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Τετάρτη 17 Ιανουαρίου 2018

Analysis of metal tolerance in Rhizobium leguminosarum strains isolated from an ultramafic soil

Abstract
Natural habitats containing high amounts of heavy metals provide a valuable source of bacteria adapted to deal with metal toxicity. A functional analysis of the population of legume endosymbiotic bacteria in an ultramafic soil was undertaken by studying a collection of Rhizobium leguminosarum bv viciae (Rlv) isolates obtained using pea as trap plant. One of the isolates, Rlv UPM1137, was selected on the basis of its higher tolerance to nickel and cobalt and presence of inducible mechanisms for such tolerance. A random transposon mutagenesis of Rlv UPM1137 allowed the generation of fourteen transposant derivatives with increased nickel sensitivity; five of these transposants were also more sensitive to cobalt. Sequencing of the insertion sites revealed that one of the transposants (D2250) was affected in a gene homologous to the Cation Diffusion Facilitator (CDF) gene dmeF first identified in the metal-resistant bacterium Cupriavidus metallidurans CH34. The symbiotic performance of D2250 and two other transposants bearing single transposon insertions was unaffected under high metal conditions, suggesting that, in contrast to previous observations in other Rlv strain, metal tolerance in UPM1137 under symbiotic conditions might be supported by functional redundancy between several mechanisms.

The unexpected function of a Flavin-dependent oxidoreductase (Fox) from Variovorax paradoxus TBEA6.

Abstract
3,3'-Thiodipropionic acid (TDP) is used as an additive in food and cosmetic industry and as precursor substrate for biotechnical polythioester production. Its catabolism was investigated in Variovorax paradoxus TBEA6 previous to this study. It was reported that the insertion of the transposon Tn5::mob into a gene showing high homology to flavin-dependent oxidoreductases (fox) resulted in impaired growth with TDP. Therefore, it was assumed that the initial cleavage of TDP is catalyzed by an FAD-dependent oxidoreductase (Fox, VPARA_05580). Accordingly, fox was heterologously expressed as a thioredoxin fusion protein. Analytical size exclusion chromatography revealed a homodimeric structure and the presence of the cofactor FAD. In vitro experiments showed that FoxTBEA6 is a D-2-hydroxy acid specific dehydrogenase and that its activity is enhanced in presence of either Ni2+, Co2+ or Zn2+. Cleavage of TDP by FoxTBEA6 was not observed. The findings are contrary to restricted growth with TDP of the transposon mutants and the previously published deletion mutant V. paradoxus TBEA6 Δfox. In this study, this contradiction was investigated by generation of additional deletion mutants, in which partial or complete deletion of fox did not affect utilization of TDP, and the mapping of single nucleotide polymorphisms (SNPs) in V. paradoxus TBEA6 Δfox.

Is consciousness intrinsically valuable?

Abstract

There are some things that we think are intrinsically valuable, or valuable for their own sake. Is consciousness—subjective, qualitative experience—one of those things? Some theorists favor the positive view, according to which consciousness is intrinsically valuable. According to a positive theorist, consciousness itself accrues intrinsic value, independent of the particular kind of experience instantiated. In contrast, I favor the neutral view, according to which consciousness is neither intrinsically valuable nor disvaluable. The primary purpose of this paper is to clarify what is at stake when we ask whether consciousness is intrinsically valuable, to carve out the theoretical space, and to evaluate the question rigorously. The secondary purpose is to show why the neutral view is attractive and why certain arguments for the positive view do not work.



Introspecting knowledge

Abstract

If we use "introspection" just as a label for that essentially first-person way we have of knowing about our own mental states, then it's pretty obvious that if there is such a thing as introspection, we know on that basis what we believe, and want, and intend, at least in many ordinary cases. I assume there is such a thing as introspection. So I think the hard question is how it works. But can you know that you know on the basis of introspection? Well, that all depends on how introspection works. I present one account of how introspection works and argue that on that account, you can know that you know ordinary empirical things on the basis of introspection. As far as how we know about them is concerned, there's no principled difference between the factive and non-factive mental states.



Calcium hydroxylapatite treatment of human skin: evidence of collagen turnover through picrosirius red staining and circularly polarized microscopy



Aicardi-Goutières syndrome: cold-induced acral blemish is not always cryoglobulinaemic vasculitis or chilblain lupus



Subcutaneous basal cell carcinoma



Dermoscopy of basal cell carcinoma

Summary

Dermoscopy is widely used in dermatological practice. The method increases the accuracy of basal cell carcinoma (BCC) detection. Pigmented and nonpigmented variants of basal cell carcinoma present different dermoscopic features. Specific dermoscopy criteria have been recognized in different subtypes of BCC. Differentiation of superficial BCC from other subtypes is the most important issue, as it may determine further management decisions.



Acute generalized exanthematous pustulosis induced by a digestive enzyme drug, Festal®



The relationship between target joints and direct resource use in severe haemophilia

Target joints are a common complication of severe haemophilia. While factor replacement therapy constitutes the majority of costs in haemophilia, the relationship between target joints and non drug-related dir...

Hair Cortisol is Elevated in Erythropoietic Protoporphyria Patients and Correlates with Body Mass Index and Quality of Life



Entartungsrisiko von gutartigen Knochenläsionen

Zusammenfassung

Ziel

Benigne Knochenläsionen wie einige Tumoren oder nichtneoplastische Läsionen besitzen in bestimmten Fällen ein nicht unerhebliches Risiko einer malignen Entartung. Das Wissen um dieses ist wesentlich, da die Patientenberatung und -führung entsprechend angepasst werden muss. Ziel dieser Arbeit ist es, die typischen Läsionen aufzuzeigen sowie das relative Risiko und den potenziellen Verlauf darzustellen.

Material und Methoden

Aus der vorhandenen Literatur und der klinischen Erfahrung wurden jene Knochenläsionen benannt, bei denen ein Potenzial zur sekundären Malignisierung besteht oder vermutet wird. Dieses wurde dann in einer dezidierten Literaturrecherche evaluiert.

Ergebnisse

Belege für die Dedifferenzierung oder sekundäre Malignität fanden sich für kartilaginäre Exostosen, Enchondromatose, Morbus Paget, fibröse Dysplasie, osteofibröse Dysplasie, Knocheninfarkt, Osteomyelitis und die synoviale Chondromatose. Für den notochordalen Tumor, das Osteoblastom und die aneurysmale Knochenzyste ist die Datenlage zu gering, um eine solche zu postulieren.

Schlussfolgerung

Es gibt benigne Läsionen, die in einer Inzidienz von bis zu 40 % in ein sekundäres Malignom übergehen können. Dieses muss in der Patientenberatung vermittelt werden. Geeignete Vorsorgeuntersuchungen, wie z. B. das Ganzkörper-MRT bei den multiplen chondroiden Läsionen, sind aufwendig, in diesen Fällen jedoch auch zu rechtfertigen.



Multicenter French harmonization study for PD-L1 IHC testing in non-small cell lung cancer

Abstract
Background
Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT).
Methods
IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers), platforms. For each matching platform, 22C3, 28-8 and SP263 assays were performed. For non-matching platforms and other antibodies, LDT were developed in each center. A total of 35 stainings were performed for each case across different platforms and antibodies. PD-L1 staining was assessed in tumor cells and immune cells by seven trained thoracic pathologists. For statistical analysis, 1%, 50% and 1%, 5%, 10% expression thresholds were used for tumor cells and immune cells, respectively.
Results
28-8, 22C3 and SP263 assays were highly concordant for tumor cells staining across the 5 Dako or Ventana platforms. Among 27 LDT developed in 7 centers on Dako, Ventana and Leica platforms, 14 (51.8%) demonstrated similar concordance as compared to reference assays for tumor cell staining. Clone SP263 achieved the highest concordance rate across all platforms.Lower concordance was observed for immune cells staining when using a 4-categories scale.
Conclusion
28-8, 22C3 and SP263 assays had close analytical performance for tumor cell staining across 7 centers. Some LDT on Dako, Ventana and Leica platform achieved similar concordance, but caution is warranted for their validation. These LDT will be further validated in order to provide recommendations for the use of assays and LDT for PD-L1 testing in NSCLC.

A mutational signature associated with alcohol consumption and prognostically significantly mutated driver genes in esophageal squamous cell carcinoma

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced and incurable stage. Information on driver genes and prognosticators in ESCC remains incomplete. The objective was to elucidate significantly mutated genes (SMGs), mutational signatures, and prognosticators in ESCC.
Patients and Methods
Three MutSig algorithms (i.e. MutSigCV, MutSigCL and MutSigFN) and "20/20+" ratio-metric were employed to identify SMGs. Nonnegative matrix factorization was used to decipher mutational signatures. Kaplan-Meier survival analysis, multivariate Cox and logistic regression models were applied to analyze association between mutational features and clinical parameters.
Results
We identified 26 SMGs, including eight novel (NAV3, TENM3, PTCH1, TGFBR2, RIPK4, PBRM1, USP8 and BAP1) and 18 that have been previously reported. Three mutational signatures were identified to be prevalent in ESCC including clocklike C>T at CpG, APOBEC overactive C>T at TpCp[A/T], and a signature featured by T>C substitution. The T>C mutational signature was significantly correlated with alcohol consumption (OR: 3.59; 95% CI: 2.30-5.67; P < 0.001). This alcohol consumption signature was also observed in liver cancer and head and neck squamous cell carcinoma, and its mutational activity was substantially higher in samples with mutations in TP53. Survival analysis revealed that TENM3 mutations (HR: 5.54; CI: 2.68-11.45; P < 0.001) and TP53 hotspot mutation p.R213* (HR: 3.37; CI: 1.73-8.06; P < 0.001) were significantly associated with shortened survival outcome. The association remained statistically significant after controlling for age, gender, TNM stage and tumor grade.
Conclusions
We have uncovered several new SMGs in ESCC and defined an alcohol consumption related mutational signature. TENM3 mutations and the TP53 hotspot mutation p.R213* are independent prognosticators for poor survival in ESCC.

In reply to “Concurrent Cisplatin and radiotherapy versus Cetuximab and radiotherapy, an unsolved problem” by Guler et al.



Joint Adolescent - Adult Early Phase Clinical Trials to Improve Access to New Drugs for Adolescents with Cancer Proposals from the Multi-stakeholder Platform - ACCELERATE

Abstract
The impressive progress recently observed in adult cancers through the introduction of new drugs has not yet been translated to adolescents between 12 and 17 years of age. Currently adolescents are grouped with children, so their access to new, effective drugs already available for adults is delayed because paediatric drug development starts late relative to adult programmes. Moreover, specific early phase trials designed exclusively for adolescents in rare diseases recruit poorly, even if conducted internationally. Evidence has shown that adolescents demonstrate similar toxicity profiles, maximum tolerated doses and pharmacokinetic parameters to adults. Although they may have specific vulnerabilities and their interests should be protected, they are, in many countries in Europe, entitled to provide informed consent themselves. There are no insurmountable scientific, medical, or regulatory barriers to their participation in Phase-I to III adult trials. Based on a review of the literature, the multi-stakeholder platform ACCELERATE, with representatives from academia, patient/parent advocacy groups, regulatory agencies and pharmaceutical companies, proposes the inclusion of adolescents in adult Phase-I to III trials of cancer drugs targeting a relevant disease or mechanism of action, without requiring preceding specific paediatric trials. The trials, however, should be delivered in age-appropriate clinical care settings by clinicians with adolescent trial expertise. Joint adolescent-adult trials will not exclude adolescents from participating in paediatric trials, as these approaches are complementary. This strategy is considered to be safe, rational, efficient and would provide more clinical trial options and accelerate drug development for adolescents with cancer.

Critical appraisal of the oxidative stress pathway in vitiligo: a systematic review and meta-analysis

Abstract

Background

The pathogenesis of vitiligo remains a topic of extensive debate. This is partly due to the moderate efficacy of current treatments. The role of oxidative stress pathway in vitiligo is a popular although controversial research topic.

Objective

To clarify the role of the oxidative stress pathway in vitiligo compared to other inflammatory skin disorders and to assess the therapeutic role of antioxidants.

Methods

We conducted a systematic search of the existing literature on the aberrancies of the oxidative stress pathway in vitiligo. Subsequently, the efficacy of both topical and oral antioxidants in clinical trials was investigated.

Results

A deregulated oxidative pathway is clearly evident with elevated superoxide dismutase (SOD), decreased catalase (CAT) and increased lipid peroxidation. However, similar results have been obtained in other inflammatory skin diseases such as psoriasis, atopic dermatitis, lichen planus and urticaria. This questions the unique role of oxidative stress in the development of vitiligo. Some isolated successes have been reported with oral ginkgo biloba, polypodium leucotomos and vitamin C and E preparations, while other clinical trials have failed to show reproducible results. The use of topical antioxidants delivers in general no beneficial results.

Conclusion

The oxidative pathway is affected in vitiligo but its unique initiating or contributory role in the pathogenesis is less evident. Interesting data support the added value of oral antioxidants in vitiligo although confirmatory studies are missing.

This article is protected by copyright. All rights reserved.



Atypical presentation of eosinophilic annular erythema in a 5-year old girl

Abstract

A 5-year-old female presented with a 1-year history of slightly pruritic erythematous annular plaques covering her trunk and limbs (Figure 1). The remaining integument as wells as the mucous membranes were not affected. The lesions persisted for about one week slowly developing a more violaceous hue before disappearing.

This article is protected by copyright. All rights reserved.



Dermoscopy versus reflectance confocal microscopy for the diagnosis of lentigo maligna

Abstract

Background

Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques.

Objective

We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images.

Methods

223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination were compared. Inter-investigator variability and confidence level in the diagnosis were also evaluated.

Results

Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, versus 61%) and less specific (81% versus 92%) than dermoscopy for LM/LMM. In particular RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher inter-investigator agreement and a higher confidence level in the diagnosis than dermoscopy.

Conclusion

RCM and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM.

This article is protected by copyright. All rights reserved.



Socioeconomic Deprivation and the Burden of Head and Neck Cancer- Regional variations of Incidence and Mortality in Merseyside and Cheshire, North West, England

Abstract

Objectives

The aim of this longitudinal study is to examine the distribution of head and neck cancer (HANC) disease burden across the region comparing it to national trends.

Design

We undertook a retrospective study of routine data combining it with indicators of deprivation and lifestyle at small geographical areas within the nine Local Authorities (LAs) of Merseyside and Cheshire Network (MCCN)for head and neck cancers.

Data from the North West of England and England were used as comparator regions.

Setting

This research was undertaken by the Cheshire and Merseyside Public Health Collaborative, UK.

Participants

The Merseyside and Cheshire Region serves a population of 2.2 million. Routine data allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and C30-C32 within three cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis.

Main Outcome Measures

Directly age standardised incidence rates and directly age standardised mortality rates in the LAs and comparator regions were measured. Lifestyle and deprivation indicators were plotted against themand measured by Pearson's correlation coefficients.

Results

The incidence of head and neck cancer has increased across the region from 1998-2000 to 2008-2010 with a peak incidence for Liverpool males at 35/100,000 population.

Certain Middle Super Output Areas contribute disproportionately to the significant effect of incidence and mortality within LAs. Income deprivation had the strongest correlation with incidence (r =0.59) and mortality (r =0.53) of head and neck cancer.

Conclusion

Our study emphasizes notable geographical variations within the region which need to be addressed through public health measures

This article is protected by copyright. All rights reserved.



Τρίτη 16 Ιανουαρίου 2018

False-positive result when a diphenylcarbazide spot test is used on trivalent chromium-passivated zinc surfaces

Summary

Background

A colorimetric 1,5-diphenylcarbazide (DPC)-based spot test can be used to identify hexavalent chromium on various metallic and leather surfaces. DPC testing on trivalent chromium-passivated zinc surfaces has unexpectedly given positive results in some cases, apparently indicating the presence of hexavalent chromium; however, the presence of hexavalent chromium has never been confirmed with more sensitive and accurate test methods.

Objectives

To examine the presence of hexavalent chromium on trivalent chromium-passivated zinc surfaces with a DPC-based spot test.

Methods

A colorimetric DPC spot test was used for the initial detection of hexavalent chromium on new and 1-year-aged trivalent chromium-passivated zinc surfaces. Then, X-ray photoelectron spectroscopy (XPS) was performed for all samples.

Results

The DPC spot test indicated the presence of hexavalent chromium in aged, but not new, trivalent chromium passivation on zinc; however, subsequent analysis by XPS could not confirm the presence of chromium in a hexavalent state.

Conclusions

Unintended oxidation of DPC induced by atmospheric corrosion is suggested as a possible reason for the false-positive reaction of the DPC test on a trivalent chromium-passivated zinc surface. Further validation of the use of the DPC test for chromium-containing metallic surfaces is required.



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.



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.



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.



Systemic delayed hypersensitivity reaction to chlorambucil: a case report and literature review



Comparing patch test results of methylchloroisothiazolinone/methylisothiazolinone tested with both TRUE Test® and 100 ppm using investigator-loaded chambers



First case report of acute generalized exanthematous pustulosis (AGEP) caused by gadolinium confirmed by patch testing



Allergic contact dermatitis caused by hydroxyacetophenone in a face cream



Allergic contact dermatitis caused by Olanedine® (olanexidine gluconate), a new antiseptic



Is p-phenylenediamine a marker of sulfasalazine allergy?



First report of allergic contact dermatitis caused by sorbitan caprylate



Baboon syndrome caused by anti-haemorrhoidal ointment



Erythema of the penis after use of a latex condom – latex allergy or something else?



Issue Information



‘Chaturthy fingers’ caused by Hibiscus rosasinensis



Fungal kerion of the vulva



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.



Occupational allergic respiratory disease (rinoconjunctivitis and asthma) in a cheese factory worker

Publication date: Available online 17 January 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Elisa Gómez Torrijos, Carmen García Rodriguez, Beatriz Veleiro Pérez, Borja Bartolomé, Marcos Prado Barragan, Rosa Garcia Rodriguez




Increased Use of Adrenaline in the Management of Childhood Anaphylaxis Over the Last Decade

Publication date: Available online 17 January 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Kristina Rueter, Brennan Ta, Natasha Bear, Michaela Lucas, Meredith L. Borland, Susan L. Prescott
BackgroundWe recently determined that allergy training programs have improved physician recognition and diagnosis of pediatric anaphylaxis in the last decade.ObjectiveTo investigate for changes in management, in particular the appropriate use of adrenaline for the treatment of anaphylaxis in a tertiary pediatric emergency department (PED).MethodsWe conducted a retrospective case note study including children aged 0 to 16 years coded and verified for anaphylaxis comparing cases in years 2003/2004 with 2012. This included standardized information on clinical presentation, demographic characteristics, vital signs, mode of transport, and management of anaphylaxis including the use of adrenaline and/or adjunct therapy. Follow-up management plans were also recorded.ResultsIn 2003/2004, a total of 92 cases were coded and verified for anaphylaxis from 83,832 PED presentations compared with 159 cases from 71,822 PED presentations in 2012. A significantly higher proportion of cases were appropriately managed with adrenaline in 2012 compared with 2003/2004, when intensive training programs had not yet been introduced (P = .03). Vital signs were more frequently documented in 2012 (P < .001) than in 2003/2004, and there was significantly less administration of other medications (corticosteroids, bronchodilators, and antihistamines) (P < .05). Also, changes in discharge management occurred with an improved dispensing/prescription of adrenaline autoinjectors and more frequent follow-up arrangement with specialist allergy services (P < .001).ConclusionsThere was a significant improvement in the management of anaphylaxis over this 10-year period. This change was observed after the introduction of intensified physician training programs in which anaphylaxis management was a key component highlighting the importance of cooperation between pediatric emergency and allergy services.



Travelers’ diarrhea in Thailand: a quantitative analysis using TaqMan® Array Card

Abstract
Background
Travelers' diarrhea (TD) is a common illness experienced by travelers from developed countries visiting developing countries. Recent questionnaire-based surveillance studies reported that approximately 6–16% of travelers experienced TD while visiting Thailand; however, a majority of TD information was limited mainly to US military populations.
Methods
A TD surveillance study was conducted at Bumrungrad International Hospital in 2012–2014 in Bangkok, Thailand. Enteropathogens were identified by conventional methods and TaqMan® Array Card (TAC) which employs real-time PCR for the simultaneous detection of multiple pathogens. Analyses to determine pathogen-disease and symptoms association were performed to elucidate the clinical relevance of each enteropathogen.
Results
TAC identified more pathogens per sample than conventional methods. Campylobacter spp. were the most prevalent, followed by the diarrheagenic Escherichia coli, and norovirus GII. These agents had significant pathogen-disease associations as well as high attributable fractions (AF) among diarrheal cases. A wide range of pathogen loads for Campylobacter spp. was associated with TD, while heat-labile toxin enterotoxigenic Escherichia coli (LT-ETEC) was associated with an increased pathogen load. Most cases were associated with inflammatory diarrhea while Campylobacter spp. and Shigella spp. were associated with dysentery.
Conclusion
A pan-molecular diagnostic method such as TAC produces quantifiable and comparable results of all tested pathogens, thereby reducing the variability associated with multiple conventional methods. This allows better determination of the clinical relevance of each diarrhea etiologic agent, as well as their geographical relevance in Thailand.

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.



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.



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.



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



Metastatic Crohn's disease in childhood: A case report



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.



Dermoscopic features of Bednar tumor: Report of a case



Effects of urease and nitrification inhibitors on the soil mineral nitrogen dynamics and nitrous oxide (N 2 O) emissions on calcareous soil

Abstract

Urease inhibitors and nitrification inhibitors can reduce nitrogen (N) loss in agriculture soil. However, the effect of inhibitors on soil N2O emissions under the drip irrigation system remains unclear. A pot and a field experiment with two inhibitors were conducted to explore how inhibitors regulate soil nitrogen transformation and N2O emissions. In the pot experiment, three treatments included control, urea, and urea + N-(n-butyl)thiophosphoric triamide (NBPT, urease inhibitor). In the field experiment, three treatments included control, urea, and urea + NBPT + 2-chloro-6-(trichloromethyl)pyridine (nitrapyrin, nitrification inhibitor). The urease inhibition rate in the treatment of urea + NBPT was 27.5% at the 14th day of incubation (pot experiment), and NH4+-N was significantly decreased by 37–64% compared with urea alone treatment. In the field experiment, the nitrification inhibition rate in the treatment of urea + NBPT + nitrapyrin was 47.7 and 63.9% on the 3rd day after fertilization at the wheat heading and filling stages, respectively. Compared to urea treatment, NO3−-N concentration in the double-inhibitor-added treatment was significantly decreased by 32 and 20% on the 5th day after fertilization at the heading and filling stages, respectively; N2O fluxes were also decreased by 30.9 and 33.3% at the two stages of wheat, respectively. In total, adding an inhibitor reduced N loss by 7.39 and 7.44% at the 14th and 35th day in the pot experiment and by 10.53 and 6.65% at the two growing stages of wheat in the field experiment, respectively. Path and correlation analysis showed that N2O emissions were significantly correlated with soil NO3− in both pot and field experiments.



Analysis of accumulation formation of sediment contamination in reservoirs after decades of running: a case study of nitrogen accumulation in Biliuhe Reservoir

Abstract

Sediment contamination is an important influencing factor for reservoir water quality. Investigations have shown that reservoirs are facing the risk of sediment contamination after running for several decades in China. This paper proposes that the accumulation of sediment contaminant is resulted from the difference between the input and output of contaminant. Further, an accumulation model of reservoir sediment nitrogen is established based on this theory. The calculation result of Biliuhe Reservoir shows that inflow rate of total nitrogen into the reservoir is 4521.47 t/a, the outflow rate is 1033.97 t/a, nitrogen removal by denitrification is 1465.81 t/a, and the accumulation rate is 1841.68 t/a. The accumulation rate of total nitrogen is 77.84 t/a in water, 924.42 t/a in suspended solids, and 839.42 t/a in sediment. The accumulation of nitrogen resulted in the total nitrogen concentration in water increasing from 1.71 mg/L in 1995 to 3.78 mg/L in 2013, and that in sediment increasing from 779.10 mg/kg in 1993 to 2725.00 mg/kg in 2013. It is concluded that sediment contamination has the characteristics of significant accumulation trend, complex forms, and high security risks, which has been a hidden security risk for reservoirs after decades of running. Heterogeneity of the reservoir and complicated influencing factors of sediment contaminant accumulation should be concerned next.



Effect of brewery wastewater obtained from different phases of treatment plant on seed germination of chickpea ( Cicer arietinum) , maize ( Zea mays ), and pigeon pea ( Cajanus cajan )

Abstract

Brewing industry releases large quantities of wastewater after product generation. Brewery wastewater contains organic compounds which are biodegradable in nature. These biodegradable wastes can be recycled and reused and hence considered as suitable products for agriculture. But before using wastewater for agriculture, it is better to evaluate the phytotoxic effects of wastewater on crops. Hence, the main objective of this study is to evaluate the effects of brewery effluent on seed germination and growth parameters of selected crop species like chickpea (Cicer arietinum), maize (Zea mays), and pigeon pea (Cajanus cajan). Study comprised seven types of water treatments—tap water as control, diluted UASBR effluent (50% effluent + 50% distilled water): UASBR50, undiluted UASBR effluent: UASBR100, diluted TC effluent (50% effluent + 50% distilled water): ETP50,TC effluent without dilution: ETP100, 10% diluted reverse osmosis (RO10) reject (10% RO reject + 90% distilled water), and 25% diluted reverse osmosis(RO25) reject (25% RO reject + 75% distilled water) with three replications in completely randomized design. Germination test was performed in petri plates for 5 days. Parameters like germination percentage, germination rate index, seedling length, phytotoxicity index, seed vigor index, and biomass were calculated. All parameters decreased with increase in respective effluent concentration. Among all treatments, RO25 showed highest inhibitory effect on all three crops. Even though undiluted effluent of UASBR and ETP effluent showed positive effect on germination, seedling growth of three crops was promoted to the maximum by UASBR50 and ETP50. Hence, from the study, it was concluded that dilution of brewery effluent can be recommended before using it for irrigational purpose.



Investigating the composition characteristics of dissolved and particulate/colloidal organic matter in effluent-dominated stream using fluorescence spectroscopy combined with multivariable analysis

Abstract

Fluorescence excitation-emission matrix (EEM) spectroscopy combined with principal component analysis (PCA) and parallel factor analysis (PARAFAC) were used to investigate the compositional characteristics of dissolved and particulate/colloidal organic matter and its correlations with nitrogen, phosphorus, and heavy metals in an effluent-dominated stream, Northern China. The results showed that dissolved organic matter (DOM) was comprised of fulvic-like, humic-like, and protein-like components in the water samples, and fulvic-like substances were the main fraction of DOM among them. Particulate/colloidal organic matter (PcOM) consisted of fulvic-like and protein-like matter. Fulvic-like substances existed in the larger molecular form in PcOM, and they comprised a large amount of nitrogen and polar functional groups. On the other hand, protein-like components in PcOM were low in benzene ring and bound to heavy metals. It could be concluded that nitrogen, phosphorus, and heavy metals in effluent had an effect on the compositional characteristics of natural DOM and PcOM, which may deepen our understanding about the environmental behaviors of organic matter in effluent.



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.

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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.

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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).

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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.

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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.

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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.

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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.

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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.

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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.

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A Pilot Study Evaluating the Efficacy and Safety of ARTISS Human Fibrin Sealant in External Rhinoplasty

Abstract

Background

Fibrin sealant application in rhytidectomy has previously demonstrated a reduction in adverse events and drainage volume. Fibrin sealant offers multiple potential benefits including decreasing downtime, reducing complication rates, and improving patient satisfaction. In this study, we evaluated the efficacy and safety of ARTISS [fibrin sealant (human)] in external rhinoplasty.

Methods

Nine healthy participants between the ages of 18 and 50 seeking external rhinoplasty completed this study. All subjects were randomized into control and treatment groups and then underwent external rhinoplasty, with only the treatment group receiving ARTISS [fibrin sealant (Human)] during surgery. Photographs were taken before surgery and 1 day, 1 week, 1 month, 3 months and 6 months after surgery and used in a blinded assessment of recovery time and esthetic improvement with ecchymosis and satisfaction scales. Subject recovery time, downtime, and self-esteem were evaluated at 1 day, 1 week, 1 month and 6 months after surgery. Recovery time was determined by live assessment of edema and ecchymosis using categorical scales. Subject downtime was assessed through a 30-day patient diary and a downtime questionnaire. Subject self-esteem was evaluated with the Heatherton & Polivy State Self-Esteem Scale. The degree of technical ease with the product was determined by the treating investigator with a 10-cm Visual Analog Scale.

Results

Patients treated with ARTISS intra-operatively reported significantly higher self-esteem 1 month and 6 months following external rhinoplasty. The ARTISS Easyspray™ Spray Set was rated as technically easy to administer.

Conclusion

The use of ARTISS fibrin sealant in external rhinoplasties is a safe and easy method and may enhance patient self-esteem. Larger studies are warranted to either verify or challenge the validity of our findings.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



In Pursuit of Effective Volume Reduction and Enhanced Aesthetics for Treatment of Gigantomastia Using Superior Dermoglandular Pedicle

Abstract

Background

Gigantomastia is defined as extreme hypertrophy of the female breast. It is a disabling condition that presents unique challenges to plastic surgeons. Initial breast volume is an important factor affecting the success of the reduction. Usually, it is difficult to achieve small-sized breasts, and long-term results are often unsatisfactory, resulting in complications such as "bottoming-out" deformities.

Methods

This paper presents a case series involving 40 patients (mean age 44.2 ± 12.5) with gigantomastia. Reductions were performed by superior nipple–areola complex pedicle with or without liposuction. Total resection weight ranged from 2050 to 5398 g (mean 3066 ± 944.2). Generally, the literature emphasizes the unreliability of the long superior pedicle when used to reduce the size of very large breasts. The technical steps for this procedure have been clearly described, and ways in which to overcome technical difficulties and attain effective volume reduction with minimal complications were presented.

Results

The technique described here is applicable to all gigantomastia cases; even very large, pendulous breasts could be effectively reduced. Physical symptoms rapidly improved during the early postoperative period, patients' aesthetic satisfaction scores were high (4.6/5), and none of the patients complained of flat breasts. The rate of partial areola necrosis was 5%, and the rate of complete areola necrosis was 2.5%. These rates are comparable to those in the literature.

Conclusion

Using the technique described above, superior pedicle can be applied to all gigantomastia cases and enhanced aesthetic results can be obtained with minimal complications.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



The Next Generation of Melanocyte Data: Genetic, Epigenetic and Transcriptional Resource Datasets and Analysis Tools

Abstract

Genomics is a common thread linking all aspects of pigment cell biology, including melanocyte- and melanosome-related functions, pigmentary disorders, normal human pigmentation variation and melanoma. Recently, genomic-scale Next Generation Sequencing (NGS) analyses have rapidly expanded, because of reductions in sequencing costs, increased assay sensitivity, and smaller sample requirement. These NGS technologies have been adapted to assay RNA transcript expression, chromatin accessibility, DNA methylation, histone modifications, and transcription factor binding.

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Hyalinosis cutis et mucosae: A clinical investigation with special regard to mucosal changes



Trace element phytoextraction from contaminated soil: a case study under Mediterranean climate

Abstract

The current field study aims to assess the suitability of four different plant species (i.e. poplar, willow, hemp and alfalfa) to be used for trace element (TE) (i.e. Cd, Cu, Ni, Pb and Zn) phytoextraction under hot-arid Mediterranean climate conditions. Plants were grown for two consecutive years on a moderate TE contaminated soil, supplied with water and mineral nutrients. The growth and physiological parameters were assessed throughout the trial to compare the response of plants to the environmental pollution, and TE uptake rates were measured for aboveground plant tissues. The phytoextraction rate for each species was expressed as a function of aboveground biomass yield and the TE uptake and translocation within the plant. Alfalfa played a significant role in reducing extractable Ni (60.6%) and Zn (46%) in the soil, whereas hemp reduced 32% of extractable Cd and 46% of extractable Pb; poplar decreased extractable Cd (37%), Ni (49%), Pb (46%) and Zn (63%); and willow reduced the extractable Zn (73%) compared to the beginning of the trial. No change in total TE content was observed; however, poplar and willow were able to extract and accumulate the highest amount of Zn (3200 and 5200 g ha−1 year−1 respectively) and Cu (182 and 116 g ha−1 year−1), whereas hemp, with 36 g ha−1 year−1, showed the best phytoextraction potential for Pb. Overall, we found a positive correlation between the phytoextraction rate and biomass yield, extractable TE concentration and translocation factor (TF) and a negative relationship with Ca concentration in the soil.



Examining the role of Antioxidant Consumption and Active Tuberculosis



Response to Invited Commentary: Second-hand Smoke is an under Recognized Risk for Cognitive Decline



Invited Commentary: Second-hand smoke is an under recognized risk factor for cognitive decline

Abstract
Pan et al. report findings showing that second-hand smoke (SHS) exposure is associated with cognitive decline over two years in both middle-aged and older Chinese women who never smoked and also report a dose-response relationship. SHS exposure affects vulnerable people disproportionately as they have less control or choice over their living and working environment. Smoking is an established risk factor for dementia, but recent evidence reports on dementia risk increase have not included SHS. Many epidemiologic studies collect data on smoking but not SHS exposure. SHS may be one of the most prevalent and modifiable risk factors for cognitive decline and therefore represents a major potential target for dementia risk reduction. Given the high prevalence of smoking in China and other parts of the world, there is an urgent need to raise awareness of SHS reduction as part of global and national strategies to reduce cognitive decline and dementia, and to introduce legislation that protects non-smokers and vulnerable children and adults from SHS.

What is the role of vitamin A in preventing development of active tuberculosis?



Response to letters on “Dietary Intake of Antioxidant Vitamins and Carotenoids and Risk of Developing Active Tuberculosis in a Prospective Population-based Cohort”



Placental Weight and Risk of Cryptorchidism and Hypospadias in the Collaborative Perinatal Project

Abstract
Cryptorchidism and hypospadias are the most common congenital anomalies of the genitourinary tract in males, but their etiology remains unclear. Placental insufficiency has been suggested to be linked to both conditions. Placental weight is a commonly used proxy measure for placental insufficiency, thus, we examined placental weight and other placental characteristics in relation to cryptorchidism and hypospadias in the Collaborative Perinatal Project (CPP). The CPP was a mother-child cohort study conducted in the United States. Pregnant women were recruited between 1959 and 1965. The analysis contrasted boys with cryptorchidism (n = 413) and boys with hypospadias (n = 145) to boys without cryptorchidism (n = 23,799) and boys without hypospadias (n = 22,326). Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. In categorical analyses in which the middle tertile was the referent, cryptorchidism was inversely associated with placental weight (odds ratio: 0.66, 95% confidence interval: 0.46, 0.95) among white boys, and positively associated with the lowest tertile of placental weight among black boys (odds ratio = 1.70, 95% confidence interval: 1.11, 2.59). In conclusion, lower placental weight may be related to risk of cryptorchidism. Further investigation of placental functioning may offer insights into the etiology of cryptorchidism.

Targeted Estimation of the Relationship Between Childhood Adversity and Fluid Intelligence in a US Population Sample of Adolescents

Abstract
Many studies have shown inverse associations between childhood adversity and intelligence (IQ), though most are based on small clinical samples and fail to account for the effects of multiple co-occurring adversities. Using data from the 2001–2004 National Comorbidity Survey Adolescent Supplement, a cross-sectional US population study of adolescents ages 13–18 (n = 10,073), we examined the associations between 11 childhood adversities on IQ, using targeted maximum likelihood estimation. Targeted maximum likelihood estimation incorporates machine-learning to identify the relationships between exposures and outcomes without over-fitting, including interactions and non-linearity. The Kaufman Brief Intelligence Test nonverbal score was used as a standardized measure of fluid reasoning. Child adversities were grouped into deprivation- and threat-types based on recent conceptual models. Adjusted marginal mean differences compared the mean IQ score if all adolescents experienced each adversity to the mean in the absence of the adversity. The largest associations were observed for deprivation-type experiences, including poverty and low parental education, which were related to reduced IQ. Though lower in magnitude, threat events related to IQ included physical abuse and witnessing domestic violence. Violence prevention and poverty-reduction measures would improve childhood cognitive outcomes.

Examining Non-Participation to the Maternal Follow-up Within the Danish National Birth Cohort

Abstract
A follow-up questionnaire on maternal health has been distributed within the Danish National Birth Cohort (established 1996–2002) 14 years after the index birth. Answers were obtained for 41,466 of 78,010 (53.2%) eligible mothers. To ensure the appropriate use of these data, the possibility of selection bias due to non-participation must be evaluated. We estimated four selected exposure-outcome associations (pre-pregnancy weight – depression; exercise – degenerative musculoskeletal conditions; smoking – heart disease; and alcohol consumption – breast cancer). We adjusted for several factors associated with participation and applied inverse probability weighting. To estimate the degree of selection bias, we calculated relative odds ratios between the baseline cohort and the subset participating in the follow-up. Participating women were in general healthier, of better social status, and older than the baseline cohort. However, selection bias was limited in the chosen scenarios with ratios of the odds ratios ranging from −14% to +5% after adjustment for age, parity, social status, and if not the exposure, pre-pregnancy body mass index, exercise, smoking, and alcohol consumption. Applying inverse probability weighting technique did not further reduce bias. In conclusion, while participants differed somewhat from the baseline cohort, selection bias was limited after factors that associated with participation status were accounted for.

Secondhand Smoke and Women's Cognitive Function in China

Abstract
Exposure to secondhand smoke (SHS) is known to be harmful to health. However, the association between household SHS and cognitive function among middle-aged and older women in China is understudied. Lagged dependent variable regression is used to examine the association between household SHS exposure and the cognitive function of married women who have been exposed to SHS from two waves of the China Health and Retirement Longitudinal Study (CHARLS, 2011–2013). Controlling for age, educational attainment, geographic residence, household expenditures, and chronic conditions (i.e., hypertension, diabetes, and depressive symptoms), the results indicate that longer SHS exposure is associated with a greater decline in memory over two years. After comparing differences across age groups, this pattern is significant for women aged 55–64 years. Furthermore, those who are illiterate, live in rural areas, and report depressive symptoms have a greater decline in memory. With evidence linking household SHS exposure with a higher risk of cognitive decline, effective education and public health intervention programs are urgently needed. Stronger tobacco control regulations and education about the dangers of household SHS are viable strategies to reduce the impending dementia epidemic in China.

Effects of transcutaneous electrical nerve stimulation on pain intensity during application of carboxytherapy in patients with cellulite: A randomized placebo-controlled trial

Summary

Background

Carboxytherapy may generate local pain that is considered the main limiting factor in clinical practice. Transcutaneous electric nerve stimulation (TENS) is widely used in the control of acute pain; however, the effect of TENS on pain relief during carboxytherapy has not been studied to date.

Aims

To assess the effect of TENS on pain intensity during carboxytherapy in patients with cellulite in the gluteal region.

Patients/Methods

This randomized clinical trial was conducted with 84 patients, 18-44 years of age, who had moderate cellulite in the gluteal region, according to Cellulite Severity Scale, but never received carboxytherapy. Patients were randomized into 3 groups: active TENS, placebo TENS, and control group. For the intervention, skin depressions with cellulite were outlined, and the gluteal area to be treated was defined. The subcutaneous injection of CO2 was performed using 0.30 × 13 mm-needles at a 45° angle, with a controlled flow rate of 100 mL/min maintained for 1 minute at each puncture site. The parameters for TENS were as follows: frequency of 100 Hz and pulse duration of 200 μs; TENS intensity was adjusted until the patient reported strong paresthesia. The visual numeric pain rating scale was used to assess pain intensity after each puncture.

Results

The active TENS group reported lower pain intensity compared to the placebo TENS (P < .0001) and control (P < .0001) groups.

Conclusions

Transcutaneous electric nerve stimulation (TENS) was effective in reducing pain intensity during carboxytherapy in patients with cellulite in the gluteal region.



Teleological epistemology

Abstract

It is typically thought that some epistemic states are valuable—knowing, truly or accurately believing, understanding (to name a few). These are states it's thought good to be in and it's also said that we aim or want to be in them. It is then sometimes claimed that these sorts of thoughts about epistemic goods or values ground or explain our epistemic norms. For instance, we think subjects should follow their evidence when they form their beliefs. But why should they? Why not believe against the evidence or ignore it completely in deciding what to believe? Here's a compelling sort of answer: because epistemic subjects are or ought to be trying to know more and following their evidence is a means to that end or to fulfilling that obligation. In this paper I argue that this compelling thought cannot be right. Subjects who are trying to know more will regularly fail to conform to some of our most familiar epistemic norms.



Comparison of gray matter volume between migraine and “strict-criteria” tension-type headache

Despite evidently distinct symptoms, tension-type headache (TTH) and migraine are highly comorbid and exhibit many similarities in clinical practice. The purpose of this study was to investigate whether both t...

Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus

Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues inc...

Nonspecific diffuse alopecia as a single manifestation of syphilis infection: clinical and trichoscopic features



Evaluating the validity of subclassifying warfarin-associated nonuremic calciphylaxis: a retrospective cohort study

Abstract

Background

Calciphylaxis is a devastating multifactorial disorder of the subcutaneous fat that is known to be associated with hypercoagulability. Recent literature has proposed subclassifying patients with calciphylaxis as having warfarin-associated or warfarin-unassociated disease.

Aim

We aimed to determine whether patients with warfarin-associated calciphylaxis differ clinically from patients with warfarin-unassociated calciphylaxis.

Materials and methods

We performed a subgroup analysis of patients with nonuremic calciphylaxis from a previously studied cohort and compared clinical and outcomes features of patients who were taking warfarin at the time of disease onset to those of patients who were not.

Results

Nineteen patients with nonuremic calciphylaxis were identified, including 10 (53%) who had been on warfarin at the time of disease onset and 9 (47%) who had not. Of all clinical and outcomes parameters tested, no significant differences were detected between the two groups.

Discussion and Conclusions

Though this study is limited by its retrospective nature and the relatively small number of patients studied, available data do not support subclassifying patients with nonuremic calciphylaxis as having warfarin-associated or warfarin-unassociated disease. Rather, the body of literature would suggest that identification and correction of underlying disorders of hypercoagulability should be prioritized.



Histories in quantum mechanics: distinguishing between formalism and interpretation

Abstract

In spite of being a well articulated proposal, the theory of quantum histories (TQH), in its different versions, suffers from certain difficulties that have been pointed out in the literature. Nevertheless, two facets of the proposal have not been sufficiently stressed. On the one hand, it is a non-collapse formalism that should be technically appropriate to supply descriptions based on quantum properties at different times. On the other hand, it intends to provide an interpretation of quantum mechanics that solves the traditional puzzles of the theory. In this article we spell out the main criticisms to TQH and classify them into two groups: theoretical and interpretive. Whereas the latter might be ignored if the TQH were considered as a quantum formalism with its minimum interpretation, the former seems to point toward technical difficulties that must be faced in a theoretically adequate proposal. Precisely with the purpose of solving these difficulties, we introduce a different perspective, called Formalism of Generalized Contexts or Formalism of Contextual Histories (FCH), which supplies a precise condition for consistently talking of quantum properties at different times without the theoretical shortcomings of the TQH.



Uncovering behavioural diversity amongst high-strength Pseudomonas spp. surfactants at the limit of liquid surface tension reduction

Abstract
Bacterial bio-surfactants have a wide range of biological functions and biotechnological applications. Previous analyses had suggested a limit to their reduction of aqueous liquid surface tensions (γMin), and here we confirm this in an analysis of 25 Pseudomonas spp. strains isolated from soil which produce high-strength surfactants that reduce surface tensions to 25.2 ± 0.1–26.5 ± 0.2 mN.m−1 (the surface tension of sterile growth medium and pure water was 52.9 ± 0.4 mN.m−1 and 72.1 ± 1.2 mN.m−1, respectively). Comparisons of culture supernatants produced using different growth media and semi-purified samples indicate that the limit of 24.2–24.7 mN.m−1 is not greatly influenced by culture conditions, pH or NaCl concentrations. We have used foam, emulsion and oil-displacement behavioural assays as a simple and cost-effective proxy for in-depth biochemical characterisation, and these suggest there is significant structural diversity amongst these surfactants which may reflect different biological functions and offer new biotechnological opportunities. Finally, we obtained a draft genome for the strain producing the highest-strength surfactant, and identified a cluster of non-ribosomal protein synthase genes which may produce a cyclic-lipopeptide (CLP)–like surfactant. Further investigation of this group of related bacteria recovered from the same site will allow a better understanding of the significance of the great variety of surfactants produced by bacterial communities found in soil and elsewhere.

Δευτέρα 15 Ιανουαρίου 2018

Systematic review of atopic dermatitis disease definition in studies using routinely-collected health data

Abstract

Background

Routinely collected electronic health data (RCD) obtained for administrative and clinical purposes are increasingly used to study atopic dermatitis (AD). Methods for identifying AD patients in RCD differ, and it is unknown how this might affect study results.

Objectives

We sought to evaluate how AD patients have been identified in studies using RCD, to determine whether these methods were validated, and to estimate how the method for identifying AD patients affected variability in prevalence estimates.

Methods

We systematically searched PubMed, EMBASE, and Web of Science for studies utilizing RCD that reported on AD as a primary outcome. Studies of localized AD and other types of dermatitis were excluded. The protocol for this review was registered in PROSPERO (CRD42016037968).

Results

59 studies met eligibility criteria. Medical diagnosis codes for inclusion and exclusion, number of occasions of a code, type of provider associated with a code, and prescription data were used to identify AD patients. Only two studies described validation of their methods and no study reported on disease severity. Prevalence estimates ranged from 0.18%-38.33% (median 4.91%) and up to 3-fold variation in prevalence was introduced by differences in the method for identifying AD patients.

Conclusions

This systematic review highlights the need for clear reporting of methods for identifying AD patients in routinely collected electronic health data to allow for meaningful interpretation and comparison of results.

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Dermatology Training Across the Globe

Abstract

Dermatology residency program rankings often stem from assessments by practicing physicians or evaluations of scholarly achievements such as grants and publicatons.1-3 Such rankings, however, are continuously changing, and fail to account for the specific missions of dermatology training programs.2 Additionally, a global comparison of dermatology training requirements and a worldwide understanding of the ideal dermatology curriculum remains missing from the literature. Therefore, this study aims to compare and contrast accreditation requirements for dermatology training programs across the world. As a secondary objective, it attempts to identify the different missions of dermatology training programs around the world to create a global vision of what constitutes an ideal dermatology training program.

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Computerized planimetry to assess clinical responsiveness in a phase II randomized trial of topical R333 for discoid lupus erythematosus

Abstract

Background

R333 is a topical janus kinase and spleen tyrosine kinase inhibitor being evaluated for discoid lupus erythematosus (DLE) treatment. There is no validated measure to assess area of active DLE lesions.

Objectives

To evaluate R333 efficacy and assess a technique to measure responsiveness.

Methods

54 DLE patients were randomized in a double blind design to R333 or placebo. The primary endpoint was the proportion of patients achieving ≥50% decrease in erythema and scale based on lesional CLASI for all treated lesions at week 4. Two-dimensional area measurements for each lesion were recorded at baseline and week 1-6. 88 photographs (44 pre- and 44 post-treatment) were obtained from the trial and change in size of active areas was analyzed by computerized planimetry and physician assessed area change.

Results

36 patients were randomized to R333 and 18 patients were randomized to placebo. The primary endpoint was not achieved. There was a strong association between lesion activity and physician global assessment, a measure of activity of all treated lesions (p<10-6). Photos of 42 patients assessed by computerized planimetry demonstrated excellent inter-rater and intra-rater reliability. Area change by computerized planimetry showed a strong correlation with physician assessed area change (Spearman r=0.72). Area change by two-dimensional measurements showed a weak correlation with physician assessed area change (Spearman r=0.29)

Conclusion

Four weeks of R333 treatment did not result in significant improvement in lesion activity. Lesion activity and area change using computerized planimetry are better determinants of responsiveness as compared to area change using two-dimensional measurements.

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Vulvo-vaginal rejuvenation: Fact or fiction? Fractional carbon dioxide laser for genitourinary syndrome of menopause



Efficacy and safety of fezakinumab (an anti-IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments - A randomized, double-blind, phase 2a trial

IL-22 promotes epidermal hyperplasia and inhibits skin barrier function.

Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE)

Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis.

Acrodermatitis acidaemica

Summary

Methylmalonic acidaemia (MMA) is an inborn error of amino acid metabolism that may be associated with cutaneous manifestations mimicking other diagnoses, including staphylococcal scalded skin syndrome (SSSS), psoriasis and acrodermatitis enteropathica. Whether this is due to the underlying metabolic disorder itself or occurs as a consequence of dietary restriction has yet to be elucidated. Skin biopsies typically show histological features shared by a number of other metabolic disorders and nutritional deficiency-associated diseases. Some presentations, especially SSSS-like eruptions, may be associated with acute metabolic decompensation. An underlying metabolic disorder, such as MMA, should be considered in a diagnosed adult or undiagnosed child presenting with skin eruptions that resemble those listed above, so that specialist management may be initiated early.



Seasonal variation and source apportionment of PM 2.5 -bound trace elements at a coastal area in southwestern Taiwan

Abstract

The aim of this study is to investigate the seasonal variations and source apportionment on atmospheric fine particulate matter (PM2.5) mass and associated trace element concentrations at a coastal area, in Chiayi County of southwestern Taiwan. Particle measurements were conducted in 2015. Twenty-three trace elements in PM2.5 were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Multiple approaches of the enrichment factor (EF) analysis and positive matrix fraction (PMF) model were used to identify potential sources of PM2.5-bound trace elements. Daily mean concentration of PM2.5 in cold season (25.41 μg m−3) was higher than that in hot season (13.10 μg m−3). The trace elements contributed 11.02 and 10.74% in total PM2.5 mass concentrations in cold season and hot season, respectively. The results of EF analysis confirmed that Sb, Mo, and Cd were the top three anthropogenic trace elements in the PM2.5; furthermore, carcinogenic elements (Cr, Ni, and As) and other trace elements (Na, K, V, Cu, Zn, Sr, Sn, Ba, and Pb) were attributable to anthropogenic emissions in both cold and hot seasons; however, highly enriched Li and Mn were observed only in cold season. The PMF model identified four main sources: iron and steel industry, soil and road dust, coal combustion, and traffic-related emission. Each of these sources has an annual mean contribution of 8.2, 27.5, 11.2, and 53.1%, respectively, to PM2.5. The relative dominance of each identified source varies with changing seasons. The highest contributions occurred in cold season for iron and steel industry (66.2%), in hot season for traffic-related emission (58.4%), soil and road dust (22.0%), and coal combustion (2.8%). These findings revealed that the PM2.5 mass concentration, PM2.5-bound trace element concentrations, and their contributions were various by seasons.



Is there an association of ABO blood groups and Rhesus factor with alopecia areata?

Summary

Background/Objectives

Alopecia areata (AA) is an autoimmune disease characterized by noncicatricial hair loss localized on hair, beard, mustache, eyebrow, eyelash, and sometimes on the body. Although etiopathogenesis is not fully understood, many studies show remarkable associations between various diseases and ABO blood groups. However, there is no study with AA and blood groups.

Methods

Healthy people and patients with AA were included in this study. A total of 155 patients with AA and 299 healthy controls were included in the study.

Results

ABO blood group distribution in patients with AA and distribution of healthy donors were similar. However, Rhesus factor positivity in the AA group was significantly higher than in healthy donors. The relationship between stress and AA was high as known. But, ABO blood group and Rhesus factor were not in a significant connection with stress.

Conclusion

We conclude that there was no association between ABO blood group and AA, but the observed distribution of Rhesus blood group differed slightly but significantly from that of the healthy population. The result of the study shows a small but statistically significant difference in the Rh blood group between patients with AA and the healthy population blood groups. This result is important because it suggests that genetic factors may influence the development of AA. The role of blood groups in the development of AA remains to be determined. We believe that the studies which will be carried out in other centers with wider series will be more valuable to support this hypothesis.



The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients with Hematologic Malignancies Requiring Antibiotics

Abstract
Background
Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown.
Objective
To define the impact of reported BL-only allergy (BLOA) label on clinical outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy inpatients requiring systemic antibiotics.
Methods
Retrospective cohort study of adult inpatients with hematologic malignancy admitted at two tertiary care hospitals 2010-2015. The primary outcome was hospital length of stay (LOS) after first antibiotic. Secondary outcomes included re-admission, mortality, complications, total hospital charges, and antibiotic usage.
Results
In our cohort (n=4671), 38.3% had leukemia, 4.9% had Hodgkin's lymphoma, 36.1% had non-Hodgkin's lymphoma and 20.7% had multiple myeloma. Among subjects, 35.1% reported antibiotic allergy, 14.1% (n=660) had BLOA (including 9.3% with penicillin-only allergy and 3.3% cephalosporin-only allergy). Subjects with BLOA had longer median LOS compared to NBLA (11.3 vs. 7.6 days, p<0.001), which remained significant after multivariable adjustment. Patients with BLOA also had significantly worse outcomes compared to NBLA in terms of mortality rate at 30-days (7.6% vs. 15.8%, p=0.017) and 180-days (15.8% compared to 12.2%, p=0.013), 30-day re-admission rate (19.2% vs. 15.1%, p=0.008), Clostridium difficile rate (17.7% vs. 11.6%, p<0.001), total hospital charges ($223046 vs. $173256, p<0.001), antibiotic classes used (median 3 vs. 2 classes/patient, p<0.001), and antibiotic duration (median 9.0 vs. 6.0 days, p<0.001).
Conclusion
In hospitalized patients with hematologic malignancy requiring antibiotics, patients with reported BL allergy have worse clinical outcomes and higher healthcare cost than those without BL allergy label.

A nosocomial foodborne outbreak of a VIM carbapenemase-expressing Citrobacter freundii

Abstract
Background
A foodborne outbreak of VIM carbapenemase-expressing Citrobacter freundii (CPC) occurred between February and June 2016 at a major university hospital in Germany.
Methods
An explosive increase of CPC isolated from rectal swabs of patients during weekly routine screening led to the declaration of an outbreak. A hospital-wide prevalence screening was initiated as well as screening of all patients on admission and before transfer to another ward, and canteen staff, patient rooms, medical and kitchen inventory and food. Swabs were streaked out on selective plates. All CPC isolates were analysed by mass spectrometry and selected isolates by whole-genome sequencing.
Results
In total, 76 mostly unrelated cases in different wards were identified. The CPC was isolated from retained samples of prepared vegetable salads and puddings and from a mixing machine used to prepare them only after an overnight culture. The immediate ban on serving potential source food resulted in a sharp decline and finally disappearance of novel cases. Repeated testing of pre-sliced vegetables showed a high degree of contamination with C. freundii without a carbapenemase, indicating a possible source.
Conclusions
This report demonstrates that an explosive increase in carbapenemase-expressing Enterobacteriaceae contamination may be caused by a food-borne source, and suggests that pre-sliced vegetables have to be taken into account as a putative pathogen repository. It also underlines the importance of appropriate cooling, transport, re-heating and distribution of meals and indicates that probing of non-organic surfaces is limited by low sensitivity, which may be increased by additional overnight cultivation in appropriate media.

Combating Global Antibiotic Resistance: Emerging One Health Concerns in Lower- and Middle-Income Countries

Abstract
Antibiotic misuse in lower- and middle-income countries (LMICs) contributes to the development of antibiotic resistance that can disseminate globally. Strategies specific to LMICs that seek to reduce antibiotic misuse by humans, but simultaneously improve antibiotic access, have been proposed. However, most approaches to date have not considered the growing impact of animal and environmental reservoirs of antibiotic resistance, which threaten to exacerbate the antibiotic resistance crisis in LMICs. In particular, current strategies do not prioritize the impacts of increased antibiotic use for terrestrial food-animal and aquaculture production, inadequate food safety, and widespread environmental pollution. Here, we propose new approaches that address emerging, One Health challenges.

Could conjunctivitis in dupilumab treated atopic dermatitis patients be caused by colonization with Demodex and increased IL-17 levels? Reply from authors

Abstract

In studies in atopic dermatitis (AD), dupilumab has been associated with higher rates of conjunctivitis compared with placebo. Consistent with previous studies, in LIBERTY AD CAFÉ (NCT02755649), all cases but one were mild or moderate, most (62–89%) were recovered/resolved or recovering/resolving by end of treatment, and no patients permanently discontinued study treatment because of conjunctivitis.1 No patients reported atopic keratoconjunctivitis in this study.

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Mass balance of arsenic fluxes in rivers impacted by gold mining activities in Paracatu (Minas Gerais State, Brazil)

Abstract

Arsenic (As) is a dangerous and carcinogenic element and drinking water is its main pathway of human exposure. Gold mines are widely recognized as important sources of As pollution. This work proposes the assessment of As distribution along watersheds surrounding "Morro do Ouro" gold mine (Paracatu, southeastern Brazil). A balance approach between filtered As fluxes (As < 0.45 μm) and suspended particulate material (AsSPM) in different river segments was applied. Ultrafiltration procedure was used to categorize As into the following classes: particulate > 0.1 μm, colloidal < 0.1 μm to > 10 kDa, dissolved < 10 kDa to > 1 kDa, and truly dissolved < 1 kDa. By applying this approach, arsenic contributions from mining facilities were quantified in order to identify critical fluvial segments and support decision makers in actions of remediation. The mass balance indicated the occurrence of a decreasing gradient from upstream to downstream: (i) of the As concentrations higher than the limit established by Brazilian law (10 μg L−1); (ii) of the ratio between specific fluxes (g As km−2 day−1) and those determined using an uncontaminated watershed (a proxy for estimating the anthropic contribution), from 103 to 101; (iii) of the specific fluxes As < 0.45 μm and AsSPM from 102 to 100; and (iv) of the negative balance output minus input for each river segment that suggests As accumulation in sediments along the rivers in both urban and rural areas, mainly due to SPM sedimentation and sorption by Fe oxyhydroxides. Ultrafiltration shattering showed concentrations of decreasing As with particle size; the SPM load (> 0.1 μm) was almost one order higher to dissolved load (< 1 kDa).



Silicone Migration after Buttock Augmentation

imageSummary: We present the case of a 30-year-old woman who presented with enlarged inguinal lymph nodes and sacral hyperpigmentation 4 months after gluteal augmentation with silicone implants. Inguinal lymph node biopsy revealed granulomatous lymphadenitis due to foreign material. Upon right buttock implant revision, a 1.5-cm-thick capsule was noted with the absence of peri-implant inflammatory fluid and no macroscopic implant defects. Analysis of the implant by the manufacturer revealed a microscopic silicone leak. The patient's recovery was uneventful, and her symptoms resolved shortly after her reoperation.

Predictors of Success Following Muller’s Muscle-Conjunctival Resection

Purpose: This study aims to describe Muller's muscle-conjunctival resection surgery in terms of outcomes and potential factors that may predict final positions. Methods: This cross-sectional cohort study included patients undergoing Muller's muscle-conjunctival resection surgery for involutional ptosis over a 15-year period. Success was defined in 2 ways: 1) final marginal reflex distance 1 (MRD1) ≥2.5 mm (MRD1 success) and 2) final difference in MRD1 ≤1 mm between eyelids (symmetry success). Percentages of patients achieving both outcomes were calculated. Predictors of outcome were assessed using bivariate analysis and multivariate models. Results: The final sample included 315 eyes in 192 patients. The mean age (standard deviation) was 67.9 (11.9) years, and 60.0% were female. MRD1 ≥2.5 mm was achieved in 65.7% of the sample. Symmetry within 1 mm was achieved in 82.9% of the sample. Significant (p

A Novel Technique for Measuring Eyelid Force

Purpose: We present a novel technique to directly measure the eyelid upward force generation. This technique can be used during routine clinical examination using an inexpensive, portable force gauge. Methods: This prospective case series was conducted January to June 2015 in an ophthalmology clinic affiliated with a tertiary care medical center. A convenience sample of 42 patients (40–90 years of age) without known eyelid pathology participated. The eyelid upward net force generated was measured directly using a handheld dynamometer noninvasively attached to the upper eyelid. Comparison of the eyelid-brow upward force generated with eyelid upward net force generated allowed us to assess the contribution of levator and frontalis muscles to the force generated during upgaze. Data were evaluated with relation to gender and age. Results: Upper eyelid force generated was 53.3 g OD and 53.9 g OS; the generated force during frontalis muscle fixation was 38.4 g OD and 41.1 g OS. The levator and frontalis muscles showed a 3:1 ratio respectively in their contribution to the force generated during upgaze. Although no statistically significant differences were seen between eyes, gender, or within age groups, younger patients showed increased generating force which is attributed to the levator muscle. Interclass correlation coefficient showed virtually no correlation between clinical eyelid assessments and direct muscle force measurement. Reliability for repeated direct force measurements by the same physician was strong, with interclass correlation coefficient 0.951 to 0.969. No adverse events occurred. Conclusions: We describe a simple, reliable, inexpensive, new method for assessing upper eyelid upward force generation. Because the levator muscle serves as the primary contributor to eyelid elevation, this directly measurable eyelid assessment may help to increase understanding of its functional contribution and assessment when assessing eyelid pathologies. Accepted for publication July 11, 2017. Presented at Annual Conference of Ocular Microsurgery, January 8-10, 2015 in Eilat, Israel. The authors have no financial or conflicts of interest to disclose. Shay Ofir, Avner Belkin, and Arie Y. Nemet contributed to conception, design, analysis, writing, and literature search; Shay Ofir contributed to data collection, materials and patient recruitment; Arie Y. Nemet contributed to critical revision and final approval; and Shay Ofir had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Address correspondence and reprint requests to Shay Ofir, MD, Department of Ophthalmology, Meir Medical Center, 59 Tshernichovsky St., Kfar Saba 44281, Israel. E-mail: shayofirl@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Medial Buttressing in Orbital Blowout Fractures

Purpose: To study whether ethmoidectomy predisposes the orbit to medial wall fracture with lesser trauma. Methods: An interventional cadaver study of 5 heads (10 orbits); the left or right orbit was randomized to undergo endoscopic complete ethmoidectomy with the fellow orbit as control. Fractures were induced with direct globe trauma, and heads underwent CT scanning. Energy to induce fracture, peak orbital pressure at time of fracture, fracture pattern, and volume of herniated tissue were measured and analyzed. Results: Fractures were induced in both orbits of all cadavers. Experimental orbits after ethmoidectomy sustained orbital fracture at less energy required (2.14 ± 0.66 vs. 3.10 ± 0.19 J, mean difference: −0.96 ± 0.33 J, p