined use of RCM and OCT is optimal because associates the higher resolution of RCM with the greater penetration depth of OCT. OCT could be an optimal tool for treatment monitoring, especially in the cases of sub-clinical lesions. However, histopathologic and immunologic examinations remain the gold standard for establishing the final diagnosis.

This article is protected by copyright. All rights reserved.

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Cicatricial Alopecia Research Foundation Meeting, May 2016: Progress Towards the Diagnosis, Treatment, and Cure of Primary Cicatricial Alopecias

Abstract

Primary Cicatricial Alopecias (PCAs) are a group of skin diseases in which there is progressive and permanent destruction of hair follicles followed by replacement with fibrous tissue. Unfortunately, by the time patients seek clinical evaluation of their hair loss, the skin is already inflamed and/or scarred, so there is little hope for a return to their normal hair growth pattern. Clinical and basic science investigations are now focusing on three forms of human PCA, lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and central centrifugal cicatricial alopecia (CCCA). Transcriptome, lipidome, and other new technologies are providing new insight into the pathogenesis of some of these diseases that are being validated and further investigated using spontaneous and genetically engineered mouse models.

This article is protected by copyright. All rights reserved.

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Reversine inhibits MMP-1 and 3 expressions by suppressing of ROS/MAPK/AP-1 activation in UV-stimulated human keratinocytes and dermal fibroblasts

Abstract

UVB has been shown to stimulate the generation of ROS, which subsequently results in activation of various intracellular signaling pathways and transcription factors (AP-1, NF-κB), These transcription factors are regulated by MAPKs, which increase cytokine and MMP expression. We examined the preventive effects of reversine on MMP-1 and -3 expressions in NHEKs and NHDFs exposed to UVB irradiation. Also, we confirmed that reversine decreased pro-inflammatory cytokine expression in NHEKs. The mechanism underlying the MMP-inhibitory effects of reversine occurred via the suppression of UVB-induced ROS generation and MAPK/AP-1 activation. Therefore, reversine is an effective therapeutic candidate for preventing skin photoaging.

This article is protected by copyright. All rights reserved.

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Effect of Remote Ischemic Preconditioning on Systemic Toxicity and Ototoxicity Induced by Cisplatin in Rats: Role of TNF-α and Nitric Oxide

Background/Aims: Cisplatin is a chemotherapeutic agent. The use of remote ischemic preconditioning (RIPC) was proposed after the observation that ischemic preconditioning of a cardiac vascular area could protect another completely distinctly. Methods: This is an experimental study. Male Wistar rats were anesthetized, and they underwent a hearing evaluation via measurement of the brainstem auditory evoked potential (BSAEP). Then, cisplatin was administered intraperitoneally (IP) at a dose of 8 mg/kg/day for 4 consecutive days to group 1, whereas saline solution was administered IP to group 2. In groups 3 and 4, ischemia of the right hind paw was performed for 10 min, followed by reperfusion for 30 min, after which cisplatin or saline was administered IP to group 3 or group 4, respectively. Afterwards, all animals were evaluated via the BSAEP. The right cochlea was dissected for immunohistochemistry. Results: RIPC lowered the increase in BSAEP of the animals treated with cisplatin (p = 0.0146). Weight loss decreased in the animals subjected to RIPC (p p Conclusion: RIPC protects against systemic toxicity and ototoxicity induced by cisplatin in rats.
ORL 2017;79:336-346

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Clinically Relevant Reactions to Thimerosal (the “Nonallergen”) Exist!

No abstract available

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Propylene Glycol

Propylene glycol (PG), an emollient and emulsifier found in cosmetics, medications, and food, has been granted the dubious honor of being named the American Contact Dermatitis Society's Allergen of the Year for 2018. Allergic and irritant contact dermatitis and systemic cutaneous reactions to PG, which has become an increasingly common ingredient, have been documented. Propylene glycol is as contentious as it is ubiquitous because it acts as both a weak sensitizer and an irritant, confounding the results of positive patch tests. This report serves to increase awareness about PG sensitization and appropriate testing and evaluation of PG patch tests.

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Improving the Diagnosis of Allergic Contact Dermatitis Using Patch Test With Gloves

No abstract available

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Propylene Glycol in Contact Dermatitis: A Systematic Review

Propylene glycol (PG), an emollient and emulsifier found in cosmetics, medications, and food, has been granted the dubious honor of being named the American Contact Dermatitis Society's Allergen of the Year for 2018. Contact, systemic, and irritant cutaneous reactions have been documented for PG, which has become an increasingly common ingredient. Propylene glycol is as contentious as it is ubiquitous because it acts as both a weak sensitizer and an irritant, confounding the results of positive patch tests. This review serves to delve into what we know about PG from previous reports and studies so that providers will have a better understanding of PG contact dermatitis.

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Military Decorative Pin Dermatitis: Prevention for Nickel Allergy Among Service Members

No abstract available

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Glove-Related Allergic Contact Dermatitis

Hand dermatitis is a common condition with a lifetime prevalence of 20%. Glove allergic contact dermatitis (ACD) is a very important dermatitis affecting health care workers, hairdressers, cleaning personnel, kitchen workers, craftsmen, construction workers, laboratory workers, and homemakers. Occupationally related cases may be severe and can result in significant disability. Glove ACD is most commonly due to exposure to rubber accelerators, which are compounds that are added to rubber during production to increase strength and durability. Given the known allergic potential of these compounds, glove manufacturing companies have reformulated gloves leading to the introduction of new rubber allergens. In this review, we will discuss risk factors for glove ACD, both common and uncommon allergens in gloves, common contact allergens that permeate gloves, and patch testing to help uncover the inciting allergen(s).

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SELF-ASSESSMENT

No abstract available

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Predictors of Hospitalization, Length of Stay, and Costs of Care Among Adult and Pediatric Inpatients With Atopic Dermatitis in the United States

Introduction Little is known about the risk factors of hospitalization for atopic dermatitis (AD). Objectives We sought to determine associations of hospitalization for AD in the United States. Methods Data were analyzed from the 2002 to 2012 National Inpatient Sample. Atopic dermatitis hospitalizations were compared with controls, which included all hospitalizations without any diagnosis of AD excluding normal pregnancy/delivery, yielding a representative cohort of US hospitalizations. Results Both adults and children, who were admitted for AD or eczema, were more likely to have nonwhite race/ethnicity, lowest-quartile annual household income, Medicaid or no insurance, and fewer chronic conditions. Increased cost of care and prolonged length of stay were also associated with nonwhite race/ethnicities, lowest-quartile annual household income, Medicaid or no insurance, and having a higher number of chronic conditions. Conclusions There are significant racial/ethnic and socioeconomic differences between patients hospitalized with AD versus without it, suggesting that there may be racial/ethnic and/or health care disparities in AD.

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Pet Consort Dermatitis: The Importance of Asking About Pets

No abstract available

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Contact Dermatitis Associated With Skin Cleansers: Retrospective Analysis of North American Contact Dermatitis Group Data 2000–2014

Background There is limited information regarding contact dermatitis (CD) associated with skin cleansers (SCs). Objective The aim of the study was to evaluate the prevalence of allergic patch test (APT) reactions and irritant CD (ICD) associated with SCs. Methods A retrospective cross-sectional analysis was performed using North American Contact Dermatitis Group data, 2000–2014. Results Of 32,945 tested patients, 1069 (3.24%) had either APT reaction or ICD associated with SCs. Of these, 692 (64.7%) had APT reaction only, 350 (32.7%) had ICD only, and 27 (2.5%) had both. Individuals with APT reaction and/or ICD were more likely to have occupationally related skin disease (relative risk [RR] = 3.8 [95% confidence interval {CI} = 3.3–4.5] for APT reaction and 10.0 [95% CI = 8.2–12.2] for ICD, respectively, P

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Consumer Hair Dye Kits Frequently Contain Isothiazolinones, Other Common Preservatives and Fragrance Allergens

No abstract available

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Shiitake Dermatitis After Consumption of Homemade Soup

No abstract available

http://ift.tt/2EPe5sL

Comparison of Contact Allergens in Bar Soaps and Liquid Body Washes

No abstract available

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The Diagnostic Value of Impulse Oscillometry and Plethysmography for the Assessment of Exercise-Induced Bronchoconstriction in Asthmatic Children

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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In This Issue [This Week in PNAS]

Perineuronal nets and recall of distant fear memories PNN (green) around a parvalbumin-expressing inhibitory neuron (red) in rat V2L. Perineuronal nets (PNN) are gauzy, carbohydrate-rich structures that envelop subsets of neurons in the central nervous system, forming a long-lived extracellular matrix that stabilizes synaptic connections between neurons. PNNs are thought...

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Action of steroids and plant triterpenoids on CatSper Ca2+ channels in human sperm [Biological Sciences]

The sperm-specific Ca2+ channel CatSper (cation channel of sperm) controls the intracellular Ca2+ concentration and, thereby, the swimming behavior of sperm. Human CatSper is activated by progesterone (1, 2), an oviductal hormone, which stimulates Ca2+ influx and motility responses. By patch-clamp recording from human sperm, Mannowetz et al. (3) studied...

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Silk-based multilayered angle-ply annulus fibrosus construct to recapitulate form and function of the intervertebral disc [Medical Sciences]

Recapitulation of the form and function of complex tissue organization using appropriate biomaterials impacts success in tissue engineering endeavors. The annulus fibrosus (AF) represents a complex, multilamellar, hierarchical structure consisting of collagen, proteoglycans, and elastic fibers. To mimic the intricacy of AF anatomy, a silk protein-based multilayered, disc-like angle-ply construct...

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Reply to Brenker et al.: The plant triterpenoid pristimerin inhibits calcium influx into human spermatozoa via CatSper [Biological Sciences]

In the letter by Brenker et al. (1), the authors assessed actions of various steroids toward the human calcium channel of sperm (CatSper). The experiments, carried out with calcium imaging, are minimally supplemented by electrophysiology. The authors show that all tested steroids activate CatSper with different efficiencies. However, the plant...

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Cargo navigation across 3D microtubule intersections [Biophysics and Computational Biology]

The eukaryotic cell's microtubule cytoskeleton is a complex 3D filament network. Microtubules cross at a wide variety of separation distances and angles. Prior studies in vivo and in vitro suggest that cargo transport is affected by intersection geometry. However, geometric complexity is not yet widely appreciated as a regulatory factor...

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Considering hypertonicity in the interpretation and analysis of cell type-specific gene expression pattern in the collecting duct [Biological Sciences]

The different parts of the renal nephron have different functions that are related to reabsorption or secretion processes. This is mediated by genes that show a distinct expression pattern along the renal nephron segments (1). The majority of the segments contain only one epithelial cell type. However, the collecting duct...

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Localizing softness and stress along loops in 3D topological metamaterials [Physics]

Topological states can be used to control the mechanical properties of a material along an edge or around a localized defect. The rigidity of elastic networks is characterized by a topological invariant called the polarization; materials with a well-defined uniform polarization display a dramatic range of edge softness depending on...

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Reply to Edemir: Physiological regulation and single-cell RNA sequencing [Biological Sciences]

Tacitly, Edemir (1) points to an important issue in the interpretation of data from single-cell RNA-sequencing experiments. Any given cell can exist in a variety of regulatory states that are affected both by extracellular signals and the prior history of the cell. Consequently, data from single-cell RNA sequencing, such as...

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Slow domain reconfiguration causes power-law kinetics in a two-state enzyme [Biophysics and Computational Biology]

Protein dynamics are typically captured well by rate equations that predict exponential decays for two-state reactions. Here, we describe a remarkable exception. The electron-transfer enzyme quiescin sulfhydryl oxidase (QSOX), a natural fusion of two functionally distinct domains, switches between open- and closed-domain arrangements with apparent power-law kinetics. Using single-molecule FRET...

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Profile of David M. Sabatini [Profile]

As a young doctoral candidate at the Johns Hopkins University School of Medicine, David M. Sabatini was allowed to choose his own research project for his thesis. He chose to investigate the molecular mechanism of rapamycin, a compound with antifungal, antitumor, and immunosuppressant properties. The decision was pivotal, because Sabatini...

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Aridity weakens population-level effects of multiple species interactions on Hibiscus meyeri [Ecology]

Predicting how species' abundances and ranges will shift in response to climate change requires a mechanistic understanding of how multiple factors interact to limit population growth. Both abiotic stress and species interactions can limit populations and potentially set range boundaries, but we have a poor understanding of when and where...

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Profile of Joachim Frank, Richard Henderson, and Jacques Dubochet, 2017 Nobel Laureates in Chemistry [Profile]

In 2017, the Nobel Prize in Chemistry was awarded to three key pioneers in the birth and development of cryoelectron microscopy (cryo-EM): Jacques Dubochet, Joachim Frank, and Richard Henderson. As a starting graduate student in England, moving from physics to biology and the study of macromolecular structure, I had the...

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Somatostatin and parvalbumin inhibitory synapses onto hippocampal pyramidal neurons are regulated by distinct mechanisms [Neuroscience]

Excitation–inhibition balance is critical for optimal brain function, yet the mechanisms underlying the tuning of inhibition from different populations of inhibitory neurons are unclear. Here, we found evidence for two distinct pathways through which excitatory neurons cell-autonomously modulate inhibitory synapses. Synapses from parvalbumin-expressing interneurons onto hippocampal pyramidal neurons are regulated...

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Microbial proteins for organic material degradation in the deep ocean [Ecology]

Organic material is synthesized in the sunlit surface layer of the oceans and that is where most of it is decomposed back to carbon dioxide and other inorganic constituents. However, a small fraction escapes immediate degradation and makes its way into deeper waters, some as far as the bottom thousands...

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Engineering posttranslational proofreading to discriminate nonstandard amino acids [Systems Biology]

Incorporation of nonstandard amino acids (nsAAs) leads to chemical diversification of proteins, which is an important tool for the investigation and engineering of biological processes. However, the aminoacyl-tRNA synthetases crucial for this process are polyspecific in regard to nsAAs and standard amino acids. Here, we develop a quality control system...

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Endless skulls most beautiful [Evolution]

The amazing disparity of living birds is self-apparent, yet immensely challenging to fully quantify. After all, birds are represented by nearly 11,000 living species, comprising a mind-boggling spectrum of shapes, sizes, and colors (1). This incredible variability manifests in an incalculable number of ways (from habitat type to diet to...

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Evolution of real contact area under shear and the value of static friction of soft materials [Applied Physical Sciences]

The frictional properties of a rough contact interface are controlled by its area of real contact, the dynamical variations of which underlie our modern understanding of the ubiquitous rate-and-state friction law. In particular, the real contact area is proportional to the normal load, slowly increases at rest through aging, and...

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Searching for the neural causes of criminal behavior [Neuroscience]

All behavior is proximally caused by the brain, but the neural causes of most complex behaviors are still not understood. Much of our ignorance stems from the fact that complex behavior depends on distributed neural control. Unlike a reflex, where the arc from sensation to action can be traced through...

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Identification of a ubiquitin-binding interface using Rosetta and DEER [Biophysics and Computational Biology]

ExoU is a type III-secreted cytotoxin expressing A2 phospholipase activity when injected into eukaryotic target cells by the bacterium Pseudomonas aeruginosa. The enzymatic activity of ExoU is undetectable in vitro unless ubiquitin, a required cofactor, is added to the reaction. The role of ubiquitin in facilitating ExoU enzymatic activity is...

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Dynamics and mechanisms of intracellular calcium waves elicited by tandem bubble-induced jetting flow [Engineering]

One of the earliest events in cellular mechanotransduction is often an increase in intracellular calcium concentration associated with intracellular calcium waves (ICWs) in various physiologic or pathophysiologic processes. Although cavitation-induced calcium responses are believed to be important for modulating downstream bioeffects such as cell injury and mechanotransduction in ultrasound therapy,...

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Mittelohr

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Dank an die Gutachter 2017

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Rhinoplastik – State of the Art

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Caffeine Ingestion Attenuates Fatigue-induced Loss of Muscle Torque Complexity

ABSTRACTThe temporal structure, or complexity, of muscle torque output decreases with neuromuscular fatigue. The role of central fatigue in this process is unclear.PurposeWe tested the hypothesis that caffeine administration would attenuate the fatigue-induced loss of torque complexity.MethodsEleven healthy participants performed intermittent isometric contractions of the knee extensors to task failure at a target torque of 50% maximal voluntary contraction, with a 60% duty factor (6-s contraction, 4-s rest), 60 min after ingesting 6 mg·kg−1 caffeine or a placebo. Torque and surface EMG signals were sampled continuously. Complexity and fractal scaling of torque were quantified using approximate entropy (ApEn) and the detrended fluctuation analysis (DFA) α scaling exponent. Global, central, and peripheral fatigue was quantified using maximal voluntary contractions with femoral nerve stimulation.ResultsCaffeine ingestion increased endurance by 30% ± 16% (mean ± SD; P = 0.019). Complexity decreased in both trials (decreased ApEn, increased DFA α; both P

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Physical Fitness in Young Men between 1975 and 2015 with a Focus on the Years 2005–2015

ABSTRACTPurposeThe purpose of the present study was to investigate changes in physical fitness and anthropometry of young men entering the military service in Finland during the years 1975–2015.MethodsThe study included the fitness test results of 627,142 healthy young male conscripts (age 19.1 ± 0.4 yr). Data included results of aerobic capacity, muscle fitness tests, and anthropometric characteristics.ResultsThe results show that the increase in mean body mass of young men has slowed down during the last 10 yr. However, the total increase in body mass was 6.8 kg (8.8%, P ≤ 0.001) between 1993 and 2015. The mean distance achieved in the 12-min running test decreased by 337 m (12.2%, P ≤ 0.001) between the peak in 1980 and 2015. The relative number of conscripts who ran less than 2200 m increased from 3.6% to 25.9% (P ≤ 0.001) between 1980 and 2015, and the proportion who ran more than 3000 m decreased from 25.1% to 6.5% (P ≤ 0.001). The relative number of conscripts who achieved an excellent or good muscle fitness index decreased from 66.8% to 40.1% (P ≤ 0.001) between 1992 and 2000, and remained unchanged between 2000 and 2010. However, the proportion who achieved a poor muscle fitness index increased from 8.1% to 31.4% (P ≤ 0.001) between 1992 and 2010.DiscussionThe present study shows that the increase in mean body mass of young male conscripts has slowed down during the last 10 yr. However, their aerobic capacity has still decreased during recent decades. In addition, the proportion of conscripts with poor muscle fitness has increased. From the national defense and health perspective, more initiatives are needed to encourage young men to increase their level of daily physical activity to be fit and ready for operations. Purpose The purpose of the present study was to investigate changes in physical fitness and anthropometry of young men entering the military service in Finland during the years 1975–2015. Methods The study included the fitness test results of 627,142 healthy young male conscripts (age 19.1 ± 0.4 yr). Data included results of aerobic capacity, muscle fitness tests, and anthropometric characteristics. Results The results show that the increase in mean body mass of young men has slowed down during the last 10 yr. However, the total increase in body mass was 6.8 kg (8.8%, P ≤ 0.001) between 1993 and 2015. The mean distance achieved in the 12-min running test decreased by 337 m (12.2%, P ≤ 0.001) between the peak in 1980 and 2015. The relative number of conscripts who ran less than 2200 m increased from 3.6% to 25.9% (P ≤ 0.001) between 1980 and 2015, and the proportion who ran more than 3000 m decreased from 25.1% to 6.5% (P ≤ 0.001). The relative number of conscripts who achieved an excellent or good muscle fitness index decreased from 66.8% to 40.1% (P ≤ 0.001) between 1992 and 2000, and remained unchanged between 2000 and 2010. However, the proportion who achieved a poor muscle fitness index increased from 8.1% to 31.4% (P ≤ 0.001) between 1992 and 2010. Discussion The present study shows that the increase in mean body mass of young male conscripts has slowed down during the last 10 yr. However, their aerobic capacity has still decreased during recent decades. In addition, the proportion of conscripts with poor muscle fitness has increased. From the national defense and health perspective, more initiatives are needed to encourage young men to increase their level of daily physical activity to be fit and ready for operations.

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Exercise Prescription and Adherence for Breast Cancer: One Size Does Not FITT All

ABSTRACTPurposeTo prospectively assess adherence to oncologist-referred, exercise programming consistent with current recommendations for cancer survivors among women with early breast cancer across the trajectory of adjuvant treatment.MethodsSixty-eight women participated in supervised, hour-long, moderate-intensity, aerobic, and resistance exercise thrice per week during adjuvant chemotherapy ± radiation, with a step-down in frequency for 20 additional weeks. Adherence to exercise frequency (i.e., attendance), intensity, and time/duration, and barriers to adherence were tracked and compared during chemotherapy versus radiation, and during treatment (chemotherapy plus radiation, if received) versus after treatment.ResultsAttendance decreased with cumulative chemotherapy dose (cycles 1–2 vs cycles 3–8, cycle 3 vs cycles 7–8, all P ≤ 0.05) and was lower during chemotherapy than radiation (64% ± 25% vs 71% ± 32%, P = 0.02) and after treatment than during treatment (P

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Perioperative Coagulation Management in Liver Transplant Recipients

We review contemporary coagulation management for patients undergoing liver transplantation. A better understanding of the complex physiologic changes that occur in patients with end-stage liver disease has resulted in significant advances in anesthetic and coagulation management. A group of internationally recognized experts have critically evaluated current approaches for coagulopathy detection and management. Strategies for blood component and factor replacement have been evaluated and recommended therapies proposed. Pharmacologic treatment and prevention of coagulopathy, management of patients receiving antiplatelet medications, and the role of transesophageal echocardiography for early detection and management of thromboses are presented. Corresponding Author: Dmitri Bezinover MD., PhD, Associate Professor of Anesthesiology, Department of Anesthesiology and Perioperative Medicine, Penn State Hershey Medical Center, Penn State College of Medicine, 500 University Drive, P.O. Box 850, Hershey, PA 17033-0850 Authorship Dmitri Bezinover: Participated in research design, participated in the performance of the research; participated in writing, correction, and preparation of the final version of the manuscript. Daniel Dirkmann: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. James Findlay: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Cosmin Guta: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Matthias Hartmann: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Ramona Nicolau- Raducu: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Ahmed M. Mukhtar: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Marina Moguilevitch: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Evan Pivalizza: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. David Rosenfeld: Participated in research design, participated in the performance of the research, participated in the writing and correction of the manuscript. Fuat Saner: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Christopher Wray: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Gebhardt Wagener: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. James West: Participated in research design, participated in the performance of the research, participated in writing and correction of the manuscript. Disclosure: Dr. Fuat Saner has received honoraria for presentations not related to this project from the following companies: CSL Behring, TEM International, Biotest, Gilead, and AstraZeneca, MSD. Dr. Matthias Hartmann has received an unrestricted grant for data analyses from CSL Behring GmbH, Marburg, Germany. All other authors declare no competing interests. Funding: Authors did not receive any financial support for this work. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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In Response

No abstract available

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Valveless Trocar Systems and Respiratory Mechanics: Need for Revaluation

No abstract available

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Ultrasound in Anesthesia, Critical Care, and Pain Management: A Critic’s Review

No abstract available

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Continuous Pulse Oximetry Does Not Measure Blood Pressure

No abstract available

http://ift.tt/2FEXMQB

Evaluation of Almitrine Infusion During Veno-Venous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome in Adults

This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%–75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%–43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use. Accepted for publication November 28, 2017. Funding: None. The authors declare no conflicts of interest. The study was approved by the Ethics Review Board of the French Language Society of Critical Care Medicine (CE SRLF17-05). The Ethics Committee approved the study and waived the requirement for informed consent from the patients or patient's kin given the observational and retrospective nature of the study. Reprints will not be available from the authors. Address correspondence to Pierre Esnault, MD, Service de Réanimation, Hôpital d'Instruction des Armées Sainte Anne, Blvd Sainte Anne, 83000 Toulon France. Address e-mail to pierre.esnault@gmail.com. © 2018 International Anesthesia Research Society

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Effects of Electrical Transcutaneous Vagus Nerve Stimulation on the Perceived Intensity of Repetitive Painful Heat Stimuli: A Blinded Placebo- and Sham-Controlled Randomized Crossover Investigation

BACKGROUND: Transcutaneous vagus nerve stimulation (TVNS) is a promising treatment for acute and chronic pain. However, experimental studies yielded controversial results. We examined if TVNS reduces the perceived intensity of repetitive painful heat stimulation and temporal summation of pain (TSP) in healthy volunteers in comparison with placebo and sham stimulation, as well as no intervention. METHODS: In 4 sessions, 90 heat pulse stimuli at individual pain tolerance temperature were applied to the ventral forearm of 49 healthy volunteers (25 women) using a Contact Heat Evoked Potential Stimulator thermode (Medoc, Ramat Yishai, Israel). Pain intensity was assessed with verbal ratings on a numeric pain scale (0–100) at every tenth heat pulse. After the first session in which pain intensities without intervention were evaluated, participants completed 3 sessions in a single-blinded randomized crossover manner: (1) sham stimulation applied at the earlobes, (2) placebo stimulation (inactive device), or (3) TVNS applied at the cymbas conchae. Primary data were analyzed using analysis of variance for repeated measures and t test for paired samples. RESULTS: Pain intensity decreased during all interventions as compared to no intervention (ηp2 = 0.22, P

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In Response

No abstract available

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Comparing Methods for Cardiac Output: Intraoperatively Doppler-Derived Cardiac Output Measured With 3-Dimensional Echocardiography Is Not Interchangeable With Cardiac Output by Pulmonary Catheter Thermodilution

BACKGROUND: Estimation of cardiac output (CO) is essential in the treatment of circulatory unstable patients. CO measured by pulmonary artery catheter thermodilution is considered the gold standard but carries a small risk of severe complications. Stroke volume and CO can be measured by transesophageal echocardiography (TEE), which is widely used during cardiac surgery. We hypothesized that Doppler-derived CO by 3-dimensional (3D) TEE would agree well with CO measured with pulmonary artery catheter thermodilution as a reference method based on accurate measurements of the cross-sectional area of the left ventricular outflow tract. METHODS: The primary aim was a systematic comparison of CO with Doppler-derived 3D TEE and CO by thermodilution in a broad population of patients undergoing cardiac surgery. A subanalysis was performed comparing cross-sectional area by TEE with cardiac computed tomography (CT) angiography. Sixty-two patients, scheduled for elective heart surgery, were included; 1 was subsequently excluded for logistic reasons. Inclusion criteria were coronary artery bypass surgery (N = 42) and aortic valve replacement (N = 19). Exclusion criteria were chronic atrial fibrillation, left ventricular ejection fraction below 0.40 and intracardiac shunts. Nineteen randomly selected patients had a cardiac CT the day before surgery. All images were stored for blinded post hoc analyses, and Bland-Altman plots were used to assess agreement between measurement methods, defined as the bias (mean difference between methods), limits of agreement (equal to bias ± 2 standard deviations of the bias), and percentage error (limits of agreement divided by the mean of the 2 methods). Precision was determined for the individual methods (equal to 2 standard deviations of the bias between replicate measurements) to determine the acceptable limits of agreement. RESULTS: We found a good precision for Doppler-derived CO measured by 3D TEE, but although the bias for Doppler-derived CO by 3D compared to thermodilution was only 0.3 L/min (confidence interval, 0.04–0.58), there were wide limits of agreement (−1.8 to 2.5 L/min) with a percentage error of 55%. Measurements of cross-sectional area by 3D TEE had low bias of −0.27 cm2 (confidence interval, −0.45 to −0.08) and a percentage error of 18% compared to cardiac CT angiography. CONCLUSIONS: Despite low bias, the wide limits of agreement of Doppler-derived CO by 3D TEE compared to CO by thermodilution will limit clinical application and can therefore not be considered interchangeable with CO obtained by thermodilution. The lack of agreement is not explained by lack of agreement of the 3D technique. Accepted for publication December 7, 2017. Funding: Supported by the Department of Cardiothoracic Anaesthesiology and the Research Committee at the Heart Centre. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Karin Graeser, MD, Department of Cardiothoracic Anaesthesiology 4141, The Heart Centre, Rigshospitalet, Blegdamsvej 9, 2200 Copenhagen, Denmark. Address e-mail to Karin.graeser.01@regionh.dk. © 2018 International Anesthesia Research Society

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Update on metal-induced occupational lung disease

Purpose of review Occupational and environmental exposures to metals can result in multiple pulmonary conditions. This article will review recent epidemiologic and mechanistic studies that have enhanced our understanding of the association between particular lung diseases and exposure to specific metals. Recent findings Recent studies have broadened our understanding of the mechanisms of lung diseases such as CBD in established industries and drawn attention to conditions that may arise from exposure to metals such as indium in developing technologies. New diagnostic techniques such as elemental tissue analysis may help establish a diagnosis of metal-induced occupational lung disease. Electronic cigarette devices, environmental pollutants, and the growing use of nanoparticle-sized metals pose additional risks to workers and consumers. Summary Recognizing the risks of pulmonary disease in workers exposed to metals and performing a thorough occupational history and diagnostic work-up in patients with unexplained respiratory findings is necessary to promote understanding and prevention of metal-induced lung disease. Correspondence to Stella E. Hines, MD, MSPH, Division of Pulmonary and Critical Care Medicine and Division of Occupational and Environmental Medicine, Department of Medicine, University of Maryland School of Medicine, 11 S. Paca Street, 2nd Floor, Baltimore, MD 21201, USA. E-mail: shines@som.umaryland.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Update on metal-induced occupational lung disease

Purpose of review Occupational and environmental exposures to metals can result in multiple pulmonary conditions. This article will review recent epidemiologic and mechanistic studies that have enhanced our understanding of the association between particular lung diseases and exposure to specific metals. Recent findings Recent studies have broadened our understanding of the mechanisms of lung diseases such as CBD in established industries and drawn attention to conditions that may arise from exposure to metals such as indium in developing technologies. New diagnostic techniques such as elemental tissue analysis may help establish a diagnosis of metal-induced occupational lung disease. Electronic cigarette devices, environmental pollutants, and the growing use of nanoparticle-sized metals pose additional risks to workers and consumers. Summary Recognizing the risks of pulmonary disease in workers exposed to metals and performing a thorough occupational history and diagnostic work-up in patients with unexplained respiratory findings is necessary to promote understanding and prevention of metal-induced lung disease. Correspondence to Stella E. Hines, MD, MSPH, Division of Pulmonary and Critical Care Medicine and Division of Occupational and Environmental Medicine, Department of Medicine, University of Maryland School of Medicine, 11 S. Paca Street, 2nd Floor, Baltimore, MD 21201, USA. E-mail: shines@som.umaryland.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Sputum cytology during late phase responses to inhalation challenge with different allergens

Abstract

Background

In mouse models of allergic asthma, exposure to different allergens can trigger distinct inflammatory subtypes in the airways. We investigated if this observation extends to humans.

Methods

We compared the frequency of sputum inflammatory subtypes between mild allergic asthma subjects (n=129) exposed to different allergens in inhalation challenge tests. These tests were performed using a standardized protocol as part of clinical trials of experimental treatments for asthma, prior to drug randomization. Five allergen types were represented: the house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, ragweed, grass and cat.

Results

Of 118 individuals with a sputum sample collected before allergen challenge (baseline), 45 (38%) had paucigranulocytic, 51 (43%) eosinophilic, 11 (9%) neutrophilic and 11 (9%) mixed granulocytic sputum. Of note, most individuals with baseline paucigranulocytic sputum developed eosinophilic (48%) or mixed granulocytic (43%) sputum seven hours after allergen challenge, highlighting the dynamic nature of sputum inflammatory subtype in asthma. Overall, there was no difference in the frequency of sputum inflammatory subtypes following challenge with different allergen types. Similar results were observed at 24 hours after allergen challenge.

Conclusions

Unlike reported in mice, in humans the sputum inflammatory subtype observed after an allergen-induced asthma exacerbation is unlikely to be influenced by the type of allergen used.

This article is protected by copyright. All rights reserved.

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Hybrid Central Odontogenic Fibroma/Central Giant Cell Lesion: A Missing Report

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Dermatologic Lesions Submitted to an Oral and Maxillofacial Pathology Biopsy Service: An Analysis of 2487 Cases

Abstract

Skin lesions are often submitted to oral and maxillofacial pathology practices. The purpose of this study is to evaluate the frequency, distribution, variability, and composition of dermatologic lesions within a large oral and maxillofacial pathology biopsy service. An IRB-approved retrospective search of skin lesions diagnosed at University of Florida oral and maxillofacial pathology biopsy service between 1994 and 2015 was performed. 2487 cases were included in the study. Gender was reported in 2466 cases, of which 59% were male and 41% female. Age was provided in 2367 cases and ranged from 2 weeks to 96 years with an average of 55 years. Location was indicated in 2473 cases. Lips were the most common (41.7%), followed by face (25.3%), neck (7.4%), nose (6.5%), periorbital (5.3%), ear (4.1%), and scalp (3.8%). Of the 2487 cases, five diagnoses (actinic keratosis/cheilitis, intradermal nevus, epidermal inclusion cyst, seborrheic keratosis, and basal cell carcinoma) constituted 84.4% of the cases. 69 of 2487 cases (2.8%) resulted in dermatopathologic consultation prior to final reporting. Skin lesions accounted for ~ 1.0% of all lesions submitted to an oral and maxillofacial pathology biopsy service. This study found a large variation in the dermatologic lesions submitted to an oral pathology biopsy service. Although most were routine in complexity, dermatopathology consultation was an important tool in the diagnosis of the more challenging cases. This study may help pathologists gain a better understanding of the frequency and variability of dermatologic lesions submitted to an oral and maxillofacial pathology biopsy service and promote more interdisciplinary consultation within the field. This study evaluated the incidence and scope of dermatologic lesions submitted to a large oral and maxillofacial pathology biopsy service over a long time period. A wide scope of lesions was found, and dermatopathology consultation was important to quality assurance.

http://ift.tt/2ENYKcd

Hybrid Central Odontogenic Fibroma/Central Giant Cell Lesion: A Missing Report

http://ift.tt/2FGb4fN

Dermatologic Lesions Submitted to an Oral and Maxillofacial Pathology Biopsy Service: An Analysis of 2487 Cases

Abstract

Skin lesions are often submitted to oral and maxillofacial pathology practices. The purpose of this study is to evaluate the frequency, distribution, variability, and composition of dermatologic lesions within a large oral and maxillofacial pathology biopsy service. An IRB-approved retrospective search of skin lesions diagnosed at University of Florida oral and maxillofacial pathology biopsy service between 1994 and 2015 was performed. 2487 cases were included in the study. Gender was reported in 2466 cases, of which 59% were male and 41% female. Age was provided in 2367 cases and ranged from 2 weeks to 96 years with an average of 55 years. Location was indicated in 2473 cases. Lips were the most common (41.7%), followed by face (25.3%), neck (7.4%), nose (6.5%), periorbital (5.3%), ear (4.1%), and scalp (3.8%). Of the 2487 cases, five diagnoses (actinic keratosis/cheilitis, intradermal nevus, epidermal inclusion cyst, seborrheic keratosis, and basal cell carcinoma) constituted 84.4% of the cases. 69 of 2487 cases (2.8%) resulted in dermatopathologic consultation prior to final reporting. Skin lesions accounted for ~ 1.0% of all lesions submitted to an oral and maxillofacial pathology biopsy service. This study found a large variation in the dermatologic lesions submitted to an oral pathology biopsy service. Although most were routine in complexity, dermatopathology consultation was an important tool in the diagnosis of the more challenging cases. This study may help pathologists gain a better understanding of the frequency and variability of dermatologic lesions submitted to an oral and maxillofacial pathology biopsy service and promote more interdisciplinary consultation within the field. This study evaluated the incidence and scope of dermatologic lesions submitted to a large oral and maxillofacial pathology biopsy service over a long time period. A wide scope of lesions was found, and dermatopathology consultation was important to quality assurance.

http://ift.tt/2ENYKcd

A Rare Case of Eosinophilic Granulomatosis with Polyangiitis Associated with Cryoglobulinemia Presenting with a Bullous Skin Eruption of the Lower Limbs

Background. Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody- (ANCA-) associated small vessel vasculitis with multisystem involvement. It is characterized with asthma, eosinophilia, and renal and peripheral nervous system involvement. However, EGPA presenting with bullous skin eruption is an uncommon dermatological manifestation. We report a rare case of EGPA overlapped with mixed essential cryoglobulinemia presenting with a bullous skin eruption. Case Presentation. A 49-year-old female presented with bilateral lower limb erythematous bullous rash with bilateral lower limb numbness. She had bilateral ankle edema with frothyuria and a recent onset wheeze. Blood investigations revealed a marked peripheral eosinophilia with positive P-ANCA. Skin biopsy was suggestive of leukocytoclastic vasculitis. She also had positive cryoglobulins with a high rheumatoid factor titre. The patient was diagnosed of having EGPA with overlapping mixed essential cryoglobulinemia. Her skin eruptions and systemic manifestations improved with prednisolone and cyclophosphamide therapy. Conclusion. EGPA can rarely present with a bullous skin eruption and may rarely associate with secondary cryoglobulinemia. Early recognition of these rare manifestations and prompt treatment would prevent further complications and death.

http://ift.tt/2FHq7pH

Study Title: Peri-operative Immuno-Chemotherapy in Operable Oesophageal and Gastric Cancer

Conditions:   Gastric Adenocarcinoma;   Oesophageal Adenocarcinoma
Intervention:   Drug: FOLFOX-A
Sponsors:   Royal Marsden NHS Foundation Trust;   Merck Serono International SA
Recruiting

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Hybrid Central Odontogenic Fibroma/Central Giant Cell Lesion: A Missing Report

http://ift.tt/2FGb4fN

Dermatologic Lesions Submitted to an Oral and Maxillofacial Pathology Biopsy Service: An Analysis of 2487 Cases

Abstract

Skin lesions are often submitted to oral and maxillofacial pathology practices. The purpose of this study is to evaluate the frequency, distribution, variability, and composition of dermatologic lesions within a large oral and maxillofacial pathology biopsy service. An IRB-approved retrospective search of skin lesions diagnosed at University of Florida oral and maxillofacial pathology biopsy service between 1994 and 2015 was performed. 2487 cases were included in the study. Gender was reported in 2466 cases, of which 59% were male and 41% female. Age was provided in 2367 cases and ranged from 2 weeks to 96 years with an average of 55 years. Location was indicated in 2473 cases. Lips were the most common (41.7%), followed by face (25.3%), neck (7.4%), nose (6.5%), periorbital (5.3%), ear (4.1%), and scalp (3.8%). Of the 2487 cases, five diagnoses (actinic keratosis/cheilitis, intradermal nevus, epidermal inclusion cyst, seborrheic keratosis, and basal cell carcinoma) constituted 84.4% of the cases. 69 of 2487 cases (2.8%) resulted in dermatopathologic consultation prior to final reporting. Skin lesions accounted for ~ 1.0% of all lesions submitted to an oral and maxillofacial pathology biopsy service. This study found a large variation in the dermatologic lesions submitted to an oral pathology biopsy service. Although most were routine in complexity, dermatopathology consultation was an important tool in the diagnosis of the more challenging cases. This study may help pathologists gain a better understanding of the frequency and variability of dermatologic lesions submitted to an oral and maxillofacial pathology biopsy service and promote more interdisciplinary consultation within the field. This study evaluated the incidence and scope of dermatologic lesions submitted to a large oral and maxillofacial pathology biopsy service over a long time period. A wide scope of lesions was found, and dermatopathology consultation was important to quality assurance.

http://ift.tt/2ENYKcd

Evening Hours May Pose Higher Risk for Overeating, Especially When Under Stress, Study Finds

Experiments with a small group of overweight men and women have added to evidence that "hunger hormone" levels rise and "satiety (or fullness) hormone" levels decrease in the evening. The findings also suggest that stress may increase hunger hormone levels more in the evening, and the impact of hormones on appetite may be greater for people prone to binge eating.

http://ift.tt/2mBWxJp

Numerical simulation of two consecutive nasal respiratory cycles: toward a better understanding of nasal physiology

Background

Computational fluid dynamic (CFD) simulations have greatly improved the understanding of nasal physiology. We postulate that simulating the entire and repeated respiratory nasal cycles, within the whole sinonasal cavities, is mandatory to gather more accurate observations and better understand airflow patterns.

Methods

A 3-dimensional (3D) sinonasal model was constructed from a healthy adult computed tomography (CT) scan which discretized in 6.6 million cells (mean volume, 0.008 mm³). CFD simulations were performed with ANSYS©FluentTMv16.0.0 software with transient and turbulent airflow (k-ω model). Two respiratory cycles (8 seconds) were simulated to assess pressure, velocity, wall shear stress, and particle residence time.

Results

The pressure gradients within the sinus cavities varied according to their place of connection to the main passage. Alternations in pressure gradients induced a slight pumping phenomenon close to the ostia but no movement of air was observed within the sinus cavities. Strong movements were observed within the inferior meatus during expiration contrary to the inspiration, as in the olfactory cleft at the same time. Particle residence time was longer during expiration than inspiration due to nasal valve resistance, as if the expiratory phase was preparing the next inspiratory phase. Throughout expiration, some particles remained in contact with the lower turbinates. The posterior part of the olfactory cleft was gradually filled with particles that did not leave the nose at the next respiratory cycle. This pattern increased as the respiratory cycle was repeated.

Conclusion

CFD is more efficient and reliable when the entire respiratory cycle is simulated and repeated to avoid losing information.

http://ift.tt/2B4V3fZ

Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non-eosinophilic chronic rhinosinusitis

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2 phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue eosinophilia and easily recurrent, is distinguished from other non-eosinophilic CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear.

Methods

Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis. Bioinformatics approaches (eg, Ingenuity Pathway Analysis [IPA]) were used to interrogate the data sets.

Results

Hierarchical clustering and principal component analysis (PCA) collectively showed that ECRSwNP and NECRSwNP had distinct gene expression patterns. Of note, these genes could be divided into 8 distinctive clusters having different expression patterns and functions. Upstream Regulator Analysis revealed that not only T-helper 2 (Th2) and the eosinophilia–related molecules (interleukin 4 [IL4], IL5, and colony stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a tissue fibrosis–related molecule (transforming growth factor β [TGFβ]) were identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in NECRSwNP.

Conclusion

These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP.

http://ift.tt/2DikKjf