Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Δευτέρα 5 Νοεμβρίου 2018

Binge eating disorder and night eating syndrome in adults with type 2 diabetes: a systematic review

Abstract

Background

Type 2 diabetes (T2DM) is increasing in prevalence worldwide, and is closely linked to obesity. Binge Eating Disorder (BED) and Night Eating Syndrome (NES) are eating disorders that are common in obesity, and may affect the management as well as long term outcomes of T2DM. Therefore, the aim of this review was to assess the prevalence and associations of BED or NES in adults with T2DM.

Methods

We conducted a systematic review. The databases MEDLINE, CINAHL and AMED were searched for articles which met the inclusion criteria; including patients > 18 years old, with T2DM, and BED and/or NES. The reference lists of included studies were also searched. Meta-analysis was not attempted due to the limited number of studies that measured the outcomes of interest.

Results

A total of 10 studies (2 included NES) were included in this systematic review. The number screened for BED and NES were 6527 and 1039 participants, respectively. Point prevalence was 1.2–8.0% for BED and 3.8–8.4% for NES. Patients with T2DM and BED had higher BMI than patients with T2DM without BED in the two studies that reported BMI. There was no statistically significant difference in HbA1c between patients with and without BED in the two studies that measured HbA1c.

Conclusions

BED and NES are common in adults with T2DM, and BED is associated with higher BMI in patients with T2DM. However, only two studies reported important outcomes measures such as BMI and HbA1c in patients with T2DM. Hence, further well-designed studies are needed to assess the impact of BED and NES in patients with T2DM. Health Care Professionals should consider the diagnosis of BED and NES in patients with T2DM.



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The revised short-form of the Eating Beliefs Questionnaire: Measuring positive, negative, and permissive beliefs about binge eating

Abstract

Background

The Eating Beliefs Questionnaire (EBQ) is a self-report assessment tool that measures positive and negative beliefs about food and eating that are believed to play a key role in maintaining binge eating behaviour that occurs in individuals with Bulimia Nervosa, Binge Eating Disorder and other atypical eating disorders. The present study aimed to further refine this measure with the addition of a third scale to assess permissive beliefs about eating, also thought to play a crucial role in the maintenance of binge eating. Permissive beliefs are defined as beliefs about eating that provide justification for the individual to engage in a binge eating episode.

Methods

After consultation with the literature and endorsement from 10 experts in eating disorders, 19 permissive belief items were generated. Eight hundred eighty-three participants were recruited to complete a test battery online that included the EBQ and the new permissive items.

Results

An exploratory factor analysis (n = 441) found a three-factor solution (positive, negative and permissive beliefs) explaining 63.4% of variance. A confirmatory factor analysis (n = 442) provided support for the three-factor model, with the data best supporting a shorter 18-item questionnaire. The revised scale demonstrated good internal consistency, as well as good convergent validity with measures of related eating disorder symptoms, emotional regulation, mood and anxiety.

Conclusions

With the addition of a third scale to measure permissive beliefs, the revised short-form of the EBQ offers clinicians and researchers a brief comprehensive tool for the measurement of positive, negative and permissive beliefs about binge eating.



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An Unusual Position of Retromandibular Vein in Relation to Facial Nerve: A Rare Case Report

Knowledge of different anatomical structures is very important in parotid surgery to preserve facial nerve. Retromandibular vein is one of the landmarks used to identify facial nerve. So, the relation of the vein with facial nerve is very important in parotid surgery. The typical position of RMV is deep to facial nerve in almost 88% of cases reported in various literatures. Here, we present an unusual position of RMV found during parotid surgery for pleomorphic adenoma.

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Impact of Brain Fatty Acid Signaling on Peripheral Insulin Action in Mice

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0735-9533

Aims and Methods Glucose homeostasis and energy balance are under control by peripheral and brain processes. Especially insulin signaling in the brain seems to impact whole body glucose homeostasis and interacts with fatty acid signaling. In humans circulating saturated fatty acids are negatively associated with brain insulin action while animal studies suggest both positive and negative interactions of fatty acids and insulin brain action. This apparent discrepancy might reflect a difference between acute and chronic fatty acid signaling. To address this question we investigated the acute effect of an intracerebroventricular palmitic acid administration on peripheral glucose homeostasis. We developed and implemented a method for simultaneous monitoring of brain activity and peripheral insulin action in freely moving mice by combining radiotelemetry electrocorticography (ECoG) and euglycemic-hyperinsulinemic clamps. This method allowed gaining insight in the early kinetics of brain fatty acid signaling and its contemporaneous effect on liver function in vivo, which, to our knowledge, has not been assessed so far in mice. Results Insulin-induced brain activity in the theta and beta band was decreased by acute intracerebroventricular application of palmitic acid. Peripherally it amplified insulin action as demonstrated by a significant inhibition of endogenous glucose production and increased glucose infusion rate. Moreover, our results further revealed that the brain effect of peripheral insulin is modulated by palmitic acid load in the brain. Conclusion These findings suggest that insulin action is amplified in the periphery and attenuated in the brain by acute palmitic acid application. Thus, our results indicate that acute palmitic acid signaling in the brain may be different from chronic effects.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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



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Associations of Bone Mineral Density and Bone Metabolism Indices with Urine Albumin to Creatinine Ratio in Chinese Patients with Type 2 Diabetes

05-2018-0197-dia_10-1055-a-0762-0341-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0762-0341

Objective To identify correlations of bone mineral density (BMD) and bone metabolism indices with the urine albumin to creatinine ratio (ACR) as an indicator of nephropathy in Chinese patients with type 2 diabetes (T2D). Methods In this retrospective analysis, 297 patients with T2D were divided into 3 groups according to the urine ACR. Patients' data were analyzed to identify associations of general conditions, blood glucose level, lipid levels, and uric acid level with BMD and bone metabolism indices. Results BMD at every location tested (femoral neck, trochanter, inside hip, Ward's triangle, total hip, and lumbar vertebrae) was negatively correlated with the urine ACR (all p<0.05). Osteocalcin, beta-C-terminal telopeptide (β-CTX), and procollagen type 1 N- peptide (P1NP) were positively correlated with urine ACR (all p<0.05). Finally, 25-hydroxyvitamin D [25(OH)D] was negatively correlated with urine ACR (p<0.05). Multiple regression analysis with adjustment for age, body mass index, disease duration, and other clinical measurements revealed no significant correlation between urine ACR and BMD measurements or β-CTX (p>0.05). However, significant correlations remained between urine ACR and osteocalcin, P1NP, and 25(OH)D (p<0.05). The same results were obtained for postmenopausal women specifically, with the exception of a significant correlation between the ACR and β-CTX (p<0.05). Conclusion In the early stage of diabetic nephropathy, BMD changes and bone transformation acceleration may occur, and the acceleration of bone transformation may occur before the change in BMD. Therefore, it is important to monitor bone metabolism indices in the early stage of diabetic nephropathy in T2D patients.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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



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American Thyroid Association: Dr. Elizabeth Pearce to Lead 2018-2019 Board of Directors

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October 17, 2018—The American Thyroid Association (ATA) announces with pleasure that Elizabeth Pearce, MD, MSc, began a one-year term as president of the Board of Directors at the close of the Annual Meeting, October 7 in Washington, DC. Dr. Pearce has served for the past year as President-Elect.

Newly elected board members are:

Martha Zeiger, MD, President-Elect
Jacqueline Jonklaas, MD, Secretary-Elect
Joshua Klopper, MD, Director
Angela Leung, MD, MSc, Director

Elizabeth Pearce, MD, MSc, Board President

Elizabeth Pearce, MD, MSc, Board PresidentDr. Pearce is professor of medicine in the Endocrinology, Diabetes, and Nutrition Section at Boston University School of Medicine. She received her undergraduate and medical degrees from Harvard and a masters' degree in epidemiology from the Boston University School of Public Health. She completed her residency in internal medicine at Beth Israel Deaconess Medical Center, and her fellowship in endocrinology at Boston University under the mentorship of Dr. Lewis Braverman. Her research interests include: the sufficiency of dietary iodine in the U.S. and globally; thyroid function in pregnancy; thyroidal effects of exposure to environmental endocrine disruptors; and the cardiovascular effects of subclinical thyroid dysfunction. She has been part of the leadership of the Iodine Global Network (IGN; formerly ICCIDD) since 2009. She is a member of the AACE Thyroid Disease State Network and serves as faculty for the Endocrine Society's annual board review course. She has served on multiple editorial boards, including those for Endocrine Practice, Journal of Clinical Endocrinology and Metabolism, Clinical Endocrinology, European Journal of Clinical Nutrition, and Lancet Diabetes & Endocrinology.

Dr. Pearce has been a member of the American Thyroid Association since 2000. She has chaired both the ATA's Publications and Public Health Committees. She cochaired the 2012 Annual Meeting Program Committee and the 2009 and 2016 Spring Symposia and was a member of the Program Committee for the 2015 International Thyroid Congress. Dr. Pearce has also served as a member of the ATA Finance Committee and the Guidelines Policy Task Force. She was one of the leaders in establishing the ATA's Braverman Lectureship and cochaired the task force for the 2017 Pregnancy Guidelines. She is associate editor for both Thyroid and Clinical Thyroidology journals. She served as a member of the Board of Directors from 2009­ to 2013 and again as president-elect for the past year. Dr. Pearce was the 2011 recipient of the Van Meter Award for outstanding contributions to research on the thyroid gland.

Martha Zeiger, MD, President-Elect

Martha Zeiger, MD, President-ElectDr. Martha Zeiger is the S. Hurt Watts professor and chair of surgery at the University of Virginia School of Medicine. Regarded as a world leader in endocrine surgery, she is also an expert in the molecular aspects of thyroid cancer and an experienced academic leader. Her surgical training includes a surgical oncology fellowship, focused on endocrine surgery, at the National Cancer Institute, NIH, prior to joining the faculty at Johns Hopkins University School of Medicine in 1993. There, she built her endocrine surgery practice, established an endocrine surgery fellowship program, and directed an NIH-funded molecular biology laboratory for over 20 years. Today, her research team continues at Johns Hopkins, focusing on the molecular aspects of thyroid cancer.

While at John Hopkins, Dr. Zeiger took the lead as: associate dean for postdoctoral affairs; professor of surgery, oncology, cellular and molecular medicine; associate vice chair of surgery faculty development; and medical director of business development, strategic alliance, and venture technology. While associate dean for postdoctoral affairs, she oversaw 1,200 research fellows in the School of Medicine. She also established a formal program for international postdoctoral fellows.

Dr. Zeiger has held numerous leadership positions in national medical societies: the American Association of Endocrine Surgeons, the American Association of Clinical Endocrinologists, and the ATA. Through AAES, she founded Endocrine Surgery University, an annual course for all endocrine surgery fellows in North America.

She has served on the ATA Board of Directors and many ATA committees, including publications, membership, conflict of interest task force.  She co-chaired the annual meeting program committee in 2011.

Jacqueline Jonklaas, MD, Secretary-Elect

Jacqueline Jonklaas, MD, Secretary-ElectDr. Jonklaas is currently a professor in the endocrinology division at Georgetown University in Washington, DC, where she completed her medical degree, residency, and fellowship training. As a clinical researcher in the thyroid field, her time is divided between research, clinical activities, and teaching. Dr. Jonklaas's research has focused on the management of hypothyroidism and thyroid cancer. Current research involves examining patient-reported outcomes after radioiodine therapy. Her recent publications address topics such as how to optimize the treatment of hypothyroidism and the outcomes of thyroid cancer patients based on their treatment, age, and gender.

She is the program director of the Georgetown University Clinical Research Unit. She is involved in translational research and the activities of the Georgetown University's Clinical and Translational Science Award. She recently directed the endocrinology courses for Georgetown University Medical School's first- and second-year medical students. She currently teaches in these courses.

She serves on the editorial board of the Journal of Clinical Endocrinology and Metabolism. She is involved in teaching at the national level as a member of the Endocrine Society Self-Assessment Committee.

Dr. Jonklaas has been a member of the ATA since 1999. She has served on several past ATA committees, including the Patient Education and Advocacy Committee, the Surgical Task Force Committee, and the Awards Committee. She was cochair of the ATA Task Force on Thyroid Hormone Replacement, whose guidelines were published in 2014. She previously served on the Board of Directors from 2013–2017, and recently completed a term as the cochair of the Guidelines and Statement Committee. Currently she serves on the Program Committee. She also serves on the editorial board of the ATA journal Thyroid.

Joshua Klopper, MD, Director (Endocrinologist in Community Practice)

DJoshua Klopper, MD, Directorr. Klopper joined the Colorado Permanente Medical Group (CPMG) of Kaiser Permanente in July 2015 and was appointed chief of the department in April 2016. He was appointed associate clinical professor of medicine in the Division of Endocrinology, Metabolism, and Diabetes at the University of Colorado School of Medicine in October 2015.

He earned a B.S. in psychology in 1995 from Indiana University in Bloomington, Indiana. In 1999 he received his medical degree from the Emory University School of Medicine in Atlanta, Georgia. He completed his internship and residency in internal medicine at the University of Colorado Health Sciences Center in 2002. Dr. Klopper then completed a postdoctoral research fellowship in the Endocrinology Division, prior to starting his endocrinology fellowship at the University of Colorado at Denver Health Sciences Center, completed in 2006.

Dr. Klopper was a full-time faculty member in the Division of Endocrinology at the University of Colorado School of Medicine from 2006–2015, where he specialized in the evaluation and management of thyroid nodules and thyroid cancer, including advanced thyroid cancer. During his academic career, he received grant funding at the local, state, and national level including from the American Cancer Society. He has published original research on the evaluation and management of thyroid nodules and advanced thyroid cancer and has written several book chapters and reviews. Additionally, he participated as an original member of the Thyroid Cancer Care Collaborative development committee. He has served on the Clinical Affairs and Development committees of the ATA as well as on the Endocrine Society Annual Meeting Steering committee. Currently, Dr. Klopper is on the Medical Specialty Peer Review Committee for CPMG and has been codirector of the Endocrine Society's Introductory Hands-On Thyroid Ultrasound Workshop since 2014.

Angela Leung, MD, MSc, Director (Endocrinologist in Academic Practice)

Angela Leung, MD, MSc, DirectorAngela M. Leung, MD, MSc, is an assistant professor of medicine in the Division of Endocrinology, Diabetes, and Metabolism at the UCLA David Geffen School of Medicine and in the VA Greater Los Angeles Healthcare System, and an associate program director of the UCLA/VA endocrinology fellowship program.

She received her undergraduate degree at Occidental College in Los Angeles, her medical degree from the Boston University School of Medicine, and a masters' degree in epidemiology from the Boston University School of Public Health. She completed her internal medicine residency and a clinical and research endocrine fellowship at Boston University Medical Center. Her research areas of interest include iodine deficiency and excess, thyroid toxicant exposures, and maternal-child thyroid health. She is a member of the AACE Thyroid Disease State Network and the editorial board of Endocrine Practice, has participated in the AACE Endocrine Training Support Committee, and was a recipient of the Endocrine Society Early Investigator Award. She has reviewed for several NIH standing and early-career award endocrine study sections; for the U.S. EPA's Biologically-Based Dose Response model to guide perchlorate regulation in U.S. drinking water; and for the EPA's draft toxicity assessments of the thyroid disruptors GenX and perfluorobutane sulfonate. Through the Endocrine Society, she participates in reviewing the effects of thyroid toxicants for the Organization for Economic Cooperation and Development, a global initiative focused on the regulatory policies of endocrine disruptors.

Dr. Leung has been involved in multiple ATA programs and initiatives. She serves on the editorial boards of three ATA journals: Thyroid, Clinical Thyroidology, and Clinical Thyroidology for the Public. She is past Chair of the ATA Public Health Committee (2012–16), during which she led the publication of the ATA's statements on iodine excess and the use of potassium iodide in nuclear accidents; was a member of the Program Committee for the 2016 ATA Annual Meeting; and served as clinical cochair for the 2017 ATA Annual Meeting in Victoria, British Columbia.

The ATA thanks this year's Nominating Committee, chaired by David Steward, and the Secretary-Elect Selection Task Force, chaired by John Morris. We are extremely grateful to all who serve on the Board of Directors. Special thanks go to those who will retire from the Board this year: Regina Castro, MD, Christine Spitzweg, MD, and outgoing Past-President John C. Morris, MD.

###

The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international membership medical society with over 1,700 members from 43 countries around the world. Celebrating its 95th anniversary, the ATA continues to deliver its mission of being devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health.  These efforts are carried out via several key endeavors:

  • The publication of the highly regarded professional journals Thyroid, Clinical Thyroidology, and VideoEndocrinology
  • Annual scientific meetings
  • Biennial clinical and research symposia
  • Research grant programs for young investigators
  • Support of online professional, public, and patient educational programs
  • Development of guidelines for clinical management of thyroid disease and thyroid cancer

 The ATA promotes thyroid awareness and information online through Clinical Thyroidology for the Public and extensive, authoritative explanations of thyroid disease and thyroid cancer in both English and Spanish. The ATA website serves as the clinical resource for patients and the public who look for reliable information on the Internet. Every fifth year, the American Thyroid Association joins with the Latin American Thyroid Society, the European Thyroid Association, and the Asia and Oceania Thyroid Association to cosponsor the International Thyroid Congress (ITC).

The post American Thyroid Association: Dr. Elizabeth Pearce to Lead 2018-2019 Board of Directors appeared first on American Thyroid Association.



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Radiofrequency Ablation vs. Cryoablation for Localized Hepatocellular Carcinoma: A Propensity-matched Population Study

Background/Aim: To compare overall survival (OS) and liver cancer-specific survival (LCSS) of Surveillance, Epidemiology and End Results (SEER) hepatocellular carcinoma (HCC) database patients treated with cryoablation (cryo) or radiofrequency ablation (RFA). Materials and Methods: This was a retrospective review of Stage I or II HCC patients from the SEER database treated with cryo and RFA from 2004-2013. Kaplan–Meier and Cox regressions were performed on pooled and propensity-matched cohort. Results: Out of 3,239 patients, RFA showed a significant survival advantage over cryo in liver cancer specific survival (LCSS) (HR=1.634 p=0.0004). A total of 91 propensity-matched pairs had similar OS (HR=1.006 p=0.9768), but no difference in LCSS was observed between the groups [HR=1.412 (95%CI=0.933-2.137) p=0.1023]. Survival Cox models did not reveal treatment type as an independent prognostic factor. Conclusion: Propensity-matched cohort showed no significant difference in terms of OS and LCSS was found for patients treated with either cryo or RFA for localized HCC.



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Cancer Patients in the Emergency Department: A "Nightmare" that Might Become a Virtuous Clinical Pathway

Background/Aim: Emergency departments (EDs) often face overcrowding issues while simultaneously confronting with the increasing clinical needs of patients, such as cancer patients, with both acute and chronic illnesses. In order to guarantee a prompt and specialized treatment of ED-attending cancer patients and reduce inappropriate inpatient admissions, a dedicated ED cancer pathway (EDCP) consisting of ED-bound Medical Oncology (MO) resident doctor and direct admission for candidate patients exclusively to the MO division was established at the Tor Vergata University Hospital in April 2015. Patients and Methods: Consecutive cancer patients attending the ED in two reference three-month periods were enrolled: pre-EDCP period, from 1st October 2014 to 31st December 2014, and post-EDCP period, from 1st October 2014 to 31st December 2015. Inpatient admission rate, mortality rate and both ED and inpatient length of stay were compared between the two analyzed periods, pre- and post-EDCP. Results: In the pre- and post-EDCP periods 127 and 123 cancer patients, respectively, were included. Most of the analyzed indicators were improved by EDCP implementation: Inpatient admission rate from 70% to 41% (p<0.0001), ED mortality rate from 10-4% (p=0.04), mean ED length of stay, from 58 to 42 h (p=0.03), mean inpatient length of stay, from 15.5 to 6.5 days (p<0.0001), in the pre- and post-EDCp period, respectively. Conclusion: EDCP implementation led to a significant improvement of health care delivery to cancer patients attending the Emergency Department.



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Behavioral Neurobiology of PTSD



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The Gut Microbiome in Health and Disease



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Statistical Methods in Medical Research



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Prebiotic Chemistry and Chemical Evolution of Nucleic Acids



https://ift.tt/2FetA2S

Nuclear-Cytoplasmic Transport



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Cell Biology and Translational Medicine, Volume 1. Stem Cells in Regenerative Medicine: Advances and Challenges



https://ift.tt/2F6krsY

Molecular Applications in Cytology



https://ift.tt/2ANmkq6

Gene Therapy in Reconstructive and Regenerative Surgery



https://ift.tt/2Fi7xID

The Heterogeneity of Cancer Metabolism



https://ift.tt/2APCU91

Genetic Epidemiology. Methods and Protocols



https://ift.tt/2F4FuvZ

Programmed Necrosis. Methods and Protocols



https://ift.tt/2AOuL4F

Stromal Immunology



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Single Cell Biomedicine



https://ift.tt/2APCQWP

Small Molecules in Oncology



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The Human Virome. Methods and Protocols



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Book Reviews



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Patterns of Recurrence After Salvage Radiotherapy Encompassing Pelvic Lymphatics in Men with High-risk Prostate Cancer

Background/Aim: The efficacy of adjuvant or salvage radiation to the regional lymph node area has not been fully investigated in high-risk prostate cancer patients; instead, radiotherapy is limited to the prostate fossa. The present study aimed to assess patterns of recurrence in prostate cancer patients with biochemical failure (BCF) who were treated with whole-pelvic salvage radiotherapy (SRT) following radical prostatectomy. Patients and Methods: The clinical data from 196 high-risk prostate cancer patients who received SRT for BCF after radical prostatectomy were reviewed. BCF after SRT was detected in 80 patients, and 59 patients underwent imaging studies. Results: Twenty four recurrences in 16 patients were identified, including 13 bone metastases, 6 vesicourethral anastomosis site recurrences, and 5 lymph node recurrences (one simultaneous with vesicourethral anastomosis). Regarding the treatment field, no in-field nodal recurrence was observed, whereas 4 out-of-field and 1 edge-of-field recurrences were detected. Conclusion: Locoregional recurrence was most common at the anastomosis site. Most nodal recurrences were located outside the pelvis, suggesting that elective pelvic nodal irradiation should be recommended in a selected patient population.



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The Adenosine Receptors



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Environmental risk assessment of psychoactive drugs in the aquatic environment

Abstract

The consumption of psychoactive pharmaceuticals has increased worldwide, and wastewater treatment plants are not able to eliminate them from the effluent. An extensive review was carried out to assess the environmental risk (ERA model) based on secondary data about potential impacts on non-target organisms of seven psychoactive drugs consumed worldwide (alprazolam, bromazepam, citalopram, clonazepam, diazepam, lorazepam, and oxazepam). Risk quotients (RQs) were calculated according to the European Medicines Agency (EMA) on ERA of Medicinal Products For Human Use based on (i) the predicted and measured environmental concentrations (PEC and MEC, respectively) of the psychoactive drug in surface water, groundwater, and wastewater effluent and (ii) the predicted no-effect concentration (PNEC) derived from ecotoxicological assays or ECOSAR software. Furthermore, this study reviews and discusses non-standardized ecotoxicity assays, such as sublethal and behavioral effects on different organisms. In total, 903 MEC entries of psychoactive drugs and 162 data on ecotoxicological assays were gathered from the literature survey addressing behavioral effects (115), acute/chronic effects (35), and sublethal effects (12). Citalopram and diazepam were the only substances that are likely to pose an environmental risk (RQ > 1) to surface waters. Even though there is considerable amount of data on behavioral effects of psychoactive drugs to aquatic species, results are currently not integrated into the EMA risk assessment framework. The large amount of data on psychoactive drug concentrations and effects on non-target organisms collected, interpreted, and discussed in the present study should be used as a baseline for future improvement of ERA strategies.



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A multivariate analysis of physiological and antioxidant responses and health hazards of wheat under cadmium and lead stress

Abstract

Soil contamination with heavy metals is a global issue confronting the environmental pollution and human/animal health. Much work has been done on physiological and antioxidant responses of wheat in hydroponic experiments and health risks from individual heavy metal contamination to human, but limited information is available on their combined application in soil. Therefore, this pot study delineates the uptake of lead and cadmium, as well as physiological responses of wheat and associated health risks under different levels of alone and combined Cd and Pb treatments. Metal uptake increased with their increasing applied levels. The highest Cd (4.24, 1.38, and 0.92 mg kg−1) and Pb (763.33, 39.63, and 16.35 mg kg−1) concentrations in root, shoot, and grain, respectively, were observed at highest applied levels (0.4 mM Cd and 10 mM Pb). Furthermore, all the treatments increased lipid peroxidation and activities of superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase, while decreased total chlorophyll contents and membrane stability index. Under combined application of Cd and Pb, the toxicity and detoxification responses of wheat increased compared to alone treatments. Multivariate analysis further confirmed the toxicity and accumulation pattern of metals under alone and combined treatments. Target hazard quotient values of Cd and Pb were < 1 under alone and combined treatments. The health hazard index values of Pb (97.07 and 87.89%) were higher than those of Cd (2.93 and 12.10%) in combined application for human and buffalo, respectively. This study highlights that the multi-metal contamination (Cd and Pb) is detrimental for wheat growth and human/animal health.



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American Thyroid Association: Dr. Elizabeth Pearce to Lead 2018-2019 Board of Directors

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October 17, 2018—The American Thyroid Association (ATA) announces with pleasure that Elizabeth Pearce, MD, MSc, began a one-year term as president of the Board of Directors at the close of the Annual Meeting, October 7 in Washington, DC. Dr. Pearce has served for the past year as President-Elect.

Newly elected board members are:

Martha Zeiger, MD, President-Elect
Jacqueline Jonklaas, MD, Secretary-Elect
Joshua Klopper, MD, Director
Angela Leung, MD, MSc, Director

Elizabeth Pearce, MD, MSc, Board President

Elizabeth Pearce, MD, MSc, Board PresidentDr. Pearce is professor of medicine in the Endocrinology, Diabetes, and Nutrition Section at Boston University School of Medicine. She received her undergraduate and medical degrees from Harvard and a masters' degree in epidemiology from the Boston University School of Public Health. She completed her residency in internal medicine at Beth Israel Deaconess Medical Center, and her fellowship in endocrinology at Boston University under the mentorship of Dr. Lewis Braverman. Her research interests include: the sufficiency of dietary iodine in the U.S. and globally; thyroid function in pregnancy; thyroidal effects of exposure to environmental endocrine disruptors; and the cardiovascular effects of subclinical thyroid dysfunction. She has been part of the leadership of the Iodine Global Network (IGN; formerly ICCIDD) since 2009. She is a member of the AACE Thyroid Disease State Network and serves as faculty for the Endocrine Society's annual board review course. She has served on multiple editorial boards, including those for Endocrine Practice, Journal of Clinical Endocrinology and Metabolism, Clinical Endocrinology, European Journal of Clinical Nutrition, and Lancet Diabetes & Endocrinology.

Dr. Pearce has been a member of the American Thyroid Association since 2000. She has chaired both the ATA's Publications and Public Health Committees. She cochaired the 2012 Annual Meeting Program Committee and the 2009 and 2016 Spring Symposia and was a member of the Program Committee for the 2015 International Thyroid Congress. Dr. Pearce has also served as a member of the ATA Finance Committee and the Guidelines Policy Task Force. She was one of the leaders in establishing the ATA's Braverman Lectureship and cochaired the task force for the 2017 Pregnancy Guidelines. She is associate editor for both Thyroid and Clinical Thyroidology journals. She served as a member of the Board of Directors from 2009­ to 2013 and again as president-elect for the past year. Dr. Pearce was the 2011 recipient of the Van Meter Award for outstanding contributions to research on the thyroid gland.

Martha Zeiger, MD, President-Elect

Martha Zeiger, MD, President-ElectDr. Martha Zeiger is the S. Hurt Watts professor and chair of surgery at the University of Virginia School of Medicine. Regarded as a world leader in endocrine surgery, she is also an expert in the molecular aspects of thyroid cancer and an experienced academic leader. Her surgical training includes a surgical oncology fellowship, focused on endocrine surgery, at the National Cancer Institute, NIH, prior to joining the faculty at Johns Hopkins University School of Medicine in 1993. There, she built her endocrine surgery practice, established an endocrine surgery fellowship program, and directed an NIH-funded molecular biology laboratory for over 20 years. Today, her research team continues at Johns Hopkins, focusing on the molecular aspects of thyroid cancer.

While at John Hopkins, Dr. Zeiger took the lead as: associate dean for postdoctoral affairs; professor of surgery, oncology, cellular and molecular medicine; associate vice chair of surgery faculty development; and medical director of business development, strategic alliance, and venture technology. While associate dean for postdoctoral affairs, she oversaw 1,200 research fellows in the School of Medicine. She also established a formal program for international postdoctoral fellows.

Dr. Zeiger has held numerous leadership positions in national medical societies: the American Association of Endocrine Surgeons, the American Association of Clinical Endocrinologists, and the ATA. Through AAES, she founded Endocrine Surgery University, an annual course for all endocrine surgery fellows in North America.

She has served on the ATA Board of Directors and many ATA committees, including publications, membership, conflict of interest task force.  She co-chaired the annual meeting program committee in 2011.

Jacqueline Jonklaas, MD, Secretary-Elect

Jacqueline Jonklaas, MD, Secretary-ElectDr. Jonklaas is currently a professor in the endocrinology division at Georgetown University in Washington, DC, where she completed her medical degree, residency, and fellowship training. As a clinical researcher in the thyroid field, her time is divided between research, clinical activities, and teaching. Dr. Jonklaas's research has focused on the management of hypothyroidism and thyroid cancer. Current research involves examining patient-reported outcomes after radioiodine therapy. Her recent publications address topics such as how to optimize the treatment of hypothyroidism and the outcomes of thyroid cancer patients based on their treatment, age, and gender.

She is the program director of the Georgetown University Clinical Research Unit. She is involved in translational research and the activities of the Georgetown University's Clinical and Translational Science Award. She recently directed the endocrinology courses for Georgetown University Medical School's first- and second-year medical students. She currently teaches in these courses.

She serves on the editorial board of the Journal of Clinical Endocrinology and Metabolism. She is involved in teaching at the national level as a member of the Endocrine Society Self-Assessment Committee.

Dr. Jonklaas has been a member of the ATA since 1999. She has served on several past ATA committees, including the Patient Education and Advocacy Committee, the Surgical Task Force Committee, and the Awards Committee. She was cochair of the ATA Task Force on Thyroid Hormone Replacement, whose guidelines were published in 2014. She previously served on the Board of Directors from 2013–2017, and recently completed a term as the cochair of the Guidelines and Statement Committee. Currently she serves on the Program Committee. She also serves on the editorial board of the ATA journal Thyroid.

Joshua Klopper, MD, Director (Endocrinologist in Community Practice)

DJoshua Klopper, MD, Directorr. Klopper joined the Colorado Permanente Medical Group (CPMG) of Kaiser Permanente in July 2015 and was appointed chief of the department in April 2016. He was appointed associate clinical professor of medicine in the Division of Endocrinology, Metabolism, and Diabetes at the University of Colorado School of Medicine in October 2015.

He earned a B.S. in psychology in 1995 from Indiana University in Bloomington, Indiana. In 1999 he received his medical degree from the Emory University School of Medicine in Atlanta, Georgia. He completed his internship and residency in internal medicine at the University of Colorado Health Sciences Center in 2002. Dr. Klopper then completed a postdoctoral research fellowship in the Endocrinology Division, prior to starting his endocrinology fellowship at the University of Colorado at Denver Health Sciences Center, completed in 2006.

Dr. Klopper was a full-time faculty member in the Division of Endocrinology at the University of Colorado School of Medicine from 2006–2015, where he specialized in the evaluation and management of thyroid nodules and thyroid cancer, including advanced thyroid cancer. During his academic career, he received grant funding at the local, state, and national level including from the American Cancer Society. He has published original research on the evaluation and management of thyroid nodules and advanced thyroid cancer and has written several book chapters and reviews. Additionally, he participated as an original member of the Thyroid Cancer Care Collaborative development committee. He has served on the Clinical Affairs and Development committees of the ATA as well as on the Endocrine Society Annual Meeting Steering committee. Currently, Dr. Klopper is on the Medical Specialty Peer Review Committee for CPMG and has been codirector of the Endocrine Society's Introductory Hands-On Thyroid Ultrasound Workshop since 2014.

Angela Leung, MD, MSc, Director (Endocrinologist in Academic Practice)

Angela Leung, MD, MSc, DirectorAngela M. Leung, MD, MSc, is an assistant professor of medicine in the Division of Endocrinology, Diabetes, and Metabolism at the UCLA David Geffen School of Medicine and in the VA Greater Los Angeles Healthcare System, and an associate program director of the UCLA/VA endocrinology fellowship program.

She received her undergraduate degree at Occidental College in Los Angeles, her medical degree from the Boston University School of Medicine, and a masters' degree in epidemiology from the Boston University School of Public Health. She completed her internal medicine residency and a clinical and research endocrine fellowship at Boston University Medical Center. Her research areas of interest include iodine deficiency and excess, thyroid toxicant exposures, and maternal-child thyroid health. She is a member of the AACE Thyroid Disease State Network and the editorial board of Endocrine Practice, has participated in the AACE Endocrine Training Support Committee, and was a recipient of the Endocrine Society Early Investigator Award. She has reviewed for several NIH standing and early-career award endocrine study sections; for the U.S. EPA's Biologically-Based Dose Response model to guide perchlorate regulation in U.S. drinking water; and for the EPA's draft toxicity assessments of the thyroid disruptors GenX and perfluorobutane sulfonate. Through the Endocrine Society, she participates in reviewing the effects of thyroid toxicants for the Organization for Economic Cooperation and Development, a global initiative focused on the regulatory policies of endocrine disruptors.

Dr. Leung has been involved in multiple ATA programs and initiatives. She serves on the editorial boards of three ATA journals: Thyroid, Clinical Thyroidology, and Clinical Thyroidology for the Public. She is past Chair of the ATA Public Health Committee (2012–16), during which she led the publication of the ATA's statements on iodine excess and the use of potassium iodide in nuclear accidents; was a member of the Program Committee for the 2016 ATA Annual Meeting; and served as clinical cochair for the 2017 ATA Annual Meeting in Victoria, British Columbia.

The ATA thanks this year's Nominating Committee, chaired by David Steward, and the Secretary-Elect Selection Task Force, chaired by John Morris. We are extremely grateful to all who serve on the Board of Directors. Special thanks go to those who will retire from the Board this year: Regina Castro, MD, Christine Spitzweg, MD, and outgoing Past-President John C. Morris, MD.

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The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international membership medical society with over 1,700 members from 43 countries around the world. Celebrating its 95th anniversary, the ATA continues to deliver its mission of being devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health.  These efforts are carried out via several key endeavors:

  • The publication of the highly regarded professional journals Thyroid, Clinical Thyroidology, and VideoEndocrinology
  • Annual scientific meetings
  • Biennial clinical and research symposia
  • Research grant programs for young investigators
  • Support of online professional, public, and patient educational programs
  • Development of guidelines for clinical management of thyroid disease and thyroid cancer

 The ATA promotes thyroid awareness and information online through Clinical Thyroidology for the Public and extensive, authoritative explanations of thyroid disease and thyroid cancer in both English and Spanish. The ATA website serves as the clinical resource for patients and the public who look for reliable information on the Internet. Every fifth year, the American Thyroid Association joins with the Latin American Thyroid Society, the European Thyroid Association, and the Asia and Oceania Thyroid Association to cosponsor the International Thyroid Congress (ITC).

The post American Thyroid Association: Dr. Elizabeth Pearce to Lead 2018-2019 Board of Directors appeared first on American Thyroid Association.



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Comments on: "Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis”

We read an article written by Shi et al. (1) with interest. The authors performed a systematic review and meta-analysis of 18 longitudinal studies to determine whether sleep disturbances (including insomnia, sleep disordered breathing, and other sleep problems) increase the risk of dementia. The meta-analysis was done by computing overall relative risk (RR) of incident dementia. The main findings from this study showed that sleep disturbances might increase risk of all-cause dementia, Alzheimer's disease, and vascular dementia.

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The Effect of Non-Pharmacological Sleep Interventions on Depression Symptoms: A Meta-Analysis of Randomised Controlled Trials

Poor sleep is a significant risk factor for depression across the lifespan and sleep problems have been hypothesised to contribute to the onset and maintenance of depression symptoms. However, sleep problems are usually not a direct target of interventions for depression. A range of non-pharmacological treatments can reduce sleep problems but it is unclear whether these interventions also reduce other depression symptoms. The aim of this review was to examine whether non-pharmacological interventions for sleep problems are effective in reducing symptoms of depression.

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The Mitochondrial Isoform of FASTK Modulates Nonopsonic Phagocytosis of Bacteria by Macrophages via Regulation of Respiratory Complex I [INFECTIOUS DISEASE AND HOST RESPONSE]

Phagocytosis is a pivotal process by which innate immune cells eliminate bacteria. In this study, we explore novel regulatory mechanisms of phagocytosis driven by the mitochondria. Fas-activated serine/threonine kinase (FASTK) is an RNA-binding protein with two isoforms, one localized to the mitochondria (mitoFASTK) and the other isoform to cytosol and nucleus. The mitoFASTK isoform has been reported to be necessary for the biogenesis of the mitochondrial ND6 mRNA, which encodes an essential subunit of mitochondrial respiratory complex I (CI, NADH:ubiquinone oxidoreductase). This study investigates the role and the mechanisms of action of FASTK in phagocytosis. Macrophages from FASTK/ mice exhibited a marked increase in nonopsonic phagocytosis of bacteria. As expected, CI activity was specifically reduced by almost 50% in those cells. To explore if decreased CI activity could underlie the phagocytic phenotype, we tested the effect of CI inhibition on phagocytosis. Indeed, treatment with CI inhibitor rotenone or short hairpin RNAs against two CI subunits (NDUFS3 and NDUFS4) resulted in a marked increase in nonopsonic phagocytosis of bacteria. Importantly, re-expression of mitoFASTK in FASTK-depleted macrophages was sufficient to rescue the phagocytic phenotype. In addition, we also report that the decrease in CI activity in FASTK/ macrophages is associated with an increase in phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) and that its inhibition using Compound C reverted the phagocytosis phenotype. Taken together, our results clearly demonstrate for the first time, to our knowledge, that mitoFASTK plays a negative regulatory role on nonopsonic phagocytosis of bacteria in macrophages through its action on CI activity.



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Leukocyte CD300a Contributes to the Resolution of Murine Allergic Inflammation [INNATE IMMUNITY AND INFLAMMATION]

CD300a is an inhibitory receptor for mast cells and eosinophils in allergic inflammation (AI); however, the spatiotemporal expression of CD300a and its potential roles in the resolution of AI are still to be determined. In this study, employing a mouse model of allergic peritonitis, we demonstrate that CD300a expression on peritoneal cells is regulated from inflammation to resolution. Allergic peritonitis–induced CD300a–/– mice had a rapid increase in their inflammatory cell infiltrates and tryptase content in the peritoneal cavity compared with wild type, and their resolution process was significantly delayed. CD300a–/– mice expressed lower levels of ALX/FPR2 receptor on peritoneal cells and had higher levels of LXA4 in the peritoneal lavage. CD300a activation on mouse bone marrow–derived mast cells regulated ALX/FPR2 expression levels following IgE-mediated activation. Together, these findings indicate a role for CD300a in AI and its resolution, in part via the specialized proresolving mediator LXA4 and ALX/FPR2 receptor pathway activation.



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Does T Cell Activation Require a Quorum of Lymphocytes? [BRIEF REVIEWS]

Recent reports suggest a quorum of T cells is required to activate T lymphocytes and that this requirement may help explain why scarce lymphocytes, specific for peripheral self-antigen, are rarely activated by Ag. This proposal runs counter to the commonly held framework that the Ag-dependent, but CD4 T lymphocyte–independent, activation of CD8 T lymphocytes, and the activation of CD4 T lymphocytes themselves, can occur when a single CD8 or CD4 T lymphocyte encounters Ag under appropriately dangerous circumstances. We argue that a review of older literature often ignored, as well as of contemporary studies, supports the quorum concept and is difficult to reconcile with the Danger Model.



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MAbTope: A Method for Improved Epitope Mapping [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Abs are very efficient drugs, ~70 of them are already approved for medical use, over 500 are in clinical development, and many more are in preclinical development. One important step in the characterization and protection of a therapeutic Ab is the determination of its cognate epitope. The gold standard is the three-dimensional structure of the Ab/Ag complex by crystallography or nuclear magnetic resonance spectroscopy. However, it remains a tedious task, and its outcome is uncertain. We have developed MAbTope, a docking-based prediction method of the epitope associated with straightforward experimental validation procedures. We show that MAbTope predicts the correct epitope for each of 129 tested examples of Ab/Ag complexes of known structure. We further validated this method through the successful determination, and experimental validation (using human embryonic kidney cells 293), of the epitopes recognized by two therapeutic Abs targeting TNF-α: certolizumab and golimumab.



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The Diverse Family of MR1-Restricted T Cells [BRIEF REVIEWS]

Mucosal-associated invariant T (MAIT) cells are characterized by a semi-invariant TCR that recognizes vitamin B metabolite Ags presented by the MHC-related molecule MR1. Their Ag restriction determines a unique developmental lineage, imbuing a tissue-homing, preprimed phenotype with antimicrobial function. A growing body of literature indicates that MR1-restricted T cells are more diverse than the MAIT term implies. Namely, it is increasingly clear that TCR α- and TCR β-chain diversity within the MR1-restricted repertoire provides a potential mechanism of Ag discrimination, and context-dependent functional variation suggests a role for MR1-restricted T cells in diverse physiological settings. In this paper, we summarize MR1-restricted T cell biology, with an emphasis on TCR diversity, Ag discrimination, and functional heterogeneity.



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Myoferlin-Mediated Lysosomal Exocytosis Regulates Cytotoxicity by Phagocytes [INNATE IMMUNITY AND INFLAMMATION]

During inflammation, phagocytes release digestive enzymes from lysosomes to degrade harmful cells such as pathogens and tumor cells. However, the molecular mechanisms regulating this process are poorly understood. In this study, we identified myoferlin as a critical regulator of lysosomal exocytosis by mouse phagocytes. Myoferlin is a type II transmembrane protein with seven C2 domains in the cytoplasmic region. It localizes to lysosomes and mediates their fusion with the plasma membrane upon calcium stimulation. Myoferlin promotes the release of lysosomal contents, including hydrolytic enzymes, which increase cytotoxicity. These data demonstrate myoferlin's critical role in lysosomal exocytosis by phagocytes, providing novel insights into the mechanisms of inflammation-related cellular injuries.



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Cutting Edge: IL-1{alpha} and Not IL-1{beta} Drives IL-1R1-Dependent Neonatal Murine Sepsis Lethality [CUTTING EDGE]

Sepsis disproportionately affects the very old and the very young. IL-1 signaling is important in innate host defense but may also play a deleterious role in acute inflammatory conditions (including sepsis) by promulgating life-threatening inflammation. IL-1 signaling is mediated by two distinct ligands: IL-1α and IL-1β, both acting on a common receptor (IL-1R1). IL-1R1 targeting has not reduced adult human sepsis mortality despite biologic plausibility. Because the specific role of IL-1α or IL-1β in sepsis survival is unknown in any age group and the role of IL-1 signaling remains unknown in neonates, we studied the role of IL-1 signaling, including the impact of IL-1α and IL-1β, on neonatal murine sepsis survival. IL-1 signaling augments the late plasma inflammatory response to sepsis. IL-1α and not IL-1β is the critical mediator of sepsis mortality, likely because of paracrine actions within the tissue. These data do not support targeting IL-1 signaling in neonates.



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In This Issue [IN THIS ISSUE]



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Cutting Edge: Quantitative Determination of CD40L Threshold for IL-12 and IL-23 Production from Dendritic Cells [CUTTING EDGE]

Early secretion of IL-12 by mouse dendritic cells (DCs) instructs T cells to make IFN-. However, only activated, but not naive T cells are able to license DCs for IL-12 production. We hypothesized that it might be due to different levels of CD40L expression on the surface of these cells, as CD40 signals are required for IL-12 production. Using quantitative cell-free systems incorporating CD40L in lipid bilayers combined with total internal reflection fluorescence microscopy and flow cytometry, we show that as low as ~200 CD40L molecules/μm2 in combination with IL-4 is sufficient to induce IL-12 production by DCs. Remarkably, CD40L alone is adequate to induce IL-23 secretion by DCs. Thus, although activated T cells have somewhat higher levels of CD40L, it is the combination of CD40L and the cytokines they secrete that licenses DCs and influences the effector class of the immune response.



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Differential Activation of Hepatic Invariant NKT Cell Subsets Plays a Key Role in Progression of Nonalcoholic Steatohepatitis [INNATE IMMUNITY AND INFLAMMATION]

Innate immune mechanisms play an important role in inflammatory chronic liver diseases. In this study, we investigated the role of type I or invariant NKT (iNKT) cell subsets in the progression of nonalcoholic steatohepatitis (NASH). We used α-galactosylceramide/CD1d tetramers and clonotypic mAb together with intracytoplasmic cytokine staining to analyze iNKT cells in choline-deficient l-amino acid–defined (CDAA)-induced murine NASH model and in human PBMCs, respectively. Cytokine secretion of hepatic iNKT cells in CDAA-fed C57BL/6 mice altered from predominantly IL-17+ to IFN-+ and IL-4+ during NASH progression along with the downmodulation of TCR and NK1.1 expression. Importantly, steatosis, steatohepatitis, and fibrosis were dependent upon the presence of iNKT cells. Hepatic stellate cell activation and infiltration of neutrophils, Kupffer cells, and CD8+ T cells as well as expression of key proinflammatory and fibrogenic genes were significantly blunted in Jα18–/– mice and in C57BL/6 mice treated with an iNKT-inhibitory RAR- agonist. Gut microbial diversity was significantly impacted in Jα18–/– and in CDAA diet–fed mice. An increased frequency of CXCR3+IFN-+T-bet+ and IL-17A+ iNKT cells was found in PBMC from NASH patients in comparison with nonalcoholic fatty liver patients or healthy controls. Consistent with their in vivo activation, iNKT cells from NASH patients remained hyporesponsive to ex-vivo stimulation with α-galactosylceramide. Accumulation of plasmacytoid dendritic cells in both mice and NASH patients suggest their role in activation of iNKT cells. In summary, our findings indicate that the differential activation of iNKT cells play a key role in mediating diet-induced hepatic steatosis and fibrosis in mice and its potential involvement in NASH progression in humans.



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B Cell Development sans B Cell Receptor Responsiveness Due to Unfolded Protein Response-Triggered Mef2c Protein Degradation [IMMUNE REGULATION]

BCR engagement leads to activation and clonal expansion of B cells. The I-A12% mutant mouse possesses a branch site point mutation in the H2-Aa gene that causes highly reduced I-Aa protein expression. As I-A is a heterodimer made up of I-Aa and I-Ab, reduced I-Aa results not only in reduced surface I-A expression but also in an excess of unpaired I-Ab. B cells that develop in I-A12% mice proliferated in response to LPS stimulation but failed to do so upon BCR stimulation. Developing I-A12% B cells were engaged in unfolded protein response due to an excess of unpaired I-Ab. BCR responsiveness was restored by transduced I-Aa expression and by BiP, the unfolded protein response sensor. Reducing the load of unpaired I-Ab also restored BCR responsiveness of I-A12% B cells. Mef2c protein, a transcription factor required for BCR-stimulated proliferation, was missing in I-A12% B cells, and that transduced Mef2c expression restored BCR responsiveness. Mef2c protein appeared in I-A12% B cells after addition of proteasome inhibitors. Mef2c degradation was mediated by Skp2 E3 ligase, and that knockdown of Skp2 mRNA in I-A12% B cells restored BCR responsiveness. Our results point to a generalized incompatibility between BCR responsiveness and increased Skp2 stability. They also imply the existence of regulatory mechanisms other than Ig gene rearrangement that govern Mef2c turnover in a specific, exquisite, and dynamic fashion.



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RNA Splicing in the Transition from B Cells to Antibody-Secreting Cells: The Influences of ELL2, Small Nuclear RNA, and Endoplasmic Reticulum Stress [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

In the transition from B cells to Ab-secreting cells (ASCs) many genes are induced, such as ELL2, Irf4, Prdm1, Xbp1, whereas other mRNAs do not change in abundance. Nonetheless, using splicing array technology and mouse splenic B cells plus or minus LPS, we found that induced and "uninduced" genes can show large differences in splicing patterns between the cell stages, which could influence ASC development. We found that ~55% of these splicing changes depend on ELL2, a transcription elongation factor that influences expression levels and splicing patterns of ASC signature genes, genes in the cell-cycle and N-glycan biosynthesis and processing pathways, and the secretory versus membrane forms of the IgH mRNA. Some of these changes occur when ELL2 binds directly to the genes encoding those mRNAs, whereas some of the changes are indirect. To attempt to account for the changes that occur in RNA splicing before or without ELL2 induction, we examined the amount of the small nuclear RNA molecules and found that they were significantly decreased within 18 h of LPS stimulation and stayed low until 72 h. Correlating with this, at 18 h after LPS, endoplasmic reticulum stress and Ire1 phosphorylation are induced. Inhibiting the regulated Ire1-dependent mRNA decay with 4u8C correlates with the reduction in small nuclear RNA and changes in the normal splicing patterns at 18 h. Thus, we conclude that the RNA splicing patterns in ASCs are shaped early by endoplasmic reticulum stress and Ire1 phosphorylation and later by ELL2 induction.



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VASP Regulates NK Cell Lytic Granule Convergence [IMMUNE REGULATION]

NK cells eliminate viral-infected and malignant cells through a highly orchestrated series of cytoskeletal rearrangements, resulting in the release of cytolytic granule contents toward the target cell. Central to this process is the convergence of cytolytic granules to a common point, the microtubule-organizing center (MTOC), before delivery to the synapse. In this study, we show that vasodialator-stimulated phosphoprotein (VASP), an actin regulatory protein, localizes to the cytolytic synapse, but surprisingly, shows no impact on conjugate formation or synaptic actin accumulation despite being required for human NK cell–mediated killing. Interestingly, we also find that a pool of VASP copurifies with lytic granules and localizes with lytic granules at the MTOC. Significantly, depletion of VASP decreased lytic granule convergence without impacting MTOC polarization. Using the KHYG-1 cell line in which lytic granules are in a constitutively converged state, we find that either VASP depletion or F-actin destabilization promoted spreading of formerly converged granules. Our results demonstrate a novel requirement for VASP and actin polymerization in maintaining lytic granule convergence during NK cell–mediated killing.



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Potential Use of Genetically Engineered Variable Lymphocyte Receptor B Specific to Avian Influenza Virus H9N2 [NOVEL IMMUNOLOGICAL METHODS]

The variable lymphocyte receptor (VLR) B of jawless vertebrates functions as a secreted Ab of jawed vertebrates and has emerged as an alternative Ab with a single polypeptide chain. After observing an upregulated VLRB response in hagfish immunized with avian influenza virus (AIV) subtype H9N2, we screened AIV H9N2–specific VLRB using a mammalian expression system. To improve the binding avidity of the Ag-specific VLRB to the Ag, we enabled multimerization of the VLRB by conjugating it with C-terminal domain of human C4b-binding protein. To dramatically enhance the expression and secretion of the Ag-specific VLRB, we introduced a glycine–serine linker and the murine Ig leader sequence. The practical use of the Ag-specific VLRB was also demonstrated through various immunoassays, detected by anti-VLRB Ab (11G5). Finally, we found that the Ag-specific VLRB decreased the infectivity of AIV H9N2. Together, our findings suggest that the generated Ag-specific VLRB could be used for various immunoapplications.



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Helminth-Induced Production of TGF-{beta} and Suppression of Graft-versus-Host Disease Is Dependent on IL-4 Production by Host Cells [IMMUNE REGULATION]

Helminths stimulate the secretion of Th2 cytokines, like IL-4, and suppress lethal graft-versus-host disease (GVHD) after bone marrow transplantation. This suppression depends on the production of immune-modulatory TGF-β and is associated with TGF-β–dependent in vivo expansion of Foxp3+ regulatory T cells (Treg). In vivo expansion of Tregs is under investigation for its potential as a therapy for GVHD. Nonetheless, the mechanism of induced and TGF-β–dependent in vivo expansion of Tregs, in a Th2 polarized environment after helminth infection, is unknown. In this study, we show that helminth-induced IL-4 production by host cells is critical to the induction and maintenance of TGF-β secretion, TGF-β–dependent expansion of Foxp3+ Tregs, and the suppression of GVHD. In mice with GVHD, the expanding donor Tregs express the Th2-driving transcription factor, GATA3, which is required for helminth-induced production of IL-4 and TGF-β. In contrast, TGF-β is not necessary for GATA3 expression by Foxp3+ Tregs or by Foxp3 CD4 T cells. Various cell types of innate or adaptive immune compartments produce high quantities of IL-4 after helminth infection. As a result, IL-4–mediated suppression of GVHD does not require invariant NKT cells of the host, a cell type known to produce IL-4 and suppress GVHD in other models. Thus, TGF-β generation, in a manner dependent on IL-4 secretion by host cells and GATA3 expression, constitutes a critical effector arm of helminthic immune modulation that promotes the in vivo expansion of Tregs and suppresses GVHD.



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mTOR- and SGK-Mediated Connexin 43 Expression Participates in Lipopolysaccharide-Stimulated Macrophage Migration through the iNOS/Src/FAK Axis [INFECTIOUS DISEASE AND HOST RESPONSE]

Connexin 43 (Cx43) deficiency was found to increase mortality in a mouse model of bacterial peritonitis, and Cx43 is upregulated in macrophages by LPS treatment. In this study, we characterized a novel signaling pathway for LPS-induced Cx43 expression in RAW264.7 cells and thioglycolate-elicited peritoneal macrophages (TGEMs). LPS alone or LPS-containing conditioned medium (CM) upregulated Cx43. Overexpression or silencing of Cx43 led to the enhancement or inhibition, respectively, of CM-induced TGEM migration. This response involved the inducible NO synthase (iNOS)/focal adhesion kinase (FAK)/Src pathways. Moreover, CM-induced migration was compromised in TGEMs from Cx43+/– mice compared with TGEMs from Cx43+/+ littermates. Cx43 was upregulated by a serum/glucocorticoid-regulated kinase 1 (SGK) activator and downregulated, along with inhibition of CM-induced TGEM migration, by knockdown of the SGK gene or blockade of the SGK pathway. LPS-induced SGK activation was abrogated by Torin2, whereas LPS-induced Cx43 was downregulated by both Torin2 and rapamycin. Analysis of the effects of FK506 and methylprednisolone, common immunosuppressive agents following organ transplantation, suggested a link between these immunosuppressive drugs and impaired macrophage migration via the Cx43/iNOS/Src/FAK pathway. In a model of Escherichia coli infectious peritonitis, GSK650349-, an SGK inhibitor, or Torin2-treated mice showed less accumulation of F4/80+CD11b+ macrophages in the peritoneal cavity, with a delay in the elimination of bacteria. Furthermore, following pretreatment with Gap19, a selective Cx43 hemichannel blocker, the survival of model mice was significantly reduced. Taken together, our study suggested that Cx43 in macrophages was associated with macrophage migration, an important immune process in host defense to infection.



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Androgen and Androgen Receptor as Enhancers of M2 Macrophage Polarization in Allergic Lung Inflammation [IMMUNE REGULATION]

Allergic asthma is a disease initiated by a breach of the lung mucosal barrier and an inappropriate Th2 inflammatory immune response that results in M2 polarization of alveolar macrophages (AM). The number of M2 macrophages in the airway correlates with asthma severity in humans. Sex differences in asthma suggest that sex hormones modify lung inflammation and macrophage polarization. Asthmatic women have more M2 macrophages than asthmatic men and androgens have been used as an experimental asthma treatment. In this study, we demonstrate that although androgen (dihydrotestosterone) reconstitution of castrated mice reduced lung inflammation in a mouse model of allergic lung inflammation, it enhanced M2 polarization of AM. This indicates a cell-specific role for androgens. Dihydrotestosterone also enhanced IL-4–stimulated M2 macrophage polarization in vitro. Using mice lacking androgen receptor (AR) in monocytes/macrophages (ARfloxLysMCre), we found that male but not female mice exhibited less eosinophil recruitment and lung inflammation due to impaired M2 polarization. There was a reduction in eosinophil-recruiting chemokines and IL-5 in AR-deficient AM. These data reveal an unexpected and novel role for androgen/AR in promoting M2 macrophage polarization. Our findings are also important for understanding pathology in diseases promoted by M2 macrophages and androgens, such as asthma, eosinophilic esophagitis, and prostate cancer, and for designing new approaches to treatment.



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Differentiation of Langerhans Cells from Monocytes and Their Specific Function in Inducing IL-22-Specific Th Cells [INNATE IMMUNITY AND INFLAMMATION]

Human mucosal tissues and skin contain two distinct types of dendritic cell (DC) subsets, epidermal Langerhans cells (LCs) and dermal DCs, which can be distinguished by the expression of C-type lectin receptors, Langerin and DC-SIGN, respectively. Although peripheral blood monocytes differentiate into these distinct subsets, monocyte-derived LCs (moLCs) induced by coculture with GM-CSF, IL-4, and TGF-β1 coexpress both Langerin and DC-SIGN, suggesting that the environmental cues remain unclear. In this study, we show that LC differentiation is TGF-β1 dependent and that cofactors such as IL-4 and TNF-α promote TGF-β1–dependent LC differentiation into Langerin+DC-SIGN moLCs but continuous exposure to IL-4 blocks differentiation. Steroids such as dexamethasone greatly enhanced TNF-α–induced moLC differentiation and blocked DC-SIGN expression. Consistent with primary LCs, dexamethasone-treated moLCs express CD1a, whereas monocyte-derived DCs (moDCs) express CD1b, CD1c, and CD1d. moDCs but not moLCs produced inflammatory cytokines after stimulation with CD1b and CD1d ligands mycolic acid and α-galactosylceramide, respectively. Strikingly, CD1a triggering with squalene on moLCs but not moDCs induced strong IL-22-producing CD4+ helper T cell responses. As IL-22 is an important cytokine in the maintenance of skin homeostasis, these data suggest that CD1a on LCs is involved in maintaining the immune barrier in the skin.



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IL-6 Promotes T Cell Proliferation and Expansion under Inflammatory Conditions in Association with Low-Level ROR{gamma}t Expression [IMMUNE REGULATION]

IL-6 is a critical driver of acute and chronic inflammation and has been reported to act as a T cell survival factor. The influence of IL-6 on T cell homeostasis is not well resolved. We demonstrate that IL-6 signaling drives T cell expansion under inflammatory conditions but not during normal homeostasis. During inflammation, IL-6Rα–deficient T cells are unable to effectively compete with wild type T cells. IL-6 promotes T cell proliferation, and this is associated with low-level expression of the RORt transcription factor. T cells upregulate Rorc mRNA at levels substantially diminished from that seen in Th17 cells. Blockade of RORt through genetic knockout or a small molecule inhibitor leads to T cell expansion defects comparable to those in IL-6Rα–deficient T cells. Our results indicate that IL-6 plays a key role in T cell expansion during inflammation and implicates a role for the transient induction of low-level RORt.



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Differential and Overlapping Immune Programs Regulated by IRF3 and IRF5 in Plasmacytoid Dendritic Cells [INNATE IMMUNITY AND INFLAMMATION]

We examined the signaling pathways and cell type–specific responses of IFN regulatory factor (IRF) 5, an immune-regulatory transcription factor. We show that the protein kinases IKKα, IKKβ, IKK, and TANK-binding kinase 1 each confer IRF5 phosphorylation/dimerization, thus extending the family of IRF5 activator kinases. Among primary human immune cell subsets, we found that IRF5 is most abundant in plasmacytoid dendritic cells (pDCs). Flow cytometric cell imaging revealed that IRF5 is specifically activated by endosomal TLR signaling. Comparative analyses revealed that IRF3 is activated in pDCs uniquely through RIG-I–like receptor (RLR) signaling. Transcriptomic analyses of pDCs show that the partitioning of TLR7/IRF5 and RLR/IRF3 pathways confers differential gene expression and immune cytokine production in pDCs, linking IRF5 with immune regulatory and proinflammatory gene expression. Thus, TLR7/IRF5 and RLR–IRF3 partitioning serves to polarize pDC response outcome. Strategies to differentially engage IRF signaling pathways should be considered in the design of immunotherapeutic approaches to modulate or polarize the immune response for specific outcome.



https://ift.tt/2quvKkF

IL-4 and IL-13 Guide Early Thymic Progenitors To Mature toward Dendritic Cells [IMMUNE SYSTEM DEVELOPMENT]

Recently we reported that IL-4 and IL-13 signaling in murine early thymic progenitors (ETPs) expressing the heteroreceptor (HR) comprising IL-4 receptor α (IL-4Rα) and IL-13 receptor α 1 (IL-13Rα1) activate STAT6 and inhibit ETP maturation potential toward T cells. In this study, we asked whether IL-4 and IL-13 signaling through the HR mobilizes other STAT molecules to shape ETP fate decision. The findings indicate that HR+ ETPs undergoing cytokine signaling display increased STAT1, but not STAT3, phosphorylation in addition to STAT6 activation. In parallel, the ETPs had a STAT1-dependent heightened expression of IRF-8, a transcription factor essential for development of CD8α+ dendritic cells (DCs). Interestingly, STAT1 phosphorylation and IRF-8 upregulation, which are independent of STAT6 activation, guided ETP maturation toward myeloid cells with a CD8α+ DC phenotype. Furthermore, these CD8α+ DCs display a thymic resident phenotype, as they did not express SIRPα, a molecule presumed to be involved in cell migration. These findings suggest that IL-4 and IL-13 cytokine-induced HR signaling provides a double-edged sword that simultaneously blocks T cell lineage potential but advances myeloid maturation that could impact T cell selection and central tolerance.



https://ift.tt/2qtFBXV

Post-obturation pain following the use of carrier-based system with AH Plus or iRoot SP sealers: a randomized controlled clinical trial

Abstract

Objectives

The aim of this study was to compare the postoperative pain after root canal treatment using a carrier-based obturation system and two different sealers.

Materials and methods

In this prospective randomized clinical trial, 160 patients were selected. Patients with vital and devital teeth were randomized into four groups using a randomized block design with block sizes of 10 patients each. The groups were devital/vital teeth treated with iRoot SP sealer and devital/vital teeth treated with AH Plus sealer. Patients were prescribed ibuprofen, a 200-mg analgesic, if needed, and postoperative pain was recorded by visual analogue scale at 6, 12, 24, and 72 h after obturation. Pain score and frequency of tablet intake were recorded and statistically analyzed.

Results

Results showed that there was no significant difference between groups in the incidence of postoperative pain; however, iRoot SP sealer was associated with less analgesic intake compared to AH Plus sealer.

Conclusion

The use of different sealers did not significantly affect pain levels.

Clinical relevance

iRoot SP sealer was associated with less analgesic intake compared to AH Plus sealer.



https://ift.tt/2ANQKbL

Pharmacologic inhibition of hypoxia inducible factor (HIF)‐hydroxylases ameliorates allergic contact dermatitis

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2D51W5q

Preventive sublingual immunotherapy with House Dust Mite extract modulates epitope diversity in pre‐school children

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PceH5G

Pulsed‐dye laser as a novel therapeutic approach for post‐filler bruises

Dermatologic Therapy, EarlyView.


https://ift.tt/2D2KOxo

Vestibular assessment in the pediatric population

The Laryngoscope, EarlyView.


https://ift.tt/2PcKtPJ

Pulsed‐dye laser as a novel therapeutic approach for post‐filler bruises

Dermatologic Therapy, EarlyView.


https://ift.tt/2D2KOxo

A farewell from your Editor

Clinical and Experimental Dermatology, Volume 43, Issue 8, Page 867-867, December 2018.


https://ift.tt/2zvPQ25

Issue Information

Clinical and Experimental Dermatology, Volume 43, Issue 8, Page i‐ii, 865-866, December 2018.


https://ift.tt/2SNse1B

A farewell from your Editor

Clinical and Experimental Dermatology, Volume 43, Issue 8, Page 867-867, December 2018.


https://ift.tt/2zvPQ25

Issue Information

Clinical and Experimental Dermatology, Volume 43, Issue 8, Page i‐ii, 865-866, December 2018.


https://ift.tt/2SNse1B

Subacute cutaneous lupus erythematosus triggered by an antiviral treatment combination for hepatitis C virus infection

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2D5wfsY

The frequency of arthritis in Adamantiades‐Behçet's disease in Greek patients

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PddxXi

HrQoL in hair loss affected patients with Alopecia Areata, Androgenetic Alopecia and Telogen Effluvium: The role of personality traits and psychosocial anxiety

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2D5wa8E

Morphological classification of melanoma metastasis with reflectance confocal microscopy

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2P9lAoe

Characteristics of IgG subclasses and complement deposition in BP230‐type bullous pemphigoid

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2D5w5lm

Detailed ANA dynamics under adalimumab therapy show no significant correlation to PASI response and MTX co‐treatment: a retrospective study of 98 psoriasis patients

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Pd2qOj

Intravaginal CO2 laser as an emergent treatment of genitourinary syndrome

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2D5vXCo

Rates of Antibiotic Resistance / Sensitivity in Bacterial Cultures of Hidradenitis Suppurativa Patients

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PbYeyp

Prediction of Insulin Resistance with Anthropometric and Clinical Laboratory Measures in Nondiabetic Teenagers

Metabolic Syndrome and Related Disorders, Ahead of Print.


https://ift.tt/2D5vPmo

Peptide mimetic of N‐terminal ghrelin enhances ghrelin induced growth hormone secretion and c‐Fos expression in mice

Journal of Neuroendocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2F2prih

Inverse Association Between Antiviral Immunity and Lupus Disease Activity

Viral Immunology, Ahead of Print.


https://ift.tt/2RD94du

Robot-Assisted Reconstruction in Head and Neck Surgical Oncology: The Evolving Role of the Reconstructive Microsurgeon

1023657

Transoral robotic surgery (TORS) is gaining more widespread use among head and neck surgical procedures. As experience grows with this technique, so do the indications of when and in which patients it can be used. Already established in the treatment of small oral cavity tumours, it is expanding into larger multi-site resections and resections, such as through-and-through-into-the-neck defects, that will require reconstruction. With robot-assisted surgery advancing, so robot-assisted reconstruction (RAR) is evolving. In this paper, we discuss the evolving role of reconstruction in post-TORS defects as well as the role of RAR in today's practice.
ORL 2018;80:178–185

https://ift.tt/2Dne7eN

Transoral Robotic Surgery Total Laryngectomy

224270?imgType=4

Objective: The aim of our study is to demonstrate our technique for performing transoral robotic surgical total laryngectomy (TORS-TL) with the use of the da Vinci robotic system. Materials and Methods: We provide a comprehensive description of the TORS-TL operative techniques. Two fresh-frozen human cadavers were selected after ethics approval to describe the appropriate step-by-step surgical resection. We adopted a 5-step procedure that was later applied to 2 of our patients. The first patient presented initially with a squamous cell carcinoma (SCC) in the laryngeal glottis area. A lack of clinical response to initial treatment by chemoradiotherapy led to the decision of performing salvage TL surgery. The second patient had a previous history of head and neck SCC (HNSCC); he had no recurrence of his primary tumor but suffered significantly from postoperative breathing and swallowing difficulties due to severe laryngeal incompetence. Results: TORS-TL was successfully performed in all cases. The operative time for the cadavers was approximately 65 and 55 min, respectively. It was significantly longer for the patients, 210 and 235 min, respectively, despite the fact that exactly the same steps were followed throughout all procedures. There were no intra- or postoperative complications or surgical morbidity related to the use of the da Vinci system. Conclusion: TORS-SL for SCC was performed in a safe, reliable, and smooth manner and was shown to be successful in treating our patients. We thus believe that our step-by-step surgical technique for TORS-SL is efficient and reproducible.
ORL 2018;80:171–177

https://ift.tt/2JEUZJP

Hauterkrankungen und Fertilitäts‑/Hormonstörungen

Zusammenfassung

Die männliche Fertilität kann durch eine Vielzahl von Faktoren gestört werden. Neben Umwelt- und Lifestylefaktoren wie Stress, Lärm, Rauchen und Übergewicht können sich auch diverse Erkrankungen negativ auf die Zeugungsfähigkeit und den Hormonhaushalt, insbesondere den Testosteronspiegel, auswirken. Bei vielen Erkrankungen gehen die aktuellen Daten leider noch nicht über Beobachtungen eingeschränkter Fertilität hinaus. In diesem Beitrag sollen v. a. die Erkrankungen aus dem Behandlungsfeld der Dermatologie im Vordergrund stehen. Besonderes Augenmerk wird auf die chronisch entzündlichen und autoimmunen Hauterkrankungen gelegt. Hier zeigen Daten aus den letzten Jahren, dass die überschießende Entzündungsreaktion, die diesen Erkrankungen gemein ist, aller Wahrscheinlichkeit nach auch Einflüsse auf die Fertilität hat und in Interaktion mit der Testosteronkonzentration im Serum steht. Daneben wird auf die Auswirkung von hereditären Hauterkrankungen auf die männliche Fertilität eingegangen, die über Schädigung der Hypothalamus-Hypophysen-Gonaden-Achse direkten Einfluss auf die Zeugungsfähigkeit des Mannes haben können.



https://ift.tt/2JEagKJ

Tagungsbericht vom 13. Kongress der Deutsch-Japanischen Dermatologischen Gesellschaft



https://ift.tt/2Do8uNE

Diagnostic performance of temporal artery ultrasound for the diagnosis of giant cell arteritis: a systematic review and meta-analysis of the literature

Publication date: Available online 5 November 2018

Source: Autoimmunity Reviews

Author(s): Marina Rinagel, Emmanuel Chatelus, Sandrine Jousse-Joulin, Jean Sibilia, Jacques-Eric Gottenberg, François Chasset, Laurent Arnaud

Abstract

Despite major recent advances in the therapeutic management of Giant cell arteritis (GCA), the diagnosis accuracy of temporal artery ultrasound remains controversial in this disease. We performed a systematic review to determine the sensitivity, specificity, and summary positive (LR+) and negative (LR-) likelihood ratios of temporal artery ultrasound for the diagnosis of GCA. For this, we searched EMBASE, MEDLINE and the Cochrane Database of Systematic Reviews without language restriction. Original articles reporting on diagnostic accuracy of temporal artery ultrasound compared to temporal artery biopsy, for the diagnosis of GCA, were selected. Sensitivity and specificity from each study were used to fit a bivariate diagnosis accuracy model. Of 1280 articles identified, 48 underwent full-text review, and 25 were included. Based on a total of 20 studies, the sensitivity and specificity of hypoechoic halo compared to positive temporal artery biopsy were respectively of 68% (95% CI: 57–78) and 81% (95%CI: 75–86). The summary mean positive and negative likelihood ratios were respectively of 3.64 (95%CI: 2.76–4.73) and 0.40 (0.28–0.52). Taking into account 11 studies reporting on the presence of any abnormal sign on temporal artery ultrasound yielded similar results with largely overlapping 95% confidence interval regions. This study provides the summary estimates of the diagnostic properties of temporal artery ultrasound compared to temporal artery biopsy, for the diagnosis of GCA. Those parameters allow the calculation of the post-test probability of GCA in a given patient, based on the results of temporal artery ultrasound and will help improving the diagnosis strategy for this common disease.



https://ift.tt/2qutN7B

Autoimmune diseases in myelodysplastic syndrome favors patients survival: A case control study and literature review

Publication date: Available online 5 November 2018

Source: Autoimmunity Reviews

Author(s): Julie Seguier, Véronique Gelsi-Boyer, Mikael Ebbo, Zeinab Hamidou, Aude Charbonnier, Emmanuelle Bernit, Jean-Marc Durand, Jean-Robert Harlé, Norbert Vey, Nicolas Schleinitz

Abstract
Background

We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis.

Results

From all MDS patients 11% presented with AIMs. These were heterogeneous and the most frequent where polyarthritis (25%) and autoimmune cytopenias (17%). No difference for frequency and type of AIMs was observed for the WHO 2016 MDS subgroups (p=.3). In the case control study WHO classification, karyotype abnormalities, IPSS-R and IPSS were similar in both groups. The overall survival from MDS diagnosis was better in the group with AIMs [10.3 ± 0.6 (IC95% 6.2–12.9) versus 4.8 ± 1.1 years (IC95% 4.2–8.7), p=.04]. The better survival was restricted to MDS with low or intermediate-1 IPSS [11.1 ± 1.5 (IC95% 9.9-NR) versus 8.7 ± 1.3 years (IC95% 4.8–10.3), p=.006]. The better survival was only observed when AIMs diagnosis was timely associated or appeared after MDS diagnosis (p=.04). Factors associated with a better overall survival and survival without AML were steroid dependence [respectively HR = 0.042, p=.003, (IC95% 0.005–0.33) and HR = 0.07, p=.002, (IC95% 0.013–0.39)], a diagnosis of AIMs and MDS timely associated [respectively HR = 0.05, p=.009, (IC95% 0.006–0.478) and HR = 0.1, p=.008, (IC95% 0.018–0.54)] or a diagnosis of AIMs after MDS [respectively HR = 0.024, p=.009, (IC95% 0.001–0.39) and HR = 0.04, p=.008, (IC95% 0.003–0.43)].

Conclusion

Autoimmune and inflammatory diseases associated to MDS are heterogeneous. AIMs diagnosed after or concomitantly to MDS seems associated with a better survival. Prospective studies are necessary to demonstrate that autoimmunity is associated to a better control of the MDS clone.



https://ift.tt/2QiTGCB

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis

Publication date: Available online 5 November 2018

Source: Autoimmunity Reviews

Author(s): Roberto Giacomelli, Antonella Afeltra, Alessia Alunno, Elena Bartoloni-Bocci, Onorina Berardicurti, Michele Bombardieri, Alessandra Bortoluzzi, Roberto Caporali, Francesco Caso, Ricard Cervera, Maria Sole Chimenti, Paola Cipriani, Emmanuel Coloma, Fabrizio Conti, Salvatore D'Angelo, Salvatore De Vita, Salvatore Di Bartolomeo, Oliver Distler, Andrea Doria, Eugen Feist

Abstract

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care.

The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.



https://ift.tt/2qsHSTd

Immunogenicity, safety and tolerability of anti-pneumococcal vaccination in systemic lupus erythematosus patients: An evidence-informed and PRISMA compliant systematic review and meta-analysis

Publication date: Available online 5 November 2018

Source: Autoimmunity Reviews

Author(s): Nicola Luigi Bragazzi, Dennis McGonagle, Samaa Watad, Mohammad Adawi, Naim Mahroum, Giovanni Damiani, Rosalynn Conic, Charlie Bridgewood, Hussein Mahagna, Luca Giacomelli, Roberto Eggenhöffner, Mahmud Mahamid, Paolo Daniele Maria Pigatto, Howard Amital, Abdulla Watad

Abstract

The immunological perturbations associated with systemic lupus erythematosus (SLE) puts many patients at higher risk of infections including pneumococcal pneumonia. However, the uptake and utility of anti-pneumococcal vaccines in SLE patient is both controversial and not completely agreed on. Indeed, several epidemiological studies of anti-pneumococcal vaccine safety and efficacy in SLE have reported short term immunogenicity with elevated anti-pneumococcal antibody titres but inconsistent long term findings with some studies finding poor responses, mainly for long-term immune protection. Moreover, the safety and efficacy of the pneumococcal vaccine in SLE patients remains controversial due to the different types of anti-pneumococcal vaccines, and the heterogeneity of SLE patients. Several reviews addressing anti-pneumococcal vaccination in SLE patients exist, however, to the best of our knowledge, the present is the first systematic review and meta-analysis. To better understand the efficacy and safety of pneumococcal vaccination in SLE, a comprehensive literature search was performed identifying 18 studies in the present systematic reviews and meta-analysis. All studies were designed as longitudinal investigations, two, in particular, were of high quality, being randomized, double-blind trials (RCTs). Four studies had control groups. Sample size ranged from 12 to 204 participants. Vaccine immunogenicity in terms of subjects with protective antibody titers ranged from 36.0% to 97.6%. According to our metanalysis high erythrocyte sedimentation rate (ESR), older earlier SLE, high disease activity, and immunosuppressive therapy were predictors of poor immunogenicity, although belimumab was found to have no significant impact. With regard to safety, no serious adverse events were found, with up to third of cases reporting mild/low-grade and complaints.

In conclusion, due to the high risk of pneumococcal infection in SLE patients and given the safety and, at least partial, effectiveness according our study in such patients, preventive strategies mainly by immunization are required in all age groups and in those needing immunosuppressive therapy, immunization should be given prior the initiation of the treatment.

PROSPERO registration code 103605.



https://ift.tt/2Qp8ZtP

Systemic sclerosis and exposure to heavy metals

Publication date: Available online 4 November 2018

Source: Autoimmunity Reviews

Author(s): Isabelle Marie

Abstract

As a mirror image of the Roman god Janus Bifrons, the environment has a hidden face. To highlight this hidden face of the environment in the field of systemic sclerosis (SSc) will allow to identify responsible agents emerging in the future. To date, there is, in fact, a growing scientific evidence that environmental factors have a crucial impact on both alterations and modulation of epigenetic determinants, resulting in SSc onset and progression. It has been well established that there is a marked correlation between SSc onset and occupational exposure to crystalline silica and organic solvents. More recently, an association between SSc and exposure to heavy metals has further been found, including: antimony, cadmium, lead, mercury. These latter findings interestingly underscore that occupational exposure to heavy metals should be systematically checked in all SSc patients at diagnosis, as the identification of the occupational toxic agent will allow its interruption, which may result in potential improvement of SSc outcome.



https://ift.tt/2Qs0iP2

Diagnostic performance of temporal artery ultrasound for the diagnosis of giant cell arteritis: a systematic review and meta-analysis of the literature

Publication date: Available online 5 November 2018

Source: Autoimmunity Reviews

Author(s): Marina Rinagel, Emmanuel Chatelus, Sandrine Jousse-Joulin, Jean Sibilia, Jacques-Eric Gottenberg, François Chasset, Laurent Arnaud

Abstract

Despite major recent advances in the therapeutic management of Giant cell arteritis (GCA), the diagnosis accuracy of temporal artery ultrasound remains controversial in this disease. We performed a systematic review to determine the sensitivity, specificity, and summary positive (LR+) and negative (LR-) likelihood ratios of temporal artery ultrasound for the diagnosis of GCA. For this, we searched EMBASE, MEDLINE and the Cochrane Database of Systematic Reviews without language restriction. Original articles reporting on diagnostic accuracy of temporal artery ultrasound compared to temporal artery biopsy, for the diagnosis of GCA, were selected. Sensitivity and specificity from each study were used to fit a bivariate diagnosis accuracy model. Of 1280 articles identified, 48 underwent full-text review, and 25 were included. Based on a total of 20 studies, the sensitivity and specificity of hypoechoic halo compared to positive temporal artery biopsy were respectively of 68% (95% CI: 57–78) and 81% (95%CI: 75–86). The summary mean positive and negative likelihood ratios were respectively of 3.64 (95%CI: 2.76–4.73) and 0.40 (0.28–0.52). Taking into account 11 studies reporting on the presence of any abnormal sign on temporal artery ultrasound yielded similar results with largely overlapping 95% confidence interval regions. This study provides the summary estimates of the diagnostic properties of temporal artery ultrasound compared to temporal artery biopsy, for the diagnosis of GCA. Those parameters allow the calculation of the post-test probability of GCA in a given patient, based on the results of temporal artery ultrasound and will help improving the diagnosis strategy for this common disease.



https://ift.tt/2qutN7B

Autoimmune diseases in myelodysplastic syndrome favors patients survival: A case control study and literature review

Publication date: Available online 5 November 2018

Source: Autoimmunity Reviews

Author(s): Julie Seguier, Véronique Gelsi-Boyer, Mikael Ebbo, Zeinab Hamidou, Aude Charbonnier, Emmanuelle Bernit, Jean-Marc Durand, Jean-Robert Harlé, Norbert Vey, Nicolas Schleinitz

Abstract
Background

We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis.

Results

From all MDS patients 11% presented with AIMs. These were heterogeneous and the most frequent where polyarthritis (25%) and autoimmune cytopenias (17%). No difference for frequency and type of AIMs was observed for the WHO 2016 MDS subgroups (p=.3). In the case control study WHO classification, karyotype abnormalities, IPSS-R and IPSS were similar in both groups. The overall survival from MDS diagnosis was better in the group with AIMs [10.3 ± 0.6 (IC95% 6.2–12.9) versus 4.8 ± 1.1 years (IC95% 4.2–8.7), p=.04]. The better survival was restricted to MDS with low or intermediate-1 IPSS [11.1 ± 1.5 (IC95% 9.9-NR) versus 8.7 ± 1.3 years (IC95% 4.8–10.3), p=.006]. The better survival was only observed when AIMs diagnosis was timely associated or appeared after MDS diagnosis (p=.04). Factors associated with a better overall survival and survival without AML were steroid dependence [respectively HR = 0.042, p=.003, (IC95% 0.005–0.33) and HR = 0.07, p=.002, (IC95% 0.013–0.39)], a diagnosis of AIMs and MDS timely associated [respectively HR = 0.05, p=.009, (IC95% 0.006–0.478) and HR = 0.1, p=.008, (IC95% 0.018–0.54)] or a diagnosis of AIMs after MDS [respectively HR = 0.024, p=.009, (IC95% 0.001–0.39) and HR = 0.04, p=.008, (IC95% 0.003–0.43)].

Conclusion

Autoimmune and inflammatory diseases associated to MDS are heterogeneous. AIMs diagnosed after or concomitantly to MDS seems associated with a better survival. Prospective studies are necessary to demonstrate that autoimmunity is associated to a better control of the MDS clone.



https://ift.tt/2QiTGCB

Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis

Publication date: Available online 5 November 2018

Source: Autoimmunity Reviews

Author(s): Roberto Giacomelli, Antonella Afeltra, Alessia Alunno, Elena Bartoloni-Bocci, Onorina Berardicurti, Michele Bombardieri, Alessandra Bortoluzzi, Roberto Caporali, Francesco Caso, Ricard Cervera, Maria Sole Chimenti, Paola Cipriani, Emmanuel Coloma, Fabrizio Conti, Salvatore D'Angelo, Salvatore De Vita, Salvatore Di Bartolomeo, Oliver Distler, Andrea Doria, Eugen Feist

Abstract

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care.

The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.



https://ift.tt/2qsHSTd

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