Ιατρικά Άρθρα: 02/02/18

Παρασκευή 2 Φεβρουαρίου 2018

Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111

Publication date: Available online 3 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Kenya Matsushita, Tomomi Nakata, Naoko Takeda-Okuda, Satomi Nadanaka, Hiroshi Kitagawa, Jun-ichi Tamura
We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1–4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1–4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibodies 2H6 and LY111, both of which are known to bind with CS-A, while CS-DD was shown for the first time to bind with both antibodies.

Graphical abstract

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Design, synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment

Publication date: Available online 2 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Zhongcheng Cao, Jie Yang, Rui Xu, Qin Song, Xiaoyu Zhang, Hongyan Liu, Xiaoming Qiang, Yan Li, Zhenghuai Tan, Yong Deng
A series of 4′-OH-flurbiprofen-chalcone hybrids were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (60.0% and 78.2%, respectively) and Cu²⁺-induced Aβ1-42 aggregation (52.4% and 95.0%, respectively). Moreover, these two representative compounds also exhibited good antioxidant activities, MAO inhibitions, biometal chelating abilities and anti-neuroinflammatory activities in vitro. Furthermore, compound 7m displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 7k and 7m as promising candidates for further development of multi-functional drugs against AD.

Graphical abstract

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Synthesis and biological evaluation of aminothiazoles against Histoplasma capsulatum and Cryptococcus neoformans

Publication date: Available online 2 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Keisuke Ishita, Stavros Stefanopoulos, Ahmed Khalil, Xiaolin Cheng, Werner Tjarks, Chad Rappleye
The design and synthesis of a library of forty novel 2-aminoazole analogues as well as their evaluation as antifungal compounds against Histoplasma capsulatum and Cryptococcus neoformans is described. These structures were derived from N-[5-(1-naphthalenylmethyl)-2-thiazolyl]cyclohexanecarboxamide (41F5), a fungistatic agent previously identified through phenotypic screening (Antimicrob Agents Chemother. 2013; 57:4349). Modifications to improve potency and water-solubility of 41F5 focused primarily on the 5-naphthalenyl group, the thiazole core, and the methylene linker between these two structural elements. In general, compounds with lipophilic [5+6] bicyclics ring systems, such as the 7-benzothiophenyl- and 4-indanyl groups, at the 5-position were 2-3 times more active against both fungal species as compard to 41F5. Also, introduction of a carbonyl group at the methylene linker of 41F5 resulted in a 2-3 fold increase in potency. These highly active compounds also showed generally low toxicities against murine P388D1 macrophages resulting in selectivity indices ranging from 63 to >200. Compounds that were highly active against fluconazole-sensitive C. neoformans strains had almost identical activity against fluconazole-resistant variants of this fungus indicating that 14α-demethylase is not their molecular target. Highly active compounds also retained activity against H. capsulatum phagocytosed into P388D1 macrophages.

Graphical abstract

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Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor

Publication date: Available online 3 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Chieyeon Chough, Misuk Joung, Sunmin Lee, Jaemin Lee, Jong Hoon Kim, B. Moon Kim
A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib's core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC50 11, 2.4x10², 2.8x10³, and 1.1x10² nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.

Graphical abstract

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Hepatic NAD+ levels and NAMPT abundance are unaffected during prolonged high-fat diet consumption in C57BL/6JBomTac mice

Publication date: Available online 2 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Morten Dall, Melanie Penke, Karolina Sulek, Madlen Matz-Soja, Birgitte Holst, Antje Garten, Wieland Kiess, Jonas T. Treebak
Dietary supplementation of nicotinamide adenine dinucleotide (NAD⁺) precursors has been suggested as a treatment for non-alcoholic fatty liver disease and obesity. In the liver, NAD⁺ is primarily generated by nicotinamide phosphoribosyltransferase (NAMPT), and hepatic levels of NAMPT and NAD⁺ have been reported to be dependent on age and body composition. The aim of the present study was to identify time-course-dependent changes in hepatic NAD content and NAD⁺ salvage capacity in mice challenged with a high-fat diet (HFD). We fed 7-week-old C57BL/6JBomTac male mice either regular chow or a 60% HFD for 6, 12, 24, and 48 weeks, and we evaluated time course-dependent changes in whole body metabolism, liver steatosis, and abundance of hepatic NAD-associated metabolites and enzymes. Mice fed a 60% HFD rapidly accumulated fat and hepatic triglycerides, with associated changes in respiratory exchange ratio (RER) and a disruption of the circadian feeding pattern. The HFD did not alter hepatic NAD⁺ levels, but caused a decrease in NADP⁺ and NADPH levels. Decreased NADP⁺ content was not accompanied by alterations in NAD kinase (NADK) abundance in HFD-fed mice, but NADK levels increased with age regardless of diet. NAMPT protein abundance did not change with age or diet. HFD consumption caused a severe decrease in protein lysine malonylation after six weeks, which persisted throughout the experiment. This decrease was not associated with changes in SIRT5 abundance. In conclusion, hepatic NAD⁺ salvage capacity is resistant to long-term HFD feeding, and hepatic lipid accumulation does not compromise the hepatic NAD⁺ pool in HFD-challenged C57BL/6JBomTac male mice.

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Epigenetic regulation of male fate commitment from an initially bipotential system

Publication date: Available online 2 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): S. Alexandra Garcia-Moreno, Michael P. Plebanek, Blanche Capel
A fundamental goal in biology is to understand how distinct cell types containing the same genetic information arise from a single stem cell throughout development. Sex determination is a key developmental process that requires a unidirectional commitment of an initially bipotential gonad towards either the male or female fate. This makes sex determination a unique model to study cell fate commitment and differentiation in vivo. We have focused this review on the accumulating evidence that epigenetic mechanisms contribute to the bipotential state of the fetal gonad and to the regulation of chromatin accessibility during and immediately downstream of the primary sex-determining switch that establishes the male fate.

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Partial growth hormone insensitivity and dysregulatory immune disease associated with de novo germline activating STAT3 mutations

Publication date: Available online 3 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Mariana Gutiérrez, Paula Scaglia, Ana Keselman, Lucía Martucci, Liliana Karabatas, Sabina Domené, Ayelen Martin, Patricia Pennisi, Miguel Blanco, Nora Sanguineti, Liliana Bezrodnik, Daniela Di Giovanni, María Soledad Caldirola, María Esnaola Azcoiti, María Isabel Gaillard, Lee A. Denson, Kejian Zhang, Ammar Husami, Nana-Hawa Yayah Jones, Vivian Hwa, Santiago Revale, Martín Vázquez, Héctor Jasper, Ashish Kumar, Horacio Domené
Germinal heterozygous activating STAT3 mutations represent a novel monogenic defect associated with multi-organ autoimmune disease and, in some cases, severe growth retardation. By using whole-exome sequencing, we identified two novel STAT3 mutations, p.E616del and p.C426R, in two unrelated pediatric patients with IGF-I deficiency and immune dysregulation. The functional analyses showed that both variants were gain-of-function (GOF), although they were not constitutively phosphorylated. They presented differences in their dephosphorylation kinetics and transcriptional activities under interleukin-6 stimulation. Both variants increased their transcriptional activities in response to growth hormone (GH) treatment. Nonetheless, STAT5b transcriptional activity was diminished in the presence of STAT3 GOF variants, suggesting a disruptive role of STAT3 GOF variants in the GH signaling pathway. This study highlights the broad clinical spectrum of patients presenting activating STAT3 mutations and explores the underlying molecular pathway responsible for this condition, suggesting that different mutations may drive increased activity by slightly different mechanisms.

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Prostaglandin E2 (PGE2) is a testicular peritubular cell-derived factor involved in human testicular homeostasis

Publication date: Available online 2 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Verónica Rey-Ares, Soledad Paola Rossi, Kim-Gwendolyn Dietrich, Frank-Michael Köhn, J. Ulrich Schwarzer, Harald Welter, Mónica Beatriz Frungieri, Artur Mayerhofer
In man, blockage of prostaglandin (PG)-production e.g. by non-steroidal anti-inflammatory drug (NSAIDs) may have negative testicular side effects, implying beneficial actions of PGs in the testis. We examined human testicular samples and isolated human testicular peritubular cells (HTPCs) to explore sites of PG-synthesis and targets. HTPCs express cyclooxygenase 1 (COX1) and secrete PGE2. Receptors (EP1, 2, 4) were specifically identified in peritubular cells. In HTPCs PGE2 significantly increased mRNA levels of the contractility protein calponin, but did not induce contractions. PGE2, as well as EP1 and EP4 receptor agonists, significantly increased glia cell line derived neurotrophic factor (GDNF) mRNA and/or protein levels. Importantly, the NSAID ibuprofen reduced PGE2 and this action also lowered SMA and calponin mRNA levels and levels of secreted GDNF protein. The results reveal an unknown PGE2 system in the human testis, in involving peritubular cells, which may be prone to interference by NSAIDs.

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Electrodiagnostic applications of somatosensory evoked high-frequency EEG oscillations: Technical considerations

Publication date: March 2018
Source:Brain Research Bulletin, Volume 137
Author(s): A.J. Simpson, M.O. Cunningham, M.R. Baker
IntroductionHigh frequency oscillations (HFOs) embedded within the somatosensory evoked potential (SEP) are not routinely recorded/measured as part of standard clinical SEPs. However, HFOs could provide important additional diagnostic/prognostic information in various patient groups in whom SEPs are tested routinely. One area is the management of patients with hypoxic ischaemic encephalopathy (HIE) in the intensive care unit (ICU). However, the sensitivity of standard clinical SEP recording techniques for detecting HFOs is unknown.MethodsSEPs were recorded using routine clinical methods in 17 healthy subjects (median nerve stimulation; 0.5 ms pulse width; 5 Hz; maximum 4000 stimuli) in an unshielded laboratory. Bipolar EEG recordings were acquired (gain 50 k; bandpass 3Hz–2 kHz; sampling rate 5 kHz; non-inverting electrode 2 cm anterior to C3/C4; inverting electrode 2 cm posterior to C3/C4). Data analysis was performed in MATLAB.ResultsSEP-HFOs were detected in 65% of controls using standard clinical recording techniques. In 3 controls without significant HFOs, experiments were repeated using a linear electrode array with higher spatial sampling frequency. SEP-HFOs were observed in all 3 subjects.ConclusionsCurrently standard clinical methods of recording SEPs are not sufficiently sensitive to permit the inclusion of SEP-HFOs in routine clinical diagnostic/prognostic assessments. Whilst an increase in the number/density of EEG electrodes should improve the sensitivity for detecting SEP-HFOs, this requires confirmation. By improving and standardising clinical SEP recording protocols to permit the acquisition/analysis of SEP-HFOs, it should be possible to gain important insights into the pathophysiology of neurological disorders and refine the management of conditions such as HIE.

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Ensemble support vector machine classification of dementia using structural MRI and mini-mental state examination

Publication date: Available online 3 February 2018
Source:Journal of Neuroscience Methods
Author(s): Lauge Sørensen, Mads Nielsen
BackgroundThe International Challenge for Automated Prediction of MCI from MRI data offered independent, standardized comparison of machine learning algorithms for multi-class classification of normal control (NC), mild cognitive impairment (MCI), converting MCI (cMCI), and Alzheimer's disease (AD) using brain imaging and general cognition.New methodWe proposed to use an ensemble of support vector machines (SVMs) that combined bagging without replacement and feature selection. SVM is the most commonly used algorithm in multivariate classification of dementia, and it was therefore valuable to evaluate the potential benefit of ensembling this type of classifier.ResultsThe ensemble SVM, using either a linear or a radial basis function (RBF) kernel, achieved multi-class classification accuracies of 55.6% and 55.0% in the challenge test set (60 NC, 60 MCI, 60 cMCI, 60 AD), resulting in a third place in the challenge. Similar feature subset sizes were obtained for both kernels, and the most frequently selected MRI features were the volumes of the two hippocampal subregions left presubiculum and right subiculum. Post-challenge analysis revealed that enforcing a minimum number of selected features and increasing the number of ensemble classifiers improved classification accuracy up to 59.1%.Comparison with existing method(s)The ensemble SVM outperformed single SVM classifications consistently in the challenge test set.ConclusionsEnsemble methods using bagging and feature selection can improve the performance of the commonly applied SVM classifier in dementia classification. This resulted in competitive classification accuracies in the International Challenge for Automated Prediction of MCI from MRI data.

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Editorial Board

Publication date: 1 February 2018
Source:Journal of Neuroscience Methods, Volume 295

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Sweet syndrome associated with ipilimumab in a patient with metastatic melanoma

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Use of a novel 1-hour protocol for rapid frozen section immunocytochemistry, in a case of squamous cell carcinoma treated with Mohs micrographic surgery

Summary

For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue.

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A new discussion of the cutaneous vascular reactivity in sensitive skin: A sub-group of SS?

Abstract

Background

Sensitive skin (SS) seems not to be a one-dimensional condition and many scholars concentrate on skin barrier disruption or sensorineural change, but few focus on its increased vascular reactivity. This study explored the possibility of using the different selection methods and measurement methods to verify a high vascular reactivity in SS without an impaired cutaneous barrier function.

Methods

Sixty "self-perceived sensitive skin" volunteers were enlisted and each one completed three kinds of screening tests: assess cutaneous sensory using questionnaire survey and Lactic Acid Sting Test (LAST); assess barrier function using Sodium lauryl sulphate (SLS) skin irritation test and assess cutaneous vascular reactivity using 98% DMSO test and non-invasive measurement. Volunteers were divided into different groups based on response to SLS. The DMSO clinical score and the biophysical parameters obtained by non-invasive measurement were subsequently analysed.

Results

(1) The positive correlations could be seen between sum LAST score and sum DMSO score regardless of the observation time; (2) The biological parameters (CBF、a*values and L* values) are all keeping with DMSO score; (3) If the participants were divided into SLS reactors and non-reactors, a composition ratio of DMSO score was significant difference in these two groups and in SLS non-reactors, there were still seven participants showed high reaction to DMSO.

Conclusions

There is a sub-group of SS for characteristics of a high vascular reactivity without an impaired cutaneous barrier function. The DMSO test and novel non-invasive measurements which are conducive to assess cutaneous vascular reactivity, combined with SLS skin irritation test could help us to screen this kind of SS.

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An innovative method to quantitate tissue integration of hyaluronic acid-based dermal fillers

Abstract

Background/purpose

Following intradermal injection, hyaluronic acid (HA)-based fillers tend to spread within the reticular dermis and to distribute between the dermal fibers. This biointegration is commonly measured qualitatively using histological methods. We developed a "toolbox" consisting of a visual scoring and a semi-automatic image analysis method using internal developed algorithm to quantitate the biointegration of Restylane® in histological sections.

Methods

Restylane^® was injected intradermally in the abdominal skin of 10 healthy human subjects scheduled for abdominoplasty. The injections were performed either in vivo before surgery or ex vivo on samples taken post-surgery at different time points. The samples were processed for histology by visual scoring and image analysis using algorithms developed in Definiens to assess biointegration.

Results

The image analysis segmentation was accurate with <5% manual changes. Furthermore, the results calculated with the semi-automatic method were consistent with the visual scores obtained on injected human skin samples by means of a 5-grade photographic scale. A modified hematoxylin-eosin staining was found adequate to visualize both, the filler and the general morphology, on the same section. An excellent correlation was observed between the integration results obtained with PAS/Alcian Blue and HE-stained slides, allowing for a single staining in future studies.

Conclusion

We developed a modified HE staining histological method and a new histomorphometric image analysis tool to quantitate biointegration of HA-based fillers in human skin. The results obtained in this study confirmed the known intermediate biointegration properties of Restylane®, thus validating these innovative methods.

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First data from a population based cancer registry in Ethiopia

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Genebo Timotewos, Asmare Solomon, Assefa Mathewos, Adamu Addissie, Solomon Bogale, Tigeneh Wondemagegnehu, Abraha Aynalem, Bekele Ayalnesh, Hailemariam Dagnechew, Wondatir Bireda, Eric Sven Kroeber, Rafael Mikolajczyk, Freddie Bray, Ahmedin Jemal, Eva Johanna Kantelhardt
BackgroundThe Addis Ababa City Cancer Registry, established in September 2011, is the only population-based cancer registry in Ethiopia, covering a catchment population of just over three million habitants. Herein, we report incidence data based on the first two years of registration, 2012–2013.MethodsNewly-diagnosed cancer cases in the capital city were actively collected from 22 hospitals, clinics, and diagnostic facilities.ResultsDuring 2012–2013, a total of 4139 newly diagnosed cases were recorded, with the majority (67%) occurring in females. Cancers of the breast (31.5%) and cervix (14.1%) were the two most common cancers among females, while colorectal cancers (10.6%) and non-Hodgkin lymphomas (10.2%) were the most common cancers among males. The average annual age-standardized rate for all sites 2012–13 were 136.2 (per 100,000) and 70.7 in females and males, respectively. Female age-standardized rates were 40.6 for breast cancer and 21.5 for cervix, while equivalent rates in males were 7.6 per 100,000 for colorectal cancer and 6.8 per 100,000 for non-Hodgkin lymphoma.ConclusionIn general, these incidence patterns were similar to those reported in neighboring countries, which suggests that the majority of cancer cases occurring in Addis Ababa are captured within this starting phase of the registry. However, our finding of colorectal cancer as the most commonly-diagnosed cancer in males is novel and requires further investigation.

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A highly efficient polymer non-fullerene organic solar cell enhanced by introducing a small molecule as a crystallizing-agent

Publication date: Available online 1 February 2018
Source:Materials Today
Author(s): Yifan Zheng, Jiang Huang, Gang Wang, Jaemin Kong, Di Huang, Megan Mohadjer Beromi, Nilay Hazari, André D. Taylor, Junsheng Yu
Non-fullerene organic solar cells (OSCs) have attracted tremendous interest because of their potential to replace traditional expensive fullerene-based OSCs. To further increase the power conversion efficiency (PCE), it is necessary to offset the narrow absorption of the non-fullerene materials, which is often achieved by adding an additive (>10 wt%) to form a ternary blend. However, a high ratio of the third component can often be detrimental to the active layer morphology and can increase the complexity in understanding the device physics toward rationally designed improvements. In this work, we introduce 2,4-bis-[(N,N-diisobutylamino)-2,6-dihydroxyphenyl]-4-(4-diphenyliminio) squaraine (ASSQ) in the poly [(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl) benzo [1,2-b:4,5-b′] dithiophene)-co-(1,3-di(5-thiophene-2-yl)-5,7-bis(2-ethylhexyl) benzo [1,2-c:4,5-c′] dithiophene-4,8-dione)] (PBDB-T): 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno [2,3-d:2′,3′-d′]-s-indaceno [1,2-b:5,6-b′] dithiophene (ITIC) as an active layer "crystallizing-agent". Through detailed morphology characterization, we find that the addition of 4 wt% ASSQ assists ITIC organization order and promotes PDBD-T:ITIC aggregation in the preferential face-on orientation. In addition, we demonstrate that the ASSQ and PBDB-T show efficient exciton dissociation in the ternary blend over Förster resonance energy transfer (FRET). We reveal using surface potential and solubility measurements that a ASSQ-ITIC co-crystalline structure forms which facilitates a significant improvement in the device PCE, from 8.98% to 10.86%.

Graphical abstract

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Deformable conductors for human–machine interface

Publication date: Available online 1 February 2018
Source:Materials Today
Author(s): Jiangxin Wang, Meng-Fang Lin, Sangbaek Park, Pooi See Lee
Soft electronic systems are emerging that are heralded to bring revolution and a frontier for the interactions between human beings and machines. Interactive interfaces enable integrated bidirectional functionalities of sensing the external stimulus and providing interactive response to the users. Human body is considerably soft and stretchable; this characteristic puts forward the need for good mechanical conformabilities for the interfacing electronic devices. As a vital and indispensable component in electronic systems, soft and deformable conductor is of great importance to establish the enabling technologies. Significant progresses have been developed with new strategies and materials being exploited to improve the performance of elastic conductors. In this article, we review the latest advances in deformable conductors and their applications to enable soft electronic devices for human–machine interfaces. We first focus on the important characteristics of the deformable conductors in their stretchability, conductivity, and transparency. Representative soft electronic systems that are categorized into "receptive devices" and "responsive devices" are then reviewed.

Graphical abstract

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From biomaterial-based data storage to bio-inspired artificial synapse

Publication date: Available online 1 February 2018
Source:Materials Today
Author(s): Ziyu Lv, Ye Zhou, Su-Ting Han, V.A.L. Roy
The implementation of biocompatible and biodegradable information storage would be a significant step toward next-generation green electronics. On the other hand, benefiting from high density, multifunction, low power consumption and multilevel data storage, artificial synapses exhibit attractive future for built-in nonvolatile memories and reconstructed logic operations. Here, we provide a comprehensive and critical review on the developments of bio-memories with a view to inspire more intriguing ideas on this area that may finally open up a new chapter in next-generation consumer electronics. We will discuss that biomolecule-based memory employed evolutionary natural biomaterials as data storage node and artificial synapse emulated biological synapse function, which is expected to conquer the bottleneck of the traditional von Neumann architecture. Finally, challenges and opportunities in the aforementioned bio-memory area are presented.

Graphical abstract

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Superconducting stacks

Publication date: Available online 1 February 2018
Source:Materials Today
Author(s): M.A. Torres, Sh. Rasekh, M.A. Madre, J.C. Diez, A. Sotelo

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Lithium-ion conductive ceramic textile: A new architecture for flexible solid-state lithium metal batteries

Publication date: Available online 2 February 2018
Source:Materials Today
Author(s): Yunhui Gong, Kun Fu, Shaomao Xu, Jiaqi Dai, Tanner R. Hamann, Lei Zhang, Gregory T. Hitz, Zhezhen Fu, Zhaohui Ma, Dennis W. McOwen, Xiaogang Han, Liangbing Hu, Eric D. Wachsman
Designing solid-state lithium metal batteries requires fast lithium-ion conductors, good electrochemical stability, and scalable processing approaches to device integration. In this work, we demonstrate a unique design for a flexible lithium-ion conducting ceramic textile with the above features for use in solid-state batteries. The ceramic textile was based on the garnet-type conductor Li7La3Zr2O12 and exhibited a range of desirable chemical and structural properties, including: lithium-ion conducting cubic structure, low density, multi-scale porosity, high surface area/volume ratio, and good flexibility. The solid garnet textile enabled reinforcement of a solid polymer electrolyte to achieve high lithium-ion conductivity and stable long-term Li cycling over 500 h without failure. The textile also provided an electrolyte framework when designing a 3D electrode to realize ultrahigh cathode loading (10.8 g/cm² sulfur) for high-performance Li-metal batteries.

Graphical abstract

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RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis

Publication date: Available online 2 February 2018
Source:Cancer Cell
Author(s): Jose R. Cortes, Alberto Ambesi-Impiombato, Lucile Couronné, S. Aidan Quinn, Christine S. Kim, Ana C. da Silva Almeida, Zachary West, Laura Belver, Marta Sanchez Martin, Laurianne Scourzic, Govind Bhagat, Olivier A. Bernard, Adolfo A. Ferrando, Teresa Palomero
Angioimmunoblastic T cell lymphoma (AITL) is an aggressive tumor derived from malignant transformation of T follicular helper (Tfh) cells. AITL is characterized by loss-of-function mutations in Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val) in the RHOA small GTPase. Yet, the specific role of RHOA G17V in AITL remains unknown. Expression of Rhoa G17V in CD4⁺ T cells induces Tfh cell specification; increased proliferation associated with inducible co-stimulator (ICOS) upregulation and increased phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase signaling. Moreover, RHOA G17V expression together with Tet2 loss resulted in development of AITL in mice. Importantly, Tet2^−/−RHOA G17V tumor proliferation in vivo can be inhibited by ICOS/PI3K-specific blockade, supporting a driving role for ICOS signaling in Tfh cell transformation.

Graphical abstract

Teaser

Cortes et al. show that expression of Rhoa G17V in CD4⁺ T cells drives proliferation and Tfh polarization, and they develop an angioimmunoblastic T cell lymphoma model by combining Rhoa G17V expression and Tet2 loss. These tumors show increased ICOS and PI3K/MAPK signaling and are sensitive to pathway inhibition.

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Plasticizers used in food-contact materials affect adipogenesis in 3T3-L1 cells

Publication date: Available online 2 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Valentina Pomatto, Erika Cottone, Paolo Cocci, Matteo Mozzicafreddo, Gilberto Mosconi, Erik Russel Nelson, Francesco Alessandro Palermo, Patrizia Bovolin
Recent studies suggest that exposure to some plasticizers, such as Bisphenol A (BPA), play a role in endocrine/metabolic dispruption and can affect lipid accumulation in adipocytes. Here, we investigated the adipogenic activity and nuclear receptor interactions of four plasticizers approved for the manufacturing of food-contact materials (FCMs) and currently considered safer alternatives. Differentiating 3T3-L1 mouse preadipocytes were exposed to scalar concentrations (0.01-25 µM) of DiNP (Di-iso-nonyl-phthalate), DiDP (Di-iso-decyl-phthalate), DEGDB (Diethylene glycol dibenzoate), or TMCP (Tri-m-cresyl phosphate). Rosiglitazone, a well-known pro-adipogenic peroxisome proliferator activated receptor gamma (PPARγ) agonist, and the plasticizer BPA were included as reference compounds. All concentrations of plasticizers were able to enhance lipid accumulation, with TMCP being the most effective one. Accordingly, when comparing in silico the ligand binding efficiencies to the nuclear receptors PPARγ and retinoid-X-receptor-alpha (RXRα), TMPC displayed the highest affinity to both receptors. Differently from BPA, the four plasticizers were most effective in enhancing lipid accumulation when added in the mid-late phase of differentiation, thus suggesting the involvement of different intracellular signalling pathways. In line with this, TMCP, DiDP, DiNP and DEGDB were able to activate PPARγ in transient transfection assays, while previous studies demonstrated that BPA acts mainly through other nuclear receptors. qRT-PCR studies showed that all plasticizers were able to increase the expression of CCAAT/enhancer binding protein β (Cebpβ) in the early steps of adipogenesis, and the adipogenesis master gene Pparγ2 in the middle phase, with very similar efficacy to that of Rosiglitazone. In addition, TMCP was able to modulate the expression of both Fatty Acid Binding Protein 4/Adipocyte Protein 2 (Fabp4/Ap2) and Lipoprotein Lipase (Lpl) transcripts in the late phase of adipogenesis. DEGDB increased the expression of Lpl only, while the phthalate DiDP did not change the expression of either late-phase marker genes Fabp4 and Lpl. Taken together, our results suggest that exposure to low, environmentally relevant doses of the plasticizers DiNP, DiDP DEGDB and TMCP increase lipid accumulation in 3T3-L1 adipocytes, an effect likely mediated through activation of PPARγ and interference at different levels with the transcriptional cascade driving adipogenesis.

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Pendant/bridged/mesoporous silsesquioxane nanoparticles: Versatile and biocompatible platforms for smart delivery of therapeutics

Publication date: Available online 2 February 2018
Source:Chemical Engineering Journal
Author(s): Achraf Noureddine, C. Jeffrey Brinker
Silsesquioxane nanoparticles are composed of repetitive organosilica fragments in their frameworks and are now recognized to have outstanding functional fertility. Depending on the organosilane and the synthetic pathways, silsesquioxane NPs can be pendant, bridged, dense or porous. Recently the diverse functionalities of mesoporous silsesquioxane nanoparticles have been exploited for the sake of drug-related biomedicine. Fine-tuning the silsesquioxane nanoparticles characteristics allow not only a superior retention capacity of therapeutics without the need of any further modification, but also a controlled release through various environmentally-stimulated triggers. The main focus of the present review is to highlight the different types of silsesquioxane nanoparticles and their exceptional features focused on controlled delivery of drugs, proteins, antibodies and DNA through pH, redox or light stimuli.

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Efficient chlorine atom functionalization at nanodiamond surfaces by electron beam irradiation

Publication date: February 2018
Source:Diamond and Related Materials, Volume 82
Author(s): Jieying Zhou, Christian Laube, Wolfgang Knolle, Sergej Naumov, Andrea Prager, Frank-Dieter Kopinke, Bernd Abel
Surface functionality of nanodiamonds is of crucial importance for their desired chemical, optical and electromagnetic properties. Chlorinated surfaces are expected to enable an easy further modification of diamond surfaces via various substitution reactions for targeted molecule grafting, particularly interesting for biochemical applications. Previously reported chlorination approaches of diamonds required troublesome handling of hazardous chemicals, such as chlorine gas, and long chlorination time or high temperature. Here, we describe a radiation chemistry approach using electron beam irradiation for efficient surface chlorination of nanodiamonds (with averaged diameter of ca. 30 nm) at ambient temperature. Nanodiamonds with hydrogenated and graphitized surfaces were used for chlorination in CCl4, CHCl3 and CH2Cl2 at increasing radiation doses. A comprehensive set of measurements, including XPS, ATR-FTIR and in-source thermal desorption mass spectrometry (IS-TD-MS) was applied to characterize the chlorinated products. Density functional theory (DFT) calculations were performed to assist the discussion of reaction mechanisms. It is confirmed that remarkable covalently chlorine-covered surfaces bearing adequate stability against air and water were achieved for hydrogenated nanodiamonds in CCl4 by applying doses ≥500 kGy.

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Comparison of a foam rolling session with active joint motion and without joint motion: A randomized controlled trial

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Scott W. Cheatham, Kyle R. Stull
BackgroundFoam rolling has become a popular form of self-myofascial release or roller massage among health and fitness professionals. Due to this popularity, foam roller devices can be found in many clinical and fitness settings. Despite the popularity, there are still several unknowns regarding foam rolling such the optimal technique. Specifically, there is a lack of research analyzing different foam roll techniques such as combining active joint motion with foam rolling.PurposeThe purpose of this study was to compare the effects of a foam rolling session to the left quadriceps with active joint motion and without joint motion on passive knee flexion range of motion (ROM) and pressure pain thresholds (PPT).MethodsThirty healthy adults were randomly allocated to one of two intervention groups: active joint motion and no joint motion. Each foam roll intervention to the left quadriceps lasted a total of 2 min. Dependent variables included passive knee flexion ROM and pressure pain threshold measures (PPT). Statistical analysis included subject demographic calculations and appropriate parametric and non-parametric tests to measure changes within and between intervention groups.ResultsFor left knee ROM, the active joint motion group demonstrated the greatest immediate increase in passive ROM (8°, p < .001) than the non-motion group (5°, p < .001). For PPT, the active joint motion group demonstrated the greatest immediate increase (180 kPa, p < .001) followed by the non-motion group (133 kPa, p < .001). Between group comparisons revealed a significance between groups for passive knee ROM (p < .001) and PPT (p < .001).ConclusionA short session of foam rolling with active joint motion appears to have a greater effect on passive joint ROM and PPT than rolling without motion. These observed changes may be influenced by the agonistic muscle activity during active motion. This activity may modulate activity of the antagonist muscle through reciprocal inhibition and other neural pathways. Future research is needed to confirm these findings.

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Knowledge of self-myofascial release among allied health students in the United States: A descriptive comparison survey

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Scott W. Cheatham, Kyle R. Stull
BackgroundUniversity and collegiate education of the human myofascial system is commonly taught in basic science courses such as anatomy. Allied health programs may expand upon these concepts by teaching interventions such as myofascial release in clinical education courses. Self-myofascial release (SMR) with a device such as a foam roller is an emerging intervention that has become popular among clinicians and active individuals. Currently, it's unknown if allied health programs provide SMR education.PurposeThe purpose of this study was to survey and document responses in the knowledge of SMR among allied health students.Methods12 undergraduate and graduate allied health programs in the United States were sent a 12-question electronic survey that represented three areas: 1) respondent demographics and beliefs, 2) experience with SMR, 3) future practice and education. Descriptive data including response frequency and percentage was calculated and reported for the 12 questions.ResultsA total of 502 students from the different allied health programs completed the survey which represented a 33.00% response rate (502/1521). Approximately, half of respondents (49.6%, N = 249) reported learning about SMR in their degree program and the other half (50.40%, N = 253) report receiving no education. Most respondents (>50%) currently use or have used an SMR device and believe that SMR produces therapeutic benefits. Furthermore, most respondents (≥50%) had an idea of how they would integrate SMR into their future practice and where to purchase an SMR device.ConclusionA more global consensus on education for emerging therapeutic intervention such as SMR is needed in order to standardize and develop best teaching practices in allied health. This study highlighted the difference among allied health programs in the United States. This research should be a starting point for future survey research on this topic.

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Therapeutic heat and cold around the elbow on the response of median neurodynamic test 1

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Winora Conchita Gomes, Kavitha Vishal, Ganesh Balthillaya
ObjectiveTo compare the effects of the application of therapeutic heat and cold on the mechanical response of the median nerve neurodynamic testing.DesignSingle-blinded randomized crossover trial.Methodology56 asymptomatic university students (mean age = 21.82 ± 1.64 years) of either gender with a limited elbow extension range of motion during a Median Neurodynamic Test 1 were recruited. Each subject was administered 3 testing conditions on separate days with a 24-hr washout period. The interventions included 1) therapeutic moist heat around the elbow, 2) therapeutic cold around the elbow and 3) no thermal agent as a controlled condition. Outcome measure of elbow extension range of motion at the Onset of pain and Submaximal pain was recorded before the intervention, immediately after the removal of the thermal agents and at 2 subsequent readings of 30min and 1 h after the removal of the thermal agent.Resultsthere was a significant effect of using a thermal agent with time on the elbow range of motion at the onset of pain [F(2,165) = 3.622, p = 0.029] and submaximal pain[F(2,165) = 3.841, p = 0.023] at the 20th min. A posthoc comparison indicated that at the 20th min the mean elbow range at the onset of pain and submaximal pain for the therapeutic heat condition (m = 33.5, S.D = 13.37 and m = 16.80, S.D = 12.99 respectively) was significantly different than the no thermal agent condition (m = 40.17, S.D = 12.34 and m = 23.4, S.D = 13.82 respectively). However. Therapeutic cold condition did not significantly differ from both the other conditions.ConclusionTherapeutic heat causes an immediate increase in elbow extension range of motion during a Median Neurodynamic Test1 and testing post the application of thermal agents can alter the test response.

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Dry needling in chronic abdominal wall pain of uncertain origin

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Rajkannan Pandurangan, Rajagopalan Vijayaraghavan
BackgroundAbdominal wall pain is considered as pain that arises from the abdominal muscles rather than the underlying viscera or the spine. It is frequently overlooked and is often misdiagnosed, as these patients continue to suffer with pain. Many such patients would have even been subjected to a psychiatric evaluation in view of the absence of any ostensible clinical cause for the pain. In this study, we describe the role of myofascial trigger points in the abdominal wall pain that could be a cause of chronic pain and present our findings of pain relief by dry needling technique.ObjectivesTo report the effect of dry needling treatment for patients who suffer from chronic abdominal wall pain of uncertain etiology and in whom specific myofascial trigger points were identified.MethodsTwelve patients diagnosed with chronic abdominal wall pain were included in the study. All patients were clinically evaluated and subjected to a combination of imaging techniques. Once categorized as patients suffering from chronic abdominal wall pain, they were subjected to a thorough palpation of the abdominal wall to identify the presence of myofascial trigger points (MTrPs) over the abdominal muscles. All had MTrPs over one or more abdominal muscles either unilaterally or bilaterally. Dry Needling using a standard technique was done based on the side and localization of the myofascial trigger points. Numerical pain rating scale (NPRS) was used to measure pain before and after treatment and at the end of four months. All patients were then seen by the primary clinician and re-evaluated.ResultsEleven out of twelve patients had significant reduction with a mean difference 5.95 in NPRS in their pain levels at four months follow up. Seven patients had complete resolution of the pain. Some patients had improvement in complaints such as Dysmenorrhea, Urinary Frequency and constipation.ConclusionDry Needling can be a useful adjunct in treating chronic abdominal wall pain especially in those patients in whom Myofascial Trigger Points in the muscles of abdomen are identified by palpation.Level of evidenceLevel 4.

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Comparison of muscular activities between subjects with and without scapular downward rotation impairment during diagonal pattern of exercises

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Se-Yeon Park, Du-Jin Park
BackgroundsOne form of abnormal scapular alignment is scapular downward rotation (SDR). Changes in muscle function in SDR have not been clearly identified, and SDR exercises also require investigation. Although a diagonal pattern of exercise is commonly used as part of the exercise protocol, a direct comparison of shoulder and scapular diagonal exercises has not yet been conducted. The objectives of this study were to determine the altered activation of the scapular musculature in the SDR group and to investigate which diagonal pattern of exercise effectively activates the scapular musculature.MethodsThirty-two participants (18 in the control group and 14 in the SDR group) volunteered to participate in this study. Electromyographic signals were collected from four muscles, the upper trapezius (UT), lower trapezius (LT), serratus anterior (SA), and anterior deltoid (AD), during standing performance of diagonal shoulder and scapular exercises.ResultsThe control group showed significantly lower UT activity, UT/LT ratio, and UT/SA values than the SDR group (p < .05). Activation of the AD was significantly higher in the SDR than in the control group (p < .05). SA and AD activation were significantly higher in shoulder diagonal pattern exercises than in scapular diagonal pattern exercises (p < .05). The scapular posterior elevation pattern exercise showed significantly higher UT and LT activities than anterior elevation and shoulder diagonal pattern exercises (p < .05).ConclusionOur findings suggest that reduced activation of the UT could lead to greater activation in the AD in SDR. Scapular posterior elevation exercise is advantageous as selectively activates the trapezius musculature, and shoulder diagonal pattern exercise is advantageous in activating the SA and AD.

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Immediate effects and one-week follow-up after neuromuscular electric stimulation alone or combined with stretching on hamstrings extensibility in healthy football players with hamstring shortening

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Luis Espejo-Antúnez, María Carracedo-Rodríguez, Fernando Ribeiro, João Venâncio, Blanca De la Cruz-Torres, Manuel Albornoz-Cabello
ObjectiveTo assess the immediate and mid-term (after 7 days) effects of electric current combined with simultaneous muscle stretching (EME technique) per comparison to the isolated use of the same current (without applying simultaneous muscle stretching), over the hamstring extensibility in football players with hamstring shortening, and to estimate the clinical benefit of the interventions according to the muscular extensibility.MethodsForty-eight participants were randomized to receive one session of EME technique (n = 26) or one session of the electrical current (EC) alone (n = 22). The measurement of the hamstrings extensibility through the active knee test was carried out before and immediately after each intervention and one week later.ResultsA significant interaction group x time was observed (F2,84 = 7.112, p = 0.001; partial eta squared = 0.145). The hamstrings extensibility changed significantly immediately after the EME technique (147.3° ± 16.4° to 153.5° ± 14.2°, p < 0.05), but not after the EC only (144.2 ± 10.2° to 141.7 ± 7.8°, p > 0.05). One week after the intervention no significant differences were found to the baseline values in both groups. The number needed to treat to prevent one new case of hamstring shortening was 3.ConclusionThe combination of electric current with simultaneous stretching is an effective technique to acutely increase the hamstring extensibility of football players with hamstring shortness.

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The Impact of Ethnicity on the Prevalence and Severity of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder associated with multiple adverse health consequences and its prevalence is increasing in parallel with rising obesity trends. Early support for ethnic differences in OSA prevalence and severity has been derived from studies of relatively homogenous ethnic groups. However, between-study comparisons are problematic given differing methodologies. Recent large inter-ethnic studies examining different ethnic populations using standardized protocols support the notion that Chinese have an increased OSA prevalence and severity compared to those of European descent.

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A systematic review and meta-analysis of sleep architecture and chronic traumatic brain injury

Sleep quality appears to be altered by traumatic brain injury (TBI). However, whether persistent post-injury changes in sleep architecture are present is unknown and relatively unexplored. We conducted a systematic review and meta-analysis to assess the extent to which chronic TBI (>6 months since injury) is characterized by changes to sleep architecture. We also explored the relationship between sleep architecture and TBI severity. In the fourteen included studies, sleep was assessed with at least one night of polysomnography in both chronic TBI participants and controls.

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Characterization of Cervical Neuromuscular Response to Head-neck Perturbation in Active Young Adults

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Publication date: Available online 2 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Bara Alsalaheen, Ryan Bean, Andrea Almeida, James Eckner, Matthew Lorincz
BackgroundThe majority of studies examining the role of cervical muscles on head-neck kinematics focused on musculoskeletal attributes (e.g. strength). Cervical neuromuscular response to perturbation may represent a divergent construct that has not been examined under various perturbation conditions. This study examined the association between cervical musculoskeletal attributes and cervical neuromuscular response of the sternocleidomastoid (SCM) to perturbation. Furthermore, this study examined the effect of anticipation and preload on the SCM neuromuscular response.MethodsNineteen participants completed measurement of SCM muscle size, cervical flexion maximal voluntary isometric contraction, and the neuromuscular response of the SCM to cervical perturbation. Cervical perturbation was delivered by dropping a 1.59 kg mass from a loading apparatus. The impulsive load was delivered under four conditions: 1) Anticipated perturbation with no preload (A-NP), 2) Unanticipated perturbation with no preload (U-NP), 3) Anticipated perturbation with preload (A-P), and 4) Unanticipated perturbation with preload (U-P).ResultsNone of the cervical musculoskeletal attributes were correlated with the SCM cervical neuromuscular response. This study demonstrated significant effect of preloading and anticipation on baseline EMG amplitude and EMG onset latency for the SCM. Furthermore, there was a significant effect of preloading on average EMG response amplitude for the SCM.DiscussionThe findings of this study indicate that cervical neuromuscular response of the SCM is different from musculoskeletal attributes and is influenced by perturbation conditions. These findings provide conceptual support to examine the neuromuscular response of the SCM in mitigating head-neck kinematics.

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