Food protein induced enterocolitis syndrome in Australia: A population based study 2012-2014

Publication date: Available online 18 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Sam Mehr, Katie Frith, Elizabeth H. Barnes, Dianne E. Campbell
BackgroundFood protein induced enterocolitis syndrome (FPIES) is a non-IgE mediated gastrointestinal allergic disorder. Large population based FPIES studies are lacking.ObjectiveTo determine the incidence and clinical characteristics of FPIES in Australian infantsMethodsAn Australia wide survey (2012-2014) was undertaken via the Australian Paediatric Surveillance Unit, with monthly notification of new cases of acute FPIES in infants aged <24 months by 1400 participating Paediatricians.Results230 infants with FPIES were identified. The incidence of FPIES in Australian infants (<24 months) was 15.4/100,000/year. Median age of first episode, diagnosis and notification were 5, 7 and 10 months respectively. There was no gender predilection. 7% of infants had siblings with a history of FPIES and 5% reacted during exclusive breastfeeding. 68% had a single food trigger (20% two, 12% three or more food triggers). The most common FPIES triggers were rice (45%), cow's milk (33%) and egg (12%). 51% of infants reacted on their first known exposure. Infants with FPIES to multiple versus single food groups were younger at initial episode (4.6 vs. 5.8 months, P=0.001) and more frequently had fruit and/or vegetable FPIES (66% vs. 21%, p<0.0001). Infants exclusively breastfed for more than 4 months had a trend to lower rates of FPIES to multiple food groups (23% vs. 36%, P=0.06). 64% of infants with multiple FPIES which included cow's milk FPIES had co-associated solid food FPIES. 42% of infants with fish-FPIES had reacted to other food groups.ConclusionsFPIES is not rare, with an estimated incidence of 15.4/100,000/year. Rice is the most common food trigger in Australia. Factors associated with multiple-FPIES included early onset disease and FPIES to fruits and/or vegetables.



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Use of vegetable oils in dermatology: an overview

Summary

Vegetable oils have been used for a wide variety of purposes since time immemorial; however, their principle use remains as skin moisturizers, especially in neonates and children. Because of their considerable efficacy and a low side effect profile and bearable cost, these oils are hugely popular as moisturizers among the common people in countries such as India. A wide variety of oils have been used, and newer ones are coming up with each passing day. This article focuses on the different types of vegetable oils and their varied uses in dermatology.

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Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8+ T Cells

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2o27YxF

Evaluation in Mice of the Immunogenicity of a Tetravalent Subunit Vaccine Candidate Against Dengue Virus Using Mucosal and Parenteral Immunization Routes

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2oMo3Vj

Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and wrinkling: A randomized, double-blind, and placebo-controlled study

Summary

Background

Photoaging is a severe skin damage that occurs as a result of exposure to external elements, primarily ultraviolet (UV) irradiation. Chronically, UV-irradiated skin exhibits the signs of sunburn and hyperpigmentation with the destruction of connective tissues. Previously, Boesenbergia pandurata (B. pandurata) and its active compound panduratin A showed antiphotoaging activities in vitro and in vivo.

Objective

The aim of this study was to investigate the clinical efficacy of B. pandurata intake on skin hydration, gloss, wrinkling, and elasticity.

Methods

A double-blind, placebo-controlled trial was conducted to clinically evaluate the effect of B. pandurata ethanol extract (BPE) containing 8% of panduratin A on human skin hydration, gloss, wrinkling, and elasticity. Ninety-two subjects were randomly assigned to receive tablets containing either BPE or placebo for 12 weeks.

Results

The test group had significantly increased skin hydration and gloss and decreased wrinkling compared to the placebo group at 12 weeks. There was no significant difference in skin elasticity between the two groups; however, the increment rate in the test group was higher than that in the placebo group at 12 weeks. None of the subjects developed adverse symptoms during the study period.

Conclusion

These results suggest that BPE can be used as a nutraceutical or nutricosmetic material for improving human skin hydration, gloss, and wrinkling.

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Revisiting Mechanisms of Extraterritorial Allodynia

http://ift.tt/2oRvX1E

Intralabyrinthäre Schwannome

Zusammenfassung

Intralabyrinthäre Schwannome (ILS) sind eine seltene Differenzialdiagnose des Hörsturzes und von Schwindelbeschwerden. In einer eigenen Fallserie von 12 Patienten fanden sich die Tumoren 6‑mal intracochleär und 3‑mal intravestibulär sowie je 1‑mal transmodiolär und im Kleinhirn-Brücken-Winkel (KHBW), 1‑mal transotisch und im KHBW und 1‑mal multilokulär. Von 9 Fällen mit chirurgischer Tumorentfernung erfolgte bei 3 Patienten die Tumorentfernung über eine Labyrinthektomie mit gleichzeitiger Cochleaimplantat(CI)-Operation, in einem Fall über eine erweiterte Cochleostomie mit gleichzeitiger Cochleaimplantation, in 3 Fällen über eine partielle oder subtotale Cochleoektomie mit partieller Cochlearekonstruktion sowie Cochleaimplantation (1-mal) oder Einlage eines CI-Elektroden-Dummies für eine evtl. spätere Cochleaimplantation nach wiederholten MRT-Kontrollen (2-mal). In 2 Fällen erfolgte die kombinierte translabyrinthär-transotische Tumorentfernung aus dem inneren Gehörgang und dem Kleinhirnbrückenwinkel bei transmodiolärem und transmakulärem bzw. transotischem Tumorwachstum. Drei Patienten entschieden sich für ein „Wait-and-test-and-scan-Vorgehen". Bei den intracochleären Tumoren konnte die Gleichgewichtsfunktion postoperativ weitgehend erhalten werden. In allen Fällen mit Cochleaimplantation war die Hörrehabilitation mittels CI erfolgreich, auch in dem Fall mit subtotaler Cochleoektomie, wenn auch hier mit eingeschränktem Sprachverstehen. Eine operative Entfernung intracochleär wachsender Schwannome durch eine partielle oder subtotale Cochleoektomie ist auch mit Erhalt der Funktion des Gleichgewichtsorgans prinzipiell möglich. Die Indikation zur Radiotherapie von ILS ist aus unserer Sicht nur in Einzelfällen gegeben. Die CI-Versorgung nach operativer Entfernung eines ILS ist prinzipiell eine Option zur auditorischen Rehabilitation. Sie stellt bei rechtzeitiger Indikationsstellung im Gegensatz zum abwartenden Verhalten („Wait-and-test-and-scan-Strategie") einen therapeutischen Ansatz dar.

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Population pharmacokinetic modelling of rupatadine solution in 6–11 year olds and optimisation of the experimental design in younger children

by Eva Santamaría, Javier Alejandro Estévez, Jordi Riba, Iñaki Izquierdo, Marta Valle

Aims

To optimise a pharmacokinetic (PK) study design of rupatadine for 2–5 year olds by using a population PK model developed with data from a study in 6–11 year olds. The design optimisation was driven by the need to avoid children's discomfort in the study.

Methods

PK data from 6–11 year olds with allergic rhinitis available from a previous study were used to construct a population PK model which we used in simulations to assess the dose to administer in a study in 2–5 year olds. In addition, an optimal design approach was used to determine the most appropriate number of sampling groups, sampling days, total samples and sampling times.

Results

A two-compartmental model with first-order absorption and elimination, with clearance dependent on weight adequately described the PK of rupatadine for 6–11 year olds. The dose selected for a trial in 2–5 year olds was 2.5 mg, as it provided a Cmax below the 3 ng/ml threshold. The optimal study design consisted of four groups of children (10 children each), a maximum sampling window of 2 hours in two clinic visits for drawing three samples on day 14 and one on day 28 coinciding with the final examination of the study.

Conclusions

A PK study design was optimised in order to prioritise avoidance of discomfort for enrolled 2–5 year olds by taking only four blood samples from each child and minimising the length of hospital stays.

http://ift.tt/2pe8gRW

Comparison of the mechanical properties of different skin sites for auricular and nasal reconstruction

Abstract

Background

Autologous and synthetic nasal and auricular frameworks require skin coverage. The surgeon's decides on the appropriate skin coverage for reconstruction based on colour matching, subcutaneous tissue thickness, expertise and experience. One of the major complications of placing subcutaneous implants is the risk of extrusion (migration through the skin) and infection. However, knowledge of lessening the differential between the soft tissue and the framework can have important implications for extrusion. This study compared the mechanical properties of the skin commonly used as skin sites for the coverage in auricular and nasal reconstruction.

Methods

Using ten fresh human cadavers, the tensile Young's Modulus of the skin from the forehead, forearm, temporoparietal, post-auricular and submandibular neck was assessed. The relaxation rate and absolute relaxation level was also assessed after 90 min of relaxation.

Results

The submandibular skin showed the greatest Young's elastic modulus in tension of all regions (1.28 MPa ±0.06) and forearm showed the lowest (1.03 MPa ±0.06). The forehead demonstrated greater relaxation rates among the different skin regions (7.8 MPa⁻⁰⁷ ± 0.1). The forearm showed the lowest rate of relaxation (4.74 MPa⁻⁰⁷ ± 0.1). The forearm (0.04 MPa ±0.004) and submandibular neck skin (0.04 MPa ±0.005) showed similar absolute levels of relaxation, which were significantly greater than the other skin regions (p < 0.05).

Conclusions

This study provides an understanding into the biomechanical properties of the skin of different sites allowing surgeons to consider this parameter when trying to identify the optimal skin coverage in nasal and auricular reconstruction.

http://ift.tt/2oLpuDb

Massive Blutung bei einer Parazentese: Übersicht anhand eines Fallberichts

Laryngo-Rhino-Otol 2017; 96: 155-159
DOI: 10.1055/s-0043-103278

Es wird über den seltenen Fall einer massiven Blutung aus dem Mittelohr nach Parazentese berichtet. Anhand des Fallberichtes wird das Vorgehen bei einer solchen Blutung im Kontext der Literatur erörtert. Bei einem 6-jährigen Jungen wurde in einem ambulanten OP-Zentrum eine Revisionsparazentese vorgenommenen. Dabei kam es zu einer massiven Blutung. Der Gehörgang wurde dort suffizient tamponiert. Der Patient wurde extubiert und als Notfall ins Klinikum verlegt. Die Computertomographie des Felsenbeins zeigte die anatomische Variante eines dehiszenten, in der Paukenhöhle hochstehenden Bulbus venae jugularis, der verletzt worden war. Bei sistierter Blutung erfolgte am dritten postoperativen Tag eine Detamponade sowie eine explorative Tympanoskopie. Beim Heben des tympanomeatalen Lappens zeigte sich der Defekt im Bulbus. Dieser wurde mit Tutopatch® Auflagen und Fibrinkleber versorgt und der Gehörgang erneut tamponiert. Die Detamponade drei Wochen postoperativ zeigte einen regelrecht verheilten Situs. Von weiteren operativen Maßnahmen wurde Abstand genommen. Die Verletzung eines dehiszenten, hochstehenden Bulbus V. jugularis im Rahmen von Ohroperationen führt zu einer massiven Blutung. Der Fall beschreibt das diagnostische und therapeutische Vorgehen bei der relativ selten vorkommenden, jedoch schweren Komplikation.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Speicheldrüsenkarzinom: Kein Vorteil durch Chemoradiotherapie

Laryngo-Rhino-Otol 2017; 96: 143-144
DOI: 10.1055/s-0042-124126

Amini A et al. Association of Adjuvant Chemoradiotherapy vs Radiotherapy Alone With Survival in Patients With Resected Major Salivary Gland Carcinoma. JAMA Otolaryngol Head Neck Surg 2016; 142: 1100–1110 Karzinome der großen Speicheldrüsen stellen eine heterogene Gruppe seltener maligner Neoplasmen dar. Die Richtlinien des National Comprehensive Cancer Network befürworten die operative Entfernung als Standardtherapie mit zusätzlicher Radiotherapie für Hochrisiko-Patienten. In dieser Studie untersuchten die Autoren, ob eine zusätzliche Chemotherapie einen Vorteil für die Gesamtüberlebensrate bietet.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Fragen für die Facharztprüfung

Laryngo-Rhino-Otol 2017; 96: 199-200
DOI: 10.1055/s-0043-101414

© Georg Thieme Verlag KG Stuttgart · New York

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Transmeatale Attikotomie zur Behandlung von Cholesteatomen in Erwachsenen

Laryngo-Rhino-Otol 2017; 96: 144-145
DOI: 10.1055/s-0042-124127

Bernardeschi D et al. Management of epi- and mesotympanic cholesteatomas by one-stage trans-canal atticotomy in adults. Eur Arch Otorhinolaryngol 2016; 273: 2941–2946 Die Operation eines Cholesteatoms soll die Erkrankung beheben, einem Wiederauftreten vorbeugen und das Hörvermögen erhalten oder wiederherstellen. Ein operativer Eingriff, der sich auf das Mesotympanon und das Epitympanon begrenzt, ist umstritten. In dieser Studie bewerteten die Autoren funktionelle und anatomische Ergebnisse einer transmeatalen Attikotomie bei Cholesteatomen, die auf Epitympanon und Mesotympanon begrenzt ist.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Aus der Gutachtenpraxis: Verwechslung von Schilddrüsengewebe und Zenker-Divertikel – ein Behandlungsfehler

Laryngo-Rhino-Otol 2017; 96: 183-184
DOI: 10.1055/s-0043-101413

Hinweis Die Gastautoren des folgenden Beitrages sind Hals-Nasen-Ohren-Arzt (Prof. Ellies) und Viszeralchirurg (Dr. Stapel) und hauptamtlich beim MDK Niederachsen tätig. Sie schildern einen ungewöhnlichen und lehrreichen Fall aus ihrer praktischen Tätigkeit. Zu den Aufgaben des MDK gehört auch die Begutachtung von Behandlungsfehlern im Auftrage von Krankenkassen. Ansprechpartner eines Patienten, der einen Behandlungsfehler vermutet, ist in einem solchen Fall die zuständige Krankenkasse, die sich dann mit dem MDK in Verbindung setzt.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Narrow-Band-Endoskopie spürt frühe Laryngopharyngeal-Karzinome am besten auf

Laryngo-Rhino-Otol 2017; 96: 145-146
DOI: 10.1055/s-0042-124128

Ni X-G et al.; Narrow band imaging versus autoflourescence imaging for head and neck squamous carcinoma detection: a prospective study; J Laryngol Otol 2016; 130: 1001–1006 Frühe Stadien von Kopf-Hals-Karzinomen lassen sich durch herkömmlichen bildgebende Verfahren wie CT oder MRT nur sehr schwer nachweisen. Neue endoskopische Methoden wie die Narrow-Band- oder Autofluoreszenz-Endoskopie können die Oberflächendarstellung der Mukosa verbessern. Unklar war bisher, welche der beiden Methoden besser zur Diagnostik von laryngopharyngealen Malignomen geeignet ist.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Der Septumschlitten zum Einbringen von Spreader Grafts bei der Rhinoplastik

Laryngo-Rhino-Otol 2017; 96: 151-154
DOI: 10.1055/s-0043-101834

© Georg Thieme Verlag KG Stuttgart · New York

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Laudatio

Laryngo-Rhino-Otol 2017; 96: 148-149
DOI: 10.1055/s-0043-101862

Prof. Dr. Jan Helms, von 1976 bis 1987 Direktor der Universitäts-HNO-Klinik Mainz, von 1987 bis 2005 in die gleiche Position an die Universität Würzburg berufen, wird am 03.03.2017 80 Jahre alt. Jan Helms ist eine Institution in der HNO-Heilkunde. Aus Kiel stammend begleitet ihn sein norddeutsch-klarer Duktus bis heute. Bereits das Studium verschlug in jedoch mit Medizinsemestern in München und Tübingen in den tiefen Süden. Er schloss das Studium 1962 in München mit der Ärztlichen Prüfung ab. 1963 erlangte er die Promotion zum Dr. med., und zwar ebenfalls in München. Nach Wanderjahren als Medizinalassistent, die ihn nach Tübingen, Bremen und Hamburg führten, folgten weitere frühe Lehrjahre als Stipendiat der DFG am Physiologisch-Chemischen Institut 1965 bis 1967 bei Prof. Karlson in Marburg. Hier bestimmten pharmakologische Untersuchungen zur toxischen Hepatopathie seine frühen Arbeiten. Diese Zeit sollte seine wissenschaftliche Laufbahn nachhaltig beeinflussen.
[...]

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Eine verlegte Stirnhöhle mit orbitaler Schwellung

Laryngo-Rhino-Otol 2017; 96: 180-182
DOI: 10.1055/s-0043-103277

© Georg Thieme Verlag KG Stuttgart · New York

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Transplantatgewinnung zur Trommelfellrekonstruktion

Laryngo-Rhino-Otol 2017; 96: 150-150
DOI: 10.1055/s-0043-101420

© Georg Thieme Verlag KG Stuttgart · New York

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Aktuelle Entwicklung der molekular zielgerichteten Therapie von Kopf-Hals-Karzinomen

Laryngo-Rhino-Otol 2017; 96: 185-198
DOI: 10.1055/s-0043-101412

© Georg Thieme Verlag KG Stuttgart · New York

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Chirurgie der inneren Nase

Laryngo-Rhino-Otol 2017; 96: 201-204
DOI: 10.1055/s-0043-101410

© Georg Thieme Verlag KG Stuttgart · New York

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Kommentar der Schriftleitung

Laryngo-Rhino-Otol 2017; 96: 141-141
DOI: 10.1055/s-0043-101418

Liebe Leserinnen und Leser,in „Referiert und diskutiert" besprechen wir eine amerikanische Krebsregister Analyse, die zeigt, dass die adjuvante Radiochemotherapie gegenüber der adjuvanten Radiotherapie nach Operation von Speicheldrüsenmalignomen keinen Vorteil bringt. Diese Meinung wird auch in den meisten deutschen Tumorboards vertreten 1. Anschließend wird eine transmeatale Attikotomie zur Operation umschriebener Cholesteatome vorgestellt. Das ist eine interessante Methode für ausgewählte Fälle. Narrow-Band-Imaging zur Frühdiagnostik von Malignomen, weil wir bessere Methoden zur Früherkennung brauchen; ob Narrow-Band-Imaging 2 dazu geeignet ist, müssen zukünftige kontrollierte klinische Studien belegen.
[...]

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Population pharmacokinetic modelling of rupatadine solution in 6–11 year olds and optimisation of the experimental design in younger children

by Eva Santamaría, Javier Alejandro Estévez, Jordi Riba, Iñaki Izquierdo, Marta Valle

Aims

To optimise a pharmacokinetic (PK) study design of rupatadine for 2–5 year olds by using a population PK model developed with data from a study in 6–11 year olds. The design optimisation was driven by the need to avoid children's discomfort in the study.

Methods

PK data from 6–11 year olds with allergic rhinitis available from a previous study were used to construct a population PK model which we used in simulations to assess the dose to administer in a study in 2–5 year olds. In addition, an optimal design approach was used to determine the most appropriate number of sampling groups, sampling days, total samples and sampling times.

Results

A two-compartmental model with first-order absorption and elimination, with clearance dependent on weight adequately described the PK of rupatadine for 6–11 year olds. The dose selected for a trial in 2–5 year olds was 2.5 mg, as it provided a Cmax below the 3 ng/ml threshold. The optimal study design consisted of four groups of children (10 children each), a maximum sampling window of 2 hours in two clinic visits for drawing three samples on day 14 and one on day 28 coinciding with the final examination of the study.

Conclusions

A PK study design was optimised in order to prioritise avoidance of discomfort for enrolled 2–5 year olds by taking only four blood samples from each child and minimising the length of hospital stays.

http://ift.tt/2pe8gRW

The risk of bias in randomized controlled trials in otorhinolaryngology: hardly any improvement since 1950

Abstract

Background

Randomized Controlled Trials (RCTs) represent the most valuable study design to evaluate the effectiveness of therapeutic interventions. However, flaws in design, conduct, analysis, and reporting of RCTs can cause the effect of an intervention to be under- or overestimated. These biased RCTs may be included in literature reviews. To make the assessment of Risk of Bias (RoB) consistent and transparent, Cochrane published a RoB tool, with which RoB is assessed per item as "low", "unclear" or "high". Our objective was to provide an overview of RoB assessments of RCTs in otorhinolaryngology over time, and to identify items where improvement is still warranted.

Methods

We retrieved Cochrane reviews in the otorhinolaryngologic research field published in 2012 and 2013. We used all judgments per item as assessed by the review authors of the included RCTs. We evaluated the association between "low RoB" vs. "unclear and high RoB" and the year of publication (time strata: '<1990', '1990–1995', '1996–2000', '2001–2005', '2006–2012') per item using binary logistic regression.

Results

We extracted the RoB assessments from 42 Cochrane reviews that had included 402 RCTs (median number of RCTs per review: 7, range 1–40). In total 2,356 items were assessed (mean number of assessed items per RCT: 5.9, standard deviation 1.8). On binary logistic regression, RCTs published in 2006–2012, compared with those published before 1990, were more likely to have a low RoB for two items: random sequence generation (odds ratio 6.09 [95% confidence interval: 3.11–11.95]) and allocation concealment (3.59 [1.87–6.90]). On all other items, there was no significant increase in the proportion of low RoB when comparing RCTs published in 2006–2012 with RCTs published before 1990.

Conclusion

Although there were some positive developments in the RoB assessments in otorhinolaryngology, a further decrease in RoB is still warranted on several items. Currently, biased RCTs are included in Cochrane reviews and effects of therapeutic interventions can be under- or overestimated, with implications for clinical patient care.

http://ift.tt/2oLtOCG

Clinical Thyroidology High-Impact Articles

FREE ACCESS through May 2, 2017
Read Now:

Levothyroxine Therapy of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy Does Not Improve Cognitive Function in the Offspring
Jerome M. Hershman

Postoperative Thyroglobulin and Neck Ultrasound Are Useful for Risk Restratification and Decision to Perform ¹³¹I Ablation
Stephanie A. Fish

Intensity of ¹⁸F-FDG Uptake in Metastatic Differentiated Thyroid Cancer Fails to Predict Growth in Individual Metastatic Lesions
Martin Biermann

Hyperthyroidism with Severe Liver Dysfunction Can Be Managed by RAI and Extracorporeal Albumin Dialysis and Hemodialysis
Jacques Orgiazzi

 

The post Clinical Thyroidology High-Impact Articles appeared first on American Thyroid Association.

http://ift.tt/2oSYc01

Contribution of health care factors to the burden of skin disease in the United States

The American Academy of Dermatology has developed an up-to-date national Burden of Skin Disease Report on the impact of skin disease on patients and on the US population. In this second of 3 manuscripts, data are presented on specific health care dimensions that contribute to the overall burden of skin disease. Through the use of data derived from medical claims in 2013 for 24 skin disease categories, these results indicate that skin disease health care is delivered most frequently to the aging US population, who are afflicted with more skin diseases than other age groups.

http://ift.tt/2oSZlVl

Apple body type information improves validity of the STOP-BANG questionnaire for detecting obstructive sleep apnea

I read with interest the article, entitled "Incorporating body-type (apple vs. pear) in STOP-BANG questionnaire improves its validity to detect OSA", by Sangkum and colleagues [1]. The authors conducted a validation study by adding extra item of "apple body type" to the STOP-BANG questionnaire for detecting obstructive sleep apnea (OSA). The authors used sleep polysomnography (PSG) as a gold standard of OSA. The authors concluded that adding the body type item to the STOP-BANG questionnaire improved not only prediction of OSA but also moderate-severe OSA by presenting odds ratio from logistic regression analysis.

http://ift.tt/2oqtfwj

Inattentional blindness - Do we really see what we see?

Vigilance is essential to safe anesthesia care. The ability for the anesthesiologist to note clinical change, analyze the events and take effective and timely action is critical to our practice. In this study, Dr. Ho and colleagues turn our attention to an understudied phenomenon- inattentional blindness [1]. This is defined as the failure to note events or actions that are in plain view, especially when that event is unexpected [2]. In this study, practicing academic anesthesiologists and medical students were asked to report on any abnormal vital signs or activities in a video of a simulated patient.

http://ift.tt/2oJydHM

The effect of dexmedetomidine on renal function in patients undergoing cardiac valve replacement under cardiopulmonary bypass: A double-blind randomized controlled trial

We attempted to explore the effect of Dex on renal function in patients with cardiac valve replacement under cardiopulmonary bypass (CPB).

http://ift.tt/2pPJYdl

The effect of handedness and laterality in a microlaryngeal surgery simulator

Publication date: Available online 18 April 2017
Source:American Journal of Otolaryngology
Author(s): Matthew R. Naunheim, Amanda Le, Matthew M. Dedmon, Ramon A. Franco, Jennifer Anderson, Phillip C. Song
PurposeThere are no controlled prospective studies evaluating the effect of dominant handedness in left- and right-sided surgery in otolaryngology. Endoscopic microlaryngeal phonosurgery is an ideal procedure to assess technical aspects of handedness and laterality, due to anatomic symmetry. In this study, we analyzed (1) choice of surgical approach and (2) outcomes based on handedness and laterality in a microlaryngeal simulator.MethodsUsing a validated high-fidelity phonosurgery model, a prospective cohort of 19 expert laryngologists undertook endoscopic resection of a simulated vocal fold lesion. These resections were video-recorded and scored by 2 blinded expert laryngologists using a validated global rating scale, procedure-specific rating scale, and a hand preference analysis.ResultsThere were 18 right-handed participants and 1 left-handed. 12 left and 7 right excisions were evaluated. Cronbach's alpha for inter-rater reliability was good (0.871, global scale; and 0.814, procedure-specific scale). Surgeons used their dominant hand 78.9% of the time for both incision and dissection. In cases where the non-dominant hand would have been preferred, surgeons used the non-dominant hand only 36.4% of the time for incision and dissection. Use of the non-dominant hand did not influence global or procedural rating (p=0.132 and p=0.459, respectively).ConclusionsIn this simulation of microlaryngeal surgery, there were measurable differences in surgical approaches based on hand dominance, with surgeons preferring to cut and perform resection with the dominant hand despite limitations in the instrumentation and exposure. Regardless of hand preference, overall outcomes based on global rating and technique specific rating scales were not significantly different.



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Interleukin-1 receptor associated kinase 1 is a potential therapeutic target of anti-inflammatory therapy for systemic lupus erythematosus

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Mingfang Li, Datang Yu, Bing Ni, Fei Hao
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas^lpr/Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6.lpr mice. IRAK-Inh treatment or knockdown of IRAK1 by specific siRNA decreased the relative levels of NF-κBp65 phosphorylation in human PBMCs from SLE patients. Therefore, IRAK1 may be a potential target for anti-inflammatory therapy for SLE and other inflammatory diseases.



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Pediatric sleep-disordered breathing: an update on diagnostic testing.

Purpose of review: Recent advances in diagnostic testing for obstructive sleep apnea in children have refined the standard tests while identifying several new tools that hold promise to radically change how we diagnose sleep apnea. Recent findings: Studies have demonstrated that the polysomnogram may be modified to permit home assessment of sleep disturbed breathing in children to ensure more widespread access to the test. Alternately, questionnaires, nocturnal oximetry, and diagnostic urinary biomarkers have shown great promise as both sensitive and specific tools to diagnose sleep apnea in children as well as track the severity of the disease. Summary: The gold standard polysomnogram has been refined to permit its application in a modified form at home and for brief examinations in children. This standard has been challenged on several fronts, including questionnaires, nocturnal oximetry, drug-induced sleep endoscopy, and noninvasive urinary biomarkers that may ultimately supplant polysomnography as the gold standard to diagnose obstructive sleep apnea syndrome in children. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The implications of immunization in the daily practice of pediatric anesthesia.

Purpose of review: Vaccination is an important prevention measure, but requires an intact immune system. Surgery and anesthesia suppress the immune system and may interfere with the benefits of immunization. Moreover, common vaccine side-effects may be misinterpreted as postsurgical complications. This review summarizes the essential basis of immunization and its potential interactions with anesthesia. Recent findings: Vaccines have mild side-effects, such as fever, but may lead to serious complications in immunocompromised patients. Surgery and anesthesia may decrease the efficacy of a vaccine, or promote vaccine-related complications. It, therefore, reasonable to schedule surgery and anesthesia with a delay either before or after vaccine administration, but there is no consensus among anesthesiologists and pediatricians regarding this timing. Summary: Inactive vaccines are generally well tolerated. Live vaccines provide an effective and long-lasting immunization, but may carry more serious complications. Elective operations should be postponed 1 week after an inactive vaccine and 3 weeks after immunization with a live vaccine. To avoid misinterpretation of vaccine-related side-effects, vaccination should be also delayed after surgery. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The Emerging Importance of Skeletal Muscle Function in Assessing Candidates for Transplantation.

No abstract available

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Paying it Forward: Live Kidney Donation now to (POSSIBLY) Benefit a Long-term Future Recipient.

No abstract available

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Short Course of Postoperative Hepatitis B Immunoglobulin plus Antivirals Prevents Reinfection of Liver Transplant Recipients.

Background: Hepatitis B immune globulin (HBIG) has been an integral component of prophylaxis against hepatitis B virus (HBV) recurrence in liver transplantation (LT) recipients, but HBIG is costly and inconvenient to administer, prompting consideration of alternative regimens. Methods: In this retrospective cohort, we report on the success of antiviral therapy combined with a short course (in hospital only) HBIG in liver transplant recipients with HBV DNA

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Graft Quality and Prediction of Outcome After Liver Transplantation.

No abstract available

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AN Evaluation of the Safety and Efficacy of Simultaneous Bilateral Nephrectomy and Renal Transplantation for Polycystic Kidney Disease A Twenty Year Experience1.

Background: Many strategies regarding timing of native nephrectomies exist for patients with symptomatic polycystic kidney disease (PCKD). Methods: This is a single-center, retrospective study of 594 adults with PCKD who had renal transplants from 1994-2014. Three groups were analyzed: renal transplant-only recipients (tx alone), recipients of simultaneous bilateral nephrectomies and transplant (simultaneous), and recipients with pretransplant bilateral nephrectomies (pre). The primary outcome was graft survival. Secondary outcomes included postoperative complications. Results: 565 adults with PCKD received kidney transplants (303 tx alone, 161 simultaneous, 27 pre). 10-year posttransplant graft survival was 68.5%, 63.6% and 65.7% for tx alone, simultaneous, and precohorts (p=0.86). No statistically significant differences were observed in rates of postoperative ileus, deep vein thrombosis, small bowel obstruction, urinary stricture, urine leak, hernia formation, and delayed graft function. More wound complications were seen in prepatients (25.9% vs 11.1% tx alone, 5.1% simultaneous; p=0.03) while simultaneous patients had a lower incidence of lymphocele (1.3% vs 11.1% pre, 10.2% tx-alone; p=0.002). Importantly, simultaneous patients had more renal vascular thromboses (4.4% vs 1.3% tx alone, 0% pre; p=0.04). 16.3% of renal transplant alone patients required nephrectomy at 10 yrs follow up. 29 patients were referred for transplant having had nephrectomies and were ultimately not transplanted. In the 4 of these patients who had data available for analysis, the mean PRA significantly increased after nephrectomy was performed. Conclusions: Simultaneous bilateral nephrectomy can be safely performed at the time of renal transplantation, however carries a significantly increased risk of renal vascular thrombosis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Alloimmunization After Cryopreserved Arterial Allografts in a Patient on a Kidney Transplantation Waiting List.

No abstract available

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Sensitivity, not Rationality, is Paramount in Addressing the Family Overrule.

No abstract available

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The Use of Continuous Hypothermic Extended Criteria Graft Perfusion Will Lead to an Increase in Transplantable Organs.

No abstract available

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Communication Skills to Increase Donor Consent Rate Based on the Concept of "Moral Imperative".

No abstract available

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Liver Transplantation in the Obese Cirrhotic Patient.

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict BMI cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss prior to transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgery have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals, and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent U.S. liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data and highlight areas where additional research is needed. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Biodistribution of Liver-Derived Mesenchymal Stem Cells Following Peripheral Injection in a Hemophilia a Patient.

Background: With the exception of liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive replacement therapy. Liver-derived stem cells are in clinical development for inborn and acquired liver diseases and could represent a curative treatment for hemophilia A. The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem cells (MSCs) have been shown to control joint bleeding in animal models of hemophilia. Adult-derived human liver stem cells (ADHLSCs) have mesenchymal characteristics and have been shown able to engraft in and repopulate both animal and human livers. Thus the objectives were to evaluate the potency of ADHLSCs to control bleeding in a hemophilia A patient and assess the biodistribution of the cells following intraveinous injection. Methods: A patient suffering from hemophilia A was injected with repeated doses of ADHLSCs via a peripheral vein (35 million 111In-oxine-labeled cells, followed by 125 million cells the next day, and 3 infusions of 250 million cells every 2 weeks thereafter; total infusion period: 50 days). Results: Following cell therapy, we found a temporary (15 weeks) decrease in the patient's FVIII requirements and severe bleeding complications, despite a lack of increase in circulating FVIII. The cells were safely administered to the patient via a peripheral vein. Biodistribution analysis revealed an initial temporary entrapment of the cells in the lungs, followed by homing to the liver and to a joint afflicted with hemarthrosis. Conclusion: These results suggest the potential use of ADHLSCs in the treatment of hemophilia A. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Population Based Analysis and Projections of Liver Supply Under Redistricting.

Background: To reduce the geographic heterogeneity in liver transplant (LT) allocation the United Network of Organ Sharing (UNOS) has proposed redistricting, which is impacted by both donor supply and LT demand. We aimed to determine the impact of demographic changes on the redistricting proposal and characterize causes behind geographic heterogeneity in donor supply. Methods: We analyzed adult donors from 2002-2014 from the UNOS database and calculated regional liver donation and utilization stratified by age, race, and body mass index. We used US population data to make regional projections of available donors from 2016 to 2025, incorporating the proposed 8-region redistricting plan. We used donors/100 000 population age 18-84 (D/100K) as a measure of equity. We calculated a coefficient of variation (standard deviation/mean) for each regional model. We performed an exploratory analysis where we used national rates of donation, utilization and both for each regional model. Results: The overall projected D/100K will decrease from 2.53 to 2.49 from 2016-2025. The coefficient of variation in 2016 is expected to be 20.3% in the 11-region model and 13.2% in the 8-region model. We found that standardizing regional donation and utilization rates would reduce geographic heterogeneity to 4.9% in the 8-region model and 4.6% in the 11-region model. Conclusion: The 8-region allocation model will reduce geographic variation in donor supply to a significant extent, however we project that geographic disparity will marginally increase over time. Though challenging, interventions to better standardize donation and utilization rates, would be impactful in reducing geographic heterogeneity in organ supply. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Patient preferences for outcomes after kidney transplantation: a best-worst scaling survey.

Background: The care of kidney transplant recipients involves a balance between maximizing graft survival and serious adverse outcomes. This study aimed to quantify patients' preferences and trade-offs for important outcomes following transplantation. Methods: A best-worst scaling survey analysed by multinomial-logit models, was used to calculate normalized preference scores (0 best, 1 worst), for varying years of graft duration and risk of dying before graft failure, cancer, cardiovascular disease, diabetes, infection, anxiety/depression, diarrhoea/nausea, and weight gain. Willingness to trade years of graft survival to minimise the risk of adverse outcomes was calculated. Results: Ninety-three transplant recipients from 2 Australian transplant units and an on-line panel (aged 18-69 years, mean time since transplantation, 7 years) completed the survey. Graft loss at 1 year was the least desirable outcome (mean preference value 0.0:95% confidence intervals:-0.05 to 0.05) and worse than a 100% risk of dying before graft loss (0.17:0.12 to 0.23). Graft duration of 5 years had the same preference scores (ie, as bad) as the maximum risk of all adverse outcomes including a 100% risk of dying before graft failure. To achieve zero risk of cancer, dying, and cardiovascular disease participants were only willing to trade 3.1(2.1 to 4.7), 1.7(1.1 to 2.5), and 1.2(0.8 to 1.8) years of graft survival respectively, and less than 1 year for all other outcomes. Conclusion: Transplant recipients regarded graft loss as worse than death and showed minimal willingness to trade a reduction in this outcome with an improvement in any other outcome. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Developing consensus-based priority outcome domains for trials in kidney transplantation: a multinational Delphi survey with patients, caregivers and health professionals.

Background: Inconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision-making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals. Methods: In a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During Round 2 and 3, participants rerated the outcomes after reviewing their own score, the distribution of the respondents' scores, and comments. We calculated the median, mean, and proportion rating 7-9 (critically important), and analyzed comments thematically. Results: 1018 participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed Round 1, and 779 (77%) completed Round 3. The top 8 outcomes that met the consensus criteria in Round 3 (mean >=7.5, median >=8 and proportion >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin) and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to 6 outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified 5 themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps. Conclusions: Graft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Toward establishing core outcome domains for trials in kidney transplantation: Report of the Standardized Outcomes in Nephrology - Kidney Transplantation (SONG-Tx) Consensus workshops.

Background: Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. Methods: We convened 2 international SONG-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. Results: Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders - inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. Conclusions: Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Kidney Paired Donation and the "Valuable Consideration" Problem: The Experiences of Australia, Canada and the United States.

As organ donation rates remain unable to meet the needs of individuals waiting for transplants, it is necessary to identify reasons for this shortage and develop solutions to address it. The introduction of kidney paired donation (KPD) programs represents 1 such innovation that has become a valuable tool in donation systems around the world. While KPD has been successful in increasing kidney donation and transplantation, there are lingering questions about its legality. Donation through KPD is done in exchange for - and with the expectation of - a reciprocal kidney donation and transplantation. It is this reciprocity that has caused concern about whether KPD complies with existing law. Organ donation systems around the world are almost universally structured to legally prohibit the commercial exchange of organs. Australia, Canada, and the United States have accomplished this goal by prohibiting the exchange of an organ for 'valuable consideration', which is a legal term that has not historically been limited to monetary exchange. Whether or not KPD programs violate this legislative prohibition will depend on the specific legislative provision being considered, and the legal system and case law of the particular jurisdiction in question. This paper compares the experiences of Australia, Canada, and the United States in determining the legality of KPD and highlights the need for legal clarity and flexibility as donation and transplantation systems continue to evolve. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Phosphatidylinositol 3-phosphate-binding protein AtPH1 controls the localization of the metal transporter NRAMP1 in Arabidopsis [Plant Biology]

"Too much of a good thing" perfectly describes the dilemma that living organisms face with metals. The tight control of metal homeostasis in cells depends on the trafficking of metal transporters between membranes of different compartments. However, the mechanisms regulating the location of transport proteins are still largely unknown. Developing...

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Correction for Zhong et al., B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial [Correction]

MEDICAL SCIENCES Correction for "B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial," by Jia Zhong, Oskar Karlsson, Guan Wang, Jun Li, Yichen Guo, Xinyi Lin, Michele Zemplenyi, Marco Sanchez-Guerra, Letizia Trevisi, Bruce Urch, Mary Speck, Liming Liang, Brent A. Coull, Petros Koutrakis,...

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Correction for Mylvaganam et al., Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection [Correction]

IMMUNOLOGY AND INFLAMMATION Correction for "Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection," by Geetha H. Mylvaganam, Daniel Rios, Hadia M. Abdelaal, Smita Iyer, Gregory Tharp, Maud Mavinger, Sakeenah Hicks, Ann Chahroudi, Rafi Ahmed, Steven E. Bosinger, Ifor R. Williams, Pamela J. Skinner, Vijayakumar Velu, and Rama...

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Parathyroid hormone controls paracellular Ca2+ transport in the thick ascending limb by regulating the tight-junction protein Claudin14 [Physiology]

Renal Ca2+ reabsorption is essential for maintaining systemic Ca2+ homeostasis and is tightly regulated through the parathyroid hormone (PTH)/PTHrP receptor (PTH1R) signaling pathway. We investigated the role of PTH1R in the kidney by generating a mouse model with targeted deletion of PTH1R in the thick ascending limb of Henle (TAL)...

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Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome [Physiology]

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess,...

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Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations [Neuroscience]

Charcot–Marie–Tooth disease type 2D (CMT2D) is a peripheral nerve disorder caused by dominant, toxic, gain-of-function mutations in the widely expressed, housekeeping gene, GARS. The mechanisms underlying selective nerve pathology in CMT2D remain unresolved, as does the cause of the mild-to-moderate sensory involvement that distinguishes CMT2D from the allelic disorder distal...

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Parietal neurons encode expected gains in instrumental information [Neuroscience]

In natural behavior, animals have access to multiple sources of information, but only a few of these sources are relevant for learning and actions. Beyond choosing an appropriate action, making good decisions entails the ability to choose the relevant information, but fundamental questions remain about the brain's information sampling policies....

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Dynamic neural architecture for social knowledge retrieval [Neuroscience]

Social behavior is often shaped by the rich storehouse of biographical information that we hold for other people. In our daily life, we rapidly and flexibly retrieve a host of biographical details about individuals in our social network, which often guide our decisions as we navigate complex social interactions. Even...

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Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis [Immunology and Inflammation]

Despite continuous interest in multiple sclerosis (MS) research, there is still a lack of neuroprotective strategies, because the main focus has remained on modulating the immune response. Here we performed in-depth analysis of neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and in in vitro studies regarding the effect of the well-established...

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International consensus (ICON) on: clinical consequences of mite hypersensitivity, a global problem

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allerg...

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Quantitative criticism of literary relationships [Computer Sciences]

Authors often convey meaning by referring to or imitating prior works of literature, a process that creates complex networks of literary relationships ("intertextuality") and contributes to cultural evolution. In this paper, we use techniques from stylometry and machine learning to address subjective literary critical questions about Latin literature, a corpus...

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Intracellular metabolite {beta}-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity [Immunology and Inflammation]

Sensing and reacting to tissue damage is a fundamental function of immune systems. Macrophage inducible C-type lectin (Mincle) is an activating C-type lectin receptor that senses damaged cells. Notably, Mincle also recognizes glycolipid ligands on pathogens. To elucidate endogenous glycolipids ligands derived from damaged cells, we fractionated supernatants from damaged...

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Climate change both facilitates and inhibits invasive plant ranges in New England [Ecology]

Forecasting ecological responses to climate change, invasion, and their interaction must rely on understanding underlying mechanisms. However, such forecasts require extrapolation into new locations and environments. We linked demography and environment using experimental biogeography to forecast invasive and native species' potential ranges under present and future climate in New England,...

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Conformational equilibria of light-activated rhodopsin in nanodiscs [Biophysics and Computational Biology]

Conformational equilibria of G-protein–coupled receptors (GPCRs) are intimately involved in intracellular signaling. Here conformational substates of the GPCR rhodopsin are investigated in micelles of dodecyl maltoside (DDM) and in phospholipid nanodiscs by monitoring the spatial positions of transmembrane helices 6 and 7 at the cytoplasmic surface using site-directed spin labeling...

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Unraveling the disease consequences and mechanisms of modular structure in animal social networks [Ecology]

Disease risk is a potential cost of group living. Although modular organization is thought to reduce this cost in animal societies, empirical evidence toward this hypothesis has been conflicting. We analyzed empirical social networks from 43 animal species to motivate our study of the epidemiological consequences of modular structure in...

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Selective Purcell enhancement of two closely linked zero-phonon transitions of a silicon carbide color center [Applied Physical Sciences]

Point defects in silicon carbide are rapidly becoming a platform of great interest for single-photon generation, quantum sensing, and quantum information science. Photonic crystal cavities (PCCs) can serve as an efficient light–matter interface both to augment the defect emission and to aid in studying the defects' properties. In this work,...

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Structure of aryl O-demethylase offers molecular insight into a catalytic tyrosine-dependent mechanism [Biochemistry]

Some strains of soil and marine bacteria have evolved intricate metabolic pathways for using environmentally derived aromatics as a carbon source. Many of these metabolic pathways go through intermediates such as vanillate, 3-O-methylgallate, and syringate. Demethylation of these compounds is essential for downstream aryl modification, ring opening, and subsequent assimilation...

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Resistance to action potential depression of a rat axon terminal in vivo [Neuroscience]

The shape of the presynaptic action potential (AP) has a strong impact on neurotransmitter release. Because of the small size of most terminals in the central nervous system, little is known about the regulation of their AP shape during natural firing patterns in vivo. The calyx of Held is a...

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Mass spectrometric identification of intermediates in the O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion in FNR [Biochemistry]

The iron-sulfur cluster containing protein Fumarate and Nitrate Reduction (FNR) is the master regulator for the switch between anaerobic and aerobic respiration in Escherichia coli and many other bacteria. The [4Fe-4S] cluster functions as the sensory module, undergoing reaction with O2 that leads to conversion to a [2Fe-2S] form with...

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SMARCE1 is required for the invasive progression of in situ cancers [Cell Biology]

Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here,...

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Structural basis of pH-dependent client binding by ERp44, a key regulator of protein secretion at the ER-Golgi interface [Biochemistry]

ERp44 retrieves some endoplasmic reticulum (ER)-resident enzymes and immature oligomers of secretory proteins from the Golgi. Association of ERp44 with its clients is regulated by pH-dependent mechanisms, but the molecular details are not fully understood. Here we report high-resolution crystal structures of human ERp44 at neutral and weakly acidic pH....

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Nasal ala reconstruction: Tunnelled island pedicle melolabial flap; jigsaw puzzle advancement flap; spiral flap; dog-ear island pedicle flap and banner melolabial transposition flap.

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Skin tumours of the nasal ala are common and surgery is the treatment
of choice. Nasal ala reconstruction is challenging due to the reduced
mobility and unique features of its thick and sebaceous skin. The
natural arc of the ala and its boundary with the cheek are difficult
features to reproduce. One should bear in mind the functional and
cosmetic risks of nasal ala reconstruction. A distorted nasal contour
may impair the nasal valve; the alar rim may notch or elevate; facial
symmetry may be disrupted by blunting of the alar crease, trapdooring,
bridging of the nasofacial sulcus and poor colour and texture match.

Our aim is to review and compare the functional and cosmetic results
of different local flaps used to correct intermediate-thickness
defects on the nasal ala after surgical excision of cutaneous tumours.
We present representative patients who were treated at our
Dermatological Surgery Unit from June 2015 to September 2016.

The choice of the flap was adapted to the patients' physiognomy and
the defects' size: tunnelled island pedicle melolabial flap [Figure
1]; jigsaw puzzle advancement flap [Figure 2]; spiral flap [Figure 3];
dog-ear island pedicle flap [Figure 4] and banner melolabial
transposition flap [Figure 5]. Surgery was performed under
loco-regional anaesthesia, in an outpatient basis, followed by
prophylactic antibiotic therapy. There were neither immediate
complications nor subsequent flap necrosis. The tumours were
completely excised.
Figure 1: Female, 86-year-old, nodular ulcerated basal cell carcinoma
in the nasal ala: tunnelled island pedicle melolabial flap. (a)
Surgical plan, (b) primary defect, (c) secondary defect after
tunnelling of the flap, (d) immediate post-operative, (e and f) result
after healing (10 months after surgery).

Click here to view
Figure 2: Male, 76-year-old, nodular basal cell carcinoma on the nasal
ala: jigsaw puzzle advancement flap. (a) surgical plan, (b) primary
and secondary defects, (c) anchoring sutures secure the flap in place;
(d) immediate post-operative, (e) result after healing (3 months after
surgery).

Click here to view
Figure 3: Female, 76-year-old, nodular basal cell carcinoma on the
nasal ala: spiral flap, a combination of advancement and rotation. (a)
Surgical plan, (b) immediate post-operative, (c) result after healing
(2 months after surgery).

Click here to view
Figure 4: Female, 76-year-old, basal cell carcinoma on the nasal ala:
dog-ear island flap, combining two flaps: cheek advancement and
rotated island pedicle. (a) Surgical plan, (b) primary defect, (c)
immediate post-operative, (d) day 7 post-operative, (e) result after
healing (1 month after surgery).

Click here to view
Figure 5: Male, 83-year-old, two nodular basal cell carcinomas on the
nasal ala and dorsum: Banner's melolabial transposition flap. (a)
Surgical plan, (b) primary defect, (c) immediate post-operative, (d)
result after healing (7 months after surgery)

Click here to view


Facial symmetry was well preserved by the spiral and jigsaw puzzle
flaps [Figure 2] and [Figure 3]. The nasal sulcus was left intact by
the spiral flap as well as the tunnelled melolabial island flap
[Figure 1] and [Figure 3]. The melolabial flaps and the dog-ear island
flap allowed for the correction of larger defects on the nasal ala
[Figure 1], [Figure 4] and [Figure 5]. The dog-ear island flap [Figure
4] obtained a good result despite the large size of the primary
defect. Banner's melolabial transposition flap [Figure 5] was used to
correct a complex defect involving not only the nasal ala but also the
nasal dorsum and resulted in facial asymmetry due to trapdooring.

The small size of the defects that can be addressed by the spiral and
puzzle flaps may explain their superior cosmetic results.[1],[2] The
tunnelled melolabial island flap, although technically demanding, may
produce excellent results; compared to the cheek-to-nose interpolation
flap, the tunnelling technique offers the advantage of being one-stage
procedure. The dog-ear island flap is an adaptation of the cheek
advancement flap; despite its apparent complexity, it offers a viable
alternative to the melolabial flaps,[3] with a lower risk of trapdoor
effect and with proper preservation of the alar contour. The discussed
flaps are useful alternatives to the bilobed transposition flap and
the skin graft for the surgical reconstruction of the nasal ala.

When planning the surgery, it is important to assess the primary
defect on the nasal ala: size and location (medial or lateral), depth,
involvement of other cosmetic units/subunits and extension to the alar
rim, nasal tip or adjacent cheek. Several techniques have been
developed that are useful for the reconstruction of defects of the
nasal ala. Based on our experience and a review of the literature, we
present an algorithm [Table 1] to optimise the choices in the
reconstruction of intermediate-thickness defects in nasal ala. In
[Table 2], we review the main advantages and caveats of some of the
most useful surgical techniques for nasal ala
reconstruction.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14]
Table 1: Nasal ala reconstruction: What is the optimal approach
according to the defects' size and location?

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Table 2: Nasal ala reconstruction: major advantages and potential
caveats of different surgical techniques

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In the nasal ala, given the paucity of surrounding skin and the
importance of minimising nasal ala distortion, flaps that recruit skin
from a distant site should be considered. Mastering different
techniques is essential for a surgeon to optimise treatment for each
patient. At the end of the day, the best choice depends on many
factors and should be adapted on a case-by-case basis and to the
surgeon's expertise.

--
Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480
alsfakia@gmail.com

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Primary Prevention of Food Allergy

Abstract

Food allergy is estimated to affect approximately 8% of children in the USA. This is a disease without any known treatment or cure and, for some, a disease that can be quite severe, even life-threatening. While recent advances in potential treatment have made remarkable strides, with two food-targeted immunotherapy products now in phase III trials, perhaps the biggest gains in the field have come in the advent of potential preventative strategies to avoid the development of food allergy in high-risk individuals. There have been multiple, randomized, controlled trials (RCTs) performed in the past 5 years that have demonstrated significant risk reduction from early allergen introduction. These include two trials for early peanut introduction and five trials for early egg introduction in the first year of life. The results indicate that primary prevention of food allergy through early allergen introduction may represent a strategy that could potentially avert tens of thousands of children from becoming food allergic. In support of the data for peanut, the National Institute of Allergy and Infectious Diseases recently sponsored an addendum to the 2010 food allergy guidelines, specifically recommending peanut be introduced in both high- and standard-risk infants to reduce the risk of developing peanut allergy. To date, no formal recommendations have been made for egg, however. This review will focus on the latest evidence supporting early introduction as a strategy to prevent food allergy, as well as on practical aspects for its successful implementation.

http://ift.tt/2oI1gvk

New Insights into Cockroach Allergens

Abstract

Purpose of Review

This review addresses the most recent developments on cockroach allergen research in relation to allergic diseases, especially asthma.

Recent Findings

The number of allergens relevant to cockroach allergy has recently expanded considerably up to 12 groups. New X-ray crystal structures of allergens from groups 1, 2, and 5 revealed interesting features with implications for allergen standardization, sensitization, diagnosis, and therapy.

Summary

Cockroach allergy is strongly associated with asthma particularly among children and young adults living in inner-city environments, posing challenges for disease control. Environmental interventions targeted at reducing cockroach allergen exposure have provided conflicting results. Immunotherapy may be a way to modify the natural history of cockroach allergy and decrease symptoms and asthma severity among sensitized and exposed individuals. The new information on cockroach allergens is important for the assessment of allergen markers of exposure and disease, and for the design of immunotherapy trials.

http://ift.tt/2oI6w0e

Impaired Vestibular Function After Cochlear Implantation in Children: Role of Static Posturography

Abstract

To identify vestibular dysfunction in children after cochlear implant surgery and to study the utility of static posturography in evaluating vestibular function in children. A prospective study was carried out on 25 children between 2 and 7 years of age with sensorineural hearing loss with no overt vestibular dysfunction. All children underwent static posturography using Synapsis Posturographic System (SPS) software (Version 3.0, REV C) using a static platform with foam. The centre of pressure (COP) shift was recorded as statokinesiogram on the software and the mean vestibular, visual and somesthetic scores were obtained. Cochlear implantation (CI) surgery was done with insertion of Med-El Pulsar standard cochlear implant with 12 twin electrodes. Children were evaluated again after 4 weeks of CI surgery (2 weeks after switch on) with static posturography on the same SPS software. The scores obtained were compared with pre op value and data analyzed statistically by paired t tests on SPSS 18 software. The mean age was 4.6 years with range 2–7 years. All the children in the study were able to complete the test with no difficulty and the mean time required for each child was 10.2 min. The mean pre op somesthetic score was 95.16 (SD 1.52) and post op score was 94.06 (SD 1.79). The mean pre op visual score was 86.64 (SD 2.24) and post op score was 82.55 (2.89). The mean pre op vestibular score was 84.11 (SD 2.20) and post op score was 73.66 (SD 4.25). Correlation and statistical analysis of the pre and post values of each score revealed statistically significant reduction in vestibular scores post CI. The vestibular system is at high risk of injury leading to vestibular dysfunction in children during CI. Our study found the static posturography as a simple, fast and efficient tool to screen children for vestibular dysfunction post CI. Identifying the dysfunction early can help in initiating early rehabilitation measures.

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Comparison of the coracoid and retroclavicular approaches for ultrasound-guided infraclavicular brachial plexus block

Abstract

Purpose

This prospective randomized study compared the coracoid and retroclavicular approaches to ultrasound-guided infraclavicular brachial plexus block (IBPB) in terms of needle tip and shaft visibility and quality of block. We hypothesized that the retroclavicular approach would increase needle tip and shaft visibility and decrease the number of needle passes compared to the coracoid approach.

Methods

A total of 100 adult patients who received IBPB block for upper limb surgery were randomized into two groups: a coracoid approach group (group C) and a retroclavicular approach group (group R). In group C, the needle was inserted 2 cm medial and 2 cm inferior to the coracoid process and directed from ventral to dorsal. In group R, the needle insertion point was posterior to the clavicle and the needle was advanced from cephalad to caudal. All ultrasound images were digitally stored for analysis. The primary aim of the present study was to compare needle tip and shaft visibility between the coracoid approach and retroclavicular approach in patients undergoing upper limb surgery. The secondary aim was to investigate differences between the two groups in the number of needle passes, sensory and motor block success rates, surgical success rate, block performance time, block performance-related pain, patient satisfaction, use of supplemental local anesthetic and analgesic, and complications.

Results

Needle tip visibility and needle shaft visibility were significantly better in group R (p = 0.040, p = 0.032, respectively). Block performance time and anesthesia-related time were significantly shorter in group R (p = 0.022, p = 0.038, respectively). Number of needle passes was significantly lower in group R (p = 0.044). Paresthesia during block performance was significantly higher in group C (p = 0.045). There were no statistically significant differences between the two groups in terms of sensory or motor block success, surgical success, block-related pain, and patient satisfaction.

Conclusion

The retroclavicular approach is associated with better needle tip and shaft visibility, reduced performance time and anesthesia-related time, less paresthesia during block performance, and fewer needle passes than the coracoid approach.

Trıal registry number

Clinicaltrials.gov (no. NCT02673086).

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Effect of oral carbohydrate with amino acid solution on serum oxidative/anti-oxidative status in healthy volunteers

Abstract

The aim of this work was to investigate the effect of oral carbohydrate with amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in healthy persons. Fourteen healthy volunteers were segregated into control and ONS groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the day of the experiment. Volunteers in the control group fasted after dinner and drank only water until 7:00 am on the day of the experiment. In both groups, blood was collected at 9:00 am. The serum total oxidant levels and antioxidant capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites) test and BAP (biological antioxidant potential) test, respectively. In the ONS group, the serum d-ROMs level was significantly lower than in the control group (297 ± 43 and 327 ± 41 U.CARR, respectively, p = 0.018), while the serum BAP level was significantly higher than the control group (2410 ± 432 and 1979 ± 397 µmol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that an ONS with arginine loading could decrease oxidative stress and increase antioxidant capacity in healthy volunteers.

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In Reply: Similarities between parasternal intercostal nerve block and subpectoral interfascial plane block

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The impact of body mass index on the risk of high spinal block in parturients undergoing cesarean delivery: a retrospective cohort study

Abstract

Purpose

To investigate the hypothesis that the risk of high spinal block is not increased in obese parturients undergoing cesarean delivery compared to non-obese parturients.

Methods

This is a retrospective study at an academic center. We searched the perioperative database for women who underwent cesarean delivery under spinal or combined spinal epidural anesthesia with hyperbaric bupivacaine ≥10.5 mg. A body mass index (BMI) ≥30 kg/m² was defined as obese. We categorized obesity into: obesity class I (BMI = 30–34.9 kg/m²), obesity class II (BMI = 35–39.9 kg/m²), obesity class III (BMI = 40–49.9 kg/m²), and super obese (BMI ≥50 kg/m²). The primary outcome was high spinal block defined as need to convert to general anesthesia within 20 min of spinal placement as a result of altered mental status, weakness, or respiratory distress resulting from the high block, or a recorded block height ≥T1.

Results

The analysis included 5015 women. High spinal blocks occurred in 29 patients (0.6%). The risk of high spinal was significantly different according to BMI (p = 0.025). In a multivariate model, BMI (p = 0.008) and cesarean delivery priority (p = 0.009) were associated with high blocks. BMI ≥50 kg/m² was associated with greater odds of high block compared to BMI <30 kg/m² [odds ratio (95% confidence interval): 6.3 (2.2, 18.5)]. Scheduled cesarean delivery was also associated with greater odds of high block compared with unscheduled delivery.

Conclusions

At standard spinal doses of hyperbaric bupivacaine used in our practice (≥10.5 mg), there were greater odds of high block in those with BMI ≥50 kg/m².

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Expression of low-density lipoprotein related receptors 5 and 6 (LRP5/6) in psoriasis skin

Abstract

Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signaling. Wnt ligands are thought to play an important role in innate immunity and psoriasis and recent studies assigned LRP5/6 anti-inflammatory properties.

The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analyzed before and after narrowband UV-B treatment.

Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin.

Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.

This article is protected by copyright. All rights reserved.

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A hypomorphic Egfr allele does not ameliorate the palmoplantar keratoderma caused by SLURP1 deficiency

Abstract

Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully recapitulates the human disease, with increased keratinocyte proliferation and thickening of the epidermis on the volar surface of the paws. There has long been speculation that SLURP1 serves as a ligand for a receptor that regulates keratinocyte growth and differentiation. We were intrigued that mutations leading to increased signaling through the epidermal growth factor receptor (EGFR) cause PPK. Here, we sought to determine whether reducing EGFR signaling would ameliorate the PPK associated with SLURP1 deficiency. To address this issue, we bred Slurp1-deficient mice that were homozygous for a hypomorphic Egfr allele. The hypomorphic Egfr allele, which leads to reduced EGFR signaling in keratinocytes, did not ameliorate the PPK elicited by SLURP1 deficiency, suggesting that SLURP1 deficiency causes PPK independently (or downstream) from the EGFR pathway.

This article is protected by copyright. All rights reserved.

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Ectopic expression of the transcription factor MafB in basal keratinocytes induces hyper-proliferation and perturbs epidermal homeostasis

Abstract

Mammalian epidermis is composed of four morphologically and functionally distinct layers of keratinocytes. The innermost basal layer consists of proliferating self-renewing keratinocytes, which also undergo asymmetric cell division to differentiate into post-mitotic suprabasal cells throughout life. Control of the balance between growth and differentiation of basal cells is important for epidermal homeostasis to prevent skin disorders including malignancies; however, the underlying mechanism remains to be elucidated. Recently, MafB was identified as one of the transcription factors that regulate epidermal keratinocyte differentiation. MafB is expressed in post-mitotic differentiating keratinocytes, and epidermal differentiation is partially impaired in MafB-deficient mice. To further establish the roles of MafB in the epidermis in vivo, we generated mice transgenic for MafB under the control of the basal cell-specific keratin (Krt) 14 promoter. In the epidermis of transgenic mice at embryonic day 18.5, the number of proliferating Krt14-positive basal-like cells was increased, and the granular and cornified layers were thickened. Furthermore, these MafB transgenic mice developed papillomas spontaneously with age. Therefore, MafB promotes differentiation in post-mitotic keratinocytes and simultaneously has potential to promote growth when ectopically expressed in undifferentiated basal keratinocytes.

This article is protected by copyright. All rights reserved.

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To Arginine Residues in the COOH-Terminal of Human β-Defensin-3 Constitute An Essential Motif for Antimicrobial Activity and IL-6 Production

Abstract

Human β-defensin-3 (HBD-3) possesses antimicrobial activities and the potential to induce proinflammatory cytokines. HBD-3 contains a unique motif of two arginine residues (Arg. R) in the COOH-terminal region. To understand the bioactive properties of the Arg residues of HBD-3, we examined antimicrobial activities against S. aureus and P. aeruginosa using synthetic HBD-2, HBD-3, and two variant peptides of HBD-3: the Arg-truncated variant designated desR HBD-3, and NRR HBD-3, in which both Arg residues were shifted to the N-terminal region. IL-6 production from keratinocytes was studied using the peptides. HBD-3 possessed approximately 5-fold more potent antimicrobial activities, evaluated as the minimum inhibitory concentration, against S.aureus compared with desR and NRR HBD-3, while no significant activity was observed in HBD-2. The antimicrobial activity of HBD-3 against S. aureus was well preserved even at high sodium chloride concentrations, but was attenuated in desR and NRR HBD-3. All the peptides exhibited similar antimicrobial activities against P. aeruginosa, but HBD-2 and desR HBD-3 showed diminished antimicrobial activities against P. aeruginosa at high salt concentrations. IL-6 production was significantly induced in keratinocytes with HBD-3, but not remarkably with stimulation by other peptide. These Arg residues are essential for the antimicrobial and biological properties of HBD-3.

This article is protected by copyright. All rights reserved.

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miR-128-1 is not required for hair pigmentation in mice

Abstract

MicroRNAs are endogenous, regulatory RNAs implicated in many biological processes including pigmentation. Software algorithms and in vitro experiments predict that microRNAs can target pigmentation pathway genes, but few have been tested in vivo. MiR-128-1, a microRNA within the strongly selected lactase locus in the human genome, has predicted pigmentation targets. To test the role of miR-128-1 in pigment regulation, we created C57BL/6 agouti miR-128-1 knockout mice and quantified melanin deposition in hair. miR-128-1 knockout mice have no detectable hair pigmentation phenotype. We conclude that miR-128-1 does not play a significant regulatory role in hair pigmentation in mice.

This article is protected by copyright. All rights reserved.

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An efficient method for gene knock-down by RNA interference in human skin mast cells

Abstract

Mast cells (MCs) from human skin have been notoriously resistant to gene manipulation, and a method to knock-down gene expression in in situ differentiated MCs is highly desired. The Dharmacon Accell^® transfection system proved successful on several "difficult-to-transfect" cells. In the present work, we therefore tested this method on skin-derived MCs using different siRNA entities. The siRNA was readily taken up, followed by pronounced, specific reduction of gene and protein expression. Hence, we present the first efficient technique for the manipulation of gene expression in primary skin MCs ex vivo, which combines high transfection rates with retained cell viability.

This article is protected by copyright. All rights reserved.

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Hair follicle dermal stem cells and skin-derived precursor cells:Exciting tools for endogenous and exogenous therapies

Abstract

Understanding the cellular interactions and molecular signals underlying hair follicle (HF) regeneration may have significant implications for restorative therapies for skin disease that diminish hair growth, whilst also serving to provide fundamental insight into the mechanisms underlying adult tissue regeneration. One of the major, yet underappreciated, players in this process is the underlying HF mesenchyme. Here, we provide an overview of a mesenchymal progenitor pool referred to as hair follicle dermal stem cells (hfDSCs), discuss their potential functions within the skin, their relationship to Skin-derived precursors (SKPs) and consider unanswered questions about the function of these specialized fibroblasts. We contend that dermal stem cells provide an important reservoir of renewable dermal progenitors that may enable development of novel restorative therapies following hair loss, skin injury or disease.

This article is protected by copyright. All rights reserved.

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A distinct cutaneous microbiota pofile in autoimmune bullous disease patients

Abstract

Bullous Pemphigoid (BP) is the most common autoimmune blistering disease in Europe. As both the incidence of the disease and the relative proportion of the elderly population continue to rise, it represents a significant medical burden. Whereas some progress has been achieved in defining genetic risk factors for autoimmune blistering diseases, no environmental agent has been conclusively identified. Emerging evidence suggests that host immunity may influence the skin microbiota while the latter modulates cutaneous immunity. Nevertheless, the relationship between skin microbial communities and autoimmune bullous disease has yet to be studied in humans. Here, we aim to characterize and compare the skin microbiome of BP patients and healthy, age-matched controls at numerous body sites. Similar to what has been shown in healthy controls, the composition of skin microbiota in BP patients appears to be very divergent and site-specific. Microbial phylum abundances differ between perilesional sites of BP patients and the same anatomic locations of control patients. A distinct cutaneous microbiota profile, which correlates with BP, further strengthens the significance of commensal-host interaction on our immune system. Moreover, these results raise the possibility that the cutaneous microbiome may contribute to the pathogenesis of BP, with important implications for the treatment of this disease.

This article is protected by copyright. All rights reserved.

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Loss of INK4a/Arf gene enhances ultraviolet radiation induced cutaneous tumor development

Abstract

The CDKN2A locus encodes for tumor suppressor genes p16^INK4aand p14^Arf which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation-induced skin tumors. Panels of INK4a/Arf^-/- mice and wild type (WT) mice were treated with a single dose of UVB (200 mJ/cm²). For long-term studies, these mice were irradiated with UVB (200 mJ/cm²) three times weekly for 30 weeks. At the end of the experiment, tissues were harvested from mice and assayed for inflammatory biomarkers and cytokines. A single dose of UVB resulted in a significant increase in reactive oxygen species (ROS) and 8-dihydroxyguanosine (8-oxo-dG) lesions in INK4a/Arf^-/- mice compared to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf^-/- mice had tumors, whereas there were no tumors in WT controls after 24 weeks of UVB exposure. The increase in tumor development correlated with a significant increase in nuclear factor (NF)-κB, cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂) and its receptors both in UVB-exposed skin and in the tumors. A significant increase was seen in inflammatory cytokines in skin samples of INK4a/Arf^-/- mice following treatment with chronic UVB radiation. Furthermore, significantly more CD11b⁺Gr1⁺ myeloid cells were present in UVB exposed INK4a/Arf^-/- mice compared to WT mice. Our data indicate that by targeting UVB-induced inflammation, it may be possible to prevent UVB-induced skin tumors in individuals that carry CDKN2A mutation.

This article is protected by copyright. All rights reserved.

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Intracellular ROS levels determine the apoptotic potential of keratinocyte by Quantum Dot via blockade of AKT Phosphorylation

Abstract

Quantum dots (QDs) have shown great potential for biomedical use in a broad range including diagnostic agents. However, the regulatory mechanism of dermal toxicity is poorly understood. In this study, we investigated how QDs-induced apoptosis is regulated in human keratinocytes. We also examined the effect of carboxylic acid coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and apoptosis-related cellular signaling. The viability of keratinocyte was inhibited by two types of QDs in a concentration-dependent manner. QDs induce ROS production and blockade of AKT phosphorylation. Moreover, the cleavage of AKT dependent pro-apoptotic proteins such as poly (ADP-ribose) polymerase, caspases-3 and caspases-9 was significantly increased. We also found that a decrease of cellular ROS level by ROS scavenger, N-acetylcysteine (NAC), resulting in the abolishment of QDs-induced AKT de-phosphorylation and cellular apoptosis. Interestingly, QD 655 had a more cytotoxic effect including oxidative stress and AKT dependent apoptosis than QD 565. In addition, QD 655 had the cytotoxic potential in the human skin equivalent model (HSEM). These data show that QD-induced intracellular ROS levels may be an important parameter in QD-induced apoptosis. These findings from the present study indicate that intracellular ROS levels might determine the apoptotic potential of keratinocyte by QD via blockade of AKT phosphorylation.

This article is protected by copyright. All rights reserved.

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Complement-independent blistering mechanisms in bullous pemphigoid

Abstract

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that clinically demonstrates tense blisters with widespread erythema, histologically demonstrates subepidermal blistering and immunologically demonstrates the presence of circulating autoantibodies against hemidesmosomal molecules. Complement activation has long been regarded as necessary for the generation of the BP. However, certain evidence has recently come to support non-complemental blistering mechanisms. The story of BP blistering mechanisms is a complicated one. This review mainly focuses on a specific blistering mechanism that highlights the role of complements in BP blistering.

This article is protected by copyright. All rights reserved.

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Transforming growth factor β inhibitor Repsox down-regulates collagen expression of scleroderma dermal fibroblasts and prevents bleomycin-induced mice skin fibrosis

Abstract

Inhibition of transforming growth factor (TGF)-β1 signaling may be one of the most reliable approaches to treat skin fibrosis of scleroderma. Although there have been a lot of basic researches of TGF-β blockade reagents, few of them was proved to have inhibitory effects on fibrosis both in vitro and in vivo. In the present study, we randomly chose four commercially available low molecular compounds (Repsox, LY2109761, LY364947, and K02288) from TGF-β1 inhibitor library, and compared their anti-fibrotic effects in vitro and in vivo.

We demonstrated that Repsox has the most potent inhibitory effects on TGF-β-induced expression of CTGF and collagen of cultured normal dermal fibroblasts in vitro and their constitutive overexpression of scleroderma fibroblast in vitro. In addition, Repsox could attenuate skin fibrosis by bleomycin in vivo, via the down-regulation of CTGF or collagen.

Our results may facilitate clinical trial of Repsox against fibrotic diseases in the future.

This article is protected by copyright. All rights reserved.

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Methods for the isolation and 3D culture of dermal papilla cells from human hair follicles

Abstract

The dermal papilla is a cluster of mesenchymal cells located at the base of the hair follicle which have a number of important roles in the regulation of hair growth. As a consequence, in vitro models of these cells are widely used to study the molecular mechanisms which underlie hair follicle induction, growth and maintenance. While dermal papilla from rodent hair follicles can be digested prior to cell isolation, the unique extracellular matrix composition found in human dermal papilla renders enzymes such as trypsin and collagenase insufficient for digestion of the dermal papilla into a single cell suspension. As such, to grow human dermal papilla cells in vitro, the papilla has to first be isolated via a micro-dissection approach from the follicle. In this paper, we describe the micro-dissection and culture methods which we use within our laboratory, for the study of human dermal papilla cells.

This article is protected by copyright. All rights reserved.

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Erkrankungen der Kopfhaut

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Tropendermatologisch relevante Erkrankungen der Kopfhaut

Zusammenfassung

Menschen, deren genetische Wurzeln tropischen oder tropennahen Regionen entstammen, weisen unter anderem auch an Kopfhaut und Kopfhaar spezifische strukturelle Merkmale auf, die sie einerseits für diese Klimazonen schützend ausrüsten, andererseits jedoch für bestimmte dermatologische Krankheitsbilder besonders empfänglich machen. Auf eine Auswahl dieser Erkrankungen autoimmuner, chronisch entzündlicher, infektiöser und mechanischer Genese wird im Folgenden vertiefend eingegangen.

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Pathogenesis of Immune Thrombocytopenia

Publication date: Available online 17 April 2017
Source:Autoimmunity Reviews
Author(s): Sylvain Audia, Matthieu Mahévas, Maxime Samson, Bertrand Godeau, Bernard Bonnotte
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8⁺ T cells also participate to thrombocytopenia by increasing platelet apoptosis. Besides this peripheral platelet destruction, inappropriate bone marrow production also exacerbates thrombocytopenia, due to an immune response against megakaryocytes. Moreover, the level of circulating thrombopoietin, the main growth factor of megakaryocytes, is low during ITP. In this review, the major mechanisms leading to thrombocytopenia, the role of the different immune cells and the different targets of treatments are described.



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The Impact of a Teaching or Singing Career on the Female Vocal Quality at the Mean Age of 67 Years: A Pilot Study

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Introduction. World War One and Intellectual Work.

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Biodegradation of polyhydroxyalkanoates

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Biodegradation of polyhydroxyalkanoates

Degradation of poly(3-hydroxybutyrate) and copolymers with 3-hydroxyvaleric acid was investigated in natural environments, and the microorganisms involved were isolated and identified. The influence of abiotic and biotic factors on the degradation is discussed.

http://ift.tt/2opmGtO

Mode of membrane insertion and sequence of a 32 amino acid peptide stretch of the penicillin-binding protein 4 of Enterococcus hirae

Analysis of water-soluble derivatives of the Enterococcus hirae 75-kDa membrane-bound penicillin-binding protein 4 (PBP4) has yielded the amino acid sequence of a 32-amino acid polypeptide stretch. This peptide is similar to peptide segments known to occur in the N-terminal domain of high-M(r) PBPs of class B. The E. hirae PBP4 probably belongs to the same class. It is anchored in the membrane at the N-terminus of the polypeptide chain.

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SOP – Behandlung und Betreuung in der Sterbephase

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Thermal Esophageal Injury following Ingestion of Boiling Mushroom Water

Thermal esophageal and gastric damage from ingestion of hot liquids is poorly studied in pediatrics. Limited case reports exist in the literature. Many cases presented with chest pain, dysphagia, and odynophagia. Variable histologic findings were reported. No definitive management guidelines exist for such injuries. We provide a report of the acute assessment and management of an obvious thermal esophageal injury and contribute to what is known about this presentation. A 16-year-old male presented with odynophagia, dysphagia, and hematemesis following ingestion of "nearly boiling" mushroom water. Ondansetron, pantoprazole, ketorolac, maintenance intravenous fluids, and a clear liquid diet were started. At sixty hours after ingestion, an esophagogastroduodenoscopy (EGD) revealed blistering and edema of the soft palate and epiglottis, circumferential erythema of the entire esophagus with an exudate likely to be desquamated mucosa, and linear erythema of the body and fundus of the stomach. An EGD one month after ingestion showed no residual effects from the injury. The pantoprazole was weaned and restrictions to his diet were lifted. To better standardize care in these rare esophageal injuries, the development of a clinical care algorithm may be beneficial to provide clinicians with a guide for management based on outcomes of previously reported cases.

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Erratum to: Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double-Blind, Vehicle-Controlled Trial

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Probiotics-impregnated bedding covers for house dust mite allergic rhinitis: a pilot randomised clinical trial

Allergic Rhinitis (AR) affects up to one third of the adult population and causes illness and disability worldwide.[1] Main symptoms include sneezing, rhinorrhea and nasal obstruction. AR is often accompanied with conjunctivitis, characterised by watery, itchy and sometimes red or swollen eyes. House Dust Mite (HDM) allergens are one of the most relevant indoor allergy triggers.[2] Treatment of AR consists of symptomatic medications (mainly antihistamines and nasal corticosteroids) and allergen specific immunotherapy (in more severe cases).[1]

This article is protected by copyright. All rights reserved.

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Modulation of Anti-tumor T Cell Responses in Cancer Patients Treated by Concomitant Radiochemotherapy

Conditions:   Lung Cancer;   Head and Neck Cancer
Intervention:   Other: Biological samples
Sponsor:   Centre Hospitalier Universitaire de Besancon
Not yet recruiting - verified April 2017

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Impaired Vestibular Function After Cochlear Implantation in Children: Role of Static Posturography

Abstract

To identify vestibular dysfunction in children after cochlear implant surgery and to study the utility of static posturography in evaluating vestibular function in children. A prospective study was carried out on 25 children between 2 and 7 years of age with sensorineural hearing loss with no overt vestibular dysfunction. All children underwent static posturography using Synapsis Posturographic System (SPS) software (Version 3.0, REV C) using a static platform with foam. The centre of pressure (COP) shift was recorded as statokinesiogram on the software and the mean vestibular, visual and somesthetic scores were obtained. Cochlear implantation (CI) surgery was done with insertion of Med-El Pulsar standard cochlear implant with 12 twin electrodes. Children were evaluated again after 4 weeks of CI surgery (2 weeks after switch on) with static posturography on the same SPS software. The scores obtained were compared with pre op value and data analyzed statistically by paired t tests on SPSS 18 software. The mean age was 4.6 years with range 2–7 years. All the children in the study were able to complete the test with no difficulty and the mean time required for each child was 10.2 min. The mean pre op somesthetic score was 95.16 (SD 1.52) and post op score was 94.06 (SD 1.79). The mean pre op visual score was 86.64 (SD 2.24) and post op score was 82.55 (2.89). The mean pre op vestibular score was 84.11 (SD 2.20) and post op score was 73.66 (SD 4.25). Correlation and statistical analysis of the pre and post values of each score revealed statistically significant reduction in vestibular scores post CI. The vestibular system is at high risk of injury leading to vestibular dysfunction in children during CI. Our study found the static posturography as a simple, fast and efficient tool to screen children for vestibular dysfunction post CI. Identifying the dysfunction early can help in initiating early rehabilitation measures.

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