Effects of an external static EF on the conformational transition of 5-HT1A receptor: A molecular dynamics simulation study.

The serotonin receptor subtype 1A (5-HT1AR), one of the G-protein-coupled receptor (GPCR) family, has been implicated in several neurological conditions. Understanding the activation and inactivation mechanism of 5-HT1AR at the molecular level is critical for discovering novel therapeutics in many diseases. Recently there has been a growing appreciation for the role of external electric fields (EFs) in influencing the structure and activity of biomolecules. In this study, we used molecular dynamics (MD) simulations to examine conformational features of active states of 5-HT1AR and investigate the effect of an external static EF with 0.02 V/nm applied on the active state of 5-HT1AR. Our results showed that the active state of 5-HT1AR maintained the native structure, while the EF led to structural modifications in 5-HT1AR, particularly inducing the inward movement of transmembrane helix 6 (TM6). Furthermore, it disturbed the conformational switches associated with activation in the CWxP, DRY, PIF, and NPxxY motifs, consequently predisposing an inclination towards the inactive-like conformation. We also found that the EF led to an overall increase in the dipole moment of 5-HT1AR, encompassing TM6 and pivotal amino acids. The analyses of conformational properties of TM6 showed that the changed secondary structure and decreased solvent exposure occurred upon the EF condition. The interaction of 5-HT1AR with the membrane lipid bilayer was also altered under the EF. Our findings reveal the molecular mechanism underlying the transition of 5-HT1AR conformation induced by external EFs, which offer potential novel insights into the prospect of employing structure-based EF applications for GPCRs.

Comparison of physical activity and physical fitness in children and adolescents of Chinese Han and Tibet ethnicity.

Background: Physical activity (PA) and physical fitness (PF) are important markers of health status in children and adolescents in different ethnicities. In this study, we aimed to compare the PA and PF indicators between Tibetan and Han children and adolescents. Methods: Children and adolescents of 4-9 grades were recruited in Shigatse (n = 963) and Shanghai (n = 2,525) respectively. The information related to demographic, PA, and PF was collected via a self-reported questionnaire. PA was assessed through the participation of moderate to vigorous PA (MVPA), muscle-strengthening exercise (MSE) and organized sport participation (OSP). PF was estimated using the International Fitness Scale containing components of overall fitness, cardiorespiratory fitness, speed and agility, muscular strength and flexibility. Results: Han (mean age = 13.45 ± 3.3 years; 49.7% girls) and Tibet (mean age = 13.8 ± 2.5 years; 48.3% girls) children and adolescents from Shanghai and Shigatse completed the questionnaire survey. It was revealed that Tibetan students had higher MVPA, MSE and OSP than children and adolescents of Han ethnicity (p < 0.01, small to medium effect size). A relatively higher percentage of student in Shanghai did not participate in any form of PA. On the other hand, less Tibetan students thought their PF indicators including overall fitness, cardiorespiratory fitness, speed and agility, muscular strength and flexibility were poor or very poor than their counterparts of Han ethnicity (p < 0.01, small to medium effect size). Conclusion: Tibetan children and adolescents have higher levels of PA and PF in comparison to their Han counterparts. More children and adolescents of Han ethnicity engage in no PA and think their PF indicators were poor.

Modulation of Heart Rate Variability and Brain Excitability through Acute Whole-Body Vibration: The Role of Frequency.

This cross-over study aimed to explore effects of acute whole-body vibration (WBV) at frequencies of 5-35 Hz on heart rate variability and brain excitability. Thirteen healthy physically active college students randomly completed eight interventions under the following conditions: static upright standing without vibration (CON), static squat exercise (knee flexion 150°) on the vibration platform (SSE), and static squat exercise (knee flexion 150°) combined with WBV at vibration frequency of 5, 9, 13, 20, 25, and 35 Hz. Five bouts × 30 s with a 30-s rest interval were performed for all interventions. The brain's direct current potentials (DCPs), frequency domain variables (FDV) including normalized low frequency power (nLF), normalized high frequency power (nHF) and the ratio of LF to HF (LF/HF), along with the mean heart rate (MHR) were collected and calculated before and after the WBV intervention. Results suggested that WBV frequency at 5 Hz had a substantial effect on decreasing DCPs [-2.13 µV, t(84) = -3.82, p < 0.05, g = -1.03, large] and nLF [-13%, t(84) = -2.31, p = 0.04, g = -0.62, medium]. By contrast, 20-35 Hz of acute WBV intervention considerably improved DCPs [7.58 µV, t(84) = 4.31, p < 0.05, g = 1.16, large], nLF [17%, t(84) = 2.92, p < 0.05, g = 0.79, large] and the LF/HF [0.51, t(84) = 2.86, p < 0.05, g = 0.77, large]. A strong (r = 0.7, p < 0.01) correlation between DCPs and nLF was found at 5 Hz. In summary, acute WBV at 20-35 Hz principally activated the sympathetic nervous system and increased brain excitability, while 5-Hz WBV activated the parasympathetic nervous system and reduced brain excitability. The frequency spectrum of WBV might be manipulated according to the intervention target on heart rate variability and brain excitability.

Molecular Insights into the Differential Effects of Acetylation on the Aggregation of Tau Microtubule-Binding Repeats.

Aggregation of tau protein into intracellular fibrillary inclusions is characterized as the hallmark of tauopathies, including Alzheimer's disease and chronic traumatic encephalopathy. The microtubule-binding (MTB) domain of tau, containing either three or four repeats with sequence similarities, plays an important role in determining tau's aggregation. Previous studies have reported that abnormal acetylation of lysine residues displays a distinct effect on the formation of pathological tau aggregates. However, the underlying molecular mechanism remains mostly elusive. In this study, we performed extensive replica exchange molecular dynamics (REMD) simulations of 144 µs in total to systematically investigate the dimerization of four tau MTB repeats and explore the impacts of Lys280 (K280) or Lys321 (K321) acetylation on the conformational ensembles of the R2 or R3 dimer. Our results show that R3 is the most prone to aggregation among the four repeats, followed by R2 and R4, while R1 displays the weakest aggregation propensity with a disordered structure. Acetylation of K280 could promote the aggregation of R2 peptides by increasing the formation of ß-sheet structures and strengthening the interchain interaction. However, K321 acetylation decreases the ß-sheet content of the R3 dimer, reduces the ability of R3 peptides to form long ß-strands, and promotes the stable helix structure formation. The salt bridge and Y310-Y310 π-π stacking interactions of the R3 dimer are greatly weakened by K321 acetylation, resulting in the inhibition of dimerization. This study uncovers the structural ensembles of tau MTB repeats and provides mechanistic insights into the influences of acetylation on tau aggregation, which may deepen the understanding of the pathogenesis of tauopathies.

The bibliometric and altmetric analysis of chronic traumatic encephalopathy research: how great is the impact?

Background: The study of chronic traumatic encephalopathy (CTE) has received great attention from academia and the general public. This study aims to analyze the research productivity on CTE and investigate the most discussed articles in academia and the general public by conducting bibliometric and altmetric analyses. Methods: Data of articles were obtained from the Web of Science Core Databases and Altmetric Explore. VOSviewer and CiteSpace software were used to analyze and visualize the articles. The correlation between Altmetric attention scores (AAS) and citation counts were assessed by Spearman correlation coefficient. Results: 788 publications of CTE were eventually gathered and analyzed, and 100 articles with highest citation counts (Top-cited) and 100 articles with highest AASs (Top-AAS) were then identified. The keywords density map showed both the general public and the scientists were particularly interested in the risk factors and pathology of CTE, and scientists were interested in the causes and characteristics of neurodegenerative diseases while the public became increasingly concerned about the detection and prevention of CTE. By examining the shared characteristics of the 44 articles (High-High articles) that overlapped between Top-cited and Top-AAS articles, we identified certain traits that may potentially contribute to their high citation rates and high AASs. Besides, significant positive correlations with varied strength between AAS and citation were observed in the 788 articles, Top-cited, Top-AAS and High-High datasets. Conclusion: This study is the first to link bibliometric and altmetric analyses for CTE publications, which may provide deeper understanding of the attention of the scientists and the general public pay to the study of CTE, and offer some guidance and inspiration for future CTE in the selection of research topics and directions.

Long-term exercise training and inflammatory biomarkers in healthy subjects: a meta-analysis of randomized controlled trials.

Objective: This meta-analysis investigated the effect of long-term exercise training (ET) including aerobic, resistance, and multicomponent ET on the levels of inflammatory biomarkers in randomized controlled trials (RCTs) involving healthy subjects. Methods: We searched seven databases for articles until May 1st, 2023. A random-effect meta-analysis, subgroup analysis, meta-regressions as well as trim and fill method were conducted using STATA 16.0. Result: Thirty-eight studies were included in the meta-analysis, involving 2,557 healthy subjects (mean age varies from 21 to 86 years). Long-term ET induced significantly decreased in the levels of interleukin-6 (IL-6) (SMD -0.16, 95% CI -0.30 to -0.03, p = 0.017), C-reactive protein (CRP) (SMD -0.18, 95% CI -0.31 to -0.06, p = 0.005), as well as tumor necrosis factor alpha (TNFα) (SMD -0.43, 95% CI -0.62 to -0.24, p < 0.001). Subgroup analysis revealed that Long-term ET conducted for more than 12 weeks and exercise of moderate intensity had greater anti-inflammatory effects. Meta-regression analysis showed that the reduction in CRP level induced by long-term ET was weakened by increasing exercise intensity. Conclusion: Long-term ET induced significant anti-inflammatory effects in healthy subjects. Long-term ET-induced anti-inflammatory effects were associated with exercise of moderate intensity and training conducted for more than 12 weeks.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/# myprospero, PROSPERO, identifier CRD42022346693.

Deciphering the Inhibitory Mechanism of Naphthoquinone-Dopamine on the Aggregation of Tau Core Fragments PHF6* and PHF6.

The formation of neurofibrillary tangles by abnormal aggregation of tau protein is considered to be an important pathological characteristic of tauopathies, including Alzheimer's disease and chronic traumatic encephalopathy. Two hexapeptides 275VQIINK280 and 306VQIVYK311 in the microtubule binding region, named PHF6* and PHF6, are known to be aggregation-prone and responsible for tau fibrillization. Previous experiments reported that naphthoquinone-dopamine (NQDA) could effectively inhibit the aggregation of PHF6* and PHF6 and disrupt the fibrillar aggregates into nontoxic species, displaying a dual effect on the amyloid aggregation. However, the underlying molecular mechanism remains mostly elusive. Herein, we performed all-atom molecular dynamics (MD) simulations for 114 µs in total to systematically investigate the impacts of NQDA on the oligomerization of PHF6* and PHF6. The conformational ensembles of PHF6* and PHF6 peptides generated by replica exchange MD simulations show that NQDA could effectively prevent the hydrogen bond formation, reduce the ability of peptides to self-assemble into long ß-strand and large ß-sheets, and induce peptides to form a loosely packed and coil-rich oligomer. The interaction analysis shows that the binding of NQDA to PHF6* is mainly through hydrophobic interactions with residue I277 and hydrogen bonding interactions with Q276; for the PHF6 peptides, NQDA displays a strong π-π stacking interaction with residue Y310, thus impeding the Y310-Y310 π-π stacking and I308-Y310 CH-π interactions. The DA group of NQDA displays a stronger cation-π interaction than the NQ group, while the NQ group exhibits a stronger π-π stacking interaction. MD simulations demonstrate that NQDA prevents the conformational conversion to ß-sheet-rich aggregates and displays an inhibitory effect on the oligomerization dynamics of PHF6* and PHF6. Our results provide a complete picture of inhibitory mechanisms of NQDA on PHF6* and PHF6 oligomerization, which may pave the way for designing drug candidates for the treatment of tauopathies.

Effects of whole-body vibration on sensorimotor deficits and brain plasticity among people with chronic ankle instability: a study protocol for a single-blind randomized controlled trial.

BACKGROUND: Chronic ankle instability (CAI) is a form of musculoskeletal disease that can occur after a lateral ankle sprain, and it is characterized by pain, recurrent ankle sprains, a feeling of "giving way" at the ankle joint, and sensorimotor deficits. There has been increasing evidence to suggest that plastic changes in the brain after the initial injury play an important role in CAI. As one modality to treat CAI, whole-body vibration (WBV) has been found to be beneficial for treating the sensorimotor deficits accompanying CAI, but whether these benefits are associated with brain plasticity remains unknown. Therefore, the current study aims to investigate the effect of WBV on sensorimotor deficits and determine its correlation with plastic changes in the brain. METHODS: The present study is a single-blind randomized controlled trial. A total of 80 participants with CAI recruited from the university and local communities will be divided into 4 groups: whole-body vibration and balance training (WBVBT), balance training (BT), whole-body vibration (WBV), and control group. Participants will be given the WBV intervention (25-38 Hz, 1.3-2 mm, 3-time per week, 6-week) supervised by a professional therapist. Primary outcome measures are sensorimotor function including strength, balance, proprioception and functional performance. Brain plasticity will be evaluated by corticomotor excitability, inhibition, and representation of muscles, as measured by transcranial magnetic stimulation. Activation of brain areas will be assessed through functional near-infrared spectroscopy. Secondary outcome measures are self-reported functional outcomes involving the Cumberland Ankle Instability Tool and the Foot and Ankle Ability Measure. All tests will be conducted before and after the WBV intervention, and at 2-week follow-up. Per­protocol and intention-to-treat analysis will be applied if any participants withdraw. DISCUSSION: This is the first trial to investigate the role of brain plasticity in sensorimotor changes brought by WBV for individuals with CAI. As plastic changes in the brain have been an increasingly important aspect in CAI, the results of the current study can provide insight into the treatment of CAI from the perspective of brain plasticity. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300068972); registered on 02 March 2023.

Mechanistic Insights into the Binding of Different Positron Emission Tomography Tracers to Chronic Traumatic Encephalopathy Tau Protofibrils.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, and it is neuropathologically defined as the accumulation of abnormally hyperphosphorylated tau (p-tau). Early detection of p-tau in the brain is of great value in the prevention and treatment of CTE. Previous experimental studies reported that positron emission tomography (PET) technique using several tau tracers are available for imaging certain neurodegenerative diseases. However, few studies have focused on the development of CTE tau tracers. In this work, we performed conventional molecular docking and molecular dynamics simulations to address the binding properties and mechanisms of PET tracers (18F-PM-PBB3, 18F-CBD-2115, 18F-PI-2620, 18F-RO-948, 18F-MK-6240, and 18F-flortaucipir) to CTE tau protofibrils. The results show that the hydrophobic cavity and the top of the concave structure of CTE tau protofibrils are the preferred binding sites for the six tracers, and 18F-PM-PBB3 has the most competitive binding affinity to CTE tau protofibrils. Further investigation into the binding patterns of the six tracers to the CTE tau protofibrils showed that 18F-CBD-2115 and 18F-PM-PBB3 have a high number of H-bonds and hydrophobic contacts with tau protofibrils, resulting in strong hydrogen bonding and hydrophobic interactions; 18F-flortaucipir/18F-PI-2620 and 18F-PI-2620/18F-RO-948 form more intense π-π and cation-π interactions with tau protofibrils, respectively. Subsequently, we conducted a detailed analysis of the binding mechanism of 18F-PM-PBB3 to CTE tau protofibrils. The benzothiazole ring of 18F-PM-PBB3 exhibits stronger π-π stacking and cation-π interactions with tau protofibrils than the pyridine ring and forms a more concentrated T-shaped π-π stacking pattern. This study contributes to understanding the binding mechanism of PET tracers to CTE tau protofibrils and provides new insights into the design of potential novel tracers.

Effects of six weeks of sub-plateau cold environment training on physical functioning and athletic ability in elite parallel giant slalom snowboard athletes.

Background: Hypoxic and cold environments have been shown to improve the function and performance of athletes. However, it is unclear whether the combination of subalpine conditions and cold temperatures may have a greater effect. The present study aims to investigate the effects of 6 weeks of training in a sub-plateau cold environment on the physical function and athletic ability of elite parallel giant slalom snowboard athletes. Methods: Nine elite athletes (four males and five females) participated in the study. The athletes underwent 6 weeks of high intensity ski-specific technical training (150 min/session, six times/week) and medium-intensity physical training (120 min/session, six times/week) prior to the Beijing 2021 Winter Olympic Games test competition. The physiological and biochemical parameters were collected from elbow venous blood samples after each 2-week session to assess the athletes' physical functional status. The athletes' athletic ability was evaluated by measuring their maximal oxygen uptake, Wingate 30 s anaerobic capacity, 30 m sprint run, and race performance. Measurements were taken before and after participating in the training program for six weeks. The repeated measure ANOVA was used to test the overall differences of blood physiological and biochemical indicators. For indicators with significant time main effects, post-hoc tests were conducted using the least significant difference (LSD) method. The paired-samples t-test was used to analyze changes in athletic ability indicators before and after training. Results: (1) There was a significant overall time effect for red blood cells (RBC) and white blood cells (WBC) in males; there was also a significant effect on the percentage of lymphocytes (LY%), serum testosterone (T), and testosterone to cortisol ratio (T/C) in females (p < 0.001 - 0.015, η p 2 = 0 . 81 - 0 . 99 ). In addition, a significant time effect was also found for blood urea(BU), serum creatine kinase (CK), and serum cortisol levels in both male and female athletes (p = 0.001 - 0.029, η p 2 = 0 . 52 - 0 . 95 ). (2) BU and CK levels in males and LY% in females were all significantly higher at week 6 (p = 0.001 - 0.038), while WBC in males was significantly lower (p = 0.030). T and T/C were significantly lower in females at week 2 compared to pre-training (p = 0.007, 0.008, respectively), while cortisol (C) was significantly higher in males and females at weeks 2 and 4 (p (male) = 0.015, 0.004, respectively; p (female) = 0.024, 0.030, respectively). (3) There was a noticeable increase in relative maximal oxygen uptake, Wingate 30 s relative average anaerobic power, 30 m sprint run performance, and race performance in comparison to the pre-training measurements (p < 0.001 - 0.027). Conclusions: Six weeks of sub-plateau cold environment training may improve physical functioning and promote aerobic and anaerobic capacity for parallel giant slalom snowboard athletes. Furthermore, male athletes had a greater improvement of physical functioning and athletic ability when trained in sub-plateau cold environments.

Atomistic Insights into the Inhibitory Mechanism of Tyrosine Phosphorylation against the Aggregation of Human Tau Fragment PHF6.

Abnormal aggregation of the microtubule-associated protein tau into intracellular fibrillary inclusions is characterized as the hallmark of tauopathies, including Alzheimer's disease and chronic traumatic encephalopathy. The hexapeptide 306VQIVYK311 (PHF6) of R3 plays an important role in the aggregation of tau. Recent experimental studies reported that phosphorylation of residue tyrosine 310 (Y310) could decrease the propensity of PHF6 to form fibrils and inhibit tau aggregation. However, the underlying inhibitory mechanism is not well understood. In this work, we systematically investigated the influences of phosphorylation on the conformational ensembles and oligomerization dynamics of PHF6 by performing extensive all-atom molecular dynamics (MD) simulations. Our replica exchange MD simulations demonstrate that Y310 phosphorylation could effectively suppress the formation of ß-structure and shift PHF6 oligomers toward coil-rich aggregates. The interaction analyses show that hydrogen bonding and hydrophobic interactions among PHF6 peptides, as well as Y310-Y310 π-π stacking and I308-Y310 CH-π interactions, are weakened by phosphorylation. Additional microsecond MD simulations show that Y310 phosphorylation could inhibit the oligomerization of PHF6 by preventing the formation of large ß-sheet oligomers and multi-layer ß-sheet aggregates. This study provides mechanistic insights into the phosphorylation-inhibited tau aggregation, which may be helpful for the in-depth understanding of the pathogenesis of tauopathies.

Lifestyle intervention during pregnancy in patients with gestational diabetes mellitus and the risk of neonatal hypoglycemia: A systematic review and meta-analysis.

Objective: Neonatal hypoglycemia is a severe adverse consequence of infants born to mothers with gestational diabetes mellitus (GDM), which can lead to neonatal mortality, permanent neurological consequences, and epilepsy. This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to explore the effect of lifestyle intervention during pregnancy in women with GDM on the risk of neonatal hypoglycemia. Methods: PubMed, Web of Science, Cochrane Library, CINAHL, and SPORTDiscus databases were searched by 1st April 2022. Data were pooled as the risk ratio (RR) with 95% CIs of neonatal hypoglycemia. Random-effects, subgroup analyses, meta-regression analysis, and leave-one-out analysis were conducted, involving 18 RCTs. Results: Prenatal lifestyle intervention could significantly reduce the risk of neonatal hypoglycemia (RR: 0.73, 95% CI: 0.54-0.98, P = 0.037). Subgroup analysis further demonstrated that the reduced risk of neonatal hypoglycemia was observed only when subjects were younger than 30 years, initiated before the third trimester, and with dietary intervention. Meta-regression analysis revealed that the risk of neonatal hypoglycemia post lifestyle intervention was lower in mothers with lower fasting glucose levels at trial entry. Conclusion: We found that prenatal lifestyle intervention in women with GDM significantly reduced the risk of neonatal hypoglycemia. Only lifestyle intervention before the third trimester of pregnancy, or dietary intervention only could effectively reduce the risk of neonatal hypoglycemia. Future studies are required to explore the best pattern of lifestyle intervention and to determine the proper diagnostic criteria of GDM in the first/second trimester of pregnancy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, PROSPERO, identifier: CRD42021272985.

Mechanistic insight into the disruption of Tau R3-R4 protofibrils by curcumin and epinephrine: an all-atom molecular dynamics study.

The accumulation of Tau protein aggregates is a pathological hallmark of tauopathy, including chronic traumatic encephalopathy (CTE). Inhibiting Tau aggregation or disrupting preformed Tau fibrils is considered one of the rational therapeutic strategies to combat tauopathy. Previous studies reported that curcumin (Cur, a molecule of a labile natural product) and epinephrine (EP, an important neurotransmitter) could effectively inhibit the formation of Tau fibrillar aggregates and disassociate preformed fibrils. However, the underlying molecular mechanisms remain elusive. In this study, we performed multiple molecular dynamics simulations for 17.5 µs in total to investigate the influence of Cur and EP on the C-shaped Tau protofibril associated with CTE. Our simulations show that the protofibrillar pentamer is the smallest stable Tau R3-R4 protofibril. Taking the pentamer as a protofibril model, we found that both Cur and EP molecules could affect the shape of the Tau pentamer by changing the ß2-ß3 and ß7-ß8 angles, leading to a more extended structure. Cur and EP display a disruptive effect on the local ß-sheets and the formation of hydrogen bonds, and thus destabilize the global protofibril structure. The contact number analysis shows that Cur has a higher binding affinity with the Tau pentamer than EP, especially in the nucleating segment PHF6. Hydrophobic, π-π and cation-π interactions together facilitate the binding of Cur and EP with the Tau pentamer. Cur exhibits stronger hydrophobic and π-π interactions with Tau than EP, and EP displays a stronger cation-π interaction. Our findings provide molecular insights into the disruptive mechanisms of the Tau R3-R4 protofibrils by curcumin and epinephrine, which may be useful for the design of effective drug candidates for the treatment of CTE.

The effect of whole body vibration on sensorimotor deficits in people with chronic ankle instability: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effects of whole body vibration on chronic ankle instability-associated sensorimotor deficits in balance, strength, joint position sense and muscle activity. DATA SOURCES: Electronic databases including Cochrane Library, PubMed, Embase, Web of Science, EBSCO, China National Knowledge Infrastructure and WanFang were searched from database inception up to 31 March 2022. METHODS: The risk of bias and methodological quality of included studies were assessed using the Cochrane tool and Physiotherapy Evidence Database (PEDro) scale respectively. Standardized mean difference (SMD) and mean differences (MD) with 95% confidence interval (CI) were calculated using the RevMan 5.3 software. Meta-regression was conducted with Stata 16. RESULTS: Eight studies, with 315 subjects were eventually included in this review with an average PEDro score of 6.1/10. Significant effects of whole body vibration on balance (SMD = 0.61, 95% CI: 0.12 to 1.09, P = 0.01), and on the posterolateral direction (MD = 5.52, 95% CI: 1.02 to 10.01, P = 0.02) and medial direction (MD = 3.90, 95% CI: 0.87 to 6.94, P = 0.01) of the star excursion balance test were found. Whole body vibration significantly improved the peak torque (SMD = 0.36, 95% CI: 0.04 to 0.69, P = 0.03), joint position sense (SMD = 0.60, 95% CI: 0.10 to 1.11, P = 0.02), and muscle activity in tibialis anterior (SMD = 0.46, 95% CI: 0.04 to 0.88, P = 0.03) and gastrocnemius (SMD = 0.68, 95% CI: 0.14 to 1.23, P = 0.01). CONCLUSIONS: The current evidence supports the use of whole body vibration to improve sensorimotor deficits involving balance, strength, joint position sense, and muscle activity in people with chronic ankle instability.

Effects of Pre-exercise Acute Vibration Training on Symptoms of Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis.

ABSTRACT: Tan, J, Shi, X, Witchalls, J, Waddington, G, Lun Fu, AC, Wu, S, Tirosh, O, Wu, X, and Han, J. Effects of pre-exercise acute vibration training on symptoms of exercise-induced muscle damage: a systematic review and meta-analysis. J Strength Cond Res 36(8): 2339-2348, 2022-Exercise-induced muscle damage (EIMD) normally occurs after unaccustomed high-intensity eccentric exercises. Symptoms of EIMD include delayed-onset muscle soreness (DOMS), tenderness, stiffness, swelling, reduced strength, and increased creatine kinase (CK) levels in the blood. Vibration training (VT) may be useful as a pre-exercise intervention in attenuating EIMD on the basis of tonic vibration reflex (TVR) through a more efficient distribution of contractile stress over muscle fibers. The objective of this meta-analysis is to examine the effects of acute VT on symptoms of EIMD when performed as the pre-exercise intervention. Randomized controlled trials (RCTs) published in the 8 databases of Cochrane Library, PubMed, Embase, Web of Science, EBSCO, China National Knowledge Infrastructure, Airiti Library and WanFang Data from 1966 (the earliest available time) to January 2019 were searched. A total of 2,324 records were identified and 448 articles were screened with the title and abstract. Two investigators identified eligible studies, extracted data, and assessed the risk of bias independently. Review Manager 5.3 designed by Cochrane was used for the current meta-analysis. Six RCTs involving 180 subjects were included in the analysis. A low-to-moderate methodological quality of the included studies was revealed using the physiotherapy evidence database scale. The results showed that acute VT was superior to the control group for the reduction of DOMS on pain visual analogue scale at 24, 48 hours and pressure pain threshold at 24 hours. In addition, superior effects of acute VT were also found on the indirect markers of muscle damage including CK at 24, 72 hours, and lactate dehydrogenase at 24 hours. The current meta-analysis has collated the evidence to demonstrate that receiving acute VT before unaccustomed high-intensity eccentric exercises may be effective in attenuating markers of muscle damage and the development of DOMS when compared with a control group. The possible mechanisms of this effect could be attributed to an improved synchronization of muscle fiber caused by TVR, which could result in even distribution of exterior loads and eventually attenuate disruptions of muscle fibers. In addition, increased blood flow may also be helpful to prevent accumulation of metabolic substances and attenuate subsequent symptoms of EIMD. Vibration training may be used as a pre-exercise intervention to alleviate symptoms of EIMD caused by unaccustomed high-intensity eccentric exercise. Because of the limited quantity and quality of included studies, more high-quality studies are required to ascertain the effect of VT on symptoms of EIMD.

Unfixed Movement Route Model, Non-Overcrowding and Social Distancing Reduce the Spread of COVID-19 in Sporting Facilities.

Localized outbreaks of COVID-19 have been reported in sporting facilities. This study used the Agent-based Modeling (ABM) method to analyze the transmission rate of COVID-19 in different sporting models, sporting spaces per capita, and situations of gathering, which contributes to understanding how COVID-19 transmits in sports facilities. The simulation results show that the transmission rate of COVID-19 was higher under the Fixed Movement Route (FMR) than under the Unfixed Movement Route (UMR) in 10 different sporting spaces per capita (1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 m2) (p = 0.000). For both FMR and UMR, the larger the sporting space per capita, the lower the virus transmission rate. Additionally, when the sporting space per capita increases from 4 m2 to 5 m2, the virus transmission rate decreases most significantly (p = 0.000). In the FMR model with a per capita sporting space of 5 m2, minimizing gathering (no more than three people) could significantly slow down the transmission rate of the COVID-19 virus (p < 0.05). This study concluded that: (1) The UMR model is suggested in training facilities or playing grounds; (2) The sporting space should be non-overcrowding, and it is recommended that the sporting space per capita in the sporting grounds should not be less than 5 m2; (3) It is important to maintain safe social distancing and minimize gathering (no more than three people) when exercising.

Laparoscopy for Hepatolithiasis: Biliary Duct Exploration with Primary Closure Versus T-Tube Drainage.

Background: A recent meta-analysis showed that the primary closure (PC) of the biliary duct in the absence of T-tube (TT) drainage is a safe alternative for cholelithiasis after laparoscopic biliary exploration. However, its feasibility, benefits, and indications in hepatolithiasis remain undefined. Patients and Methods: From October 2008 to October 2012, we enrolled 84 patients with intrahepatic bile duct stones who underwent laparoscopic bile duct exploration (LBDE) and/or hepatectomy with TT-drainage or PC. The operative outcomes, intraoperative performance, and feasibility of the procedures were compared. Results: Forty-one patients who underwent TT insertion were compared with 43 patients who underwent PC. No mortalities were observed following either procedure. The median postoperative hospital stay was shorter in PC (5.4 ± 3.5 days) versus TT (8.9 ± 3.2 days; P = .006). The median recovery time (full activity and return to work) was similarly shorter in the PC group (11.6 ± 5.1 days) compared with the TT group (22.4 ± 13.2 days; P = .005). The incidence of postoperative and biliary complications was lower in the PC versus the TT group. Conclusions: PC is beneficial in patients requiring LBDE and/or hepatectomy, and shows a similar safety profile to TT.

A Comparison of the Relative Safety and Efficacy of Laparoscopic Choledochotomy with Primary Closure and Endoscopic Treatment for Bile Duct Stones in Patients with Cholelithiasis.

Background: To date, several clinical trials have demonstated that both one-stage laparoscopic cholecystectomy (LC) combined with common bile duct exploration (LC+BDE) with primary closure and one-stage LC combined with endoscopic stone extraction (LC+ESE) are the two primary clinical approaches to treat cholelithiasis. However, no studies to date have directly compared the LC+BDE with primary closure and one-stage LC+ESE procedures. We, therefore, conducted a retrospective analysis of patients with cholelithiasis who had been treated through LC+ESE or LC+BDE to compare these two approaches for the treatment of cholecystitis and common bile duct stones (CCBDS). Methods: Consecutive CCBDS patients with cholelithiasis in our hospital who were diagnosed through Media Resource Control Protocol (MRCP) and ultrasound between June 2010 and February 2017 were randomly assigned to undergo either LC+ESE or LC+BDE, as both procedures are routinely used to treat cholelithiasis in our hospital. All patients were made aware of the risks and benefits of the surgery preoperatively, and this study was approved by the ethics committee of our institute. Outcomes in these two groups, including rates of success and reasons for operative failure, were then compared, as were data pertaining to patient demographics, clinical findings, postoperative stay duration, and medical expenses. In addition, biliary reflux as measured through computed tomography or gastrointestinal imaging was monitored for a minimum of 2 years. Results: In total, 207 CCBDS patients were identified during the study period and were randomized into the LC+ESE (n = 103) or LC+BDE (n = 104) treatment groups. We found that patients treated through LC+BDE achieved a significantly higher success rate than that achieved in patients treated through LC+ESE (93.3% versus 82.5%; P < .05). Specifically, the LC+BDE with primary closure procedure failed in patients with impacted stones located at the end of the common bile duct (CBD) and in those with stenosis of the sphincter of Oddi. The only variable that differed significantly between these two treatment groups was stone location. Variables other than stone location, CBD size, and stone size did not differ significantly between the two groups. However, the LC+BDE treatment was associated with significant reductions in patient operating time, morbidity, hospital day duration, and biliary reflux of duodenal contents relative to the LC+ESE treatment. Conclusions: We found that LC+BDE with primary closure was a safer and more effective means of treated CCBDS patients than was the LC+ESE procedure and that it was not associated with risks of sphincterotomy of duodenal papilla (EST)- or T-tube-related complications. However, our data also clearly indicate that LC+BDE cannot replace LC+ESE in all patients, and that as such both approaches should be considered as being complementary to one another, with their relative advantages in a given patient being defined based upon local resource availability and expertise. In addition, when the LC+ESE procedure fails then the LC+BDE treatment can be safely employed as a salvage approach.

Concomitant Laparoscopic Perisplenic Artery Ligation Facilitates Surgery for Hepatobiliary Disease Coexisting with Portal Hypertension.

BACKGROUND: Although liver cirrhosis with portal hypertension (PH) contributes significantly to morbidity and mortality in abdominal surgery, many authors still consider this disease as an indication for surgery. In many reports, however, numerous treatment modalities focus on hypersplenism secondary to PH, irrespective of splenomegaly and PH. The proven benefits of laparoscopy seem especially applicable to patients with this complex disease. This study evaluates the safety and efficacy of laparoscopic perisplenic artery ligation (SAL) in patients with hepatobiliary disease and PH. METHODS: From July 2004 to May 2012, the medical records of all patients with hepatobiliary disease in the context of PH at the authors' institutes, including patient demography, operative outcomes, and change of liver function, were retrospectively reviewed. RESULTS: A total of 101 patients were included in the series: 85 patients with cirrhotic Child A, B class, who underwent no intervention (Control group n = 22), splenectomy (SP group n = 29), laparoscopic SAL (SAL-1 group, n = 34) for splenomegaly, and 16 patients with cirrhotic Child C class, who only underwent laparoscopic SAL (SAL-2 group, n = 16). Among these patients, both laparoscopic SAL and open SP for splenomegaly were available to decrease morbidity rate, loss of bleeding, and improve liver function, whereas laparoscopic SAL had a lower rate of surgical-related complications. CONCLUSIONS: Although technically challenging in patients with hepatobiliary disease coexisting with PH, the present series demonstrated the safety and feasibility of laparoscopic SAL, even facilitating simultaneous surgery for hepatobiliary diseases, with a clear advantage over SP and no intervention.

Laparoscopic Liver Resection and Enucleation of Liver Hemangioma with Selective Hepatic Vascular Occlusion: Technique and Indications.

BACKGROUND: Liver resection or enucleation has been the basic treatment for liver hemangioma. However, there were few reports about laparoscopic surgery (LS) of hemangioma. The intention of this study is to explore the indication and efficacy of LS for laparoscopic hepatectomy (LH) and develop an opinion of these modern developments. PATIENTS AND METHODS: Forty-four patients with LH underwent LS, with hemihepatic vascular occlusion (HVO group n = 24) or modified vascular occlusion (MVO group n = 20), and were retrospectively reviewed, including patients' demography, surgical technique, tumor size and location, blood loss, operation time, complications, modes of hepatic vascular occlusion and changes in postoperative liver function, and the difference in patients demography and operative outcome between HVO and MVO groups were compared as well. RESULTS: There were no deaths. The mean operating time was 162 minutes, intraoperative blood loss was 335 mL, blood transfusion rate was 9.1%, postoperative complication rate was 18.2%, and length of hospital stay was 7.3 days. Although the tumor size in the HVO group was significantly larger than that in the MVO group, there were no differences concerning operating outcomes, length of stay, and postoperative serum alanine transaminase (ALT), aspertate aminotransferase (AST) level between the HVO and MVO groups. CONCLUSIONS: LS was feasible for LH with hepatic vascular occlusion with zero mortality and low complication rate.