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Spinal modulation

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https://www.readbyqxmd.com/read/29452113/technological-innovation-strategies-for-the-specific-treatment-of-chagas-disease-based-on-benznidazole
#1
REVIEW
Leslie Raphael de Moura Ferraz, Alinne Élida Gonçalves Alves, Débora Dolores Souza da Silva Nascimento, Isabela Araújo E Amariz, Aline Silva Ferreira, Salvana Priscylla Manso Costa, Larissa Araújo Rolim, Ádley Antonini Neves de Lima, Pedro José Rolim Neto
Caused by Trypanosoma cruzi, Chagas disease is responsible for public health problems greater in magnitude than those attributed to malaria, schistosomiasis, or leishmaniasis. A factor in the socioeconomic development of poor countries, Chagas disease can cause death due to a high parasitic burden during its acute phase due and irreversible damage in organs such as the heart, esophagus, and colon during its chronic phase, even when the number of parasites is minimal. For treating Chagas disease, benznidazole (BNZ) remains the drug of choice and, in Latin America, the only drug on the market for treating the disease...
February 13, 2018: Acta Tropica
https://www.readbyqxmd.com/read/29451889/effects-of-patterned-peripheral-nerve-stimulation-on-soleus-spinal-motor-neuron-excitability
#2
Samuel Jimenez, Laura Mordillo-Mateos, Michele Dileone, Michela Campolo, Carmen Carrasco-Lopez, Fabricia Moitinho-Ferreira, Tomas Gallego-Izquierdo, Hartwig R Siebner, Josep Valls-Solé, Juan Aguilar, Antonio Oliviero
Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS) of the median nerve has been shown to change spinal motoneuron excitability in the cervical spinal cord as indexed by a change in mean H-reflex amplitude in the flexor carpi radialis muscle. It is unknown whether continuous TBS of a peripheral nerve can also shift motoneuron excitability in the lower limb...
2018: PloS One
https://www.readbyqxmd.com/read/29451306/supraspinal-modulation-of-neuronal-synchronization-by-nociceptive-stimulation-induces-an-enduring-reorganization-of-dorsal-horn-neuronal-connectivity
#3
E Contreras-Hernández, D Chávez, E Hernández, E Velázquez, P Reyes, J Bejar, M Martín, U Cortés, S Glusman, P Rudomin
Despite the profuse information on the molecular and cellular mechanisms involved in the central sensitization produced by intense nociceptive stimulation, the changes in the patterns of functional connectivity between spinal neurones associated with the development of secondary hyperalgesia and allodynia remain largely unknown. Here we show that the state of central sensitization produced by the intradermal injection of capsaicin is associated with structured transformations in neuronal synchronization that lead to an enduring reorganization of the functional connectivity within a segmentally distributed ensemble of dorsal horn neurones...
February 16, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29450848/automated-pathogenesis-based-diagnosis-of-lumbar-neural-foraminal-stenosis-via-deep-multiscale-multitask-learning
#4
Zhongyi Han, Benzheng Wei, Stephanie Leung, Ilanit Ben Nachum, David Laidley, Shuo Li
Pathogenesis-based diagnosis is a key step to prevent and control lumbar neural foraminal stenosis (LNFS). It conducts both early diagnosis and comprehensive assessment by drawing crucial pathological links between pathogenic factors and LNFS. Automated pathogenesis-based diagnosis would simultaneously localize and grade multiple spinal organs (neural foramina, vertebrae, intervertebral discs) to diagnose LNFS and discover pathogenic factors. The automated way facilitates planning optimal therapeutic schedules and relieving clinicians from laborious workloads...
February 15, 2018: Neuroinformatics
https://www.readbyqxmd.com/read/29447134/histone-deacetylase-5-hdac5-regulates-neuropathic-pain-through-sry-related-hmg-box-10-sox10-dependent-mechanism-in-mice
#5
Pan Gu, Zhiqiang Pan, Xiao-Min Wang, Liting Sun, Lydia Wai Tai, Chi Wai Cheung
A strong link between histone deacetylases (HDACs) and nociceptive hypersensitivity has been indicated in different pain models. However, the underlying molecular and cellular mechanisms remain elusive. Here, we discovered that partial sciatic nerve ligation-induced mechanical allodynia and thermal hyperalgesia in mice were associated with increased mRNA and protein expressions of HDAC5 (a member of class IIa HDACs) and SRY-related HMG-box 10 (SOX10) in the ipsilateral lumbar dorsal horn. Gene knockdown of spinal HDAC5 or SOX10 attenuated partial sciatic nerve ligation-induced nociceptive hypersensitivity, companied with decrease of spinal neuronal sensitization markers, namely phosphorylated-Erk, phosphorylated-GluN1 (ser896), and c-Fos...
March 2018: Pain
https://www.readbyqxmd.com/read/29447083/in-complete-sci-patients-long-term-functional-electrical-stimulation-of-permanent-denervated-muscles-increases-epidermis-thickness
#6
Giovanna Albertin, Christian Hofer, Sandra Zampieri, Michael Vogelauer, Stefan Löfler, Barbara Ravara, Diego Guidolin, Caterina Fede, Damiana Incendi, Andrea Porzionato, Raffaele De Caro, Alfonc Baba, Andrea Marcante, Francesco Piccione, Paolo Gargiulo, Amber Pond, Ugo Carraro, Helmut Kern
Our studies have shown that atrophic Quadriceps muscles from spinal cord injury patients suffering with permanent denervation-induced atrophy and degeneration of muscle fibers, were almost completely rescued to normal size after two years of home-based functional electrical stimulation (h-bFES). Because we used surface electrodes to stimulate the muscle, we wanted to know how the skin was affected by the treatments. Here, we report preliminary data from histological morphometry of Hematoxylin-Eosin-stained paraffin-embedded skin sections harvested from the legs of three SCI patients before and after two years of h-bFES...
February 15, 2018: Neurological Research
https://www.readbyqxmd.com/read/29443664/nusinersen-versus-sham-control-in-later-onset-spinal-muscular-atrophy
#7
Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel
BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274...
February 15, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29440755/neuropathic-morc2-mutations-perturb-ghkl-atpase-dimerization-dynamics-and-epigenetic-silencing-by-multiple-structural-mechanisms
#8
Christopher H Douse, Stuart Bloor, Yangci Liu, Maria Shamin, Iva A Tchasovnikarova, Richard T Timms, Paul J Lehner, Yorgo Modis
Missense mutations in MORC2 cause neuropathies including spinal muscular atrophy and Charcot-Marie-Tooth disease. We recently identified MORC2 as an effector of epigenetic silencing by the human silencing hub (HUSH). Here we report the biochemical and cellular activities of MORC2 variants, alongside crystal structures of wild-type and neuropathic forms of a human MORC2 fragment comprising the GHKL-type ATPase module and CW-type zinc finger. This fragment dimerizes upon binding ATP and contains a hinged, functionally critical coiled-coil insertion absent in other GHKL ATPases...
February 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/29439361/voluntary-contraction-enhances-spinal-reciprocal-inhibition-induced-by-patterned-electrical-stimulation-in-patients-with-stroke
#9
Yoko Takahashi, Toshiyuki Fujiwara, Tomofumi Yamaguchi, Hikaru Matsunaga, Michiyuki Kawakami, Kaoru Honaga, Katsuhiro Mizuno, Meigen Liu
BACKGROUND: Reciprocal inhibition (RI) may be important for recovering locomotion after stroke. Patterned electrical stimulation (PES) can modulate RI in a manner that could be enhanced by voluntary muscle contraction (VC). OBJECTIVE: To investigate whether VC enhances the PES-induced spinal RI in patients with stroke. METHODS: Twelve patients with chronic stroke underwent three 20 min tasks, each on different days: (1) PES (10 pulses, 100 Hz every 2 s) applied to the common peroneal nerve; (2) VC consisting of isometric contraction of the affected-side tibialis anterior muscle; (3) PES combined with VC (PES + VC)...
2018: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/29436632/sparstolonin-b-attenuates-spinal-cord-injury%C3%A2-induced-inflammation-in-rats-by-modulating-tlr4%C3%A2-trafficking
#10
Jianjun Yuan, Xueli Zhang, Rusen Zhu, Zijian Cui, Wei Hu
The present study used a spinal cord injury (SCI) model to evaluate whether sparstolonin B was able to prevent SCI, and to investigate the underlying signaling mechanism. Sparstolonin B attenuated the SCI‑induced Batto, Beattie and Bresnahan score and water content in rats. Sparstolonin B attenuated the mRNA expression of proinflammatory cytokines interleukin (IL)‑18, IL‑6, IL‑1β, and IL‑23, decreased the levels of tumor necrosis factor‑α and interferon‑γ, and decreased caspase‑3 activity and apoptosis regulator Bax protein expression in SCI rats...
February 6, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29434670/advances-in-spinal-muscular-atrophy-therapeutics
#11
REVIEW
Valeria Parente, Stefania Corti
Spinal muscular atrophy (SMA) is a progressive, recessively inherited neuromuscular disease, characterized by the degeneration of lower motor neurons in the spinal cord and brainstem, which leads to weakness and muscle atrophy. SMA currently represents the most common genetic cause of infant death. SMA is caused by the lack of survival motor neuron (SMN) protein due to mutations, which are often deletions, in the SMN1 gene. In the absence of treatments able to modify the disease course, a considerable burden falls on patients and their families...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29434537/how-can-a-ketogenic-diet-improve-motor-function
#12
REVIEW
Charlotte Veyrat-Durebex, Pascal Reynier, Vincent Procaccio, Rudolf Hergesheimer, Philippe Corcia, Christian R Andres, Hélène Blasco
A ketogenic diet (KD) is a normocaloric diet composed by high fat (80-90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29433094/fingolimod-reduces-the-clinical-expression-of-active-demyelinating-lesions-in-ms
#13
Signoriello Elisabetta, Landi Doriana, Monteleone Fabrizia, Saccà Francesco, Nicoletti Carolina Gabri, Buttari Fabio, Sica Francesco, Marfia Girolama Alessandra, Di Iorio Giuseppe, Lus Giacomo, Centonze Diego
BACKGROUND: Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ-1a...
February 5, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29432416/sox2-regulates-common-and-specific-stem-cell-features-in-the-cns-and-endoderm-derived-organs
#14
Daniel W Hagey, Susanne Klum, Idha Kurtsdotter, Cecile Zaouter, Danijal Topcic, Olov Andersson, Maria Bergsland, Jonas Muhr
Stem cells are defined by their capacities to self-renew and generate progeny of multiple lineages. The transcription factor SOX2 has key roles in the regulation of stem cell characteristics, but whether SOX2 achieves these functions through similar mechanisms in distinct stem cell populations is not known. To address this question, we performed RNA-seq and SOX2 ChIP-seq on embryonic mouse cortex, spinal cord, stomach and lung/esophagus. We demonstrate that, although SOX2 binds a similar motif in the different cell types, its target regions are primarily cell-type-specific and enriched for the distinct binding motifs of appropriately expressed interacting co-factors...
February 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29431275/burst-spinal-cord-stimulation-review-of-preclinical-studies-and-comments-on-clinical-outcomes
#15
REVIEW
Krishnan Chakravarthy, Alexander R Kent, Adil Raza, Fang Xing, Thomas M Kinfe
BACKGROUND: Burst spinal cord stimulation (SCS) technology uses a novel waveform that consists of closely packed high-frequency electrical impulses followed by a quiescent period. Within the growing field of neuromodulation, burst stimulation is unique in that it mimics the natural burst firing of the nervous system, in particular the thalamo-cingulate rhythmicity, resulting in modulation of the affective and attentional components of pain processing (e.g., medial thalamic pathways). STUDY DESIGN: A review of preclinical and clinical studies regarding burst SCS for various chronic pain states...
February 12, 2018: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/29429794/treatment-plan-quality-and-delivery-accuracy-assessments-on-3-imrt-delivery-methods-of-stereotactic-body-radiotherapy-for-spine-tumors
#16
Long Huang, Toufik Djemil, Tingliang Zhuang, Martin Andrews, Samuel T Chao, John H Suh, Ping Xia
Stereotactic body radiotherapy (SBRT) for spine tumors has demonstrated clinical effectiveness. The treatment planning and delivery techniques have evolved from dynamic conformal arc therapy, to fixed gantry angle intensity modulated radiotherapy (IMRT), and most recently to volumetric modulated arc therapy (VMAT). A hybrid-arc (HARC) planning and delivery method combining dynamic conformal arc therapy delivery with a number of equally spaced IMRT beams is proposed. In this study we investigated plan quality, delivery accuracy, and efficiency of 3 delivery techniques: IMRT, HARC, and VMAT...
February 8, 2018: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/29427331/the-role-of-the-mucosa-in-modulation-of-evoked-responses-in-the-spinal-cord-injured-rat-bladder
#17
Claire Doyle, Vivian Cristofaro, Bryan S Sack, Fabliha Mahmood, Maryrose P Sullivan, Rosalyn M Adam
AIMS: Mounting evidence indicates that a variety of factors released from the urothelium or suburothelium can modulate smooth muscle activity. Although the relationship between the mucosa and smooth muscle has been investigated, little is known about the pathophysiologic changes in detrusor-mucosa interactions in neurogenic bladders. The goal of the study was to determine the impact of the mucosa on evoked responses in spinal cord injured (SCI) bladders. METHODS: Urinary bladders were obtained from 6wk SCI rats or age-matched uninjured controls...
February 10, 2018: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29426358/optimizing-the-prescription-isodose-level-in-stereotactic-volumetric-modulated-arc-radiotherapy-of-lung-lesions-as-a-potential-for-dose-de-escalation
#18
Mark Chan, Matthew Wong, Ronnie Leung, Steven Cheung, Oliver Blanck
BACKGROUND: To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de-escalation in stereotactic body radiotherapy for non-small cell lung carcinomas (NSCLC). METHODS: For ten patients, inverse Monte Carlo dose optimization was performed to cover 95% PTV by varying prescription isodose lines (PIL) at 60 to 80% and reference 85%. Subsequently, these were re-normalized to the median gross tumor volume dose (GTV-based prescription) to assess the impacts of PTV and normal tissue dose reduction...
February 9, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29425907/visceral-pain-novel-approaches-for-optogenetic-control-of-spinal-afferents
#19
Nick J Spencer, Tim J Hibberd, Malin Lagerström, Yoichiro Otsuka, Nigel Kelly
Painful stimuli arising within visceral organs are detected by peripheral nerve endings of spinal afferents, whose cell bodies are located in dorsal root ganglia (DRG). Recent technical advances have made it possible to reliably expose and inject single DRG with neuronal tracers or viruses in vivo. This has facilitated, for the first time, unequivocal identification of different types of spinal afferent endings in visceral organs. These technical advances paved the way for a very exciting series of in vivo experiments where individual DRG are injected to facilitate opsin expression (e...
February 6, 2018: Brain Research
https://www.readbyqxmd.com/read/29424769/emotional-modulation-of-pain-and-spinal-nociception-in-sexual-assault-survivors
#20
Natalie Hellman, Bethany L Kuhn, Edward W Lannon, Michael F Payne, Cassandra A Sturycz, Shreela Palit, Joanna O Shadlow, Jamie L Rhudy
OBJECTIVE: Sexual assault (SA) is associated with an increased risk for chronic pain and affective distress. Given that emotional processes modulate pain (e.g., negative emotions enhance pain, positive emotions inhibit pain), increased pain risk in SA survivors could stem from a disruption of emotional modulation processes. METHODS: A well-validated affective picture-viewing paradigm was used to study emotional modulation of pain in 33 healthy, pain-free SA survivors and a control group of 33 healthy, pain-free individuals with no reported history of SA (matched on age, sex, race, and number of non-SA traumas)...
February 9, 2018: Psychosomatic Medicine
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