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Purpose: The relationship between external load and creatine-kinase (CK) response at the team/position or individual level using Global Positioning Systems (GPS) has been studied. This study aimed to compare GPS-derived and Football Movement Profile (FMP) –derived CK-prediction models for national-team soccer players. The second aim was to compare the performance of general and individualized CK prediction models. Methods: Four hundred forty-four national-team soccer players (under 15 [U15] to senior) were monitored during training sessions and matches using GPS. CK was measured every morning from whole blood. The players had 19.3 (18.1) individual GPS-CK pairs, resulting in a total of 8570 data points. Machine learning models were built using (1) GPS-derived or (2) FMP-based parameters or (3) the combination of the 2 to predict the following days' CK value. The performance of general and individual-specific prediction models was compared. The performance of the models was described by R2 and the root-mean-square error (RMSE, in units per liter for CK values). Results: The FMP model (R2 =.60, RMSE = 144.6 U/L) performed similarly to the GPS-based model (R2 =.62, RMSE = 141.2 U/L) and the combination of the 2 (R2 =.62, RMSE = 140.3 U/L). The prediction power of the general model was better on average (R2 =.57 vs R2 =.37) and for 73% of the players than the individualized model. Conclusions: The results suggest that FMP-based CK-prediction models perform similarly to those based on GPS-derived metrics. General machine learning models' prediction power was higher than those of the individual-specific models. These findings can be used to monitor postmatch recovery strategies and to optimize weekly training periodization. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis aimed to (1) provide a comparison of peak changes in indirect markers of exercise-induced muscle damage (EIMD) in youths versus adults and (2) determine if the involved limb moderated this effect. Method: Studies were eligible for inclusion if they (1) provided a human youth versus adult comparison; (2) provided data on muscle strength, soreness, or creatine kinase markers beyond ≥24 hours; and (3) did not provide a recovery treatment. Effect sizes (ES) were presented alongside 95% confidence intervals. Results: EIMD exhibited larger effects on adults than in youths for muscle strength (ES = −2.01; P <.001), muscle soreness (ES = −1.52; P <.001), and creatine kinase (ES = −1.98; P <.001). The random effects meta-regression indicated that the effects of upper- and lower-limb exercise in youths and adults were significant for muscle soreness (coefficient estimate = 1.11; P <.001) but not for muscle strength or creatine kinase (P >.05). As such, the between-group effects for muscle soreness (ES = −2.10 vs −1.03; P <.05) were greater in the upper than lower limbs. Conclusion: The magnitude of EIMD in youths is substantially less than in their adult counterparts, and this effect is greater in upper than lower limbs for muscle soreness. These findings help guide practitioners who may be concerned about the potential impact of EIMD when training youth athletes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relationship between items of the Short Recovery and Stress Scale (SRSS) related to physical stress and recovery and the biomarker creatine kinase (CK) in professional handball. Methods: CK and SRSS items (physical performance capability, overall recovery, muscular stress, and overall stress) were assessed in an observational study of 16 adult male professional handball players from a team in the highest German league during the 2019–20 preseason. Their preseason training schedule included several microcycles, each consisting of 3 consecutive days of intense training followed by a rest day. On 5 of these rest days, when players were classified as nonrested, and the 5 immediately following days, when players were classified as rested, players completed the SRSS between 8:00 and 9:00 AM, followed by blood sampling. Correlations between SRSS items were performed using Kendall τ. The relationship between each SRSS item and CK levels over time was examined using a mixed-effects model with a random intercept. Results: CK levels and SRSS stress items were significantly higher and SRSS recovery items were significantly lower in nonrested players. SRSS items were significantly positively or negatively correlated (all items: P <.001) and showed a significant effect indicating lower CK levels in rested players (all items: P ≤.001; η p 2 =.1 −.32). Conclusions: The investigated SRSS items may be a viable option for assessing muscle recovery in adult male professional handball players in a cost-effective and noninvasive manner. They can be used as a single monitoring tool or as part of a multimodal approach. [ABSTRACT FROM AUTHOR]

Previous studies showed that collagen peptide supplementation along with resistance exercise enhance muscular recovery and function. Yet, the efficacy of collagen peptide supplementation in addition to standard nutritional practices in athletes remains unclear. Therefore, the objective of the study was to compare the effects of combined collagen peptide (20 g) and whey protein (25 g) supplementation with a similar daily protein dose (45 g) of whey protein alone on indices of muscle damage and recovery of muscular performance during eccentric exercise training. Young fit males participated in a 3-week training period involving unilateral eccentric exercises for the knee extensors. According to a double-blind, randomized, parallel-group design, before and after training, they received either whey protein (n = 11) or whey protein + collagen peptides (n = 11). Forty-eight hours after the first training session, maximal voluntary isometric and dynamic contraction of the knee extensors were transiently impaired by ∼10% (Ptime <.001) in whey protein and whey protein + collagen peptides, while creatine kinase levels were doubled in both groups (Ptime <.01). Furthermore, the training intervention improved countermovement jump performance and maximal voluntary dynamic contraction by respectively 8% and 10% (Ptime <.01) and increased serum procollagen type 1N-terminal peptide concentration by 10% (Ptime <.01). However, no differences were found for any of the outcomes between whey and whey protein + collagen peptides. In conclusion, substituting a portion of whey protein for collagen peptide, within a similar total protein dose, improved neither indices of eccentric muscle damage nor functional outcomes during eccentric training. [ABSTRACT FROM AUTHOR]

Supplementing with antioxidants may be one of the most efficient means of minimizing oxidative stress during workouts in obese individuals. The aim of this study is to identify the results after twelve weeks of CrossFit workouts combined with Spinach thylakoid extract on the levels of insulin resistance (insulin and Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]), fasting blood sugar (FBS), malondialdehyde (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), and superoxide dismutase (SOD), glutathione peroxidase (GPx) in obese males. Sixty-eight males with an average age of 27 ± 8 yrs and a BMI of 32.6 ± 2.6 kg.m− 2 were randomly split into four groups each consisting of seventeen individuals. : control group (CG), supplement group (SG), training group (TG), and training + supplement group (TSG). After initial assessments, the two training groups (TG and TSG) started on a 12 weeks of the CrossFit workouts program involving three sessions per week each lasting up to 60 min. Participants in supplement groups ingested 30 min before lunch, 5 gof Spinach thylakoid extract per day or one sachet of raw corn starch in the control group. Baseline and post-intervention measurements were performed 48 h pre- and post-last session, respectively. The findings revealed noteworthy relationships between the exercise groups and timefor TAC, SOD, GPx, MDA, CK, and LDH (p < 0.001, ES: 0.88, 0.88, 0.8, 0.4, 0.7, and 0.7, respectively). In addition, there were statistically significant differences among study groups after attending the intervention program in TAC (ES: 0.88), SOD (ES: 0.92), GPX (ES: 0.85), MDA (ES: 0.5), CK (ES: 0.7) and LDH (ES: 0.8). The effect sizes of insulin (0.77), glucose (0.21), and HOMA-IR (0.44) varied significantly (p < 0.05) among the groups. The results demonstrated that CrossFit workouts for 12 weeks combined with Spinach thylakoid extract in men with obesity may prevent oxidative damage caused by obesity and CrossFit workouts. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 58-year-old woman with primary hypoparathyroidism and intracranial calcifications who developed severe hyperkinetic movement disorders. Despite treatment with various medications, her condition worsened, leading to a bed-bound state. After unsuccessful attempts with medications, she underwent rescue pallidotomy, which resulted in a remarkable improvement in her movements. The report highlights the challenges in managing severe movement disorders and the potential role of surgical interventions in such cases. [Extracted from the article]

Background: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians. Objective: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians. Methods: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes. Results: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P < 0.05) and elevated the TB level (P < 0.001). Atorvastatin plasma levels were greater in CYP3A4*1B (T/T) (P < 0.05) and CYP3A5*3 (C/C) (P < 0.001) genotype carriers. Both SNPs significantly affected the pharmacokinetics of atorvastatin compared with those of Egyptian volunteers and various ethnic populations. Conclusions: The CYP3A4*1B and CYP3A5*3 variants were prevalent in the study participants and could impact the effectiveness and safety of atorvastatin therapy. The mutant genotype of the CYP3A4*1B SNP and the CYP3A5*3 SNP led to high atorvastatin levels. Both variants had a notable effect on the pharmacokinetics of atorvastatin among Egyptians compared with healthy Egyptians and volunteers from other ethnic populations. Overall, clinicians can learn more about the impact of both variants in response to atorvastatin. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood. Purpose: This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue. Materials and methods: UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin–eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking. Results: The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways. Conclusions: RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment. [ABSTRACT FROM AUTHOR]

Introduction: Athletic training requires both challenging stimuli for adaptation and sufficient recovery for improved performance. While cold water immersion (CWI) is already a popular recovery method, handheld percussive massage (PM) devices have also gained popularity in recent years. This study aims to assess the effects of CWI and PM on performance recovery after strenuous eccentric exercises compared to a passive rest (PR) control condition. Methods: Thirty-four healthy physically active participants (9 females, 25 males) were randomly divided into three groups: CWI (n = 11), PM (n = 11), and passive rest (PR) (n = 12). They underwent an exhausting eccentric exercise protocol and different measurements at six time points (baseline, POST1, POST2, POST24, POST48, and POST72) over the time course of 72 h. These included subjective assessments of muscle soreness and perceived stiffness as well as measures of skin temperature, leg volume, creatine kinase activity, and three different jump tests. The eccentric exercise protocol consisted of 15 min downhill running (slope: 12%, speed: 10 km/h) and 3 sets of successive depth jumps (dropping height: 0.5 m) until individual exhaustion. After POST1 measurements, participants received 12 min of either CWI (11 ± 0.5°C), PM (40 Hz) or PR (supine posture). Results: No significant group effects were found for the number of depth jumps performed during the exhaustion protocol. All jump tests displayed a significant group × time interaction effect. Post-hoc analysis indicated significant lower jump heights in ΔPOST2 between CWI and both PM and PR. No other significant group effects were observed at any time point. No significant group × time interaction effects were noted for CK, leg volume, and soreness. The perceived stiffness showed a significant group × time interaction effect. Post-hoc analysis revealed a significant decrease in stiffness for PM compared to PR at ΔPOST2. Conclusion: Neither CWI nor PM showed any significant improvement in performance recovery over the 72-h period following strenuous eccentric exercise compared to PR. CWI showed an immediate performance decline which may be attributed to a cold-related reduction in motor nerve conduction velocity. [ABSTRACT FROM AUTHOR]

Introduction: Football is a physically demanding sport that requires effective recovery strategies to maintain performance level and prevent injuries. This study investigated if a single 1-h hyperbaric oxygen therapy (HBOT) session affects recovery and performance after a football match in elite youth players. Methods: Twenty elite youth football players (age 17.3 ± 0.5 years) were randomly assigned to a HBOT group or a control group (CON). They played a 90-min football game and underwent either a 60-min HBOT or placebo intervention. Before (T1), at the end of the match (T2), 1 h after HBOT or CON session (T3), and 12 h after HBOT session (T4), subjects underwent biochemical (serum samples (myoglobin (MB), creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) and performance measurements (linear speed at 5 m, 10 m and 20 m, squat jump (SJ), countermovement jump (CMJ) and countermovement jump with arm swing (CMJa)). The Hooper Index (HI) was collected and heart rate was measured during the game. Results: The football match induced significant increases in all biochemical markers, but no significant differences were found between the HBOT and control group in biochemical or performance parameters at any time point. However, there was a significant interaction effect between time and group for HI (p = 0.012, η2 = 0.124), with the HBOT group showing significantly lower HI values (8.6 ± 2.41) than the control group (11.0 ± 3.23) at 1 h post-HBOT. Discussion: A single 1-h session of HBOT did not significantly affect recovery or performance parameters in elite youth football players, though it did show a moderate positive affect on the HI at 1 h post-HBOT. Further studies should explore the impact of either longer or sequential HBOT sessions on recovery. [ABSTRACT FROM AUTHOR]

Purpose: This brief report aimed to characterize inter-individual training responses following a single session of high-intense whole-body electromyostimulation (WB-EMS) using markers of muscle damage over a period of 72 h. Methods: Twelve healthy individuals (5 men, 7 women; 32.0 ± 7 years) participated in a single 20-minute high-intensity WB-EMS training session. Markers of muscle damage, creatine kinase (CK) and myoglobin (Mb), were assessed before and immediately after training, as well as at 1.5, 3, 24, 48 and 72 h post-exercise. Lactate levels were determined pre- and post-exercise. Results: Overall, WB-EMS induced significant CK elevations, peaking at 72 h (18.358 ± 21.380 U/L; p < 0.01), and correlating Mb levels peaking at 48 h (1.509 ± 1.394 ng/dl, p < 0.01). Despite significant inter-individual variability in CK levels, both slow (SR) and fast responders (FR) were identified. FR showed significant increases in CK at all time points post WB-EMS (p < 0.05), whereas CK in SR significantly elevated after 48 h. Post-WB-EMS lactate concentration was identified to predict peak CK and Mb levels (r ≥ 0.65, both p < 0.05). Conclusion: High-intensity WB-EMS has the potential to induce severe muscle damage, as indicated by elevated levels of CK and Mb. We identified two distinct groups of individuals, SR and FR, indicating variability in response to WB-EMS. Furthermore, we suggest that individual responses to WB-EMS can be predicted based on post-WB-EMS lactate concentration. [ABSTRACT FROM AUTHOR]

Context • An acute myocardial infarction (AMI) is a serious, life-threatening disease. Practitioners of traditional Chinese medicine (TCM) commonly use the Tongxinluo (TXL) capsule, a Chinese patent medicine, to treat AMIs. The benefits of TXL capsules for AMIs remain unknown. Objective • The systematic review and meta-analysis intended to investigate the effects of TXL capsules for AMI patients. Design • The research team conducted a comprehensive literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023. The team used the search terms acute myocardial infarction, myocardial infarction, TXL Capsule Therapy, and TXL Capsule. The team also performed a meta-analysis and evaluated the features of the included studies using the Cochrane Collaboration tool for assessing the risk of bias. Setting • The study took place at the Second Affiliated Hospital at Heilongjiang University of Chinese Medicine in Harbin City, Heilongjiang Province, China Outcome Measures • The research team: (1) evaluated the studies' quality using the Cochrane Collaboration tool for assessing the risk of bias; (2) analyzed the curative effect of the TXL capsules for AMI; (3) explored the effects of the TXL capsules on left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), and left ventricular ejection fraction (LVEF); and (4) explored the effects of the TXL capsules on creatine kinase isoenzyme (CK-MB) peak time, CK-MB peak value, and cardiac index. Results • The literature search found ten studies. Compared with routine treatment alone, a combination of routine treatment and TXL capsules significantly improved the curative effects (odds ratio = 3.48; 95% CI: 2.34, 5.17; P < .00001) Compared with the control groups, the TXL capsule groups' LVESD and LVEF were significantly lower, with MD=-0.23; 95% CI: -0.37, -0.10; and P = .0007 and MD=-0.43; 95% CI: -0.61, -0.25; and P < .00001, respectively, and its LVEDD was significantly higher, with MD=5.27; 95% CI: 4.33, 6.21; and P < .00001. For myocardial enzymes, the TXL capsule groups' creatine kinase isoenzyme (CKMB) peak values and cardiac indexes were significantly lower than those of the control groups, with MD=-53.11; 95% CI: -55.26, -50.97; and P < .00001 and MD=-1.87; 95% CI: -2.03, -1.70; and P < .00001, respectively. Conclusions • The meta-analysis showed that the TXL capsule can bring greater therapeutic benefits for AMI patients in combination with routine treatment. The current study was a meta-analysis, and the field needs more well-designed studies. [ABSTRACT FROM AUTHOR]

Intracellular molecules are transported by motor proteins or move by diffusion resulting from random molecular motion. Cardiomyocytes are packed with structures that are crucial for function, but also confine the diffusional spaces, providing cells with a means to control diffusion. They form compartments in which local concentrations are different from the overall, average concentrations. For example, calcium and cyclic AMP are highly compartmentalized, allowing these versatile second messengers to send different signals depending on their location. In energetic compartmentalization, the ratios of AMP and ADP to ATP are different from the average ratios. This is important for the performance of ATPases fuelling cardiac excitation‐contraction coupling and mechanical work. A recent study suggested that compartmentalization modulates the activity of creatine kinase and adenylate kinase in situ. This could have implications for energetic signaling through, for example, AMP‐activated kinase. It highlights the importance of taking compartmentalization into account in our interpretation of cellular physiology and developing methods to assess local concentrations of AMP and ADP to enhance our understanding of compartmentalization in different cell types. [ABSTRACT FROM AUTHOR]

The aim was to analyse the consequences of a congested schedule (due to the COVID-19 lockdown) on creatine kinase (CK) in elite football players using GPS tracking technology. A total of 17 elite football players were monitored in training and competition with a global positioning system. Variables including total distance, high-intensity distance, and distance acceleration and deceleration were analysed. Different measurements of serum creatine kinase (CK) concentration were performed on match day (MD) and at 24 h (MD+1), 48 h (MD+2), and 72 h (MD+3) after each match to study the muscle damage of each individual player caused during the match. The results showed a significant increase in physical demands in training (in relative terms regarding the match) at MD+3 compared to MD+1 and MD+2. Furthermore, at +72 h, CK decreases to a value almost the same as that before MD. On the other hand, the players with lower demands for high-intensity actions in the match showed a higher reduction in the concentration of CK at MD+3 compared to MD+1 and MD+2 (p < 0.05). It became evident that players with high-intensity demand and a high number of accelerations and decelerations need more time to assimilate the match load and can remain in a state of muscle fatigue for up to 3 days. In addition, a congested schedule can lead to a state of chronic fatigue in elite football players, limiting physical performance and possibly increasing the potential risk of injury for football players. [ABSTRACT FROM AUTHOR]

This systematic review synthesizes evidence on biomarker responses to physiological loads in professional male team sport athletes, providing insights into induced fatigue states. Structured searches across major databases yielded 28 studies examining various biomarkers in elite team sport players. Studies evaluated muscle damage markers, anabolic/catabolic hormones reflecting metabolic strain, inflammatory markers indicating immune activity and tissue damage, immunological markers tied to infection risk, and oxidative stress markers showing redox imbalances from excessive physiological load. Responses were examined in official matches and training across competitive seasons. The evidence shows that professional team sports induce significant alterations in all studied biomarkers, reflecting measurable physiological strain, muscle damage, oxidative stress, inflammation, and immunosuppression during intensive exercise. These effects tend to be larger and more prolonged after official matches compared to training. Reported recovery time courses range from 24-h to several days post-exercise. Monitoring biomarkers enables quantifying cumulative fatigue and physiological adaptations to training/competition loads, helping to optimize performance while mitigating injury and overtraining. Key biomarkers include creatine kinase, testosterone, cortisol, testosterone/cortisol ratio, salivary immunoglobulin-A, and markers of inflammation and oxidative stress. Further research should extend biomarker monitoring to cover psychological stress and affective states alongside physiological metrics for deeper insight into athlete wellness and readiness. [ABSTRACT FROM AUTHOR]

The objective of this randomized controlled trial was to determine if providing a rest stop including provision of feed and water between periods of continuous transportation mitigates the effect of long-distance transportation on markers of energy status and hydration in calves transported by road for 16 h. This study was conducted between September 2022 to January 2023 and included male and female Holstein and crossbred dairy calves ≥7 d old from 2 commercial dairy farms in Ontario, Canada (n = 96). On the day before transportation, calves were enrolled and randomly assigned to one of 2 treatment groups: (1) continuous transportation by road for 16 h or (2) 8 h of transport, 8 h of rest, and a further 8 h of transport to a single calf-raising facility. Calves that received a rest stop were fed 2 L of milk replacer at the time of unloading for the rest period and again immediately before reloading for the second leg of the journey. Blood samples were collected before and after transportation as well as daily for 3 d following arrival to the calf-raising facility. Serum was analyzed for concentrations of BHB, nonesterified fatty acids (NEFA), haptoglobin, and creatine kinase, and acid-base disturbances were evaluated within 1 h of collection of whole blood to assess glucose, sodium, potassium, ionized calcium, hematocrit, hemoglobin, pH, base excess, partial pressure of oxygen, total carbon dioxide, bicarbonate, partial pressure of carbon dioxide, and oxygen saturation. Mixed linear regression models with repeated measures were built to assess the effect of treatment group, age at transportation, breed, and sex on these parameters. Immediately after transportation, calves that received the rest period had lower BHB (−68.04 μmol/L, 95% CI: −99.59 to −36.49), NEFA (−0.14 mmol/L, 95% CI −0.22 to −0.07), and sodium (−1.10 mmol/L, 95% CI = −2.18 to −0.02), and higher glucose (0.48 mmol/L, 95% CI = 0.21 to 0.74), potassium (0.27 mmol/L, 95% CI = 0.11 to 0.43), ionized calcium (0.06 mmol/L, 95% CI = 0.03 to 0.08), and oxygen saturation (8.76%, 95% CI = 1.61 to 15.91) compared with calves that were continuously transported for 16 h. Additionally, calves transported between 11 and 12 d old had lower hematocrit (−1.22%, 95% CI = −2.19 to −0.25), hemoglobin (−3.07 g/L, 95% CI = −5.70 to −0.43), haptoglobin (−0.13 g/L, 95% CI = −0.23 to −0.02), and potassium (−0.13 mmol/L, 95% CI = −0.22 to −0.04) and higher sodium (0.83 mmol/L, 95% CI = 0.03 to 1.63) than 7 to 8 d old calves. Furthermore, calves that were 13 to 24 d old at transport had lower haptoglobin (−0.16 g/L, 95% CI = −0.27 to −0.06) and potassium (−0.14 mmol/L, 95% CI = −0.23 to −0.05), and higher sodium (1.02 mmol/L, 95% CI = 0.22 to 1.82) and ionized calcium (0.02 mmol/L, 95% CI = 0.002 to 0.035) compared with calves transported at 7 to 8 d old. The results of this trial demonstrate that a rest period improves energy status upon arrival to a calf-raising facility, suggesting that the benefit of a rest period may be mostly related to the provision of mid-journey milk meals. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

Introduction Warfighters are exposed to life-threatening injuries daily and according to the Joint Trauma System Military Clinical Practice Guideline—Global Snake Envenomation Management snakebites are a concerning threat in all theaters of operation. Snake venom is a complex mixture of toxins including phospholipases A2 (PLA2) and snake venom metalloproteinases (SVMP) that produce myotoxic, hemotoxic, and cytotoxic injuries. Antibody-based antivenom is the standard of care but new approaches including small-molecule inhibitors have gained attention in recent years. Doxycycline is an effective inhibitor of human metalloproteinases and PLA2. The enzymatic activities of 3 phylogenetically distinct snakes: Agkistrodon piscivorus, Naja kaouthia , and Daboia russelii were tested under inhibitory conditions using doxycycline. Materials and Methods Enzymatic activity of PLA2 and SVMP was measured in N. kaouthia, D. russelii , and A. piscivorus venom alone and with doxycycline using EnzChek Phospholipase A2 and Gelatinase Assay Kits. A 1-way ANOVA with Tukey's post-hoc test was used to conduct comparative analysis. The median lethal dose of the venoms, the effective dose of doxycycline, and creatine kinase (CK) inhibition levels were measured in a murine model with adult Bagg Albino (BALB/c) mice using intramuscular injections. Median lethal and effective doses were determined using Spearman-Karber's method and a 1-way ANOVA with Tukey's post-hoc test was used to compare CK inhibition levels. Results Phospholipases A2 activity was reduced to 1.5% to 44.0% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline when compared to venom-only controls (P  < .0001) (Fig. 1A). Snake venom metalloproteinases activity was reduced to 4% to 62% in all 3 venoms in a dose-dependent manner using 0.32, 0.16, and 0.08 mg/mL doxycycline (P  < .0001) (Fig. 1B). The lethal dose (LD50) values of the venoms in the murine model were calculated as follows: A. piscivorus  = 20.29 mg/kg (Fig. 2A), N. kaouthia  = 0.38 mg/kg (Fig. 2B), and D. russelii  = 7.92 mg/kg (Fig. 2C). The effective dose (ED50) of doxycycline in A. piscivorus was calculated to be 20.82 mg/kg and 72.07 mg/kg when treating D. russelii venom. No ED50 could be calculated when treating N. kaouthia venom (Fig. 3). Creatine kinase activity was significantly decreased in all 3 venoms treated with doxycycline (P  < .0001) (Fig. 4). FIGURE 1. In vitro doxycycline inhibition of PLA, and SVMP activity in whole venom. The AUC was calculated for PLA and SVMP activities for 20-min and 4-h time courses, respectively using EnzChek Phospholipase A2, assay kits, and EnzChek Gelatinase (SVMP) assay kits. (A) Inhibition of PLA2, with doxycycline (Dox) was tested at concentrations of 0.32 mg/mL, 0.16 mg/mL, and 0.08 mg/mL against A. piscivorus (4 μg/mL), N. kaouthia (4 μg/mL), and D. russelii (8 μg/mL) venom. A venom-only control was included. (B) Inhibition of SVMP with doxycycline was tested at concentrations of 0.32 mg/mL, 0.16 mg/mL, and 0.08 mg/mL against A. piscivorus (120 μg/ml.), N. kaouthia (125 μg/ml.), and D. russelii (250 μg/ml.). A venom-only control was included. An ordinary 1-way ANOVA with Tukey's post-hoc test was performed for inhibition assays to compare treatments to their respective venom controls. All error bars show mean ± SD, n  = 3, (****, P  < .0001). Open in new tab Download slide FIGURE 2. Percent survival of mice receiving various dosages for each venom studied and LDs, calculation. Adult BALB/c mice received intramuscular injections of various venom dosages for each venom, (A) A. piscivorus , (B) N. kaouthia , and (C) D. russelii. The resulting percent survival was measured across 48 h and the lethal dose 50 (LD50) was calculated using the Spearman-Karber method. In each graph, each treatment group (venom dosage) has n  = 5. Open in new tab Download slide FIGURE 3. Percent survival of mice receiving various doxycycline dosages for each venom studied and ED calculation. Adult BALB/c mice received intramuscular injections of various doxycycline dosages combined with 3 times the LD50 of cach venom [ A. piscivorus (AP) (60.87 mg/kg), N. kaouthia (NK) (1.14 mg/kg). D. russelii (DR) (23.76 mg/kg)] and the resulting percent survival was measured across 48 hours and the effective dose 50 (ED50) was calculated using the Spearman–Karber method. Each treatment group has n  = 5. Open in new tab Download slide FIGURE 4. Venom-induced CK activity with doxycycline-mediated inhibition. The amount of CK produced by mice exposed to one-fourth of the LD50, strength of A. piscivorus (AP) (5.07 mg/kg), N. kaouthia (NK) (0.095 mg/kg), or D. russelli (DR) (1.98 mg/kg) venom either with or without doxycycline (64 mg/kg). All error bars show mean, ± SD, n  = 5 (NaCl—Dox, AP NaCl), n-4 (NK Dox), and n-3 (AP Dox. NK NaCl, DR Dox, DR + NaCl). Statistical differences were determined using an ordinary 1-way ANOVA with Tukey's post-hoc test comparing each venom group within itself and to the doxycycline only control (**** P  < .0001). (*** P  < .001), (** P  < .01). (* P  < .05). Open in new tab Download slide Conclusion Doxycycline reduced PLA2- and SVMP-related lethality, particularly in A. piscivorus envenomings and in a limited capacity with D. russelii revealing its promise as a treatment for snakebites. In addition, CK activity, a common indicator of muscle damage was inhibited in mice that received doxycycline-treated venom. The doxycycline concentrations identified in the ED50 studies correspond to 1,456 to 5,061 mg dosages for a 70 kg human. Factors including venom yield and snake species would affect the actual dosage needed. Studies into high-dose doxycycline safety and its effectiveness against several snake species is needed to fully translate its use into humans. Based on this work, doxycycline could be used as a treatment en route to higher echelons of care, providing protection from muscle damage and reducing lethality in different snake species. [ABSTRACT FROM AUTHOR]

Objective To determine if the cardiac function and "endocrinium" of Chinese patients are associated with dopamine D2 (DRD2) (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms when treated with amisulpride. Methods This study enrolled 148 patients with schizophrenia who took amisulpride orally for 8 weeks. DRD2 (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms were detected with TaqMan-MGB allelic discrimination. Results Analysis by multivariate covariance analysis (MANCOVA) showed that after adjusting for age, gender, and the baseline level, the increase in the level of aspartate aminotransferase (AST) and creatine kinase (CK) in the rs6276 AG group was higher than that in the AA and GG groups. Similarly, the changed estradiol (E2) level in rs6276 GG and rs963468 GG groups was higher than that in the other two groups. Adjusting for covariates, the increased triglyceride (TG) level in rs6276 GG and rs963468 GG groups was the highest among their different genotype groups. The increase in the level of "AST" in the rs6280 TT group was higher than that in the CC and CT groups upon adjusting for covariates. Similarly, MANCOVA showed that the increase in the level of "CK" in the rs6280 CT group was higher than that in the CC and CT groups. Besides, the increased level of "PRL" in the rs6280 CC group and rs963468 GG group was higher than that in their other two genotypes groups. ConclusionDRD2 (rs6276) and DRD3 (rs6280, rs963468) polymorphisms can affect amisulpride tolerability since they are associated with the observed adverse reactions, including cardiac dysfunction and endocrine disorders in Chinese patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Improving energy provision in the failing heart by augmenting the creatine kinase (CK) system is a desirable therapeutic target. However, over-expression of the creatine transporter (CrT-OE) has shown that very high creatine levels result in cardiac hypertrophy and dysfunction. We hypothesise this is due to insufficient endogenous CK activity to maintain thermodynamically favourable metabolite ratios. If correct, then double transgenic mice (dTg) overexpressing both CrT and the muscle isoform of CK (CKM-OE) would rescue the adverse phenotype. In Study 1, overexpressing lines were crossed and cardiac function assessed by invasive haemodynamics and echocardiography. This demonstrated that CKM-OE was safe, but too few hearts had creatine in the toxic range. In Study 2, a novel CrT-OE line was generated with higher, homogeneous, creatine levels and phenotyped as before. Myocardial creatine was 4-fold higher in CrT-OE and dTg hearts compared to wildtype and was associated with hypertrophy and contractile dysfunction. The inability of dTg hearts to rescue this phenotype was attributed to downregulation of CK activity, as occurs in the failing heart. Nevertheless, combining both studies in a linear regression analysis suggests a modest positive effect of CKM over a range of creatine concentrations. In conclusion, we confirm that moderate elevation of creatine is well tolerated, but very high levels are detrimental. Correlation analysis lends support to the theory that this may be a consequence of limited CK activity. Future studies should focus on preventing CKM downregulation to unlock the potential synergy of augmenting both creatine and CK in the heart. [Display omitted] • Improving cardiac energetics via the creatine kinase system can be cardioprotective. • Too much creatine (>2-fold increase) causes heart failure and is not rescued by CK. • LV dysfunction causes transcriptional and post-translational down-regulation of CK. • Aim for modest increases in creatine while preventing loss of CK activity. [ABSTRACT FROM AUTHOR]

Background: Chronic pruritus of unknown origin (CPUO) is a highly debilitating disease that lacks effective treatment. There have been case reports of effective use of Janus Kinase (JAK) inhibitors in CPUO, including a case treated with baricitinib, a selective JAK 1/2 inhibitor. Objectives: To evaluate if itch in a cohort of CPUO patients was effectively reduced after treatment with baricitinib. Patients and Methods: This is a retrospective case series examining all patients with CPUO who were treated with baricitinib from February 2022 to August 2023 at the National Skin Center, Singapore. Itch scores on a 0–10 numerical rating scale (NRS) at 0.5‐point intervals were recorded and analyzed over time. Results: Sixteen patients (56% women, mean age of 62.2 ± 19.7 years old) with CPUO were included in the analysis. Their mean [range] duration of chronic itch was 15.4 [1–50] years, and the mean follow‐up period of baricitinib treatment was 10.2 ± 6.7 months. The median [IQR] NRS itch score before and after baricitinib treatment were 8.5 [6.5–10.0] and 3.5 [1.25–5.0], respectively, with a mean reduction in the itch score of 4.9 ± 2.7 (p < 0.0001). All except one patient reported significant improvement in itch severity. There were no reports of symptomatic side effects, except for a drop in hemoglobin in a patient with thalassemia and a dry throat in another patient. There were five cases of mild elevation in creatine kinase levels, three of which normalized over time, and two cases of mild elevation in creatinine levels. Conclusion: This study suggests that baricitinib can effectively reduce pruritus in patients with CPUO and supports the conduct of randomized placebo‐controlled trials to better elucidate the efficacy of JAK inhibitors in management of CPUO. [ABSTRACT FROM AUTHOR]

Introduction: del Nido cardioplegia was developed for immature myocardium to prevent myocardial damage by Ca+2 in traditional blood cardioplegia. But due to increased hemodilution and decreased colloid oncotic pressure it may cause myocardial edema and increased cardiac morbidity. Microplegia may have better cardioprotection in comparison to del Nido as there is less hemodilution. Material and methods: 60 patients from the age group of 1 to 14 years were divided into two groups i.e. del Nido based microplegia group and conventional del Nido group for studying two different cardioplegia technique. Data were collected and compared for intraoperative Hb, CPK-MB and Trop-I levels changes and requirement for defibrillation in intraoperative period. Demographic data, CPB time and ACC time were also collected. Results: Marked elevation in CPK-MB and Trop-I levels were seen in both groups. Statistically significant difference was seen in CPK-MB levels after 6 h of surgery where del Nido group has higher value in comparison to microplegia group. No statistical difference was seen in Trop-I levels in both groups. Strength of correlation (r) was also stronger for CPK-MB rise in association with CPB time and ACC time, in del Nido group but not for Trop-I. Significantly higher hemodilution was also seen in del Nido group after delivering cardioplegia. None of the patients required defibrillation in any group. Conclusion: Lesser hemodilution was seen in microplegia group. Significant cardioprotection is associated with use of microplegia solution in pediatric age group. [ABSTRACT FROM AUTHOR]

This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2–3.8 %, and within-laboratory imprecision 1.7–5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies. [ABSTRACT FROM AUTHOR]

Biological variation is a relevant component of diagnostic uncertainty. In addition to within-subject and between-subject variation, preanalytical variation also includes components that contribute to biological variability. Among these, daily recurring, i.e., diurnal physiological variation is of particular importance, as it contains both a random and a non-random component if the exact time of blood collection is not known. We introduce four time-dependent characteristics (TDC) of diurnal variations for measurands to assess the relevance and extent of time dependence on the evaluation of laboratory results. TDC address (i) a threshold for considering diurnality, (ii) the expected relative changes per time unit, (iii) the permissible time interval between two blood collections at different daytimes within which the expected time dependence does not exceed a defined analytical uncertainty, and (iv) a rhythm-expanded reference change value. TDC and their importance will be exemplified by the measurands aspartate aminotransferase, creatine kinase, glucose, thyroid stimulating hormone, and total bilirubin. TDCs are calculated for four time slots that reflect known blood collection schedules, i.e., 07:00–09:00, 08:00–12:00, 06:00–18:00, and 00:00–24:00. The amplitude and the temporal location of the acrophase are major determinates impacting the diagnostic uncertainty and thus the medical interpretation, especially within the typical blood collection time from 07:00 to 09:00. We propose to check measurands for the existence of diurnal variations and, if applicable, to specify their time-dependent characteristics as outlined in our concept. [ABSTRACT FROM AUTHOR]

Background: The efficiency and productivity of dentists are affected due to musculoskeletal disorders. Efforts should be made to monitor and reduce these disorders so that proper relation is maintained between body and work. Aims and Objectives: This research evaluates and compares the level of creatine kinase (CK) in operators working in ergonomically correct posture and incorrect posture using a newly developed digitalized alarm sensor attached to a dental operating stool. Materials and Methods: A digitalized alarming sensor was attached to half of the operating stools. Blood samples of the operators were checked for CK levels before working on patients and within 13–24 h after the operators have completed their work on patients. Results: The P value was found to be highly significant in operators without digitalized alarming sensors within 13–24 h after completing their work on patients. There was no significant difference in CK levels before patient interaction between the two groups; the presence of the alarm device had a notable impact on CK levels within 13–24 h after work. Conclusion: The group without the alarm device displayed significantly higher CK levels during this postwork timeframe, suggesting a potential association between the absence of the alarm device and increased CK levels among dental professionals. [ABSTRACT FROM AUTHOR]

Gastrodin (GAS), a bioactive compound derived from the orchid plant Gastrodia elata, exhibits numerous pharmacological effects. However, its effect on sleep deprivation (SD)–induced cardiac injury and the mechanisms are unknown. This study established SD mice model using a modified multiple platform water method and induced ferroptosis model in H9c2 cells using Erastin. The heart rate of mice was measured, and myocardial and mitochondrial structures were visualized using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). Myocardial injury, oxidative stress indicators, and Fe2+ levels were detected by the kit method. The reactive oxygen species (ROS) levels were detected by immunofluorescence, and SIRT6 and ferroptosis-associated protein expression levels were detected by Western blot. Reduced heart rate and abnormalities in myocardial tissue and mitochondrial structure were ameliorated in the SD group of mice after GAS treatment. GAS treatment reduced ROS levels in Erastin-induced H9c2 cells. GAS treatment reduced atrial natriuretic peptide (ANP), creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MAD), and Fe2+ levels, and increased superoxide dismutase (SOD) and glutathione (GSH) levels in the SD and Erastin groups. Western blot showed that GAS treatment increased the expression of sirtuin 6 (SIRT6), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) and decreased the expression of P53 in SD and Erastin groups. The SIRT6 inhibitor OSS_128167 (OSS) reversed GAS treatment of Erastin-induced ferroptosis in H9c2 cells. These observations propose that GAS prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6. [ABSTRACT FROM AUTHOR]

Cardiac biomarkers, especially high-sensitivity cardiac troponin C or I (hs-cTnC or hs-cTnI, respectively), are vital for diagnosing acute myocardial infarction (AMI). Despite the specificity of hs-cTn as a biomarker, the creatine kinase-myocardial band (CK-MB) is commonly used alongside hs-cTn in emergency departments (EDs). We analyzed 23,771 simultaneous hs-cTn (hs-cTnT or hs-cTnI) and CK-MB requests for 17,185 patients in tertiary hospital ED in 2022. The objective of this study was to assess their practical value in diagnosing AMI in real-world settings. Among all 17,185 patients tested, 98.0% underwent hs-cTnT and CK-MB tests, and substantially fewer underwent hs-cTnI testing. We observed concordance between the initial hs-cTn and CK-MB results in 71.3% of patients. Of 131 AMI cases, 57 were positive for both biomarkers, 63 for hs-cTn only, and none for CK-MB alone. CK-MB positivity was often found in the absence of AMI. Discrepancies between the hscTnT and hs-cTnI results occurred in 30.0% of patients. Indiscriminate CK-MB testing for diagnosing AMI in EDs should be reconsidered. Efficient use of CK-MB is important for reducing costs and ensuring optimal patient care. [ABSTRACT FROM AUTHOR]

Objective: No clinical trials have been conducted to establish optimal and effective treatment in patients with immune‐mediated necrotizing myopathy (IMNM), which can have a refractory course with increased morbidity from permanent muscle damage, especially in patients who experience delay in diagnosis and treatment. A subset of autoimmune necrotizing myopathy is associated with antibodies against 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR). Treatment involves withdrawing statins and using a combination of immunosuppressant and immunomodulatory treatment. Our study aims to provide longitudinally collected data on outcomes of early versus late initiation of intravenous Ig (IVIG) using our myositis center cohort of patients with anti‐HMGCR IMNM. Methods: We conducted a retrospective chart review of 31 adult patients of the Oregon Health and Science University Myositis Center who were diagnosed with anti‐HMGCR IMNM from September 2016 through October 2022 and reviewed physical examination, serologic laboratory data, and their treatment including prednisone reception as well as treatment response at 0 (the evaluation immediately before IVIG initiation), 3, 6, and 12 months on treatment. We divided this cohort into those who received IVIG at or before six months after receiving the diagnosis of anti‐HMGCR IMNM and refer this as the cohort with nondelayed treatment, and those who received IVIG after six months following their diagnosis, which we referred to as the cohort with delayed treatment. Diagnosis of anti‐HMGCR IMNM was defined as per the 2016 European Neuromuscular Centre criteria as having all three of elevated serum creatine kinase (CK), proximal muscle weakness, and anti‐HMGCR antibodies. We evaluated the response to treatment by using a limited total improvement score (TIS) as per 2016 American College of Rheumatology/EULAR myositis response criteria. Results: Among the 31 total patients, 19 were included within the cohort with nondelayed treatment, and 12 within the cohort with delayed treatment. The two cohorts had a comparable amount of time between the onset of symptoms and diagnosis; however, the cohort with delayed treatment had a significantly longer time between diagnosis and IVIG treatment (P < 0.001). At disease onset, cohorts had a comparable serum CK (P > 0.999), but patients with delayed treatment had an expected lower serum CK (P = 0.016) at the 0‐month time point. At the 0‐month time point, nine of the patients with nondelayed treatment (47%) required the use of a walker or wheelchair, whereas eight of the cohort with delayed treatment (66%) did. Patients who received nondelayed treatment demonstrated significant improvement in manual muscle testing 8 at the 12‐month intervals (P < 0.001). Average serum CK values of all patients measured at the 3, 6, and 12 months did not significantly differ between the groups with nondelayed and delayed treatment. TIS improved more in the group with nondelayed treatment than in the group with delayed treatment (P = 0.002 at 3 months, P = 0.019 at 6 months, and P = 0.001 at 12 months). Seven patients in the group with delayed treatment had permanent residual muscle weakness requiring walker or wheelchair use at 12 months, whereas none of the patients in the group with nondelayed treatment did. Conclusion: Though our results have limitations, they contribute to a growing body of evidence that suggests that IVIG may prove to be a valuable addition to an early and aggressive induction regimen in patients afflicted by anti‐HMGCRIMNM, particularly those with moderate to severe weakness requiring the use of a wheelchair or walking aids. Delay in IVIG treatment may lead to the development of permanent residual weakness and long‐term disability. [ABSTRACT FROM AUTHOR]

Background: Cardiogenic shock (CS) occurs in 5–10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development. Methods: This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h). The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24–48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed. Discussion: Early inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up. Trial registration: The Regional Ethics Committee : H-21045751. EudraCT: 2021–002028-19. ClinicalTrials.gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277–8523. [ABSTRACT FROM AUTHOR]

Background Objective Animals Methods Results Conclusion and Clinical Importance Limited information is available regarding the clinical features, treatment, and prognosis of neosporosis in adult dogs.Describe the clinical signs, laboratory findings, magnetic resonance imaging (MRI) findings, treatment and outcome in adult dogs (>6 months) diagnosed with neosporosis based on consistent clinical signs and positive serology (titer ≥1 : 800) at a referral hospital in Sydney, Australia.Twenty‐one client‐owned dogs.Retrospective case series of affected dogs between 2010 and 2023. Survival times were determined from onset of clinical signs to date of death or censoring.Clinical signs varied, and were indicative of generalized myopathy (6 dogs), multifocal intracranial disease (7 dogs), myelopathy (4 dogs), polyneuropathy (2 dogs) and single cases of focal myopathy and cerebellar disease. Serum creatine kinase activity was markedly increased (median, 3369 U/L) in most dogs. The most common MRI abnormalities were multifocal intracranial abnormalities (7/13 dogs) and muscle changes (5/13 dogs) whereas T2‐weighted cerebellar abnormalities (2/13 dogs) and cerebellar atrophy (1/13) were less common. Treatment response was complete (resolution to normal) in 8 dogs, incomplete (persistent neurological deficits) in 6 dogs, but there was minimal response in 7 dogs. Thirteen dogs (62%) were alive after 6 months and 12 dogs (57%) alive after 1 year. Relapse was common, with 4 dogs experiencing at least 1 relapse event during the follow‐up period.Adult‐onset neosporosis is uncommon and has variable clinical presentations. Treatment response also is variable, and relapse can occur, even among patients that respond completely to initial treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the clinical efficacy of the full-endoscopic posterior cervical foraminotomy (FE-PCF) and the unilateral biportal endoscopic posterior cervical foraminotomy (UBE-PCF) in the treatment of cervical spondylotic radiculopathy (CSR). Methods: Patients who underwent posterior cervical spine surgery in our hospital from January 2020 to December 2022 were retrospectively analyzed. According to the surgical method, the patients were divided into two groups: FE-PCF group and UBE-PCF group. Perioperative data included operation time, Intraoperative blood loss and postoperative hospital stay were collected. The Visual Analog Scale (VAS)-arm, VAS-neck, and Neck Diability Index (NDI) was used to evaluate the clinical outcomes at preoperative, postoperative 1 week and Last follow-up. Serum creatine phosphokinase (CPK) and C-reactive protein (CRP) levels were recorded to evaluate surgical invasiveness. Results: A total of 160 patients were included, including 89 cases of FE-PCF and 71 cases of UBE-PCF. The demographic and preoperative data showed no significant differences between the two groups (P > 0.05). The mean operating time was significantly shorter in the UBE-PCF group compared to FE-PCF group (P < 0.05). Serum CRP and CPK levels of the two groups both exhibited a pattern of rising and then falling, peaking one day following surgery and decreasing to near normal values three days after the operation. Compared with preoperative, both groups showed significant improvement in postoperative VAS and NDI scores, with a statistically significant difference (P < 0.05). However, the differences in results between the groups were not significant. Conclusions: Both UBE-PCF and FE-PCF are secure and efficient methods for treating CSR by continuous visualization. UBE-PCF offers predictable and adequate decompression within a reduced surgical duration, facilitated by its separate observation and operation channels. [ABSTRACT FROM AUTHOR]

Purpose Method Results Conclusion There is a scarcity of information regarding the effect of upper‐body eccentric exercise on biomarkers of muscle damage. This study sought to investigate the effect of eccentric arm cycling on muscle damage [exercise‐induced muscle damage (EIMD)].Ten subjects performed a 15 min eccentric arm cycling protocol (cadence 49 ± 7 rpm, power absorbed 248 ± 34 W). Maximal voluntary contraction (MVC) of the elbow flexors was evaluated at rest and at 5 min, 24 h, and 48 h post‐exercise. In addition, blood samples were drawn at rest and thereafter at 30 min, 24 h, and 48 h intervals after exercise for quantification of creatine kinase (CK), myoglobin, lactate dehydrogenase (LDH) and endothelin (ET‐1) concentrations. Delayed onset muscle soreness (DOMS) was assessed using a category ratio scale (0–10).Myoglobin was increased from baseline at 30 min post‐exercise (+114%, 46.08 ± 22.17 µg/L, p = 0.018). Individual peak values were higher than baseline values for CK (+72.8%, 204 ± 138 U/L, p = 0.046) and LDH (+17%, 3.3 ± 0.88 nmole/min/mL, p = 0.017), but not for ET‐1 (+9%, 1.4 ± 0.48 pg/mL, p = 0.45). DOMS was reported at 24 h (median 4) and 48 h (median 4) post‐exercise and MVC of the elbow flexors were reduced from baseline (216 ± 44 N) at 5 min (−34%, 147 ± 61 N, p < 0.001), 24 h (−17%, 181 ± 56 N, p = 0.005) and 48 h (−9%, 191 ± 54 N, p = 0.003).Eccentric arm cycling incites EIMD with reduced MVC and elevation of myoglobin, CK and LDH. [ABSTRACT FROM AUTHOR]

One potential complication in bariatric surgery is rhabdomyolysis, which is a condition involving muscle tissue damage that can significantly impact a patient's health. The causes of rhabdomyolysis can be broadly classified into two major categories: traumatic and non-traumatic. Early investigations into the development of intraoperative rhabdomyolysis in bariatric surgery identified the main risk factors as tissue compression—primarily affecting the lower extremities, gluteal muscles, and lumbar region—as well as prolonged periods of immobilization. Clinically, rhabdomyolysis is typically suspected when a patient presents with muscle pain, weakness, and potentially dark urine or even anuria. However, the most reliable biomarker for rhabdomyolysis is elevated serum creatine kinase levels. The primary goal in managing hydration is to correct intravascular volume depletion, with solutions such as Lactated Ringer's or 0.9% saline being appropriate options for resuscitation. Perioperative diagnosis of rhabdomyolysis poses a significant challenge for anesthesiologists, requiring a high degree of clinical suspicion, particularly in bariatric patients. In this vulnerable population, prevention is crucial. The success of treatment depends on its early initiation; however, there are still significant limitations in the therapies available to prevent renal injury secondary to rhabdomyolysis. [ABSTRACT FROM AUTHOR]

Chlamydia psittaci pneumonia (CPP) exhibits similar characteristics as of COVID-19 with respect to clustering outbreaks and onset symptoms. This study is aimed at exploring the different clinical manifestations of both pneumonias to establish a simple nomogram to distinguish them. This multicenter, retrospective, case–control study compared two independent cohorts of patients with CPP or COVID-19. The risk factors of CPP were analyzed using multivariate logistic regression, which was used to establish the nomogram. Both patients with CPP and COVID-19 exhibited similar clinical symptoms. As compared to patients with COVID-19, a higher proportion of patients with CPP had nervous system symptoms. Patients with CPP had higher inflammatory indicators, creatine kinase, and lower lymphocyte and albumin. They also had lower proportions of ground-glass opacity and bilateral lung involvement than COVID-19 patients. Furthermore, patients with CPP had higher 30 day mortality as well as higher rates of severe pneumonia, septic shock, and ICU admission. Multivariate logistic regression showed that nervous system symptoms, lymphocytes, creatine kinase, bilateral lung lesions, and ground-glass opacity were risk factors for CPP. Incorporating these five factors, the nomogram achieved good concordance index of 0.989 in differentiating CPP from COVID-19, and had well-fitted calibration curves. Despite similar clinical characteristics, nervous system symptoms, lymphocyte, creatine kinase, lesions in bilateral lungs, and ground-glass opacity may help in differentiating the pneumonias. These were combined into a clinically useful nomogram for rapid and early identification of CPP to avoid misdiagnosis and help in the decision-making process. [ABSTRACT FROM AUTHOR]

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (CKMT2). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog β-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing Ckmt2 using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet–fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of Ckmt2 improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes. Editor's summary: Increased plasma creatine is associated with type 2 diabetes, but causation has not been established. Rizo-Roca et al. show that men with type 2 diabetes had increased plasma creatine and decreased muscle phosphocreatine, which was associated with poor glucose handling. In myotubes in vitro, silencing the mitochondria-associated sarcomeric mitochondrial creatine kinase 2 (Ckmt2) gene resulted in impaired mitochondrial functions. In mice fed a high-fat diet, creatine supplementation had no effect on glucose handling, but overexpression of Ckmt2 in muscle improved mitochondrial functions. Data from humans and mice showed that exercise increased CKMT2 and metrics of mitochondrial functions. These results suggest that creatine changes are a consequence rather than a cause of insulin resistance in type 2 diabetes. —Brandon Berry [ABSTRACT FROM AUTHOR]

Background: Long-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD. Methods: This retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported. Results: Patients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients' total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment. Conclusions: The significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations. [ABSTRACT FROM AUTHOR]

Background: A growing interest in using Nigella sativa oil (NSO) in the prevention or treatment of several cardiovascular diseases has prompted this study. The research aims to investigate the effect of NSO on cardiac damage prevention after long-term administration in induced myocardial infarction (MI) in rats. Methods: NSO was analyzed for its fatty acids composition using gas chromatography-mass spectrometry (GC-MS) analysis and administered in rats before and after isoproterenol (45 mg/kg body weight) induced myocardial infarction. The following parameters were assessed: electrocardiograms, histopathological examination, serum biochemical aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase-myocardial band (CK-MB), serum and heart inflammation (tumor necrosis factor-alpha (TNF), interleukin 1 beta (IL-1b), and interleukin 6 (IL-6)), and tissue oxidative stress (total antioxidant capacity (TAC), total oxidative stress (TOS), nitric oxide (NO), malondialdehyde (MDA), and the total thiols (THIOL)). Results: Linoleic acid (C18:2n-6) and oleic acid (C18:1n-9) were approximately 89% of total fatty acids while palmitic acid (C16:0) was 6.10%. Administration of NSO for 28 days helped in preventing QT and QTc interval prolongation and reduced heart rate (HR), after MI induction. The histological assessment showed improvement in myofibrillary degeneration and necrosis and also better reduced inflammatory process in the groups treated with NSO. In serum, pro-inflammatory cytokines IL-1b and IL-6 were downregulated in chronic conditions (for IL-1b, NSO vs. control was 86.09vs 150.39 pg/mL, and for IL-6 NSO vs. control was 78.00 vs. 184.98 pg/ml). In the heart tissue, the downregulation was observed only for TNF in both acute and chronic conditions (acute NSO vs. control was 132.37 vs. 207.63 pg/mL, and chronic NSO vs. control was 135.83 vs. 183.29 pg/ml). The pro-oxidant parameters TOS, NO, MDA, and OSI, were reduced in the groups treated with NSO only after 14 days of treatment, suggesting that the NSO antioxidant effect is time-dependent. Conclusions: NSO administration might have a favourable impact on the regulation of oxidative stress and inflammation processes after MI induction in rats, and it is worth considering its administration as an adjuvant treatment. [ABSTRACT FROM AUTHOR]

Objective: Clinical practice guidelines suggest performing an electrocardiogram (EKG) in patients with chest pain within the first 10 minutes in the emergency department, warning about subdiagnosis in women. Possible differences based on sex were analyzed. Method: An observational and retrospective study in an Emergency Department, with adult patients admitted to the Chest Pain Unit in 2021. Results: There were 1,469 patients, of whom 774 were men (52.7%). The men were younger (60 vs. 65 years), were less overweight (17.18 vs. 22.16%), and had more previous admissions to the Coronary Unit (12 vs. 7%), compared to women. No gender differences were observed in EKG performance (91 vs. 90%), EKG time (median 4.1 vs. 4.5 minutes), or delay in care attention (median 25 vs. 26 minutes). In terms of healthcare resources, men underwent more biomarkers: troponins (63 vs. 55%; odds ratio [OR]: 1.35; 95% confidence interval [95%CI]: 1.10-1.67) and creatine phosphokinase (24.8 vs. 19.1%), received more aspirin (6.7 vs. 3.1%), nitrates/nitrites (6 vs. 3%), and hospitalization (17.18 vs. 10.50%; OR: 1.76; 95%CI; 1.30-2.40). Of 206 hospitalized, 112 had a final diagnosis of acute coronary syndrome (54%), more men than women (81 vs. 31). There were no significant differences in revascularization time, medication schedule at discharge, hospital stay, or mortality. Conclusions: Gender did not affect precordial pain care, diagnosis, and treatment times, highlighting the quality of hospital care. [ABSTRACT FROM AUTHOR]

Objective: Multiple acyl‐coenzyme A dehydrogenase deficiency (MADD) is a disorder of fatty acid oxidation and considered an inborn error of metabolism. In recent years, we have diagnosed an increasing number of patients where, despite extensive investigation, no disease‐causing mutations have been found. We therefore investigated a cohort of consecutive patients, with the objective to detect possible non‐genetic causes. Methods: We searched the patient records and the registry of muscle biopsies, for patients with MADD, diagnosed within the past 10 years. The patient records were reviewed regarding symptoms, clinical findings, comorbidities, drugs, diagnostic investigations, and response to treatment. In addition, complementary investigations of muscle tissue were performed. Results: We identified 9 patients diagnosed with late‐onset MADD. All presented with muscle weakness and elevated levels of creatine kinase. A lipid storage myopathy was evident in the muscle biopsies, as was elevated acylcarnitines in blood. Despite thorough genetic investigations, a probable genetic cause was found in only 2 patients. Remarkably, all 7 patients without disease‐causing mutations were treated with sertraline. In some cases, a deterioration of symptoms closely followed dose increase, and discontinuation resulted in an improved acylcarnitine profile. All 9 patients responded to riboflavin treatment with normalization of creatine kinase and muscle biopsy findings, and in 8 patients the clinical symptoms clearly improved. Interpretation: Our findings strongly suggest that sertraline may induce an acquired form of MADD in some patients. Importantly, riboflavin treatment seems to be similarly effective as in genetic MADD, but discontinuation of sertraline is reasonably warranted. ANN NEUROL 2024;96:802–811 [ABSTRACT FROM AUTHOR]

This study assessed the possible pharmacological effects of Chlorella vulgaris (Cg), Spirulina platensis (St), and silymarin (Sl) against thioacetamide (TA)-induced cardiotoxicity in rats, with a focus on their antioxidant, cardioprotective, and anti-inflammatory properties. The following is the random grouping of sixty male rats into six groups of ten animals each: the control (negative control), TA-intoxicated group (positive control; 300 mg/kg body weight (BW)), Sl + TA group (100 mg Sl/kg BW + TA), St + TA group (400 mg St/kg BW + TA), Cg + TA (400 mg Cg/kg BW + TA), and St + Cg + TA group (400 St + 400 Cg mg/kg BW + TA) were all administered for 30 days. At the start of the study, groups 2 through 6 were administered TA intraperitoneally at a dosage of 300 mg/kg BW for two consecutive days, with a 24 h gap between each dose, to induce cardiac damage. Blood samples were obtained to measure hematological parameters and perform biochemical assays, including lipid profiles and cardiac enzymes. For histopathology and immunohistochemistry determination, tissue samples were acquired. The current findings showed that TA injection caused hematological alterations and cardiac injury, as evidenced by greater serum levels of troponin I, creatine kinase-MB, and total creatine kinase (p < 0.05), as well as significantly elevated serum malondialdehyde and decreased serum total antioxidant capacity (p < 0.05) concentrations. Moreover, an increase in blood low-density lipoprotein and total cholesterol concentration (p < 0.05) was recorded in the TA group. There were alterations in the heart tissue's histological structure of the TA group compared to the control ones. These alterations were characterized by vacuolar degeneration of myocytes, loss of cross striation, coagulative necrosis, and fibrosis of interstitial tissue, which was ameliorated by the supplementation of SI, St, and Cg. The TA-intoxicated group showed weak expression of B-cell lymphoma protein 2 (p < 0.05) and strong immunoreactivity of tumor necrosis factor-α and B-cell lymphoma protein 2-associated X (p < 0.05). However, the groups receiving Sl, St, and Cg experienced the opposite. The administration of Sl, St, Cg, and St + Cg along with TA significantly improved and restored (p < 0.05) erythrogram indices, including RBCs, hemoglobin, total leukocytic count, lymphocytes, and monocyte, to the normal control values. The administration of Sl, St, and Cg alleviated the cardiotoxicity caused by TA via reducing oxidative stress, inflammatory markers, and apoptosis in heart tissue. In summary, the current findings suggest that the treatment with Sl, St, and Cg was beneficial in ameliorating and reducing the cardiotoxicity induced by TA in rats. [ABSTRACT FROM AUTHOR]

The ROS1 proto‐oncogene encodes a receptor tyrosine kinase with structural homology to other oncogenic drivers, including ALK and TRKA‐B‐C. The FDA‐approved tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have demonstrated efficacy in treating ROS1 fusion‐positive NSCLC. However, limitations such as poor blood‐brain barrier penetration and acquired resistance, particularly the ROS1 G2032R solvent‐front mutation, hinder treatment durability. Repotrectinib, a next‐generation macrocyclic TKI, was rationally designed to overcome on‐target resistance mutations and improve brain distribution through its low molecular weight. In the TRIDENT‐1 clinical trial, repotrectinib demonstrated significant efficacy in both TKI‐naïve and TKI‐pretreated patients with ROS1‐rearranged NSCLC, including those with CNS metastases and G2032R resistance mutations. In the TKI‐naïve cohort (n = 71), 79% of patients achieved an objective response, with a median progression‐free survival (PFS) of 35.7 months, surpassing all previously approved ROS1 TKIs. In patients who had received one prior ROS1 TKI but were chemotherapy‐naïve (n = 56), objective responses were observed in 38%, and median PFS was 9.0 months. The safety profile of repotrectinib was consistent with earlier‐generation ROS1 TKIs and common adverse events included anemia, neurotoxicity, increased creatine kinase levels, and weight gain. These findings underscore the potential of repotrectinib to address unmet needs in ROS1‐rearranged NSCLC, offering durable responses and improved intracranial activity. Future research should prioritize developing next‐generation, selective ROS1 inhibitors to reduce Trk‐mediated toxicities and improve treatment tolerance. [ABSTRACT FROM AUTHOR]

Introduction: There has been increasing evidence of association between cardiovascular and chronic kidney disease. Most of complications and mortality in these patients are due to development of cardiovascular disease (CVD) rather than due to chronic kidney disease (CKD) by itself. Though cardiac biomarkers are available but due to lack of clinical symptoms in early stages and delayed diagnosis mortality rate has increased. The present study was conducted to detect the cardiovascular dysfunction measured by various cardiac biomarkers like serum Cardiac high sensitivity Troponin I, Creatinine kinase and creatinine Kinase MB with eGFR in CKD patients to correlate the association of cardiovascular dysfunction in patients with CKD for early detection and initiation of aggressive treatment to reduce mortality. Methods: The present cross-sectional study was conducted on 110 patients of chronic kidney disease (CKD) at tertiary care hospital, Hyderabad. Cardiac HS Troponin I, Creatine Kinase (CPK) and Creatine Kinase-MB (CK-MB) were analysed and correlated with e-GFR, Urea and creatinine levels. Results: There was statistically significant association between Hs Troponin I, CK-MB and CPK with Chronic kidney disease. There was negative corelation of cardiac biomarkers with eGFR and positive correlation with Urea and creatinine. Multivariate regression analysis for predictors of cardiac dysfunction was done using ANOVA with renal parameters in patients with CKD which showed strong association between e-GFR and cardiac markers. Conclusion: High morbidity and mortality in patients with CKD is observed due to Cardiovascular disease. It is important to diagnose CVD with high index of suspicion and evaluate with commonly available biochemical cardiac markers. In our study there was significant elevation in Hs Trop I, CK MB and CPK in CKD patients which correlated negatively with eGFR. Routine use of these markers during follow-up of CKD patients helps in risk assessment, prevention of complications and timely interventions. [ABSTRACT FROM AUTHOR]

X‐linked recessive dystrophinopathies are the most common muscular dystrophies (MDs) in humans and dogs. To date, 20 breed‐specific MD‐associated variants are described in the canine dystrophin gene (DMD), including one associated with dystrophin‐deficient MD in the Border Collie mixed breed. Here, we report the diagnosis and follow‐up of mild dystrophin‐deficient MD in a 5‐month‐old male Border Collie, associated with a novel DMD variant. Diagnosis was based on neurological examination and laboratory evaluations including creatine kinase activity, electromyography and muscle biopsies with immunofluorescent staining. Inspection of the Sashimi plots of the RNA‐seq data from the affected muscle biopsy led to the discovery of a 162‐bp L1 pseudoexon in DMD intron 63, introducing a frameshift and a premature stop codon (NM_001003343.1: c.9271_9272insN[162] p.(Ala3091fs*21)). Reduced DMD mRNA levels were detected for both the non‐pseudoexon (50× less) and pseudoexon (3× less) containing transcripts in the affected muscle, compared with the level of the non‐pseudoexon containing transcript in a control muscle, resulting in very low dystrophin protein levels and the upregulation of utrophin. Because the variant was only found in the affected dog, not in the healthy mother and grandmother, or in 108 unrelated Border Collies from the Belgian population (46 males and 62 females), it was considered a de novo variant. Although the prognosis for dystrophinopathy is generally regarded as poor, the dog stabilised at the age of 6 months and is still clinically stable at the age of 2 years. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of different tirofiban administration time windows in patients with no-reflow myocardial infarction (MI) during percutaneous coronary intervention (PCI). Methods: This single centre retrospective observational study included patients with no-reflow MI, undergoing PCI at the Hanyang Hospital affiliated to Wuhan University of Science and Technology from March 2020 to May 2023. All patients were administered tirofiban. Patients who received tirofiban with postinterventional thrombolysis in myocardial infarction (TIMI) flow ≥ 1 were grouped as Group-I, and patients who were directly given tirofiban through the guiding catheter without forward blood flow were grouped as Group-II. TIMI blood flow classification, levels of cardiac troponin T (cTnT) and creatine kinase isoenzyme MB (CK-MB), incidence of complications and major adverse cardiovascular events (MACE) in the two groups before and after the treatment were statistically analyzed. Results: A total of 156 patients were included in this study, including 79 patients in Group-I and 77 patients in Group- II. There was no significant difference in the baseline data between the two groups (P>0.05). After treatment, TIMI blood flow classification of the two groups improved and was significantly better in Group-I compared to Group-II (P<0.05). After treatment, levels of Serum cTnT and CK-MB in the two groups decreased, and were significantly lower in Group-I than in Group-II (P<0.05). There was no significant difference in the incidence of complications between Group-I (3.80%) and Group-II (6.49%) (P>0.05). The incidence of MACE in Group-I (3.80%) was lower than that in Group-II (12.99%) (P<0.05). Conclusions: Compared with the direct application of tirofiban, tirofiban given when TIMI Grade≥ 1 for patients with no-reflow MI during PCI can more effectively regulate the blood flow status of target vessels, reduce myocardial injury, and reduce the risk of MACE. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the ryanodine receptor 1 (RYR1) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype–phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic RYR1 variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic RYR1 variant that has recently been described in another patient with severe congenital myopathy and shown to affect splicing. Segregation analyses confirmed the variants to be compound heterozygous. We compared our patient's phenotype to that of the patient from the literature as well as five additional patients with compound heterozygous RYR1 variants from our center. The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. Interestingly, both patients carrying the new intronic splice variant showed a very severe disease course. More widespread use of genome sequencing will open the way for better genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]

Background and Aims: Liver injury is one of the common complications of paraquat (PQ) poisoning, but whether the degree of liver injury is related to patient prognosis is still controversial. This study aimed to investigate whether liver injury was a risk factor for death in PQ‐poisoned patients. Methods: We conducted a retrospective cohort study of PQ‐poisoned patients from the past 10 years (2011–2020) from a large tertiary academic medical centre in China. PQ‐poisoned patients were divided into a normal liver function group (n = 580) and a liver injury group (n = 60). Propensity score matching (PSM) analysis was then performed. Results: A total of 640 patients with PQ poisoning were included in this study. To reduce the impact of bias, dose of PQ, urinary PQ concentration and time from poisoning to hospital admission were matched between the two groups. A 3:1 PSM analysis was performed, ultimately including 240 patients. Compared with the normal liver function group, patients in the liver injury group were older, had a higher R value ([ALT/ULN]/[ALP/ULN]) (p <.001) and had a higher mortality rate. Cox regression analysis showed that there was no significant association between alanine aminotransferase, alkaline phosphatase, total bilirubin levels and hazard of death, but age, PQ dose, creatine kinase isoenzyme, creatine kinase, white blood cell count, neutrophil percentage and lymphocyte percentage were associated with mortality in patients with PQ poisoning. Conclusions: The occurrence of liver injury within 48 h after PQ poisoning was a risk factor for mortality, and such liver injury was likely of a hepatocellular nature. Age, PQ dose, creatine kinase isoenzyme and white blood cell count were positively correlated with mortality, while creatine kinase, percentage of neutrophils and lymphocytes were inversely correlated. [ABSTRACT FROM AUTHOR]

Background: Well-leg compartment syndrome (WLCS) can occur due to compression and lower limb circulation disturbances caused by the surgical position during the procedure. Although rare, with an incidence of 1 in 3500 surgeries performed in the lithotomy position, it can lead to serious complications. Therefore, prevention and early diagnosis are critical. Symptoms of WLCS, such as leg pain, swelling, paresthesia, and serum creatine kinase (CK) levels are useful for diagnosis. This study aimed to investigate the risk factors for postoperative CK elevation in laparoscopic or robot-assisted colorectal cancer surgery performed in the lithotomy-Trendelenburg position. Methods: Postoperative CK levels were measured in 178 patients who underwent laparoscopic or robot-assisted colorectal cancer surgery between February 2022 and March 2023. We compared patient backgrounds, short-term outcomes, and thigh/calf circumferences between patients with CK levels ≥ 250 (n = 62) and those with CK levels < 250 (n = 116). We investigated risk factors for elevated CK levels using both univariate and multivariate analyses. Results: Four patients with CK levels of 22405 U/L, 4685 U/L, 4050 U/L, and 3824 U/L reported symptoms, which improved with conservative treatment. The following independent prognostic factors were identified by multivariate analysis: male sex (odds ratio [OR], 4.403; 95% CI, 1.960 to 9.892), rectal surgery (OR, 2.779; 95% CI, 1.249 to 6.184), continuous head-down position duration ≥ 180 min (OR, 3.523; 95% CI, 1.552 to 7.997), and preoperative calf circumference ≥ 33 cm (OR, 2.482; 95% CI, 1.154 to 5.339). Conclusions: Risk factors for CK elevation after colorectal cancer surgery in the lithotomy position include male sex, rectal surgery, an extended continuous head-down position without position changes, and a larger preoperative calf circumference. This study highlights the potential importance of intraoperative position changes every 3 h for preventing elevated CK levels, although the preventive effect was not specifically examined. [ABSTRACT FROM AUTHOR]

Emerging findings suggest that non-shivering thermogenesis in brown and beige adipocytes may effectively stimulate energy expenditure, thereby contributing to body weight reduction. Our previous report demonstrated that chrysin, a flavone found in honey and propolis, activates uncoupling protein 1 (UCP1)-dependent thermogenesis in brown fat and induces beige adipocytes. However, the effect of chrysin on UCP1-independent thermogenesis remains unexplored. In this study, we examined the effects of chrysin on UCP1-independent thermogenesis in the 3T3-L1 adipocytes and mouse model. This study showed that chrysin elevates the expression of calcium regulatory proteins, including sarcoendoplasmic reticulum Ca2+-ATPase, ryanodine receptor 2, voltage-dependent anion channel, mitochondrial calcium uniporter, and Ca2+/calmodulin-dependent protein kinase 2 in 3T3-L1 adipocytes as well as in inguinal and epididymal white adipose tissues of mice. Furthermore, our results also showed chrysin increased Ca2+ levels in 3T3-L1 adipocytes in a dose-dependent manner. In addition, our study showed chrysin upregulated creatine-mediated thermogenic markers (creatine kinase B and creatine kinase mitochondrial 2) in both in vitro and in vivo models. Mechanistically, we found that chrysin induces UCP1-independent thermogenesis by stimulating creatine- and calcium-mediated ATP-consuming futile cycle through the activation of the α1-adrenergic receptor. Combining the current and previous studies, it can be proposed that chrysin induces both UCP1-dependent and -independent thermogenesis in beige adipocytes, suggesting its possible use for effective intervention for obesity and metabolic disorders. [ABSTRACT FROM AUTHOR]

Introduction: The safety and efficacy of upadacitinib 15 mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study. Methods: Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24 weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. The safety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216. Results: The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n = 277/309) that initially received ABA. Of patients on UPA15 in the LTE (n = 547), 28.3% (n = 155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in the American College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n = 263/303, 86.8%; ABA to UPA15: n = 273/309, 88.3%) showed similar responses to the total population. Conclusions: The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343. Plain Language Summary: A long-term study looked at a drug named upadacitinib to treat people with rheumatoid arthritis (RA), a disease that causes joint pain and damage. The study included patients whose RA was not improved by other injectable medicines. The study compared upadacitinib with another drug called abatacept. After 24 weeks, patients who were taking abatacept switched to upadacitinib, and patients taking upadacitinib continued on upadacitinib treatment for over 4 years. The researchers looked at how well the treatments worked over the long-term and if there were any side effects. The side effects with upadacitinib treatment in this long-term study were similar to side effects reported in previous studies with upadacitinib. The researchers also found that upadacitinib helped to lessen the symptoms of RA over time and helped patients complete their daily activities and reduced their pain and tiredness. This was true for patients who switched from abatacept to upadacitinib after 24 weeks and for patients who took upadacitinib from the start of the study. Patients who had not responded to other medicines also had similar improvements with upadacitinib. In conclusion, upadacitinib can help people with RA over the long term and no new safety risks were found. [ABSTRACT FROM AUTHOR]

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Objective: To investigate the impact of post-activation potentiation (PAP) induced by resisted sled sprint at different loads on the subsequent 30 m ice push sled performance of Chinese skeleton athletes, and to identify the resisted sled sprint load that most effectively enhances PAP for Chinese skeleton athletes. Methods: Seven elite athletes from the Chinese skeleton team participated in four tests with more than 48 h intervals. During the tests, on the first test, athletes completed a 40 min standard warm-up, rested for 6 min, and then performed a 30 m test. On the second, third, and fourth test, athletes completed the standard warm-up, then performed 20 m sprints with resisted sled (RS) at 75%, 50%, and 25% of body mass (BM), respectively, rested for 6 min, and then performed the 30 m test. Results: No significant differences were found in morning pulse, blood urea, and creatine kinase levels among four tests. The percentage of maximum heart rate (%HRmax) within different intensity ranges showed no significant differences among four tests. However, significant differences were observed in ice push sled performance among four tests (No BMRS: 5.08 ± 0.27; 25% BMRS: 5.05 ± 0.29; 50% BMRS: 5.02 ± 0.27; 75% BMRS: 5.04 ± 0.28). Post hoc analyses revealed that the 50% BMRS test had faster speed compared to the no resistance (p < 0.05), the 25% BMRS (p < 0.05), and the 75% BMRS (p < 0.05) tests. Additionally, the 75% BMRS test had faster speed than the no resistance test (p < 0.05). Conclusion: A 20 m sprint with 50% BMRS effectively enhances the PAP effect in skeleton athletes, improving their ice push sled performance. Coaches can incorporate this resisted sled sprint in athletes' training routines for performance enhancement in both daily training and pre-competition preparations. [ABSTRACT FROM AUTHOR]