Surgery- vs Radiation-Based Therapy for p16+/HPV-Related Oropharyngeal Cancers

Abstract

Purpose of Review

Oropharyngeal cancer (OPC) has traditionally been managed by radiotherapy (RT)-based approaches. Minimally invasive surgery [transoral robotic surgery (TORS)/transoral laser microsurgery (TLMS)] is gaining popularity in T1-T2 HPV+ OPC. However, there is lack of high level evidence to guide practice. We summarize ongoing research regarding outcomes and investigational strategies for TORS/TLM- and RT-based treatments for this disease.

Recent Findings

Literature published in 2012–2017 demonstrated comparable exemplary outcomes with TORS/TLM and IMRT for selected HPV+ T1-T2 OPC. However, many TORS/TLM-treated patients also require adjuvant treatment, which impacts quality of life. Emerging RT-based de-intensification trial data suggest promising results. Ongoing investigation include indications for postoperative (chemo-)radiotherapy following TORS/TLM- and optimal RT-based de-intensification strategies.

Summary

A contemporary literature review demonstrates equal efficacy for TORS/TLM and IMRT as primary treatment for selected HPV+ T1-T2 OPC. TORS/TLM is an attractive approach when the opportunity for single modality treatment is high.

https://ift.tt/2A4MOFz

Relations between epidermal barrier dysregulation and staphylococci-dominated microbiome dysbiosis in atopic dermatitis

Publication date: Available online 24 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Can Altunbulakli, Matthias Reiger, Avidan U. Neumann, Natalie Garzorz-Stark, Megan Fleming, Claudia Huelpuesch, Francesc Castro-Giner, Kilian Eyerich, Cezmi A. Akdis, Claudia Traidl-Hoffmann

https://ift.tt/2LhZ4Yu

Keratosis Pilaris and its Subtypes: Associations, New Molecular and Pharmacologic Etiologies, and Therapeutic Options

Abstract

Keratosis pilaris is a common skin disorder comprising less common variants and rare subtypes, including keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Data, and critical analysis of existing data, are lacking, so the etiologies, pathogeneses, disease associations, and treatments of these clinical entities are poorly understood. The present article aims to fill this knowledge gap by reviewing literature in the PubMed, EMBASE, and CINAHL databases and providing a comprehensive, analytical summary of the clinical characteristics and pathophysiology of keratosis pilaris and its subtypes through the lens of disease associations, genetics, and pharmacologic etiologies. Histopathologic, genomic, and epidemiologic evidence points to keratosis pilaris as a primary disorder of the pilosebaceous unit as a result of inherited mutations or acquired disruptions in various biomolecular pathways. Recent data highlight aberrant Ras signaling as an important contributor to the pathophysiology of keratosis pilaris and its subtypes. We also evaluate data on treatments for keratosis pilaris and its subtypes, including topical, systemic, and energy-based therapies. The effectiveness of various types of lasers in treating keratosis pilaris and its subtypes deserves wider recognition.

https://ift.tt/2NGWHLn

Investigation of the mtDNA mutations in Syrian Families With Non-Syndromic Sensorineural Hearing Loss

Publication date: Available online 24 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Faten Moassass, Bassel AL-Halabi, Mohamad Sayah Nweder, Walid AL-Achkar

Abstract

Objective

Hearing loss is a common sensory disorder, and at least 50% of cases are due to a genetic etiology. Several mitochondrial DNA mutations (mtDNA) have been reported to be associated with nonsyndromic hearing loss (NSHL) in different population. However, There is no previous available data about the frequency of mtDNA mutations as etiology for deafness in Syrian. The aim of present study is to investigate the incidence of common mt DNA mutations in our families with congenital hearing loss and not related to the ototoxicity or aminoglycosides.

Methods

A total of 50 deaf families were enrolled in the present study. Direct sequencing and PCR-RFLP methods were employed to detect seven mt DNA mutations, including A1555G, A3243G, C1494T, G3316A, T7510C, A7445G, and 7472insC.

Results

Our results revealed a high prevalence of mt DNA mutation (10%) in deaf families (5/50). In surprising, the unexpected mutations were observed. The G3316A mutation was found in 2 families as homoplasmic genotype. Also, we found the homoplasmic and heteroplasmic genotype for the C1494T mutation in two families. in one family the heteroplasmic genotype for T7510C mutation was observed; this family harbor 35delG mutation in GJB2 gene. None of the common mtDNA mutations (A1555G, A3243G,) and other mutations (A7445G, 7472insC) were detected here.

Conclusion

Our findings indicate to significant contribution of the mt DNA mutations in our families with NSHL. The presented data is the first report about mt DNA and it will improve the genetic counseling of hearing impaired in Syrian families.

https://ift.tt/2mCCPxx

In utero drug exposure and hearing impairment in 2-year-old children A case-control study using the EFEMERIS database

Publication date: Available online 24 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Caroline Foch, Mélanie Araujo, Alexandra Weckel, Christine Damase-Michel, Jean-Louis Montastruc, Justine Benevent, Geneviève Durrieu, Isabelle Lacroix

https://ift.tt/2uUD36S

Sirolimus for treatment of verrucous venous malformation: A retrospective cohort study

Publication date: Available online 24 July 2018

Source: Journal of the American Academy of Dermatology

Author(s): Gaolei Zhang, Hongguang Chen, Zhen Zhen, Jianyou Chen, Sheng Zhang, Qin Qin, Xiaoyan Liu

https://ift.tt/2Lmpkkg

Methods for Decreasing the Incidence of Moist Desquamation in Patients Undergoing Radiotherapy

Publication date: Available online 24 July 2018

Source: Journal of the American Academy of Dermatology

Author(s): Raagini Suresh, Florence Yuen, Jenny E. Murase

https://ift.tt/2LGa8KW

Nail photography tricks for pediatric and geriatric patients

Publication date: Available online 24 July 2018

Source: Journal of the American Academy of Dermatology

Author(s): Sanjeev Gupta, Archana Singal, Kartikay Aggarwal, Ravi Shankar Jangra

https://ift.tt/2LgYxG1

Lightening Becker’s Nevus with Topical Glycolic Acid

Publication date: Available online 24 July 2018

Source: Journal of the American Academy of Dermatology

Author(s): Yiping Zhong, Yongjun Chen, Lining Huang, Hui Wang, Tingting Yan, Bin Yang, Mao-Qiang Man

https://ift.tt/2LGa3qC

Association of Plasma Pentraxin-3 Levels with Retinopathy and Systemic Factors in Diabetic Patients

Metabolic Syndrome and Related Disorders, Ahead of Print.


https://ift.tt/2LvSU6g

Decreasing Disease-Specific Mortality of Differentiated Thyroid Cancer in Korea: A Multicenter Cohort Study

Thyroid, Ahead of Print.


https://ift.tt/2v0S3QH

Cardiovascular Morbidity and Mortality After Treatment of Hyperthyroidism with Either Radioactive Iodine or Thyroidectomy

Thyroid, Ahead of Print.


https://ift.tt/2LwzFJK

Mammographic Density and Circulating Sex Hormones: a Cross-Sectional Study in Postmenopausal Korean Women

Abstract

Mammographic density (MD) is a strong independent risk factor for breast cancer. It has been suggested that breast cancer is related to the exposure to circulating sex hormones. However, relations between MD and hormones have been inconsistent. In addition, such relations are mainly evaluated in Western populations. Therefore, we conducted a cross-sectional study in 396 cancer-free postmenopausal Korean women who had never used hormone replacement therapy. We assayed estradiol, testosterone, and sex hormone-binding globulin (SHBG) levels. We then calculated free testosterone (cFT) levels. Total and dense areas of digital mammogram were measured using a computer-assisted thresholding method, and non-dense area and percent dense area were calculated. Linear mixed model was used for analyses. Estradiol and testosterone levels were not associated with any MD measures after adjusting for reproductive factors and body mass index. However, cFT was persistently associated with non-dense area even after adjusting for covariates, with non-dense area increased by 3.5% per 1 standard deviation increase of cFT. SHBG showed an inverse association with non-dense area, although it showed a positive association with dense area and percent dense area regardless of adjustment for covariates. Non-dense area was decreased by 5.6% while percent dense area was increased by 13.4% per 1 standard deviation increase of SHBG. These findings suggest that SHBG might be related with breast cancer risk, probably through its association with breast density.

https://ift.tt/2JTdo3Q

Low-Cd tomato cultivars ( Solanum lycopersicum L.) screened in non-saline soils also accumulated low Cd, Zn, and Cu in heavy metal-polluted saline soils

Abstract

Many reclaimed tidal flat soils feature high salinity and heavy metal (HM) accumulation. Consumption of vegetables cultivated in this type of cropland may cause health risks. Low-Cd tomato cultivars (Solanum lycopersicum L.) were identified in non-saline soil in our previous studies (Tan et al. 2014). However, further research should determine whether these low-Cd cultivars will maintain in the repeatability and stability in saline soil and whether they have low accumulation abilities for accompanying metals (such as Zn and Cu). A soil-pot trial was implemented to measure Cd, Zn, and Cu concentrations in low- and high-Cd cultivars of both common and cherry-type tomatoes grown on HM-polluted reclaimed tidal flat saline soil. Then, cultivar differences in dissolution of Cd, Zn, and Cu in soil and their uptake and redistribution in plants were analyzed. Results showed that the cherry type accumulated more Cd, Zn, and Cu than the common type. Low-Cd cultivars of both types in saline soil accumulated low concentrations of Cd, Zn, and Cu in fruits. Low HM accumulation in fruits is partly attributed to a low root/shoot (R/S) biomass ratio. Low amounts of soil HMs were dissolved because of the low level of rhizosphere organic compounds, which possibly decreased HM uptake by the roots. Low-Cd cultivars of both tomato types had a higher ability to retain HMs in the roots than their high-Cd cultivars. These findings may provide a scientific guidance for the safe cultivation of HM-polluted saline soils.

https://ift.tt/2LzdZg7

Pseudohyperkalemia: Hyperkalemia Cocktail or Alternative Diagnosis

Introduction. Hyperkalemia is a commonly encountered clinical problem. Pseudohyperkalemia is believed to be an in vitro phenomenon that does not reflect in vivo serum potassium and therefore should not be treated. Here, we present a case who unfortunately underwent unnecessary treatment because of failure to detect the common lab abnormality of pseudohyperkalemia. Case Presentation. A 91-year-old female with a history of chronic lymphocytic leukemia presented to the emergency with nausea and vomiting 24 hours after her first chemotherapy with chlorambucil. Physical examination was overall unremarkable. She had a leukocytosis of 210 × 103/µL with 96% lymphocytes along with chronic anemia with hemoglobin of 8.1 g/dL. Her initial sodium and potassium levels were normal. During the clinical course, her potassium progressively worsened and failed to improve despite standard medical treatment. Patient ultimately underwent dialysis. Conclusions. Differentiating true hyperkalemia from pseudohyperkalemia is very important in selected group of patients to avoid unnecessary medications, higher level of care, and unnecessary procedure including dialysis. We want to emphasize the importance of simple yet profound knowledge of technique of blood draws and basic metabolic panel processing for every clinician in day-to-day practice.

https://ift.tt/2Oe5RA3

Cardiac Involvement by HIV-Associated DLBCL

Non-Hodgkin's lymphoma (NHL) is a common AIDS-defining malignancy among people living with HIV. Of the different types of NHLs, diffuse large B-cell lymphoma (DLBCL) is the most common. Prognosis of DLBCL has improved over the years in the general population but remains relatively poor in HIV-positive individuals. Almost any organ system can be affected by DLBCL; however, cardiac involvement remains rare and suggests aggressive disease. We present a case of DLBCL in an HIV-positive patient, who had cardiac involvement, with the only clue to cardiac involvement being symptom being tachycardia and dysphagia.

https://ift.tt/2NBaT8C

Störungen des Kalziumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 516-528
DOI: 10.1055/s-0043-121655

Störungen des Kalziumhaushalts sind weit verbreitet. Ihre pathophysiologischen Ursachen sind sehr heterogen und die klinischen Symptome häufig unspezifisch. Daher ist eine genaue Diagnostik unerlässlich und ein schneller Ausgleich der Kalziumhomöostase essenziell. Dieser Artikel erörtert die pathophysiologischen, diagnostischen und therapeutischen Pfeiler von Hypo- und Hyperkalzämie sowie ihre Auswirkungen auf Anästhesie und Intensivmedizin.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LvGY4s

Videolaryngoskopie – Ende der Fiberoptik beim erwartet schwierigen Atemweg?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 487-488
DOI: 10.1055/a-0643-3504

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2v09YqC

Störungen des Natriumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 492-502
DOI: 10.1055/s-0043-121662

Störungen des Natriumhaushalts sind häufig auftretende Elektrolytimbalancen. Sowohl sie selbst als auch ihre unsachgemäße Therapie können schwerwiegende Komplikationen nach sich ziehen. Der vorliegende Artikel informiert über die Ätiologie von Störungen des Natriumhaushalts und stellt wichtige therapeutische Prinzipien dar.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LvGg7i

Vollelektrolyt- versus NaCl-Lösung in der Therapie kritisch kranker Erwachsener

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 488-488
DOI: 10.1055/a-0643-3479

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2v09TTQ

Orale Antikoagulanzien: Management von elektiven und Notfalleingriffen

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 543-550
DOI: 10.1055/s-0043-111006

Orale Antikoagulation bei chirurgischen Patienten erfolgt meistens mit Vitamin-K-Antagonisten (VKA) oder nicht-Vitamin-K-antagonistischen oralen Antikoagulanzien (NOAK). Während VKA wegen ihrer langen Halbwertszeit über die INR gesteuert werden, ist bei NOAK in der Regel keine Gerinnungskontrolle notwendig. Die Gabe erfolgt in festen Dosierungen. Spezifische Gerinnungswerte zur Bestimmung der Wirkung von NOAK können über die Anti-Faktor-Xa(FXa)-Aktivität (für FXa-Inhibitoren: Apixaban, Edoxaban, Rivaroxaban) und die verdünnte Thrombinzeit (für Dabigatran) erfolgen. Es gibt aktuell keine validierten Grenzwerte, die mit einem erhöhten Risiko für perioperative Blutungen einhergehen. Während VKA perioperativ auf eine parenterale Antikoagulation (z. B. niedermolekulares Heparin) umgestellt werden („Bridging"), werden NOAK pausiert. Ebenso ist nach ausreichendem Sicherheitsabstand die Durchführung von rückenmarksnahen Regionalanästhesieverfahren möglich. Falls erforderlich können NOAK auch auf ein parenterales Verfahren umgestellt werden („Switching"). Lebensbedrohliche Blutungskomplikationen können sowohl unter VKA als auch unter NOAK mit Prothrombinkomplex (PPSB) behandelt werden. Für Dabigatran steht ein Antidot zur Verfügung.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LvGewc

Glukokortikoid-Therapie im septischen Schock – ja oder nein?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 489-489
DOI: 10.1055/a-0643-3451

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2v09Pn4

Störungen des Kaliumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 504-514
DOI: 10.1055/s-0043-121654

Störungen des Kaliumhaushalts sind perioperativ und beim Intensivpatienten häufig anzutreffen – sie können sich schnell zu einer akuten Lebensbedrohung entwickeln. Dieser Beitrag geht auf die physiologischen Grundlagen des Kaliumhaushalts ein und zeigt auf, wie akute Störungen behandelt werden können.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LzcQVU

Elektrolytstörungen

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 490-491
DOI: 10.1055/a-0631-0160

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2uWbgDd

Neue Antibiotika für die Therapie von multiresistenten gramnegativen Bakterien

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 529-542
DOI: 10.1055/s-0043-110504

Die stetige Zunahme an bakteriellen Resistenzen und von multiresistenten Erregern (MRE) – vor allem im gramnegativen Bereich – ist ein weltweites Problem. Die Entwicklung neuer Wirkstoffe gegen Infektionen mit multiresistenten gramnegativen Erregern (MRGN) besitzt daher höchste Priorität. Im Folgenden werden kürzlich zugelassene oder in der fortgeschrittenen klinischen Prüfung befindliche Antibiotika mit Wirksamkeit gegen MRGN vorgestellt.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LwYPrC

Versorgung von Traumapatienten mit dem „REBEL“-Set

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 551-558
DOI: 10.1055/s-0044-102122

Die zunehmende Terrorbedrohung und ein verändertes Einsatzspektrum für den Rettungsdienst erfordern eine Anpassung und Erweiterung von Notfallrettungsmitteln und Einsatztaktik. Ein Beispiel hierfür ist die bayerische „Handlungsempfehlung für Rettungsdienst bei besonderen Einsatzlagen (REBEL)". Es werden 3 Fälle vorgestellt, bei denen „neue Hilfsmittel" wie Hämostyptika, Thoraxverschlusspflaster und Tourniquet aus dem REBEL-Set bei Rettungsdiensteinsätzen angewandt wurden.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2v0On1p

Gefährliche Patientenübergaben!

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 486-487
DOI: 10.1055/a-0643-3517

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2LsXpyx

Störungen des Kalziumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 516-528
DOI: 10.1055/s-0043-121655

Störungen des Kalziumhaushalts sind weit verbreitet. Ihre pathophysiologischen Ursachen sind sehr heterogen und die klinischen Symptome häufig unspezifisch. Daher ist eine genaue Diagnostik unerlässlich und ein schneller Ausgleich der Kalziumhomöostase essenziell. Dieser Artikel erörtert die pathophysiologischen, diagnostischen und therapeutischen Pfeiler von Hypo- und Hyperkalzämie sowie ihre Auswirkungen auf Anästhesie und Intensivmedizin.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LvGY4s

Videolaryngoskopie – Ende der Fiberoptik beim erwartet schwierigen Atemweg?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 487-488
DOI: 10.1055/a-0643-3504

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2v09YqC

Störungen des Natriumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 492-502
DOI: 10.1055/s-0043-121662

Störungen des Natriumhaushalts sind häufig auftretende Elektrolytimbalancen. Sowohl sie selbst als auch ihre unsachgemäße Therapie können schwerwiegende Komplikationen nach sich ziehen. Der vorliegende Artikel informiert über die Ätiologie von Störungen des Natriumhaushalts und stellt wichtige therapeutische Prinzipien dar.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LvGg7i

Vollelektrolyt- versus NaCl-Lösung in der Therapie kritisch kranker Erwachsener

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 488-488
DOI: 10.1055/a-0643-3479

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2v09TTQ

Orale Antikoagulanzien: Management von elektiven und Notfalleingriffen

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 543-550
DOI: 10.1055/s-0043-111006

Orale Antikoagulation bei chirurgischen Patienten erfolgt meistens mit Vitamin-K-Antagonisten (VKA) oder nicht-Vitamin-K-antagonistischen oralen Antikoagulanzien (NOAK). Während VKA wegen ihrer langen Halbwertszeit über die INR gesteuert werden, ist bei NOAK in der Regel keine Gerinnungskontrolle notwendig. Die Gabe erfolgt in festen Dosierungen. Spezifische Gerinnungswerte zur Bestimmung der Wirkung von NOAK können über die Anti-Faktor-Xa(FXa)-Aktivität (für FXa-Inhibitoren: Apixaban, Edoxaban, Rivaroxaban) und die verdünnte Thrombinzeit (für Dabigatran) erfolgen. Es gibt aktuell keine validierten Grenzwerte, die mit einem erhöhten Risiko für perioperative Blutungen einhergehen. Während VKA perioperativ auf eine parenterale Antikoagulation (z. B. niedermolekulares Heparin) umgestellt werden („Bridging"), werden NOAK pausiert. Ebenso ist nach ausreichendem Sicherheitsabstand die Durchführung von rückenmarksnahen Regionalanästhesieverfahren möglich. Falls erforderlich können NOAK auch auf ein parenterales Verfahren umgestellt werden („Switching"). Lebensbedrohliche Blutungskomplikationen können sowohl unter VKA als auch unter NOAK mit Prothrombinkomplex (PPSB) behandelt werden. Für Dabigatran steht ein Antidot zur Verfügung.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LvGewc

Glukokortikoid-Therapie im septischen Schock – ja oder nein?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 489-489
DOI: 10.1055/a-0643-3451

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2v09Pn4

Störungen des Kaliumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 504-514
DOI: 10.1055/s-0043-121654

Störungen des Kaliumhaushalts sind perioperativ und beim Intensivpatienten häufig anzutreffen – sie können sich schnell zu einer akuten Lebensbedrohung entwickeln. Dieser Beitrag geht auf die physiologischen Grundlagen des Kaliumhaushalts ein und zeigt auf, wie akute Störungen behandelt werden können.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LzcQVU

Elektrolytstörungen

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 490-491
DOI: 10.1055/a-0631-0160

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2uWbgDd

Neue Antibiotika für die Therapie von multiresistenten gramnegativen Bakterien

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 529-542
DOI: 10.1055/s-0043-110504

Die stetige Zunahme an bakteriellen Resistenzen und von multiresistenten Erregern (MRE) – vor allem im gramnegativen Bereich – ist ein weltweites Problem. Die Entwicklung neuer Wirkstoffe gegen Infektionen mit multiresistenten gramnegativen Erregern (MRGN) besitzt daher höchste Priorität. Im Folgenden werden kürzlich zugelassene oder in der fortgeschrittenen klinischen Prüfung befindliche Antibiotika mit Wirksamkeit gegen MRGN vorgestellt.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2LwYPrC

Versorgung von Traumapatienten mit dem „REBEL“-Set

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 551-558
DOI: 10.1055/s-0044-102122

Die zunehmende Terrorbedrohung und ein verändertes Einsatzspektrum für den Rettungsdienst erfordern eine Anpassung und Erweiterung von Notfallrettungsmitteln und Einsatztaktik. Ein Beispiel hierfür ist die bayerische „Handlungsempfehlung für Rettungsdienst bei besonderen Einsatzlagen (REBEL)". Es werden 3 Fälle vorgestellt, bei denen „neue Hilfsmittel" wie Hämostyptika, Thoraxverschlusspflaster und Tourniquet aus dem REBEL-Set bei Rettungsdiensteinsätzen angewandt wurden.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

https://ift.tt/2v0On1p

Gefährliche Patientenübergaben!

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 486-487
DOI: 10.1055/a-0643-3517

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2LsXpyx

FcεRI cross-linking and IL-3 protect human basophils from intrinsic apoptotic stress

Publication date: Available online 23 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Lionel Rohner, Ramona Reinhart, Björn Hagmann, Andrea Odermatt, Annet Babirye, Thomas Kaufmann, Michaela Fux

https://ift.tt/2JTZa2Y

Three-dimensional graphene-based adsorbents in sewage disposal: a review

Abstract

A kind of graphene functional materials based on three-dimensional (3D) porous structure is a new star for environmental application in the past decades because it not only inherits the perfect carbon crystal structure of two-dimensional (2D) graphene sheets but also exhibits several advantages such as extremely low density, high porosity, and big surface area, all which enable diverse contaminants to easily access and diffuse into 3D networks, and make these materials ideal adsorbents with superior adsorptivity and recyclability. This review aims to summarize the recent progress in constructing 3D graphene-based adsorbents (3DGBAs) with two hybrid systems such as graphene/polymers and graphene/inorganic nanomaterials, and to provide a fundamental understanding of synthetic methods for interconnecting these nanostructures, structure–property relationships, and extensive applications in environmental protection towards adsorption of heavy metals, dyes, oils, and organic pollutants. Furthermore, we make a forecast on the future development opportunities and technical challenges, which is hoped to make an inspiration for the researchers to exploit a new family of graphene-based adsorption materials.

Graphical abstract

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Hypoxia disrupts aryl hydrocarbon receptor signaling and the Th17 response in allergic rhinitis patients

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Wei Kou, Xuelei Li, Hongbing Yao, Cheng Zhang, Ping Wei

Abstract

Background

Hypoxic conditions area key feature of allergic rhinitis (AR), however, the role of hypoxia in AR remains to be fully understood. The aim of this study was to survey the effect of hypoxia on the Th17 response in AR patients by investigating the action of hypoxia-influenced signaling pathways on Th17 differentiation.

Methods

23 AR patients and 15 healthy controls were recruited for this study. Under normoxia and hypoxic conditions, the expression of HIF-1α, AhR, CYP1A1 and CYP1B1 and the presence of Th17 cells in CD4⁺T cells were measured. Furthermore, the amount of ARNT combined with either HIF-1α or AhR was determined after the exposure of 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl easter (ITE) with normoxia and hypoxia.

Results

HIF-1α and AhR expression were higher in CD4⁺T cells from AR patients than in those from healthy controls. In a hypoxic environment, the expression of HIF-1α was elevated in CD4⁺T cells of both AR patients and healthy controls. Meanwhile, the suppressive effects of a non-toxic AhR ligand (ITE) on the Th17 response and its positive effects on IL-10 production were suppressed in the cells of AR patients and healthy controls under hypoxia. These effects were arisen from HIF-1α out-competing AhR for ARNT binding which limited the activity of the AhR pathway.

Conclusions

The present results suggest that hypoxia is capable of promoting the Th17 response by reducing AhR activity via HIF-1α activity. Thus hypoxia may be intimately involved in the pathogenesis of AR.

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Nail photography tricks for pediatric and geriatric patients

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Methods for Decreasing the Incidence of Moist Desquamation in Patients Undergoing Radiotherapy

https://ift.tt/2OcKDTe

Lightening Becker’s Nevus with Topical Glycolic Acid

https://ift.tt/2NEj8ko

Sirolimus for treatment of verrucous venous malformation: A retrospective cohort study

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Small oral tongue cancers (≤ 4 cm in diameter) with clinically negative neck: from the 7th to the 8th edition of the American Joint Committee on Cancer

Abstract

One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12–4.99) and disease-free survival (HR 2.12, 95% CI 1.09–4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27–7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.

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Neck stiffness in a post-irradiated nasopharyngeal carcinoma adult: An unusual diagnosis

Nasopharyngeal carcinoma is a neoplasm commonly found in population of South East Asia. The mainstay of treatment is high dose irradiation. Complications from radiotherapy are not uncommon especially to those nearby structures such as vertebrae and spinal cord. A 57 year-old gentleman with nasopharyngeal carcinoma (NPC) who was treated with chemo-radiation (total of 35 fractions,70Gy) presented to us 6 months post therapy with bilateral nasal discharge and progressive neck stiffness. Nasoendoscopy showed inflamed nasophayngeal mucosa and Computed Tomography (CT) brain and cervical spine showed retropharyngeal and anterior epidural collection with extension into atlantoaxial bone and spinal cord compression.

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Leishmania donovani Exploits Tollip, a Multitasking Protein, To Impair TLR/IL-1R Signaling for Its Survival in the Host [INFECTIOUS DISEASE AND HOST RESPONSE]

IL-1R/TLR signaling plays a significant role in sensing harmful foreign pathogens and mounting effective innate and adaptive immune responses. However, the precise mechanism by which Leishmania donovani, an obligate intramacrophagic pathogen, breaches IL-1R/TLR signaling and host-protective immunity remains obscure. In this study, we report the novel biphasic role of Toll-interacting protein (Tollip), a negative regulator of the IL-1R/TLR pathway, in the disease progression of experimental visceral leishmaniasis. We observed that during early hours of infection, L. donovani induced phosphorylation of IRAK-1, resulting in the release of Tollip from the IL-1R–associated kinase (IRAK)-1 complex in J774 macrophages, which then acted as an endocytic adaptor on cell surface IL-1R1 and promoted its lysosomal degradation. In the later stage, Tollip shuttled back to IRAK-1, thereby inhibiting IRAK-1 phosphorylation in association with IRAK-M to neutralize downstream TLR signaling in infected macrophages. Moreover, during late infection, L. donovani enhanced nuclear translocation and recruitment of transcription factors early growth response protein 2, NF erythroid 2–related factor 2, and Ahr on Tollip promoter for its induction. Small interfering RNA–mediated silencing of Tollip in infected macrophages significantly enhanced NF-B activation and induced host-defensive IL-12 and TNF-α synthesis, thereby reducing amastigote multiplication. Likewise, abrogation of Tollip in L. donovani–infected BALB/c mice resulted in STAT-1–, IRF-1–, and NF-B–mediated upregulation of host-protective cytokines and reduced organ parasite burden, thereby implicating its role in disease aggravation. Taken together, we conclude that L. donovani exploited the multitasking function of Tollip for its own establishment through downregulating IL-1R1/TLR signaling in macrophages.

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From Cancer Immune Surveillance to Cancer Immunoediting: Birth of Modern Immuno-Oncology [PILLARS OF IMMUNOLOGY]

https://ift.tt/2mAVr0G

Widespread Effects of Chemokine 3' Untranslated Regions on mRNA Degradation and Protein Production in Human Cells [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Chemokines are a large family of chemotactic cytokines that play critical roles in inflammation, development, and diseases. Chemokine expression is highly regulated during development and in response to environmental stimuli. The 3' untranslated regions (3'-UTRs) of mRNA are believed to be important in the control of chemokine gene expression. However, the regulatory effects of most chemokine 3'-UTRs have not been characterized previously. In this work, we systematically studied the effects of 43 CC and CXC chemokine 3'-UTRs on gene expression in eight human cell lines and two types of human primary cells. We found that chemokine 3'-UTRs had a wide spectrum of regulatory effects on mRNA abundance and protein production that were tightly correlated with the effects on mRNA stability. In general, 3'-UTRs had remarkably similar effects across all cell types studied. The presence of AU-rich elements, microRNA targets, and Pumilio binding sites were associated with chemokine 3'-UTR activity but did not fully account for all 3'-UTR activity detected using the reporter assay. Mutational analysis illustrated how specific cis-regulatory elements contributed to the regulatory effect of chemokine 3'-UTRs. These findings bring new insights into the mechanisms by which chemokine expression is regulated by 3'-UTRs.

https://ift.tt/2mCjBIk

Pillars Article: IFN{gamma} and Lymphocytes Prevent Primary Tumour Development and Shape Tumour Immunogenicity. Nature. 2001. 410: 1107-1111 [PILLARS OF IMMUNOLOGY]

https://ift.tt/2uXQm6E

Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity [INNATE IMMUNITY AND INFLAMMATION]

Collagen VI is a ubiquitous extracellular matrix component that forms extensive microfibrillar networks in most connective tissues. In this study, we describe for the first time, to our knowledge, that the collagen VI von Willebrand factor type A–like domains exhibit a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria in human skin infections in vivo. In silico sequence and structural analysis of VWA domains revealed that they contain cationic and amphipathic peptide sequence motifs, which might explain the antimicrobial nature of collagen VI. In vitro and in vivo studies show that these peptides exhibited significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa through membrane disruption. Our findings shed new light on the role of collagen VI–derived peptides in innate host defense and provide templates for development of peptide-based antibacterial therapies.

https://ift.tt/2mBX4vd

Ebola Immunity: Gaining a Winning Position in Lightning Chess [BRIEF REVIEWS]

Zaire ebolavirus (EBOV), one of five species in the genus Ebolavirus, is the causative agent of the hemorrhagic fever disease epidemic that claimed more than 11,000 lives from 2014 to 2016 in West Africa. The combination of EBOV's ability to disseminate broadly and rapidly within the host and its high pathogenicity pose unique challenges to the human immune system postinfection. Potential transmission from apparently healthy EBOV survivors reported in the recent epidemic raises questions about EBOV persistence and immune surveillance mechanisms. Clinical, virological, and immunological data collected since the West Africa epidemic have greatly enhanced our knowledge of host–virus interactions. However, critical knowledge gaps remain in our understanding of what is necessary for an effective host immune response for protection against, or for clearance of, EBOV infection. This review provides an overview of immune responses against EBOV and discusses those associated with the success or failure to control EBOV infection.

https://ift.tt/2mEzYUW

Multiplexed Division Tracking Dyes for Proliferation-Based Clonal Lineage Tracing [NOVEL IMMUNOLOGICAL METHODS]

The generation of cellular heterogeneity is an essential feature of immune responses. Understanding the heritability and asymmetry of phenotypic changes throughout this process requires determination of clonal-level contributions to fate selection. Evaluating intraclonal and interclonal heterogeneity and the influence of distinct fate determinants in large numbers of cell lineages, however, is usually laborious, requiring familial tracing and fate mapping. In this study, we introduce a novel, accessible, high-throughput method for measuring familial fate changes with accompanying statistical tools for testing hypotheses. The method combines multiplexing of division tracking dyes with detection of phenotypic markers to reveal clonal lineage properties. We illustrate the method by studying in vitro–activated mouse CD8⁺ T cell cultures, reporting division and phenotypic changes at the level of families. This approach has broad utility as it is flexible and adaptable to many cell types and to modifications of in vitro, and potentially in vivo, fate monitoring systems.

https://ift.tt/2mDDXB7

Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism [CUTTING EDGE]

Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome–immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood. In this study, we report critical roles for prenatal microbiota composition in the development of behavioral abnormalities in a murine maternal immune activation (MIA) model of autism that is driven by the viral mimetic polyinosinic-polycytidylic acid. We show that preconception microbiota transplantation can transfer susceptibility to MIA-associated neurodevelopmental disease and that this is associated with modulation of the maternal immune response. Furthermore, we find that ablation of IL-17a signaling provides protection against the development of neurodevelopmental abnormalities in MIA offspring. Our findings suggest that microbiota landscape can influence MIA-induced neurodevelopmental disease pathogenesis and that this occurs as a result of microflora-associated calibration of gestational IL-17a responses.

https://ift.tt/2uXQcfy

Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via Targeting STING/MITA in Fish [INFECTIOUS DISEASE AND HOST RESPONSE]

Viral infection induces type I IFN production, which plays critical roles in orchestrating the antiviral defense by inducing direct antiviral activities. To establish a persistent infection, viruses have evolved numerous strategies to specifically interfere with IFN production or its downstream mediators, thereby evading the immune responses. MicroRNAs (miRNAs) are a family of small noncoding RNAs that posttranscriptionally regulate the expressions of specific target genes. Although accumulating evidence demonstrates that miRNAs play vital roles in regulating viral infection, miRNAs that target intracellular sensors and adaptors of innate immunity have not been fully uncovered. In this paper, we identify fish miR-210 as a robust regulator involved in regulating virus–host interactions. We found that rhabdovirus significantly upregulated the expression of fish miR-210. Inducible miR-210 modulates virus-triggered type I IFN and inflammatory cytokine production by targeting stimulator of IFN genes (STING), thereby promoting viral replication. Furthermore, we demonstrated that miR-210 regulates innate immune response through NF-B, IFN regulatory factor 3, and JAK/STAT signaling pathways. The collective findings indicate that inducible miR-210 plays a regulatory role in virus–host interactions through STING-mediated singling pathway by targeting STING.

https://ift.tt/2mBpoxH

Repeated Allergen Exposure in A/J Mice Causes Steroid-Insensitive Asthma via a Defect in Glucocorticoid Receptor Bioavailability [ALLERGY AND OTHER HYPERSENSITIVITIES]

The importance of developing new animal models to assess the pathogenesis of glucocorticoid (GC)-insensitive asthma has been stressed. Because of the asthma-prone background of A/J mice, we hypothesized that asthma changes in these animals would be or become resistant to GCs under repeated exposures to an allergen. A/J mice were challenged with OVA for 2 or 4 consecutive d, starting on day 19 postsensitization. Oral dexamethasone or inhaled budesonide were given 1 h before challenge, and analyses were done 24 h after the last challenge. Airway hyperreactivity, leukocyte infiltration, tissue remodeling, and cytokine levels as well as phosphorylated GC receptor (p-GCR), p-GATA-3, p-p38, MAPK phosphatase-1 (MKP-1), and GC-induced leucine zipper (GILZ) levels were assessed. A/J mice subjected to two daily consecutive challenges reacted with airway hyperreactivity, subepithelial fibrosis, and marked accumulation of eosinophils in both bronchoalveolar lavage fluid and peribronchial space, all of which were clearly sensitive to dexamethasone and budesonide. Conversely, under four provocations, most of these changes were steroid resistant. A significant reduction in p-GCR/GCR ratio following 4- but not 2-d treatment was observed, as compared with untreated positive control. Accordingly, steroid efficacy to transactivate MKP-1 and GILZ and to downregulate p-p38, p-GATA-3 as well as proinflammatory cytokine levels was also seen after two but not four provocations. In conclusion, we report that repeated allergen exposure causes GC-insensitive asthma in A/J mice in a mechanism associated with decrease in GCR availability and subsequent loss of steroid capacity to modulate pivotal regulatory proteins, such as GATA-3, p-p38, MKP-1, and GILZ.

https://ift.tt/2mEv0Yk

Ligation of the CD44 Glycoform HCELL on Culture-Expanded Human Monocyte-Derived Dendritic Cells Programs Transendothelial Migration [INNATE IMMUNITY AND INFLAMMATION]

The success of dendritic cell (DC)–based immunotherapeutics critically hinges on the capacity of the vascularly administered cells to enter tissues. Transendothelial migration (TEM) is dictated by an ordered cascade of receptor/ligand interactions. In this study, we examined the key molecular effectors of TEM of human monocyte-derived DCs (mo-DCs) generated by clinically relevant methods: CD14 selection (CD14-S) and plastic adherence selection (PA-S). Without chemokine input, CD14-S cells undergo greater TEM than PA-S cells over TNF-α–stimulated HUVECs. TEM of CD14-S mo-DCs is E-selectin/very late Ag-4 (VLA-4) dependent, and engagement of E-selectin ligands activates VLA-4 on CD14-S mo-DCs but not on PA-S mo-DCs. E-selectin binding glycoforms of P-selectin glycoprotein ligand-1 (PSGL-1) (i.e., cutaneous lymphocyte Ag [CLA]) and CD44 (i.e., hematopoietic cell E-selectin/L-selectin ligand [HCELL]) are both expressed on CD14-S mo-DCs, but only CLA is expressed on PA-S mo-DCs. To elucidate the effect of CD44 or PSGL-1 engagement, mo-DCs were pretreated with their ligands. Ligation of CD44 on CD14-S mo-DCs triggers VLA-4 activation and TEM, whereas PSGL-1 ligation does not. HCELL expression on CD14-S mo-DC can be enforced by cell surface exofucosylation, yielding increased TEM in vitro and enhanced extravasation into bone marrow in vivo. These findings highlight structural and functional pleiotropism of CD44 in priming TEM of mo-DCs and suggest that strategies to enforce HCELL expression may boost TEM of systemically administered CD14-S mo-DCs.

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Anti-Insulin B Cells Are Poised for Antigen Presentation in Type 1 Diabetes [AUTOIMMUNITY]

Early breaches in B cell tolerance are central to type 1 diabetes progression in mouse and man. Conventional BCR transgenic mouse models (VH125.Tg NOD) reveal the power of B cell specificity to drive disease as APCs. However, in conventional fixed IgM models, comprehensive assessment of B cell development is limited. To provide more accurate insight into the developmental and functional fates of anti-insulin B cells, we generated a new NOD model (V_H125^SD.NOD) in which anti-insulin VDJH125 is targeted to the IgH chain locus to generate a small (1–2%) population of class switch–competent insulin-binding B cells. Tracking of this rare population in a polyclonal repertoire reveals that anti-insulin B cells are preferentially skewed into marginal zone and late transitional subsets known to have increased sensitivity to proinflammatory signals. Additionally, IL-10 production, characteristic of regulatory B cell subsets, is increased. In contrast to conventional models, class switch–competent anti-insulin B cells proliferate normally in response to mitogenic stimuli but remain functionally silent for insulin autoantibody production. Diabetes development is accelerated, which demonstrates the power of anti-insulin B cells to exacerbate disease without differentiation into Ab-forming or plasma cells. Autoreactive T cell responses in V_H125^SD.NOD mice are not restricted to insulin autoantigens, as evidenced by increased IFN- production to a broad array of diabetes-associated epitopes. Together, these results independently validate the pathogenic role of anti-insulin B cells in type 1 diabetes, underscore their diverse developmental fates, and demonstrate the pathologic potential of coupling a critical β cell specificity to predominantly proinflammatory Ag-presenting B cell subsets.

https://ift.tt/2uXQbIw

Kidney Proximal Tubular TLR9 Exacerbates Ischemic Acute Kidney Injury [TRANSPLANTATION]

The role for kidney TLR9 in ischemic acute kidney injury (AKI) remains unclear. In this study, we tested the hypothesis that renal proximal tubular TLR9 activation exacerbates ischemic AKI by promoting renal tubular epithelial apoptosis and inflammation. To test this hypothesis, we generated mice lacking TLR9 in renal proximal tubules (TLR9^fl/fl PEPCK Cre mice). Contrasting previous studies in global TLR9 knockout mice, mice lacking renal proximal tubular TLR9 were protected against renal ischemia/reperfusion (IR) injury, with reduced renal tubular necrosis, inflammation (decreased proinflammatory cytokine synthesis and neutrophil infiltration), and apoptosis (decreased DNA fragmentation and caspase activation) when compared with wild-type (TLR9^fl/fl) mice. Consistent with this, a selective TLR9 agonist oligonucleotide 1668 exacerbated renal IR injury in TLR9^fl/fl mice but not in renal proximal tubular TLR9-null mice. Furthermore, in cultured human and mouse proximal tubule cells, TLR9-selective ligands induced NF-B activation, proinflammatory cytokine mRNA synthesis, as well as caspase activation. We further confirm in the present study that global TLR9 deficiency had no impact on murine ischemic AKI. Taken together, our studies show that renal proximal tubular TLR9 activation exacerbates ischemic AKI by promoting renal tubular inflammation, apoptosis as well as necrosis, after IR via NF-B and caspase activation. Our studies further suggest the complex nature of TLR9 activation, as renal tubular epithelial TLR9 promotes cell injury and death whereas TLR9 signaling in other cell types may promote cytoprotective effects.

https://ift.tt/2mC0DkY

Breakdown of Immune Tolerance in AIRE-Deficient Rats Induces a Severe Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-like Autoimmune Disease [AUTOIMMUNITY]

Autoimmune regulator (AIRE) deficiency in humans induces a life-threatening generalized autoimmune disease called autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), and no curative treatments are available. Several models of AIRE-deficient mice have been generated, and although they have been useful in understanding the role of AIRE in central tolerance, they do not reproduce accurately the APECED symptoms, and thus there is still a need for an animal model displaying APECED-like disease. We assessed, in this study, the potential of the rat as an accurate model for APECED. In this study, we demonstrate that in rat, AIRE is expressed by MHC class II (MCH-II)⁺ and MHC-II^– medullary thymic epithelial cells in thymus and by CD4^int conventional dendritic cells in periphery. To our knowledge, we generated the first AIRE-deficient rat model using zinc-finger nucleases and demonstrated that they display several of the key symptoms of APECED disease, including alopecia, skin depigmentation, and nail dystrophy, independently of the genetic background. We observed severe autoimmune lesions in a large spectrum of organs, in particular in the pancreas, and identified several autoantibodies in organs and cytokines such as type I IFNs and IL-17 at levels similar to APECED. Finally, we demonstrated a biased Ab response to IgG1, IgM, and IgA isotypes. Altogether, our data demonstrate that AIRE-deficient rat is a relevant APECED animal model, opening new opportunity to test curative therapeutic treatments.

https://ift.tt/2mBpw09

In This Issue [IN THIS ISSUE]

https://ift.tt/2A4cmCF

A Diverse Lipid Antigen-Specific TCR Repertoire Is Clonally Expanded during Active Tuberculosis [CLINICAL AND HUMAN IMMUNOLOGY]

Human T cells that recognize lipid Ags presented by highly conserved CD1 proteins often express semi-invariant TCRs, but the true diversity of lipid Ag–specific TCRs remains unknown. We use CD1b tetramers and high-throughput immunosequencing to analyze thousands of TCRs from ex vivo–sorted or in vitro–expanded T cells specific for the mycobacterial lipid Ag, glucose monomycolate. Our results reveal a surprisingly diverse repertoire resulting from editing of germline-encoded gene rearrangements analogous to MHC-restricted TCRs. We used a distance-based metric (TCRDist) to show how this diverse TCR repertoire builds upon previously reported conserved motifs by including subject-specific TCRs. In a South African cohort, we show that TCRDist can identify clonal expansion of diverse glucose monomycolate–specific TCRs and accurately distinguish patients with active tuberculosis from control subjects. These data suggest that similar mechanisms govern the selection and expansion of peptide and lipid Ag–specific T cells despite the nonpolymorphic nature of CD1.

https://ift.tt/2uXQ9jS

Immune Checkpoint Blockade Restores HIV-Specific CD4 T Cell Help for NK Cells [INFECTIOUS DISEASE AND HOST RESPONSE]

Immune exhaustion is an important feature of chronic infections, such as HIV, and a barrier to effective immunity against cancer. This dysfunction is in part controlled by inhibitory immune checkpoints. Blockade of the PD-1 or IL-10 pathways can reinvigorate HIV-specific CD4 T cell function in vitro, as measured by cytokine secretion and proliferative responses upon Ag stimulation. However, whether this restoration of HIV-specific CD4 T cells can improve help to other cell subsets impaired in HIV infection remains to be determined. In this study, we examine a cohort of chronically infected subjects prior to initiation of antiretroviral therapy (ART) and individuals with suppressed viral load on ART. We show that IFN- induction in NK cells upon PBMC stimulation by HIV Ag varies inversely with viremia and depends on HIV-specific CD4 T cell help. We demonstrate in both untreated and ART-suppressed individuals that dual PD-1 and IL-10 blockade enhances cytokine secretion of NK cells via restored HIV-specific CD4 T cell function, that soluble factors contribute to these immunotherapeutic effects, and that they depend on IL-2 and IL-12 signaling. Importantly, we show that inhibition of the PD-1 and IL-10 pathways also increases NK degranulation and killing of target cells. This study demonstrates a previously underappreciated relationship between CD4 T cell impairment and NK cell exhaustion in HIV infection, provides a proof of principle that reversal of adaptive immunity exhaustion can improve the innate immune response, and suggests that immune checkpoint modulation that improves CD4/NK cell cooperation can be used as adjuvant therapy in HIV infection.

https://ift.tt/2A4JKJm

B7-H4 Modulates Regulatory CD4+ T Cell Induction and Function via Ligation of a Semaphorin 3a/Plexin A4/Neuropilin-1 Complex [IMMUNE REGULATION]

The potent immune regulatory function of an agonistic B7-H4-Ig fusion protein (B7-H4Ig) has been demonstrated in multiple experimental autoimmune models; however, the identity of a functional B7-H4 receptor remained unknown. The biological activity of B7-H4 is associated with decreased inflammatory CD4⁺ T cell responses as supported by a correlation between B7-H4–expressing tumor-associated macrophages and Foxp3⁺ T cells within the tumor microenvironment. Recent data indicate that members of the semaphorin (Sema)/plexin/neuropilin (Nrp) family of proteins both positively and negatively modulate immune cell function. In this study, we show that B7-H4 binds the soluble Sema family member Sema3a. Additionally, B7-H4Ig–induced inhibition of inflammatory CD4⁺ T cell responses is lost in both Sema3a functional mutant mice and mice lacking Nrp-1 expression in Foxp3⁺ T cells. These findings indicate that B7-H4Ig binds to Sema3a, which acts as a functional bridge to stimulate an Nrp-1/Plexin A4 heterodimer to form a functional immunoregulatory receptor complex resulting in increased levels of phosphorylated PTEN and enhanced regulatory CD4⁺ T cell number and function.

https://ift.tt/2mBzMFJ

Blocking TIR Domain Interactions in TLR9 Signaling [INNATE IMMUNITY AND INFLAMMATION]

Interaction of TLR9 with ligands activates NF-B, leading to proinflammatory cytokine production. Excessive TLR activation is a pathogenic factor for inflammatory diseases. This study has examined cell-permeating decoy peptides (CPDPs) derived from the TLR9 Toll/IL-1R resistance (TIR) domain. CPDP 9R34, which included AB loop, β-strand B, and N-terminal BB loop residues, inhibited TLR9 signaling most potently. CPDPs derived from α-helices C, D, and E (i.e., 9R6, 9R9, and 9R11) also inhibited TLR9-induced cytokines but were less potent than 9R34. 9R34 did not inhibit TLR2/1, TLR4, or TLR7 signaling. The N-terminal deletion modification of 9R34, 9R34-N, inhibited TLR9 as potently as the full length 9R34. Binding of 9R34-N to TIR domains was studied using cell-based Förster resonance energy transfer/fluorescence lifetime imaging approach. Cy3-labeled 9R34-N dose-dependently decreased fluorescence lifetime of TLR9 TIR–Cerulean (Cer) fusion protein. Cy3–9R34-N also bound TIRAP TIR, albeit with a lesser affinity, but not MyD88 TIR, whereas CPDP from the opposite TIR surface, 9R11, bound both adapters and TLR9. i.p. administration of 9R34-N suppressed oligonucleotide-induced systemic cytokines and lethality in mice. This study identifies a potent, TLR9-specific CPDP that targets both receptor dimerization and adapter recruitment. Location of TIR segments that represent inhibitory CPDPs suggests that TIR domains of TLRs and TLR adapters interact through structurally homologous surfaces within primary receptor complex, leading to formation of a double-stranded, filamentous structure. In the presence of TIRAP and MyD88, primary complex can elongate bidirectionally, from two opposite ends, whereas in TIRAP-deficient cells, elongation is unidirectional, only through the αE side.

https://ift.tt/2A4JIBe

Active mTORC2 Signaling in Naive T Cells Suppresses Bone Marrow Homing by Inhibiting CXCR4 Expression [IMMUNE REGULATION]

Recirculation of naive T cells between secondary lymphoid organs to receive survival cues and scan for signs of infection or other pathologic conditions is important for immune homeostasis and effective immune responses. Although the mechanisms that specifically guide the entry of naive T cells into secondary lymphoid organs are well studied, the mechanisms that keep them from fluxing into inappropriate or undesirable compartments, such as healthy tissues or bone marrow, are less well understood. In this study, we report an unexpected finding that under steady state, bone marrow homing of naive T cells is actively suppressed by mTORC2 signaling. We found that in mice, T cell–specific deletion of an essential mTORC2 component Sin1 results in increased accumulation of naive T cells in the bone marrow. Mechanistically, we show that loss of mTORC2 signaling in naive T cells results in enhanced FOXO1 activity, which leads to increased CXCR4 expression and chemotactic response to CXCL12, a key chemokine that promotes bone marrow homing and retention of T cells. Together, the results of our study reveal a novel role of mTORC2 in T cell homeostasis via active suppression of naive T cell bone marrow homing by the mTORC2–FOXO1–CXCR4 axis.

https://ift.tt/2uXQ7Zi

MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas

The investigation and management of unilateral adrenal incidentalomas have been extensively considered in the last decades. While bilateral adrenal incidentalomas represent about 15% of adrenal incidentalomas (AIs), they have been less frequently discussed. The differential diagnosis of bilateral incidentalomas includes metastasis, primary bilateral macronodular adrenal hyperplasia and bilateral cortical adenomas. Less frequent etiologies are bilateral pheochromocytomas, congenital adrenal hyperplasia (CAH), Cushing's disease or ectopic ACTH secretion with secondary bilateral adrenal hyperplasia, primary malignancies, myelolipomas, infections or hemorrhage. The investigation of bilateral incidentalomas includes the same hormonal evaluation to exclude excess hormone secretion as recommended in unilateral AI, but diagnosis of CAH and adrenal insufficiency should also be excluded. This review is focused on the differential diagnosis, investigation and treatment of bilateral AIs.

https://ift.tt/2LeXdnb

ANNIVERSARY REVIEW: 50 years since the discovery of bromocriptine

Ergotism is the long-term ergot poisoning by ingestion of rye or other grains infected with the fungus Claviceps purpurea and more recently by excessive intake of ergot drugs. It has either neuropsychiatric or vascular manifestations. In the Middle Ages, the gangrenous poisoning was known as St. Anthony's fire, after the order of the Monks of St. Anthony who were particularly skilled at treating the condition. In 1917, Prof. Arthur Stoll returned home to Switzerland from Germany, to lead the development of a new pharmaceutical department at Sandoz Chemical Company. Stoll, using the special methods of extraction learned from his work with his mentor Willstetter, started his industrial research work with ergot. He succeeded in isolating, from the ergot of rye, ergotamine as an active principle of an old popular remedy for excessive post-partum bleeding. The success of this discovery occurred in 1918 and was translated into a pharmaceutical product in 1921 under the trade name Gynergen. In subsequent work, Stoll and his team were leaders in identifying the structure of the many other alkaloids and amines produced by Claviceps purpurea. This was the cultural background and scientific foundation on which bromocriptine was discovered.

https://ift.tt/2JORkYb

Surviving ectopic Cushings syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushings disease during long-term follow-up

Objective

Aim of our study was to analyze long-term outcome of patients with the ectopic Cushing's syndrome (ECS) compared to patients with Cushing's disease (CD) regarding cardiovascular, metabolic, musculoskeletal and psychiatric comorbidities.

Design

Cross-sectional study in patients with ECS and CD in two German academic tertiary care centers.

Methods

Standardized clinical follow-up examination was performed including health-related quality of life (QoL) in 21 ECS patients in long-term remission (≥18 months since successful surgery). Fifty-nine patients with CD in remission served as controls.

Results

Time from first symptoms to diagnosis of Cushing's syndrome (CS) was shorter in ECS than in CD (8.5 (IQR: 30.3) vs 25 (IQR: 39.0) months, P = 0.050). ECS patients had lower self-reported psychiatric morbidity compared to CD (19% vs 43%, P = 0.050) at follow-up. Moreover, female ECS patients reported favorable scores for QoL in the SF-36 questionnaire (mental health: 92 (IQR: 30) vs 64 (IQR: 32) in CD, P = 0.010) and a Cushing-specific QoL questionnaire (73 (IQR: 18) vs 59 (IQR: 36) in CD, P = 0.030). In a pooled analysis of ECS and CD patients, QoL correlated with time from first symptoms until diagnosis of CS, but not with urinary free cortisol levels or serum cortisol after dexamethasone at the time of diagnosis. Long-term outcomes regarding hypertension, metabolic parameters, bone mineral density and grip strength were comparable in ECS and CD.

Conclusions

Our data support the concept that time of exposure to glucocorticoid excess appears to be a better predictor than peak serum cortisol levels at the time of diagnosis regarding long-term psychiatric morbidity and QoL.

https://ift.tt/2LhXUff

The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women

Objective

Human aging is accompanied by a decrease in growth hormone secretion and serum insulin-like growth factor (IGF)-1 levels. Also, loss of muscle mass and strength and impairment of physical performance, ending in a state of frailty, are seen in elderly. We aimed to investigate whether handgrip strength, physical performance and recurrent falls are related to serum IGF-1 levels in community-dwelling elderly.

Design

Observational cohort study (cross-sectional and prospective).

Methods

We studied the association between IGF-1 and handgrip strength, physical performance and falls in participants of the Longitudinal Aging Study Amsterdam. A total of 1292 participants were included (633 men, 659 women). Serum IGF-1 levels were divided into quartiles (IGF-1-Q1 to IGF-1-Q4). Data on falls were collected prospectively for a period of 3 years. All analyses were stratified for age and physical activity and adjusted for relevant confounders.

Results

Men with a low physical activity score in IGF-1-Q1 and IGF-1-Q2 of the younger age group had a lower handgrip strength compared to IGF-1-Q4. In younger more active males in IGF-1-Q2 physical performance was worse. Recurrent fallers were less prevalent in older, low active males with low IGF-1 levels. In females, recurrent fallers were more prevalent in older, more active females in IGF-1-Q2. IGF-1 quartile may predict changes in handgrip strength and physical performance in men and women.

Conclusions

Our results indicate that lower IGF-1 levels are associated with lower handgrip strength and worse physical performance, but less recurrent fallers especially in men. Associations were often more robust in IGF-1-Q2. Future studies on this topic are desirable.

https://ift.tt/2JMViAJ

MECHANISMS OF ENDOCRINOLOGY: Cell cycle regulation in adrenocortical carcinoma

Adrenocortical carcinomas (ACCs) are rather rare endocrine tumors that often have a poor prognosis. The reduced survival rate associated with these tumors is due to their aggressive biological behavior, combined with the scarcity of effective treatment options that are currently available. The recent identification of the genomic alterations present in ACC have provided further molecular mechanisms to develop consistent strategies for the diagnosis, prevention of progression and treatment of advanced ACCs. Taken together, molecular and genomic advances could be leading the way to develop personalized medicine in ACCs similarly to similar developments in lung or breast cancers. In this review, we focused our attention to systematically compile and summarize the alterations in the cell cycle regulation that were described so far in ACC as they are known to play a crucial role in cell differentiation and growth. We have divided the analysis according to the major transition phases of the cell cycle, G1 to S and G2 to M. We have analyzed the most extensively studied checkpoints: the p53/Rb1 pathway, CDC2/cyclin B and topoisomerases (TOPs). We reached the conclusion that the most important alterations having a potential application in clinical practice are the ones related to p53/Rb1 and TOP 2. We also present a brief description of on-going clinical trials based on molecular alterations in ACC. The drugs have targeted the insulin-like growth factor receptor 1, TOP 2, polo-like kinase1, cyclin-dependent kinase inhibitors, p53 reactivation and CDC25.

https://ift.tt/2LfTG7W

Characterization of an activating R1353H insulin-like growth factor 1 receptor variant in a male with extreme tall height

Objective

The insulin-like growth factor1 receptor (IGF1R) is important in growth and development, and inactivating IGF1R mutations cause short stature and relatively high levels of serum IGF-I. We identified an unclassified IGF1R^R1353H variant in a male with extreme tall height, very low levels of serum IGF-I and delayed and prolonged growth spurt. The index case's mother and three sons all carried the variant, but so far only the eldest son (age 18 years) presented with tall height. We hypothesized that the variant could constitute an activating mutation.

Design

The IGF1R^R1353H variant was investigated in Igf1r^–/– mouse embryonic fibroblasts (R-cells) by cell cycle, colony formation and transcriptome analyses.

Results

The IGF1R^R1353H (R-1353) exhibited significantly increased cell proliferation, G1-S progression and colony formation in soft agar. RNA sequencing identified 195 differentially expressed genes between R-WT and R-1353 (adjusted P < 1E-100). Most genes were upregulated in R-1353, including the gene encoding the androgen receptor (AR). Gene expression profiling showed the most significant enrichment in extracellular matrix organization (P = 2.76E-7), collagen biosynthesis (P = 1.21E-5) and cell adhesion (P = 7.38E-5). Retrospective biochemical analysis of the index case revealed decreased testosterone and sex hormone-binding globulin levels, whereas LH and FSH were within normal ranges. This profile suggests an increased sensitivity to androgen, which is compatible with the enhanced expression of Ar in R-1353 cells.

Conclusions

Our findings suggest that R1353H constitutes an activating IGF1R variant. The possible deregulation of collagen turnover and increased androgen sensitivity implicates an association to tall phenotype in male carriers.

https://ift.tt/2LIWNBE

False-positive findings on 6-[18F]fluor-L-3,4-dihydroxyphenylalanine PET (18F-FDOPA-PET) performed for imaging of neuroendocrine tumors

Background/aim

PET with 6-[18F]fluor-l-3,4-dihydroxyphenylalanine (¹⁸F-FDOPA) has been shown to be a useful imaging tool with a high sensitivity for the visualization of neuroendocrine tumors (NETs). ¹⁸F-FDOPA uptake in tumors other than NETs has been suggested previously, but data on this phenomenon are limited. We therefore studied the non-physiological, false-positive uptake of ¹⁸F-FDOPA in a large population of patients with a NET or with a high clinical suspicion of harboring a NET.

Patients and methods

Retrospective single-center study among adult patients in whom ¹⁸F-FDOPA PET scintigraphy was performed between January 2004 and December 2014. The original scan report was compared with the original pathology report corresponding with the ¹⁸F-FDOPA PET-positive lesion. In case this was inconsistent with the diagnosis of a NET, both the scan and the pathology slides were reassessed. Specimens of these non-NET tissues were immunohistochemically stained for AADC.

Results

1070 ¹⁸F-FDOPA PET scans from 705 patients were evaluated. Focal or multiple ¹⁸F-FDOPA-avid lesions were described in 709 ¹⁸F-FDOPA PET scans (66%). Histology of these ¹⁸F-FDOPA PET-positive lesions was present in 508 (72%) cases. In seven cases, the histopathology was not compatible with NET but showed squamous cell carcinoma of the cervix, multiple myeloma (two cases), hepatocellular carcinoma, Schwannoma, adrenocortical carcinoma and a skeletal myxoid chondrosarcoma, with positive immunohistochemical staining for AADC in 67%.

Conclusions

Pathological uptake of ¹⁸F-FDOPA does not always indicate the presence of a NET. The possibility of ¹⁸F-FDOPA uptake by tumor types other than NETs, although rare, should be considered.

https://ift.tt/2LiWWzp

Reproductive drugs and environmental contamination: quantum, impact assessment and control strategies

Abstract

Industrial and municipal solid wastes, noise, pesticides, fertilizers and vehicular emission are visible pollutants responsible for environmental contamination and ill-effects on health of all living systems. But, environmental contamination due to drugs or medicines used for different purposes in humans and animals goes unseen largely and can affect the health of living system severely. During the last few decades, the usage of drugs has increased drastically, resulting in increased drug load in soil and water. Contraceptive and fertility drugs are extensively and effectively used in humans as well as animals for different purposes. Usage of these reproductive drugs in humans is increased manifold to manage reproductive problems and/or for birth control with changing lifestyles. These drugs are excreted in urine and faeces as metabolite or conjugated forms, leading to contamination of water, milk and animal produce, which are consumed directly by humans as well as animals. These drugs are not eliminated even by water treatment plant. Consumption of such contaminated water, milk, meat and poultry products results in reproductive disorders such as fertility loss in men and increase risk of different types of cancers in humans. Therefore, assessment of impact of environmental contamination by these drugs on living system is of paramount importance. The purpose of this review article is to provide a comprehensive analysis of various research and review reports on different contraceptive and fertility drugs used in human and animals, their occurrence in the environment and their ill-effects on living systems. The approaches to control this invisible menace have also been proposed.

https://ift.tt/2mAYl5L

Neck stiffness in a post-irradiated nasopharyngeal carcinoma adult: An unusual diagnosis

Publication date: Available online 23 July 2018

Source: Auris Nasus Larynx

Author(s): Kang Ni Lorna Ting, Yew Toong Liew, Zulkiflee Abu Bakar, Prepageran Narayanan

Abstract

Nasopharyngeal carcinoma is a neoplasm commonly found in population of South East Asia. The mainstay of treatment is high dose irradiation. Complications from radiotherapy are not uncommon especially to those nearby structures such as vertebrae and spinal cord. A 57 year-old gentleman with nasopharyngeal carcinoma (NPC) who was treated with chemo-radiation (total of 35 fractions,70 Gy) presented to us 6 months post therapy with bilateral nasal discharge and progressive neck stiffness. Nasoendoscopy showed inflamed nasophayngeal mucosa and Computed Tomography (CT) brain and cervical spine showed retropharyngeal and anterior epidural collection with extension into atlantoaxial bone and spinal cord compression. Histopathological specimen revealed features of chronic inflammations with multiple actinomycetes colonies. Our patient suffered severe neck stiffness and loss of sensations on both upper limbs. He was treated conservatively with Halo vest and intravenous antibiotics for 8 weeks and recovered fully.

Irradiation in NPC is known to cause devastating complications to cervical spine such as osteoradionecrosis, osteomyelitis. It also renders tissues hypoxic and risk of getting rare infection like actinomycosis. This report can represent a great diagnostic and therapeutic challenge with differentials of tumor recurrence, osteoradionecrosis or osteomyelitis. Patients must be regularly followed up to look for possible cervical complications as a result from irradiation, to prevent devastating outcome or prognosis.

https://ift.tt/2LhJThD

Corrigendum to “From periodontal mechanoreceptors to chewing motor control: A systematic review” [Arch. Oral Biol. 78 (2017) 109–121]

Publication date: Available online 23 July 2018

Source: Archives of Oral Biology

Author(s): Grazia Piancino Maria, Isola Gaetano, Cannavale Rosangela, Cutroneo Giuseppina, Vermiglio Giovanna, Bracco Pietro, Pio Anastasi Giuseppe

https://ift.tt/2NAWlGg

Indoor and outdoor concentrations of BTEX and formaldehyde in Tehran, Iran: effects of building characteristics and health risk assessment

Abstract

BTEX (benzene, toluene, ethylbenzene, xylene) and formaldehyde are toxic compounds that can induce adverse health effect in humans. This study measured in-home and ambient concentrations of BTEX and formaldehyde across Tehran, Iran. These pollutants were sampled from the indoor and adjacent outdoor air of 45 houses (9 in each city zone) during the winter of 2015. Sampling was repeated three times for each house. The analyses were performed according to NIOSH procedures. The effect of flooring material, wall covering, ventilation system, heating system, height above ground, presence of attached garages, and distance from highways was evaluated. In addition, carcinogenic and non-carcinogenic risks of these compounds were assessed. The average indoor concentrations of benzene, toluene, ethylbenzene, xylene, and formaldehyde were 53.2, 21.5, 14.4, 21.1, and 17.9 μg/m³, respectively. The average outdoor concentrations of benzene, toluene, ethylbenzene, xylene, and formaldehyde were 43.5, 26.2, 10.0, 19.1, and 6.9 μg/m³, respectively. Separate regression models showed that wall coating, ventilation system, heating system, flat level, and distance from highways explained 29, 60, 16, 60, and 59% of the BTEX concentrations, respectively. Houses with oil painted walls and parquet flooring had higher concentrations of BTEX and formaldehyde, respectively. The health risk assessment found that the carcinogenic risks of benzene and formaldehyde exceeded 1 × 10⁻⁴ and represent a definite risk. New buildings can be designed based on the results of this study to use better materials and optimum building designs to reduce exposure to these toxic air pollutants.

https://ift.tt/2uKFaLd

Promoting effect of Nb doping on catalytic performance for deep oxidation of 1, 2-dichloroethane over (Ce,Cr) x O 2 -Nb 2 O 5 catalysts

Abstract

A series of Nb-doped (Ce,Cr)_xO₂-Nb₂O₅ mixed oxides with varying (Ce,Cr)_xO_2/Nb₂O₅ mass ratio were prepared by a co-precipitation method and evaluated for the catalytic performance of eliminating 1,2-dichloroethane (DCE). The results indicate that there exists a strong synergistic effect between acid sites and redox species in (Ce,Cr)_xO₂-Nb₂O₅ improving the catalytic activity for DCE oxidation. Appropriate Nb doping could promote the high dispersion and the interaction of metal oxides in the (Ce,Cr)_xO₂-Nb₂O₅ catalysts, resulting in the formation of more Cr⁶⁺ species with strong oxidizing ability and excellent mobility of oxygen species from bulk to surface to create more active sites for DCE deep oxidation. The (Ce,Cr)_xO₂-Nb₂O₅ catalysts with (Ce,Cr)_xO₂/Nb₂O₅ ratios of 2/1~1/2 exhibit excellent catalytic activity and durability for DCE degradation in dry air as well as benzene or water vapor, and less chlorinated byproduct is produced during the degradation of DCE.

https://ift.tt/2LJE5Ki

Molecular profiling of regulatory T cells in pulmonary sarcoidosis

Publication date: Available online 23 July 2018

Source: Journal of Autoimmunity

Author(s): Neli Kachamakova-Trojanowska, Agnieszka Jazwa-Kusior, Krzysztof Szade, Lukasz Kasper, Jerzy Soja, Anna Andrychiewicz, Bogdan Jakiela, Hanna Plutecka, Marek Sanak, Alicja Jozkowicz, Krzysztof Sladek, Jozef Dulak

Abstract

Background

Sarcoidosis is characterized by exaggerated immune response to unknown agent and can affect different organs. One of the main players in the pathology of the disease are regulatory T cells (Tregs), however, up to date the mechanisms of the possible molecular alterations of this particular cell subset are not known.

Methods

In the current study we looked for the global transcriptomic changes of miRNAs, using predefined array, and mRNAs (RNA seq analysis) of Tregs of patients with the most predominant form of the disease - acute pulmonary sarcoidosis (PS). For this purpose sorted CD4+/CD25+/CD127- Tregs from peripheral blood (PB) and CD4+/CD25 + Tregs from bronchoalveolar lavage (BAL) were used.

Results

MiRNA analysis revealed that Tregs isolated from PB and BAL display significantly different miRNA profile, suggesting an important role of the pulmonary microenvironment in creating these changes. Among disease-related miRNAs of PB Tregs we identified miR-155 and miR-223. Moreover, looking at the global transcriptome of PB Tregs, we recognized alterations in TLR-2 signaling pathway and in the downstream of NF-κB apoptosis and proliferation signals. However, induction of TLR-2 expression was found not only in Tregs, but also in the heterogeneous population of peripheral blood mononuclear cells (PBMC) as well as two PBMC subpopulations (CD4+/CD25-and CD4-/CD25-) of patients with PS. This indicates that activation of TLR signaling pathway in sarcoidosis does not occur only in Tregs.

Conclusion

Our findings offer a deeper insight into the molecular mechanisms of Tregs reduced suppression and increased apoptosis in patients with PS. Based on the current results, future studies should focus on possible therapeutic effect of TLR-2 signaling inhibition.

https://ift.tt/2O8EbN0

Altered distribution and function of splenic innate lymphoid cells in adult chronic immune thrombocytopenia.

Publication date: Available online 23 July 2018

Source: Journal of Autoimmunity

Author(s): Sylvain Audia, Thomas Moulinet, Marion Ciudad-Bonté, Maxime Samson, Olivier Facy, Pablo Ortega-Deballon, Philippe Saas, Bernard Bonnotte

Abstract

Innate lymphoid cells (ILCs) have been characterized as innate immune cells capable to modulate the immune response in the mucosae. Human ILCs have been rarely described in secondary lymphoid organs except in tonsils. Moreover, their function and phenotype in human secondary lymphoid organs during autoimmune diseases have never been studied. We took advantage of splenectomy as a treatment of immune thrombocytopenia (ITP) to describe and compare splenic ILC from 18 ITP patients to 11 controls. We first confirmed that ILC3 represented the most abundant ILC subset in human non-inflamed spleens, accounting for 90% of total ILC, and that they were mostly constituted of NKp44^- cells. On the contrary, proportions of ILC1 and ILC2 in spleens were lower than in blood. Splenic IL-2- and IFN-γ-producing ILC1 were increased in ITP. While the frequencies of total splenic ILC3 were similar in the two groups, splenic GM-CSF-producing ILC3 were increased in ITP.

This is the first description of human ILC in a major secondary lymphoid organ during an autoimmune disease, ITP. We observed an expansion of splenic ILC1 that could participate to the Th1 skewing, while the increased production of GM-CSF by splenic ILC3 could stimulate splenic macrophages which play a key role in ITP pathophysiology.

https://ift.tt/2NDof49

The increasing carbon dioxide (CO 2 ) due to global climate change strengthens the plants and inhibits pathogenic infection

https://ift.tt/2Oa5Z3G

Analysis of the audiogram shape in patients with idiopathic sudden sensorineural hearing loss using a cluster analysis

Tetsuo Watanabe, MD, PhD; Masashi Suzuki, MD, PhD

Abstract

We performed a cluster analysis to classify the audiogram shape in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). We also investigated whether the audiogram shape is a prognostic indicator in the management of ISSNHL. A total of 115 inpatients with ISSNHL treated between 2001 and 2010 were analyzed. The data collected included age, sex, duration of hearing loss at the time of treatment, and the presence or absence of tinnitus, vertigo, diabetes, nystagmus, and canal paresis. A hierarchical cluster analysis was performed using the hearing threshold for each frequency on audiograms as variables. A logistic regression model was used for the prognostic analysis. The audiogram shape was classified into four clusters: (1) crossing horizontally pattern of all tones; (2) up-sloping pattern of low-tone loss; (3) deaf pattern; and (4) down-sloping pattern of high-tone loss. The age of the patient, presence of canal paresis, and audiogram shape showed statistically significant relationships with hearing improvement. The audiogram shape based on the cluster analysis demonstrated a significant relationship with hearing improvement in patients with ISSNHL. Further studies are needed to elucidate the underlying etiology of each audiogram shape.

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Analyzing Medicare payments to otologists

T. Edward Imbery, MD; Brian D. Nicholas, MD; Parul Goyal, MD, MBA

Abstract

The study objective was to analyze Medicare payment data to otologists compared to otolaryngologists, using the publicly released Centers for Medicare and Medicaid Services dataset. Charges, payments, and common Current Procedural Terminology codes were obtained. Otology providers were selected from the roster of the American Otological Society. Descriptive statistics and unequal variance two-tailed t tests were used for comparisons between otologists (n = 147) and otolaryngologists (n = 8,318). The mean overall submitted charge was $204,851 per otology provider and was $211,209 per other otolaryngology providers (non-otologists) (p = 0.92). The mean payment to otologists was $56,191 (range: $297 to $555,274, standard deviation [SD] ±$68,540) and significantly lower (p = 0.005) than $77,275 to otolaryngologists (range: $94 to $2,123,900, SD ±$86,423). The mean submitted charge-to-payment ratio (fee multiplier) per otology provider was 3.87 (range 1.50 to 9.10, SD ±1.70), which was significantly higher (p < 0.0001) than the ratio for otolaryngologists (mean 2.91; range: 1.25 to 17.51, SD ±1.22). Office visit evaluation and management (E&M) codes made up the majority in terms of use and payments. Interestingly, allergy-based services comprised a substantial amount of repeat use among a small subset of otologists. Audiology services were billed by a similar percentage of otologists and other otolaryngologists (52%), but otologists received a significantly higher overall payment for these services.

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Ocular vestibular evoked myogenic potentials and intravestibular intralabyrinthine schwannomas

Massimo Ralli, MD, PhD; Giuseppe Nola, MD; Massimo Fusconi, MD; Luca Sparvoli, MD; Giovanni Ralli, MD

Abstract

Intravestibular intralabyrinthine schwannomas (ILSs) are uncommon benign tumors that arise from the saccular, utricular, and lateral and superior ampullary nerves. According to the literature, there is an average delay of 8 years between the onset of symptoms and diagnosis. The diagnosis is based on an audiovestibular examination and magnetic resonance imaging (MRI). We describe a case of intravestibular ILS in which we included the ocular vestibular evoked myogenic potentials (oVEMPs) test in the diagnostic workup. The oVEMPs test is a relatively new neurophysiologic diagnostic modality that evaluates the superior vestibular pathway and the ascending contralateral pathway through the vestibulo-ocular reflex. In our case, a 65-year-old man presented with progressive right-sided sensorineural hearing loss, dizziness, and tinnitus and fullness in his right ear. Audiovestibular examination and MRI detected an intravestibular ILS on the right. We found that oVEMPs were absent on the contralateral side, which contributed to the diagnostic process. The detection of oVEMPs can provide detailed information on the functionality of the macula of the utricle and the lateral and superior ampullary nerves, with a precise identification of the affected area. Based on our findings, we discuss the role of oVEMPs in the diagnosis of an intravestibular ILS.

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Warthin tumor of the larynx: A case report and review of the literature

Irit Duek, MD; Miki Paker, MD; Ziv Gil, MD, PhD; Jacob T. Cohen, MD

Abstract

Warthin tumor (papillary cystadenoma lymphomatosum) is a benign salivary gland tumor that occurs almost exclusively in the parotid gland. As far as we know, only 15 cases of laryngeal Warthin tumor have been previously reported worldwide. We describe the case of a 75-year-old woman with a supraglottic tumor that mimicked a mucoepidermoid carcinoma. The tumor was completely excised via a transcervical approach. Pathology identified it as a Warthin tumor. At follow-up, the patient maintained good oral intake. Computed tomography 3 months postoperatively confirmed complete tumor resection and detected no evidence of residual disease or recurrence. We also discuss our review of the literature on benign laryngeal salivary gland tumors, which included an analysis of 112 cases. The most common tumors were oncocytic cystadenomas (n = 65), pleomorphic adenomas (n = 28), and Warthin tumors (n = 15); we also found 2 cases each of basal cell adenomas and myoepitheliomas. The most common single tumor site was the glottis (n = 25), followed by the supraglottis (n = 24), and the subglottis (n = 22); 5 cases occurred in multiple sites, and the specific site was not reported in 36 cases. Benign laryngeal neoplasms of salivary gland origin should be carefully evaluated. Distinguishing these tumors from malignant lesions and establishing the correct diagnosis are crucial for treatment planning. Large lesions with extralaryngeal extension can be resected completely via an open external approach.

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Endoscopic view of a sinonasal osteoma

Dewey A. Christmas, MD; Joseph P. Mirante, MD, MBA, FACS; Eiji Yanagisawa, MD, FACS

Surgical intervention is indicated only in the event of symptoms or complications caused by the osteoma.

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Inflammatory myofibroblastic tumor of the larynx

Yu-Hsuan Wang, MD; Yi-Shing Leu, MD; Wei-Chin Chang, MD

Inflammatory myofibroblastic tumor usually involves the lungs, bronchopulmonary tree, and abdominal viscera.

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Accessory submandibular duct sialolithiasis identified during sialendoscopy

Andrew J. Thomas, MD; Kevin F. Wilson, MD

Abstract

We describe a unique case of a 62-year-old patient with recurrent right submandibular sialadenitis. He initially appeared to have extensive sialolithiasis of the right submandibular duct on computed tomography imaging and examination, but sialendoscopy demonstrated a normal-appearing right submandibular duct. An accessory duct posterior and parallel to the normal duct was identified at the time of sialendoscopy and was found to have extensive sialolithiasis, which required removal by both an endoscopic and intraoral technique. To the best of our knowledge, this is the first report of sialolithiasis of an accessory submandibular duct identified at the time of sialendoscopy; the other few reported cases in the literature are based primarily on findings from traditional sialography or magnetic resonance sialography. Identification of accessory salivary ducts requires intraoperative consideration of this entity during sialendoscopy. Open approaches to sialolithiasis, however, may be aided by appropriate preoperative imaging.

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Esophageal perforation as a complication of the Heimlich maneuver in a pediatric patient: A case report

Shira L. Koss, MD; William E. Karle, MD; Gregory Dibelius, MD; Ameet Kamat, MD; Craig Berzofsky, MD

Abstract

We report a case of cervical esophageal perforation caused by the Heimlich maneuver in a healthy 16-year-old boy. The patient reported a short coughing episode while eating rice, and his mother performed the Heimlich maneuver on him. Five days later, he presented to the emergency department with throat pain, odynophagia, secretion intolerance, muffled voice, and neck stiffness. He was admitted to the pediatric intensive care unit for conservative management. The next day he underwent transcervical incision and drainage of purulence, but the esophageal perforation could not be visualized at that time. The perforation was identified several days later and successfully repaired surgically. Esophageal perforation as a complication of the Heimlich maneuver is exceedingly rare, but the clinician should be aware of this entity in the differential diagnosis, as it is associated with a high mortality rate and warrants multidisciplinary care, including timely surgical intervention.

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HPV-related sinonasal carcinoma with adenoid cystic-like features with intracranial invasion

Yuntsung Hung, MD; Yu-Yen Chung, MD; Mei-Ling Chen, MD; Jyun-Ying Guo, MD

HPV-related sinonasal carcinoma with adenoid cystic-like features is a recently described tumor with less than 10 cases reported in the literature to date.

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