Head and Neck Medicine by Alexandros G.Sfakianakis: 09/16/16

Παρασκευή 16 Σεπτεμβρίου 2016

Long-term mid-facial growth of patients with a unilateral complete cleft of lip, alveolus and palate treated by two-stage palatoplasty: cephalometric analysis

Abstract

Objectives

The aim of this study is to evaluate long-term facial growth in adults previously treated for an isolated unilateral complete cleft lip, alveolus and palate by two-stage palatoplasty.

Materials and methods

Unilateral cleft lip and palate (UCLP) patients of 17 years and older treated by two-stage palatoplasty were invited for long-term follow-up. During follow-up, lateral cephalograms were obtained (n = 52). Medical history was acquired from their medical files. Outcome was compared to previously published normal values and the Eurocleft study.

Results

Soft and hard palate closure were performed at the age of 8 (SD 5.9) months and 3 (SD 2.2) years, respectively. The mean maxillary and mandibular angle (SNA, SNB) were 74.9° (SD 4.2) and 75.8° (SD 3.8). Maxillary and maxillomandibular relationships (SNA, ANB) were comparable to all Eurocleft Centres, except for Centre D. We observed a significantly steeper upper interincisor angle compared to the Eurocleft Centres.

Conclusions

This study describes the long-term craniofacial morphology in adults treated for a UCLP with hard palate closure at a mean age of 3 years. The mean maxillary angle SNA and mandibular angle SNPg were comparable to previous studies both applying early and delayed hard palate closure. The observed upper incisor proclination is likely caused by orthodontic overcorrection in response to the unfavourable jaw relationships. No clear growth benefit of this protocol could be demonstrated.

Clinical relevance

The present study shows the long-term craniofacial morphology of UCLP adults after the Utrecht treatment protocol which includes two-stage palate closure.

http://ift.tt/2d3OdNc

Phase 1 study evaluating the safety and pharmacokinetics of pralatrexate in relapsed/refractory advanced solid tumors and lymphoma patients with mild, moderate, and severe renal impairment

Abstract

Purpose

Pralatrexate is a folate analogue indicated for the treatment of relapsed or refractory peripheral T-cell lymphoma. It has not been formally tested in patients with renal impairment. This study evaluated the pharmacokinetic (PK) profile of pralatrexate in patients with renal impairment and with relapsed/refractory advanced solid tumors and lymphoma.

Methods

This was an open-label, nonrandomized, phase 1 study. Eligible patients received pralatrexate administered as an IV push over 3–5 min once weekly for 6 weeks in 7-week cycles until progressive disease or intolerable toxicity. Four cohorts of 6 patients were planned for a total of 24 patients. Patients with normal renal function (Cohort A), mild (Cohort B), and moderate renal impairment (Cohort C) received 30 mg/m² pralatrexate once weekly for 6 weeks in 7-week cycles, and patients with severe renal impairment (Cohort D) were to be administered 20 mg/m² once weekly for 6 weeks. Plasma and urine samples were collected at pre-specified time points to determine the PK profile of pralatrexate in each treatment cohort. Patients were followed for safety and tolerability.

Results

A total of 29 patients were enrolled and 27 patients (14 male) received at least 1 dose of pralatrexate. Because of a qualifying toxicity in Cohort C, the starting dose for Cohort D was reduced to 15 mg/m². Chronic renal impairment led to a decrease in renal clearance of the pralatrexate diastereomers, PDX-10a and PDX-10b, but systemic exposure to these diastereomers was not dramatically affected by renal impairment. Pralatrexate exposure in Cohort D (15 mg/m²) was similar to the exposure in other cohorts (30 mg/m²). No apparent difference in toxicity between the four treatment cohorts was observed, except for an increase in cytopenias in patients with severe renal impairment.

Conclusion

Pralatrexate exposure, at a dose of 30 mg/m², in patients with mild or moderate renal impairment was similar to the exposure in patients with normal renal function. For patients with severe renal impairment only, a pralatrexate dose of 15 mg/m² is recommended.

http://ift.tt/2cjuOJq

A Novel Approach for Targeted Delivery to Motoneurons Using Cholera Toxin-B Modified Protocells

Publication date: Available online 15 September 2016
Source:Journal of Neuroscience Methods
Author(s): Maria A. Gonzalez Porras, Paul N. Durfee, Ashley M. Gregory, Gary C. Sieck, C. Jeffrey Brinker, Carlos B. Mantilla
BackgroundTrophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, aging, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions.New MethodWe describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes.ResultsCTB modified protocells showed significantly greater motoneuron uptake compared to unmodified protocells after 24h of treatment (60% vs. 15%, respectively). CTB-protocells showed specific uptake by motoneurons compared to muscle cells and demonstrated cargo release of a surrogate drug. Protocells showed a lack of cytotoxicity and unimpaired cellular proliferation. In isolated diaphragm muscle-phrenic nerve preparations, preferential axon terminal uptake of CTB-modified protocells was observed compared to uptake in surrounding muscle tissue. A larger proportion of axon terminals displayed uptake following treatment with CTB-protocells compared to unmodified protocells (40% vs. 6%, respectively).Comparison with Existing Method(s)Current motoneuron targeting strategies lack the functionality to load and deliver multiple cargos. CTB-protocells capitalizes on the advantages of liposomes and mesoporous silica nanoparticles allowing a large loading capacity and cargo release. The ability of CTB-protocells to target motoneurons at the NMJ confers a great advantage over existing methods.ConclusionsCTB-protocells constitute a viable targeted motoneuron delivery system for drugs and genes facilitating various therapies for neuromuscular diseases.

http://ift.tt/2csxJ0e

Artificial nutrition dependence after cetuximab versus cisplatin combined with radiotherapy for advanced head and neck cancer: A propensity score–matched analysis

ABSTRACT

Background

The purpose of this study was to compare the effect of cetuximab-based radiotherapy (RT) with cisplatin-based concomitant chemoradiotherapy (CCRT) on artificial nutrition dependence in locoregional advanced head and neck cancer.

Methods

We identified patients treated with cetuximab-based RT or CCRT between 2012 and 2014 in a Japanese national database, and used propensity score-matched analyses to evaluate artificial nutrition dependence for 30 days after starting chemotherapy and at hospital discharge.

Results

Of 3935 eligible patients, propensity score matching generated 250 pairs. Thirty-day artificial nutrition dependence was significantly lower in the cetuximab-based RT group than in the CCRT group (25.6% vs 35.2%; odds ratio [OR] = 0.67; 95% confidence interval [CI] = 0.46–0.97; p = .036). No significant difference in artificial nutrition dependence at hospital discharge was shown (6.2% vs 7.2%; OR = 1.07; 95% CI = 0.52–2.17; p = .861). Difference in duration of hospitalization was insignificant.

Conclusion

http://ift.tt/2ceXm8z

Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis

Publication date: Available online 15 September 2016
Source:Journal of Dermatological Science
Author(s): Yayoi Kamata, Utako Kimura, Hironori Matsuda, Suhandy Tengara, Atsuko Kamo, Yoshie Umehara, Kyoichi Iizumi, Hiroaki Kawasaki, Yasushi Suga, Hideoki Ogawa, Mitsutoshi Tominaga, Kenji Takamori
BackgroundAtopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H1-antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear.ObjectiveThis study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients.MethodsPlasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays.ResultsPlasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD.ConclusionPlasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD.

http://ift.tt/2ccP4Jx

Vascular targeting of nanoparticles for molecular imaging of diseased endothelium

Publication date: Available online 15 September 2016
Source:Advanced Drug Delivery Reviews
Author(s): Prabhani U. Atukorale, Gil Covarrubias, Lisa Bauer, Efstathios Karathanasis
This review seeks to highlight the enormous potential of targeted nanoparticles for molecular imaging applications. Being the closest point-of-contact, circulating nanoparticles can gain direct access to targetable molecular markers of disease that appear on the endothelium. Further, nanoparticles are ideally suitable to vascular targeting due to geometrically enhanced multivalent attachment on the vascular target. This natural synergy between nanoparticles, vascular targeting and molecular imaging can provide new avenues for diagnosis and prognosis of disease with quantitative precision. In addition to the obvious applications of targeting molecular signatures of vascular diseases (e.g., atherosclerosis), deep-tissue diseases often manifest themselves by continuously altering and remodeling their neighboring blood vessels (e.g., cancer). Thus, the remodeled endothelium provides a wide range of targets for nanoparticles and molecular imaging. To demonstrate the potential of molecular imaging, we present a variety of nanoparticles designed for molecular imaging of cancer or atherosclerosis using different imaging modalities.

Graphical abstract

http://ift.tt/2cjo5z5

Bioengineered and biohybrid bacteria-based systems for drug delivery

Publication date: Available online 15 September 2016
Source:Advanced Drug Delivery Reviews
Author(s): Zeinab Hosseinidoust, Babak Mostaghaci, Oncay Yasa, Byung-Wook Park, Ajay Vikram Singh, Metin Sitti
The use of bacterial cells as agents of medical therapy has a long history. Research that was ignited over a century ago with the accidental infection of cancer patients has matured into a platform technology that offers the promise of opening up new potential frontiers in medical treatment. Bacterial cells exhibit unique characteristics that make them well-suited as smart drug delivery agents. Our ability to genetically manipulate the molecular machinery of these cells enables the customization of their therapeutic action as well as its precise tuning and spatio-temporal control, allowing for the design of unique, complex therapeutic functions, unmatched by current drug delivery systems. Early results have been promising, but there are still many important challenges that must be addressed. We present a review of promises and challenges of employing bioengineered bacteria in drug delivery systems and introduce the biohybrid design concept as a new additional paradigm in bacteria-based drug delivery.

Graphical abstract

http://ift.tt/2cjnVb7

Primary cutaneous cryptococcosis during infliximab therapy

http://ift.tt/2cu7ADw

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.

http://ift.tt/2d0e9NK

Prosthodontic decision-making relating to dentitions with compromised molars: the perspective of Swedish General Dental Practitioners

Summary

The aim of this investigation was to study the clinical prosthodontic decision-making process relating to dentitions with compromised molars among Swedish general dental practitioners (GDPs). Eleven Swedish GDPs were purposively selected, and all agreed to participate. Then, in-depth, semi-structured interviews were conducted and covered treatment considerations concerning two authentic patient cases, initially with complete dental arches, and later, a final treatment based on a shortened dental arch (SDA) was discussed. The cases involved patients with compromised teeth situated mainly in the molar regions. One patient suffered from extensive caries and the other from severe periodontal disease. Qualitative content analysis was used to analyse the data. In the systematic analysis, two main categories were identified: holistic and functional approach. Among the interviewed GDPs, focus was put on patients' needs, background history and motivation for treatment as well as the preservation of molar support. Within the limitations of this study, the following can be concluded: keeping a dental arch with molars seems to be important to Swedish general dental practitioners. The SDA concept does not seem to have a substantial impact on the prosthodontic decision-making relating to dentitions with compromised molars. The dentist's experiences, as well as colleagues' or consulting specialist advice together with aetiological factors and the patient's individual situation, influence the decision-making more than the SDA concept. The conflicting results in the prosthetic decision-making process concerning the relevance of age and the need for molar support need further investigation, for example based on decisions made in the dentist′s own clinical practice.

http://ift.tt/2cEqr92

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

http://ift.tt/2cwg4qc

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

http://ift.tt/2cwgk91

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

http://ift.tt/2cOVlAS

Launch of British Association of Oral and Maxillofacial Surgeons book: Important oral and maxillofacial presentations for the primary care clinician -educating and promoting our specialty to general practitioners across the UK

We are delighted to inform colleagues about a new book funded by the BAOMS, which is to be launched at the General Practitioners' Conference, Harrogate, in October 2016.

http://ift.tt/2cwau7r

Minimally-invasive neck dissection and free flap reconstruction in patients with cancer of the head and neck

We describe our experience of cervical lymphadenectomy with microvascular anastomoses involving levels I to V through a minimally-invasive neck dissection. We retrospectively studied 12 patients who had levels I to IV neck dissection with free flap reconstruction between July 2013 and April 2015 at Poole Hospital (male:female ratio 8:4, mean (range) age 66 (49 – 83) years). The mean (range) operating time was 7 (5 – 8) hours, and the total volume drained from the neck was 105 (60-300) ml. The mean (range) number of harvested lymph nodes was 26 (13-39) from levels I to III, and 33 (20-42) from levels I to IV.

http://ift.tt/2ctWFtA

Effect of high-frequency yoga breathing on pulmonary functions in patients with asthma

Bronchial asthma is one of the most common respiratory disorders with significant morbidity and mortality. Patients with asthma experience declined lung function. Among patients with asthma, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were found to be lower than in age- and height-matched healthy individuals.1 To arrest the decline in ventilatory function is one of the major objectives of management of asthma.

http://ift.tt/2cj9N1I

Mental practice in postgraduate training: a randomized controlled trial in mastoidectomy skills

Mental practice, the cognitive rehearsal of a task in the absence of overt physical movement, has been successfully used in teaching complex psychomotor tasks including sports and music, and recently, surgical...

http://ift.tt/2cOCC5l

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

Influence of temporomandibular joint disc displacement on mandibular advancement in patients without pre-treatment condylar resorption

The purpose of this study was to clarify the correlation between pre-treatment anterior disc displacement and mandibular stability after orthognathic and orthodontic treatment among patients with a skeletal class II malocclusion and without pre-treatment condylar resorption. Thirty-seven patients were included (7 male, 30 female). The mean length of follow-up was 6.76±3.06 years. Patients with condylar resorption before treatment were excluded. Magnetic resonance images and lateral cephalometric radiographs were taken before treatment (T0), after treatment (T1), and at follow-up (T2).

http://ift.tt/2cCbbwZ

The split crest technique and dental implants: a systematic review and meta-analysis

This systematic review aimed to determine: (1) the expected bone volume gain with the split crest technique, and (2) how the use of surgical instruments affects the performance of this technique. An electronic search was performed in the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Embase, PubMed/MEDLINE, Scopus, and Web of Science databases. Twenty-seven articles met the selection criteria and were subjected to meta-analysis of bone gain and survival rate; 17 reported the use of conventional surgical instruments and nine the use of surgical ultrasound.

http://ift.tt/2d3hEiG

Labels, identity and narratives in children with primary speech and language impairments

.

http://ift.tt/2ctHNLt

Gender differences in onabotulinum toxin A dosing for adductor spasmodic dysphonia

Objectives/Hypothesis

The objective of this study was to determine the influence of gender on onabotulinum toxin A dosing for the treatment of adductor spasmodic dysphonia symptoms.

Study Design

Retrospective review.

Methods

A chart review of the senior author's database of botulinum toxin injections was performed. Patients diagnosed with adductor spasmodic dysphonia who received onabotulinum toxin A (BoNTA) injections to the thyroarytenoid muscle for at least 5 years were included for study. Patients who received alternate formulations of botulinum toxin (Myobloc, Dysport, or Xeomin) and patients with alternate diagnoses, such as abductor spasmodic dysphonia, tremor, and oromandibular dystonia, were excluded. The average BoNTA dose was calculated for each patient and statistical analysis was performed comparing the male and female groups.

Results

A total of 201 patients (52 males and 149 females) met inclusion criteria. The average follow-up times for the male and female groups were 10.2 ± 3.6 and 11.1 ± 4 years, respectively. The average BoNTA doses for the male and female groups were 0.6 ± 0.42 U and 1.3 ± 1.1 U, respectively. Statistical analysis was performed using an independent samples two-tailed t test yielding a P value of .0000000002. A large effect size was noted with Cohen's d = 0.85.

Conclusions

The data from this retrospective chart review reveal a statistically and clinically significant correlation between female gender and higher average BoNTA dose for symptom control in adductor spasmodic dysphonia. Explanations for this observation are speculative and include a possible inverse relationship between optimal BoNTA dose and vocal fold mass and possibly greater neutralizing antibody formation among female patients.

Level of Evidence

4. Laryngoscope, 2016

http://ift.tt/2cKPxqu

Oncologic outcomes of selective neck dissection in HPV-related oropharyngeal squamous cell carcinoma

Objectives

To examine outcomes of selective neck dissection (SND) in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) who present with clinical neck disease.

Study Design

Multi-institutional retrospective review.

Methods

Two institutional databases of patients with HPV-related OPSCC were reviewed to identify patients with clinical (c) N1-N3 neck disease who underwent SND ± adjuvant therapy.

Results

Three hundred and twenty-four patients were identified with a median follow-up of 49 months (range 3–199 months). All patients underwent transoral resection of the primary tumor and SND, including levels II–IV and ± levels I or V, with resection of additional nonlymphatic tissue (extended SND) as indicated by extent of disease, including the spinal accessory nerve (7%), the internal jugular vein (13%), and the sternocleidomastoid muscle (8%). Two hundred and seventy (83%) patients underwent adjuvant radiation. There were 13 (4%) regional recurrences and 19 (6%) distant recurrences. Regional control following salvage was 98%. On univariable analysis, absence of radiation was associated with regional recurrence (odds ratio [OR] 9.2, 95% confidence interval [CI] 2.9–29.4). On multivariable analysis, adjuvant radiation was associated with improved disease-free survival (DFS) (OR 0.27, 95% CI 0.14–0.53) but lost significance for overall (OS) and disease-specific survival (DSS) (P > 0.05). Five-year Kaplan-Meier estimates for OS, DSS, and DFS were 88% (95% CI 84%–92%), 93% (95% CI 89%–96%), and 83% (95% CI 78%–87%), respectively.

Conclusion

In HPV-related OPSCC presenting with clinical neck disease, a SND ± additional tissue resection and adjuvant therapy, when indicated, provides excellent long-term regional control. Omission of radiotherapy increases the risk of regional recurrence, although it may not significantly impact OS or DSS. It appears unnecessary to routinely perform a comprehensive neck dissection.

Level of Evidence

4. Laryngoscope, 2016

http://ift.tt/2cTzhAG

Three different turbinoplasty techniques combined with septoplasty: Prospective randomized trial

Objectives/Hypothesis

Septal deviation and hypertrophic inferior turbinates are a frequent cause of nasal breathing disorders. The goal of this study was to prove the effectiveness and safety of three current turbinoplasty techniques.

Study Design

This is a prospective, three-arm, single-blinded, single-center, randomized controlled trial.

Methods

Sixty patients were randomly assigned to either anterior turbinoplasty (ATP) (n = 20), radiofrequency ablation (RFA) (n = 19; Celon Pro Breath), or novel submucous radial diode laser ablation (DLA) (n = 21; ELVeS Radial PainLess, wavelength = 1,470 nm), each in combination with standard septoplasty. Acoustic rhinometry, rhinomanometry, subjective nose questionnaire, and saccharin test served as outcome parameters for preoperative and 3-month, 1-year, and 2-year postoperative examinations.

Results

After 3 months 47/60 patients were evaluated, 28/60 patients were evaluated after 1 year, and 26/60 patients were evaluated in the 2-year follow-up visit. An improvement of nasal breathing was observed in all three groups in all follow-up visits. The increase of endonasal volume 2 (volume between the nasal valve and body of the inferior turbinate) was statistically significant in the ATP and RFA group after 3 months and 2 years, and in the RFA group also after 1 year. The DLA group failed to reach significance level in all follow-up visits. Subjective evaluation of nasal breathing improved in all three groups.

Conclusions

In this trial, three different current techniques of turbinate surgery in combination with standard septoplasty were effective for the improvement of nasal breathing. The ATP and RFA techniques were more effective in the long term than DLA.

Level of Evidence

1b. Laryngoscope, 2016

http://ift.tt/2cKPA5F

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

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

http://ift.tt/2cBY6no

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.

http://ift.tt/2ciOkpk

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.

http://ift.tt/2cDCfsq

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

http://ift.tt/2ceiEmV

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.

http://ift.tt/2cO16yB

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.

http://ift.tt/2cArd90

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.

http://ift.tt/2cO3qp4

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.

http://ift.tt/2cAqS5R

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.

http://ift.tt/2cBDsUp

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.

http://ift.tt/2d2KoYG

Αρχειοθήκη ιστολογίου

Παρασκευή 16 Σεπτεμβρίου 2016

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Abstract

Purpose

Methods

Results

Conclusion

ABSTRACT

Background

Methods

Results

Conclusion

Graphical abstract

Graphical abstract

Summary

Graphical abstract

Graphical abstract

Abstract

Objectives/Hypothesis

Study Design

Methods

Results

Conclusions

Level of Evidence

Objectives

Study Design

Methods

Results

Conclusion

Level of Evidence

Objectives/Hypothesis

Study Design

Methods

Results

Conclusions

Level of Evidence

Abstract

Graphical abstract

Teaser

Graphical abstract

Teaser

Graphical abstract

Teaser

Summary

Background

Aims

Materials and Methods

Results

Conclusion

Graphical abstract

Teaser

Graphical abstract