Incidence and severity of chronic pain after caesarean section: A systematic review with meta-analysis.

BACKGROUND: The frequency of caesarean section has increased dramatically in recent decades. Despite this, robust data regarding the consequences of caesarean section in terms of developing chronic postsurgical pain (CPSP) are still lacking. OBJECTIVE: This systematic review analysed the incidence and severity of CPSP in women 3 to less than 6, 6 to less than 12, and at least 12 months after caesarean section. DESIGN: Systematic review of prospective and retrospective observational studies and randomised controlled trials with meta-analysis. DATA SOURCE: We searched MEDLINE to May 2015. ELIGIBILITY CRITERIA: We included all studies investigating the incidence and/or severity of CPSP at least 3 months after caesarean section. The primary outcome was chronic postsurgical wound pain (CPSP 'wound'). Secondary outcomes were persistent pain in the back area, pelvic region or reported as residual pain, and severity of 'birth-related' chronic pain. RESULTS: Meta-analysis using the random-effects model based on 15 studies (n = 4475) reporting CPSP 'wound' at 3 to less than 6 months after caesarean section revealed an incidence of 15.4% [95% confidence interval (CI): 9.9 to 20.9%]. For 6 to less than 12 and at least 12 months after caesarean section, the incidence of CPSP 'wound' was estimated at 11.5% (95% CI: 8.1 to 15.0%, n = 3345) and 11.2% (95% CI: 7.4 to 15.0%, n = 3451), respectively. Meta-regression analysis using the publication year as predictor revealed stable CPSP 'wound' incidences at each postoperative time slot from 2002 to the present. Of those patients who reported chronic pain, 9.6% (95% CI: 0.0 to 21.0%) had severe pain, 23.5% (95% CI: 10.0 to 37.0%) had moderate pain and 49.2% (95% CI: 18.9 to 79.4%) had mild pain at 6 months. LIMITATIONS: Major limitations are high statistical heterogeneity of the meta-analyses and inconsistencies in reporting severity of chronic 'birth-related' pain. CONCLUSION: This meta-analysis finds a clinically relevant incidence of CPSP 'wound' after caesarean section ranging from 15% at 3 months to 11% at 12 months or longer that has been largely stable in recent years. (C) 2016 European Society of Anaesthesiology

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Recommended practice for out-of-hospital emergency anaesthesia in adults: Statement from the Out-of-Hospital Emergency Anaesthesia Working Group of the Emergency Medicine Research Group of the German Society of Anaesthesiology and Intensive Care.

No abstract available

http://ift.tt/2cEhaj0

Impact of age on anaesthesiologists' competence: A narrative review.

The international anaesthesia community is getting older, in line with trends worldwide, and as men and women age there is the risk that psychophysiological decline could have an impact on clinical practice. Impairment of technical and nontechnical skills could have a negative impact on patients' safety and outcomes. The ageing process may not necessarily go hand-in-hand with a predictable pattern of decreased competence as not all aspects of functional decline are affected at the same rate and to the same extent. The development of simulation has provided a means of detecting and perhaps reversing the decline in ability associated with age. The introduction of recertification based on an assessment of competence at simulation sessions could play a crucial role in maintaining a high standard of patient care and an appropriate level of patient safety. (C) 2016 European Society of Anaesthesiology

http://ift.tt/2cRhv5l

Modelling of the optimal bupivacaine dose for spinal anaesthesia in ambulatory surgery based on data from systematic review.

BACKGROUND: Spinal bupivacaine is used for day-case surgery but the appropriate dose that guarantees hospital discharge is unknown. OBJECTIVE: We sought to determine the spinal bupivacaine dose that prevents delayed hospital discharge in ambulatory surgery. DESIGN: Systematic review of clinical trials. DATA SOURCES: Comprehensive search in electronic databases of studies published between 1996 and 2014 reporting the use of spinal bupivacaine in ambulatory patients. Additional articles were retrieved through hyperlinks and by manually searching reference lists in original articles, review articles and correspondence published in English and French. MAIN OUTCOME MEASURES: Data were used to calculate, motor block duration and discharge time, an estimated maximal effect (Emax: maximum theoretical time of motor block) and the effective dose to obtain half of Emax (D50) with 95% confidence intervals (CIs). A simulation was performed to determine the dose corresponding to a time to recovery of 300 min for motor function, and 360 min for discharge, in 95% of the patients. RESULTS: In total, 23 studies (1062 patients) were included for analysis of the time to recovery of motor function, and 12 studies (618 patients) for the time to hospital discharge. The Emax for recovery of motor function was 268 min [95% CI (189 to 433 min)] and the D50 was 3.9 mg [95% CI (2.3 to 6.2 mg)]. A 7.5-mg dose of bupivacaine enables resolution of motor block and ambulation within 300 min in 95% of the patients. A 5-mg dose or less was associated with an unacceptable failure rate. CONCLUSION: Ambulatory surgery is possible under spinal anaesthesia with bupivacaine although the dose range that ensures reliable anaesthesia with duration short enough to guarantee ambulatory management is narrow. (C) 2016 European Society of Anaesthesiology

http://ift.tt/2cEj4jH

T cell subpopulations in juvenile idiopathic arthritis and their modifications after biotherapies

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Laura Maggi, Lorenzo Cosmi, Gabriele Simonini, Francesco Annunziato, Rolando Cimaz
Inflammatory T cells are thought to be central to the pathogenesis of juvenileidiopathicarthritis. In particular, recentevidencehasunderlined the importance of a balance between Th17 and Tregcells. Severalmechanismshave come to light that control thisreciprocalrelationship.Moreover, ithasbeenshownthat in certainconditions Th17 cells can shifttoward a non classic Th1 phenotype. Anti-rheumaticbiologictherapiesmayinterfere with thesemechanisms and re-establish immune tolerance.



http://ift.tt/2cxSpWA

The industrial food additive microbial transglutaminase, mimics the tissue transglutaminase and is immunogenic in celiac disease patients

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): T. Matthias, P. Jeremias, S. Neidhöfer, A. Lerner
Microbial transglutaminase (mTg) is capable of cross-linking numerous molecules. It is a family member of human tissue transglutaminase (tTg), involved in CD. Despite declarations of mTg industrial use safety, direct evidence for immunogenicity of the enzyme is lacking.The serological activity of mTg, tTg, gliadin complexed mTg (mTg neo-epitope) and gliadin complexed tTg (tTg neo-epitope) were studied in: 95 pediatric celiac patients (CD), 99 normal children (NC) 79 normal adults (NA) and 45 children with nonspecific abdominal pain (AP). Sera were tested by ELISAs, detecting IgA, IgG or both IgA and IgG (check): AESKULISA® tTg (tTg), AESKULISA® tTg New Generation (tTg neo-epitope (tTg-neo)), microbial transglutaminase (mTg) and mTg neo-epitope (mTg-neo). Marsh criteria were used for the degree of intestinal injury. Parallel, mTg and tTg neo-epitopes were purified by asymmetric field flow fractionation, confirmed by multi light scattering and SDS-page, and analyzed on the adult CD and controls group by competition ELISAs.No sequence homology but active site similarity were detected on alignment of the 2 Tgs. Comparing pediatric CD patients with the 2 normal groups: mTg-neo IgA, IgG and IgA+IgG antibody activities exceed the comparable mTg ones (p<0.0001). All mTg-neo and tTg-neo levels were higher (p<0.001). tTg IgA and IgG+IgA were higher than mTg IgA and IgA+IgG (p<0.0001). The levels of tTg-neo IgA/IgG were higher than tTg IgA/IgG (p<0.0001). The sequential antibody activities reflecting best the increased intestinal damage were: tTg-neo check>tTg-neo IgA≥mTg-neo IgG>tTg-neo IgG>mTg-neo check > mTg-neo IgA. Taken together, tTg-neo check, tTg-neo IgA and mTg-neo IgG correlated best with intestinal pathology (r²=0.6454, r²=0.6165,r²=0.5633 p<0.0001, p<0.0001, p<0.0001, respectively). Purified mTg-neo IgG and IgA showed an increased immunoreactivity compared to single mTg and gliadin (p<0.001) but similar immunoreactivity to the tTg-neo IgG and IgA ELISA. Using a competition ELISA, the mTg neo-epitopes and tTg neo-epitopes have identical outcomes in CD sera both showing a decrease in optical density of 55±6%, (p<0.0002).mTg is immunogenic in children with CD and by complexing to gliadin its immunogenicity is enhanced. Anti-mTg-neo-epitope IgG antibodies correlate with intestinal damage to a comparable degree as anti-tTg-neo IgA. mTg and tTg display a comparable immunopotent epitope. mTg-neo IgG is a new marker for CD. Further studies are needed to explore the pathogenic potential of anti-mTg antibodies in CD.



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Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): M Alvarado-Cardenas, A Marin, MA Martínez, L Martínez, I Pinal-Fernandez, M Labrador-Horrillo, E Balada, X Mundet-Tuduri, L Gonzalez-Mera, J Casademont, E Martínez Acebes, PJ Moreno, C Juarez, JM Grau-Junyent, R Pujol-Borrell, A Selva-O'Callaghan
Background and objectiveStatin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies.Patients and methodsTwenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls.Results21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95.ConclusionsA new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.



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Plant materials for gastrointestinal diseases used in Chawang District, Nakhon Si Thammarat Province, Thailand

Publication date: 24 December 2016
Source:Journal of Ethnopharmacology, Volume 194
Author(s): Oratai Neamsuvan, Thanchanok Phumchareon, Wanisa Bunphan, Wayanan Kaosaeng
Ethnopharmacological relevanceIn Thailand, gastrointestinal diseases have occurred since the past, consequently healers know well how to use herbs for treatment. Currently, some groups of Thai people continue to be interested in treating diseases by herbs. Therefore, the aims of this study were to (1) compile a list of species of medicinal plants and their source, (2) document the diseases treated and their frequency of citation, (3) record the parts used, methods of preparation and route of administration of traditional medicines, and (4) compare the folk knowledge to that in other relevant reports.Materials and methodsTen folk healers were included in the study. Semi-structured interviews were used to compile data, namely plant parts used, preparation, route of administration and properties. The data were analyzed by interpretation and descriptive statistics.ResultsSixty-two species in 28 families were identified. The most used plants (11 species) were grouped in Zingiberaceae. The highest level of relative frequency of citation (RFC) was found in Zingiber officinale Roscoe (1.0). Most plants were applied for treating constipation. Powder was the most common preparation form of folk drug. A total of 174 use lists were recorded, however, more than two thirds were reported as new uses in this study.ConclusionA literature review revealed that the remaining 37 species for pharmacological activities and 42 species for toxicity should be further studied to validate the folk use of these medicinal resource.

Graphical abstract

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Ginsenosides attenuate d-galactose- and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease

Publication date: 24 December 2016
Source:Journal of Ethnopharmacology, Volume 194
Author(s): Yan Zhang, Zifeng Pi, Fengrui Song, Zhiqiang Liu
Ethnopharmacological relevancePanax ginseng C.A.Mey. is a traditional Chinese herbal medicine, which has been used to treat Alzheimer's disease (AD) for thousands of years. Ginsenoside is one of the major compounds found in P. ginseng. This study aimed to explore the attenuation of spatial memory impairment by ginsenosides and its correlation with restoring the dysfunction of the neurotransmitter systems in AD model rats to understand the mechanism underlying the anti-AD effect of P. ginseng.Materials and methodsIn this study, the AD model was established by combining d-galactose (d-gal) with AlCl3 (Al) for 60 days. From day 30, the ginsenosides group was intragastrically administered with ginsenosides for 30 days. The ethology of rats was tested through the Morris water maze test(MWM). Histopathological changes in the hippocampus of rats were observed through hematoxylin and eosin staining. The expressions of amyloid β peptide (Aβ) and phospho-tau (p-tau) in the hippocampus and cortex of rats were detected by immunohistochemistry. A liquid chromatography–mass spectrometry assay was used to measure neurotransmitter concentrations in the hippocampus, cortex, and blood.ResultsGinsenosides could significantly decrease the escape latency time and the average latency time in the place navigation test and increase the times of crossing the platform area, the percentage of residence time, and the distance in the original platform quadrant in the spatial probe test. Ginsenosides could repair the damage of the hippocampus and reduce the expressions of Aβ and p-tau. Ginsenosides could also increase γ-aminobutyric acid, acetylcholine, and dopamine levels and decrease glutamate and aspartic acid levels in the hippocampus and cortex and increase glycine and serotonin levels in the blood.ConclusionsAfter effectively administrated, ginsenosides attenuate d-gal- and Al-induced spatial memory impairment. The possible mechanism of the beneficial effect is restoring the dysfunction of various neurotransmitters.

Graphical abstract

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The antioxidant transcription factor Nrf2 contributes to the protective effect of mild thermotolerance (40°C) against heat shock-induced apoptosis

Publication date: October 2016
Source:Free Radical Biology and Medicine, Volume 99
Author(s): Audrey Glory, Diana A. Averill-Bates
The exposure of cells to low doses of stress induces adaptive survival responses that protect cells against subsequent exposure to toxic stress. The ability of cells to resist subsequent toxic stress following exposure to low dose heat stress at 40°C is known as mild thermotolerance. Mild thermotolerance involves increased expression of heat shock proteins and antioxidants, but the initiating factors in this response are not understood. This study aims to understand the role of the Nrf2 antioxidant pathway in acquisition of mild thermotolerance at 40°C, and secondly, whether the Nrf2 pathway could be involved in the protective effect of thermotolerance against heat-shock (42°C)-induced apoptosis. During cell preconditioning at 40°C, protein expression of the Nrf2 transcription factor increased after 15–60min. In addition, levels of the Nrf2 targets MnSOD, catalase, heme oxygenase-1, glutamate cysteine ligase and Hsp70 increased at 40°C. Levels of these Nrf2 targets were enhanced by Nrf2 activator oltipraz and decreased by shRNA targeting Nrf2. Levels of pro-oxidants increased after 30–60min at 40°C. Pro-oxidant levels were decreased by oltipraz and increased by knockdown of Nrf2. Increased Nrf2 expression and catalase activity at 40°C were inhibited by the antioxidant PEG-catalase and by p53 inhibitor pifithrin-α. These results suggest that mild thermotolerance (40°C) increases cellular pro-oxidant levels, which in turn activate Nrf2 and its target genes. Moreover, Nrf2 contributes to the protective effect of thermotolerance against heat-shock (42°C)-induced apoptosis, because Nrf2 activation by oltipraz enhanced thermotolerance, whereas Nrf2 knockdown partly reversed thermotolerance. Improved knowledge about the different protective mechanisms that mild thermotolerance can activate is crucial for the potential use of this adaptive survival response to treat stress-related diseases.



http://ift.tt/2cwm59T

Sensitive detection and estimation of cell-derived peroxynitrite fluxes using fluorescein-boronate

Publication date: Available online 15 September 2016
Source:Free Radical Biology and Medicine
Author(s): Natalia Rios, Lucía Piacenza, Madia Trujillo, Alejandra Martínez, Verónica Demicheli, Carolina Prolo, María Noel Álvarez, Gloria V. López, Rafael Radi
The specific and sensitive detection of peroxynitrite (ONOO^‒/ONOOH) in biological systems is a great challenge due to its high reactivity towards several biomolecules. Herein, we validated the advantages of using fluorescein-boronate (Fl-B) as a highly sensitive fluorescent probe for the direct detection of peroxynitrite under biologically-relevant conditions in two different cell models. The synthesis of Fl-B was achieved by a very simply two-step conversion synthetic route with high purity (> 99 %) and overall yield (∼ 42%). Reactivity analysis of Fl-B with relevant biological oxidants including hydrogen peroxide (H2O2), hypochlorous acid (HOCl) and peroxynitrite were performed. The rate constant for the reaction of peroxynitrite with Fl-B was 1.7 x 10⁶ M^-1s^-1, a million times faster than the rate constant measured for H2O2 (k = 1.7 M^-1s^-1) and 2,700 faster than HOCl (6.2 x 10² M^-1s^-1) at 37° C and pH 7.4. The reaction of Fl-B with peroxynitrite was significant even in the presence of physiological concentrations of CO2, a well-known peroxynitrite reactant. Experimental and simulated kinetic analyses confirm that the main oxidation process of Fl-B takes place with peroxynitrite itself via a direct bimolecular reaction and not with peroxynitrite-derived radicals. Fl-B was successfully applied for the detection of endogenously- generated peroxynitrite by endothelial cells and in macrophage-phagocyted parasites. Moreover, the generated data allowed estimating the actual intracellular flux of peroxynitrite. For instance, ionomycin-stimulated endothelial cells generated peroxynitrite at a rate of ∼ 0.1 μM s^-1, while immunostimulated macrophages do so in the order of ∼ 1 μM s^-1 inside T. cruzi-infected phagosomes. Fl-B revealed not to be toxic in concentrations up to 1 mM for 24 h. Cellular peroxynitrite detection was achieved by conventional laboratory fluorescence-based methods including flow cytometry and epi-fluorescence microscopy. Fl-B was shown to be more sensitive than the coumarin boronate due to a higher molar absorption coefficient and quantum yield. Overall, our results show that Fl-B is a kinetically selective and highly sensitive probe for the direct detection of cell-derived peroxynitrite.



http://ift.tt/2cxNPHM

Interactions between neurokinin B and kisspeptin in mediating estrogen feedback in healthy women

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2ckO6hw

Diabetic Ketoacidosis without Diabetes

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cGK54v

Adhesion G-protein coupled receptor G1 (ADGRG1/GPR56) and pancreatic β-cell function

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2ckNzwe

Impact of completion axillary lymph node dissection in patients with breast cancer and isolated tumour cells or micrometastases in sentinel nodes

Publication date: November 2016
Source:European Journal of Cancer, Volume 67
Author(s): G. Houvenaeghel, J.M. Boher, F. Reyal, M. Cohen, J.R. Garbay, J.M. Classe, R. Rouzier, S. Giard, C. Faure, H. Charitansky, C. Tunon de Lara, E. Daraï, D. Hudry, P. Azuar, P. Gimbergues, R. Villet, P. Sfumato, E. Lambaudie
BackgroundOmission of completion axillary lymph node dissection (ALND) is a standard practice in patients with breast cancer (BC) and negative sentinel nodes (SNs) but has shown insufficient evidence to be recommended in those with SN invasion.MethodsA retrospective analysis of a cohort of patients with BC and micrometastases (Mic) or isolated tumour cells (ITCs) in SN. Factors associated with ALND were identified, and patients with ALND were matched to patients without ALND. Overall survival (OS) and recurrence-free survival (RFS) were estimated in the overall population, in Mic and in ITC cohorts.FindingsAmong 2009 patients analysed, 1390 and 619 had Mic and ITC in SN, respectively. Factors significantly associated with ALND were SN status, histological type, age, number of SN harvested and absence of adjuvant chemotherapy. After a median follow-up of 60.4 months, ALND omission was independently associated with reduced OS (hazard ratio [HR] 2.41, 90 confidence interval [CI] 1.36–4.27, p = 0.0102), but not with increased RFS (HR 1.21, 90 CI 0.74–2.0, p = 0.52) in the overall population. In matched patients, the increased risk of death in case of ALND omission was found only in the Mic cohort (HR 2.88, 90 CI 1.46–5.69), not in the ITC cohort. The risk of recurrence was also significantly increased in the subgroup of matched Mic patients (HR 1.56, 90 CI 0.90–2.73).InterpretationA separate analysis of Mic and ITC groups, matched for the determinants of ALND, suggested that patients with Mic had increased recurrence rates and shorter OS when ALND was not performed. Our results are consistent with those of previous studies for patients with ITC but not for those with Mic. Randomised controlled clinical trials are still warranted to show with a high level of evidence if ALND can be safely omitted in patients with micrometastatic disease in SN.



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Neutrophil-to-lymphocyte ratio as a prognostic marker in locally advanced nasopharyngeal carcinoma: A pooled analysis of two randomised controlled trials

Publication date: November 2016
Source:European Journal of Cancer, Volume 67
Author(s): Melvin Lee Kiang Chua, Sze Huey Tan, Grace Kusumawidjaja, Ma Than Than Shwe, Shie Lee Cheah, Kam Weng Fong, Yoke Lim Soong, Joseph Tien Seng Wee, Terence Wee Kiat Tan
PurposeTo assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with International Union Against Cancer (UICC)–staged III/IVA,B nasopharyngeal carcinoma (NPC), who were enrolled into two randomised controlled trials of concurrent/adjuvant chemotherapy when added to radiotherapy (SQNP01), and induction chemotherapy when added to chemoradiotherapy (NCC0901).Material and methodsA post hoc analysis of pooled cohorts from SQNP01 (N = 221) and NCC0901 (N = 172) was performed. We employed a threshold of pre-treatment NLR = 3.0 (median) to stratify patients. Survival outcomes were compared using log-rank test. Multivariable Cox regression analyses were performed to assess association between NLR and overall survival (OS), disease-free survival (DFS), distant metastasis–free survival (DMFS), and locoregional recurrence–free survival (LRFS).ResultsHigh NLR (≥3.0) was associated with advanced T-status (p = 0.002), N-status (p = 0.002), overall UICC stage (p = 0.004), and high pre-treatment Epstein–Barr virus DNA titre (p = 0.001). High NLR was not associated with OS (0.94 [0.67–1.32], p = 0.7), DFS (0.98 [0.73–1.33], p = 0.9), DMFS (1.02 [0.66–1.57], p = 0.9), and LRFS (1.37 [0.84–2.22], p = 0.2) on univariable and multivariable analyses, while conventional clinical indices (T-status, N-status, and overall UICC stage) were prognostic of clinical outcomes. High NLR also did not predict for a treatment effect with the experimental arms in both trials.ConclusionOur pooled analyses that were confined to a homogenous patient population of locally advanced NPC do not suggest that NLR adds prognostic value to conventional clinical indices in identifying patients with unfavourable disease.



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Associations between childhood height and morphologically different variants of melanoma in adulthood

Publication date: November 2016
Source:European Journal of Cancer, Volume 67
Author(s): Kathrine Damm Meyle, Michael Gamborg, Lisbet Rosenkrantz Hölmich, Jennifer Lyn Baker
Aim of the studyMelanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants.MethodA cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7–13 years who were born from 1930 to 1989. Melanoma cases were identified via linkage to the national Danish Cancer Registry and subdivided into subtypes. Cox proportional hazards regressions were performed.ResultsA total of 2223 cases of melanoma distributed as 60% superficial spreading melanoma (SSM), 27.5% melanoma not otherwise specified (NOS), 8.5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95% confidence intervals [CI]: 1.13–1.27) for SSM, 1.19 (95% CI: 1.09–1.29) for melanoma NOS, and 1.21 (95% CI: 1.04–1.41) for NM. Further, growth patterns were linked to the melanoma variants with persistently tall children having an increased risk of developing SSM, melanoma NOS, or NM.ConclusionChildhood height is positively associated with the majority of the melanoma variants. These results suggest that the underlying processes contributing to childhood height and growth patterns interconnect early-life events with the predisposition to melanomagenesis in adulthood.



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Retrolaminar Migration of Intraocular Silicone Oil.

Background: Migration of intravitreal silicone to the retrolaminar optic nerve was detected pathologically in 1983, symptomatic migration to the subarachnoid space of the optic nerve was reported in 1994, and asymptomatic intraventricular silicone was first seen radiographically in 1999. Since then, little advance has been made in understanding this phenomenon despite numerous case reports. Although some authors have restricted their attention to cases of intraventricular silicone, we believe that these represent part of a clinical spectrum and that all cases with retrolaminar silicone should be considered. The pathophysiology of silicone migration may have significant implications for the management of patients after vitrectomy. Evidence Acquisition: Two patients were evaluated by the authors. An internet-based literature review was conducted, beginning with the key search terms "intraventricular, intracranial, subarachnoid, or optic nerve silicone," and "complications of vitrectomy or intravitreal silicone." Further searches cascaded from the initial search results. An additional 24 cases of retrolaminar migration of silicone oil were found and summarized. The relevant anatomy and pathophysiology were reviewed, with attention to additional information from enucleation studies, as well as to gaps in the current understanding of this process. Results: Retrolaminar migration of silicone oil may be more common than previously thought, especially in at-risk patient groups, and may be associated with visual and neurologic symptoms. Some impressions regarding the cause and significance of this syndrome seem incorrect. Although this process is likely linked to postoperative elevations of intraocular pressure, the exact mechanisms of silicone entry into the subarachnoid space remain undefined. A number of anatomic factors may influence the movement of silicone from the orbit and in the various compartments of the subarachnoid space and ventricular system, resulting in variability of clinical presentations and radiologic findings. Implications for clinical decision making and directions for further research are discussed. Conclusion: Greater awareness on the part of treating physicians, systematic study of at-risk populations, and advances in imaging technology will allow further insight into this phenomenon. (C) 2016 by North American Neuro-Ophthalmology Society

http://ift.tt/2cQDGWh

Avoiding Clinical Misinterpretation and Artifacts of Optical Coherence Tomography Analysis of the Optic Nerve, Retinal Nerve Fiber Layer, and Ganglion Cell Layer.

Background: Optical coherence tomography (OCT) has become an important tool for diagnosing optic nerve disease. The structural details and reproducibility of OCT continues to improve with further advances in technology. However, artifacts and misinterpretation of OCT can lead to clinical misdiagnosis of diseases if they go unrecognized. Evidence Acquisition: A literature review using PubMed combined with clinical and research experience. Results: We describe the most common artifacts and errors in interpretation seen on OCT in both optic nerve and ganglion cell analyses. We provide examples of the artifacts, discuss the causes, and provide methods of detecting them. In addition, we discuss a systematic approach to OCT analysis to facilitate the recognition of artifacts and to avoid clinical misinterpretation. Conclusions: While OCT is invaluable in diagnosing optic nerve disease, we need to be cognizant of the artifacts that can occur with OCT. Failure to recognize some of these artifacts can lead to misdiagnoses and inappropriate investigations. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially. (C) 2016 by North American Neuro-Ophthalmology Society

http://ift.tt/2d7x3kO

Obesity and Weight Loss in Idiopathic Intracranial Hypertension: A Narrative Review.

Background: Most patients with idiopathic intracranial hypertension (IIH) are obese. Weight loss is felt to be an important factor in improving IIH. The mechanism by which weight loss leads to a reduction in elevated intracranial pressure is unclear. Evidence from prospective studies evaluating the role of weight loss in IIH is lacking. Evidence Acquisition: We performed a detailed review of the published literature regarding the association of IIH and obesity, including proposed pathogenetic mechanisms, and the effect of weight loss and weight-loss interventions in IIH. References were identified by searching PubMed with the terms idiopathic intracranial hypertension and weight loss. Additional citations were found in the identified references. Results: Over 90% of IIH patients are obese or overweight. The risk of IIH increases as a function of body mass index (BMI) and weight gain over the preceding year. The risk of IIH-induced vision loss also increases with increasing BMI, especially with BMI >40 kg/m2. Several mechanisms have been proposed linking obesity to the development of IIH but the pathophysiology remains unknown. Published studies and clinical observations strongly support weight loss as an effective treatment, although there are no prospective controlled trials. Weight loss in the range of 6%-10% often leads to IIH remission. Weight loss of >=5% at 1 year is achieved in roughly 50%-70% of patients if they are enrolled in a high-intensity lifestyle modification program and in 20%-35% of patients if they direct their own weight loss. Weight is typically regained over 1-3 years but about a third of patients maintain >=5% weight loss over the long term. Patients treated initially with lifestyle modification therapy show a modest persisting benefit over self-directed patients. Selected commercial weight loss programs also may improve long-term maintenance of weight loss. New antiobesity drugs significantly improve the proportion of obese patients who have >=5% loss of weight at 1 year. Conclusions: Obesity is an important contributing factor for the development of IIH, although the pathophysiological mechanism linking obesity to IIH is unknown. The risk of developing IIH and associated visual loss increases with increasing BMI. Weight loss is an effective treatment for IIH. Long-term maintenance of initial weight loss is helped modestly by lifestyle modification programs and possibly by selected commercial weight loss programs. New antiobesity drugs may provide further options for IIH therapy in the future. (C) 2016 by North American Neuro-Ophthalmology Society

http://ift.tt/2cQEaMf

Re-Treatment With Ethambutol After Toxic Optic Neuropathy.

There are no data in the literature regarding the safety of re-treatment with ethambutol for recurrent mycobacterial infection after prior ethambutol-induced optic neuropathy. We describe a patient who developed optic neuropathy attributed to ethambutol, recovered fully after drug withdrawal, and tolerated a 14-month long re-treatment 10 years later without developing recurrent optic neuropathy. (C) 2016 by North American Neuro-Ophthalmology Society

http://ift.tt/2d7wZ4B

IgG4 Disease: Is It or Isn't It?.

No abstract available

http://ift.tt/2cQEsmt

Low-level laser therapy reduces the fatigue index in the ankle plantar flexors of healthy subjects

Abstract

Low-level laser therapy (LLLT) has been suggested as a resource capable of increasing resistance to fatigue and enhancing muscle performance through its metabolic and photochemical effects. This study evaluated the immediate effects of the application of LLLT on neuromuscular performance of the plantar ankle flexors in healthy subjects through a fatigue-induced protocol. This is a randomized controlled clinical trial, attended by 60 young and physically active volunteers of both genders. The subjects were randomly assigned into three groups, control, placebo, and laser, and underwent a preliminary evaluation of the isokinetic performance of plantar flexors and electromyographic activity of the soleus muscle to ensure homogeneity between groups. After the application of the respective intervention protocols, participants were induced to fatigue by performing 100 isokinetic concentric contractions of ankle plantar flexors at a speed of 90°/s. The dynamometric fatigue index (DFI) and median frequency were recorded during the fatigue protocol for comparison between groups. The group receiving the laser application showed significantly lower dynamometric fatigue index (p = 0.036) when compared to control and placebo groups. In relation to the median frequency during the fatigue test, there was a decrease in all groups, however with no differences between them. We suggest that LLLT being applied prior to exercise can reduce the fatigue index in the ankle plantar flexors of healthy subjects.

http://ift.tt/2cGGLGv

Photobiomodulation therapy reduces apoptotic factors and increases glutathione levels in a neuropathic pain model

Abstract

Neuropathic pain (NP) is caused by damage to the nervous system due to reactive oxygen spices (ROS) increase, antioxidants reduction, ATP production imbalance, and induction of apoptosis. In this investigation, we applied low-level laser 660 nm (photobiomodulation therapy) as a new strategy to modulate pain. In order to study the effects of photobiomodulation therapy (660 nm) on NP, chronic constriction injury (CCI) model was selected. Low-level laser of 660 nm was used for 2 weeks. Thermal and mechanical hyperalgesia were measured before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. Expression of p2x3, Bax, and bcl2 protein was measured by western blotting. The amount of glutathione (GSH) was measured in the spinal cord by continuous spectrophotometric rate determination method. The results are presented as mean ± SD. Statistical analysis of data was carried out using SPSS 21. CCI decreased the pain threshold, 2-week photobiomodulation therapy significantly increased mechanical and thermal threshold, decreased P2X3 expression (p < 0.001), and increased bcl2 expression (p < 0.01), but it was not effective on the Bax expression. We speculated that although photobiomodulation therapy increased ROS generation, it increased antioxidants such as GSH. Increase in bcl2 is another mitochondrial protection mechanism for cell survival and that pain relief and decrease in P2X3 expression confirm it.

http://ift.tt/2ckM1SK

Increase in the nitric oxide release without changes in cell viability of macrophages after laser therapy with 660 and 808 nm lasers

Abstract

The aim of this study was to evaluate the influence of low-level laser therapy (LLLT) with different parameters and wavelengths on nitric oxide (NO) release and cell viability. Irradiation was performed with Ga-Al-As laser, continuous mode and wavelengths of 660 and 808 nm at different energy and power densities. For each wavelength, powers of 30, 50, and 100 mW and times of 10, 30, and 60 s were used. NO release was measured using Griess reaction, and cell viability was evaluated by mitochondrial reduction of bromide 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to formazan. LLLT promoted statistically significant changes in NO release and MTT value only at the wavelength of 660 nm (p < 0.05). LLLT also promoted an increase in the NO release and cell viability when the energy densities 64 (p = 0.04) and 214 J/cm² (p = 0.012), respectively, were used. LLLT has a significant impact on NO release without affecting cell viability, but the significance of these findings in the inflammatory response needs to be further studied.

http://ift.tt/2cGGJyq

Modulation of nociception by medial pre-optic area orexin a receptors and its relation with morphine in male rats

Publication date: Available online 15 September 2016
Source:Brain Research Bulletin
Author(s): Amir Hossein Emam, Naeimeh Hajesfandiari, Siamak Shahidi, Alireza Komaki, Maziar Ganji, Abdolrahman Sarihi
IntroductionRecent studies have shown that medial pre-optic area (MPOA) of hypothalamus are involved in nociception. Orexin A (hypocretin 1) has been found to have numerous applications including pain modulation. However, the role of orexin A receptors in the MPOA on the nociception has not been yet studied. Therefore, the aim of the present study is to investigate the effect of orexin A microinjection on MPOA on the nociception transmission and morphine induced analgesia in adult male rats.MethodsUsing stereotaxic surgery, a cannula was implanted at a site 1mm above the MPOA in the anesthetized rats. After the recovery period, tail-flick (TF) latency was measured as 0, 15, 30, 45 and 60min following the onset of two experimental protocols. Two experiments were carried out. Experiment 1: The male rats received intra-MPOA of 25, 100, 1000, 10000pmol/0.5μl orexin A or 0.5μl of aCSF (control, just 5min before the TF assay. Experiment 2: The aim of this experiment was to examine the effect of orexin microinjection into MPOA on morphine analgesia (3mg/kg,s.c). Morphine was administered 30min before orexin A intra-MPOA microinjection (four doses similar to experiment 1) or aCSF, then TF latency was measured.ResultsThe results indicated that microinjection of orexin A into the MPOA showed anti-nociceptive effect in a time-dependent manner. Dose response curve results also revealed that the maximum effective dose of orexin A injection into MPOA for pain inhibition is 1000pmol/0.5μl. Co-administration of systemic morphine and orexin into the MPOA has additive analgesia with different time course compared morphine or orexin alone.ConclusionIt can be concluded that MPOA OrexinA receptors play an important role in the modulation of pain in normal and morphine treated male rats.



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When machine vision meets histology: A comparative evaluation of model architecture for classification of histology sections

Publication date: January 2017
Source:Medical Image Analysis, Volume 35
Author(s): Cheng Zhong, Ju Han, Alexander Borowsky, Bahram Parvin, Yunfu Wang, Hang Chang
Classification of histology sections in large cohorts, in terms of distinct regions of microanatomy (e.g., stromal) and histopathology (e.g., tumor, necrosis), enables the quantification of tumor composition, and the construction of predictive models of genomics and clinical outcome. To tackle the large technical variations and biological heterogeneities, which are intrinsic in large cohorts, emerging systems utilize either prior knowledge from pathologists or unsupervised feature learning for invariant representation of the underlying properties in the data. However, to a large degree, the architecture for tissue histology classification remains unexplored and requires urgent systematical investigation. This paper is the first attempt to provide insights into three fundamental questions in tissue histology classification: I. Is unsupervised feature learning preferable to human engineered features? II. Does cellular saliency help? III. Does the sparse feature encoder contribute to recognition? We show that (a) in I, both Cellular Morphometric Feature and features from unsupervised feature learning lead to superior performance when compared to SIFT and [Color, Texture]; (b) in II, cellular saliency incorporation impairs the performance for systems built upon pixel-/patch-level features; and (c) in III, the effect of the sparse feature encoder is correlated with the robustness of features, and the performance can be consistently improved by the multi-stage extension of systems built upon both Cellular Morphmetric Feature and features from unsupervised feature learning. These insights are validated with two cohorts of Glioblastoma Multiforme (GBM) and Kidney Clear Cell Carcinoma (KIRC).

Graphical abstract

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Primary cutaneous cryptococcosis during infliximab therapy

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Trabectedin as a chemotherapy option for patients with brca deficiency

Publication date: Available online 15 September 2016
Source:Cancer Treatment Reviews
Author(s): Bradley J. Monk, Domenica Lorusso, Antoine Italiano, Stan B. Kaye, Miguel Aracil, Adnan Tanović, Maurizio D'Incalci
Trabectedin is a marine-derived product that was originally isolated from the Caribbean sea squirt Ecteinascidia turbinata and the first anticancer marine drug to be approved by the European Union. It is currently used as a single agent for the treatment of patients with soft tissue sarcoma after failure of anthracyclines and ifosfamide, or for those patients who are unsuited to receive these agents, and in patients with relapsed, platinum-sensitive ovarian cancer in combination with pegylated liposomal doxorubicin. Trabectedin has a unique multi-faceted mechanism of action that involves transcription regulation and DNA repair systems, including transcription-coupled nucleotide excision repair and homologous recombination repair (HRR) as the main hallmarks of its antiproliferative activity. In addition, trabectedin has shown the ability to modulate the tumor microenvironment. Indeed, the activity of trabectedin is related to altered function and expression of DNA repair genes, such as BRCA1 (BReast-CAncer susceptibility gene 1) and BRCA2. The particular sensitivity of sarcoma, ovarian and breast cancer cells deficient in HRR, previously observed in preclinical models, now has been confirmed in the clinical setting as well, suggesting that BRCA mutations are associated with improved clinical responses to trabectedin. Current efforts are focused on the evaluation of these unique features of trabectedin and on the identification of predictive factors for patients with an objective to determine whether a deficiency of HRR DNA repair pathway could impact the clinical benefit achieved from trabectedin.



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Exploring the venom of the forest cobra snake: Toxicovenomics and antivenom profiling of Naja melanoleuca

Publication date: 6 January 2017
Source:Journal of Proteomics, Volume 150
Author(s): Line P. Lauridsen, Andreas H. Laustsen, Bruno Lomonte, José María Gutiérrez
A toxicovenomic analysis of the venom of the forest cobra, N. melanoleuca, was performed, revealing the presence of a total of 52 proteins by proteomics analysis. The most abundant proteins belong to the three-finger toxins (3FTx) (57.1wt%), which includes post-synaptically acting α-neurotoxins. Phospholipases A2 (PLA2) were the second most abundant group of proteins (12.9wt%), followed by metalloproteinases (SVMPs) (9.7wt%), cysteine-rich secretory proteins (CRISPs) (7.6wt%), and Kunitz-type serine proteinase inhibitors (3.8wt%). A number of additional protein families comprised each <3wt% of venom proteins. A toxicity screening of the fractions, using the mouse lethality test, identified toxicity in RP-HPLC peaks 3, 4, 5 and 8, all of them containing α-neurotoxins of the 3FTx family, whereas the rest of the fractions did not show toxicity at a dose of 0.53mg/kg. Three polyspecific antivenoms manufactured in South Africa and India were tested for their immunoreactivity against crude venom and fractions of N. melanoleuca. Overall, antivenoms immunorecognized all fractions in the venom, the South African antivenom showing a higher titer against the neurotoxin-containing fractions. This toxicovenomic study identified the 3FTx group of α-neurotoxins in the venom of N. melanoleuca as the relevant targets to be neutralized.Biological significanceA toxicovenomic analysis of the venom of the forest cobra, also known as black cobra, Naja melanoleuca, was performed. Envenomings by this elapid species are characterized by a progressive descending paralysis which starts with palpebral ptosis and, in severe cases, ends up with respiratory arrest and death. A total of 52 different proteins were identified in this venom. The most abundant protein family was the three-finger toxin (3FTx) family, which comprises almost 57.1wt% of the venom, followed by phospholipases A2 (PLA2) (12.9wt%). In addition, several other protein families were identified in a much lower percentage in the venom. A toxicity screening of the fractions, using the mouse lethality assay, identified four peaks as those having toxicity higher than that of the crude venom. These fractions predominantly contain α-neurotoxins of the 3FTx family. This toxicovenomic characterization agrees with the clinical and experimental manifestations of envenomings by this species, in which a strong neurotoxic effect predominates. Therefore, our findings suggest that immunotherapy against envenomings by N. melanoleuca should be directed towards the neutralization of 3FTxs; this has implications for the improvement of current antivenoms and for the development of novel antivenoms based on biotechnological approaches. A screening of the immunoreactivity of three antivenoms being distributed in sub-Saharan Africa revealed that they immunoreact with the fractions containing α-neurotoxins, although with different antibody titers.

Graphical abstract

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Multicentric study of the effect of pre-analytical variables in the quality of plasma samples stored in biobanks using different complementary proteomic methods

Publication date: 6 January 2017
Source:Journal of Proteomics, Volume 150
Author(s): Jesús Mateos, Isabel Carneiro, Fernando Corrales, Felix Elortza, Alberto Paradela, Manuel Sánchez del Pino, Ibon Iloro, Miguel Marcilla, Maria Isabel Mora, Luz Valero, Sergio Ciordia, Verónica Fernández, Maria Antonia Fortuño, Isabel García-Sánchez, Rosario Martínez, Maria Angeles Muñoz, Clara Rodriguez, Nieves Doménech
Analytical proteomics has experienced exponential progress in the last decade and can be expected to lead research studies on diagnostic and therapeutic biomarkers in the near future. Because the development of this type of analysis requires the use of a large number of human samples with a minimum of quality requirements, our objective was to identify appropriate indicators for quality control of plasma samples stored in biobanks for research in proteomics. To accomplish this, plasma samples from 100 healthy donors were obtained and processed according to the pre-analytical variables of: a) time delay for the first centrifugation of the original blood sample (4 or 24h) and b) number of freeze/thaw cycles (1, 2 or 3) of the processed plasma samples. The analyses of samples were performed by different and complementary methods such as SPE MALDI-TOF, DIGE, shotgun (iTRAQ, nLC MALDI TOF/TOF) and targeted nLC MS/MS proteomic techniques (SRM). In general, because the distribution of proteins in all samples was found to be very similar, the results shown that delayed processing of blood samples and the number of freeze/thaw cycles has little or no effect on the integrity of proteins in the plasma samples.SignificanceThe results of the present work indicate that blood proteins in plasma are broadly insensitive to such preanalytical variables as delayed processing or freeze/thaw cycles when analyzed at the peptide level. Although there are other studies related to protein stability of clinical samples with similar results, what is remarkable about our work is the large number of plasma samples examined and that our analyses assessed protein integrity by combining a wide set of complementary proteomic approaches performed at different proteomic platform participating laboratories that all yielded similar results. We believe our study is the most comprehensive performed to date to determine the changes in proteins induced by delayed sample processing and plasma freeze/thaw cycles.

Graphical abstract

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A Phase 1 Study of Arginase Inhibitor CB-1158 in Combination With Immune Checkpoint Therapy in Solid Tumors

Conditions:   Metastatic Cancer;   Solid Tumors;   Non-small Cell Lung Cancer;   Colo-Rectal Cancer;   Gastric Cancer;   Renal Cell Carcinoma;   Squamous-cell Carcinomas of the Head and Neck
Interventions:   Drug: CB-1158;   Drug: Nivolumab
Sponsor:   Calithera Biosciences, Inc
Recruiting - verified September 2016

http://ift.tt/2cTQz0G

Editorial Board and Contents

Publication date: October 2016
Source:Trends in Cell Biology, Volume 26, Issue 10





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CD28 / CTLA-4/ICOS haplotypes confers susceptibility to Graves’ disease and modulates clinical phenotype of disease

Abstract

Graves' disease, an autoimmune disease with heterogeneous symptoms including Graves' orbitopathy, has a combined genetic/environmental background, where variations within CD28/CTLA-4/ICOS genes are considered as disease markers.

Association of CD28c.17+3T>C(rs3116496), CTLA-4g.319C>T(rs5742909), CTLA-4c.49A>G(rs231775), CTLA-4g.*642AT(8_33), CT60(rs3087243), Jo31(rs11571302), ICOSc.1554+4GT(8_15) polymorphisms with susceptibility to Graves' disease and clinical outcome was investigated. The study group comprised of 561 Polish Caucasians, including 172 unrelated Graves' disease patients. CTLA-4c.49A>G, CTLA-4g.319C>T, and CT60 were genotyped by PCR–RFLP; Jo31 and CD28c.17+3C>T by minisequencing; CTLA-4g.*642AT(8_33) and ICOSc.1554+4GT(8_15)—PCR and fluorescence-based technique. CD28c.17+3T>C(rs3116496)T/CTLA-4g.319C>T(rs5742909)C/CTLA-4c.49A>G(rs231775)G/CTLA-4g.*642AT(8_33)(AT_16–21)/CT60(rs3087243)G/Jo31(rs11571302)G/ICOSc.1554+4GT(8_15)(m) and TCA(AT_<16)GT(m) haplotypes increased risk of Graves' disease, especially in males, as well as overall Graves' orbitopathy development with severe outcome. TCG(AT_16–21)GG(l) haplotype increased risk of Graves' disease and reduced the chance of successful medical treatment. Although this haplotype was mainly observed in patients without signs of Graves' orbitopathy, if Graves' orbitopathy developed it favored a Graves' orbitopathy outcome. Haplotype TCA(AT_>21)GT(m) increased Graves' disease risk in women and, in all patients, was linked to Graves' disease without Graves' orbitopathy. TCG(AT_<16)GG(m) haplotype was predominantly observed in patients without Graves' orbitopathy, whereas TCA(AT_16–21)GG(m) was absent in those patients. TCA(AT_16–21)GG(m) occurred in patients with a mild Graves' orbitopathy outcome. The marker CTLA-4g.*642AT(8_33) was the only independent Graves' disease risk factor, whereas CT60 was an independent factor for disease progression. Sporadic Graves' disease was related to presence of CTLA-4c.49A>G[A] and the rare CTLA-4g.319C>T[T] allele variant. Familial background of the disease was exclusively associated with CTLA-4g.*642AT(8_33)[AT_>21]/[AT_>21] genotype. CD28/CTLA-4/ICOS loci may confer inherited susceptibility to Graves' disease or may be involved in susceptibility to Graves' disease and play a pathogenetic role.

http://ift.tt/2ccrJrr

Late-onset nonlesional nondominant frontal lobe seizures presenting as ictal dyscalculia

Publication date: Available online 15 September 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Meng-Tsang Hsieh, Ming-Chi Lai, Kao-Min Lin, Chin-Wei Huang




http://ift.tt/2cC8bk4

CD28 / CTLA-4/ICOS haplotypes confers susceptibility to Graves’ disease and modulates clinical phenotype of disease

Abstract

Graves' disease, an autoimmune disease with heterogeneous symptoms including Graves' orbitopathy, has a combined genetic/environmental background, where variations within CD28/CTLA-4/ICOS genes are considered as disease markers.

Association of CD28c.17+3T>C(rs3116496), CTLA-4g.319C>T(rs5742909), CTLA-4c.49A>G(rs231775), CTLA-4g.*642AT(8_33), CT60(rs3087243), Jo31(rs11571302), ICOSc.1554+4GT(8_15) polymorphisms with susceptibility to Graves' disease and clinical outcome was investigated. The study group comprised of 561 Polish Caucasians, including 172 unrelated Graves' disease patients. CTLA-4c.49A>G, CTLA-4g.319C>T, and CT60 were genotyped by PCR–RFLP; Jo31 and CD28c.17+3C>T by minisequencing; CTLA-4g.*642AT(8_33) and ICOSc.1554+4GT(8_15)—PCR and fluorescence-based technique. CD28c.17+3T>C(rs3116496)T/CTLA-4g.319C>T(rs5742909)C/CTLA-4c.49A>G(rs231775)G/CTLA-4g.*642AT(8_33)(AT_16–21)/CT60(rs3087243)G/Jo31(rs11571302)G/ICOSc.1554+4GT(8_15)(m) and TCA(AT_<16)GT(m) haplotypes increased risk of Graves' disease, especially in males, as well as overall Graves' orbitopathy development with severe outcome. TCG(AT_16–21)GG(l) haplotype increased risk of Graves' disease and reduced the chance of successful medical treatment. Although this haplotype was mainly observed in patients without signs of Graves' orbitopathy, if Graves' orbitopathy developed it favored a Graves' orbitopathy outcome. Haplotype TCA(AT_>21)GT(m) increased Graves' disease risk in women and, in all patients, was linked to Graves' disease without Graves' orbitopathy. TCG(AT_<16)GG(m) haplotype was predominantly observed in patients without Graves' orbitopathy, whereas TCA(AT_16–21)GG(m) was absent in those patients. TCA(AT_16–21)GG(m) occurred in patients with a mild Graves' orbitopathy outcome. The marker CTLA-4g.*642AT(8_33) was the only independent Graves' disease risk factor, whereas CT60 was an independent factor for disease progression. Sporadic Graves' disease was related to presence of CTLA-4c.49A>G[A] and the rare CTLA-4g.319C>T[T] allele variant. Familial background of the disease was exclusively associated with CTLA-4g.*642AT(8_33)[AT_>21]/[AT_>21] genotype. CD28/CTLA-4/ICOS loci may confer inherited susceptibility to Graves' disease or may be involved in susceptibility to Graves' disease and play a pathogenetic role.

http://ift.tt/2ccrJrr

Pesticide exposure and neurodevelopment in children aged 6 to 9 years from Talamanca, Costa Rica

Publication date: Available online 15 September 2016
Source:Cortex
Author(s): Berna van Wendel de Joode, Ana María Mora, Christian H. Lindh, David Hernández-Bonilla, Leonel Córdoba, Catharina Wesseling, Jane A. Hoppin, Donna Mergler
Certain pesticides may affect children's neurodevelopment. We assessed whether pesticide exposure was associated with impaired neurobehavioral outcomes in children aged 6 to 9 years.We conducted a cross-sectional study in 140 children living near banana plantations and plantain farms in the Talamanca County, Costa Rica and assessed their neurobehavioral performance. Exposure was determined by analyzing urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy), mancozeb (ethylenethiourea, ETU), and pyrethroids (3-phenoxybenzoic acid, 3-PBA). Repeated urine samples were obtained for 36 children. We estimated associations of pesticide concentrations with neurobehavioral outcomes using multivariable linear and logistic regression models.Median (25th-75th percentiles) TCPy, ETU, and 3-PBA concentrations were 1.4 (0.7-3.1), 1.2 (0.7-3.0), and 0.8 (0.5-1.5) μg/L, respectively. Intraclass correlation coefficients (ICC) ranged between 0.43 and 0.63. After adjustment for potential confounders, higher urinary TCPy concentrations were associated with poorer working memory in boys (n=59) (β per 10-fold increase in TCPy concentrations = -7.5, 95% CI: -14.4, -0.7); poorer visuo-motor coordination (β = -1.4, 95% CI: -2.7, -0.1); increased prevalence of parent-reported cognitive problems/inattention (adjusted OR per 10-fold increase in urinary concentrations = 3.9, 95% CI: 1.0, 16.0), oppositional disorders (aOR= 5.8, 95% CI: 1.6, 22.9), and ADHD (aOR = 6.8, 95% CI: 1.8, 28.6), and; decreased ability to discriminate colors (aOR = 6.6, 95% CI: 1.6, 30.3; the higher the score the worse). Higher ETU concentrations were associated with poorer verbal learning outcomes (β = -7.0, 95% CI: -12.7, -1.3). Higher 3-PBA concentrations were associated with poorer processing speed scores, particularly in girls (β = -8.8, 95% CI: -16.1, -1.4).Our findings indicate that children living near banana and plantain plantations are exposed to pesticides that may affect their neurodevelopment, which for certain domains may differ between boys and girls. We recommend the implementation of measures to reduce pesticide exposure in children living nearby banana plantations.

Graphical abstract

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Scholar : These new articles for Bulletin of Spanish Studies are available online

The online platform for Taylor & Francis Online content New for Bulletin of Spanish Studies and online now on Taylor & Francis Online: Original Articles 'Me juzgo por natural de Madrid': Vincencio Carducho, Theorist and Painter of Spain's Court Capital Laura R. Bass & Jean Andrews Pages: 1-37 | DOI: 10.1080/14753820.2016.1227040 Passionate about social media? Read our Social Media Research collection. This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for AIDS Care are available online

The online platform for Taylor & Francis Online content New for AIDS Care and online now on Taylor & Francis Online: Original Articles Mobile phone use for a social strategy to improve antiretroviral refill experience at a low-resource HIV clinic: patient responses from Nigeria Adedotun A. Adetunji, Sufiyan A. Muyibi, Martins Imhansoloeva, Olusola M. Ibraheem, Adegbenga Sunmola, Olubunmi O. Kolawole, Oluwasina O. Akinrinsola, James O. Ojo-Osagie, Olusola A. Mosuro, Josephine O. Abiolu, Achiaka E. Irabor, Prosper Okonkwo, Isaac F. Adewole & Babafemi O. Taiwo Pages: 1-4 | DOI: 10.1080/09540121.2016.1226476 Routledge Journals Gerontology Portfolio - find out more here: http://ift.tt/2crU79K This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

One-Carbon Metabolism in Health and Disease

Publication date: Available online 15 September 2016
Source:Cell Metabolism
Author(s): Gregory S. Ducker, Joshua D. Rabinowitz
One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention.

Teaser

One-carbon metabolism supports biosynthesis, amino acid homeostasis, epigenetic maintenance, and redox defense. Ducker and Rabinowitz review this metabolism, from the biochemical basics of folate to organismal physiology, with an emphasis on recent advances in understanding one-carbon metabolic cycles, compartmentalization, and pathway activity both in normal physiology and in human disease.


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LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells

Publication date: Available online 15 September 2016
Source:Cell Metabolism
Author(s): Almut Brand, Katrin Singer, Gudrun E. Koehl, Marlene Kolitzus, Gabriele Schoenhammer, Annette Thiel, Carina Matos, Christina Bruss, Sebastian Klobuch, Katrin Peter, Michael Kastenberger, Christian Bogdan, Ulrike Schleicher, Andreas Mackensen, Evelyn Ullrich, Stefan Fichtner-Feigl, Rebecca Kesselring, Matthias Mack, Uwe Ritter, Maximilian Schmid, Christian Blank, Katja Dettmer, Peter J. Oefner, Petra Hoffmann, Stefan Walenta, Edward K. Geissler, Jacques Pouyssegur, Andreas Villunger, André Steven, Barbara Seliger, Stephan Schreml, Sebastian Haferkamp, Elisabeth Kohl, Sigrid Karrer, Mark Berneburg, Wolfgang Herr, Wolfgang Mueller-Klieser, Kathrin Renner, Marina Kreutz
Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Here we show that LDHA-associated lactic acid accumulation in melanomas inhibits tumor surveillance by T and NK cells. In immunocompetent C57BL/6 mice, tumors with reduced lactic acid production (Ldha^low) developed significantly slower than control tumors and showed increased infiltration with IFN-γ-producing T and NK cells. However, in Rag2^–/–γc^–/– mice, lacking lymphocytes and NK cells, and in Ifng^–/– mice, Ldha^low and control cells formed tumors at similar rates. Pathophysiological concentrations of lactic acid prevented upregulation of nuclear factor of activated T cells (NFAT) in T and NK cells, resulting in diminished IFN-γ production. Database analyses revealed negative correlations between LDHA expression and T cell activation markers in human melanoma patients. Our results demonstrate that lactic acid is a potent inhibitor of function and survival of T and NK cells leading to tumor immune escape.

Graphical abstract

Teaser

Brand et al. link altered tumor glucose metabolism and immune escape and show that increased lactic acid production by LDHA in cancer cells impairs cytokine production, in particular IFN-γ, in tumor-infiltrating T cells and NK cells, thereby inhibiting tumor immunosurveillance and promoting tumor growth.


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AMPK/α-Ketoglutarate Axis Dynamically Mediates DNA Demethylation in the Prdm16 Promoter and Brown Adipogenesis

Publication date: Available online 15 September 2016
Source:Cell Metabolism
Author(s): Qiyuan Yang, Xingwei Liang, Xiaofei Sun, Lupei Zhang, Xing Fu, Carl J. Rogers, Anna Berim, Shuming Zhang, Songbo Wang, Bo Wang, Marc Foretz, Benoit Viollet, David R. Gang, Buel D. Rodgers, Mei-Jun Zhu, Min Du
Promoting brown adipose tissue (BAT) development is an attractive strategy for the treatment of obesity, as activated BAT dissipates energy through thermogenesis; however, the mechanisms controlling BAT formation are not fully understood. We hypothesized that as a master regulator of energy metabolism, AMP-activated protein kinase (AMPK) may play a direct role in the process and found that AMPKα1 (PRKAA1) ablation reduced Prdm16 expression and impaired BAT development. During early brown adipogenesis, the cellular levels of α-ketoglutarate (αKG), a key metabolite required for TET-mediated DNA demethylation, were profoundly increased and required for active DNA demethylation of the Prdm16 promoter. AMPKα1 ablation reduced isocitrate dehydrogenase 2 activity and cellular αKG levels. Remarkably, postnatal AMPK activation with AICAR or metformin rescued obesity-induced suppression of brown adipogenesis and thermogenesis. In summary, AMPK is essential for the epigenetic control of BAT development through αKG, thus linking a metabolite to progenitor cell differentiation and thermogenesis.

Graphical abstract

Teaser

Yang et al. show that AMPK is essential for brown adipose tissue development through the elevation of α-ketoglutarate, which facilitates TET-mediated DNA demethylation of the Prdm16 promoter, committing progenitor cells to brown adipogenic differentiation. Postnatal AMPK activation by metformin rescues the obesity-induced attenuation of brown adipogenesis.


http://ift.tt/2cDBUG9

Toward a model-based patient selection strategy for proton therapy: External validation of photon-derived normal tissue complication probability models in a head and neck proton therapy cohort

Publication date: Available online 15 September 2016
Source:Radiotherapy and Oncology
Author(s): Pierre Blanchard, Andrew J. Wong, G. Brandon Gunn, Adam S. Garden, Abdallah S.R. Mohamed, David I. Rosenthal, Joseph Crutison, Richard Wu, Xiaodong Zhang, X. Ronald Zhu, Radhe Mohan, Mayankkumar V. Amin, C. David Fuller, Steven J. Frank
ObjectiveTo externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT).MethodsThis prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve.Results192 patients were included. The most prevalent tumor site was oropharynx (n=86, 45%), followed by sinonasal (n=28), nasopharyngeal (n=27) or parotid (n=27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6months after PBT; 0.70 versus 0.80 for dry mouth 6months after PBT; and 0.73 versus 0.85 for hypothyroidism 12months after PBT.ConclusionAlthough a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC.



http://ift.tt/2d4LTbP

The effects of a multigrowth factor-containing cream on recovery after laser treatment: a double-blinded, randomized, split-face controlled study

Summary

Background

Patients who receive laser treatments may experience transient erythema, edema, and crusts for several days. Although a variety of growth factor-containing creams for promoting recovery after laser treatment are available, evidence for their efficacy remains insufficient.

Aims

We performed a randomized controlled split-face study to assess the effects of a multigrowth factor (MGF)-containing cream on patients recovering from laser treatment.

Materials and Methods

Twenty patients underwent treatment using an ablative fractional laser and were randomized with respect to the side of the face treated with an MGF-containing cream or control cream. We measured post-treatment erythema and pigmentation using the erythema and melanin indices, respectively, and evaluated the total area of microcrusts with dermoscopy. Additionally, patient satisfaction levels and global improvement scores were assessed.

Results

We found that the area of microcrusts was significantly smaller in the MGF-treated regions. Global improvement scores for post-treatment edema and wrinkles were also significantly higher for MGF cream-treated sides than for the control sides.

Conclusion

The MGF cream-treated regions showed a more rapid recovery from crusts and edema. Thus, the use of an MGF-containing cream after laser treatment can effectively reduce recovery time.

http://ift.tt/2crOcl4

Global Landscape and Regulatory Principles of DNA Methylation Reprogramming for Germ Cell Specification by Mouse Pluripotent Stem Cells

Publication date: Available online 15 September 2016
Source:Developmental Cell
Author(s): Kenjiro Shirane, Kazuki Kurimoto, Yukihiro Yabuta, Masashi Yamaji, Junko Satoh, Shinji Ito, Akira Watanabe, Katsuhiko Hayashi, Mitinori Saitou, Hiroyuki Sasaki
Specification of primordial germ cells (PGCs) activates epigenetic reprogramming for totipotency, the elucidation of which remains a fundamental challenge. Here, we uncover regulatory principles for DNA methylation reprogramming during in vitro PGC specification, in which mouse embryonic stem cells (ESCs) are induced into epiblast-like cells (EpiLCs) and then PGC-like cells (PGCLCs). While ESCs reorganize their methylome to form EpiLCs, PGCLCs essentially dilute the EpiLC methylome at constant, yet different, rates between unique sequence regions and repeats. ESCs form hypomethylated domains around pluripotency regulators for their activation, whereas PGCLCs create demethylation-sensitive domains around developmental regulators by accumulating abundant H3K27me3 for their repression. Loss of PRDM14 globally upregulates methylation and diminishes the hypomethylated domains, but it preserves demethylation-sensitive domains. Notably, female ESCs form hypomethylated lamina-associated domains, while female PGCLCs effectively reverse such states into a more normal configuration. Our findings illuminate the unique orchestration of DNA methylation and histone modification reprogramming during PGC specification.

Graphical abstract

Teaser

DNA methylation reprogramming is important for germ cell development and embryogenesis. Shirane et al. constructed DNA methylation maps of mouse primordial germ cell (PGC)-like cells, produced from embryonic stem-cell-derived epiblast-like cells, as a model of PGC specification. These analyses suggest distinct methylation regulation in stem cells versus germ cells.


http://ift.tt/2cBNhkS

Ultrastrong trapping of VEGF by graphene oxide: Anti-angiogenesis application

Publication date: December 2016
Source:Biomaterials, Volume 109
Author(s): Pei-Xin Lai, Chung-Wein Chen, Shih-Chun Wei, Tzu-Yu Lin, Hong-Jyuan Jian, Irving Po-Jung Lai, Ju-Yi Mao, Pang-Hung Hsu, Han-Jia Lin, Wen-Shyong Tzou, Shiow-Yi Chen, Scott G. Harroun, Jui-Yang Lai, Chih-Ching Huang
Angiogenesis is the process of formation of new blood vessels, which is essential to human biology, and also plays a crucial role in several pathologies such as tumor growth and metastasis, exudative age-related macular degeneration, and ischemia. Vascular endothelial growth factor (VEGF), in particular, VEGF-A165 is the most important pro-angiogenic factor for angiogenesis. Thus, blocking the interaction between VEGFs and their receptors is considered an effective anti-angiogenic strategy. We demonstrate for that first time that bovine serum albumin-capped graphene oxide (BSA−GO) exhibits high stability in physiological saline solution and possesses ultrastrong binding affinity towards VEGF-A165 [dissociation constant (Kd) ∼3 × 10⁻¹² M], which is at least five orders of magnitude stronger than that of high-abundant plasma proteins such as human serum albumin, fibrinogen, transferrin, and immunoglobulin G. Due to the surprising binding specificity of BSA−GO for VEGF-A165 in complex plasma fluid, we have also studied the anti-angiogenic effects in vitro and in vivo. Results show that BSA−GO not only effectively inhibits the proliferation, migration and tube formation of human umbilical vein endothelial cells, but also strongly disturbs the physiological process of angiogenesis in chick chorioallantoic membrane and blocks VEGF-A165-induced blood vessel formation in rabbit corneal neovascularization. Our findings indicate that GO nanomaterials can potentially act as therapeutic anti-angiogenic agents via ultrastrong VEGF adsorption and its activity suppression.

Graphical abstract

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Treatment of spinal cord injury by an advanced cell transplantation technology using brain-derived neurotrophic factor-transfected mesenchymal stem cell spheroids

Publication date: December 2016
Source:Biomaterials, Volume 109
Author(s): Satoshi Uchida, Kentaro Hayakawa, Toru Ogata, Sakae Tanaka, Kazunori Kataoka, Keiji Itaka
Curing spinal cord injury (SCI) is challenging because of the onset of multiple and irreversible pathological responses to such injury. To suppress the responses, we employed an advanced cell transplantation technology integrating three-dimensional spheroid cell transplantation with non-viral gene transfection using biodegradable polycations. Brain-derived neurotrophic factor (BDNF)-transfected mesenchymal stem cell (MSC) spheroids were transplanted at thoraces level (Th9) to SCI region in mice. BDNF-transfected MSC spheroid transplantation led to a significantly enhanced recovery of hindlimb motor function in acute phase of SCI with myelinated axons preserved at the SCI region, while use of either technology in isolation, BDNF transfection or spheroid culture, exerted only a limited therapeutic effect, demonstrating the importance of integrated approaches. Secretion of endogenous therapeutic proteins, such as anti-inflammatory factors, was greater in MSC spheroids than in monolayer culture MSCs, and these factors appeared to act synergistically alongside BDNF secretion in SCI treatment. This study forms a basis for cell therapy regulating complex pathophysiologic processes.



http://ift.tt/2cehNm0

Commentary on ‘Monitoring of Foot Oxygenation with Near-infrared Spectroscopy in Patients with Critical Limb Ischemia Undergoing Percutaneous Transluminal Angioplasty: A Pilot Study’

Publication date: Available online 15 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): N. De Luccia




http://ift.tt/2cvC4S4

Racial differences in association of serum calcium with mortality and incident cardio- and cerebrovascular events

The Journal of Clinical Endocrinology &Metabolism, Early Release.


http://ift.tt/2cKr0Cg

The role of microRNAs in the pathogenesis of autoimmune diseases

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Ji-Qing Chen, Gábor Papp, Péter Szodoray, Margit Zeher
MicroRNAs (miRNAs) are single-stranded, endogenous non-coding small RNAs, ranging from 18 to 25 nucleotides in length. Growing evidence suggests that miRNAs are essential in regulating gene expression, cell development, differentiation and function. Autoimmune diseases are a family of chronic systemic inflammatory diseases. Recent findings on miRNA expression profiles have been suggesting their role as biomarkers in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. In this review, we summarize the characteristics of miRNAs and their functional role in the immune system and autoimmune diseases including systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis, systemic sclerosis, multiple sclerosis and psoriasis; moreover, we depict the advantages of miRNAs in modern diagnostics.



http://ift.tt/2cAqLHH

Dry eye disease and uveitis: a closer look at immune mechanisms in animal models of two ocular autoimmune diseases

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Tanima Bose, Maria Diedrichs-Moehring, Gerhild Wildner
Understanding the immunopathogenesis of autoimmune and inflammatory diseases is a prerequisite for specific and effective therapeutical intervention. This review focuses on animal models of two common ocular inflammatory diseases, dry eye disease (DED), affecting the ocular surface, and uveitis with inflammation of the inner eye. In both diseases autoimmunity plays an important role, in idiopathic uveitis immune reactivity to intraocular autoantigens is pivotal, while in dry eye disease autoimmunity seems to play a role in one subtype of disease, Sjögren's syndrome (SjS). Comparing the immune mechanisms underlying both eye diseases reveals similarities, and significant differences. Studies have shown genetic predispositions, T and B cell involvement, cytokine and chemokine signatures and signaling pathways as well as environmental influences in both DED and uveitis. Uveitis and DED are heterogeneous diseases and there is no single animal model, which adequately represents both diseases. However, there is evidence to suggest that certain T cell-targeting therapies can be used to treat both, dry eye disease and uveitis. Animal models are essential to autoimmunity research, from the basic understanding of immune mechanisms to the pre-clinical testing of potential new therapies.



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Psoriasis and autoimmunity

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Michael Sticherling
Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.



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Cognitive Disorders and Antiphospholipid Antibodies

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Cécile M. Yelnik, Elizabeth Kozora, Simone Appenzeller
Cognitive disorders have frequently been described in the field of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Nevertheless, the relationship between those disorders and antiphospholipid antibodies (aPL) remains unclear and seems to involve various mechanisms. Overlap with systemic lupus erythematosus, the small sample size of studies, and discrepancies in antiphospholipid antibodies and cognitive impairment determinations complicate analyzes of the literature data. In this paper, we summarize current knowledge on epidemiologic, clinical data, imaging findings and treatment of cognitive dysfunction associated with aPL. We analyzed separately data on aPL-positive carriers without history of clinical feature of APS; APS patients without overlaps autoimmune disease; and SLE associated aPL patients.



http://ift.tt/2cAso88

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): Characteristics, treatment and outcome in 251 cases from the literature

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Charlotte Laurent, Jean Capron, Bluenn Quillerou, Guy Thomas, Sonia Alamowitch, Olivier Fain, Arsène Mekinian
BackgroundSteroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) is characterized by encephalopathy and the presence of antithyroid antibodies. We describe the clinical presentation, outcome and treatments for SREAT by a systematic review of the literature.MethodsMEDLINE via PubMed, Web of Science and the Cochrane Library were searched for articles published until 2015. Inclusion criteria were unexplained encephalopathy with antithyroid antibodies.ResultsWe found reports of 251 patients (median age 52years [range 18–86], 73% females, 80 [32%] with preexisting thyroiditis). Patients presented encephalitis signs with convulsions (n=117; 47%), confusion (n=115, 46%), speech disorder (n=91, 37%), memory impairment (n=107, 43%), gait disturbance (n=67, 27%) and persecutory delusions (n=61, 25%). Twenty-eight patients (11%) presented progressive memory impairment and 26 (10%) isolated psychiatric disorders. In serum, 34% of patients were positive for anti-thyroid peroxidase (TPO) antibodies, 7% for anti-thyroglobulin (TG) antibodies, and 69% both. Thyroid-stimulating hormone levels were usually normal, at 2 UI/ml [0.001–205]. Cerebrospinal fluid from 10/53 patients (19%) was positive for anti-TPO antibodies, 2/53 (4%) anti-TG antibodies and 28 (53%) both. Electroencephalography findings were abnormal for 82% of patients, showing diffuse slowing consistent with encephalopathy (70%) or epileptic activity (14%). The first-line treatment was steroids in 193 patients and other immunosuppressive drugs in 10 cases. At a median follow-up of 12months [range 0.2–110], 91% of patients showed complete or partial neurological response, with anti-TPO and -TG antibody titers at 347 UI/ml [0–825000] and 110 UI/ml [0–50892], respectively. During follow-up, 40 patients (16%) experienced at least one relapse. Relapse was more frequent in patients with initial coma (26% vs 13%, p=0.08).ConclusionThe diagnosis of SREAT should be suspected in case of encephalopathy without obvious cause, to quickly start corticosteroid treatment. The exact modalities of treatment must be defined.



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Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of 500 patients from the International CAPS Registry

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Ignasi Rodríguez-Pínto, Marta Moutinho, Irene Santacreu, Yehuda Shoenfeld, Doruk Erkan, Gerard Espinosa, Ricard Cervera
ObjectiveTo analyze the clinical and immunologic manifestations of patients with catastrophic antiphospholipid syndrome (CAPS) from the "CAPS Registry".MethodsThe demographic, clinical and serological features of 500 patients included in the website-based "CAPS Registry" were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test while T-test for independent variables was used to compare groups regarding continuous variables.Results500 patients (female: 343 [69%]; mean age 38±17) accounting for 522 episodes of CAPS where included in the analysis. Forty percent of patients had an associated autoimmune disease, mainly systemic lupus erythematosus (SLE) (75%). The majority of CAPS episodes were triggered by a precipitating factor (65%), mostly infections (49%). Clinically, CAPS was characterized by several organ involvement affecting kidneys (73%), lungs (60%), brain (56%), heart (50%), and skin (47%). Lupus anticoagulant, IgG anticardiolipin and IgG anti-β2-glycprotein antibodies were the most often implicated antiphospholipid antibodies (83%, 81% and 78% respectively). Mortality accounted for 37% of episodes of CAPS.Several clinical differences could be observed based on the age of presentation and its association to SLE. Those cases triggered by a malignancy tended to occur in older patients, while CAPS episodes in young patients were associated with an infectious trigger and peripheral vessels involvement. Additionally, CAPS associated with SLE were more likely to have severe cardiac and brain involvement leading to a higher mortality (48%).ConclusionAlthough the presentation of CAPS is characterized by multiorgan thrombosis and failure, clinical differences among patients exist based on age and underlying chronic diseases, e.g. malignancy, SLE.



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The association of other autoimmune diseases in patients with autoimmune thyroiditis: Review of the literature and report of a large series of patients

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Poupak Fallahi, Silvia Martina Ferrari, Ilaria Ruffilli, Giusy Elia, Marco Biricotti, Roberto Vita, Salvatore Benvenga, Alessandro Antonelli
We have evaluated prospectively the prevalence of other autoimmune disorders in outpatient clinic in 3069 consecutive patients with diagnosed chronic autoimmune thyroiditis (AT), with respect to two age- and sex-matched control groups: a) a control group of 1023 subjects, extracted from a random sample of the general population without thyroid disorders; b) 1023 patients with non-toxic multinodular goiter extracted from the same random sample of the general population, with similar odine intake. The results of our study demonstrate a significant increase of the prevalence of autoimmune disorders in AT patients (with respect to both controls), for the following diseases: chronic autoimmune gastritis (CAG), vitiligo (Vit), rheumatoid arthritis, polymialgia rheumatica (Polym), celiac disease, diabetes, sjogren disease, multiple sclerosis, systemic lupus erythematosus, sarcoidosis, alopecia, psoriathic arthritis, systemic sclerosis, HCV-related cryoglobulinemia. While the statistical analysis reached near the significance for Addison's disease and ulcerative colitis. Interestingly, the association of three autoimmune disorders was observed almost exclusively in AT patients, and the most frequent associations were AT+CAG+Vit and AT+CAG+Polym.We suggest that patients with AT who remain unwell, or who develop new not specific symptoms (despite adequate treatment) should be screened for other autoimmune disorders, avoiding the delay in the diagnosis of these disorders.



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Prevalence and predictors of valvular heart disease in patients with systemic lupus erythematosus

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): Florencia Vivero, Cristina Gonzalez-Echavarri, Beatriz Ruiz, Irene Maderuelo, Guillermo Ruiz-Irastorza
ObjectivesWe aimed to study the frequency, severity and predictors of valvular heart disease (VHD) in our lupus cohort.Material and Methods211 patients were included. A transthoracic echocardiogram was used for this study. Significant valvular lesions were classified into two groups: valvular thickening and valvular dysfunction. Univariate logistic regression was performed in order to find associations with valvular thickening and dysfunction. Those variables with a p value ≤0.1 in the univariate analysis were subsequently included in multiple logistic regression models.ResultsSignificant valve lesions were found in 53 patients (25%). The independent predictors of valvular thickening were the age at the time of the echocardiogram (OR 1.05, 95% CI 1.02–1.7), lymphopenia (OR 3.6, 95%CI 1.4–9.5), thrombocytopenia (OR 2.65, 95%CI 1.24–5.72), and anti-Sm antibodies (OR 3.28, 95%CI 1.44–7.33). The independent predictors of valvular dysfunction were age at the time of the echocardiogram (OR 1.045, 95%CI 1.009–1.083), thrombocytopenia (OR 5, 95%CI 1.66–14.86), hypertension (OR 6.2, 95%CI 2.1–18.4) and aPL (OR 6.2, 95%CI 2.1–18.4). Regarding the latter, the independent relation with valvular dysfunction was only seen for the double positivity aCL/LA, (OR 13.2, 95%CI 3.8–45.2, p<0.0001).ConclusionsOur study confirms the high prevalence of significant VHD in SLE patients. Clinical variables related with persistent inflammatory activity were associated with VHD. The association between VHD and aPL positivity was confirmed. Double-positive aCL/LA patients were most likely to suffer from valvular dysfunction.



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Inactivation of p27kip1 promoted nonspecific inflammation by enhancing macrophage proliferation in islet transplantation

Endocrinology, Early Release.


http://ift.tt/2cKi3bY

Foxo1 is Required for Normal Somatotrope Differentiation

Endocrinology, Early Release.


http://ift.tt/2cSZvDu

The Bone Sparing Effects of 2-methoxyestradiol are Mediated via Estrogen Receptor-α in Male Mice

Endocrinology, Early Release.


http://ift.tt/2cKhmiO

Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice

Endocrinology, Early Release.


http://ift.tt/2cSZ0cv