Development and validation of a nomogram for assessment postoperative sodium disturbance in PAs patients: a retrospective cohort study.

Background: Pituitary adenomas (PAs) are neuroendocrine tumors located in the sellar region. Surgery, being the primary treatment option for most PAs, is known to cause disruptions in sodium metabolism. Objective: To develop and validate a nomogram for assessment the incidence of postoperative sodium disturbance (SD) in patients with PAs. Methods: In this retrospective study, 208 patients with PAs who underwent resection surgery between 2013 and 2020 were included. Various demographic characteristics, clinical features and laboratory data were analyzed as potential predictors of postoperative sodium disturbance (SD). LASSO regression were used to identify independent preoperative variables associated with SD. Logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A nomogram was constructed to visualize these results and evaluated using metrics such as the area under the curve (AUC) for discrimination, the Hosmer-Lemeshow test for calibration and decision curve for usefulness assessment. Results: The incidence of SD was 44.23% (92 cases out of 208). Six preoperative factors, including sex, types of PAs, phosphocreatine kinase (CK), serum iron (Fe), free fatty acids (NEFA) and mean corpuscular volume (MCV), were identified for constructing a predictive nomogram. The nomogram showed high accuracy, with AUC values of 0.851 (95% CI [0.799-0.923]) and 0.771 (95% CI [0.681-0.861]) in the training and validation datasets, respectively. Calibration assessment and decision curve analysis confirmed its good agreement and clinical utility. Conclusion: A practical and effective nomogram for predicting SD after PAs surgery is presented in this study.

[Value of serum procalcitonin and acute physiology and chronic health evaluation II score on predicting the prognosis of sepsis in elderly patients].

OBJECTIVE: To explore the value of serum procalcitonin (PCT) and acute physiology and chronic health evaluation II (APACHE II) score on predicting prognosis of elderly patients with sepsis. METHODS: A retrospective cohort study, patients with sepsis who admitted to the department of emergency and the department of geriatric medicine of Peking University Third Hospital from March 2020 to June 2021 were enrolled. Patients' demographics, routine laboratory examinations, APACHE II score that within 24 hours of admission were obtained from their electronic medical records. The prognosis during the hospitalization and one year after discharge were collected, retrospectively. Univariate and multivariate analysis of prognostic factors were performed. And Kaplan-Meier survival curves were used to examine overall survival. RESULTS: A total of 116 elderly patients met inclusion criteria, 55 were alive and 61 were died. On univariate analysis, clinical variables such as lactic acid [Lac, hazard ratio (HR) = 1.16, 95% confidence interval (95%CI) was 1.07-1.26, P < 0.001], PCT (HR = 1.02, 95%CI was 1.01-1.04, P < 0.001), alanine aminotransferase (ALT, HR = 1.00,95%CI was 1.00-1.00, P = 0.143), aspartate aminotransferase (AST, HR = 1.00, 95%CI was 1.00-1.01, P = 0.014), lactate dehydrogenase (LDH, HR = 1.00, 95%CI was 1.00-1.00, P < 0.001), hydroxybutyrate dehydrogenase (HBDH, HR = 1.00, 95%CI was 1.00-1.00, P = 0.001), creatine kinase (CK, HR = 1.00, 95%CI was 1.00-1.00, P = 0.002), MB isoenzyme of creatine kinase (CK-MB, HR = 1.01, 95%CI was 1.01-1.02, P < 0.001), Na (HR = 1.02, 95%CI was 0.99-1.05, P = 0.183), blood urea nitrogen (BUN, HR = 1.02, 95%CI was 0.99-1.05, P = 0.139), fibrinogen (FIB, HR = 0.85, 95%CI was 0.71-1.02, P = 0.078), neutrophil ratio (NEU%, HR = 0.99, 95%CI was 0.97-1.00, P = 0.114), platelet count (PLT, HR = 1.00, 95%CI was 0.99-1.00, P = 0.108) and total bile acid (TBA, HR = 1.01, 95%CI was 1.00-1.02, P = 0.096) shown to be associated with poor prognosis. On multivariable analysis, level of PCT was an important factor influencing the outcome of sepsis (HR = 1.03, 95%CI was 1.01-1.05, P = 0.002). Kaplan-Meier survival curve showed that there was no significant difference with respect to the overall survival between the two groups, with patients of PCT ≤ 0.25 µg/L and PCT > 0.25 µg/L (P = 0.220). It also showed that the overall survival rate in patients with high APACHE II score (> 27 points) was significantly lower than that in patients with low APACHE II score (≤ 27 points, P = 0.015). CONCLUSIONS: Serum PCT level is valuable prognostic factors of elderly patients with sepsis, and higher APACHE II score (> 27 points) indicates a poor prognosis.

Longitudinal Assessment of Creatine Kinase, Creatine/Creatinineratio, and Myostatin as Monitoring Biomarkers in Becker Muscular Dystrophy.

BACKGROUND AND OBJECTIVES: The slow and variable disease progression of Becker muscular dystrophy (BMD) urges the development of biomarkers to facilitate clinical trials. We explored changes in 3 muscle-enriched biomarkers in serum of patients with BMD over 4-year time and studied associations with disease severity, disease progression, and dystrophin levels in BMD. METHODS: We quantitatively measured creatine kinase (CK) using the International Federation of Clinical Chemistry reference method, creatine/creatinineratio (Cr/Crn) using liquid chromatography-tandem mass spectrometry, and myostatin with ELISA in serum and assessed functional performance using the North Star Ambulatory Assessment (NSAA), 10-meter run velocity (TMRv), 6-Minute Walking Test (6MWT), and forced vital capacity in a 4-year prospective natural history study. Dystrophin levels were quantified in the tibialis anterior muscle using capillary Western immunoassay. The correlation between biomarkers, age, functional performance, mean annual change, and prediction of concurrent functional performance was analyzed using linear mixed models. RESULTS: Thirty-four patients with 106 visits were included. Eight patients were nonambulant at baseline. Cr/Crn and myostatin were highly patient specific (intraclass correlation coefficient for both = 0.960). Cr/Crn was strongly negatively correlated, whereas myostatin was strongly positively correlated with the NSAA, TMRv, and 6MWT (Cr/Crn rho = -0.869 to -0.801 and myostatin rho = 0.792 to 0.842, all p < 0.001). CK showed a negative association with age (p = 0.0002) but was not associated with patients' performance. Cr/Crn and myostatin correlated moderately with the average annual change of the 6MWT (rho = -0.532 and 0.555, p = 0.02). Dystrophin levels did not correlate with the selected biomarkers nor with performance. Cr/Crn, myostatin, and age could explain up to 75% of the variance of concurrent functional performance of the NSAA, TMRv, and 6MWT. DISCUSSION: Both Cr/Crn and myostatin could potentially serve as monitoring biomarkers in BMD, as higher Cr/Crn and lower myostatin were associated with lower motor performance and predictive of concurrent functional performance when combined with age. Future studies are needed to more precisely determine the context of use of these biomarkers.

Epidemiological, toxicological and physiopathological characteristics of scorpion stings and their management in Morocco: A literature review.

All around the world, scorpion envenomation represents a public health issue. In Morocco, it represents the first cause of poisoning. The aim of this review is to highlight the epidemiological, toxicological and physiopathological characteristics of scorpion stings and envenomation in Morocco as well as their management. According to the bibliography, the most areas affected by scorpion stings and envenomation are those in the center and south of Morocco. Lethality rate is more important in children than adult. Age, admission class, season, serum venom concentration, and the time elapsed between the scorpion sting and medical intervention are risk factors for a poor prognosis. Until now, we have only known the LD50 of 14 scorpion species from three genera: Androctonus, Buthus and Hottentota, and only 6 species, out of 61 moroccan scorpions, have been assessed for their venom toxicity on mice organs. The venom of harmful moroccan scorpions induces several histopathological changes in the myocardium, brain, liver, pulmonary alveoli, and kidneys in rats, as well as severe consequences in the lungs with intra-alveolar hemorrhage. There was also a significant increase in serum enzyme levels of aspartate transaminase (AST), alanine transaminase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH), as well as high levels of plasma albumin, creatine and glucose. In the absence of a specific treatment, the management of scorpion envenomation is based only on symptomatic therapy. We noted a widely use of traditional remedies. Despite the magnitude of the scorpion problem in Morocco, it remains understudied and continues to claim lives, particularly given the lack of an efficient etiological cure.

Individualised reference ranges for markers of muscle recovery assessment in soccer.

Recently an individualisation algorithm has been developed and shown to significantly improve the diagnostic accuracy of creatine kinase (CK) and urea in endurance sports and Badminton. In this study, the applicability and benefit of this algorithm was evaluated using repeated measures data from 161 professional German soccer players monitored during the 2015-2017 seasons. Venous blood samples were collected after a day off (recovered state) and after a minimum of two strenuous training sessions within 48 h (non-recovered state) and analysed for CK and urea. Group-based reference ranges were derived from that same dataset to ensure the best possible reference for comparison. A z-test was conducted to analyse differences in error rates between individualised and group-based classifications. CK values for the individualised approach showed significantly lower error rates in the assessment of muscle recovery compared to both a population-based (p < .001; z-value: -17.01; test-pass error rate: 21 vs. 67%; test-fail: 19 vs. 64%) and a group-based cut-off (p < .001; z-value: -15.29; test-pass error rate: 65%; test-fail: 67%). It could be concluded that the assessment of muscle recovery in soccer using individualised interpretations of blood-borne markers may offer higher diagnostic accuracy than a population-based and a sample-specific group-based approach.HighlightsAssessing muscle recovery via CK using individualised ranges seems to offer a higher diagnostic accuracy than a sample-specific group-based analysis.Using an individualised algorithm seems to be a promising approach to overcome diagnostic problems arising from large inter- and intraindividual variability in blood parameters as it significantly improved the diagnostic accuracy of CK as a recovery marker.As recovery assessment in elite soccer ultimately aims at the accurate detection of differences in the individual player this algorithm seems to offer coaches and sport scientists a more sensitive approach compared to group-specific evaluations.

Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Assessment toxic effects of exposure to 3-indoleacetic acid via hemato-biochemical, hormonal, and histopathological screening in rats.

The current study purposed to investigate the 3-indoleacetic acid (IAA) possible adverse impacts on hematological parameters, hepatorenal function, cardiac, and skeletal muscles as well as testes of rats and histopathological alterations of respective organs and to determine the extent of reversing any adverse impacts occurred in animals after IAA withdrawal. Rats were exposed orally to 500 mg/kg BW by gastric intubation once daily for 14 days, after which one-half was sacrificed and the remaining half left for a further 14 days without IAA exposure. The exposure of rats to IAA produced anemia, leukopenia, neutrophilia, lymphopenia, and a significant increase in activities of serum transaminase, gamma-glutamyl transferase, creatine kinase-myocardial band, creatine kinase-muscle type, and levels of serum creatinine, sodium, chloride, and potassium. Furthermore, serum levels of testosterone, gonadotropins, and leptin significantly declined. The changes in most of measured parameters continued after IAA withdrawal. Histopathological alterations in different tissues supported these changes. In conclusion, subacute exposure to IAA at a high concentration could exert hematotoxicity and toxic effects on many soft organs and its withdrawal led to incomplete recovery of animals. Thus, IAA should be used cautiously as extensive use of it at high concentrations can cause harmful effects on the environment, animals and human beings.

Serum biomarkers for the assessment of muscle damage in various surgical approaches in primary total hip arthroplasty: a systematic review of comparative studies.

PURPOSE: Using serum biomarkers, this systematic review assessed soft tissue injury following different total hip arthroplasty surgical approaches. The purposes were to determine if there is any advantage between the standard and minimal invasive approaches, and to compare tissue damage of the respective surgical approaches using biomarkers such as creatine kinase, myoglobin, c-reactive protein, erythrocyte sedimentation rate, skeletal troponin and interleukins. METHOD: A search in Pubmed/MEDLINE, Scopus and Web of Science databases was conducted in October 2021 with the use of PRISMA guidelines. Search items were ("biomarkers" OR "markers" OR "tissue damage" OR "muscle damage") AND "approach" AND ("total hip arthroplasty" OR "total hip replacement"). Inclusion criteria were prospective, randomized, controlled trials or prospective, comparative studies, comparing serum markers for muscle damage in two or more surgical approaches for primary total hip arthroplasty. Exclusion criteria were study protocols, case reports, systematic reviews, meta-analyses, studies in non-English language or without available full text, and studies not recording biomarkers of muscle damage. RESULTS: Initial search revealed 508 studies; after subtraction of duplicates, and exclusion criteria, 31 studies remained for analysis. No advantage between different approaches was found when evaluating biomarkers, and no specific biomarkers had a distinct role in tissue damage in total hip arthroplasty. Anterior and minimally invasive approaches were associated with lower values of soft tissue (creatine kinase) and inflammation (c-reactive protein) biomarkers compared to the standard approaches. CONCLUSION: Measurement of serum biomarkers after primary total hip arthroplasty for the estimation of tissue damage has unclear or little clinical value. TRIAL REGISTRATION: PROSPERO Registration: CRD42022303959.

Assessment of serum CK-MM level as a bioindicator for work-related musculoskeletal injuries among Emergency hospital workers.

Musculoskeletal disorders (MSDs) are considered a growing problem among healthcare personnel, especially service workers. The emergency room (ER) service workers are highly exposed to work-related risk factors which predispose them to MSDs. A cross-sectional study was performed on 78 ER workers. Full medical and occupational histories were taken. The Standardized Nordic Questionnaire (SNQ) was used for the assessment of musculoskeletal symptoms. Clinical examination was done with special emphasis on the locomotors system, and serum levels of muscle enzymes, including creatine kinase (CK) and creatine kinase isoenzyme (CK-MM), were measured. The study aims to detect the prevalence of occupational musculoskeletal disorders (MSDs) among ER workers at University hospitals, and assessment of CK-MM as a biomarker used in the early detection of MSDs. We found that 71.8% of the participants were complaining of musculoskeletal disorder in the last 7 days before the study, while only 34.6% were complaining of musculoskeletal disorder in the last 12 months before the study. The knee joint was the most commonly affected site in the past 7 days, by 39.7%. On the other hand, the highest prevalent disorder in the last 12 months was for the ankle joint (17.9%) with significantly high levels of serum CK-MM. In conclusion, musculoskeletal injuries are a common complaint among healthcare occupations, especially among ER service workers that need regular health education and ergonomic training programs. Monitoring of serum CK-MM level with cut-off value 90 ng\ml could be used as a novel approach for the early detection of work-related musculoskeletal disorders.

Sex Differences in Neuromuscular Fatigue and Changes in Cost of Running after Mountain Trail Races of Various Distances.

INTRODUCTION: Women have been shown to experience less neuromuscular fatigue than men in knee extensors (KE) and less peripheral fatigue in plantar flexors (PF) after ultratrail running, but it is unknown if these differences exist for shorter trail running races and whether this may impact running economy. The purpose of this study was to characterize sex differences in fatigability over a range of running distances and to examine possible differences in the postrace alteration of the cost of running (Cr). METHODS: Eighteen pairs of men and women were matched by performance after completing different races ranging from 40 to 171 km, divided into SHORT versus LONG races (<60 and >100 km, respectively). Neuromuscular function and Cr were tested before and after each race. Neuromuscular function was evaluated on both KE and PF with voluntary and evoked contractions using electrical nerve (KE and PF) and transcranial magnetic (KE) stimulation. Oxygen uptake, respiratory exchange ratio, and ventilation were measured on a treadmill and used to calculate Cr. RESULTS: Compared with men, women displayed a smaller decrease in maximal strength in KE (-36% vs -27%, respectively, P < 0.01), independent of race distance. In SHORT only, women displayed less peripheral fatigue in PF compared with men (Δ peak twitch: -10% vs -24%, respectively, P < 0.05). Cr increased similarly in men and women. CONCLUSIONS: Women experience less neuromuscular fatigue than men after both "classic" and "extreme" prolonged running exercises but this does not impact the degradation of the energy Cr.

Electroconvulsive therapy use in the adult U.S. correctional setting: A case report and literature review.

Mr. C is a 45-year-old male inmate who was found in his cell unresponsive and mute. He had poor food and fluid intake for the last four days and was later found standing in place, frozen, and resistant to movement when encouraged by a corrections officer to rest in his bed. His symptoms were consistent with catatonia, a severe motor syndrome that can be life-threatening. The patient had a psychiatric history of bipolar I disorder with multiple past episodes of catatonia. Lorazepam was ineffective at reversing his catatonic symptoms, and his serum creatinine kinase level eventually began to rise, suggestive of muscle breakdown and worsening severity. The treating psychiatrist wanted access to electroconvulsive therapy (ECT) to treat Mr. C's catatonia but encountered numerous legal and logistical barriers which made this treatment option unavailable. The article reviews the scant literature on ECT use in the adult U.S. correctional system, identifies barriers, and discusses a recommended ECT referral process for inmates.

Decreased running economy is not associated with decreased force production capacity following downhill running in untrained, young men.

The present study investigated the relationships between changes in running economy (RE) and indirect muscle damage markers following downhill running (DHR) to test the hypothesis that decreased RE after DHR would be associated with decreases in muscle function. Forty-five young men ran downhill (-15%) for 30 min at the velocity corresponding to 70% of their peak oxygen uptake (VO2peak). Oxygen uptake (VO2) and other parameters possibly associated with RE (blood lactate concentration, perceived exertion, stride length and frequency) were measured during 5-minute level running at the velocity corresponding to 80%VO2peak before, immediately after and 1-3 days after DHR. Knee extensor maximal voluntary contraction torque (MVC), rate of torque development, vertical jump performance, muscle soreness and serum creatine kinase activity were assessed at the same time points. The values of the dependent variables were compared among time points by one-way ANOVAs followed by Bonferroni post-hoc tests when appropriate. Pearson's correlation tests were used to examine relationships between changes in VO2 (RE parameter) and changes in muscle damage parameters. VO2 during the level run increased (p < 0.05) immediately after DHR (18.3 ± 4.6%) and sustained until 2 days post-DHR (11.7 ± 4.2%). MVC decreased (p < 0.05) immediately (-21.8 ± 6.1%) to 3 days (-13.6 ± 5.9%) post-DHR, and muscle soreness developed 1-3 days post-DHR. The magnitude of changes in VO2 did not significantly (p < 0.05) correlate with the changes in muscle damage makers (r = -0.02-0.13) nor stride length (r = -0.05) and frequency (r = -0.05). The absence of correlation between the changes in VO2 and MVC suggests that strength loss was not a key factor affecting RE.

Kinetic modelling of myocardial necrosis biomarkers offers an easier, reliable and more acceptable assessment of infarct size.

Infarct size is a major prognostic factor in ST-segment elevation myocardial infarction (STEMI). It is often assessed using repeated blood sampling and the estimation of biomarker area under the concentration versus time curve (AUC) in translational research. We aimed at developing limited sampling strategies (LSS) to accurately estimate biomarker AUC using only a limited number of blood samples in STEMI patients. This retrospective study was carried out on pooled data from five clinical trials of STEMI patients (TIMI blood flow 0/1) studies where repeated blood samples were collected within 72 h after admission to assess creatine kinase (CK), cardiac troponin I (cTnI) and muscle-brain CK (CK-MB). Biomarker kinetics was assessed using previously described biomarker kinetic models. A number of LSS models including combinations of 1 to 3 samples were developed to identify sampling times leading to the best estimation of AUC. Patients were randomly assigned to either learning (2/3) or validation (1/3) subsets. Descriptive and predictive performances of LSS models were compared using learning and validation subsets, respectively. An external validation cohort was used to validate the model and its applicability to different cTnI assays, including high-sensitive (hs) cTnI. 132 patients had full CK and cTnI dataset, 49 patients had CK-MB. For each biomarker, 180 LSS models were tested. Best LSS models were obtained for the following sampling times: T4-16 for CK, T8-T20 for cTnI and T8-T16 for CK-MB for 2-sample LSS; and T4-T16-T24 for CK, T4-T12-T20 for cTnI and T8-T16-T20 for CK-MB for 3-sample LSS. External validation was achieved on 103 anterior STEMI patients (TIMI flow 0/1), and the cTnI model applicability to recommended hs cTnI confirmed. Biomarker kinetics can be assessed with a limited number of samples using kinetic modelling. This opens the way for substantial simplification of future cardioprotection studies, more acceptable for the patients.

Assessment of muscle fiber adaptation in footballers using a new ELISA assay of myosin isoforms.

BACKGROUND: To measure the impact of training models on injury incidence, data of health and performance were integrated to study fiber adaptation during a competitive season. We studied football players over a season, analyzing hours of exposure to sport by serum changes in fast and slow myosin, creatine kinase and lactate dehydrogenase. METHODS: A new assay was developed to measure the myosin isoforms in 49 non-sporting volunteers and in 27 professional football players. RESULTS: Myosin isoforms in volunteers with mean ages of 30±8 were 1553 µg/L fast and 1284 µg/L slow; in the group with of 56±7 were 1426 µg/L fast and 1046 µg/L slow. Slow myosin was significantly lower in older subjects (-18%). Samples from the players in preseason had lower mean scores for fast myosin (1123 µg/L) and higher for slow myosin (2072 µg/L) than reference volunteers. During the season, myosins reached the maximum with the maximum load (1537 µg/L fast, 2195 µg/L slow but decreased and adapted to the high level of demand (425 µg/L fast, 1342 µg/L slow). CK and LDH were maximal at the pre-season (227 U/L, 333 U/L) while myosin levels were maximal at the beginning of season (1537 µg/L, 2195 µg/L). CONCLUSIONS: Measuring serum myosin isoforms we identify the type and amount of damage caused by training and matches, making it a new control tool capable of advising training towards a minimum of blood slow myosin but controlling the fast fiber participating and be able to improve the performance of the players.

Routine creatine kinase testing does not provide clinical utility in the emergency department for diagnosis of acute coronary syndromes.

BACKGROUND: Despite the high sensitivity and negative predictive value of contemporary high-sensitivity troponin T assays (hsTnT), creatine kinase (CK) continues to be routinely tested for the diagnosis of acute coronary syndrome (ACS). We conducted a study to identify the clinical utility of routine CK measurement, its relevance in clinical decision making in the era of hsTnT, and the potential cost-savings achievable by limiting its use. METHODS: We conducted a retrospective review of all adult patients presenting to a tertiary care center in the year 2017. We identified patients presenting with cardiac complaints who had non-diagnostic hsTnT and positive CK. These patients underwent chart review to determine whether a diagnosis of AMI was made. RESULTS: A total of 36,251 presentations were reviewed. 9951 had cardiac complaints and 8150 had CK measured. 82% of these patients had hsTnT and CK measured; 2012 of these patients had non-diagnostic hsTnT with positive CK. Of these 2012 patients, only 1 was subsequently diagnosed with AMI (0.012%). CK provided no diagnostic benefit over hsTnT alone in > 99.9% of cases. With a cost for CK of $4/test, we estimated that routine CK testing costs at least $32,000 per year in our center, and over $100,000 per year across the region. CONCLUSION: Routine CK testing does not provide a significant benefit to patient care and therefore represents an unnecessary system cost. Routine CK testing for the diagnosis of AMI should be eliminated from emergency departments in the era of hsTnT assays.

Assessment of plasma creatine kinase as biomarker for levodopa-induced dyskinesia in Parkinson's disease.

We tested in a translational approach the usefulness of plasma creatine kinase (CK) as an objective biomarker for levodopa-induced dyskinesia (LID). Plasma CK levels were measured in five dyskinetic parkinsonian non-human primates (NHP) and in ten PD patients with LID who participated in a treatment trial with simvastatin. Plasma CK levels were increased in dyskinetic NHP and correlated with LID severity while they were not affected by LID severity in PD patients.

Thermoregulation and markers of muscle breakdown in malignant hyperthermia susceptible volunteers during an acute heat tolerance test.

OBJECTIVES: The study was undertaken to compare the thermal and biochemical responses to a heat tolerance test (HTT) of malignant hyperthermia (MH) susceptible individuals, volunteers who have suffered heat illness (HI) and control volunteers. METHODS: Three groups of male volunteers (n=6 in each group) were recruited to the study: MHS - civilian volunteers previously diagnosed as MH susceptible; EHI - military volunteers with a history of exertional HI; CON - military volunteers with no history of HI or MH. For the HTT, volunteers walked on a treadmill at 60% maximal oxygen uptake in a hot environment. Measurements were made of core and skin temperatures, heat flow, whole body sweat rate and serum lactate, creatine kinase and myoglobin concentrations. RESULTS: There were no differences in deep body temperature, oxygen uptake or serum lactate and creatine kinase concentrations between the three groups. One MHS volunteer and two EHI volunteers failed to achieve thermal balance with rectal temperature continuing to rise throughout the test and reaching 39.5°C, the rectal temperatures of the other volunteers plateaued at a mean (SD) of 38.7 (0.4)°C demonstrating thermal tolerance on this test. Serum myoglobin concentration and the increase in serum myoglobin was higher in MHS than EHI and CON Post HHT (P<0.05). CONCLUSION: MH susceptibility does not always predispose an individual to heat intolerance during an acute HTT, but does appear to increase muscle breakdown. The inclusion of serum myoglobin measurements to a HTT may help to distinguish patients that are potentially MHS, and who otherwise demonstrate thermal tolerance.

Mitochondrial Diagnostics: A Multiplexed Assay Platform for Comprehensive Assessment of Mitochondrial Energy Fluxes.

Chronic metabolic diseases have been linked to molecular signatures of mitochondrial dysfunction. Nonetheless, molecular remodeling of the transcriptome, proteome, and/or metabolome does not necessarily translate to functional consequences that confer physiologic phenotypes. The work here aims to bridge the gap between molecular and functional phenomics by developing and validating a multiplexed assay platform for comprehensive assessment of mitochondrial energy transduction. The diagnostic power of the platform stems from a modified version of the creatine kinase energetic clamp technique, performed in parallel with multiplexed analyses of dehydrogenase activities and ATP synthesis rates. Together, these assays provide diagnostic coverage of the mitochondrial network at a level approaching that gained by molecular "-omics" technologies. Application of the platform to a comparison of skeletal muscle versus heart mitochondria reveals mechanistic insights into tissue-specific distinctions in energy transfer efficiency. This platform opens exciting opportunities to unravel the connection between mitochondrial bioenergetics and human disease.

Isometric pre-conditioning blunts exercise-induced muscle damage but does not attenuate changes in running economy following downhill running.

Running economy (RE) is impaired following unaccustomed eccentric-biased exercises that induce muscle damage. It is also known that muscle damage is reduced when maximal voluntary isometric contractions (MVIC) are performed at a long muscle length 2-4 days prior to maximal eccentric exercise with the same muscle, a phenomenon that can be described as isometric pre-conditioning (IPC). We tested the hypothesis that IPC could attenuate muscle damage and changes in RE following downhill running. Thirty untrained men were randomly assigned into experimental or control groups and ran downhill on a treadmill (-15%) for 30 min. Participants in the experimental group completed 10 MVIC in a leg press machine two days prior to downhill running, while participants in the control group did not perform IPC. The magnitude of changes in muscle soreness determined 48 h after downhill running was greater for the control group (122 ±â€¯28 mm) than for the experimental group (92 ±â€¯38 mm). Isometric peak torque recovered faster in the experimental group compared with the control group (3 days vs. no full recovery, respectively). No significant effect of IPC was found for countermovement jump height, serum creatine kinase activity or any parameters associated with RE. These results supported the hypothesis that IPC attenuates changes in markers of muscle damage. The hypothesis that IPC attenuates changes in RE was not supported by our data. It appears that the mechanisms involved in changes in markers of muscle damage and parameters associated with RE following downhill running are not completely shared.

Genetic analysis and clinical assessment of four patients with Glycogen Storage Disease Type IIIa in China.

BACKGROUND: Glycogen Storage Disease Type III (GSD III) is a rare autosomal recessive metabolic disorder caused by AGL gene mutation. There is significant heterogeneity between the clinical manifestations and the gene mutation of AGL among different ethnic groups. However, GSD III is rarely reported in Chinese population. CASE PRESENTATION: In this study, we aimed to study the genetic and clinical characteristics of four patients with GSD IIIa from China, especially the neurological manifestations. Meanwhile, we conducted a literature review of GSD IIIa cases reported in Chinese population to investigate the relationship between genotype and phenotype. CONCLUSIONS: Three different AGL gene mutations were identified in our patients: c.206dupA, c.1735 + 1G > T and c.2590 C>T. Moreover, progressive myopathy accompanied by elevated creatine kinase level was the main manifestation of our patients in adolescents. Our results showed that AGL c.206dupA was a novel mutation and caused severe clinical manifestations. AGL c.1735 + 1G > T might be a recurrent mutation in the Chinese population. Genetic analysis of AGL gene mutation combined with muscle magnetic resonance imaging (MRI) might provide greater benefit to the patient in diagnosing GSD IIIa, rather than an invasive diagnostic procedure of biopsy.