Various large studies have provided unprecedented insights into the genetics of autism spectrum disorders (ASDs). This Review discusses the challenges and opportunities of translating genetic and biological insights into clinical progress for ASDs, in areas including genetic testing, ASD classification, genetic counselling, comorbidities and therapeutics.
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Κυριακή 5 Μαρτίου 2017
Autism genetics: opportunities and challenges for clinical translation
Diagnostic Utility of Testosterone Priming Prior to Dynamic Tests to Differentiate Constitutional Delay in Puberty from Isolated Hypogonadotropic Hypogonadism
Abstract
Context
Differentiation between constitutional delay in puberty (CDP) and isolated hypogonadotropic hypogonadism (IHH) during adolescence is a great clinical challenge and the available diagnostic tests are of limited value.
Objective
To study the effect of withdrawal of short term, low dose testosterone therapy (testosterone priming) on the discriminatory power of dynamic tests for hypothalamo-pituitary-testicular axis to differentiate CDP from IHH.
Design
A prospective study (n=30) consisting of 20 boys with delayed puberty (Group A) and 10 patients with IHH (Group B).
Intervention
Patients in groups A and B underwent Triptorelin and hCG stimulation tests, prior to and 2 months after withdrawal of 'testosterone priming' (100 mg intramuscularly 4 weekly for 3 months) and were followed up until onset of puberty or 18 years of age, whichever was earlier.
Results
At baseline, Triptorelin-stimulated 4h LH, with a cut-off of 2.8 IU/l, and hCG-stimulated day 7 testosterone with a cut-off of 3.8 nmol/L had sensitivities of 80% each, and specificities of 93% and 87%, respectively, to diagnose CDP. After withdrawal of testosterone,a 4h LH cut-off of 14.7IU/l and day 7 testosterone cut-off of 10.3nmol/L had sensitivities of 93% and 88% respectively, and specificity and positive predictive value of 100% each. A basal inhibin B >94.7ng/l was discriminatory for diagnosing CDP after withdrawal of testosterone priming.
Conclusions
Inhibin B levels or 4 h LH after Triptorelin stimulation are the best discriminatory tests to differentiate CDP from IHH, when performed after withdrawal of 'testosterone priming'.
This article is protected by copyright. All rights reserved.
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VideoEndocrinology™ High-Impact Videos
FREE ACCESS through March 14, 2017.
Transoral Endoscopic Total Parathyroidectomy in Renal Hyperparathyroidism Patient
Thanyawat Sasanakietkul, Wirada Wandee, Pornpeera Jitpratoom, Angkoon Anuwong
Transoral Endoscopic Thyroidectomy Vestibular Approach
Thanyawat Sasanakietkul, Tobias Carling
Robotic Bilateral Cortical-Preserving Adrenalectomy in an MEN2A Patient with Steroid Allergy
Nisar Zaidi, Zanati Ahmed, Jesse Gutnick, Eren Berber
The post VideoEndocrinology™ High-Impact Videos appeared first on American Thyroid Association.
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Plasticity of hippocampal memories in humans
Source:Current Opinion in Neurobiology, Volume 43
Author(s): Aidan J Horner, Christian F Doeller
The human hippocampus is a brain region that supports episodic and spatial memory. Recent experiments have drawn on animal research and computational modelling to reveal how the unique computations and representations of the hippocampus support episodic and spatial memory. Invasive electrophysiological recordings and non-invasive functional brain imaging have provided evidence for the rapid formation of hippocampal representations, as well as the ability of the hippocampus to both pattern-separate and pattern-complete input from the neocortex. Further, recent evidence has shown that hippocampal representations are in constant flux, undergoing a continual process of strengthening, weakening and altering. This research offers a glimpse into the highly plastic and flexible nature of the human hippocampal system in relation to episodic memory.
http://ift.tt/2mtrmBL
A Comparison of Two Cadaveric Acellular Dermal Matrices for Immediate Breast Reconstruction: A Prospective Randomized Trial
AlloDerm RTU® and AlloMaxTM are two acellular dermal matrices (ADMs) used in implant based breast reconstruction. In this study, we examined whether different processing methods for the ADMs lead to a disparity in histologic, clinical, and financial outcomes after breast reconstruction. Thirty patients were randomized into AlloMax or AlloDerm arms (n=15, each). ADM was placed at the time of immediate reconstruction. Patients were evaluated for complications on post-operative days 7, 14, and 30. During implant exchange, ADM biopsies were taken and compared histologically for vascular and cellular infiltration.
http://ift.tt/2lQ8YQ4
Improved prediction of protein–protein interactions using novel negative samples, features, and an ensemble classifier
Source:Artificial Intelligence in Medicine
Author(s): Leyi Wei, Pengwei Xing, Jiancang Zeng, JinXiu Chen, Ran Su, Fei Guo
Computational methods are employed in bioinformatics to predict protein–protein interactions (PPIs). PPIs and protein–protein non-interactions (PPNIs) display different levels of development, and the number of PPIs is considerably greater than that of PPNIs. This significant difference in the number of PPIs and PPNIs increases the cost of constructing a balanced dataset. PPIs can be classified as either physical or genetic. However, ready-made PPNI databases were proven only to have no physical interactions and were not proven to have no genetic interactions. Hence, ready-made PPNI databases contain false negative non-interactions. In this study, two PPNI datasets were artificially generated from a PPI database. In contrast to various traditional PPI feature extraction methods based on sequential information, two types of novel feature extraction methods were proposed. One is based on secondary structure information, and the other is based on the physicochemical properties of proteins. The experimental results of the RandomPairs dataset validate the efficiency and effectiveness of the proposed prediction model. These results reveal the potential of constructing a PPI negative dataset to reduce false negatives. Related datasets, tools, and source codes are accessible at http://ift.tt/2mUCNQH.
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Pharmacological and antihyperalgesic properties of the novel α2/3 preferring GABAA receptor ligand MP-III-024
Source:Brain Research Bulletin
Author(s): Bradford D. Fischer, Raymond J. Schlitt, Bryan Z. Hamade, Sabah Rehman, Margot Ernst, Michael M. Poe, Guanguan Li, Revathi Kodali, Leggy A. Arnold, James M. Cook
γ-Aminobutyric acid type A (GABAA) receptors are located in spinal nociceptive circuits where they modulate the transmission of pain sensory signals from the periphery to higher centers. Benzodiazepine-type drugs bind GABAA, receptors containing α1, α2, α3, and α5 subunits (α1GABAA, α2GABAA, α3GABAA, and α5GABAA receptors, respectively) through which they inhibit the transmission of these signals. However, the role of these different GABAA receptor subtypes in the antihyperalgisic properties of benzodiazepine-type drugs has not been characterized fully and is limited by currently available compounds. In the present study we describe the novel benzodiazepine site positive allosteric modulator modulator methyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate (MP-III-024). MP-III-024 displayed preference for α2GABAA and α3GABAA receptors relative to α1GABAA and α5GABAA receptors as well as an improved metabolic profile relative to subtype-selective positive modulators that are available currently. MP-III-024 produced a dose- and time-dependent reversal of mechanical sensitivity. On locomotor activity and schedule-controlled responding, MP-III-024 was ineffective across the doses tested. These data provide further evidence that α2GABAA and α3GABAA receptors play an important role in the antihyperalgiesic effects and may not be involved in some of the off target effects of benzodiazepine-like drugs. Further, these findings suggest that MP-III-024 is an ideal research tool for investigating the role of α2GABAA and α3GABAA receptors in the behavioral properties of benzodiazepine-like drugs in mice.
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Characterizations of CD4-1, CD4-2 and CD8β T cell subpopulations in peripheral blood leucocytes, spleen and head kidney of Japanese flounder (Paralichthys olivaceus)
Source:Molecular Immunology, Volume 85
Author(s): Jing Xing, Junjie Ma, Xiaoqian Tang, Xiuzhen Sheng, Wenbin Zhan
In the previous study, antibodies against CD3 molecule have been produced and were used in labeling T cells in Japanese flounder (Paralichthys olivaceus). In this paper, CD4+ and CD8+ lymphocytes subpopulations in peripheral blood leucocytes (PBL), spleen and head kidney of flounder were investigated. The flounder CD4-1, CD4-2 and CD8β recombinant proteins and their antibodies (Abs) were produced, then the cross-reactivity of the Abs to CD4-1, CD4-2 and CD8β was detected by Western blotting, respectively, and the reactions of Abs to PBL were analyzed by immunofluorescence staining (IFS) and flow cytometry (FCM). CD4-1+/CD3+, CD4-2+/CD3+, and CD8β+/CD3+ lymphocytes in PBL, spleen and head kidney were observed by double IFS, then their proportions were analyzed using two-color FCM, respectively. Further, CD4-1/CD8β, CD4-2/CD8β, or CD4-1/CD4-2 lymphocytes were analyzed using double-IFS and two-color FCM. Finally, CD4-1+, CD4-2+, and CD8β+ lymphocytes in spleen and head kidney were observed by immunohistochemistry. The results showed that the Abs were specific for CD4-1, CD4-2 and CD8β molecules, respectively. The proportions of CD4-1+/CD3+, CD4-2+/CD3+, and CD8β+/CD3+ lymphocytes were 6.7±2.0%, 8.6±2.8%, 2.1±1.3% in PBL; 13.6±3.6%, 15.6±5.2%, 2.8±1.4% in spleen; 20.0±4.6%, 20.5±4.6%, 3.2±1.5% in head kidney, respectively. Most CD4+ and CD8+ cell subpopulations belonged to CD3+ cells; there were no cross-reactivity between CD4+ and CD8+ cells. CD4-1+/CD4-2−, CD4-1−/CD4-2+, and CD4-1+/CD4-2+ cells presented different proportions in PBL, spleen and head kidney, among them, CD4-1+/CD4-2+ cell is the majority of CD4T cell subpopulation.
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Inhibition of Bcl-2/xl with ABT-263 selectively kills senescent Type II pneumocytes and reverses persistent pulmonary fibrosis induced by ionizing radiation in mice
Publication date: Available online 4 March 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jin Pan, Deguan Li, Yanfeng Xu, Junling Zhang, Yueying Wang, Mengyi Chen, Shuai Lin, Lan Huang, Eun Joo Chung, Deborah E. Citrin, Yingying Wang, Martin Hauer-Jensen, Daohong Zhou, Aimin Meng
PurposeIonizing radiation (IR)-induced pulmonary fibrosis (PF) is an irreversible and severe late effect of thoracic radiotherapy. The goal of this study was to determine whether clearance of senescent cells with ABT-263, a senolytic drug that can selectively kill senescent cells, can reverse PF.Methods and MaterialsC57BL/6J mice were exposed to a single dose of 17 Gy on the right side of the thorax. Sixteen weeks after IR, they were treated with 2 cycles of vehicle or ABT-263 (50 mg/kg/day for 5 days per cycle) by gavage. The effects of ABT-263 on IR-induced increases in senescent cells, elevation in the expression of selective inflammatory cytokines, matrix metalloproteinases (Mmps) and tissue inhibitors of Mmps (Timps), and the severity of the tissue injury and fibrosis in the irradiated lungs were evaluated 3 weeks after the last treatment, in comparison with the changes observed in the irradiated lungs before the treatment or after vehicle treatment.ResultsThe results show that 16 weeks after exposure of C57BL/6 mice to a single dose of 17 Gy thoracic irradiation resulted in persistent pulmonary fibrosis associated with a significant increase in senescent cells. Treatment of the irradiated mice with ABT-263 after they had developed persistent pulmonary fibrosis reduced senescent cells and reversed the disease.ConclusionsTo our knowledge, this is the first study to demonstrate that PF can be reserved by a senolytic drug such as ABT-263 after it becomes a progressive disease. Therefore, ABT-263 has the potential to be developed as a new treatment for PF.
Teaser
Ionizing radiation (IR)-induced pulmonary fibrosis (PF) is an irreversible and severe late effect of thoracic radiotherapy. Our studies show that ABT-263, a specific Bcl-2/xl inhibitor and a newly identified senolytic drug that can selectively kill senescent cells, could reverse PF even when the pulmonary fibrosis had already became persistent in mice after thoracic irradiation. This finding suggests that ABT-263 has the potential to be used as an effective treatment for PF.http://ift.tt/2mIeh8r
Interim 18FDG PET/CT during chemo-radiotherapy in the management of head-neck cancer patients: a systematic review
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Cristina Garibaldi, Sara Ronchi, Marta Cremonesi, Laura Gilardi, Laura Travaini, Mahila Ferrari, Daniela Alterio, Johannes H.A.M. Kaanders, Delia Ciardo, Roberto Orecchia, Barbara Alicja Jereczek-Fossa, Chiara Maria Grana
Positron-Emission-Tomography (PET) is an imaging modality widely applied in oncology for tumor staging, volume delineation in radiotherapy planning, and therapy response assessment. 18F-fluorodeoxyglucose PET combined with Computed Tomography (18F-FDG-PET/CT) plays a significant role in the management of locally advanced head-neck cancer patients in the pre-treatment setting to predict outcome and prognosis and after chemo-radiotherapy (CRT) to assess tumor response. This review aims to evaluate the use of FDG-PET acquired during CRT, ad interim FDG (FDGint), in order to identify tumor response at an early stage, modify the treatment plan if necessary or setup alternative strategies to enhance the therapeutic ratio. Most of the works confirmed the value of FDGint in predicting the response to CRT, while a few highlighted the poor predictive value of FDGint compared to FDG acquired two-four months after the end of CRT, which was well correlated with local and regional control and survival. Such findings deserve to be further analyzed in a more numerous and homogeneous series according to the tumor site and CRT schedules. The best time to assess tumor response during RT remains a matter of debate, although two weeks seem most favorable, still providing opportunity to adapt the treatment strategy.
http://ift.tt/2n2Shky
Outcomes of Routine Intensity Modulated Radiotherapy Quality Assurance in a large Head and Neck Cancer Center
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Isuru Amarasena, Ieta D'Costa, Tsien Fua, Albert Tiong, Vaughan Geddes, Phillip Tran, Chen Liu, June Corry
This is a retrospective analysis of a prospective database analysing an IMRT QA programme utilised in routine clinical practice at a large HNC center. The programme resulted in significant percentage of Major changes that were implemented and the time required for the QA process was less than expected. This study can inform discussion on optimal RT QA processes in routine clinical practice.
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Long-term growth decline in Toona ciliata in a moist tropical forest in Bangladesh: Impact of global warming
Publication date: April 2017
Source:Acta Oecologica, Volume 80
Author(s): Mizanur Rahman, Rofiqul Islam, Mahmuda Islam
Tropical forests are carbon rich ecosystems and small changes in tropical forest tree growth substantially influence the global carbon cycle. Forest monitoring studies report inconsistent growth changes in tropical forest trees over the past decades. Most of the studies highlighted changes in the forest level carbon gain, neglecting the species-specific growth changes which ultimately determine community-level responses. Tree-ring analysis can provide historical data on species-specific tree growth with annual resolution. Such studies are inadequate in Bangladesh, which is one of the most climate sensitive regions in the tropics. In this study, we investigated long-term growth rates of Toona ciliata in a moist tropical forest of Bangladesh by using tree-ring analysis. We sampled 50 trees of varying size, obtained increment cores from these trees and measured tree-ring width. Analyses of growth patterns revealed size-dependent growth increments. After correcting for the effect of tree size on tree growth (ontogenetic changes) by two different methods we found declining growth rates in T. ciliata from 1960 to 2013. Standardized ring-width index (RWI) was strongly negatively correlated with annual mean and maximum temperatures suggesting that rising temperature might cause the observed growth decline in T. ciliata. Assuming that global temperatures will rise at the current rate, the observed growth decline is assumed to continue. The analysis of stable carbon and oxygen isotopes may reveal more insight on the physiological response of this species to future climatic changes.
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Non-mammalian models reveal the role of alternative ligands for thyroid hormone receptors
Source:Molecular and Cellular Endocrinology
Author(s): Aurea Orozco, Iván Lazcano, Gabriela Hernández-Puga, Aurora Olvera
Thyroid hormones, or THs, are well-known regulators of a wide range of biological processes that occur throughout the lifespan of all vertebrates. THs act through genomic mechanisms mediated by thyroid hormone receptors (TRs). The main product of the thyroid gland is thyroxine or T4, which can be further transformed by different biochemical pathways to produce at least 15 active or inactive molecules. T3, a product of T4 outer-ring deiodination, has been recognized as the main bioactive TH. However, growing evidence has shown that other TH derivatives are able to bind to, and/or activate TRs, to induce thyromimetic effects. The compiled data in this review points to at least two of these TR alternative ligands: TRIAC and T2. Taking this into account, non-mammalian models have proven to be advantageous to explore new TH derivatives with potential novel actions, prompting a re-evaluation of the role and mechanism of action of TR alternative ligands that were previously believed to be inactive. The functional implications of these ligands across different vertebrates may require us to reconsider current established notions of thyroid physiology.
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Facing two faces: Defense activation varies as a function of personal relevance
Source:Biological Psychology
Author(s): Florian Bublatzky, Georg W. Alpers
It can be unsettling to be watched by a group of people, and when they express anger or hostility, this can prime defensive behavior. In contrast, when others smile at us, this may be comforting. This study tested to which degree the impact of facial expressions (happy, neutral, and angry) varies with the personal relevance of a social situation. Modelling a triadic situation, two faces looked either directly at the participant, faced each other, or they were back to back. Results confirmed that this variation constitutes a gradient of personal relevance (directed frontally > towards > away), as reflected by corresponding defensive startle modulation and autonomic nervous system activity. This gradient was particularly pronounced for angry faces and it was steeper in participants with higher levels of social anxiety. Thus, sender-recipient constellations modulate the processing of facial emotions in favor of adequate behavioral responding (e.g., avoidance) in group settings.
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Automating Cell Detection and Classification in Human Brain Fluorescent Microscopy Images Using Dictionary Learning and Sparse Coding
Source:Journal of Neuroscience Methods
Author(s): Maryana Alegro, Panagiotis Theofilas, Austin Nguy, Patricia A. Castruita, William Seeley, Helmut Heinsen, Daniela M. Ushizima, Lea T. Grinberg
BackgroundImmunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility.New methodDictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set.ResultsOur method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings.Comparison with existing methodsWe compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples.ConclusionThe proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks.
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Isometric endurance test of the cervical flexor muscles – reliability and normative reference values
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Jari Ylinen, Petri Salo, Salme Järvenpää, Arja Häkkinen, Riku Nikander
ObjectiveTo obtain reference values for the isometric endurance test (IET) of the cervical flexor muscles, investigate its reproducibility, and compare the results with the maximal isometric strength test (MIST) of the cervical flexor muscles.DesignCross-sectional non-comparative study with single group repeated measurements.MethodsAltogether 219 healthy females aged 20 to 59 years volunteered to participate in the study. The IET was performed in the supine position and MIST seated. The reproducibility was evaluated by the intraclass correlation coefficient (ICC) and an analysis described by Bland and Altman. The relationship between the two measuring methods was evaluated by Pearson's correlation coefficient.ResultsThe mean (SD) IET time was 60 (33) seconds with no significant differences between the age groups of each decade. The ICC for intrarater repeatability was 0.80. However, the Bland-Altman analysis suggested moderate variation in repeated measurements. Pearson's correlation coefficient between the IET and MIST was 0.56.ConclusionNormative reference values for the IET are presented. Although the ICC showed good repeatability, one should consider that the change at follow-up visits has to be considerable to be clinically relevant. The correlation between the endurance time and maximal flexion strength was moderate. Thus IET of the cervical flexor muscles may be used in the clinic like the Biering-Sorenson test has been used to assess fatigue of the trunk extensor muscles.
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Low handgrip strength levels among adolescents in a city in Southern Brazil
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Diego Augusto Santos Silva, Andreia Pelegrini, João Antônio Chula de Castro, Tiago Rodrigues de Lima, Gabriel Renaldo de Sousa, João Marcos Ferreira de Lima Silva, Edio Luiz Petroski
ObjectiveTo estimate the prevalence of low handgrip strength (HGS) levels and sociodemographic characteristics, health behaviours and body fatness status related in adolescents. Method: Cross-sectional epidemiological study with 636 adolescents aged 14-19 years in a city in southern Brazil. HGS was measured by dynamometer. Sociodemographic and behavioural data were collected using self-report questionnaires. Body mass and height was measured by Body Mass Index. Results: Prevalence of low HGS levels was 47% (63.5% boys, 37.7% girls). Boys aged 14-16 years were more likely to have low HGS levels. Girls who were of higher socioeconomic status and who were less physically active were more likely to have low HGS levels. Overweight girls were less likely to have low HGS levels. Conclusions: High prevalence of low HGS levels was observed in adolescents. Increased HGS levels should be focused on younger boys and normal-weight girls with higher socioeconomic status and lower levels of physical activity.
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The effects of neck mobilization in patients with chronic neck pain: A randomized controlled trial
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Muhammad Nazim Farooq, Mohammad A. Mohseni-Bandpei, Syed Amir Gilani, Muhammad Ashfaq, Qamar Mahmood
ObjectiveTo determine the effect of mobilization and routine physiotherapy on pain, disability, neck range of motion (ROM) and neck muscle endurance (NME) in patients having chronic mechanical neck pain (NP).MethodsSixty eight patients with chronic mechanical NP were randomly allocated into two groups by using a computer generated random sequence table with 34 patients in the multi-modal mobilization group and 34 patients in the routine physiotherapy group. Baseline values for pain, disability, NME, and neck ROM were recorded using visual analogue scale (VAS), neck disability index (NDI), neck flexor muscle endurance test and universal goniometer respectively, before the treatment. Each patient received 10 treatment sessions over a period of four weeks and at the end of four weeks all the outcome measures were recorded again.ResultsA paired t-test revealed significant pre to post treatment differences for all outcome measures in both groups (p < 0.001 in all instances). An independent t-test revealed statistically significant differences for pain, disability, NME, and neck rotation in favor of the multi-modal mobilization group with a between group difference of 1.57 cm for VAS (p < 0.001), 11.74 points for NDI (p = 0.001), 18.45 seconds for NME (p < 0.001) and 6.06 to 8.24 degrees for neck ROM (p < 0.05).ConclusionThe results suggest that a combination of cervical mobilization with routine physiotherapy is more effective for reducing pain and disability and improving NME and neck ROM in patients with chronic mechanical NP compared to routine physiotherapy alone.
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The effects of clinical Pilates exercises on patients with shoulder pain: A randomized clinical trial
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Esra Atılgan, Aydan Aytar, Aslıcan Çağlar, Ayça Aytar Tığlı, Gamze Arın, Gökmen Yapalı, Pınar Kısacık, Utku Berberoğlu, Hülya Özlem Şener, Edibe Ünal
AimThe purpose of this study was to determine the effect of Clinical Pilates exercises on patients with shoulder pain.Material and MethodsThirty-three patients, experiencing shoulder pain continuously for at least four weeks were selected as study subjects. The patients were randomly divided into two groups, namely Clinical Pilates exercise (n=17) group and conventional exercise (n=16) group. The patients were treated for five days a week, the total treatment being carried out for 10 days. The assessment of pain and disability amongst the patients were done at the baseline and at the end of the treatment sessions, using Visual Analogue Scale (VAS) and Shoulder Pain and Disability Index (SPADI).ResultsThe clinical Pilates exercise group showed a significant improvement in all scores used for assessment (p<0.05), while the conventional exercise group demonstrated a significant improvement only in the SPADI total score (p<0.05). A comparison of scores for the VAS, SPADI-Pain and SPADI-Total between the two groups, revealed a significant improvement in the Clinical Pilates exercise group (p<0.05).ConclusionIt was demonstrated by the study that Clinical Pilates exercise is an efficient technique for patients experiencing shoulder pain, as it helps reduce pain and disability among them.
http://ift.tt/2mTorzQ
Reliability of Kinematic Measures in Subjects With Anterior Cruciate Ligament Deficiency During Dual-Task Walking
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Salman Nazary-Moghadam, Mahyar Salavati, Ali Esteki, Behnam Akhbari, Sohrab Keyhani, Afsaneh Zeinalzadeh
ObjectiveTo define the throughout within- and between-day reliability of gait parameters in single - and dual-task conditions in subjects with and without anterior cruciate ligament deficiency (ACLD).MethodsFourteen subjects with ACLD and 14 healthy subjects completed a walking task on a treadmill with three levels of velocity (self-selected, high and low), with or without performing an auditory Stroop task over two sessions each 3-5 days apart. The gait kinematic parameters, including maximum and minimum hip flexion, total hip range of motion, maximum and minimum knee flexion and total knee range of motion were recorded using a motion analysis system. The intraclass correlation coefficient (ICC), the standard error of measurement (SEM), and the coefficient of variation (CV) were used to determine inter- and intrasession reliability of kinematic and cognitive measures.ResultsICCs for ACLD group in dual-task and single task conditions ranged between 0.50 to 0.93 and 0.53 to 0.93, respectively. ICC values for healthy groups in dual-task and single task conditions ranged between 0.36 to 0.90 and 0.39 to 0.87, respectively. When comparing relative reliability across kinematic variables in different velocities, ICC values were generally identical in all three levels of velocity.ConclusionThe findings suggest that dual-tasking could also be applied reliably for the assessment of functional activities in subjects with and without ACLD.
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Postural insoles on gait in children with cerebral palsy: Randomized controlled double-blind clinical trial
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Hugo Pasin Neto, Luanda André Collange Grecco, Luis Alfredo Braun Ferreira, Natália Almeida Carvalho Duarte, Manuela Galli, Claudia Santos Oliveira
The aim of the present study was to assess the effect of postural insoles on gait performance in children with Cerebral Palsy (CP).Twenty four children between four and 12 years of age were randomly allocated either the control group (n = 12) or experimental group (n = 12).The control group used placebo insoles and the experimental group used postural insoles. Three-dimensional gait analysis was performed under three conditions: barefoot, in shoes and in shoes with insoles. Three evaluations were carried out: 1)immediately following placement of the insoles; 2)after three months of insole use; and 3)one month after suspending insole use. Regarding the immediate effects and after three months use of insole, significant improvements in gait velocity and cadence were found in the experimental group, along with an increase in foot dorsiflexion, a reduction in knee flexion and a reduction in internal rotation. Conversely, these changes were not maintained in the third assessment, one month after withdrawal of the insoles. The use of postural insoles led to improvements in gait performance in children with CP.
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Effect of Movement Control and stabilization Exercises in People with Extension Related Non -Specific Low Back Pain- A pilot Study
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Sara Salamat, Saeed Talebian, Hosein Bagheri, Nader Maroufi, Mohammad Jafar Shaterzadeh, Gitta Kalbasi, Kieran O'Sullivan
BackgroundExercise is considered an effective treatment strategy for non-specific chronic low back pain (NSCLBP).In spite of the wide use of exercise protocols, it is not clear what type of exercise is more effective in decreasing pain, disability and normalizing muscle activation patterns in people with chronic low back pain.ObjectivesTo assess the effects of two exercise protocols (stabilization vs movement control) on pain and disability scores and the flexion relaxation ratio (FRR) of lumbar multifidus (LM) and iliocostalis lumbarum pars thoracic (ICLT) in people with extension related non-specific chronic low back pain.Study designPilot randomized control trial.Methods32 subjects with active extension pattern chronic low back pain (stabilization group=16, movement control group=16) participated in this study. Treatment groups received 4 weeks of exercise therapy. Outcomes were based on pain score (Numeric rating Scale-NRS), disability (Oswestry Disability Index- ODI) and FRR of the LM and ICLT.ResultsFour people dropped out of the study in each group for reasons unrelated to the protocols of the study. Pain and disability reduced in both groups, with no significant difference between the groups. The FRR of LM did not change in either treatment group after treatment. However, the FRR of ICLT was significantly increased after treatment in the movement control group.ConclusionBoth movement control and stabilization exercises reduced pain and disability in the short-term among people with extension pattern NSCLBP, with no difference in effectiveness between the groups. However, movement control exercises were more effective in normalizing back muscle activation patterns than stabilization exercises.
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Immediate effect of common peroneal nerve electrical stimulation on quadriceps muscle arthrogenic inhibition in patients with knee osteoarthritis
Publication date: Available online 4 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Hossein Rafsanjani, Khosro Khademi-Kalantari, Asghar Rezasoltani, Sedigheh Sadat Naimi, Mehri Ghasemi, Shapour Jaberzadeh
ObjectiveTo investigate the immediate effect of electrical stimulation of the common peroneal nerve on the maximum voluntary activation of the quadriceps muscle in patients with knee osteoarthritis.MethodologyFifteen subjects with knee osteoarthritis (mean age: 50.5±13 years) participated in this study. To measure the arthrogenic inhibition ratio of quadriceps, a burst of electrical stimulation was superimposed on the maximum voluntary contraction, and the percentage of change in the force production was computed. The same measurement was also performed with concurrent electrical stimulation of the common peroneal nerve.ResultsAll the patients with knee osteoarthritis showed significant arthrogenic inhibition of the quadriceps muscle. The stimulation of the common peroneal nerve was able to reduce this inhibition and increase the capacity of the muscle to produce a significantly higher knee extension force (p=0.028).ConclusionsElectrical stimulation of the common peroneal nerve concurrent with the maximum voluntary effort can remove the arthrogenic inhibition of the quadriceps muscle in patients with knee osteoarthritis. This finding could have clinical implications in the management of patients with knee disorders.
http://ift.tt/2mTEaPh
Smartphone–based enzymatic biosensor for oral fluid L-lactate detection in one minute using confined multilayer paper reflectometry
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Donato Calabria, Cristiana Caliceti, Martina Zangheri, Mara Mirasoli, Patrizia Simoni, Aldo Roda
The development of smartphone–based biosensors for point-of-care testing (POCT) applications allows realizing "all in one" instruments, with large potential distribution among the general population. With this respect, paper color-based detection performed by reflectance measurement is the most popular, simple, inexpensive and straightforward method. Despite the large number of scientific publications related to these biosensors, they still suffer from a poor detectability and reproducibility related to inhomogeneity of color development, which leads to low assay reproducibility. To overcome these problems, we propose a smartphone paper-based biosensor, in which all the reagents necessary to complete the analysis are co-entrapped on paper in a "wafer"-like bilayer film of polyelectrolytes (Poly (allyl amine hydrochloride/poly(sodium 4-styrene sulfonate)). Using a 3D printing low-cost technology we fabricated the smartphone-based device that consists in a cover accessory attached to the smartphone and incorporating a light diffuser over the flash to improve the image quality, a mini dark box and a disposable analytical cartridge containing all the reagents necessary for the complete analysis. The biosensor was developed exploiting coupled enzyme reactions for quantifying L-lactate in oral fluid, which is considered a biomarker of poor tissue perfusion, a key element in the management of severe sepsis, septic shock and in sports performance evaluation. The developed method is sensitive, rapid, and it allows detecting L-lactate in oral fluid in the relevant physiological range, with a limit of detection of 0.1mmolL−1. The extreme simplicity of assay execution (no reagents need to be added) and flexibility of fabrication of the device, together with the high assay versatility (any oxidase can be coupled with HRP-based color change reaction) make our approach suitable for the realization of smartphone-based biosensors able to non-invasively detect a large variety of analytes of clinical interest.
http://ift.tt/2lNJlzq
Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability
Publication date: Available online 4 March 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Behling Cheng, Fatema H. Al-Shammari, Isra'a A. Ghader, Fatima Sequeira, Jitendra Thakkar, Thazhumpal C. Mathew
Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRβ (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRβ and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions. Cells immunostained for RXRα were primarily localized in zona fasciculata (ZF) and medulla, although some stained cells were found in zona glomerulosa (ZG) and zona reticularis (ZR). In contrast, cells immunostained for RXRβ were concentrated principally in ZG, although some stained cells were seen in ZR, ZF, and medulla (in descending order, qualitatively). Analysis of adrenal lipid extracts by LC/MS did not detect 9-cis-retinoic acid (a potent RXR-ligand) but identified all-trans retinoic acid. Since C20 and C22 polyunsaturated fatty acids (PUFAs) can also activate RXR, subcellular availabilities of unesterified fatty acids were investigated by GC/MS. As results, arachidonic acid (C20:4), adrenic acid (C22:4), docosapentaenoic acid (C22:5), and cervonic acid (C22:6) were detected in the lipids extracted from each subcellular fraction. Thus, the RXR-agonizing PUFAs are available in all the main subcellular compartments considerably. The present findings not only shed light on the adrenal network of RXRs but also provide baseline information for further investigations of RXR heterodimers in the regulation of adrenal steroidogenesis.
http://ift.tt/2mT5A7R
Reorganization of Anterior and Posterior Hippocampal Networks Associated with Memory Performance in Mesial Temporal Lobe Epilepsy
Source:Clinical Neurophysiology
Author(s): Hong Li, Caihong Ji, Lujia Zhu, Peiyu Huang, Biao Jiang, Xiaojun Xu, Jianzhong Sun, Zhong Chen, Meiping Ding, Minming Zhang, Shuang Wang
ObjectiveTo investigate the pattern of functional demarcation of hippocampal network and its relationship with memory performance in mesial temporal lobe epilepsy (mTLE) with unilateral hippocampal sclerosis.MethodsResting state fMRI data were acquired from fifteen left mTLE patients, fourteen right mTLE patients and twenty healthy subjects. We explore the hippocampal-cortical alterations and corresponding inter-hemispheric functional connectivity (FC) across anterior and posterior hippocampal networks. The association between FC and memory performance was assessed.ResultsLeft mTLE showed increased intra-hemispheric FC in anterior hippocampal networks, including left anterior hippocampal-entorhinal cortex and right anterior hippocampal-orbitofrontal cortex, and decreased inter-hemispheric FC between anterior hippocampus, entorhinal cortex and posterior cingulate cortex. Right mTLE was associated with extensive reduction in inter-hemispheric FC along the areas of anterior and posterior hippocampal networks. Intra-hemispheric FC between left anterior hippocampus and entorhinal cortex was positively correlated with verbal memory in left mTLE. Inter-hemispheric FC between posterior parahippocampal gyrus was negatively correlated with verbal memory in right mTLE.ConclusionsOur findings suggested that left and right mTLE exhibit different neural reorganization patterns of anterior and posterior hippocampal networks associated with verbal memory.SignificanceThe findings may facilitate the characterization of mTLE associated with memory deficit.
http://ift.tt/2mrSpgN
Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation
Source:European Journal of Cancer, Volume 76
Author(s): Stefanie Zschäbitz, Felix Lasitschka, Boris Hadaschik, Ralf-Dieter Hofheinz, Kathleen Jentsch-Ullrich, Marcus Grüner, Dirk Jäger, Carsten Grüllich
IntroductionTreatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity.Patients and methodsWe analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts.ResultsSeven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining.InterpretationWe consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted.
http://ift.tt/2n1Qoob
More than 5000 patients with metastatic melanoma in Europe per year do not have access to recommended first-line innovative treatments
Source:European Journal of Cancer, Volume 75
Author(s): L. Kandolf Sekulovic, K. Peris, A. Hauschild, A. Stratigos, J.-J. Grob, P. Nathan, R. Dummer, A.-M. Forsea, C. Hoeller, H. Gogas, L. Demidov, C. Lebbe, C. Blank, J. Olah, L. Bastholt, D. Herceg, B. Neyns, R. Vieira, J. Hansson, P. Rutkowski, I. Krajsova, M. Bylaite-Bucinskiene, I. Zalaudek, J. Maric-Brozic, N. Babovic, M. Banjin, K. Putnik, G. Weinlich, V. Todorovic, K. Kirov, J. Ocvirk, A. Zhukavets, M. Kukushkina, L. De La Cruz Merino, A. Ymeri, M. Risteski, C. Garbe
BackgroundDespite the efficacy of innovative treatments for metastatic melanoma, their high costs has led to disparities in cancer care among different European countries. We analysed the availability of these innovative therapies in Europe and estimated the number of patients without access to first-line recommended treatment per current guidelines of professional entities such as the European Society for Medical Oncology (ESMO), the European Organisation for Research and Treatment of Cancer (EORTC), the European Association of Dermato-Oncology (EADO), and European Dermatology Forum (EDF).Materials and methodsWeb-based online survey was conducted in 30 European countries with questions about the treatment schedules from 1st May 2015 to 1st May 2016: number of metastatic melanoma patients, registration and reimbursement of innovative medicines (updated data, as of 1st October 2016), percentage of patients treated and availability of clinical studies and compassionate-use programmes.ResultsThe recommended BRAF inhibitor (BRAFi) + MEK inhibitor (MEKi) combination was both registered and fully reimbursed in 9/30 (30%) countries, and in 13/30 (43%) (all from Eastern Europe) not reimbursed. First-line immunotherapy with anti-PD1 antibodies was registered and fully reimbursed in 14/30 (47%) countries, while in 13/30 (43%) (all from Eastern Europe) not reimbursed. It was estimated that in Europe 19,600 patients with metastatic melanoma are treated, and 5238 (27%) do not have access to recommended first-line therapy. Significant correlation was found between human development index (HDI, UNDP report 2015), (r = 0.662; p < 0.001), health expenditure per capita (r = 0.695; p < 0.001) and the Mackenbach score of health policy performance (r = 0.765; p < 0.001) with the percentage of patients treated with innovative medicines and a number of reimbursed medicines.ConclusionsGreat discrepancy exists in metastatic melanoma treatment across Europe. It is crucial to increase the awareness of national and European policymakers, oncological societies, melanoma patients' associations and pharma industry.
http://ift.tt/2maDBlU
Continuous membrane potential fluctuations in motor cortex and striatum neurons during voluntary forelimb movements and pauses
Source:Neuroscience Research
Author(s): Satoshi Nonomura, Yoko Fujiwara-Tsukamoto, Takafumi Kajihara, Fumino Fujiyama, Yoshikazu Isomura
Theoretical simulations suggest that spike rate is regulated by varying both membrane potential and its fluctuation. We investigated whether membrane potential fluctuation functionally changes in motor cortex and striatum neurons during discrete forelimb movements and pauses, or at rest, using whole-cell recording in task-performing rats. Membrane potential fluctuation was diminished by task performance, but maintained overall in the alpha/beta and gamma bands during forelimb movements and pauses. By contrast, membrane potential itself was correlated with spike rate in task-related neurons. Thus, membrane potential, but not its fluctuation, is a critical determinant of execution and pausing of discrete movements.
http://ift.tt/2mpjDEz
Redox-responsive mesoporous selenium delivery of doxorubicin targets MCF-7 cells and synergistically enhances its anti- tumor activity
Publication date: Available online 4 March 2017
Source:Acta Biomaterialia
Author(s): Shuang Zhao, Qianqian Yu, Jiali Pan, Yanhui Zhou, Chengwen Cao, Jian-Ming Ouyang, Jie Liu
To reduce the side effects and enhance the anti-tumor activities of anticancer drugs in the clinic, the use of nano mesoporous materials, with mesoporous silica (MSN) being the best-studied, has become an effective method of drug delivery. In this study, we successfully synthesized mesoporous selenium (MSe) nanoparticles and first introduced them to the field of drug delivery. Loading MSe with doxorubicin (DOX) is mainly driven by the physical adsorption mechanism of the mesopores, and our results demonstrated that MSe could synergistically enhance the antitumor activity of DOX. Coating the surface of MSe@DOX with Human serum albumin (HSA) generated a unique redox-responsive nanoparticle (HSA-MSe@DOX) that demonstrated glutathione-dependent drug release, increased tumor-targeting effects and enhanced cellular uptake throug nanoparticle interact with SPARC in MCF-7 cells. In vitro, HSA-MSe@DOX prominently induced cancer cell toxicity by synergistically enhancing the effects of MSe and DOX. Moreover, HSA-MSe@DOX possessed tumor-targeting abilities in tumor-bearing nude mice and not only decreased the side effects associated with DOX, but also enhanced its antitumor activity. Therefore, HSA-MSe@DOX is a promising new drug that warrants further evaluation in the treatments of tumors.Statement of significanceTo reduce the side effects and enhance the anti-tumor activities of anticancer drugs, we successfully synthesized mesoporous selenium (MSe) nanoparticles and first introduced them to the field of drug delivery. Loading MSe with doxorubicin (DOX) is mainly driven by the physical adsorption mechanism of the mesopores. Coating the surface of MSe@DOX with Human serum albumin (HSA) generated a unique redox-responsive nanoparticle (HSA-MSe@DOX) that demonstrated glutathione-dependent drug release, increased tumor-targeting effects and enhanced cellular uptake throug nanoparticle interact with SPARC in MCF-7 cells. In vitro and in vivo, HSA-MSe@DOX possessed tumor-targeting abilities and not only decreased the side effects associated with DOX, but also enhanced its antitumor activity. Therefore, HSA-MSe@DOX is a promising new drug that warrants further evaluation in the treatments of tumors.
Graphical abstract
http://ift.tt/2lKSRSV
Effect of modified flux on MIG arc brazing-fusion welding of aluminum alloy to steel butt joint
Publication date: July 2017
Source:Journal of Materials Processing Technology, Volume 245
Author(s): Guoliang Qin, Yang Ji, Hong Ma, Zhiyong Ao
Pulsed MIG arc brazing-fusion welding process was applied to realize the butt joining of galvanized steel and 5052 aluminum alloy with no enclosed slot or groove adopted. A modified flux mixture was developed to improve the butt joint performance. After applying the modified flux, weld appearance became better and the spreadability of filler metal was also greatly improved. During brazing-fusion welding process, flux floating on the surface of welding pool weakened the surface tension between filler metal and Fe and reduced the evaporation of Zn, which both led to the greatly enhanced spreadability. The analysis of intermetallic compounds (IMCs) at brazed interface showed that Fe3Al was formed at upper side of steel plate, while Fe2Al5 was formed at other areas with the consideration of its lowest Gibbs free energy under certain temperature range. With modified flux, the tensile strength of the joint could reach up to 120MPa, which was about 60% of that of 5052 aluminum alloy base metal. From the fractured surface, two different fracture modes were identified, tear fracture and intergranular fracture, which confirmed that joint fractured in a brittle mode. The crack initiated at the front side of brazed interface due to the thicker IMCs layer, then propagated to the surface before the whole joint failed. The improved spreadability of filler metal on the top and back sides of steel plate due to the application of flux, contributed to the improvement of joint strength.
Graphical abstract
http://ift.tt/2mawrhD
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