To assess the effects of clinical-like cryotherapy on inflammatory signs (in vivo neutrophil migration, cytokines, and joint inflammation), pain, joint swelling, balance, and motor coordination in ...mice with knee arthritis. Young C57BL/6 mice were randomly divided into three groups (8 to 10 mice per group): Control group: mice with no intervention; antigen-induced arthritis (AIA) group: mice sensitized and immunized with intra-articular (i.a.) injection of methylated bovine serum albumin (mBSA); and AIA + cryotherapy group: mice sensitized, immunized with i.a. injection of mBSA, and submitted to a clinical-like cryotherapy protocol. After 21 days of sensitization, AIA and AIA + cryotherapy groups received i.a. injection of mBSA (100 μg/joint) to induce joint inflammation, and a clinical-like cryotherapy protocol was applied to AIA + cryotherapy group (crushed ice bag, two cryotherapy sessions of 20 min every two hours). Experimental analysis was conducted in the initial (immediately after i.a. injection of mBSA) and final periods (two hours after the second cryotherapy session). The number of synovial fluid neutrophils, cytokine levels, joint histology, pain, joint swelling, and motor performance were also analyzed. Our results showed that clinical-like cryotherapy in mice with acute knee arthritis reduced inflammatory signs, pain, and joint swelling, and improved balance and motor coordination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Studies in neurologically intact subjects suggest that the gradual presentation of small perturbations (errors) during learning results in better transfer of a newly learned walking ...pattern to overground walking. Whether the same result would be true after stroke is not known. Objective. To determine whether introducing gradual perturbations, during locomotor learning using a split-belt treadmill influences learning the novel walking pattern or transfer to overground walking poststroke. Methods. Twenty-six chronic stroke survivors participated and completed the following walking testing paradigm: baseline overground walking; baseline treadmill walking; split-belt treadmill/adaptation period (belts moving at different speeds); catch trial (belts at same speed); post overground walking. Subjects were randomly assigned to the Gradual group (gradual changes in treadmill belts speed during adaptation) or the Abrupt group (a single, large, abrupt change during adaptation). Step length asymmetry adaptation response on the treadmill and transfer of learning to overground walking was assessed. Results. Step length asymmetry during the catch trial was the same between groups (P = .195) confirming that both groups learned a similar amount. The magnitude of transfer to overground walking was greater in the Gradual than in the Abrupt group (P = .041). Conclusions. The introduction of gradual perturbations (small errors), compared with abrupt (larger errors), during a locomotor adaptation task seems to improve transfer of the newly learned walking pattern to overground walking poststroke. However, given the limited magnitude of transfer, future studies should examine other factors that could impact locomotor learning and transfer poststroke.
SARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these ...drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment.
Despite the fast development of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still circulating and generating variants of concern (VoC) that escape the humoral immune ...response. In this context, the search for anti-SARS-CoV-2 compounds is still essential. A class of natural polyphenols known as flavonoids, frequently available in fruits and vegetables, is widely explored in the treatment of different diseases and used as a scaffold for the design of novel drugs. Therefore, herein we evaluate seven flavonoids divided into three subclasses, isoflavone (genistein), flavone (apigenin and luteolin) and flavonol (fisetin, kaempferol, myricetin, and quercetin), for COVID-19 treatment using cell-based assays and in silico calculations validated with experimental enzymatic data. The flavonols were better SARS-CoV-2 inhibitors than isoflavone and flavones. The increasing number of hydroxyl groups in ring B of the flavonols kaempferol, quercetin, and myricetin decreased the 50% effective concentration (EC50) value due to their impact on the orientation of the compounds inside the target. Myricetin and fisetin appear to be preferred candidates; they are both anti-inflammatory (decreasing TNF-α levels) and inhibit SARS-CoV-2 mainly by targeting the processability of the main protease (Mpro) in a non-competitive manner, with a potency comparable to the repurposed drug atazanavir. However, fisetin and myricetin might also be considered hits that are amenable to synthetic modification to improve their anti-SARS-CoV-2 profile by inhibiting not only Mpro, but also the 3′–5′ exonuclease (ExoN).
Objective and reliable measurements to investigate daily behavior patterns in people with stroke could help therapeutic interventions after a stroke.
To evaluate whether the Activity Monitoring for ...Rehabilitation (AMoR) platform has adequate concurrent validity and reliability for step counting and time spent sitting/lying in people post-stroke and to investigate its percentage accuracy for step counting at different walking speeds.
Cross-sectional observational study. Fifty chronic post-stroke subjects used the AMoR platform and SAM simultaneously while a Video camera recorded the same activities during clinical trials. Spearman's correlation coefficient, the mean absolute percentage error, the intraclass correlation coefficient and Bland-Altman plot analyses were used to estimate the validity and reliability of the AMoR platform and StepWatch
TM
Activity Monitor (SAM). The accuracy percentage was calculated for each device and plotted as a function of the walking speed during the 10-meter walk test (10MWT).
There was a very high correlation for step counting in all tests and a high correlation for time spent sitting/lying. The mean absolute percentage error values remained below 4% for step counting and time sitting/lying. The AMoR platform also showed excellent reliability for step counting and sitting/lying time, with values within the limit of agreement in the Bland-Altman plots. A high percentage of accuracy for step counting in the AMoR platform was observed during the 10MWT.
The AMoR platform is valid and reliable for step counting and time spent sitting/lying, with a high percentage of accuracy at different walking speeds in the post-stroke population.
Research over the last two decades has highlighted the critical role of Brain-derived neurotrophic factor (BDNF) in brain neuroplasticity. Studies suggest that physical exercise may have a positive ...impact on the release of BDNF and therefore, brain plasticity. These results in animal and human studies have potential implications for the recovery from damage to the brain and for interventions that aim to facilitate neuroplasticity and, therefore, the rehabilitation process.
The aim of this study was to carry out a systematic review of the literature investigating how aerobic exercises and functional task training influence BDNF concentrations post-stroke in humans and animal models.
Searches were conducted in PubMed (via National Library of Medicine), SCOPUS (Elsevier), CINAHL with Full Text (EBSCO), MEDLINE 1946-present with daily updates (Ovid) and Cochrane.
All of the database searches were limited to the period from January, 2004 to May, 2017.
Two reviewers extracted study details and data. The methodological quality of the studies that used animal models was assessed using the ARRIVE Guidelines, and the study that evaluated human BDNF was assessed using the PEDro Scale.
Twenty-one articles were included in this review. BDNF measurements were performed systemically (serum/plasma) or locally (central nervous system). Only one study evaluated human BDNF concentrations following physical exercise, while 20 studies were experimental studies using a stroke model in animals. A wide variation was observed in the training protocol between studies, although treadmill walking was the most common type of intervention among the studies. Studies were of variable quality: the studies that used animal models scored from 8/20 to 15/20 according to the ARRIVE Guidelines. The only study that evaluated human subjects scored 5/10 according to the PEDro scale and, which indicates a quality classified as "fair".
The results of the current systematic review suggest that aerobic exercise promotes changes in central BDNF concentrations post-stroke. On the other hand, BDNF responses following functional exercises, such as reaching training and Constraint Induced Movement Therapy (CIMT), seem to be still controversial. Given the lack of studies evaluating post-stroke BDNF concentration following physical exercise in humans, these conclusions are based on animal work.
ABSTRACT
Introduction
It is not clear if electrical stimulation (ES) can affect muscle reinnervation. This study aimed to verify if ES affects neuromuscular recovery after nerve crush injury in rats.
...Methods
Denervated muscles were electrically stimulated daily for 6 or 14 days. Neuromuscular performance and excitability, and muscle morphology were determined. Muscle trophism markers (atrogin‐1, MuRF‐1, and myoD), as well as neuromuscular junction (NMJ) organization (muscle‐specific receptor tyrosine kinase MuSK, cytoplasmic protein downstream of kinase‐7 Dok‐7, nicotinic ACh receptor nAChR, and neural cell adhesion molecule N‐CAM) were assessed.
Results
ES impaired neuromuscular recovery at day 14 postdenervation. Muscle hypoexcitability was accentuated by ES at 6 and 14 days postdenervation. Although ES reduced the accumulation of atrogin‐1, MuRF1, and myoD mRNAs, it increased muscle atrophy. Gene expression of MuSK, Dok‐7, nAChR, and the content of N‐CAM protein were altered by ES.
Discussion
ES can delay the reinnervation process by modulating factors related to NMJ stability and organization, and inducing dysfunction, hypoexcitability, and muscle atrophy. Muscle Nerve 56: E108–E118, 2017
Rheumatoid arthritis is an autoimmune and inflammatory disease that affects synovial joint tissues and skeletal muscle. Clinical-like cryotherapy benefits signs of joint inflammation in knee ...osteoarthritis after 60 days of anterior cruciate ligament transection surgery. However, it is unknown whether it also benefits acute knee arthritis (e.g., reduces inflammatory process and protects neuromuscular junction NMJ and muscle fibers). We aimed to analyze the effects of clinical-like cryotherapy on NMJ and quadriceps muscle fibers in a model of acute knee arthritis. Twenty-four male C57BL/6 mice (20 to 25 g) were randomly allocated into three groups: control (mice with no intervention), antigen-induced arthritis (AIA; mice sensitized and immunized with intra-articular i.a. injection of methylated bovine serum albumin mBSA), and AIA+cryotherapy (mice sensitized, immunized with i.a. injection of mBSA, and submitted to a clinical-like cryotherapy protocol). Twenty-one days after sensitization, arthritis was induced in immunized mice via i.a. injection of mBSA (100 μg/joint). Two clinical-like cryotherapy sessions (crushed ice pack for 20 min) were applied two hours apart. The first session was applied immediately after i.a. injection of mBSA. The quadriceps was removed two hours after the second clinical-like cryotherapy session for morphological analysis of muscle fibers (cross-sectional area), frequency distribution of muscle fiber area (%), and NMJ (area, perimeter, and maximum diameter). Gene expressions of mRNA involved in NMJ signaling (γ-nAChR, α1-nAChR, ε-nAChR, Agrin-MusK-Rapsyn, α-dystrobrevin, and utrophin) and atrophy (muscle RING-finger protein-1 and Atrogin-1) pathways were analyzed. Inflammatory signs were assessed in knee joint (swelling, articular surface temperature, and neutrophil migration in synovial fluid). Regarding morphological analysis of muscle fibers, 180 to 270 and >270 μm2 classes were higher in the AIA+cryotherapy than the AIA group. Area, perimeter, and maximum diameter of NMJ also increased in the AIA+cryotherapy compared with the control group. Agrin mRNA expression increased in the AIA+cryotherapy compared with the control and AIA groups. In the atrophy pathway, Atrogin-1 increased compared with the control and AIA groups. The AIA+cryotherapy group reduced knee swelling and neutrophil migration compared with the AIA group. In conclusion, clinical-like cryotherapy increased Agrin expression, contributing to NMJ maintenance and increased Atrogin-1 expression, thus protecting NMJ and muscle fiber. Furthermore, clinical-like cryotherapy reduced inflammatory signs (swelling and neutrophil migration) of acute knee arthritis.
This study aimed to evaluate the validity and reliability of the T-shirt test (TST) in assessing sitting stability under three thigh support conditions and with timed outcomes derived in six ways ...among individuals with a spinal cord injury (SCI). The TST was performed five times under three thigh support conditions (85%, 55% and 25% of total thigh length) in two evaluations spaced between 7-14 days. For each thigh condition, six different outcomes were derived (average or best time from 2, 3, and 5 trial). All outcomes derivation showed excellent reliability on test day (intraclass correlation coefficient; ICC ≥ 0.997) and excellent test-retest reliability (ICC ≥ 0.874) for each thigh support condition. The TST showed high inverse correlations with the Spinal Cord Independence Measure III (SCIM)-mobility score for all outcomes and support conditions (ρ≥-0.706), except for Best-5; moderate inverse correlations with total SCIM-total scores for most outcome derivations and support conditions (ρ≥-0.636); and a moderate inverse correlation with confidence and capacity domains of Wheelchair Skills Test-Questionnaire for most outcome derivation and support conditions (ρ≥-0.504). The TST could discriminate cervical from high and low thoracic levels of injuries under minimal thigh support condition. Overall, all the TST-derived outcomes and support conditions showed adequate validity and test-retest reliability, but Best-5 had inconsistency. Under the minimal thigh support condition, all outcome derivations except Best-3 could discriminate cervical from other injury-level groups. Although all outcome derivations and thigh support conditions provided reliable results, we recommend using the average of 3 trials under the maximal thigh support condition.
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