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Τρίτη 31 Οκτωβρίου 2017
Scholar : Bulletin of Spanish Studies, Volume 94, Issue 7, August 2017 is now available online on Taylor & Francis Online
Microvascular reactivity, assessed by near-infrared spectroscopy and a vascular occlusion test, is associated with patient outcomes following cardiac surgery: A prospective observational study.
http://ift.tt/2A3MgLR
Δευτέρα 30 Οκτωβρίου 2017
Dermatological and environmental toxicological impact of the sunscreen ingredient oxybenzone/benzophenone-3
Summary
Oxybenzone (Benzophenone-3) is an emerging human and environmental contaminant used in sunscreens and personal care products to help minimize the damaging effects of ultraviolet radiation. The Center for Disease Control fourth national report on human exposure to environmental chemicals demonstrated that approximately 97% of the people tested have oxybenzone present in their urine, and independent scientists have reported various concentrations in waterways and fish worldwide. Oxybenzone can also react with chlorine, producing hazardous by-products that can concentrate in swimming pools and wastewater treatment plants. Moreover, adverse reactions could very well be increased by the closed loop of ingesting fish contaminated with oxybenzone and/or washing the ingredient off our bodies and having it return in drinking water as treatment plants do not effectively remove the chemical as part of their processing protocols. In humans, oxybenzone has been reported to produce contact and photocontact allergy reactions, implemented as a possible endocrine disruptor and has been linked to Hirschsprung's disease. Environmentally, oxybenzone has been shown to produce a variety of toxic reactions in coral and fish ranging from reef bleaching to mortality. Lastly, with the rise in skin cancer rates and the availability of more effective sunscreen actives such as micronized zinc oxide and titanium dioxide, serious doubts about the relative prevention benefit of personal care products containing oxybenzone must be raised and compared with the potential negative health and environmental effects caused by the accumulation of this and other chemicals in the ecosystem.
http://ift.tt/2z2pwvF
The pathogenesis of cutaneous squamous cell carcinoma in organ transplant recipients
Summary
The pathogenesis of keratinocyte carcinoma following organ transplantation is multifactorial, and recent evidence suggests a complex and often synergistic interplay between the carcinogenic effects of ultraviolet radiation, compromised immune surveillance, direct pro- and anticarcinogenic effects of drugs, oncogenic viruses (in particular, beta-genus human papillomaviruses) and host genetic susceptibility factors. We present an overview of those factors for which there is currently the most convincing evidence and highlight important gaps in our knowledge. In particular, a clear understanding of the interdependence and relative contributions of these co-factors is currently lacking, yet has important implications for rational development of clinically relevant biomarkers and targeted strategies for treatment and prevention of post-transplant keratinocyte cancers.
http://ift.tt/2z0OnAb
Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients
Summary
Although tremendous progress has been made in recent years in skin cancer care for organ transplant recipients, significant gaps remain in data-driven clinical guidelines, particularly for the treatment and prevention of cutaneous squamous cell carcinoma (cSCC), the most common malignancy among this population. In this review, we aim to summarize current knowledge around the management of cSCC and highlight the most significant gaps in knowledge that continue to pose challenges in the delivery of skin cancer care for organ transplant recipients. We suggest future directions for research that will bridge existing gaps and establish evidence-driven guidelines for primary prevention, screening and treatment of cSCC in this high-risk patient population.
http://ift.tt/2iMl549
Introduction to the 2017 Cardiovascular Surgery-Themed Issue of Circulation.
http://ift.tt/2yfMeDD
Does Use of Bilateral Internal Mammary Artery Grafting Reduce Long-Term Risk of Repeat Coronary Revascularization?: A Multicenter Analysis.
http://ift.tt/2lwWWj8
Bilateral Versus Single Internal Mammary Artery Bypass Grafting: Do We Have the Answer?.
http://ift.tt/2yfcmyd
Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting: The VICO Randomized Clinical Trial (Vein Integrity and Clinical Outcomes).
http://ift.tt/2lukncF
Immediate and Midterm Cardiac Remodeling After Surgical Pulmonary Valve Replacement in Adults With Repaired Tetralogy of Fallot: A Prospective Cardiovascular Magnetic Resonance and Clinical Study.
http://ift.tt/2ygWhIf
Left Ventricular Assist Device Malfunctions: It Is More Than Just the Pump.
http://ift.tt/2lujZLf
A Population-Based Study of Abdominal Aortic Aneurysm Treatment in Finland 2000 to 2014.
http://ift.tt/2yhdb9X
Opportunities for Improving Population-Based Management of Abdominal Aortic Aneurysms.
http://ift.tt/2lu9Yhg
The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set.
http://ift.tt/2yfXT56
Mechanisms, Consequences, and Prevention of Coronary Graft Failure.
http://ift.tt/2lvaqfb
Interventions and Outcomes in Children With Hypoplastic Left Heart Syndrome Born in England and Wales Between 2000 and 2015 Based on the National Congenital Heart Disease Audit.
http://ift.tt/2yfXEqI
Ousting RAGE in melanoma: A viable therapeutic target?
Source:Seminars in Cancer Biology
Author(s): Deeba N. Syed, Ahmed Aljohani, Durdana Waseem, Hasan Mukhtar
Melanoma remains an important health concern, given the steady increase in incidence and acquisition of resistance to systemic therapies. The receptor for advanced glycation end products (RAGE) initially identified for its binding to advanced glycation end products was subsequently acknowledged as a pattern recognition receptor given its ability to recognize similar structural elements within numerous ligands. Recent studies have elucidated a plausible role of RAGE in melanoma progression through modulation of inflammatory, proliferative and invasive cellular responses. Several of its ligands including the S100 proteins and HMGB1 are being investigated for their involvement in melanoma metastasis and as potential biomarkers of the disease. Targeting RAGE signaling represents a viable therapeutic strategy which remains underexplored in cutaneous malignancies. Here we have summarized current knowledge on the functionality of RAGE with special focus on specific ligands enumerated in various in vitro and in vivo melanoma models.
http://ift.tt/2zkapkc
Epigenetics of Malignant Melanoma
Source:Seminars in Cancer Biology
Author(s): Bruce Moran, Romina Silva, Antoinette S. Perry, William M. Gallagher
Patients with malignant melanoma generally have a good prognosis if the disease presents prior to metastasis. Due to progress with targeted and immunotherapies, the median survival of metastatic melanoma patients is now over 2 years. The disease is characterised by one of the highest somatic mutation rates observed amongst cancer types, with a specific mutational signature based on UV radiation damage evident. Highly prevalent mutations, such as the BRAFV600E, in the MAPK cascade indicate truncal involvement of this pathway in the earliest stage of melanoma. The molecular sub-classification of melanoma based on genetic alterations is now well established. This has paved the way for researchers in epigenetics to investigate specific pathways of known importance, and the involvement of the diverse range of epigenetic mechanisms. Herein, we review the literature to highlight that epigenetic alterations are integrally involved in this malignancy. We focus on the most current evidence around the epigenetic mechanisms: DNA methylation and demethylation including 5-hydroxy-methylcytosine; histone post-translational modifications including variant histones; chromatin remodelling complexes and in particular the polycomb-repressive complex PRC2 and its histone methyltransferase subunit EZH2; and non-coding RNAs. Each mechanism is described generally, studies involving melanoma are assessed and clinical relevance is highlighted where possible.
http://ift.tt/2iOTzml
Oxidation, glycation and glycoxidation—The vicious cycle and lung cancer
Source:Seminars in Cancer Biology
Author(s): Saheem Ahmad, Mohd Yasir Khan, Zeeshan Rafi, Hamda Khan, Zeba Siddiqui, Shahnawaz Rehman, Uzma Shahab, Mohd Sajid Khan, Mohd Saeed, Sultan Alouffi, Mohd Shahnawaz Khan
The combine effect of oxidative and glycative stress predisposed to glycoxidation, and their outcomes that play critical role in lung cancer have been examined in different ways. The therapeutic approaches for lung cancer are still unsatisfactory. We observe some unclear and decisive pathways which might play an important role in targeting lung cancer. The roadmap of signaling pathway includes p38 MAPK, NF-ƙB, TNF-α and AGE-RAGE binding affinity play role in the cell growth, proliferation, apoptosis inhibition and metastasis. The goal of this review is to achieve a new signaling map inside the lung cancer which is mediated by glycoxidative products mainly reactive dicarbonyls and advanced glycation end products (AGEs). Additionally, AGE-RAGE binding critically regulates the suppression and promotion of lung cancer via inhibition and activation of different signaling pathways. Hence, this review suggests the role of oxidation, glycation, and glycoxidation in lung cancer.
http://ift.tt/2zkfFEz
KRAS, YAP, and obesity in pancreatic cancer: a signaling network with multiple loops
Source:Seminars in Cancer Biology
Author(s): Guido Eibl, Enrique Rozengurt
Pancreatic ductal adenocarcinoma (PDAC) continues to be a lethal disease with no efficacious treatment modalities. The incidence of PDAC is expected to increase, at least partially because of the obesity epidemic. Increased efforts to prevent or intercept this disease are clearly needed. Mutations in KRAS are initiating events in pancreatic carcinogenesis supported by genetically engineered mouse models of the disease. However, oncogenic KRAS is not entirely sufficient for the development of fully invasive PDAC. Additional genetic mutations and/or environmental, nutritional, and metabolic stressors, e.g. inflammation and obesity, are required for efficient PDAC formation with activation of KRAS downstream effectors. Multiple factors "upstream" of KRAS associated with obesity, including insulin resistance, inflammation, changes in gut microbiota and GI peptides, can enhance/modulate downstream signals. Multiple signaling networks and feedback loops "downstream" of KRAS have been described that respond to obesogenic diets. We propose that KRAS mutations potentiate a signaling network that is promoted by environmental factors. Specifically, we envisage that KRAS mutations increase the intensity and duration of the growth-promoting signaling network. As the transcriptional activator YAP plays a critical role in the network, we conclude that the rationale for targeting the network (at different points), e.g. with FDA approved drugs such as statins and metformin, is therefore compelling.
http://ift.tt/2iOyZTf
Editorial Board & Publication Information
Publication date: October 2017
Source:Seminars in Cancer Biology, Volume 46
http://ift.tt/2iLJV4a
THE ROLE OF DIETARY PATTERN, FOODS, NUTRIENTS AND NUTRACEUTICALS IN SUPPORTING CANCER PREVENTION AND TREATMENT
Source:Seminars in Cancer Biology, Volume 46
http://ift.tt/2zkfER1
Outcomes With Transcatheter Mitral Valve Repair in the United States: An STS/ACC TVT Registry Report
AbstractBackground
Post-market surveillance is needed to evaluate the real-world clinical effectiveness and safety of U.S. Food and Drug Administration–approved devices.
ObjectivesThe authors examined the commercial experience with transcatheter mitral valve repair for the treatment of mitral regurgitation.
MethodsData from the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with transcatheter mitral valve repair were analyzed. The study population consisted of 2,952 patients treated at 145 hospitals between November 2013 and September 2015. In 1,867 patients, data were linked to patient-specific Centers for Medicare and Medicaid Services administrative claims for analyses.
ResultsThe median age was 82 years (55.8% men), with a median Society of Thoracic Surgery predicted risk of mortality of 6.1% (interquartile range: 3.7% to 9.9%) and 9.2% (interquartile range: 6.0% to 14.1%) for mitral repair and replacement, respectively. Overall, in-hospital mortality was 2.7%. Acute procedure success occurred in 91.8%. Among the patients with Centers for Medicare and Medicaid Services linkage data, the mortality at 30 days and at 1 year was 5.2% and 25.8%, respectively, and repeat hospitalization for heart failure at 1 year occurred in 20.2%. Variables associated with mortality or rehospitalization for heart failure after multivariate adjustment were increasing age, lower baseline left ventricular ejection fraction, worse post-procedural mitral regurgitation, moderate or severe lung disease, dialysis, and severe tricuspid regurgitation.
ConclusionsOur findings demonstrate that commercial transcatheter mitral valve repair is being performed in the United States with acute effectiveness and safety. Our findings may help determine which patients have favorable long-term outcomes with this therapy.
http://ift.tt/2yXzIbl
A Test in Context: D-Dimer
Abstract
D-dimer is a soluble fibrin degradation product that results from ordered breakdown of thrombi by the fibrinolytic system. Numerous studies have shown that D-dimer serves as a valuable marker of activation of coagulation and fibrinolysis. Consequently, D-dimer has been extensively investigated for the diagnosis of venous thromboembolism (VTE) and is used routinely for this indication. In addition, D-dimer has been evaluated for determining the optimal duration of anticoagulation in VTE patients, for diagnosing and monitoring disseminated intravascular coagulation, and as an aid in the identification of medical patients at high risk for VTE. Thus, quantification of D-dimer levels serves an important role in guiding therapy. This review: 1) describes how D-dimer is generated; 2) reviews the assays used for its detection; and 3) discusses the role of D-dimer determination in these various conditions.
http://ift.tt/2gWSF78
Mechanisms of Very Late Bioresorbable Scaffold Thrombosis: The INVEST Registry
AbstractBackground
Very late scaffold thrombosis (VLScT) occurs more frequently after bioresorbable scaffold (Absorb BVS 1.1, Abbott Vascular, Santa Clara, California) implantation than with metallic everolimus-eluting stents.
ObjectivesThe purpose of this study was to elucidate mechanisms underlying VLScT as assessed by optical coherence tomography (OCT).
MethodsThe INVEST (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis) registry is an international consortium of investigators who used OCT to examine patients with VLScT.
ResultsBetween June 2013 and May 2017, 36 patients with 38 lesions who had VLScT underwent OCT at 19 centers. VLScT occurred at a median of 20 months (interquartile range: 16 to 27 months) after implantation. At the time of VLScT, 83% of patients received aspirin monotherapy and 17% received dual-antiplatelet therapy. The mechanisms underlying VLScT were (in descending order) scaffold discontinuity (42.1%), malapposition (18.4%), neoatherosclerosis (18.4%), underexpansion or scaffold recoil (10.5%), uncovered struts (5.3%), and edge-related disease progression (2.6%). Discontinuity (odds ratio [OR]: 110; 95% confidence interval [CI]: 73.5 to 173; p < 0.001), malapposed struts (OR: 17.0; 95% CI: 14.8 to 19.7; p < 0.001), and uncovered struts (OR: 7.3; 95% CI: 6.2 to 8.8; p < 0.001) were more frequent in the thrombosed than the nonthrombosed scaffold regions. In 2 of 16 patients with scaffold discontinuity, intercurrent OCT before VLScT provided evidence of circularly apposed scaffold struts with minimal tissue coverage.
ConclusionsThe leading mechanism underlying VLScT was scaffold discontinuity, which suggests an unfavorable resorption-related process, followed by malapposition and neoatherosclerosis. It remains to be determined whether modifications in scaffold design and optimized implantation can mitigate the risk of VLScT. (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis [INVEST]; NCT03180931)
http://ift.tt/2yXzJfp
Sex-Related Differences in Vasomotor Function in Patients With Angina and Unobstructed Coronary Arteries
AbstractBackground
Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries.
ObjectivesThe purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test).
MethodsBetween 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression.
ResultsThe mean patient age was 62 years, and 42% were male. There were 813 patients (59%) with a pathological ACH test, 33% for CMD and 26% for epicardial vasospasm. A pathological test was more common in females (70% vs. 43%; p < 0.001). In a multivariable logistic regression model the sex difference was statistically significant with a female–male odds ratio for CMD and epicardial vasospasm of 4.2 (95% confidence interval: 3.1 to 5.5; p < 0.001) and 2.3 (95% confidence interval: 1.7 to 3.1; p < 0.001), respectively. Effort-related symptoms, but neither risk factors nor noninvasive stress tests, contributed to predicting a pathological test. Female patients were more sensitive to acetylcholine with vasomotor dysfunction occurring at lower ACH doses compared with male patients.
ConclusionsVasomotor dysfunction is frequent in patients with angina and unobstructed coronaries in a European population. Female patients have a higher prevalence of vasomotor dysfunction (especially CMD) compared with male patients. A pathological ACH test was observed at lower ACH doses in women compared with men.
http://ift.tt/2gUS8Cm
The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics
Abstract
The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide–dependent and –independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin; thus, nitroglycerin is available in a number of preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch, as well as intravenous formulations. Organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major limitation of the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only 1 method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-h period. Nitric oxide's important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator.
http://ift.tt/2yZ2fgE
2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways
Abstract
Mitral regurgitation (MR) is a complex valve lesion that can pose significant management challenges for the cardiovascular clinician. This Expert Consensus Document emphasizes that recognition of MR should prompt an assessment of its etiology, mechanism, and severity, as well as indications for treatment. A structured approach to evaluation based on clinical findings, precise echocardiographic imaging, and when necessary, adjunctive testing, can help clarify decision making. Treatment goals include timely intervention by an experienced heart team to prevent left ventricular dysfunction, heart failure, reduced quality of life, and premature death.
http://ift.tt/2yXdc2f
Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes
AbstractBackground
Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported.
ObjectivesBased on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM.
MethodsThe study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.
ResultsMedian age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026).
ConclusionsEM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.
http://ift.tt/2gWTP26
Prognostic Value of Serial ST2 Measurements in Patients With Acute Heart Failure
AbstractBackground
Several clinical studies have evaluated the association between ST2 and outcome in patients with heart failure (HF). However, little is known about the predictive value of frequently measured ST2 levels in patients with acute HF.
ObjectivesThis study sought to describe the prognostic value of baseline and repeated ST2 measurements in patients with acute HF.
MethodsIn the TRIUMPH (Translational Initiative on Unique and novel strategies for Management of Patients with Heart failure) clinical cohort study, 496 patients with acute HF were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. ST2 and N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels were measured in a central laboratory. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. Associations between repeated biomarker measurements and the primary endpoint were assessed using a joint model.
ResultsMedian age was 74 years, and 37% of patients were women. The primary endpoint was reached in 188 patients (40%) during a median follow-up of 325 days (interquartile range: 85 to 401). The median baseline ST2 level was 71 ng/ml (interquartile range: 46 to 102). After adjustment for clinical factors and NT-proBNP, baseline ST2 was associated with an increased risk of the primary endpoint, and the hazard ratio per 1 SD increase of the baseline ST2 level (on the log2 scale) was 1.30 (95% confidence interval: 1.08 to 1.56; p = 0.005). When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the ST2 level (on the log2 scale) during follow-up increased to 1.85 (95% confidence interval: 1.02 to 3.33; p = 0.044), adjusted for clinical factors and repeated measurements of NT-proBNP. Furthermore, ST2 levels appeared to elevate several weeks before the time of the primary endpoint.
ConclusionsRepeated ST2 measurements appeared to be a strong predictor of outcome in patients with acute HF, independent of repeatedly measured NT-proBNP. Hence ST2 may be helpful in clinical practice for prognostication and treatment monitoring. (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure [TRIUMPH]; NTR1893)
http://ift.tt/2gWnY1S
Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck
Interventions: Drug: Pembrolizumab; Drug: Epacadostat
Sponsor: University of Chicago
Not yet recruiting
http://ift.tt/2hpI15Q
Serum Immunological Profiles in Head and Neck Cancer Patients Receiving Curative Radiotherapy
Intervention: Diagnostic Test: Serum levels of immunologic profiles
Sponsor: National Taiwan University Hospital
Recruiting
http://ift.tt/2zSmf11
Views of Dermatopathologists about Clonality Assays in the Diagnosis of Cutaneous T cell and B cell Lymphoproliferative Disorders
Background
Appropriate use criteria have been developed for many tests using expert judgment, evidence-based practice, and clinical experience. In this context, the opinions of practitioners about clonality assays in various clinical scenarios where cutaneous lymphoma is suspected are reported.
Methods
An Appropriate Use Criteria Task Force sponsored by the American Society of Dermatopathology (ASDP) synthesized clinical scenarios for cutaneous lymphoproliferative disorders (LPD). We conducted, summarized, and presented a relevant literature search to an audience of 144 dermatopathologists with a variety of practice experiences at the 53rd Annual Meeting of the ASDP in Chicago, IL.
Results
27 clinical scenarios for lymphoproliferative disorders (13 T cell and 14 B cell) were defined. 40 relevant studies for T-cell receptor gene clonality assays and 20 relevant studies for IgH/IgK clonality assays were identified. Audience response data from participating dermatopathologists reflected a wide variety of approaches to the application of clonality assays in the evaluation of LPDs, based on practice setting, personal experience and test availability.
Conclusions
Our clinical scenario analysis and literature review revealed well supported clinical scenarios and identified opportunities for additional research to further define the utility of clonality assays in some clinical scenarios.
http://ift.tt/2iMeHtA
Risk Factors stratifying malignancy of nodules in contralateral thyroid lobe in patients with preoperative ultrasound indicated unilateral papillary thyroid carcinoma: A retrospective analysis from single center
Summary
Objective
Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma with a favorable clinical outcome. For unilateral PTC patients with thyroid nodules in the contralateral lobes, the necessity of total thyroidectomy (TT) is still in doubt. In this study, we aimed to define clinical factors that could be indicators for malignancy in nodules in the contralateral thyroid lobe, which could aid the clinician in selecting the appropriate operation approach.
Design, Patients and Measurements
This is a retrospective study from Jan 2014 to Dec 2016 conducted in Shanghai Ruijin Hospital. 1442 cases with unilateral PTC and ultrasonographically benign nodules in the contralateral lobe who underwent TT at a single institution were enrolled. All patients underwent preoperative ultrasonography (US) and all the cases were confirmed by board-certified pathologists. Clinicopathological features such as age, gender, tumor location, tumor size, TgAb and TPOAb levels, capsular invasion, multifocality, central lymph node metastases and BRAF mutation were examined to evaluate the rate of malignancy in the contralateral thyroid nodules.
Results
In total, 47% of patients (677 cases)were confirmed to have malignancy in the contralateral lobe. Univariant analysis indicated that capsular invasion, Hashimoto's thyroiditis, multifocal loci, central lymph node metastases as well as BRAF mutation predicted a high incidence of occult contralateral carcinoma. Multivariant analysis showed capsular invasion, multifocal ipsilateral thyroid lobe, central lymph node metastases as well as BRAF mutation can serve as independent predictors for malignancy in the contralateral thyroid lobe.
Conclusions
Malignancy in the contralateral lobe was found in 47% of patients. This finding was associated with multifocal primary carcinomas involvement, capsular invasion, Hashimoto's thyroiditis history, central lymph node metastases and BRAF mutation, which should therefore be taken into consideration when planning therapeutic strategy for the patients.
This article is protected by copyright. All rights reserved.
http://ift.tt/2yWyMUt
Cosmetics, Vol. 4, Pages 45: Non-Targeted Secondary Metabolite Profile Study for Deciphering the Cosmeceutical Potential of Red Marine Macro Alga Jania rubens—An LCMS-Based Approach
Cosmetics, Vol. 4, Pages 45: Non-Targeted Secondary Metabolite Profile Study for Deciphering the Cosmeceutical Potential of Red Marine Macro Alga Jania rubens—An LCMS-Based Approach
Cosmetics doi: 10.3390/cosmetics4040045
Authors: Dhara Dixit C. R. K. Reddy
This study aims to unveil the cosmeceutical traits of Jania rubens by highlighting its mineral composition, antioxidant potential, and presence of bioactive molecules using non-targeted metabolite profiling. This study showed that among minerals, (macro), Ca (14790.33 + 1.46 mg/100 g dry weight (DW)) and in (micro) Fe (84.93 + 0.89 mg/100 g DW) was the highest. A total of 23 putative metabolites in the +ESI (Electrospray Ionization) mode of LCMS-TOF (Liquid Chromatography Mass Spectrometry-Time of Flight) were detected. Two anthocyanins—malonylshisonin and 4′′′-demalonylsalvianin (m/z 825.19; anti-aging, antioxidant, anticancer properties) were detected. Two flavonoids, viz, medicocarpin and agecorynin C, 4′-O-methylglucoliquiritigenin—a flavonoid-7-O-glycoside, and 5,6,7,8,3′,4′,5′-heptamethoxyflavone, a polymethoxygenated flavone (m/z 415.15), were detected. Maclurin 3-C-(2″,3″,6″-trigalloylglucoside) (m/z 863.15) (antioxidant, antimicrobial and anticancer traits) and theaflavonin (m/z 919.18), belonging to the class of theaflavins (whitening and anti-wrinkle agent), were obtained. Pharmacologically active metabolites like berberrubin (m/z 305.1; antitumor activity), icaceine (m/z 358.24; anticonvulsant properties), agnuside (m/z 449.15; constituent for treatment of premenstrual syndrome), γ-coniceine (m/z 108.12; formulations to treat breast cancer), eremopetasitenin B2, and eremosulphoxinolide A (m/z 447.18; therapeutic effect of allergy and asthma) were observed. 6-O-Methylarmillaridin (m/z 445.18) (antimicrobial and antifungal) and simmondsin 2-ferulate, (m/z 534.21) (insecticidal, antifungal and antifeedant) were detected. Aromatic lignans, viz, 8-Acetoxy-4′-methoxypinoresinol, sesartemin, and cubebinone (m/z 413.16), in addition to an aromatic terpene glycoside, tsangane L3 glucoside (m/z 357.23), were detected. Zizybeoside I, benzyl gentiobioside, and trichocarposide were also detected. The determination of antioxidant potential was performed through assays such as like DPPH (2,2-diphenyl-1-picrylhydrazyl), FRAP (Ferric Ion Reducing Antioxidant Power), ABTS (2,2′-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid)), and total antioxidants. Therefore, this study progresses the probability for the inclusion of J. rubens as an ingredient in modern day cosmetic formulations.
http://ift.tt/2iL5QID
A novel technique for clinical examination of buried head and neck free flaps
Abstract
Monitoring buried flaps within the head and neck presents a unique challenge to the microsurgeon. We conducted an independent review of the literature using Medline, PubMed and Q Read performed up to February 2017. This showed that head and neck free flaps have contemporary success rates of between 92 and 98%, which is similar to rates reported for all types of flaps (90–98%). Studies looking specifically at buried free flaps were scarce, with success rates (90–98%) precisely mirroring those of studies looking at all flaps. In studies in which both buried and non-buried flaps were stratified, buried flaps did have lower rates of success (93.5 vs. 98.2% and 93 vs. 98%). While overall success rates may have been similar, lower rates of salvage were clearly shown for buried flaps. Salvage rates ranged from 0 to 75%. The highest rate was achieved using implantable Doppler, which has been shown to increase salvage rates by up to 21%. However, this technique is associated with significant rates of false positives, which have been shown to be between 8 and 40.4% Another monitoring technique in use for buried flaps was externalised monitoring segments, which has been associated with higher rates of pharyngeal fistula in head and neck reconstruction. In this article, we present a variation of the Acland's empty-and-refill test which may be used to monitor buried flaps that have a venous anastomosis in an end-to-end fashion to the external jugular vein.
Level of Evidence: Level IV, diagnostic study.
http://ift.tt/2gUm2Xz
Evaluation of the effect of new formulation, food, or a proton pump inhibitor on the relative bioavailability of the smoothened inhibitor glasdegib (PF-04449913) in healthy volunteers
Abstract
Purpose
This phase I open-label study investigated the oral bioavailability of two novel maleate salt-based glasdegib (PF-04449913) tablet formulations (small- and large-particle size) relative to the current clinical formulation (diHCl salt-based). In addition, the effect of a gastric pH-altering agent (rabeprazole) and food on the pharmacokinetics of the large-particle size formulation of glasdegib were evaluated. The pharmacokinetics of glasdegib oral solution was also assessed.
Methods
Thirty-four healthy subjects received glasdegib 100 mg as three different formulations in the fasted state (diHCl salt or small- or large-particle size maleate formulation); 13 received the large-particle maleate formulation (fed), and 14 concurrently with rabeprazole (fasted); six subjects received glasdegib 50 mg oral solution (fasted).
Results
For both new tablet formulations of glasdegib, ratios (Test:Reference) of adjusted geometric means (90% confidence interval) of area under the concentration–time curve from 0 to infinity and maximum plasma concentration were within 80–125% compared with the diHCl formulation (fasted). For the large-particle size formulation (fed), these ratios were 86.3% (81.0–92.0%) and 75.7% (65.3–87.7%), respectively, compared with fasted. When the large-particle maleate formulation was administered concurrently with rabeprazole versus alone (fasted), these ratios were 111.9% (102.8–121.9%) and 87.2% (75.9–100.3%), respectively. The pharmacokinetics of oral solution was similar to the tablet.
Conclusions
The maleate salt-based tablet formulations were bioequivalent to the diHCl tablet formulation. The extent of the observed effect of a high-fat, high-calorie meal or concurrent rabeprazole treatment on glasdegib exposure is not considered clinically meaningful.
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Correction to: Innovative intraoral cooling device better tolerated and equally effective as ice cooling
Unfortunately, the online published article has error in Table 1. The correct Table 1 is given in the following page.
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Therapeutic potential of the metabolic modulator Metformin on osteosarcoma cancer stem-like cells
Abstract
Purpose
Osteosarcoma is the most common primary bone tumour appearing in children and adolescents. Recent studies demonstrate that osteosarcoma possesses a stem-like cell subset, so-called cancer stem-like cells, refractory to conventional chemotherapeutics and pointed out as responsible for relapses frequently observed in osteosarcoma patients. Here, we explored the therapeutic potential of Metformin on osteosarcoma stem-like cells, alone and as a chemosensitizer of doxorubicin.
Methods
Stem-like cells were isolated from human osteosarcoma cell lines, MNNG/HOS and MG-63, using the sphere-forming assay. Metformin cytotoxicity alone and combined with doxorubicin were evaluated using MTT/BrdU assays. Protein levels of AMPK and AKT were evaluated by Western Blot. Cellular metabolic status was assessed based on [18F]-FDG uptake and lactate production measurements. Sphere-forming efficiency and expression of pluripotency transcription factors analysed by qRT-PCR were tested as readout of Metformin effects on stemness features.
Results
Metformin induced a concentration-dependent decrease in the metabolic activity and proliferation of sphere-forming cells and improved doxorubicin-induced cytotoxicity. This drug also down-regulated the expression of master regulators of pluripotency (OCT4, SOX2, NANOG), and decreased spheres' self-renewal ability. Metformin effects on mitochondria led to the activation and phosphorylation of the energetic sensor AMPK along with an upregulation of the pro-survival AKT pathway in both cell populations. Furthermore, Metformin-induced mitochondrial stress increased [18F]-FDG uptake and lactate production in parental cells but not in the quiescent stem-like cells, suggesting the inability of the latter to cope with the energy crisis induced by metformin.
Conclusions
This preclinical study suggests that Metformin may be a potentially useful therapeutic agent and chemosensitizer of osteosarcoma stem-like cells to doxorubicin.
http://ift.tt/2hotcAl
Massive adrenal incidentalomas and late diagnosis of congenital adrenal hyperplasia in prostate cancer
Summary
In a 61-year-old Caucasian male with prostate cancer, leuprolide and bicalutamide failed to suppress the androgens. He presented to endocrinology with persistently normal testosterone and incidental massive (up to 18 cm) bilateral adrenal myelolipomas on CT scan. Blood test did not reveal metanephrine excess. The patient was noted to have short stature (151 cm) and primary infertility. Elementary school photographs demonstrated precocious puberty. Physical examination revealed palpable abdominal (adrenal) masses. Abiraterone and glucocorticoid treatment was commenced with excellent suppression of testosterone. Genetic testing revealed a mutation in CYP21A2 confirming 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). Association of large myelolipomas with CAH has been reported in the literature. Our case highlights the importance of considering CAH in patients with non-suppressed testosterone despite androgen deprivation therapy. Large myelolipomas should raise the suspicion of congenital adrenal hyperplasia.
Learning points:Adrenal myelolipomas are rare benign lesions that are more common in patients with longstanding untreated congenital adrenal hyperplasia thought to be due to ACTH stimulation.
Consider undiagnosed congenital adrenal hyperplasia in patients with adrenal myelolipoma.
Glucocorticoid replacement may be an efficacious treatment for patients with prostate cancer and CAH. Abiraterone therapy has a risk of adrenal crisis if glucocorticoids are not replaced.
http://ift.tt/2gVLA6v
Atypical manifestation of parathyroid carcinoma with late-onset distant metastases
Summary
Parathyroid carcinoma is an extremely rare endocrine malignancy that accounts for less than 1% of cases of primary hyperparathyroidism. We report a 44-year-old woman who presented with fatigue and diffuse bone pain. Laboratory findings revealed highly elevated serum calcium and parathyroid hormone (PTH) levels and a 4.5 × 3 × 2.5 cm cystic lesion in the lower pole of the right thyroid lobe that was shown histologically to be a parathyroid carcinoma. Ten years later, the patient developed brain and pulmonary metastases and recurrence of PTH-related hypercalcemia. Treatment of hypercalcemia along with localized radiotherapy and various chemotherapy regimens failed to induce a biochemical or radiological response. In conclusion, parathyroid carcinoma is a rare neoplasia that may develop metastases even after prolonged follow-up, for which there is no evidence-based treatment besides surgery. Different chemotherapeutic schemes did not prove to be of any benefit in our case highlighting the need for registering such patients to better understand tumor biology and develop specific treatment.
Learning points:Metastases can develop many years after parathyroid cancer diagnosis.
Surgery is the only curative treatment for parathyroid carcinoma.
Chemotherapy and radiotherapy prove to be ineffective in parathyroid cancer treatment.
Patient registering is required in order to delineate underlining pathology and offer specific treatment.
http://ift.tt/2yWZvO9
Massive adrenal incidentalomas and late diagnosis of congenital adrenal hyperplasia in prostate cancer
In a 61-year-old Caucasian male with prostate cancer, leuprolide and bicalutamide failed to suppress the androgens. He presented to endocrinology with persistently normal testosterone and incidental massive (up to 18 cm) bilateral adrenal myelolipomas on CT scan. Blood test did not reveal metanephrine excess. The patient was noted to have short stature (151 cm) and primary infertility. Elementary school photographs demonstrated precocious puberty. Physical examination revealed palpable abdominal (adrenal) masses. Abiraterone and glucocorticoid treatment was commenced with excellent suppression of testosterone. Genetic testing revealed a mutation in CYP21A2 confirming 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). Association of large myelolipomas with CAH has been reported in the literature. Our case highlights the importance of considering CAH in patients with non-suppressed testosterone despite androgen deprivation therapy. Large myelolipomas should raise the suspicion of congenital adrenal hyperplasia.
Learning points:Adrenal myelolipomas are rare benign lesions that are more common in patients with longstanding untreated congenital adrenal hyperplasia thought to be due to ACTH stimulation.
Consider undiagnosed congenital adrenal hyperplasia in patients with adrenal myelolipoma.
Glucocorticoid replacement may be an efficacious treatment for patients with prostate cancer and CAH. Abiraterone therapy has a risk of adrenal crisis if glucocorticoids are not replaced.
http://ift.tt/2gVLA6v
Outcome and prognostic factors in single brain metastases from small-cell lung cancer
Abstract
Purpose
Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1–4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT.
Methods
A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS.
Results
The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06–4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11–0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14–4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35–0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15–0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09–4.45; p = 0.028).
Conclusions
Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.
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Corrected and Republished: Misaligned pCONus Device: Case Report of a Unique Complication
Journal of Clinical Imaging Science 2017 7(1):41-41
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Scholar : These new articles for Critical Discourse Studies are available online
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How to get thicker hair
Many people want to help their hair look thick and full without chemical treatments. We look at several natural hair treatments, from eggs to castor oil.
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Cutaneous manifestations of phosphate solution extravasation
Summary
Extravasation injuries are common in patients receiving multiple intravenous infusions. Although such injuries are closely associated with the infusion of cytotoxic chemotherapy, they have also been been associated with extravasation of noncytotoxic drugs. Extravasation injuries can lead to skin ulceration and nerve and tendon damage, and therefore to permanent disability. We report three cases of phosphate solution extravasation leading to unusual cutaneous manifestations.
http://ift.tt/2gMyN2I
Κυριακή 29 Οκτωβρίου 2017
Effectiveness and safety of polidocanol for the treatment of hemangiomas and vascular malformations: A meta-analysis
Abstract
A meta-analysis was conducted to investigate the efficacy and safety of polidocanol versus other conventional therapies in treating hemangiomas (HMs) and vascular malformations (VMs). Literature search was conducted in the Cochrane, Embase, PubMed, Web of Science, CNKI, CBM, VIP, and WanFang databases until March 5, 2017. A meta-analysis was conducted using Revman 5.3 software. A total of 19 randomized controlled trials (RCTs) involving 1,514 participants met the inclusion criteria. Regarding the effectiveness, statistically significant differences were observed between polidocanol and all the independent treatments (p = .006), but not between polidocanol and pingyangmycin (p = .16). Combination therapy of polidocanol with any other conventional treatments (p = .0001), pingyangmycin (p = .005) or hemoclip (p = .008) elicited a better response compared to treatment with these treatments independently. A meta-analysis on the risk of adverse events (AEs) showed a lower risk for polidocanol versus other treatments, for example, all the conventional treatments used independently (p < .00001) and pingyangmycin (p < .00001). Combination therapy of polidocanol with pingyangmycin also yielded a significantly lower risk of AEs (p < .00001). Polidocanol is at least as effective as other conventional therapies on HMs and VMs (especially venous malformations). The former is much safer. Combining its use with other treatments may produce excellent results. Our study provides strong evidence supporting the use of polidocanol for HMs and VMs.
http://ift.tt/2zQKo8o
Comparison of clinical efficacy and safety of thermotherapy versus cryotherapy in treatment of skin warts: A randomized controlled trial
Abstract
The effect of thermotherapy in the treatment of skin warts in comparison to cryotherapy, as the standard conventional method, has remained uncertain. This study aimed to assess the clinical efficacy and safety of thermotherapy and cryotherapy in removing skin warts. This randomized controlled trial was conducted on 52 patients aged 18 years and over with ≤ 10 skin warts. The participants were randomly assigned into two groups to receive cryotherapy (every 2 to 3 weeks up to six sessions if required) or thermotherapy (one session). The patients in both groups were followed every 2 to 3 weeks for the first three months, and then three months after the last treatment session. The clearance rate was 79.2% in the thermotherapy group and 58.3% in the cryotherapy group with no significant difference (p = 0.212). The rate of scarring in the thermotherapy group was 20% (p = .018). A higher clearance rate was achieved in the thermotherapy group. However, this result was not statistically significant. There were some minimal post-treatment complications. Patients needed only one session of thermotherapy. Due to the risk of scarring, we suggest thermotherapy only as a suitable treatment method for palmoplantar warts.
http://ift.tt/2ho7uMZ
Bioavailability and toxicity of trace metals (Cd, Cr, Cu, Ni, and Zn) in sediment cores from the Shima River, South China
Publication date: February 2018
Source:Chemosphere, Volume 192
Author(s): Lei Gao, Zhuowei Wang, Shaoheng Li, Jianyao Chen
Five sediment cores (S1−S5) were collected from the Shima River to determine the bioavailability of trace metals (Cd, Cr, Cu, Ni, and Zn) using the modified European Community Bureau of Reference (BCR) procedure. The toxic effects of polluted sediment were assessed using the LUMISTox® bioassay with Vibrio fischeri and chemical models such as the toxicity unit (TU) of each metal, sum of all TUs (∑TU), and toxic risk index (TRI). The results showed that Cd, Ni, and Zn were present mainly in the acid-soluble and residual fractions, and the residual fraction of Cr accounted for the majority of the metal content (44%), while Cu was present mainly in the reducible and residual fractions. Cd had a mean enrichment factor (EF) of 15.1 and was considered to be severely enriched, while there was a minor enrichment of Cr and moderately severe enrichment of Zn, Cu, and Ni. From the LUMISTox® bioassay, an acute TU (TUa) value exceeding 0.4 was found at the upper and middle reach sites and was considered to represent slightly acute toxicity, whereas little acute toxicity was found at the lower reach site. The acid-soluble fraction of trace metals was the geochemical fraction mainly responsible for the acute toxicity of the sediment, and acid-soluble Zn and Ni were identified as important contributors to sediment toxicity.
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2. Do repeated limbic seizures induce depression-like behavior in rats?
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): W. McIntyre Burnham, Brian W. Scott
It has been reported that rapid kindling of the hippocampus produces lasting depression-like behavior in rats, as evidenced by increased immobility in the forced swim test and a loss of preference for sweetened water (Mazarati et al., 2007). This might suggest that repeated limbic seizure activity could be the cause of the depression often seen in patients with temporal lobe epilepsy.Sixty-day old male Wistar rats were implanted with electrodes in the amygdala and ventral hippocampus and kindled (or sham kindled) daily to a criterion of 10 stage 5 seizures. Two weeks later subjects were tested in the forced swim and sweet taste preference tests. No differences were found between the kindled and sham kindled animals.Subsequently, twenty-one day old male Wistar rat pups were implanted and quick kindled (or sham kindled) in the ventral hippocampus. Kindling was accomplished in a single day by stimulating every 5min for 84 stimulations. Four days or two weeks later they were tested in the forced swim and sweet taste preference tests. No differences were found between the kindled and sham kindled animals.The present data do not support the idea that repeated limbic seizures induce depression-like behavior in rats.
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Machine-based classification of ADHD and nonADHD participants using time/frequency features of event-related neuroelectric activity
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): Hüseyin Öztoprak, Mehmet Toycan, Yaşar Kemal Alp, Orhan Arıkan, Elvin Doğutepe, Sirel Karakaş
ObjectiveAttention-deficit/hyperactivity disorder (ADHD) is the most frequent diagnosis among children who are referred to psychiatry departments. Although ADHD was discovered at the beginning of the 20th century, its diagnosis is still confronted with many problems.MethodA novel classification approach that discriminates ADHD and nonADHD groups over the time-frequency domain features of event-related potential (ERP) recordings that are taken during Stroop task is presented. Time-Frequency Hermite-Atomizer (TFHA) technique is used for the extraction of high resolution time-frequency domain features that are highly localized in time-frequency domain. Based on an extensive investigation, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) was used to obtain the best discriminating features.ResultsWhen the best three features were used, the classification accuracy for the training dataset reached 98%, and the use of five features further improved the accuracy to 99.5%. The accuracy was 100% for the testing dataset. Based on extensive experiments, the delta band emerged as the most contributing frequency band and statistical parameters emerged as the most contributing feature group.ConclusionThe classification performance of this study suggests that TFHA can be employed as an auxiliary component of the diagnostic and prognostic procedures for ADHD.SignificanceThe features obtained in this study can potentially contribute to the neuroelectrical understanding and clinical diagnosis of ADHD.
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Interindividual variability in response to continuous theta-burst stimulation in healthy adults
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Ali Jannati, Gabrielle Block, Lindsay M. Oberman, Alexander Rotenberg, Alvaro Pascual-Leone
ObjectiveWe used complete-linkage cluster analysis to identify healthy subpopulations with distinct responses to continuous theta-burst stimulation (cTBS).Methods21 healthy adults (age±SD, 36.9±15.2years) underwent cTBS of left motor cortex. Natural log-transformed motor evoked potentials (LnMEPs) at 5–50min post-cTBS (T5–T50) were calculated.ResultsTwo clusters were found; Group 1 (n=12) that showed significant MEP facilitation at T15, T20, and T50 (p's<0.006), and Group 2 (n=9) that showed significant suppression at T5–T15 (p's<0.022). LnMEPs at T10 and T40 were best predictors of, and together accounted for 80% of, cluster assignment.In an exploratory analysis, we examined the roles of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms in the cTBS response. Val66Met participants showed greater facilitation at T10 than Val66Val participants (p=0.025). BDNF and cTBS intensity predicted 59% of interindividual variability in LnMEP at T10. APOE did not significantly affect LnMEPs at any time point (p's>0.32).ConclusionsData-driven cluster analysis can identify healthy subpopulations with distinct cTBS responses. T10 and T40 LnMEPs were best predictors of cluster assignment. T10 LnMEP was influenced by BDNF polymorphism and cTBS intensity.SignificanceHealthy adults can be sorted into subpopulations with distinct cTBS responses that are influenced by genetics.
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Effect of local cooling on excitation-contraction coupling in myasthenic muscle: Another mechanism of ice-pack test in myasthenia gravis
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Daisuke Yamamoto, Tomihiro Imai, Emiko Tsuda, Takayoshi Hozuki, Rika Yamauchi, Shin Hisahara, Jun Kawamata, Shun Shimohama
ObjectiveThe ice-pack test is a convenient diagnostic testing procedure for myasthenia gravis (MG). We investigated the underlying mechanism of the ice-pack test performed on bilateral masseters.MethodsWe performed trigeminal repetitive nerve stimulation (RNS), excitation-contraction (E-C) coupling assessment (Imai's method) and bite force measurement before and after cooling of the masseters in MG patients and normal controls. After placing the ice-pack on the masseters for 3min, serial recordings of the three tests were performed at various time intervals during 10min after cooling.ResultsThe bite force increased significantly after cooling in ice-pack-positive MG patients. The acceleration and acceleration ratio (acceleration at a given time to baseline acceleration) of jaw movement increased significantly after cooling of the masseters in ice-pack-positive MG patients compared to ice-pack-negative patients and normal controls. The prolonged effect of cooling continued until the end of recording even though decremental response to RNS had returned to baseline value.ConclusionsCooling of myasthenic muscle may induce two effects. One is relatively short effect on electrical synaptic transmission at the endplate, and another is prolonged effect on E-C coupling in the muscle.SignificanceThe ice-pack test induces a prolonged effect of ameliorating impaired E-C coupling in MG.
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Reduced motor cortical inhibition in migraine: A blinded transcranial magnetic stimulation study
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): J.P. Neverdahl, P.M. Omland, M. Uglem, M. Engstrøm, T. Sand
ObjectiveTo investigate motor cortical excitability, inhibition, and facilitation with navigated transcranial magnetic stimulation (TMS) in migraine in a blinded cross-sectional study.MethodsResting motor threshold (RMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were compared in 27 interictal migraineurs and 33 controls. 24 female interictal migraineurs and 27 female controls were compared in subgroup analyses. Seven preictal migraineurs were also compared to the interictal group in a hypothesis-generating analysis. Investigators were blinded for diagnosis during recording and analysis of data.ResultsSICI was decreased in interictal migraineurs when compared to healthy controls (p=0.013), CSP was shortened in female interictal migraineurs (p=0.041). ICF was decreased in preictal compared to interictal migraineurs (p=0.023). RMT and ICF were not different between interictal migraineurs and controls.ConclusionCortical inhibition was decreased in migraineurs between attacks, primarily in a female subgroup, indicating an importance of altered cortical inhibition in migraine.SignificancePrevious studies on motor cortical excitability in migraineurs have yielded varying results. This relatively large and blinded study provides support for altered cortical inhibition in migraine. Measuring intracortical facilitation in the period preceding migraine attacks may be of interest for future studies.
http://ift.tt/2yVJmbR
Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects
Source:Clinical Neurophysiology, Volume 128, Issue 12
Author(s): Tamara Gedankien, Peter J. Fried, Alvaro Pascual-Leone, Mouhsin M. Shafi
ObjectiveWe studied the correlation between motor evoked potentials (MEPs) and early TMS-evoked EEG potentials (TEPs) from single-pulse TMS before and after intermittent Theta Burst Stimulation (iTBS) to the left primary motor cortex (M1) in 17 healthy older participants.MethodsTMS was targeted to the hand region of M1 using a MRI-guided navigated brain stimulation system and a figure-of-eight biphasic coil. MEPs were recorded from the right first dorsal interosseous muscle using surface EMG. TEPs were extracted from a 61-channel EEG recording. Participants received 90 single TMS pulses at 120% of resting motor threshold before and after iTBS.ResultsAcross all participants, the change in N15-P30 TEP and MEP amplitudes were significantly correlated (r=0.69; p<0.01). Average TEP responses did not change significantly after iTBS, whereas MEP amplitudes showed a significant increase.ConclusionsChanges in corticospinal reactivity and cortical reactivity induced by iTBS are related. However, the effect of iTBS on TEPs, unlike MEPs, is not straightforward.SignificanceOur findings help elucidate the relationship between changes in cortical and corticospinal excitability in healthy older individuals. Going forward, TEPs may be used to evaluate the effects of theta-burst stimulation in non-motor brain regions.
http://ift.tt/2z0lLsM
Corticomuscular coherence in the acute and subacute phase after stroke
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Lisbeth Hoejkjaer Larsen, Ivan Chrilles Zibrandtsen, Troels Wienecke, Troels Wesenberg Kjaer, Mark Schram Christensen, Jens Bo Nielsen, Henning Langberg
ObjectiveStroke is one of the leading causes of physical disability due to damage of the motor cortex or the corticospinal tract. In the present study we set out to investigate the role of adaptations in the corticospinal pathway for motor recovery during the subacute phase after stroke.MethodsWe examined 19 patients with clinically diagnosed stroke and 18 controls. The patients had unilateral mild to moderate weakness of the hand. Each patient attended two sessions at approximately 3days (acute) and 38days post stroke (subacute). Task-related changes in the communication between motor cortex and muscles were evaluated from coupling in the frequency domain between EEG and EMG during movement of the paretic hand.ResultsCorticomuscular coherence (CMC) and intermuscular coherence (IMC) were reduced in patients as compared to controls. Paretic hand motor performance improved within 4–6weeks after stroke, but no change was observed in CMC or IMC.ConclusionsCMC and IMC were reduced in patients in the early phase after stroke. However, changes in coherence do not appear to be an efficient marker for early recovery of hand function following stroke.SignificanceThis is the first study to demonstrate sustained reduced coherence in acute and subacute stroke.
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Editorial Board
Source:Clinical Neurophysiology, Volume 128, Issue 11
http://ift.tt/2z1olP4
Contents
Source:Clinical Neurophysiology, Volume 128, Issue 11
http://ift.tt/2yXiS9Q
4. Prevention of trauma-induced epileptogenesis in mice via manipulation of the network excitability
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): S. Soltani, J. Seigneur, S. Chauvette, I. Timofeev
A large proportion of patients with severe brain damage become epileptic several months to years after the trauma. The mechanisms leading to the development of epilepsy (epileptogenesis) are unknown. We hypothesize that brain damage leads to partial deafferentation and a drop in excitability of the affected area. To compensate, the brain employs a variety of mechanisms to restore this drop of excitability and if not properly controlled, this leads to epilepsy. We performed undercut in the somatosensory area in adult C57/BL6 mice and implanted LFP and EMG electrodes for continuous electrographic recordings for at least two months. We proposed to manipulate (increase or decrease) network activities in order to prevent/enhance epileptogenesis applying DREADD technology. Target cortical regions were injected with AAV-hM3D(Gq) or AAV-hM4D(Gi). Activation of the designed receptor in infected neurons was achieved by clozapine-N-oxide continuously injected via an osmotic pump. Activation of hM3D(Gq) leads to depolarization and increased firing in infected neurons, while the activation of hM4D(Gi) induces a hyperpolarization of neurons. If our hypothesis is true, we expect to obtain epileptogenesis in adult mice without DREADD manipulations, either abolition or strong reduction of epileptogenesis in hM3D(Gq) mice, and increased epileptogenesis symptoms in hM4D(Gi) mice. In the following weeks all adult mice without DREADD manipulations revealed recurrent seizure activities. Mice in which hM4D(Gi) was activated revealed earlier and more severe seizures. Mice with hM3D(Gq) activation did not reveal paroxysmal activities. These results will lead to the development of new preventive treatments of epileptogenesis induced by brain damage.Supported by CIHR and NSERC.
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Electrical impedance myography changes after incomplete cervical spinal cord injury: An examination of hand muscles
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Le Li, Henry Shin, Argyrios Stampas, Xiaoyan Li, Ping Zhou
ObjectiveThis study was to apply the newly developed electrical impedance myography (EIM) technique to examine hand muscles in patients with an incomplete cervical spinal cord injury (SCI).MethodsEIM was performed on the thenar, hypothenar, and first dorsal interosseous (FDI) muscles of SCI (n=16) and age-matched healthy control (n=18) subjects. By sending low intensity and high frequency current through the skin and measuring the consequent voltage, EIM estimates the major impedance parameters, which include resistance (R), reactance (X) and phase angle (θ).ResultsThe SCI group had lower reactance and phase angle (p<0.0001) as compared to the control group in all three muscles, and lower resistance in the thenar muscle (p<0.05). The SCI group also demonstrated a smaller anisotropy in resistance (p<0.0001) and larger anisotropy in phase angle (p<0.05) compared to those from healthy controls.ConclusionThe reduced reactance and phase angle of paralyzed muscles could be due tochanges of membrane integrity and fat infiltration, whereas the change in the anisotropy may reflect the rearrangement of muscle fiber geometry.SignificanceThe EIM provides a quick and convenient tool for examination of muscle alterations after SCI.
http://ift.tt/2yVJhVB
Plasticity induced by non-invasive transcranial brain stimulation: A position paper
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Ying-Zu Huang, Ming-Kue Lu, Andrea Antal, Joseph Classen, Michael Nitsche, Ulf Ziemann, Michael Ridding, Masashi Hamada, Yoshikazu Ugawa, Shapour Jaberzadeh, Antonio Suppa, Walter Paulus, John Rothwell
Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. Non-invasive transcranial brain stimulation may modulate cortical excitability outlasting the period of non-invasive transcranial brain stimulation itself from several minutes to more than one hour. Quite a few lines of evidence, including pharmacological, physiological and behavioral studies in humans and animals, suggest that the effects of non-invasive transcranial brain stimulation are produced through effects on synaptic plasticity. However, there is still a need for more direct and conclusive evidence. The fragility and variability of the effects are the major challenges that non-invasive transcranial brain stimulation currently faces. A variety of factors, including biological variation, measurement reproducibility and the neuronal state of the stimulated area, which can be affected by factors such as past and present physical activity, may influence the response to non-invasive transcranial brain stimulation. Work is ongoing to test whether the reliability and consistency of non-invasive transcranial brain stimulation can be improved by controlling or monitoring neuronal state and by optimizing the protocol and timing of stimulation.
http://ift.tt/2z3l3L9
After-effects of transcranial alternating current stimulation on evoked delta and theta power
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Miles Wischnewski, Dennis J.L.G. Schutter
ObjectivePhase synchronization is suggested to be among the mechanisms that can explain the effects of transcranial alternating current stimulation (tACS). However, little is known about the effects of tACS on event-related oscillatory activity. Therefore the objective was to investigate frequency-related effects of frontal tACS on event-related oscillatory power.MethodsIn a double blind randomized controlled cross-over design, twenty-four participants received 12min of delta (2.5Hz), theta tACS (5Hz) and sham tACS at an intensity of 1mA peak-to-peak. Event-related delta- and theta-related oscillatory activity was recorded to reward- and punishment-related feedback signals.ResultsDelta tACS decreased feedback-related oscillatory power in the 1.5 and 3.5Hz frequency range. This effect was driven by power changes below the tACS frequency stimulation.ConclusionExogenous field potentials can attenuate event-related oscillatory activity in a rhythm slightly below the stimulation frequency. Our findings suggest an interaction between tACS and event-related rhythmic activity that extends beyond phase synchronization.SignificanceThese findings add novel insights into the mechanisms of tACS after-effects.
http://ift.tt/2yVJeJp
1. Across all the seven seas: Fifty years in neurology, EEG and epilepsies
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Paul Hwang
Since the 1960s, major neuroscience advances have facilitated the development of new antiepilepsy drugs (AEDs) targeting specific neurotransmitter-receptor systems, particularly the GABAergic, the NMDA-receptors and voltage-gated ion channels. In addition to the classical AEDs, carbamazepine and cogeners act at the voltage-gates sodium channels, while ethosuxumide acts at the calcium channel, improving the treatment of partial and generalized seizures. But approximately 30% of partial complex seizures remain refractory to AEDs, leading to novel AEDs: levetiracetam, tiagabine, lacosamide, perampanel and others. The pharmacoresistant epilepsies are typically dyscognitive partial-onset, arising from limbic structures of mesial temporal lobes, better visualised by improved neuroimaging methods eg. MRI and PET. Together with invasive intracranial monitoring in specialized units with long-term recording of multichannelled EEG and videorecording of behaviour, the localization of the seizure-onset zone has allowed targeted excision of the epileptogenic tissue for better outcome.Functional neurosurgical methods include vagal nerve stimulation and deep brain stimulation of selected targets in affected circuits, mapped by new EEG criteria including gamma rhythm, HFOs, ripples and clusters. Novel intervention in refractory epilepsies include the ketogenic diet and variants, neurosteroids, hormones eg. progestins and ACTH. A number of genetic mutations and copy number variants have been linked to epilepsies. It remains to be seen how expanded knowledge of the genetic bases of the epilepsies and epileptic encephalopathies leads to new intervention improving long-term prognosis and quality of life in persons afflicted with this ancient curse of the human condition, 'The Falling Sickness' also known as 'The Sacred Disease' (Hippocrates).In the words of Sir William Osler: 'He who studies medicine without books sails an uncharted sea, but he who studies medicine without patients does not go to sea at all' ('Aequanimitas' by Osler), quoted in Herbert Ho Ping Kong, 'The Art of Medicine: Healing and the Limits of Technology' (ECW Press, 2014 Toronto).
http://ift.tt/2z1mM3M
3. Asymmetric hypsarrythmia: An insight into the pathophysiology of infantile spasms. A retrospective cohort
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): B. Desnous, M. Arbour, H.S. Nguyen, A. Lortie, D. Chartrand, E. Rossignol, P. Diadori, P. Major, L. Carmant, A. Birca
Infantile spasms (IS) is a catastrophic epilepsy where treatment precocity improves outcome. Previous studies demonstrated an association between asymmetric hypsarrhythmia on EEG and ipsilateral hemispheric lesions on MRI, suggesting a possible role of cortical lesions in the initiation of IS. Epileptiform abnormalities appearing during early infancy have also been linked to IS emergence. We hypothesized that focal lateralized EEG abnormalities during the prehyspasrrhythmic period will be associated with asymmetric hypsarrhythmia at IS onset.We recruited a retrospective cohort of 80 infants, 7.4±3.6months old at the onset of hypsarrhythmia and IS, admitted to Sainte-Justine Hospital between 2007 and 2016. Seven infants showed an asymmetric hypsarrhythmia pattern and, as expected, all of them had lateralized lesions on MRI. Of the remaining 73, 42 had abnormal MRI, but only 3 infants had lateralized lesions (100% vs 7.1%, p<0.01). Thirty-four patients had pre-hypsarrhythmic EEG recordings at the age of 4.6±2.6months, 3±2months before IS onset, including four infants with asymmetric hypsarrhythmia. Five infants had no pre-hypsarrhythmic epileptiform abnormalities.Six had focal lateralized, while 23 multifocal abnormalities. The proportion of patients with focal abnormalities was higher in those who developed asymmetric compared to symmetric hypsarrhythmia (50% vs 13.3%, p<0.05).Our data confirm the link between asymmetric hypsarrhythmia and lateralized MRI lesions. Moreover, we show that focal lateralized EEG abnormalities precede asymmetric hypsarrythmia, which supports the involvement of cerebral cortex in the IS genesis. More sensitive EEG biomarkers of high IS risk may help developing preventative treatments that will improve outcomes in IS.
http://ift.tt/2yYqMA8
Neural network topology in ADHD; evidence for maturational delay and default-mode network alterations
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): T.W.P. Janssen, A. Hillebrand, A. Gouw, K. Geladé, R. Van Mourik, A. Maras, J. Oosterlaan
ObjectiveAttention-deficit/hyperactivity disorder (ADHD) has been associated with widespread brain abnormalities in white and grey matter, affecting not only local, but global functional networks as well. In this study, we explored these functional networks using source-reconstructed electroencephalography in ADHD and typically developing (TD) children. We expected evidence for maturational delay, with underlying abnormalities in the default mode network.MethodsElectroencephalograms were recorded in ADHD (n=42) and TD (n=43) during rest, and functional connectivity (phase lag index) and graph (minimum spanning tree) parameters were derived. Dependent variables were global and local network metrics in theta, alpha and beta bands.ResultsWe found evidence for a more centralized functional network in ADHD compared to TD children, with decreased diameter in the alpha band (ηp2=0.06) and increased leaf fraction (ηp2=0.11 and 0.08) in the alpha and beta bands, with underlying abnormalities in hub regions of the brain, including default mode network.ConclusionsThe finding of a more centralized network is in line with maturational delay models of ADHD and should be replicated in longitudinal designs.SignificanceThis study contributes to the literature by combining high temporal and spatial resolution to construct EEG network topology, and associates maturational-delay and default-mode interference hypotheses of ADHD.
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5. Epilepsy and EEG activity in early-onset Alzheimer’s disease
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Ángela Milán-Tomás, Paul Hwang
ObjectiveThe aim of this review was to evaluate and summarize the current literature regarding the incidence and features of epileptic seizures in early onset Alzheimer's disease (AD) as well as its epileptiform characteristics as described by electroencephalography (EEG).BackgroundThe incidence of epilepsy in AD is higher than in the general population, although the true prevalence of seizures has remained unclear due to methodological problems detecting these events in a cognitively impaired population.Design/MethodsA literature search using Medline with PubMed and EMBASE was carried out identifying papers published focusing on EEG and epilepsy in early-onset Alzheimer's disease (EOAD). A total of 767 abstracts were obtained, 55 full publications were screened and references were checked for additional material where appropriate.ResultsOnly 20 studies included EEG data regarding epilepsy in Alzheimer's disease of which 11 were animal models. AD due to amyloid precursor protein (APP) mutations has been described as one of the most common early-onset AD forms presenting with epileptic seizures. Neurodegeneration of the hippocampal region causing aberrant excitatory neuronal activity is the most accepted hypothesis for the occurrence of epilepsy in AD.ConclusionsThere is a need for better methodological studies addressing the role of EEG in the diagnosis and characterization of seizures in AD. Subclinical epileptiform activity may lead to a faster decline in cognition and they occur more often during sleep stages, therefore a prolonged sleep EEG can be an effective diagnostic tool for detecting this activity.
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Contents Continued
Publication date: December 2017
Source:Neurobiology of Aging, Volume 60
http://ift.tt/2xysczz
Age-dependent association of thyroid function with brain morphology and microstructural organization: evidence from brain imaging
Source:Neurobiology of Aging, Volume 61
Author(s): Layal Chaker, Lotte G.M. Cremers, Tim I.M. Korevaar, Marius de Groot, Abbas Dehghan, Oscar H. Franco, Wiro J. Niessen, M. Arfan Ikram, Robin P. Peeters, Meike W. Vernooij
Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60.2, range 45.6–89.9 years). Higher FT4 levels were associated with larger total intracranial volumes (β = 6.73 mL, 95% confidence interval = 2.94–9.80). Higher FT4 levels were also associated with larger total brain and white matter volumes in younger individuals, but with smaller total brain and white matter volume in older individuals (p-interaction 0.02). There was a similar interaction by age for the association of FT4 with mean diffusivity on diffusion tensor imaging (p-interaction 0.026). These results are in line with differential effects of TH during neurodevelopmental and neurodegenerative processes and can improve the understanding of the role of thyroid function in neurodegenerative disorders.
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Intercellular transfer of pathogenic α-synuclein by extracellular vesicles is induced by the lipid peroxidation product 4-hydroxynonenal
Source:Neurobiology of Aging, Volume 61
Author(s): Shi Zhang, Erez Eitan, Tsung-Yu Wu, Mark P. Mattson
Parkinson's disease (PD) is characterized by accumulations of toxic α-synuclein aggregates in vulnerable neuronal populations in the brainstem, midbrain, and cerebral cortex. Recent findings suggest that α-synuclein pathology can be propagated transneuronally, but the underlying molecular mechanisms are unknown. Advances in the genetics of rare early-onset familial PD indicate that increased production and/or reduced autophagic clearance of α-synuclein can cause PD. The cause of the most common late-onset PD is unclear, but may involve metabolic compromise and oxidative stress upstream of α-synuclein accumulation. As evidence, the lipid peroxidation product 4-hydroxynonenal (HNE) is elevated in the brain during normal aging and moreso in brain regions afflicted with α-synuclein pathology. Here, we report that HNE increases aggregation of endogenous α-synuclein in primary neurons and triggers the secretion of extracellular vesicles (EVs) containing cytotoxic oligomeric α-synuclein species. EVs released from HNE-treated neurons are internalized by healthy neurons which as a consequence degenerate. Levels of endogenously generated HNE are elevated in cultured cells overexpressing human α-synuclein, and EVs released from those cells are toxic to neurons. The EV-associated α-synuclein is located both inside the vesicles and on their surface, where it plays a role in EV internalization by neurons. On internalization, EVs harboring pathogenic α-synuclein are transported both anterogradely and retrogradely within axons. Focal injection of EVs containing α-synuclein into the striatum of wild-type mice results in spread of synuclein pathology to anatomically connected brain regions. Our findings suggest a scenario for late-onset PD in which lipid peroxidation promotes intracellular accumulation and then extrusion of EVs containing toxic α-synuclein species; the EVs are then internalized by adjacent neurons, so propagating the neurodegenerative process.
http://ift.tt/2zSAIu1
Parkin absence accelerates microtubule aging in dopaminergic neurons
Source:Neurobiology of Aging, Volume 61
Author(s): Daniele Cartelli, Alida Amadeo, Alessandra Maria Calogero, Francesca Vittoria Marialuisa Casagrande, Carmelita De Gregorio, Mariarosa Gioria, Naoko Kuzumaki, Ilaria Costa, Jenny Sassone, Andrea Ciammola, Nobutaka Hattori, Hideyuki Okano, Stefano Goldwurm, Laurent Roybon, Gianni Pezzoli, Graziella Cappelletti
Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dopaminergic neuron cell bodies and fibers, localized in the substantia nigra and corpus striatum, respectively. Interestingly, in PARK2 knockout mice, changes of MT stability preceded the alteration of mitochondria transport. Moreover, in-cell experiments confirmed that loss of parkin affects mitochondria mobility and showed that this defect depends on MT system as it is rescued by paclitaxel, a well-known MT-targeted agent. Furthermore, both in PC12 neuronal cells and in patients' induced pluripotent stem cell–derived midbrain neurons, we observed that parkin deficiencies cause the fragmentation of stable MTs. Therefore, we suggest that parkin acts as a regulator of MT system during neuronal aging, and we endorse the hypothesis that MT dysfunction may be crucial in the pathogenesis of Parkinson's disease.
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Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid beta in differentiated SH-SY5Y cells
Source:Neurobiology of Aging, Volume 60
Author(s): Valerie Sackmann, Anna Ansell, Christopher Sackmann, Harald Lund, Robert A. Harris, Martin Hallbeck, Camilla Nilsberth
Neuroinflammation plays an influential role in Alzheimer's disease (AD), although the mechanisms underlying this phenomenon remain largely unknown. Microglia are thought to be responsible for the majority of these effects and can be characterized into resting (M0), proinflammatory (M1), or anti-inflammatory (M2) functional phenotypes. We investigated the effects of conditioned macrophage media, as an analogue to microglia, on the transfer of oligomeric amyloid beta (oAβ) between differentiated SH-SY5Y cells. We also investigated how the different inflammatory environments related to intercellular and intracellular changes. We demonstrate that M2 products decrease interneuronal transfer of oAβ, while recombinant interleukin (IL)-4, IL-10, and IL-13 increase transfer. There were no alterations to the mRNA of a number of AD-related genes in response to the combination of oAβ and M0, M1, or M2, but several intracellular proteins, some relating to protein trafficking and the endosomal/lysosomal system, were altered. Stimulating microglia to an M2 phenotype may thus slow down the progression of AD and could be a target for future therapies.
http://ift.tt/2zPQXrU
Response to a letter to the editor: sleep disturbance as a stressor event in elderly's life
Source:Neurobiology of Aging, Volume 60
Author(s): Sami Ouanes, José Haba-Rubio, Julius Popp
http://ift.tt/2hlwCnv
Altered mGluR5 binding potential and glutamine concentration in the 6-OHDA rat model of acute Parkinson's disease and levodopa-induced dyskinesia
Source:Neurobiology of Aging, Volume 61
Author(s): Melissa Crabbé, Anke Van der Perren, Akila Weerasekera, Uwe Himmelreich, Veerle Baekelandt, Koen Van Laere, Cindy Casteels
Several lines of evidence point to alterations in glutamatergic signaling in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), involving the metabotropic glutamate receptor type 5 (mGluR5). Using small-animal positron emission tomography (PET) with [18F]FPEB and proton magnetic resonance spectroscopy, we investigated cerebral changes in the mGluR5 and glutamate/glutamine availability in vivo in PD rats and following onset of LIDs. In parallel, behavioral tests were performed. Comparing PD to control rats, mGluR5 binding potential was decreased in a cluster comprising the bilateral caudate-putamen (CP), ipsilateral motor cortex and somatosensory cortex, and the contralateral somatosensory cortex and parietal association cortex, with the most pronounced reduction in the ipsilateral CP. mGluR5 binding potentials were not significantly altered upon levodopa (L-DOPA) treatment. However, following L-DOPA, an increase in relative mGluR5 uptake was present in the contralateral motor cortex and somatosensory cortex. Glutamate and glutamine concentrations did not differ between control and untreated PD rats or between hemispheres. Though, glutamine levels were higher in the contralateral CP of saline- and L-DOPA-treated rats as compared to the ipsilateral side. Relative mGluR5 uptake in the CP of levodopa-treated rats was also found positively correlated with abnormal involuntary movement scores. Conclusively, mGluR5 availability and glutamine concentrations in the CP are involved in PD, whereas mGluR5 availability in cortical regions may be involved in LID pathology.
http://ift.tt/2zQGLiN
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
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Abstract Noise pollution is a major factor of environmental complaints in many cities, which has significant impacts on human health. As a...
