Delayed Onset
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2021 ◽  
Vol 45 (1) ◽  
Natthanichar Rattanaseth ◽  
Patteera Panyarapeepat ◽  
Janisa Andrea Muljadi ◽  
Kornkit Chaijenkij ◽  
Jatupon Kongtharvonskul

Abstract Background There are multiple strategies that have been suggested to attenuate delayed onset muscle soreness (DOMS). Curcumin has been shown to reduce exercise-induced oxidative stress (OS) and inflammation. However, currently, there is still controversy. Main body of the abstract We conduct this meta-analysis according to the PRISMA guidelines. Relevant studies were included from Medline and Scopus from the date of inception to May 04th, 2021 that reported VAS score, blood markers (creatinine kinese (CK), tumor necrotic factor (TNF)-α and interleukin (IL)-6) and range of motion of either group. There were total of 13 studies including 202 and 176 persons in curcumin and placebo group. The unstandardized mean difference (UMD) of VAS muscle soreness in post-exercise, 1, 2, 3 and 4 days was − 0.12 (95% CI − 0.46, 0.22), − 0.38 (− 0.83, 0.08), − 0.67 (− 1.19, − 0.16), − 0.86 (− 1.38, − 0.34), − 0.81 (− 1.27, − 036) and − 1.24 (− 1.50, − 0.99) scores lower in curcumin when compared to placebo. The UMD of CK was − 11.07 (95% CI − 24, 1.86), − 37.51 (− 68.04, − 6.97), − 45.40 (− 95.67, 4.86), − 53.33 (− 128.11, 21.45), − 90.98 (− 173.45, − 8.51) and 117.84 (− 338.69, 574.37) lower in curcumin when compared to placebo. No statistically significantly differences were noted for IL-6, TNF-α and ROM between two groups. Short conclusion This meta-analysis suggested that curcumin supplement reduced delayed onset muscle soreness and CK after exercise in 1, 2, 3, and 4 days when compared to placebo. However, TNF and IL were not affected by curcumin ingestion. Level of evidence I.

Balázs Sonkodi ◽  
Endre Varga ◽  
László Hangody ◽  
Gyula Poór ◽  
István Berkes

Abstract Background Anterior cruciate ligament injury arises when the knee anterior ligament fibers are stretched, partially torn, or completely torn. Operated patients either end up re-injuring their reconstructed anterior cruciate ligament or majority develop early osteoarthritis regardless of the remarkable improvements of surgical techniques and the widely available rehabilitation best practices. New mechanism theories of non-contact anterior cruciate ligament injury and delayed onset muscle soreness could provide a novel perspective how to respond to this clinical challenge. Main body A tri-phasic injury model is proposed for these non-contact injuries. Mechano-energetic microdamage of the proprioceptive sensory nerve terminals is suggested to be the first-phase injury that is followed by a harsher tissue damage in the second phase. The longitudinal dimension is the third phase and that is the equivalent of the repeated bout effect of delayed onset muscle soreness. Current paper puts this longitudinal injury phase into perspective as the phase when the long-term memory consolidation and reconsolidation of this learning related neuronal injury evolves and the phase when the extent of the neuronal regeneration is determined. Reinstating the mitochondrial energy supply and ‘breathing capacity’ of the injured proprioceptive sensory neurons during this period is emphasized, as avoiding fatigue, overuse, overload and re-injury. Conclusions Extended use, minimum up to a year or even longer, of a current rehabilitation technique, namely moderate intensity low resistance stationary cycling, is recommended preferably at the end of the day. This exercise therapeutic strategy should be a supplementation to the currently used rehabilitation best practices as a knee anti-aging maintenance effort.

2021 ◽  
Leo Holguin ◽  
Liliana Echavarria ◽  
John C. Burnetta

Humanized mouse models are based on the engraftment of human cells in immunodeficient mouse strains, most notably the NSG strain. Most used models have a major limitation in common, the development of graft-versus-host disease (GVHD). GVHD not only introduces variabilities into the research data but also leads to animal welfare concerns. A new mouse strain, B6.129S-Rag2 tm1Fwa CD47 tm1Fpl Il2rg tm1Wjl /J which lacks Rag1, IL2rg, and CD47 (triple knockout or TKO), is resistant to GVHD development. We transplanted TKO mice with human peripheral blood mononuclear cells (PBMCs) to establish a new humanized PBMC (hu-PBMC) mouse model. A cohort of these mice was infected with HIV-1 and monitored for plasma HIV viremia and CD4 + T cell depletion. The onset and progression of GVHD were monitored by clinical signs. This study demonstrates that TKO mice transplanted with human PBMCs support engraftment of human immune cells in primary and secondary lymphoid tissues, rectum, and brain. Moreover, the TKO hu-PBMC model supports HIV-1 infection via intraperitoneal, rectal, or vaginal routes, as confirmed by robust plasma HIV viremia and CD4 + T cell depletion. Lastly, TKO mice showed a delayed onset of GVHD clinical signs (∼28 days) and exhibited significant decreases in plasma levels of TNFβ. Based on these results, the TKO hu-PBMC mouse model not only supports humanization and HIV-1 infection but also has a delayed onset of GVHD development, making this model a valuable tool in HIV research. Importance Currently, there is no cure or vaccine for HIV infection, thus continued research is needed to end the HIV pandemic. While many animal models are used in HIV research, none is used more than the humanized mouse model. A major limitation with current humanized mouse models is the development of graft-versus-host disease (GVHD). Here, we show a novel humanized-PBMC mouse model that has a delayed onset GVHD development and supports and models HIV infection comparable to well-established humanized mouse models.

2021 ◽  
Vol 45 (1) ◽  
Janisa Andrea Maljadi ◽  
Patsorn Kaewphongsri ◽  
Kornkit Chaijenkij ◽  
Jatupon Kongtharvonskul

Abstract Background There are multiple strategies that have been suggested to attenuate delayed-onset muscle soreness (DOMS). Caffeine has been shown to assist with blocking pain associated with DOMS. However, currently there is still controversy over the effects of caffeine use. Main body We conducted a meta-analysis to compare pain associated with muscle soreness by both the VAS and indirect markers by CK of caffeine and placebo after exercise. The meta-analysis was carried out in accordance with the PRISMA guidelines. Relevant studies from Medline and Scopus published up to May 20, 2021, were included, which resulted in a total of 477 and 132 studies being retrieved from Scopus and Medline, respectively. Seven studies met the inclusion criteria, and in these, there were 68 persons in the caffeine group and 74 persons in the placebo group. A visual analog score of muscle soreness was recorded pre-exercise, immediately post-exercise, and at one to four days post-exercise; the scores at these time points in the caffeine group as compared to those in the placebo group progressed from 0.00 (95% CI − 0.51, 0.50) to − 0.20 (− 1.09, 0.69), − 0.92 (− 2.20, 0.36), − 1.02 (− 1.86, − 0.19), 0.00 (− 0.36, 0.36), and 0.18 (− 0.56, 0.92), respectively. No statistically significant differences were noted for CK between the two groups at 24 h post-exercise. Short conclusion Our meta-analysis results indicate that caffeine supplements reduce delayed-onset muscle soreness when compared to a placebo 48 h after exercise. However, at 24 h post-exercise, caffeine can reduce DOMS only in people who worked on resistant exercise. The CK used in this meta-analysis did not show any differences. Trial registration: PROSPERO CRD42021260248. Level of evidence I.

2021 ◽  
Vol 12 ◽  
Frederik Staels ◽  
Tom Collignon ◽  
Albrecht Betrains ◽  
Margaux Gerbaux ◽  
Mathijs Willemsen ◽  

Inborn errors of immunity (IEI) are a heterogenous group of disorders driven by genetic defects that functionally impact the development and/or function of the innate and/or adaptive immune system. The majority of these disorders are thought to have polygenic background. However, the use of next-generation sequencing in patients with IEI has led to an increasing identification of monogenic causes, unravelling the exact pathophysiology of the disease and allowing the development of more targeted treatments. Monogenic IEI are not only seen in a pediatric population but also in adulthood, either due to the lack of awareness preventing childhood diagnosis or due to a delayed onset where (epi)genetic or environmental factors can play a role. In this review, we discuss the mechanisms accounting for adult-onset presentations and provide an overview of monogenic causes associated with adult-onset IEI.

Laura K. Gunther ◽  
Joseph A Cirilo ◽  
Rohini Desetty ◽  
Christopher M. Yengo

Class III myosins are actin-based motors proposed to transport cargo to the distal tips of stereocilia in the inner ear hairs cells and/or to participate in stereocilia length regulation, which is especially important during development. Mutations in the MYO3A gene are associated with delayed onset deafness. A previous study demonstrated that L697W, a dominant deafness mutation, disrupts MYO3A ATPase and motor properties but does not impair its ability to localize to the tips of actin protrusions. In the current study, we characterized the transient kinetic mechanism of the L697W motor ATPase cycle. Our kinetic analysis demonstrates that the mutation slows the ADP release and ATP hydrolysis steps, which results in a slight reduction in the duty ratio and slows detachment kinetics. Fluorescence recovery after photobleaching (FRAP) of filopodia tip localized L697W and WT MYO3A in COS-7 cells revealed that the mutant does not alter turnover or average intensity at the actin protrusion tips. We demonstrate that the mutation slows filopodia extension velocity in COS-7 cells which correlates with its 2-fold slower in vitro actin gliding velocity. Overall, this work allowed us to propose a model for how the motor properties of MYO3A are crucial for facilitating actin protrusion length regulation.

2021 ◽  
Vol 27 (6) ◽  
pp. 646-654
Roberto Lohn Nahon ◽  
Jaqueline Santos Silva Lopes ◽  
Anibal Monteiro de Magalhães Neto ◽  
Aloa de Souza Machado ◽  
Luiz Claudio Cameron

ABSTRACT Objective: To investigate the effectiveness of pharmacological interventions in the treatment of delayed onset muscle soreness (DOMS). Design: A systematic review and meta-analysis of randomized controlled clinical trials (RCTs). Data sources: The PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs published prior to August 3, 2020. Eligibility criteria for selecting studies: Studies that 1) used an RCT design; 2) evaluated the effectiveness of steroidal or nonsteroidal anti-inflammatory drugs (NSAIDs) in treating DOMS; and 3) therapeutically used drugs after exercise were included. Results: In total, 26 studies (patients = 934) were eligible for inclusion in the qualitative analysis on the treatment of DOMS. The results of the meta-analysis showed no superiority between the use and non-use of NSAIDs in the improvement of late muscle pain, as no statistically significant differences were verified (21 studies, n= 955; standard mean difference (SMD)= 0.02; 95% confidence interval (CI) −0.58, 0.63; p=0.94; I2=93%). The quality of the synthesized evidence was very low according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and there was significant heterogeneity among the included studies. Conclusion: The results demonstrate that NSAIDs are not superior to controls/placebos in treating DOMS. The inclusion of both studies with dose-response protocols and those with exercise protocols may have influenced the results. In addition, the high risk of bias identified reveals that limitations need to be considered when interpreting the results. Level of evidence I; ystematic review of RCT (Randomized and Controlled Clinical Trials).

2021 ◽  
Vol Publish Ahead of Print ◽  
Lucas D. Foster ◽  
Heather M. McDonald ◽  
Tom G. Sheidow

2021 ◽  
Vol Publish Ahead of Print ◽  
Nishant Radke ◽  
Miaoli Lin ◽  
Hiu Ying Leung ◽  
Zhe Xu

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2056-2056
Douglas W. Blayney ◽  
Mengru Chang ◽  
Lan Huang ◽  
Ramon Mohanlal

Abstract Introduction Plinabulin (Plin), a small molecule selective immune-enhancing microtubulin binding agent (SIMBA) has anti-cancer activity, and also prevents chemotherapy (Chemo) induced neutropenia (CIN). Plin has a rapid onset CIN prevention (1 st week) and G-CSF a delayed onset (2 nd week) of the cycle. Single agent Plin has non-inferior protection against CIN compared to Peg. Combining Plin with pegfilgrastim (Peg) has superior protection against CIN throughout the entire Chemo cycle (Blayney ASCO 2021). Plinabulin protected LSK cells in mice receiving myelosuppressive Chemo, which are cells equivalent to CD34+ in humans (Tonra Cancer Chemotherapy and Pharmacology. 2020). We evaluated the mechanism of Plin's rapid onset for CIN prevention in patients (pts). Methods Data from the CIN phase 2/3 Plin trials PROTECTIVE-1 (NCT03102606) with docetaxel 75 mg/m2 in pts with NSCLC, Breast Cancer, Prostate Cancer and PROTECTIVE-2 (NCT0329457) with docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (TAC) in early stage Breast Cancer was analyzed for pts receiving either Plin (n=228) or Control (no Plin); n=172). Both studies 105 and 106 had patients randomized to either Plin or Pegfilgrastim, which latter was given on the next day of Chemo, on day (D)2. The safety blood draw, taken on D2 at predose Pegfilgrastim, served as a no-treatment Control on D2 in this blood cell analysis for comparison with Plin, which was given on D1. The Plin dose was 20 mg/m2 or 40 mg, and was given as a single dose per cycle, by 30 min IV infusion, 30 min after Chemo on day (D)1. The 40 mg fixed dose is equivalent to 20 mg/m2 Plin. Absolute neutrophil count (ANC), monocyte (M), eosinophil (E), basophil (B), lymphocyte (L), erythrocyte (RBC), and platelet (P) counts were obtained from peripheral blood draws and analyzed by Central Laboratory (Covance). The primary analysis was to compare cell counts between Plin and Control in blood draws taken 24 hour (hr)post-Chemo (thus D2). Separately, we also established Spearman correlation coefficients (r) of scatter plots between ANC and M,E,B,L,RBC, or P count on D2, in a broader dataset that also included Plin doses of 5,10 and 30 mg/m2 in addition to 0 and 20 mg/m2 (40 mg fixed) doses to allow for dose-response evaluation (total n=451). D2 cell counts were expressed as change from pre-dose D1, in absolute values. Results At predose D1 (baseline), counts of ANC, M,E,B,L,RBC, and P were similar between the Plin and Control groups (p=NS). On D2, at 24 hr post-Chemo, ANC, M,E and B ,had all significantly decreased compared to D1 in the Control group (indicating myelosuppression by Chemo), whereas significantly increased with Plin (suggesting reversal of this myelosuppression), albeit within normal range (Table below). At 24 hr post-Chemo, counts for L and RBC had significantly decreased compared to D1 with both Control and Plin, however this decrease was ~50% less with Plin compared to Control (P<0.001). No difference in P counts were observed between Plin and Control at 24 hr post Chemo (p=0.69). Correlative analyses showed that at 24 hr post-Chemo (D2), ANC was positively correlated with counts of M (r=+0.42; p<0.0001), E (r=+0.16; p=0.0008), B (r=+0.20; p<0.0001), L (r=+0.32; p<0.0001), RBC (r=+0.07; p=0.1187) and P (r=+0.18; p=0.0002). Thus, with larger increase in ANC counts on D2, the larger were the increase in the other blood cell types. The observed results were Plin dose-dependent, and consistent between pts receiving either docetaxel alone or TAC . Shown below are mean (SD) of absolute cell count on D2, expressed as change from predose D1. Conclusion Plin rapidly (within 24 hours) reversed myelosuppression induced by Chemo, by protecting granulocyte-monocyte-progenitor (GMP) stem cells (responsible for producing ANC, M, B and E cells) or progenitor cells further upstream in the hematopoietic lineage tree. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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