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Background Creatine kinase (CK) and aspartate aminotransferase (AST) activity can be increased with myositis associated with Toxoplasma and Neospora infection in dogs. Hypothesis/Objectives Serum activity of CK and AST can be used as a rapid screen for predicting positive serology in meningoencephalitis caused by Toxoplasma gondii or Neospora caninum in dogs compared to dogs with noninfectious meningoencephalitis. Animals Eighty dogs with meningoencephalitis based on magnetic resonance imaging and cerebrospinal fluid analysis. Methods Retrospective case‐control study. Serological cutoffs (≥1:800 immunofluorescence for Neospora and ≥1:400 IgG or ≥1:64 IgM or both for Toxoplasma) categorized dogs as infected (n = 21, all neosporosis) or noninfected (n = 59). Activities of CK and AST between infected and noninfected groups were compared using a Mann‐Whitney U test and receiver operating characteristic curve analysis. Results No dogs were diagnosed with toxoplasmosis. Serum CK and AST activities were significantly increased (P 99%. An AST cutoff of 57 U/L had 94.44% sensitivity and 85.71% specificity with an estimated negative predicative value of 99%. Conclusions and Clinical Importance High serum CK and AST activity can increase suspicion for neosporosis while awaiting serological tests for dogs with meningoencephalitis.

OBJECTIVES To evaluate the efficacy of low-intensity focused ultrasound (LIFU) treatment on rapid relief of delayed-onset muscle soreness (DOMS) triggered by high-intensity exercise. METHODS A total of 16 healthy male college students were randomly divided into two groups: the LIFU group (n = 8) and the Sham group (n = 8). After the exercise protocol, the LIFU group received treatment, which parameters included that the power output was 2.5 W/cm2 , the frequency was 1 MHz, and the treating time was 20 minutes. The Sham group was treated with LIFU without energy output. Visual analog scale was used to evaluate the level of DOMS in every participant. The activities of plasma creatine kinase, lactate dehydrogenase, and the plasma concentration were measured by spectrophotometry. Tumor necrosis factor-α and interleukin-6 of serum were analyzed by enzyme-linked immunosorbent assay. RESULTS The visual analog scale of quadriceps femoris and/or calf muscles in the LIFU group decreased significantly at 24 hours (P

Objective To evaluate the clinical outcome of manual reduction combined with pedicle fixation through Wiltse paraspinal approach (WPA) in the treatment of thoracolumbar fractures. Methods From May 2017 to May 2019, 48 thoracolumbar fractures patients without neurological symptoms were enrolled in this study. Forty‐eight patients were randomly divided into two groups based on the different surgical treatment. Group 1 was manual reduction combined with pedicle screw fixation through Wiltse paraspinal approach treatment group. Group 2 was pedicle screw fixation through traditional posterior approach treatment group. The operation time (OT), intraoperative blood loss (BL), postoperative drainage (PD), time of brace (TB) and the cobb angle recovery of the injured kyphosis in the prone position were obtained and compared between the two groups, respectively. Comparison of cobb angle changes, serum creatine kinase (CK) level, pain visual analogue score (VAS), Oswestry disability index (ODI), and multifidus cross‐sectional (MCS) area changes were achieved between the two groups, respectively. Results Forty‐eight patients were enrolled in this study and each group had 24 patients. There was no significant difference between the two groups in patient's age, height, weight, and body mass index (BMI). There were 20 males and four females in group 1. The mean age, height, weight, and BMI of patients were 61.99 ± 11.00 years (range, 42–75 years), 175.21 ± 4.49 cm, 76.71 ± 4.87 kg, and 24.98 ± 1.03 kg/m2 in group 1, respectively. Group 2 had 18 males and six females, and the mean age, height, weight, and BMI of patients were 57.95 ± 9.22 years (range, 44–77 years), 176.37 ± 4.56 cm, 77.42 ± 4.61 kg, and 24.87 ± 1.10 kg/m2 in group 2, respectively. The mean bleeding volume of group 1 was significantly less than group 2 (64.13 ± 9.77 ml and 152.13 ± 10.73 ml, respectively) (P, In this study, the results showed that preoperative manual reduction could help restore the height of injured vertebrae. Wiltse intermuscular approach has less intraoperative blood loss, shorter operation time and paraspinal muscle damage.

Background Omega 3 fatty acids supplementation may have an attenuative effect on exercise‐induced muscle damage (EIMD) through the cell membrane stabilization. The purpose of the present meta‐analysis was to evaluate the effects of omega 3 fatty acids supplementation, on indirect blood markers of muscle damage following EIMD in trained and untrained individuals. Methods Scopus, Medline, and Google scholar systematically searched up to January 2021. The Cochrane Collaboration tool was used for the quality of studies. Random‐effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were applied for the overall effect estimating. The heterogeneity between studies was evaluated applying the chi‐squared and I2 statistic. Results The outcomes showed a significant effect of omega 3 supplementation on reducing creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb) concentrations. In addition, a subgroup analysis indicated a significant reduction in CK, LDH, and Mb concentrations, based on follow‐ups after exercise, studies duration, time of supplementation, and training status. Conclusion The current meta‐analysis indicated an efficacy of omega 3 in reducing CK, LDH, and Mb serum concentration among healthy individuals, overall and in subgroups analysis. Thus, omega 3 should be considered as a priority EIMD recovery agent in interventions., The current meta‐analysis indicated an efficacy of omega 3 in reducing CK, LDH, and Mb serum concentration among healthy individuals, overall, and in subgroups analysis, based on follow‐ups after exercise, omega 3 doses, studies duration, time of supplementation, exercise type, and training status.

Aims To explore the correlation between cardiac‐related comorbidities, cardiac biomarkers, acute myocardial injury, and severity level, outcomes in COVID‐19 patients. Method Pubmed, Web of Science, Embase, CNKI, VIP, Wanfang, Cochrane Library databases, medRxiv, and Sinomed were reviewed systemically. Various types of clinical research reporting cardiac‐related comorbidities, cardiac biomarkers including lactate dehydrogenase (LDH), troponin I (TnI), high sensitivity troponin I (hs‐TnI), creatine kinase (CK), creatine kinase–MB (CK‐MB), myoglobin (Myo), N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) and acute cardiac injury grouped by severity of COVID‐19 were included. Outcome measures were events and total sample size for comorbidities, acute cardiac injury, and laboratory parameters of these biomarkers. The study was performed with Stata version 15.1. Results Seventy studies, with a total of 15,354 cases were identified. The results showed that COVID‐19's severity was related to cardiovascular disease. Similar odds ratios (ORs) were achieved in hypertension except for severe versus critical group (OR = 1.406; 95% CI, 0.942–2.097; p = .095). The relative risk (RR) of acute cardiac injury is 7.01 (95% CI, 5.64–8.71) in non‐survivor cases. When compared with the different severity of cardiac biomarkers, the pool OR of CK, CK‐MB, TnI, Myo and LDH were 2.683 (95% CI, 0.83–8.671; p = .106; I 2 = 0%), 2.263 (95% CI, 0.939–5.457; p = .069), 1.242 (95% CI, 0.628–2.457; p = .534), 1.756 (95% CI, 0.608–5.071; p = .298; I 2 = 42.3%), 1.387 (95% CI, 0.707–2.721; p = .341; I 2 = 0%) in the critical versus severe group, whose trends were not similar to other groups. The standard mean differences (SMD) of CK and TnI in the critical versus severe group were 0.09 (95% CI, −0.33 to 0.50; p = .685; I 2 = 65.2%), 0.478 (95% CI, −0.183 to 1.138; p = .156; I 2 = 76.7%), which means no difference was observed in the serum level of these indicators. Conclusion Most of the findings clearly indicate that hypertension, cardiovascular disease, acute cardiac injury, and related laboratory indicators are associated with the severity of COVID‐19. What is now needed are cross‐national prospectively designed observational or clinical trials that will help improve the certainty of the available evidence and treatment decisions for patients., We use a meta‐analysis to explore the correlation between cardiac‐related comorbidities, cardiac biomarkers, acute myocardial injury, and severity level, outcomes in patients with COVID‐19. Most of the findings clearly indicate that hypertension, cardiovascular disease, acute cardiac injury, and related laboratory indicators are associated with the severity of COVID‐19. What is now needed are cross‐national prospectively designed observational or clinical trials that will help improve the certainty of the available evidence and treatment decision for patients.

Duchenne muscular dystrophy (DMD) is a genetic disorder that results in the absence of dystrophin, a cytoskeletal protein. Individuals with this disease experience progressive muscle destruction, which leads to muscle weakness. Studies have been conducted to find solutions for the relief of individuals with this disease, several of which have shown that utrophin, a protein closely related to dystrophin, when overexpressed in mdx neonatal mice (the murine model of DMD), is able to prevent the progressive muscle destruction observed in the absence of dystrophin. Furthermore, recent studies have shown that L‐arginine induces utrophin upregulation in adult mdx mice. We hypothesized that L‐arginine treatment also induces utrophin upregulation to prevent the development of muscle weakness in neonatal mdx mice. Hence, L‐arginine should also prevent progressive muscle destruction via utrophin upregulation in mdx neonatal mice. Mdx neonatal mice were injected intraperitoneally daily with 800 mg/kg of L‐arginine for 6 weeks, whereas control mice were injected with a physiological saline. The following experiments were performed on the tibialis anterior (TA) muscle: muscle contractility and resistance to mechanical stress; central nucleation and peripheral nucleation, utrophin, and creatine kinase quantification as well as a nitric oxide (NO) assay. Our findings show that early administration of L‐arginine in mdx neonatal mice prevents the destruction of the tibialis anterior (TA) muscle. However, this improvement was related to nitric oxide (NO) production rather than the expected utrophin upregulation.

Cardiomyopathy syndrome (CMS), caused by piscine myocarditis virus (PMCV), is a serious challenge to Atlantic salmon (Salmo salar L.) aquaculture. Regrettably, husbandry techniques are the only tool to manage CMS outbreaks, and no prophylactic measures are available at present. Early diagnosis of CMS is therefore desirable, preferably with non-lethal diagnostic methods, such as serum biomarkers. To identify candidate biomarkers for CMS, the protein content of pools of sera (4 fish/pool) from salmon a CMS outbreak (3 pools) and from clinically healthy salmon (3 pools) were compared using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Overall, seven proteins were uniquely identified in the sera of clinically healthy fish, while twenty seven proteins were unique to the sera of CMS fish. Of the latter, 24 have been associated with cardiac disease in humans. These were grouped as leakage enzymes (creatine kinase, lactate dehydrogenase, glycogen phosphorylase and carbonic anhydrase); host reaction proteins (acute phase response proteins - haptoglobin, fibrinogen, α2-macroglobulin, ceruloplasmin; and complement-related proteins); and regeneration/remodelling proteins (fibronectin, lumican and retinol). Clinical evaluation of the suitability of these proteins as biomarkers of CMS, either individually or as part of a panel, is a logical next step for the development of early diagnostic tools for CMS.

10‐Gingerol (10‐Gin), an active ingredient extracted from ginger, has been reported to have beneficial effects on the cardiovascular system. However, 10‐Gin has not been proved to offer protection against cardiomyocyte injury induced by hypoxia/reoxygenation (H/R). This study aimed to investigate the protective effects of 10‐Gin against H/R‐induced injury and its potential mechanisms in cardiomyocytes. A H/R injury model of H9c2 cardiomyocytes was established using 600 μmol/L CoCl2 to induce hypoxia in the cells for 24 hr and then reoxygenated for 3 hr. 10‐Gin was pretreated with H9c2 cardiomyocytes for 24 hr to assess its cardiomyocyte protection. Our results showed that 10‐Gin improved the viability of H9c2 cardiomyocytes in the H/R model and decreased the activities of creatine kinase, lactate dehydrogenase, and the generation of reactive oxygen species. By intracellular Ca2+ ([Ca2+]i) fluorescence, we found that 10‐Gin could significantly reduce the [Ca2+]i concentration. 10‐Gin administration increased the activities of antioxidase and reduced malondialdehyde content and inflammatory cytokine levels. 10‐Gin also reduced the apoptosis levels. Importantly, 10‐Gin administration decreased the gene and protein expressions of Wnt5a and Frizzled‐2. In conclusion, 10‐Gin alleviates H/R‐induced cardiomyocyte injury, which is associated with the antioxidation, anti‐inflammation, antiapoptosis action, and reduction of [Ca2+]i overload by suppressing the Wnt5a/Frizzled‐2 pathway., 10‐Gingerol can attenuate the injury caused by hypoxia /reoxygenation reduce oxidative stress, Ca2+ overload, inflammation, and apoptosis, which is related to the inhibition of the Wnt5a/Frizzled‐2 pathway. Our research provides an experimental basis and new treatment strategies for MIRI. However, further research will be needed before these treatments can be used in clinics.

Although severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS‐CoV‐2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID‐19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS‐CoV‐2 RNA detection in blood in 96 pediatric patients with confirmed COVID‐19. Among all patients, 6 (6%) had SARS‐CoV‐2 RNAaemia. Out of the six patients with SARS‐CoV‐2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS‐CoV‐2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID‐19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS‐CoV‐2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS‐CoV‐2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS‐CoV‐2 RNAemia with area under the curve levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS‐CoV‐2 RNAaemia showed a severe COVID‐19 and one‐third of the patients with SARS‐CoV‐2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS‐CoV‐2 RNAaemia.

KEY POINTS We used 31-phosphorus magnetic resonance spectroscopy to quantify in vivo skeletal muscle metabolic economy (ME; mass-normalized torque or power produced per ATP consumed) during three 24 s maximal-effort contraction protocols: (1) sustained isometric (MVIC), (2) intermittent isokinetic (MVDCIsoK ), and (3) intermittent isotonic (MVDCIsoT ) in the knee extensor muscles of young and older adults. ME was not different between groups during the MVIC but was lower in older than young adults during both dynamic contraction protocols. These results are consistent with an increased energy cost of locomotion, but not postural support, with age. The effects of old age on ME were not due to age-related changes in muscle oxidative capacity or ATP flux. Specific power was lower in older than young adults, despite similar total ATP synthesis between groups. Together, this suggests a dissociation between cross-bridge activity and ATP utilization with age. ABSTRACT Muscle metabolic economy (ME; mass-normalized torque or power produced per ATP consumed) is similar in young and older adults during some isometric contractions, but less is known about potential age-related differences in ME during dynamic contractions. We hypothesized that age-related differences in ME would exist only during dynamic contractions, due to the increased energetic demand of dynamic versus isometric contractions. Ten young (Y; 27.5 ± 3.9 years, 6 men) and 10 older (O; 71 ± 5 years, 5 men) healthy adults performed three 24 s bouts of maximal contractions: (1) sustained isometric (MVIC), (2) isokinetic (120°·s-1 , MVDCIsoK ; 0.5 Hz), and (3) isotonic (load = 20% MVIC, MVDCIsoT ; 0.5 Hz). Phosphorus magnetic resonance spectroscopy of the vastus lateralis muscle was used to calculate ATP flux (mM ATP·s-1 ) through the creatine kinase reaction, glycolysis and oxidative phosphorylation. Quadriceps contractile volume (cm3 ) was measured by MRI. ME was calculated using the torque-time integral (MVIC) or power-time integral (MVDCIsoK and MVDCIsoT ), total ATP synthesis and contractile volume. As hypothesized, ME was not different between Y and O during the MVIC (0.12 ± 0.03 vs. 0.12 ± 0.02 Nm. s. cm-3. mM ATP-1 , mean ± SD, respectively; P = 0.847). However, during both MVDCIsoK and MVDCIsoT , ME was lower in O than Y adults (MVDCIsoK : 0.011 ± 0.003 vs. 0.007 ± 0.002 J. cm-3. mM ATP-1 ; P < 0.001; MVDCIsoT : 0.011 ± 0.002 vs. 0.008 ± 0.002; P = 0.037, respectively), despite similar muscle oxidative capacity, oxidative and total ATP flux in both groups. The lower specific power in older than young adults, despite similar total ATP synthesis between groups, suggests there is a dissociation between cross-bridge activity and ATP utilization with age.

Aims To characterize the clinical and histopathological characteristics and treatment outcomes of juvenile idiopathic inflammatory myopathies (JIIMs) with anti‐3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) antibodies in a Chinese cohort. Methods We detected anti‐HMGCR antibodies in a series of Chinese JIIM by ELISA and indirect immunofluorescence assay on HEK293 cells, and summarized the clinical findings of these anti‐HMGCR antibody‐positive patients. Results Of 32 JIIM patients, 5 (15.63%) were found to be anti‐HMGCR antibody‐positive. The disease duration was 1.20 ± 0.45 months. Statin exposure was not found. Four patients had skin lesions, while typical pathological features of dermatomyositis such as perifascicular atrophy or myxovirus resistance protein A expression were not found. The mean creatine kinase level was 16771.60 U/L. Among the four patients who received long‐term (10.46 ± 1.42 years) follow‐up, three exhibited favorable outcomes with prednisone and additional immunosuppressants. Conclusions Our study indicates that anti‐HMGCR antibodies may not be rare in Chinese JIIM. These anti‐HMGCR‐positive JIIMs were characterized by acute onset, substantially elevated creatine kinase level, and skin lesions without perifascicular changes in muscle pathology. The treatment outcome is generally favorable with the combination of steroid and immunosuppressant., Anti‐HMGCR antibody may not be rare in Chinese juvenile idiopathic inflammatory myopathy (JIIM). These anti‐HMGCR‐positive JIIMs were characterized by acute onset, high creatine kinase level, and skin lesions without perifascicular changes in muscle pathology. The treatment outcome is generally favorable with the combination of steroid and immunosuppressant. Anti‐HMGCR antibody testing should be seen as routine test for juvenile patients.

Objective This report summarizes the clinical features and 1‐month follow‐up observations for pediatric patients who were hospitalized with coronavirus disease 2019 (COVID‐19) in Wuhan Women and Children's Hospital. Methods The 1‐month follow‐up data included clinical manifestations and results from serum severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG and IgM tests, reverse‐transcription polymerase chain reaction (RT‐PCR) for SARS‐CoV‐2, lung computed tomography (CT) scans, and laboratory tests. Results Between January 20 and March 15, 2020, 127 patients aged 0–15 years were hospitalized for COVID‐19 treatment, including 3 severe cases and 124 mild or moderate cases. The main therapies included inhalation of aerosolized interferon‐α (122/127) and additional antiviral drugs (28/127). Among the 81 patients who had pneumonia at admission, 35 with right lobe pneumonia had the longest hospital stay (mean 14.5 ± 7 days); 17 with left lobe pneumonia had the highest creatine kinase (154 ± 106 U/L) and creatine kinase myocardial band (CK‐MB, 43 ± 48 U/L) levels; and 29 with bilateral pneumonia had the highest white blood cell counts (8.3 ± 4 × 109/L). Among the 46 patients who were successfully followed up 1 month after discharge, two notable findings were right lobe pneumonia in 22% (95% confidence interval [CI]: 11%–37%) of patients and persistently elevated serum creatine kinase and CK‐MB levels. The median duration of elevated CK‐MB was 45 days. The mean concentrations of serum SARS‐CoV‐2 IgG and IgM in 41 patients were 8.0 ± 7.5 and 98 ± 40 ng/ml, respectively. At follow‐up, four patients retested positive for SARS‐CoV‐2. Conclusions The involvement of different lung lobes in patients with COVID‐19 was associated with variations in the persistence of pneumonia and elevation of CK‐MB levels and body temperature.

Objective Existing studies reported the potential prognostic role of non‐thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid‐stimulating hormone (TSH), mainly in severe COVID‐19. None considered the significant impact of SARS‐CoV‐2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild‐to‐moderate COVID‐19 patients. Design A prospective study of COVID‐19 patients. Patients and Measurements Consecutive adults admitted to Queen Mary Hospital for confirmed COVID‐19 from July to December 2020 were prospectively recruited. SARS‐CoV‐2 viral load was represented by cycle threshold (Ct) values from real‐time reverse transcription‐polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline. Results We recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty‐three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS‐CoV‐2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration (p 50 years (p = .011) and elevated creatine kinase (p = .017). Conclusions Non‐thyroidal illness syndrome was not uncommon even in mild‐to‐moderate COVID‐19 patients. NTIS on admission could predict clinical deterioration in COVID‐19, independent of SARS‐CoV‐2 viral load, age and markers of inflammation and tissue injury.

Wnt/β‐catenin signaling is indispensable for many biological processes, including embryonic development, cell cycle, inflammation, and carcinogenesis. Aberrant activation of the Wnt/β‐catenin signaling can promote tumorigenicity and enhance metastatic potential in hepatocellular carcinoma (HCC). Targeting this pathway is a new opportunity for precise medicine for HCC. However, inhibiting Wnt/β‐catenin signaling alone is unlikely to significantly improve HCC patient outcome due to the lack of specific inhibitors and the complexity of this pathway. Combination with other therapies will be an important next step in improving the efficacy of Wnt/β‐catenin signaling inhibitors. Protein kinases play a key and evolutionarily conserved role in the Wnt/β‐catenin signaling and have become one of the most important drug targets in cancer. Targeting Wnt/β‐catenin signaling and its regulatory kinase together will be a promising HCC management strategy. In this review, we summarize the kinases that modulate the Wnt/β‐catenin signaling in HCC and briefly discuss their molecular mechanisms. Furthermore, we list some small molecules that target the kinases and may inhibit Wnt/β‐catenin signaling, to offer new perspectives for preclinical and clinical HCC studies., In this review, we summarize the kinases that modulate the Wnt/β‐catenin signaling in HCC and briefly discuss their molecular mechanisms. Furthermore, we list some small molecules that target the kinases and may inhibit Wnt/β‐catenin signaling to offer new perspectives for preclinical and clinical HCC studies.

BACKGROUND Reference intervals for haematology and serum biochemistry parameters were developed for free-ranging Lumholtz's tree-kangaroo (Dendrolagus lumholtzi) using 35 samples from 12 female and 15 male free-ranging animals. Captive tree-kangaroos (n = 12) were also sampled for comparison. Differences were found between free-ranging and captive animals in white blood cell and neutrophil counts, and levels of aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, phosphate, triglycerides and lipase. These differences may be attributed to diet, activity, capture methods or age group. Reference intervals generated may be used for both free-ranging and captive Lumholtz's tree-kangaroos. This study provides a valuable tool for the assessment of health in rescued and captive tree-kangaroos and will aid in investigations into population health and disease in free-ranging Lumholtz's tree-kangaroos. OBJECTIVE To develop reference intervals (RIs) for haematology and serum biochemistry parameters in Lumholtz's tree-kangaroos. METHODS Haematological and serum biochemical RIs were determined using 35 samples from 27 clinically healthy Lumholtz's tree-kangaroos from the Atherton Tablelands region of Queensland examined between 2014 and 2019. Haematology and serum biochemistry parameters were measured from 16 samples from 12 captive animals for comparison. RESULTS Reference intervals based on 35 samples from free-ranging animals showed higher mean and standard deviation values for white blood cell and neutrophil counts, and levels of aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, phosphate, triglycerides and lipase than results for 16 samples from captive animals. Captive individuals showed higher mean values than free-ranging individuals for albumin, protein, creatinine as well as Hb, MCV, MCH and MCHC. CONCLUSION The haematological and serum biochemistry RIs developed for Lumholtz's tree-kangaroos in this study will provide a valuable tool during clinical examination and investigations into disease and population health by veterinarians and researchers. The differences in parameters between free-ranging and captive animals are consistent with differences in diet, age cohort, activity or capture methods. Reference intervals generated from free-ranging animals should also be valid for captive Lumholtz's tree-kangaroos.

We tested the hypothesis that the magnitude of changes in indirect muscle damage markers would be greater after maximal elbow flexor eccentric exercise in the supinated (shorter biceps brachii) than neutral wrist (longer) position, and the difference in the magnitude would be associated with greater elongation over contractions for the supinated than neutral position, rather than the initial muscle length. Ten untrained men (21-39 years) performed two bouts of 10 sets of 6 maximal isokinetic eccentric contractions of the elbow flexors in the supinated position for one arm and neutral position for the other arm separated by 2 weeks in a randomized order. Biceps brachii myotendinous junction (MTJ) movements during eccentric contractions were recorded by B-mode ultrasonography, and the displacement from the start to end of each contraction was quantified. Peak torque (supinated: 367.8 ± 112.5 Nm, neutral: 381.5 ± 120.4 Nm) and total work (1816 ± 539 J, 1865 ± 673 J) produced during eccentric contractions were similar between conditions. The average MTJ displacement increased (P < .05) from the 1st set (8.0 ± 2.0 mm) to 10th set (15.8 ± 1.9 mm) for the supinated condition, but no such increase was found in the neutral condition (1st set: 5.1 ± 1.0 mm, 10th set: 5.0 ± 0.8 mm). Changes in indirect muscle damage markers (maximal voluntary isometric contraction torque, range of motion, serum creatine kinase activity, and muscle soreness) after exercise were greater (P < .05) for the supinated than neutral condition. These results suggest that the greater muscle damage marker changes for the supinated than neutral wrist position was associated with the greater muscle lengthening (strain).

PURPOSE Phosphorus saturation-transfer experiments can quantify metabolic fluxes noninvasively. Typically, the forward flux through the creatine kinase reaction is investigated by observing the decrease in phosphocreatine (PCr) after saturation of γ-ATP. The quantification of total ATP utilization is currently underexplored, as it requires simultaneous saturation of inorganic phosphate ( Pi ) and PCr. This is challenging, as currently available saturation pulses reduce the already-low γ-ATP signal present. METHODS Using a hybrid optimal-control and Shinnar-Le Roux method, a quasi-adiabatic RF pulse was designed for the dual saturation of PCr and Pi to enable determination of total ATP utilization. The pulses were evaluated in Bloch equation simulations, compared with a conventional hard-cosine DANTE saturation sequence, before being applied to perfused rat hearts at 11.7 T. RESULTS The quasi-adiabatic pulse was insensitive to a >2.5-fold variation in B1 , producing equivalent saturation with a 53% reduction in delivered pulse power and a 33-fold reduction in spillover at the minimum effective B1 . This enabled the complete quantification of the synthesis and degradation fluxes for ATP in 30-45 minutes in the perfused rat heart. While the net synthesis flux (4.24 ± 0.8 mM/s, SEM) was not significantly different from degradation flux (6.88 ± 2 mM/s, P = .06) and both measures are consistent with prior work, nonlinear error analysis highlights uncertainties in the Pi -to-ATP measurement that may explain a trend suggesting a possible imbalance. CONCLUSIONS This work demonstrates a novel quasi-adiabatic dual-saturation RF pulse with significantly improved performance that can be used to measure ATP turnover in the heart in vivo.

Objective To explore the associations between serum creatinine and creatine kinase (CK) levels with survival in male and female ALS patients. Methods A prospective cohort study was carried out including 346 ALS patients with repeated serum creatinine and CK measurements. Kaplan Meier analysis and multivariable Cox regression were used to perform survival analysis. Results There were 218 male and 128 female patients, and the males had significantly higher baseline serum creatinine and CK levels than females. After multivariable Cox regression analysis, lower baseline serum creatinine levels were associated with a short survival in both male (≤61 μmol/L, HR: 1.629; 95%CI: 1.168–2.273) and female ALS patients (≤52 μmol/L, HR: 1.677; 95%CI: 1.042–2.699), whereas, the serum CK levels were not correlated with survival. Besides, creatinine levels were positively associated with ALSFRS‐R scores, and inversely with the decline rate of ALSFRS‐R per month. During follow‐up, serum creatinine levels tended to be decreased along with the disease progression, and the higher decline rate of creatinine per month (>1.5) showed significantly shorter survival, compared to the lower group (≤1.5) (30.0 months vs. 65.0 months, Chi square = 28.25, P

The present study tested the hypothesis that 30 low-intensity (10%) eccentric contractions (10%EC) or two maximal voluntary isometric contractions at a long muscle length (2MVIC) that were performed at two days before maximal eccentric exercise of the elbow flexors consisting of five sets of six maximal eccentric contractions (MaxEC) would reduce increases in biceps brachii distal myotendinous junction displacement (MTJd) over the eccentric contractions during MaxEC. Sedentary young men were randomly placed (n = 12/group) to a control group that performed two bouts of MaxEC (CONT-1st, CONT-2nd) separated by two weeks, or one of two preconditioning groups that performed 10%EC or 2MVIC at 20° elbow flexion at two days prior to MaxEC. All exercises were performed by the non-dominant arm. MTJd of each contraction was assessed by B-mode ultrasound, and its changes over sets were compared among the groups. The average MTJd from the start to the end of six eccentric contractions in the first set was similar among the groups (6.4 ± 0.7 mm). The MTJd increased from the first to fifth set, but the increase was smaller (P

This study analyzed the impact of performing four consecutive football matches separated by 48-72 hours during a FIFA tournament on physical load, technical performance and plasma markers of redox state, muscle damage and inflammation in elite female players. Forty-eight players from three national teams were evaluated at seven time points: before (baseline) and throughout the tournament (after each match and before two training sessions). Only data from players who played all matches were included in the analyses (N = 13). The players were divided into high-rank (N = 6) and low-rank (N = 7) team players according to FIFA standards. Plasma creatine kinase (CK), C-reactive protein (CRP), total antioxidant status (TAS), and uric acid (UA) were analyzed at the selected time points. Technical performance and physical load were also quantified according to team rank. Players from low-rank teams played significantly more time than high-rank players (85 ± 10 vs 67 ± 15 minutes; P =.02; d = 1.51). Low-rank team players presented higher values in technical performance actions than the high-rank team players, but most of the differences were explained by the longer match time played. UA content differed across the matches, increasing from baseline (F(4,40) = 3.90; P =.01) and more in the high-rank team players (F(1,10) = 20.46; P =.001), while CRP only differed across the matches (F(4,36) = 2.66; P =.05), also increasing from baseline. A large time effect was shown for UA only in the high-rank players (η2p = 0.50; P =.02). Four consecutive matches did not result in considerable alterations in plasma stress markers, physical load, and technical performance in elite female football players from distinct rank levels.

INTRODUCTION: This two-part study explored the safety, feasibility, and efficacy of a mild-moderate resistance isometric leg exercise program in ambulatory boys with Duchenne Muscular Dystrophy (DMD). METHODS: First, we used a dose escalation paradigm with varying intensity and frequency of leg isometric exercise to determine the dose response and safety in 10 boys. Second, we examined safety and feasibility of a 12-week in-home, remotely-supervised, mild-moderate intensity strengthening program in 8 boys. Safety measures included T(2) MRI, creatine kinase levels, and pain. Peak strength and function (time to ascend/descend 4 stairs) were also measured. RESULTS: Dose-escalation revealed no signs of muscle damage. Seven of the 8 boys completed the 12-week in-home program with a compliance of 84.9%, no signs of muscle damage, and improvements in strength (knee extensors p < 0.01; knee flexors p < 0.05) and function (descending steps p < 0.05). DISCUSSION: An in-home, mild-moderate intensity leg exercise program is safe with potential to positively impact both strength and function in ambulatory boys with DMD.

Aims Patients who survive acute myocardial infarction (AMI) are at risk of being rehospitalized owing to the occurrence of acute decompensated heart failure (HF). However, the clinical characteristics of HF after AMI, especially the frequency of each HF subtype, are unclear. Methods and results We retrospectively studied 1055 patients with AMI. We excluded 257 patients, who were admitted >48 h after the onset of AMI, died during hospitalization or after discharge, and whose echocardiogram data at index hospitalization and follow‐up data were missing. The remaining 798 patients (mean age: 66.5 ± 11.7 years) were investigated for a mean follow‐up period of 4.9 years. All patients underwent emergency coronary angiography. The mean maximum creatine kinase levels were 2898 ± 2627 IU/L, and mean left ventricular ejection fraction (LVEF) was 58.9 ± 10.2%. Eighty‐one patients (10.2%) were rehospitalized because of unexpected worsening of HF. Echocardiography data were available for 74 of the 81 patients during the acute phase of the second hospitalization, of which 30, 20, and 24 patients (41%, 27%, and 32%, respectively) were diagnosed as having HF with preserved LVEF (LVEF ≥ 50%), HF with mid‐range LVEF (40% ≤ LVEF

CYP1A1 was induced in lung of mice by LPS treatment with an aryl hydrocarbon receptor‐independent manner, while Toll‐like receptor 4 knockout abolished CYP1A1 overexpression. CYP1A1 deficiency elevated pro‐inflammatory cytokines in lung tissues of septic mice by targeting NF‐κB (p65) and increased lung injury in response to LPS or E. coli challenge., Acute lung injury (ALI) is accompanied by overactivation of multiple pro‐inflammatory factors. Cytochrome P450 1A1 (CYP1A1) has been shown to aggravate lung injury in response to hyperoxia. However, the relationship between CYP1A1 and lipopolysaccharide (LPS)‐induced ALI is unknown. In this study, CYP1A1 was shown to be upregulated in mouse lung in response to LPS. Using CYP1A1‐deficient (CYP1A1−/−) mice, we found that CYP1A1 knockout enhanced LPS‐induced ALI, as evidenced by increased TNF‐α, IL‐1β, IL‐6, and nitric oxide in lung; these effects were mediated by overactivation of NF‐κB and iNOS. Furthermore, we found that aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatinine levels were elevated in serum of LPS‐induced CYP1A1−/− mice. Altogether, these data provide novel insights into the involvement of CYP1A1 in LPS‐induced lung injury.

Cardiovascular-related diseases continue to be a leading cause of death globally. Among ischemic-induced cardiac diseases, myocardial infarction (MI) is reported to be of an alarming value. Despite numerous improvements in the medical intrusions, still this armamentarium fails to be effective in managing the illness without setbacks. Ferruginol (FGL) is a major polyphenols and terpenoids with numerous pharmacological activities including antioxidant and anti-inflammatory. Following, this work was aimed to explore the cardio protective effect of FGL (50 mg/kg) in isoprenaline hydrochloride (ISO)-induced MI in experimental rats. After treatment with FGL in ISO-induced MI in rats, noticeable changes were observed in the experimental rats. Injection of ISO to rats resulted in the augmented cardiac weight, serum cardiac markers (creatine kinase, creatine kinase-MB, cardiac troponin T, and Cardiac troponin I), lipid peroxidation end products (thiobarbituric acid-reactive substance and lipid hydroperoxides), reduced endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione), reduced ATPase activity, and escalated pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and nuclear factor-κB) levels. Interestingly, the FGL supplementation to the ISO-treated rats revealed the diminished heart weight, reduced cardiac markers, and lipid peroxidation. FGL also possessed the improved antioxidants status and diminished pro-inflammatory mediator levels. The outcomes of histological analysis also evidenced the cardio protective role of FGL. Treatment with FGL reduced the cardiac damage biomarkers maintained to near normal levels in ISO-induced rats. These study findings disclose the prospective capability of FGL in the treatment of MI in the future.

Sulfur mustard (SM) is a toxic chemical warfare agent deployed in several conflicts within the last 100 years and still represents a threat in terroristic attacks and warfare. SM research focuses on understanding the pathophysiology of SM and identifying novel biomarkers of exposure. SM is known to alkylate nucleophilic moieties of endogenous proteins, for example, free thiol groups of cysteine residues. The two-dimensional-thiol-differences in gel electrophoresis (2D-thiol-DIGE) technique is an initial proteomics approach to detect proteins with free cysteine residues. These amino acids are selectively labeled with infrared-maleimide dyes visualized after GE. Cysteine residues derivatized by alkylating agents are no longer accessible for the maleimide-thiol coupling resulting in the loss of the fluorescent signal of the corresponding protein. To prove the applicability of 2D-thiol-DIGE, this technology was exemplarily applied to neat human serum albumin treated with SM, to lysates from human cell culture exposed to SM as well as to human plasma exposed to CEES (chloroethyl ethyl sulfide, an SM analogue). Exemplarily, the most prominent proteins modified by SM were identified by matrix-assisted laser desorption/ionization time-of-flight (tandem) mass spectrometry, MALDI-TOF MS(/MS), as creatine kinase (CK) from human cells and as alpha-1 antitrypsin (A1AT) from plasma samples. Peptides containing the residue Cys282 of CK and Cys232 of A1AT were unambiguously identified by micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry (μLC-ESI MS/HR MS) as being alkylated by SM bearing the specific hydroxyethylthioethyl-(HETE)-moiety. Both peptides might represent potential biomarkers of SM exposure. This is the first report introducing these endogenous proteins as targets of SM alkylation.

Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of central and peripheral vascular disorders, including carotid, coronary and peripheral arterial diseases, and Raynaud's phenomenon. Recently, associations of plasma homocysteine levels with autoimmune diseases such as systemic lupus erythematodes and systemic sclerosis have been reported. However, no study analyzed the association between plasma homocysteine levels and dermatomyositis (DM). The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with DM. Plasma homocysteine levels in 28 Japanese patients with DM and 22 healthy controls were examined. We found that the plasma homocysteine levels in DM patients were significantly higher than those in healthy individuals (15.8 ± 1.1 vs 8.5 ± 0.5 µmol/L, P < 0.01). Presence of mechanic's hand, complication of interstitial lung disease (ILD), high serum Krebs von den Lungen-6 (KL-6), surfactant protein-D and creatine kinase levels, and anti-aminoacyl-tRNA synthetase (ARS) antibody (Ab) positivity were significantly more prevalent among DM patients with elevated plasma homocysteine levels. The plasma homocysteine levels in DM patients with mechanic's hand, ILD and anti-ARS Ab were significantly higher than those in DM without those features. Furthermore, the plasma homocysteine levels were positively correlated with serum KL-6 levels. These results suggest that the pathogenesis of elevated plasma homocysteine levels may be associated with ILD in DM patients, especially with anti-ARS Ab, and further examination is required.

While clinical innovation has improved, cancer or malignant growth stays a genuine medical issue and has been perceived as a significant factor in mortality and morbidity. Current work aimed to define the cardiac defensive effects of curcumin nanoparticles (Cur Nps) against EAC induced cardiac toxicity, injury, and alterations in apoptosis, proliferation, and cytokines immunoreactivity. Forty female mice were aimlessly and equally divided into four groups [Gp1, Control; Gp2, Cur NPs; Gp3, Ehrlich ascites carcinoma (EAC); Gp4, Co-treatment of EAC with Cur NPs (Cur NPs + EAC)]. Serum lactate dehydrogenase (LDH), phosphocreatine kinase (CPK), creatine kinase myoglobin (CK-MB), alkaline phosphatase (ALP), glutamic oxaloacetic transaminase (GOT), cholesterol, triglycerides, potassium ions, cardiac injury, P53, vascular endothelial growth factor protein (VEGF), Bax, and tumor necrosis factor alpha (TNFα) expressions were significantly elevated while sodium ions levels were significantly depleted in EAC when compared to control. Co-treatment of EAC with Cur NPs (Cur NPs + EAC) improved these parameters as compared with EAC group. So, our results indicate that; Cur NPs induced protection to the blood and heart tissue during Ehrlich ascites carcinoma.

Background Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by the loss of dystrophin, which results in inflammation, fibrosis, and the inhibition of myoblast differentiation in skeletal muscle. Catalpol, an iridoid glycoside, improves skeletal muscle function by enhancing myogenesis; it has potential to treat DMD. We demonstrate the positive effects of catalpol in dystrophic skeletal muscle. Methods mdx (loss of dystrophin) mice (n = 18 per group) were treated with catalpol (200 mg/kg) for six consecutive weeks. Serum analysis, skeletal muscle performance and histology, muscle contractile function, and gene and protein expression were performed. Molecular docking and ligand–target interactions, RNA interference, immunofluorescence, and plasmids transfection were utilized to explore the protective mechanism in DMD by which catalpol binding with transforming growth factor‐β–activated kinase 1 (TAK1) in skeletal muscle. Results Six weeks of catalpol treatment improved whole‐body muscle health in mdx mice, which was characterized by reduced plasma creatine kinase (n = 18, −35.1%, P

Purpose Two-dimensional creatine CEST (2D-CrCEST), with a slice thickness of 10-20 mm and temporal resolution (τRes ) of about 30 seconds, has previously been shown to capture the creatine-recovery kinetics in healthy controls and in patients with abnormal creatine-kinase kinetics following the mild plantar flexion exercise. Since the distribution of disease burden may vary across the muscle length for many musculoskeletal disorders, there is a need to increase coverage in the slice-encoding direction. Here, we demonstrate the feasibility of 3D-CrCEST with τRes of about 30 seconds, and propose an improved voxel-wise B 1 + -calibration approach for CrCEST. Methods The current 7T study with enrollment of 5 volunteers involved collecting the baseline CrCEST imaging for the first 2 minutes, followed by 2 minutes of plantar flexion exercise and then 8 minutes of postexercise CrCEST imaging, to detect the temporal evolution of creatine concentration following exercise. Results Very good repeatability of 3D-CrCEST findings for activated muscle groups on an intraday and interday basis was established, with coefficient of variance of creatine recovery constants (τCr ) being 7%-15.7%, 7.5%, and 5.8% for lateral gastrocnemius, medial gastrocnemius, and peroneus longus, respectively. We also established a good intraday and interday scan repeatability for 3D-CrCEST and also showed good correspondence between τCr measurements using 2D-CrCEST and 3D-CrCEST acquisitions. Conclusion In this study, we demonstrated for the first time the feasibility and the repeatability of the 3D-CrCEST method in calf muscle with improved B 1 + correction to measure creatine-recovery kinetics within a large 3D volume of calf muscle.

Ischaemia/reperfusion (I/R) injury can lead to severe arrhythmia and aggravate myocardial damage. Exosomes are small-membrane vesicles that play a protective role in myocardial I/R injury. This study aimed to explore the protective effects of ischaemic preconditioning (IPC)-induced serum exosomes (IPC-Exo) on myocardial I/R injury in rats and its underlying mechanism. Serum exosomes were extracted from IPC rats and quantified using a bicinchoninic acid assay kit. IPC-Exo (50 μg) was injected into the infarcted myocardium immediately after ligation. Rats were randomly divided into Sham, I/R, IPC-Exo + I/R, I/R + LY294002, and I/R + IPC-Exo + LY294002 groups. Haemodynamic parameters were measured by physiological recording. Transthoracic echocardiography was used to detect cardiac function. The serum levels of creatine kinase isomer-MB, lactate dehydrogenase, aspartate transaminase, tumour necrosis factor-alpha, interleukin (IL)-1β, and IL-10 were detected by enzyme-linked immunosorbent assay. Triphenyl tetrazolium chloride staining was used to measure the myocardial infarct size. Apoptosis in myocardial tissues was detected by TUNEL staining. Western blotting was used to detect the levels of PI3K/AKT and apoptosis-related proteins. Our results showed that treatment with IPC-Exo ameliorated cardiac function and reduced inflammatory factor production, cardiomyocyte apoptosis, and myocardial infarct size. Moreover, IPC-Exo treatment promoted the protein expression of Bcl-2, p-PI3K, and p-AKT but inhibited that of caspase-3 and Bax. However, treatment with LY294002 significantly reversed that IPC-Exo-induced increase in p-PI3K and p-AKT levels, improvement of haemodynamics, and decrease of inflammatory factor production and apoptosis in the I/R + IPC-Exo group. Taken together, our results suggest that IPC-Exo may alleviate I/R injury via activating the PI3K/AKT signalling pathway.

Immune‐mediated necrotizing myopathy (IMNM) has emerged as a new subgroup of idiopathic inflammatory myopathy in the past decade, associated with the presence of two autoantibodies against signal recognition particle and 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR). We aim to analyze the clinical, pathological, and imaging phenotypes of the patients with anti‐HMGCR myopathy in our cohort. Five patients with anti‐HMGCR myopathy have been enrolled who were all female; three were pediatric and two were adult patients. The muscle pathology of patients met the diagnostic criteria of IMNM. On muscle magnetic resonance imaging, adductors were earliest affected while lower legs were relatively preserved with highest degree of involvement in medial head of gastrocnemius. In upper extremities, biceps brachii was the most severely involved, followed by triceps. All patients were refractory to steroid mono‐therapy. For pediatric patients, all three patients eventually became responsive to steroid with either intravenous immunoglobulin or rituximab despite variable motor function recovered at present due to different intervention timing. For adult patients, one with statin exposure responded well to steroid and azathioprine use and the motor function returned to the baseline. The other adult patient finally got stabilized and slowly improved with steroid and methotrexate 13 years after the start of therapy. The creatine kinase (CK) levels of all patients were decreased along with clinical severity. In conclusion, muscle imaging might be of help for the diagnosis. Treatment with immuno‐suppressants could be considered together with steroid from the beginning.

African elephants (Loxodonta Africana) are currently considered a vulnerable species. One key to improving methods of species management is to better monitor and understand elephant nutrition. Analyzing circulating nutrients is one of the best and least invasive methods of monitoring managed elephant nutrition, but limited reference values are available. This study examined the circulating basic hematology concentrations, minerals, vitamins A, D, and E, and fatty acids of six African elephants (two males and four females) at the North Carolina Zoo collected monthly from March 2016 to April 2017 and compared levels among seasons. Creatinine (CRE) and albumin had seasonal differences (p ≤ .05). Calcium, magnesium, phosphorus, potassium, selenium, zinc, cobalt, manganese, and molybdenum displayed seasonal differences (p ≤ .05). Retinol and 25-hydroxyvitamin D2 had seasonal differences (p ≤ .05). Linoleic acid, α-linolenic acid, arachidonic acid, total omega-3 fatty acids, total omega-6 fatty acids, and the omega-6 to omega-3 ratio showed seasonal differences (p ≤ .05). Findings suggest that exogenous vitamin E supplements may not be necessary with a mixed feedstuff diet (hay, fortified concentrate pellet, browse, and produce) based on circulating values. This data offer updated information on circulating reference values and novel circulating concentrations of nutrients for Southeastern US managed African elephants that can be used to inform nutritional and health management in all similar habitats.