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There is a lack of evidence on the additional benefits of combining caffeine (CAF) and creatine (CRE) supplementation on anaerobic power and capacity. Thus, the aim of the present study was to test the effects of combined and isolated supplementation of CAF and CRE on anaerobic power and capacity. Twenty-four healthy men performed a baseline Wingate anaerobic test and were then allocated into a CRE (n = 12) or placebo (PLA; n = 12) group. The CRE group ingested 20 g/day of CRE for 8 days, while the PLA group ingested 20 g/day of maltodextrin for the same period. On the sixth and eighth days of the loading period, both groups performed a Wingate anaerobic test 1 hr after either CAF (5 mg/kg of body mass; CRE + CAF and PLA + CAF conditions) or PLA (5 mg/kg of body mass of cellulose; CRE + PLA and PLA + PLA conditions) ingestion. After the loading period, changes in body mass were greater (p <.05) in the CRE (+0.87 ± 0.23 kg) than in the PLA group (+0.13 ± 0.27 kg). In both groups, peak power was higher (p =.01) in the CAF (1,033.4 ± 209.3 W) than in the PLA trial (1,003.3 ± 204.4 W), but mean power was not different between PLA and CAF trials (p >.05). In conclusion, CAF, but not CRE ingestion, increases anaerobic power. Conversely, neither CRE nor CAF has an effect on anaerobic capacity. [ABSTRACT FROM AUTHOR]

Background: Alcohol septal ablation (ASA) is recommended for moderate to severe symptomatic patients with hypertrophic obstructive cardiomyopathy. The current guidelines don not recommend particular alcohol doses and the amount of alcohol injected into the septal artery is based more on the interventionalist's decision rather than on systematic evidence. Our objective is to execute a comprehensive assessment of the efficacy and safety of low alcohol doses (1–2 ml)) in comparison to large ones (2–4 ml). Methods: Multiple databases, encompassing PubMed, WOS, Scopus, Embase, and Cochrane library were systemically assessed from inception to October 2023. Randomized controlled trials (RCTs) and observational studies comparing low-alcohol and high-alcohol dose in patients with HOCM was included. The main outcome was creatine kinase-MB (CK-MB). The secondary ones are septal thickness, left ventricular outflow pressure gradient, and atrioventricular (AV) block. Results: Eight studies, with a total of 1446 individuals, were finally involved in our investigation. low alcohol doses showed lower CK-MB levels relative to high ones (MD=-0.93, 95% CI [-1.15 to -0.72], P = 0.00001). Furthermore, in terms of septal thickness, left ventricular outflow pressure gradient, and AV block, neither of the two doses was preferred. Conclusion: We propose that the low alcohol dose is equally effective as the high dose. moreover, the low alcohol dose was associated with a lower CK-MB levels in comparison to the high one. PROSPERO registration: CRD42024511537 [ABSTRACT FROM AUTHOR]

Introduction: Skeletal muscle satellite cells (SC) contribute to the adaptive process of resistance exercise training (RET) and may be influenced by nutritional supplementation. However, little research exists on the impact of multi-ingredient supplementation on the SC response to RET. Purpose: We tested the effect of a multi-ingredient supplement (MIS) including whey protein, creatine, leucine, calcium citrate, and vitamin D on SC content and activity as well as myonuclear accretion, SC and myonuclear domain compared with a collagen control (COL) throughout a 10-wk RET program. Methods: Twenty-six participants underwent a 10-wk linear RET program while consuming either the MIS or COL supplement twice daily. Muscle biopsies were taken from the vastus lateralis at baseline and 48 h after a bout of damaging exercise, before and after RET. Muscle tissue was analyzed for SC and myonuclear content, domain, acute SC activation, and fiber cross-sectional area (fCSA). Results: MIS resulted in a greater increase in type II fCSA following 10 wk of RET (effect size (ES) = 0.89) but not myonuclear accretion or SC content. Change in myonuclei per fiber was positively correlated with type I and II and total fiber hypertrophy in the COL group only, indicating a robust independent effect of MIS on fCSA. Myonuclear domain increased similarly in both groups, whereas SC domain remained unchanged following RET. SC activation was similar between groups for all fiber types in the untrained state but showed a trend toward greater increases with MIS after RET (ES = 0.70). Conclusions: SC responses to acute damaging exercise and long-term RET are predominantly similar in MIS and COL groups. However, MIS can induce greater increases in type II fCSA with RET and potentially SC activation following damage in the trained state. [ABSTRACT FROM AUTHOR]

Purpose The objective of this study was to evaluate the impact of a pharmacist consult service on rates of hypoglycemia in adult inpatients with renal dysfunction receiving antidiabetic medications. Methods This was a single-center, institutional review board–approved, quasi-experimental, 2-phase prospective study. Adult inpatients admitted within 48 to 96 hours of hospitalization with a creatine clearance of less than 30 mL/min or estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 and an active antidiabetic medication order were included. Patients located in a critical care unit or with a previous or planned transplantation were excluded. Each phase was conducted over 4 months. The primary endpoint was the change in the incidence of hypoglycemic episodes (blood glucose [BG] of <70 mg/dL) per 100 patient days when comparing the cohorts. Secondary endpoints included the incidence of recurrent and severe (BG of <40 mg/dL) episodes of hypoglycemia per 100 patient days, occurrence of a BG concentration of higher than 300 mg/dL, and length of stay. Results Overall, 150 patients were included in the retrospective preimplementation phase and 172 were included in the prospective postimplementation phase. In the postimplementation group, there was a significant decrease in the rate of hypoglycemia per 100 patient days when compared to the retrospective group (5.8 vs 9.0; incidence rate ratio, 1.55; 95% confidence interval, 1.2-2.0; P < 0.05). There was no difference in secondary endpoints between the groups. Conclusion The implementation of a pharmacy consult service resulted in lower rates of hypoglycemic events, which supports pharmacist involvement to prevent hypoglycemia in this at-risk population. Additional studies involving pharmacists working under collaborative practice agreements may reinforce the results. [ABSTRACT FROM AUTHOR]

The cerebellum is a key structure in working and procedural memory. The aim of the present prospective exploratory study was to investigate, the metabolic characteristics of the cerebellum in posterior fossa tumor (PFT) survivors using 3D proton magnetic resonance spectroscopy imaging (3D MRSI), to determine whether metabolites could be useful biomarkers of memory impairment. Sixty participants were included in the IMPALA study, divided into three groups: 22 irradiated PFT, 17 nonirradiated PFT, and 21 healthy controls matched with irradiated PFT for age, sex, and handedness. PFT survivors were treated at least 5 years ago, either by surgery or a combination of surgery, chemotherapy, and radiotherapy. All participants underwent working and procedural memory tests and multimodal MRI including a 3D MRSI sequence. N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac) metabolite values were extracted from the cerebellum for comparisons between groups, correlations with neurocognitive test scores, and radiotherapy doses. Median (range) age at neurocognitive tests was 18 (7–26) years. Median Cho, Cr, NAA, and Lac values, and the ratio of NAA to the sum of metabolites were significantly lower for PFT survivors than for healthy controls (p < 0.05). Scores on working and procedural memory tests were significantly lower for PFT survivors (p < 0.004) and correlated with median and maximum Cho and NAA values (0.28 < r < 0.49, p < 0.04). Except for creatine, the other metabolites were not significantly different between irradiated and nonirradiated survivors. MRSI values in the cerebellum were not correlated with either total dose or doses received by this structure. Results revealed changes in cerebellar metabolic values in PFT survivors that were closely correlated with memory deficits, suggesting that some metabolites could be used as markers of cognitive decline, but this will require validation on a larger sample size. • 3D MRSI was used to assess metabolic profile of cerebellum in posterior fossa tumor (PFT) survivors. • Cerebellar metabolic values were lower in PFT survivors. • Metabolite values were closely correlated with memory deficits. • Some metabolites could be used as markers of memory impairment. [ABSTRACT FROM AUTHOR]

Objective: Complications from diabetic foot wounds, including bacterial infection, ulceration and gangrene, are major causes of hospitalisation and are responsible for 85% of amputations in patients with diabetes. Given that orally administered investigational therapeutic Cytoreg (Cytorex de Venezuela SA, Venezuela), a defined aqueous mixture of hydrofluoric, hydrochloric, sulfuric, phosphoric, citric and oxalic acids, has been shown to increase levels of arterial blood oxygen in a Wistar rat model, oral and oral+topical Cytoreg were tested on patients with diabetic foot ulcers (DFUs) under a humanitarian, compassionate-use protocol. Method: All patients received oral Cytoreg (5.0 ml concentrate in fruit juice) for 30 days; half also received weekly wound washing with Cytoreg concentrate in isotonic saline (1:50 volume/volume) (oral+topical group). In addition to standard clinical observations, wounds were monitored against the Saint Elian checklist system for the diabetic foot. Results: A total of 10 patients took part in the study. Complete wound closure was observed in 4/5 patients in the oral+topical group; in the remaining patient, necrotic and fibrin tissues on the wound edges were eliminated. Half (2/4) of the patients receiving oral-only Cytoreg experienced complete wound closure; one patient in this group was removed prematurely because of an unrelated illness and was not replaced. During the study, no significant differences were observed between groups in either the oxygen saturation of the affected tissues or in insulin and glycaemia levels (p<0.05). Significant increases in arterial haemoglobin and arterial oxygen partial pressure (p<0.05) were observed, and significant decreases were measured in the levels of glycosylated haemoglobin, aspartate aminotransferase, glutamic-pyruvic transaminase, creatine and urea (p<0.05). Conclusion: The results of this study justify an expanded clinical study for the treatment of DFUs with Cytoreg. [ABSTRACT FROM AUTHOR]

Background: Although recent studies have increasingly focused on examining the potential benefits of creatine supplementation to improve performance in swimming events, the impact of creatine supplementation on swimming performance remains a topic of debate and controversy. A comprehensive meta-analytical review was undertaken to evaluate the effects of creatine supplementation on the performance, physiological response, and body composition among swimmers. Methods: The research methodology adhered strictly to the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was conducted across six databases (Cochrane Library, Web of Science, Scopus, Embase, PubMed, and SPORTDiscus) until March 23, 2024. Eligible studies that investigated the impact of creatine supplementation on swimming time, physiological parameters, and body composition in swimmers were included. For the meta-analysis, a random-effects model was employed to determine the collective effect and assess variations across distinct subgroups defined by swimming time, physiological metrics, and body composition. Meta-regression analysis was conducted on datasets comprising ten or more studies. Standardized mean differences (SMD) along with their corresponding 95% confidence intervals (CI) were calculated. To evaluate the methodological rigor of the included studies, the Physiotherapy Evidence Database (PEDro) scale was utilized. Results: The systematic review included seventeen studies with a total of 361 subjects. No significant differences were observed in the overall effect during single sprint swimming (SMD: -0.05, 95% CI: -0.26, 0.15; p = 0.61), repeated interval swimming (SMD: -0.11; 95% CI: -0.46, 0.25; p = 0.56), physiological response (SMD: 0.04, 95% CI: -0.16, 0.23; p = 0.71), and body composition (SMD: 0.18; 95% CI: -0.05, 0.41; p = 0.12) between creatine and placebo groups. Conclusions: Creatine supplementation exhibited ineffectiveness in enhancing the performance, physiological response, and body composition among swimmers. Key Points: No significant evidence to support that creatine supplementation can improve swimming performance was found. Creatine supplementation showed no significant impact on physiological response. No significant effects of creatine supplementation on body composition were found. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) with multiple structures are formed at the sites where carbonyl groups of reducing sugars bind to free amino groups of proteins through the Maillard reaction. In recent years, it has been highlighted that the accumulation of AGEs, which are generated when carbonyl compounds produced in the process of sugar metabolism react with proteins, is involved in various diseases. Creatine is a biocomponent that is homeostatically present throughout the body and is known to react nonenzymatically with α-dicarbonyl compounds. This study evaluated the antiglycation potential of creatine against methylglyoxal (MGO), a glucose metabolite that induces carbonyl stress with formation of AGEs in vitro. Further, to elucidate the mechanism of the cytoprotective action of creatine, its effect on the accumulation of carbonyl proteins in the cells and the MGO-induced cellular damage were investigated using neuroblastoma cells. The results revealed that creatine significantly inhibits protein carbonylation by directly reacting with MGO, and creatine added to the culture medium suppressed MGO-derived carbonylation of intracellular proteins and exerted a protective effect on MGO-induced cytotoxicity. These findings suggest that endogenous and supplemented creatine may contribute to the attenuation of carbonyl stress in vivo. [ABSTRACT FROM AUTHOR]

Endometriosis, a chronic inflammatory disease, significantly impairs the quality of life of women in their reproductive years; however, its pathogenesis remains poorly understood. The accumulation of retrograde menstruation and recurrent bleeding fosters a high‐iron environment in ectopic lesions, triggering ferroptosis in ectopic endometrial stromal cells (EESCs), thereby hindering the establishment of endometriosis. However, abnormal EESCs demonstrate resistance to ferroptosis in high‐iron environments, promoting the progression of this disease. Here, novel findings on the accumulation of creatine, derived from endogenous synthesis, in both peritoneal fluid and EESCs of patients with endometriosis are presented. Creatine supplementation reduces cellular iron concentrations, mitigating oxidative stress and lipid peroxidation, thereby enhancing cell viability and preventing ferroptosis under high‐iron conditions. Utilizing the drug affinity–responsive target stabilization (DARTS) assay, prion protein (PrP) as a potential creatine‐sensing protein is identified. Mechanistically, creatine binds to the active site of PrP, inhibits the conversion of trivalent iron to divalent iron, and decreases iron uptake, promoting the tolerance of EESCs to ferroptosis. This interaction contributes to the development of endometriosis. The novel association between creatine and ferroptosis provides valuable insights into the role of creatine in endometriosis progression and highlights its potential as a therapeutic target for endometriosis. [ABSTRACT FROM AUTHOR]

The main objective of this pilot study was to compare the effects of short‐term supplementation with a mixture containing creatine and guanidinoacetic acid (GAA) versus creatine alone on body composition indices in men and women. Twenty‐three apparently healthy young adults (mean age: 21.4 ± 0.6 years; 10 females) were randomly assigned to receive either a mixture (consisting of 2 g of creatine monohydrate and 2 g of GAA) or an equimolar amount of creatine monohydrate in a pretest–posttest control group experimental crossover design. After the intervention period, participants entered a 2‐week washout phase to minimize any residual effects of the treatment. Body composition was assessed using a multifrequency bioelectrical impedance analysis at baseline (preadministration) and at the 7‐day follow‐up (postadministration). A significant interaction effect was found for extracellular mass (p = 0.009), with creatine–GAA outperforming creatine in augmenting extracellular mass across the whole sample. In the male subsample, creatine was superior to the mixture in increasing intracellular water (p = 0.049), whereas the mixture increased extracellular mass, contrasting with the reduction observed with creatine alone (p = 0.008). No significant differences between interventions were reported in the female subsample (p > 0.05), indicating that adding GAA to creatine may produce unique, sex‐specific effects on body composition. Further studies are needed to validate our findings across different demographic cohorts and various interventional regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: Creatine is a metabolite that animals use to store energy within tissues. Animals, including cattle, can synthesize creatine by first generating guanidinoacetic acid from the amino acids glycine and arginine, followed by conversion of guanidinoacetic acid to creatine. In some situations, the body's production of creatine is not adequate to support maximal growth. We examined the supplementation of guanidinoacetic acid to calves fed milk replacer to determine if growth performance would be enhanced. Supplementation of guanidinoacetic acid tended to improve the growth of the calves, which may suggest that milk replacer alone was not sufficient to supply adequate amounts of creatine through the combination of diet and endogenous production in the body. Thus, dietary supplementation with guanidinoacetic acid may be a feasible means of improving growth in calves fed diets containing inadequate amounts of creatine. Guanidinoacetic acid (GAA) is the direct precursor to creatine, which serves as an energy reserve mechanism in the body. We evaluated the effects of GAA supplementation on the growth performance of calves fed milk replacer. Forty-five Holstein–Angus steer calves (40.9 kg, approximately 1 week old) were assigned to 1 of 3 treatments to assess growth performance and data from 41 calves were analyzed. Treatments were provided in the milk replacer for 42 d and included 0, 1, or 2 g GAA/d. Calves were fed 2.84 L milk replacer twice daily with ad libitum access to starter feed and water. Treatments ended on day 42 prior to a 17-day weaning period. Supplementation of GAA increased (p < 0.01) plasma concentrations of GAA (0.42, 0.51, and 0.67 mg/L for 0, 1, and 2 g GAA/d, respectively) and creatine (18.7, 22.1, and 24.4 mg/L for 0, 1, and 2 g GAA/d, respectively). Bodyweight tended to linearly increase (p = 0.09) with increasing GAA on d 59 (91.2, 98.3, and 98.6 kg for 0, 1, and 2 g GAA/d, respectively). Daily gains from day 0 to 59 tended to increase with GAA provision (p = 0.09; 0.86, 0.97, and 0.98 kg/d for 0, 1, and 2 g GAA/d, respectively). Starter feed dry matter intake tended to linearly increase (p = 0.06) with GAA supplementation (0.201, 0.278, and 0.286 kg/d for 0, 1, and 2 g GAA/d, respectively). Treatments providing 1 and 2 g GAA/d affected performance similarly. No differences among treatments were observed for health (respiratory and fecal) scores during the application of treatments or during the subsequent weaning period. The inclusion of GAA in milk replacer tended to increase the gain of calves, and this was associated with elevated starter feed intake. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming. Here, we applied spatial metabolomics to achieve high-throughput, in situ identification of metabolites within the liver metastases of AML mice. Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics. This study showed a downregulation in arginine's contribution to polyamine biosynthesis and urea cycle, coupled with an upregulation of the creatine metabolism. The upregulation of creatine synthetases Gatm and Gamt, as well as the creatine transporter Slc6a8, resulted in a marked accumulation of creatine within tumor foci. This process further enhances oxidative phosphorylation and glycolysis of leukemia cells, thereby boosting ATP production to foster proliferation and infiltration. Importantly, we discovered that inhibiting Slc6a8 can counter these detrimental effects, offering a new strategy for treating AML by targeting metabolic pathways. The creatine pathway significantly upregulated in the metabolic reprogramming of AML mice, driven by both biosynthesis and the creatine transporter Slc6a8. The elevated creatine supports metastatic leukemia cell survival by enhancing OXPHOS and glycolysis. The Slc6a8 inhibitor ompenaclid could effectively inhibit AML cell proliferation and infiltration both in vitro and in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

Although physical exercise is extremely important for health and a good lifestyle, it can trigger oxidative stress, inflammation, and muscle fatigue. The aim of this study was to determine changes in dental tissues and the mandible created by creatines monohydrate (CrM) supplementation together with low and high‐intensity exercise (HIE). The study material comprised Balb/c male mices, which were separated into two groups for the application of low and HIE on a running band. CrM supplement was administered together with the exercise. At the end of the experiment period, dental tissue samples were surgically removed and examined histopathologically and immunohistochemically (TNF‐α and lL‐1β).As a result of the histopathological examinations, in the pulp, oedema, vascular congestion, and capillary dilatation were seen to be statistically significantly increased in the Group 3 mices that performed HIE compared to the control group (p = 0.001, p = 0.003, p = 0.001, respectively). A statistically significant increase was observed in periodontal ligament (PDL) degeneration, and disruption of the continuity and separation of collagen fibers in Group 3 compared to the control group (p = 0.001). In the immunohistochemical examination, TNF‐α and IL‐1β positivity was observed in Group 3, and this was significantly increased compared to the control group (p = 0.001, p = 0.000).Exposure of the mices to low and HIE caused histological and immunohistochemical changes in dental pulp and PDL, and it was determined that the use of CrM could have a protective effect against these changes. Research Highlights: The results of this study showed negative effects of HIE in the dental pulp and PDL, which play an important role in dental health.CrM was seen to be effective in preventing these negative effects. [ABSTRACT FROM AUTHOR]

Background: This study examines whether creatine supplementation combined with strength training mitigates muscle mass loss in women during early rehabilitation post-bariatric surgery, as its effectiveness remains untested in this context. Methods: Fifteen women (37.8 ± 9.6 years; BMI, 38.8 ± 5.6 kg/m2) completed the intervention (creatine group = 7; placebo group = 8). Both groups followed a strength training program three times a week for 8 weeks. The dosage for both the creatine and placebo was 8 g prior to each exercise session. Body weight, skeletal muscle mass, fat mass, handgrip strength, and physical activity levels were measured before and after the intervention. Results: The creatine group showed a reduction of 9.5 ± 1.5 kg in body weight, with a 0.72 ± 0.6 kg decrease in muscle mass and an 8.64 ± 1.2 kg reduction in fat mass. The placebo group had a reduction of 9.6 ± 3.5 kg in body weight, with a 0.6 ± 1.2 kg decrease in muscle mass and an 8.88 ± 3.2 kg reduction in fat mass, without significant differences between groups (p > 0.05). Conclusion: The pre-session strength exercise training creatine supplementation is not superior to placebo regarding body weight and fat mass losses and the attenuation of muscle mass loss during the first weeks of rehabilitation following bariatric surgery. [ABSTRACT FROM AUTHOR]

Background: Severe trauma is the leading cause of disability and mortality in the patients under 35 years of age. Surgical site infections (SSI) represent a significant complication in this patient population. However, they are often inadequately investigated, potentially impacting the quality of patient outcomes. The aim of this study was to investigate the epidemiology of SSI and risk factors in severe trauma patients. Methods: We conducted a multicenter retrospective cohort study screening the severe trauma patients (STP) admitted to two intensive care units of an academic institution in Marseille between years2018 and 2019. Those who underwent orthopedic or spinal surgery within 5 days after admission were included and classified into two groups according to the occurrence of SSI (defined by the Centers for Disease Control (CDC) international diagnostic criteria) or not. Our secondary goal was to evaluate STP survival at 48 months, risk factors for SSI and microbiological features of SSI. Results: Forty-seven (23%) out of 207 STP developed an SSI. Mortality at 48-months did not differ between SSI and non-SSI patients (12.7% vs. 10.0%; p = 0.59). The fractures of 22 (47%) severe trauma patients with SSI were classified as Cauchoix 3 grade and 18 (38%) SSI were associated with the need for external fixators. Thirty (64%) severe trauma patients with SSI had polymicrobial infection, including 34 (72%) due to Gram-positive cocci. Empirical antibiotic therapy was effective in 31 (66%) cases. Multivariate analysis revealed that risk factors such as low hemoglobin, arterial oxygenation levels, hyperlactatemia, high serum creatinine and glycemia, and Cauchoix 3 grade on the day of surgery were associated with SSI in severe trauma patients. The generated predictive model showed a good prognosis performance with an AUC of 0.80 [0.73–0.88] and a high NPV of 95.9 [88.6–98.5] %. Conclusions: Our study found a high rate of SSI in severe trauma patients, although SSI was not associated with 48-month mortality. Several modifiable risk factors for SSI may be effectively managed through enhanced perioperative monitoring and the implementation of a patient blood management strategy. [ABSTRACT FROM AUTHOR]

Value-based care (VBC) aims to improve patient health outcomes relative to the cost of care by shifting from traditional fee-for-service models to patient-centered, outcome-driven approaches. This framework is particularly important in nephrology, where high costs associated with chronic kidney disease (CKD) and end stage kidney disease have prompted the adoption of new care models. Key programs such as the Comprehensive End-Stage Renal Disease Care Model and the Kidney Care Choices program have introduced multidisciplinary teams and early-stage CKD interventions to improve patient outcomes and reduce costs. This article highlights the essential role of interdisciplinary collaboration in VBC, with registered nurses, nurse practitioners, pharmacists, social workers, dietitians, and physicians coordinating care to address clinical and non-clinical needs. Case studies demonstrate the effectiveness of coordinated efforts in medication management, patient education, and addressing social determinants of health. These examples underscore the potential for VBC to significantly improve patient outcomes in kidney care while addressing health care inequities and reducing overall costs. Findings emphasize the importance of early interventions, interdisciplinary teamwork, and targeted support for patients with CKD in achieving VBC outcomes. [ABSTRACT FROM AUTHOR]

Aims Widespread brain metabolite abnormalities in those with alcohol use disorder (AUD) were reported in numerous studies, but the effects of the pro-atherogenic conditions of hypertension, type 2 diabetes mellitus, hepatitis C seropositivity, and hyperlipidemia on metabolite levels were not considered. These conditions were associated with brain metabolite abnormalities in those without AUD. We predicted treatment-seeking individuals with AUD and pro-atherogenic conditions (Atherogenic+) demonstrate lower regional metabolite markers of neuronal viability [N-acetylaspartate (NAA)] and cell membrane turnover/synthesis [choline-containing compounds (Cho)], compared with those with AUD without pro-atherogenic conditions (Atherogenic−) and healthy controls (CON). Methods Atherogenic+ (n = 59) and Atherogenic− (n = 51) and CON (n = 49) completed a 1.5 T proton magnetic resonance spectroscopic imaging study. Groups were compared on NAA, Cho, total creatine, and myoinositol in cortical gray matter (GM), white matter (WM), and select subcortical regions. Results Atherogenic+ had lower frontal GM and temporal WM NAA than CON. Atherogenic+ showed lower parietal GM, frontal, parietal and occipital WM and lenticular nuclei NAA level than Atherogenic− and CON. Atherogenic− showed lower frontal GM and WM NAA than CON. Atherogenic+ had lower Cho level than CON in the frontal GM, parietal WM, and thalamus. Atherogenic+ showed lower frontal WM and cerebellar vermis Cho than Atherogenic− and CON. Conclusions Findings suggest proatherogenic conditions in those with AUD were associated with increased compromise of neuronal integrity and cell membrane turnover/synthesis. The greater metabolite abnormalities observed in Atherogenic+ may relate to increased oxidative stress-related compromise of neuronal and glial cell structure and/or impaired arterial vasoreactivity/lumen viability. [ABSTRACT FROM AUTHOR]

Simple Summary: Guanidinoacetic acid (GAA) is a natural derivative of amino acids. They are acted upon by enzymes in the liver and transformed into essential components of the energy metabolism of muscle and nervous tissue. Although the animal synthesizes creatine, the amount is less than necessary for high growth rates, according to researchers. GAA consumed by cattle reduces fat between muscle fibers and serum cholesterol. It has a mild but positive effect on the fatty acid profile of meat—i.e., it increases myristoleic, linoleic, and arachidonic acids. We also concluded that GAA consumption increases the amount of volatile fatty acids in the rumen, especially acetic, propionic, and butyric acid. We draw attention to the acetic acid related to lipid synthesis. With the increase in population, it is increasingly necessary to produce food more efficiently. This has expanded the market for additives, which are products that directly (nutritional effect) or indirectly (effect on animal health) favor productivity. Guanidinoacetic acid (GAA) is a natural precursor of creatine. It acts as an energy reserve in skeletal muscle. In addition to being a compound with more significant bioavailability, it is more thermally stable and less expensive than creatine. Therefore, this study aimed to determine whether adding GAA to the cattle diet would alter the meat's composition and fatty acid profile. We used 24 Holstein cattle males (409 ± 5.6 kg), approximately 15 months old, and separated them into four homogeneous groups, one being the control group and three groups with various dosages of GAA in the diets (3.3; 6.6, and 9.9 g/animal/day), for an experimental period of 60 days. Blood, rumen fluid, and animal weighing were performed at three points (days 1, 30, and 60), and daily feed consumption was measured. Steers fed with GAA (9.9 g/d) showed a 16.9% increase in average daily gain (ADG) compared to the control group. These same animals (T-9.9 group) fed with GAA showed a 20% increase in fed efficiency compared to the control group. Lower leukocyte, lymphocyte, and granulocyte counts and lower cholesterol levels were observed in animals that consumed 6.6 g and 9.9 g/d GAA compared to the control group. Animals from the T-6.6 and T-9.9 groups showed 30% and 27.6% reduced bacterial activity in the rumen compared to the control group, respectively. Steers from the T-6.6 and T-9.9 groups fed with GAA showed a 20% and 37% increase in short-chain fatty acids (SCFAs) compared to the control group, respectively. A higher concentration of acetic, propionic, and butyric acids in the ruminal fluid of cattle T-9.9 group was observed at day 60. The two highest doses of GAA showed lower fat levels in the meat, just as the cattle that received 9.9 g/d showed higher levels of total polyunsaturated fatty acids. Complementary data results draw attention to the dose of 9.9 g/d GAA in cattle diets, as anti-inflammatory action can be seen and combined with a higher concentration of SCFAs, consequently increases weight gain. We concluded that consuming this GAA increases the concentration of some unsaturated fatty acids (omegas) in the meat, which adds quality to the product for the consumer. [ABSTRACT FROM AUTHOR]

Summary: Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. Purpose: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. Methods: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. Results: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. Conclusion: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Relaxation correction is an integral step in quantifying brain metabolite concentrations measured by in vivo magnetic resonance spectroscopy (MRS). While most quantification routines assume constant T1 relaxation across age, it is possible that aging alters T1 relaxation rates, as is seen for T2 relaxation. Here, we investigate the age dependence of metabolite T1 relaxation times at 3 T in both gray‐ and white‐matter‐rich voxels using publicly available metabolite and metabolite‐nulled (single inversion recovery TI = 600 ms) spectra acquired at 3 T using Point RESolved Spectroscopy (PRESS) localization. Data were acquired from voxels in the posterior cingulate cortex (PCC) and centrum semiovale (CSO) in 102 healthy volunteers across 5 decades of life (aged 20–69 years). All spectra were analyzed in Osprey v.2.4.0. To estimate T1 relaxation times for total N‐acetyl aspartate at 2.0 ppm (tNAA2.0) and total creatine at 3.0 ppm (tCr3.0), the ratio of modeled metabolite residual amplitudes in the metabolite‐nulled spectrum to the full metabolite signal was calculated using the single‐inversion‐recovery signal equation. Correlations between T1 and subject age were evaluated. Spearman correlations revealed that estimated T1 relaxation times of tNAA2.0 (rs = −0.27; p < 0.006) and tCr3.0 (rs = −0.40; p < 0.001) decreased significantly with age in white‐matter‐rich CSO, and less steeply for tNAA2.0 (rs = −0.228; p = 0.005) and (not significantly for) tCr3.0 (rs = −0.13; p = 0.196) in graymatter‐rich PCC. The analysis harnessed a large publicly available cross‐sectional dataset to test an important hypothesis, that metabolite T1 relaxation times change with age. This preliminary study stresses the importance of further work to measure age‐normed metabolite T1 relaxation times for accurate quantification of metabolite levels in studies of aging. [ABSTRACT FROM AUTHOR]

Purpose: Demonstrate the feasibility and evaluate the performance of single‐shot diffusion trace‐weighted radial echo planar spectroscopic imaging (Trace DW‐REPSI) for quantifying the trace ADC in phantom and in vivo using a 3T clinical scanner. Theory and Methods: Trace DW‐REPSI datasets were acquired in 10 phantom and 10 healthy volunteers, with a maximum b‐value of 1601 s/mm2 and diffusion time of 10.75 ms. The self‐navigation properties of radial acquisitions were used for corrections of shot‐to‐shot phase and frequency shift fluctuations of the raw data. In vivo trace ADCs of total NAA (tNAA), total creatine (tCr), and total choline (tCho) extrapolated to pure gray and white matter fractions were compared, as well as trace ADCs estimated in voxels within white or gray matter‐dominant regions. Results: Trace ADCs in phantom show excellent agreement with reported values, and in vivo ADCs agree well with the expected differences between gray and white matter. For tNAA, tCr, and tCho, the trace ADCs extrapolated to pure gray and white matter ranged from 0.18–0.27 and 0.26–0.38 μm2/ms, respectively. In sets of gray and white matter‐dominant voxels, the values ranged from 0.21 to 0.27 and 0.24 to 0.31 μm2/ms, respectively. The overestimated trace ADCs from this sequence can be attributed to the short diffusion time. Conclusion: This study presents the first demonstration of the single‐shot diffusion trace‐weighted spectroscopic imaging sequence using radial echo planar trajectories. The Trace DW‐REPSI sequence could provide an estimate of the trace ADC in a much shorter scan time compared to conventional approaches that require three separate measurements. [ABSTRACT FROM AUTHOR]

Abstract Background Although recent studies have increasingly focused on examining the potential benefits of creatine supplementation to improve performance in swimming events, the impact of creatine supplementation on swimming performance remains a topic of debate and controversy. A comprehensive meta-analytical review was undertaken to evaluate the effects of creatine supplementation on the performance, physiological response, and body composition among swimmers. Methods The research methodology adhered strictly to the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was conducted across six databases (Cochrane Library, Web of Science, Scopus, Embase, PubMed, and SPORTDiscus) until March 23, 2024. Eligible studies that investigated the impact of creatine supplementation on swimming time, physiological parameters, and body composition in swimmers were included. For the meta-analysis, a random-effects model was employed to determine the collective effect and assess variations across distinct subgroups defined by swimming time, physiological metrics, and body composition. Meta-regression analysis was conducted on datasets comprising ten or more studies. Standardized mean differences (SMD) along with their corresponding 95% confidence intervals (CI) were calculated. To evaluate the methodological rigor of the included studies, the Physiotherapy Evidence Database (PEDro) scale was utilized. Results The systematic review included seventeen studies with a total of 361 subjects. No significant differences were observed in the overall effect during single sprint swimming (SMD: -0.05, 95% CI: -0.26, 0.15; p = 0.61), repeated interval swimming (SMD: -0.11; 95% CI: -0.46, 0.25; p = 0.56), physiological response (SMD: 0.04, 95% CI: -0.16, 0.23; p = 0.71), and body composition (SMD: 0.18; 95% CI: -0.05, 0.41; p = 0.12) between creatine and placebo groups. Conclusions Creatine supplementation exhibited ineffectiveness in enhancing the performance, physiological response, and body composition among swimmers.

Acute myeloid leukemia (AML) is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming. Here, we applied spatial metabolomics to achieve high-throughput, in situ identification of metabolites within the liver metastases of AML mice. Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics. This study showed a downregulation in arginine's contribution to polyamine biosynthesis and urea cycle, coupled with an upregulation of the creatine metabolism. The upregulation of creatine synthetases Gatm and Gamt, as well as the creatine transporter Slc6a8, resulted in a marked accumulation of creatine within tumor foci. This process further enhances oxidative phosphorylation and glycolysis of leukemia cells, thereby boosting ATP production to foster proliferation and infiltration. Importantly, we discovered that inhibiting Slc6a8 can counter these detrimental effects, offering a new strategy for treating AML by targeting metabolic pathways.

Abstract Autosomal dominant Fanconi syndrome due to a GATM variant (GATM‐FS), causes accumulation of misfolded arginine‐glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM‐FS presents during childhood and progresses to end‐stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known GATM variant and the effect of creatine supplementation in kidney organoids. Plasma and urine metabolites were measured by mass spectrometry. Brain creatine was assessed by magnetic resonance spectroscopy (MRS). Guanidinoacetate (GAA) synthesis by the AGAT mutant was measured in patient‐derived immortalized lymphocytes using stable isotopes of arginine and glycine. The effect of creatine on GATM expression was assessed in human kidney cells and organoids. Several family members from two unrelated families were diagnosed with Fanconi syndrome and had the c.1022C>T (p. P341L) variant in GATM. Two affected individuals in both families had moderately reduced plasma GAA levels. In comparison to wild‐type cells, GAA synthesis by patient‐derived GATMP341L+/− lymphoblastoid cell lines (LCL) was reduced, but not absent as in GATM cells from a patient with creatine deficiency syndrome. In vitro studies on human kidney organoids revealed reduced AGAT expression after treatment with creatine. Finally, we showed in one patient that creatine supplementation (5 g daily) substantially increased plasma creatine levels. We report low plasma and urine GAA in patients with autosomal dominant GATM‐FS and show that creatine downregulates AGAT in human kidney cells.

Purpose: Several preliminary studies suggest dietary guanidinoacetic acid (GAA) might impact methyl group availability and/or methylation biomarkers, fueling ongoing debates. This study aimed to explore the relationship between dietary GAA intake and plasma indicators of the methylation cycle in individuals aged one year and older, using data from the 2001–2002 National Health and Nutrition Examination Survey (NHANES). Methods: Dietary information was obtained from individuals who completed a 24-hour Dietary Recall, with total daily intake of GAA calculated by aggregating all relevant food items. Relevant variables related to the methylation cycle, such as red blood cell (RBC) folate and serum folate, vitamin B12, total homocysteine (tHCy), and methylmalonic acid (MMA), were identified from the NHANES 2001–2002 laboratory assessments. Results: A total of 9,115 individuals (51.3% females) were included in the final analysis. Linear regression unveiled a significant association between higher GAA intake and diminished RBC folate (p < 0.001), serum folate (p < 0.001), and MMA levels (p = 0.007). It also revealed an elevation in tHCy levels with increased GAA intake (p < 0.001). These associations remained significant even after adjusting for demographic variables and dietary factors pertinent to the methylation cycle (p < 0.05). Conclusion: Our findings suggest that dietary exposure to GAA (resulting in conversion to creatine) could be considered a nutritional factor associated with the consumption of methyl groups in the general population. [ABSTRACT FROM AUTHOR]

Background: Creatine, a naturally occurring compound plays a crucial role in cellular energy metabolism, particularly in tissues with high energy demands like muscles and the brain. Beyond its well-established role in physical performance enhancement, recent research has revealed its potential benefits for cognitive functions and mood regulation. This review paper aims to comprehensively analyze the existing literature on creatine supplementation's effects on cognitive functions and mood. State of Knowledge: Findings suggest that creatine supplementation enhances memory, attention, and executive functions, especially under conditions of stress or sleep deprivation. Moreover, it exhibits mood-stabilizing effects, potentially offering relief for symptoms of depression and fatigue. Creatine's ability to augment brain energy metabolism, alongside its neuroprotective properties, underlies its cognitive and mood-enhancing effects. While generally safe, caution is advised, particularly in populations with kidney diseases or those using medications affecting kidney function. Summary: Creatine emerges as a promising adjunct therapy for enhancing cognitive functions and promoting emotional well-being beyond its traditional role in physical performance. The review underscores the need for further research to elucidate the precise mechanisms of creatine's effects and explore its synergistic potential with other cognitive-enhancing supplements. [ABSTRACT FROM AUTHOR]

Purpose: To implement rosette readout trajectories with compressed sensing reconstruction for fast and motion‐robust CEST and magnetization transfer contrast imaging with inherent correction of B0 inhomogeneity. Methods: A pulse sequence was developed for fast saturation transfer imaging using a stack of rosette trajectories with a higher sampling density near the k‐space center. Each rosette lobe was segmented into two halves to generate dual‐echo images. B0 inhomogeneities were estimated using the phase difference between the images and corrected subsequently. The rosette‐based imaging was evaluated in comparison to a fully sampled Cartesian trajectory and demonstrated on CEST phantoms (creatine solutions and egg white) and healthy volunteers at 3 T. Results: Compared with the conventional Cartesian acquisition, compressed sensing reconstructed rosette images provided image quality with overall higher contrast‐to‐noise ratio and significantly faster readout time. Accurate B0 map estimation was achieved from the rosette acquisition with a negligible bias of 0.01 Hz between the rosette and dual‐echo Cartesian gradient echo B0 maps, using the latter as ground truth. The water‐saturation spectra (Z‐spectra) and amide proton transfer weighted signals obtained from the rosette‐based sequence were well preserved compared with the fully sampled data, both in the phantom and human studies. Conclusions: Fast, motion‐robust, and inherent B0‐corrected CEST and magnetization transfer contrast imaging using rosette trajectories could improve subject comfort and compliance, contrast‐to‐noise ratio, and provide inherent B0 homogeneity information. This work is expected to significantly accelerate the translation of CEST‐MRI into a robust, clinically viable approach. [ABSTRACT FROM AUTHOR]

Abstract Maintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research.

Abstract Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest l-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

Introduction: Some papers describe the presence of creatine in plants, based on a singlet signal at 3.02-3.05 ppm in the 1H NMR spectra. Although is there creatine in plants? Therefore, to answer this question, a comprehensive NMR investigation has been performed aiming the unambiguous assignment of the compound responsible for that signal. Objective: Determine whether the compound behind the signal at 3.05 ppm is truly creatine or if it was just a misassignment, instead. Methods: Samples of leaves and cherries from Eugenia uniflora in their natural swollen state were submitted to HR-MAS NMR analysis. Results: It was found that the signal at 3.05 ppm was misassigned to creatine. The exhaustive NMR investigation revealed that the signal is related to the amino acid 4-hydroxy-N-methyl proline, instead. Conclusion: The comprehensive NMR investigation revealed that there is no creatine in plants, it was just a misassignment. [ABSTRACT FROM AUTHOR]

AbstractDoxorubicin (Dox) is an effective and commonly used anticancer drug; however, it leads to several side effects including cardiotoxicity which contributes to poor quality of life for cancer patients. Creatine (Cr) is a promising intervention to alleviate Dox-induced cardiotoxicity. This study aimed to examine the effects of Cr beforeDox on cardiac mitochondrial creatine kinase (MtCK). Male rats were randomly assigned to one of two 4-week Cr feeding interventions (standard Cr diet or Cr loading diet) or a control diet (Con, n = 20). Rats in the standard Cr diet (Cr1, n = 20) were fed 2% Cr for 4-weeks. Rats in the Cr loading diet (Cr2, n = 20) were fed 4% Cr for 1-week followed by 2% Cr for 3-weeks. After 4-weeks, rats received either a bolus injection of 15 mg/kg Dox or a placebo saline injection (Sal). Five days post-injections left ventricle (LV) was excised and analyzed for MtCK expression using Western blot and ELISA. A significant drug effect was observed for LV mass (p < 0.05), post hoc testing revealed LV mass of Con + Dox and Cr2 + Dox was significantly lower than Con + Sal (p < 0.05). A significant drug effect was observed for MtCK (p = 0.03) through Western blot. A significant drug effect (p = 0.03) and interaction (p = 0.02) was observed for MtCK using ELISA. Post hoc testing revealed that Cr2 + Dox had significantly higher MtCK than Cr1 + Sal and Cr2 + Sal. Data suggest that a reduction in LV mass and MtCK may contribute to Dox-induced cardiotoxicity, and Cr supplementation may play a potential role in mitigating cardiotoxicity by preserving mitochondrial CK. [ABSTRACT FROM AUTHOR]

Epilepsy can be caused by a variety of causes, such as inborn errors of metabolism, organic acid disorders are the most significant type of metabolic disorders that cause seizures. The clinical manifestations of these diseases are generally nonspecific, and the types of seizures are different. Screening for multisystem clinical symptoms and identifying the underlying etiology are crucial for early treatment of epileptic seizures. This article provides a comprehensive summary of the pathogenesis, clinical features, diagnosis and treatment of epilepsy associated with organic acid metabolism disorders. Furthermore, relevant literature has also been reviewed to assist clinicians in the diagnosis of cases characterized by the coexistence of multisystemic symptoms and epileptic manifestations. [ABSTRACT FROM AUTHOR]

Introduction Creatine, a supplement popular especially among athletes, is gaining increasive attention from scientists worldwide due to its potential health benefits, among other things, in the context of its anti-cancer application. Materials and methods The following review of studies is based on scientific articles from recent years available in the PubMed and Google Scholar databases. Key search terms included: "creatine", "creatine supplementation", "creatine in sports", "supplementation in sports", "creatine in cancer”. Results The literature review unequivocally demonstrates the beneficial impact of creatine supplementation on numerous health and athletic aspects. Creatine has been observed to have a positive effect on selected aspects of cancer treatment, such as reducing tumor mass, complementing the action of commonly used anticancer drugs, and slowing down the wasting associated with cancer diseases. Conclusion The promising results of the cited studies indicate that further research into creatine supplementation and its mechanisms of action is necessary. There is a need for further research on the positive impact of creatine supplementation in the treatment of cancer diseases. The significant potential of creatine supplementation may enable its inclusion in clinical practice in the future and the development of an effective therapeutic strategy based on it in the treatment of cancer diseases. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a prevalent psychiatric disorder that affects 1% of the global population. Schizophrenia frequently begins in late adolescence or early adulthood, causing significant educational, social, and economic costs for people and society. Functional neuroimaging research on schizophrenia physiopathology has been beneficial. Arterial spin labelling (ASL) is one of functional magnetic resonance imaging (fMRI) technologies that assess brain function without radiation. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Arterial spin labelling (ASL) is one of the functional magnetic resonance imaging (fMRI) technologies that assess the brain function without radiation hazards. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Many publications were performed on role of different advanced MRI techniques in schizophrenia, but our study insisted on the added value of combined ASL and MRS over the conventional MRI in schizophrenic Egyptian population sample. Aim of the work: The purpose of this work was to evaluate the added value of combined ASL-perfusion MRI and MRS in schizophrenic patients. Methods: This prospective case–control study was carried out on two groups: First group was 30 patients who were diagnosed clinically as schizophrenic patients, and second group was 20 healthy volunteers as a control group for comparison in the period from August 2021 till July 2022. Results: The majority of newly diagnosed cases had significant higher positive symptoms than chronic cases. According to arterial spin labelling (ASL) data, rCBF was noticed to be reduced in anterior cingulate, frontal lobe, and parietal lobe of both patients' subgroups but more significant in chronically ill patients. Convergent results of decreased rCBF were also found in the parietal lobe and occipital lobe. Magnetic resonance spectroscopic analysis showed that NAA was decreased in the anterior cingulate cortex, thalami and basal ganglia of the newly diagnosed cases more than chronic cases. The ASL-MRI perfusion accurately detected the hypo-perfusion of different brain regions with sensitivity 100%, specificity 66.67%, positive predictive value 96.43%, negative predictive value 100%, and accuracy 96.67%, while MR spectroscopy showed sensitivity 100%, specificity 33.33%, positive predictive value 93.10%, negative predictive value 100%, and accuracy 93.33% in evaluation of changes of brain metabolites. Conclusion: ASL is a promising functional MRI technique that can produce together with MRS quantitative information about the metabolites of different brain regions. The ASL-MRI appears as a reliable non-invasive technique to measure cerebral blood flow and identify decreased rCBF without any contrast administration, and it could be repeatable which helps in early diagnosis as well as follow-up of the progression of the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1,6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. METHODS Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase, CK, high-sensitivity C-reactive protein, alpha-hydroxybutyrate dehydrogenase and cardiac troponin I, the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, intensive care unit and postoperative hospitalization. RESULTS Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, lactate dehydrogenase, CK, cardiac troponin I, alpha-hydroxybutyrate dehydrogenase and high-sensitivity C-reactive protein at T1∼4 were lower in the FDP group than in the NS group (P  <   0.001). Compared with the NS group, the dosage of dopamine administered 1–90 min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P  <   0.001, P  <   0.001 and P  =   0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group (median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm; P  <   0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group (50.3 [12.3] min vs 34.6 [6.9] min; P  <   0.001). CONCLUSIONS The FDP postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation. [ABSTRACT FROM AUTHOR]

Total amount of creatine (Cr) and phosphocreatine, or total creatine (tCr), may have a significant impact on the performance of skeletal muscles. In sports such as bodybuilding, it is popular to take Cr supplements to maintain tCr level. However, no study has explored the quantitative relationship between exercise intensity and the induced change in muscle's tCr. In this well‐controlled study, straight‐leg plantar flexion with specific load and duration was performed by 10 healthy subjects inside an MRI scanner, immediately followed by 1H MR spectroscopy (MRS) for measuring tCr concentration in gastrocnemius. For repeatability assessment, the experiment was repeated for each subject on two different days. Across all the subjects, baseline tCr was 46.6 ± 2.4 mM, ranging from 40.6 to 50.1 mM; with exercise, tCr significantly decreased by 10.9% ± 1.0% with 6‐lb load and 21.0% ± 1.3% with 12‐lb load (p < 0.0001). Between two different days, baseline tCr, percentage decrease induced by exercise with a 6‐lb and 12‐lb load differed by 2.2% ± 2.3%, 11.7% ± 6.0% and 4.9% ± 3.2%, respectively. In conclusion, the proposed protocol of controlled exercise stimulation and MRS acquisition can reproducibly monitor tCr level and its exercise‐induced change in skeletal muscles. The measured tCr level is sensitive to exercise intensity, so can be used to quantitatively assess muscle performance or fatigue. [ABSTRACT FROM AUTHOR]

Background: Older patients with cardiovascular disease (CVD) are highly susceptible to adverse drug reactions due to age-related physiological changes and the presence of multiple comorbidities, polypharmacy, and potentially inappropriate medications (PIMs). Objective: This study aimed to develop a predictive model to identify the use of PIMs in older patients with CVD. Methods: Data from 2012 to 2021 from the Changhua Christian Hospital Clinical Research Database (CCHRD) and the Kaohsiung Medical University Hospital Research Database (KMUHRD) were analyzed. Participants over the age of 65 years with CVD diagnoses were included. The CCHRD data were randomly divided into a training set (80% of the database) and an internal validation set (20% of the database), while the KMUHRD data served as an external validation set. The training set was used to construct the prediction models, and both validation sets were used to validate the proposed models. Results: A total of 48,569 patients were included. Comprehensive data analysis revealed significant associations between the use of PIMs and clinical factors such as total cholesterol, glycated hemoglobin (HbA1c), creatinine, and uric acid levels, as well as the presence of diabetes, hypertension, and cerebrovascular accidents. The predictive models demonstrated moderate power, indicating the importance of these factors in assessing the risk of PIMs. Conclusions: This study developed predictive models that improve understanding of the use of PIMs in older patients with CVD. These models may assist clinicians in making informed decisions regarding medication safety. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP‐induced cardiac damage. Thirty‐six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin‐I, Creatine kinase‐myocardial band (CK‐MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP‐ribose) polymerase‐1 (PARP‐1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme‐linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein‐1 (FSP1), transforming growth factor‐beta‐ 1 (TGF‐β1) and α‐smooth muscle actin (α‐SMA) expressions were determined in heart tissue. The CYP group's troponin‐I, total cholesterol, triglyceride, CK‐MB, ROS, PARP‐1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP‐induced pathological damage, TRPM2, FSP1, TGF‐β1 and α‐SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF‐β1, FSP1 and α‐SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP‐induced cardiac damage. [ABSTRACT FROM AUTHOR]

Background/Objectives: The aim of this study was to evaluate brain metabolism using MR spectroscopy (MRS) after recovery from Coronavirus disease (COVID-19) and to test the impact of disease severity on brain metabolites. Methods: We performed MRS on 81 individuals (45 males, 36 females, aged 40–60), who had normal MRI findings and had recovered from COVID-19, classifying them into mild (17), moderate (36), and severe (28) groups based on disease severity during the acute phase. The study employed two-dimensional spectroscopic imaging above the corpus callosum, focusing on choline (Cho), creatine (Cr), and N-acetylaspartate (NAA). We analyzed Cho/Cr and NAA/Cr ratios as well as absolute concentrations using water as an internal reference. Results: Results indicated that the Cho/Cr ratio was higher with increasing disease severity, while absolute Cho and NAA/Cr ratios showed no significant differences across the groups. Notably, absolute Cr and NAA levels were significantly lower in patients with severe disease. Conclusions: These findings suggest that the severity of COVID-19 during the acute phase is associated with significant changes in brain metabolism, marked by an increase in Cho/Cr ratios and a reduction in Cr and NAA levels, reflecting substantial metabolic alterations post-recovery. [ABSTRACT FROM AUTHOR]

Maintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research. [ABSTRACT FROM AUTHOR]

In this work, the solubility of creatine, creatinine, guanidinoacetic acid and their hydrochlorides in water at atmospheric pressure and in the temperature range T 293.15-313.15 K was determined by the gravimetric method. The thermodynamic parameters of dissolution in water for the mentioned compounds were calculated. The solubility increases significantly by converting the zwitterionic structures of creatine and guanidinoacetic acid into a cationic form, i.e., hydrochloride salt. The effect of increasing solubility is more pronounced for guanidinoacetic acid and decreases with temperature for both compounds. A simple process of transforming the electrically neutral zwitterionic structures into cations represents a good way to increase the solubility in water and bioavailability of biologically active compounds. [ABSTRACT FROM AUTHOR]

Objective: To identify the lifetime prevalence and correlates of appearance- and performance-enhancing drugs and substances (APEDS) use among a national sample of US college and university students. Participants: Student participants from the 2020–2021 Healthy Minds Study (N = 7,401; ages 18–30 years). Methods: Lifetime prevalence of five forms of APEDS was estimated. Modified Poisson regression analyses were conducted to determine the sociodemographic correlates of protein and creatine supplement use. Results: Lifetime protein (23.8%) and creatine (7.7%) supplement use were most common among the sample. Older age within young adulthood, male sex, perceiving oneself to be normal weight or somewhat overweight, any athletics participation, and 2–3 or ≥ 5 h/week of exercise were associated with greater likelihood of lifetime protein and creatine supplement use. Conclusions: Awareness and prevention efforts on the potential harms of APEDS use are needed on campuses, particularly among males and those who participate in athletics and high-frequency exercise. [ABSTRACT FROM AUTHOR]

The use of nutritional supplements can lead to doping risk and no data exist on high school athletes' use of certified third-party tested supplements. A cross-sectional cohort design was developed using an anonymous survey. Descriptive data for supplement use, use of third-party tested supplements, and knowledge in high school athletes were reported. A total of 225 high school athletes, ranging from 14-19 years of age, from a private high school in the western US, were included in the analysis of the results. A total of 94% (n=211) of athletes reported nutritional supplement use within the past year with an average of six (interquartile range: 3-9) individual supplements, ranging from 0-20 supplements per person. Most frequently reported were sports drinks (72%), vitamins (65%), sports bars (60%), protein powder (58%), caffeine (37%, as part of normal beverages, or 13% as a supplement), followed by creatine (23%). A total of 24% claimed to know for sure that all their supplements were third-party tested. In addition, the recognition of third-party testing organization icons was low (46% in supplement users vs. 14% in nonusers). Athletes also scored low in reporting how to find (22%) and how to order (25%) third-party tested supplements. In conclusion, almost all athletes in this study reported the use of multiple nutritional supplements annually. Only one-fourth of the athletes reported consistently using third-party tested supplements. Knowledge of where and how tested supplements could be purchased was limited in this high school athlete population. [ABSTRACT FROM AUTHOR]

The hormonal changes in women influence creatine dynamics, emphasizing its potential importance during menstruation, pregnancy, postpartum, menopause, and postmenopause. Yet, limited research explores creatine's impact on female reproductive health at the population level. Our study investigated the relationship between dietary creatine intake and reproductive health indices in US women using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). We extracted a dataset containing females aged 12 years and above who provided details about their reproductive health and dietary habits. Daily creatine intake was quantified as a relative amount (mg per kg body mass) and did not include creatine from dietary supplements and pharmacological agents. A daily requirement for dietary creatine for healthy women was employed to classify respondents into two separate subpopulations: (1) suboptimal intake of creatine (<13 mg per kg body mass per day) or (2) recommended intake (dietary creatine ≥ 13 mg per kg body mass per day). A total of 4522 female participants from the NHANES study (age 44.5 ± 20.5 years) provided data on their reproductive health and dietary intake. The average daily creatine intake for the group was 10.5 ± 10.8 mg per kg body mass. The odds ratio for having irregular periods in women consuming ≥13 mg of creatine per kg body mass daily (recommended intake) compared to those with suboptimal intake was 0.75 (95% CI, from 0.66 to 0.86), indicating a significant association between higher intake of dietary creatine and lower risk of oligomenorrhea (p <.001). Moreover, women consuming less than 13 mg of creatine per kg body mass faced an increased risk of fetal macrosomia (OR 1.26; p =.04), pelvic infection (OR 1.68; p =.01), hysterectomy (OR 1.42; p <.001), oophorectomy (OR 1.54; p <.001), and receiving hormone replacement therapy (OR 1.26; p =.02). Consuming a creatine‐rich diet has been linked to lower risks of reproductive issues in US women aged 12 and above. Those consuming ≥13 mg of creatine per kg body mass daily showed notably lower risks of irregular menstrual periods, obstetric conditions, and pelvic pathology. Further studies are needed to confirm these potential benefits. [ABSTRACT FROM AUTHOR]

The 1,2‐dicarbonyl compound methylglyoxal (MGO) can react with and thereby impair the function of proteins and DNA, leading to pathophysiological pathways in vivo. However, studies on the bioavailability of dietary MGO and its reactions during digestion have diverging results. Therefore, simulated digestion experiments of MGO, protein, and creatine were performed in the dynamic, in vitro model of the upper gastrointestinal tract (TIM‐1). This multicompartment model continuously adjusts pH values and has realistic gastrointestinal transit times while also removing water and metabolites by dialysis. Samples were analyzed with HPLC‐UV for MGO and HPLC–MS/MS for creatine and glycated amino compounds. MGO reacted with creatine during simulated digestion in TIM‐1 to form the hydroimidazolone MG‐HCr in similar amounts as in a human intervention study. 28%–69% of MGO from the meal were passively absorbed in TIM‐1, depending on the addition of creatine and protein. Simultaneous digestion of MGO with ovalbumin led to the formation of the lysine adduct Nε‐carboxyethyllysine (CEL) and the methylglyoxal‐derived hydroimidazolone of arginine (MG‐H1). The formation of both compounds decreased with added creatine. Hence, glycation compounds are formed during digestion and significantly contribute to other ingested dietary glycation compounds, whose physiological consequences are critically discussed. [ABSTRACT FROM AUTHOR]

Background: The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to promoting growth of young ruminants. This study investigated effects of guanidino acetic acid (GAA) and rumen‐protected betaine (RPB) supplementation on growth, dietary nutrient digestion and GAA metabolism in the small intestine of sheep. Methods: Eighteen healthy Kazakh rams (27.46 ± 0.10 kg of body weight and 3‐month old) were categorized into control, test group I and test group II, which were fed a basal diet, 1500 mg/kg GAA and 1500 mg/kg GAA + 600 mg/kg RPB, respectively. Results: Compared with control group, test group II had increased (p < 0.05) average daily gain, plasma creatine level, ether extract (EE) and phosphorus digestibility on day 30. On day 60, the EE apparent digestibility, jugular venous plasma GAA, GAA content in the duodenal mucosa and GAA content in the jejunal and ileal mucosa of test group II were higher (p < 0.05) than other groups. Transcriptome analysis revealed that the differentially expressed genes (DEGs) involved in the duodenal pathways of oxidative phosphorylation and non‐alcoholic fatty liver disease were significantly altered in test group II versus test group I (p < 0.05). Moreover, in the jejunum, the MAPK signalling pathway, complement and coagulation cascade and B‐cell receptor signalling pathway were significantly enriched, with ATPase, solute carrier transporter protein, DHFR, SI, GCK, ACACA and FASN being the significantly DEGs (p < 0.05). Conclusion: Dietary supplementation of RPB on top of GAA in sheep diets may promote sheep growth and development by improving the body's energy, amino acid, glucose and lipid metabolism capacity. [ABSTRACT FROM AUTHOR]

Creatine is a naturally occurring compound found in muscles that plays a vital role in energy metabolism. It has been shown to have beneficial effects on skeletal muscle function and exercise performance, but recent studies have investigated its potential role in various fields of medicine. The study aimed to analyze accessible literature and illustrate the current state of knowledge on the use of creatine in these settings, as well as make predictions for further research. A link between low creatine concentrations and poorer mental well-being has been proven in the central nervous system. After many studies and insightful conclusions about the molecular mechanisms of action of creatine in the brain and the finding that it acts as a neurotransmitter, creatine began to be successfully studied as an antidepressant - both in monotherapy and as an adjunct to treatment with SSRI drugs. Years of research have shown creatine to act in various, not fully understood mechanisms on the course and recovery of stroke. The use of creatine as an additional treatment in stroke prevention for at-risk groups and rehabilitation of stroke patients seems possible shortly. One of the most important aspects of chronic heart failure is metabolic dysfunction that occurs in cardiomyocytes, including impairment of CR/PCR/ATP shuttle. Multiple studies undertaking the role of creatine supplementation in patients with cardiovascular diseases present various findings. Therefore, creatine appears as a promising substance with supportive effects in the above-mentioned conditions; however, further research is needed to confirm that the benefit outweighs the risks. [ABSTRACT FROM AUTHOR]

Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties. The objective of the study was to evaluate the efficacy of direct fetal creatine supplementation to reduce inflammation and oxidative stress in fetal lungs arising from an in utero proinflammatory stimulus. Fetal lambs (n = 51) were instrumented at 90 days gestation to receive a continuous infusion of creatine monohydrate (6 mg·kg-1 ·h-1) or saline for 17 days. Maternal chorioamnionitis was induced with intra-amniotic lipopolysaccharide (LPS; 1 mg, O55:H6) or saline 7 days before delivery at 110 days gestation. Tissue creatine content was assessed with capillary electrophoresis, and inflammatory markers were analyzed with Luminex Magpix and immunohistochemistry. Oxidative stress was measured as the level of protein thiol oxidation. The effects of LPS and creatine were analyzed using a two-way ANOVA. Fetal creatine supplementation increased lung creatine content by 149% (PCr < 0.0001) and had no adverse effects on lung morphology. LPS-exposed groups showed increased levels of interleukin-8 in the bronchoalveolar lavage (PLPS < 0.0001) and increased levels of CD45 þ leukocytes (PLPS < 0.0001) and MPO þ (PLPS < 0.0001) cells in the lung parenchyma. Creatine supplementation significantly reduced the levels of CD45 þ (PCr = 0.045) and MPO þ cells (PCr = 0.012) in the lungs and reduced thiol oxidation in plasma (PCr < 0.01) and lung tissue (PCr = 0.02). In conclusion, fetal creatine supplementation reduced markers of inflammation and oxidative stress in the fetal lungs arising from chorioamnionitis.NEW & NOTEWORTHY We evaluated the effect of antenatal creatine supplementation to reduce pulmonary inflammation and oxidative stress in the fetal lamb lungs arising from lipopolysaccharide (LPS)-induced chorioamnionitis. Fetal creatine supplementation increased lung creatine content and had no adverse effects on systemic fetal physiology and overall lung architecture. Importantly, fetuses that received creatine had significantly lower levels of inflammation and oxidative stress in the lungs, suggesting an anti-inflammatory and antioxidant benefit of creatine. [ABSTRACT FROM AUTHOR]

Deep vein thrombosis (DVT) is the development of blood clots in the deep veins of the extremities, classically described secondary to periods of inactivity. In some reports, creatine supplementation in the context of dehydration has been demonstrated to increase the likelihood of the development of DVTs in patients who were otherwise healthy. The purpose of this study is to conduct a scoping review of incidences of DVTs related to creatine supplementation and urge future research to investigate the mechanism of this adverse effect. Following the standard PRISMA guidelines for scoping reviews, the authors searched PubMed and Google Scholar using the terms "deep vein thrombosis", "DVT", and "creatine intake or supplementation." All relevant articles were included if they described an association between DVT and creatine supplementation. Once included, each study was qualitatively analyzed for relevant information. Any dispute of the articles for inclusion or exclusion were discussed until consensus was achieved. Four articles were included within this review from the case report and case series literature. While these articles reaffirmed the overall safety of creatine, there is an emphasis on ensuring adequate hydration in those taking this supplement. This should provoke further research into the role that creatine and other exercise supplements might play in provoking deep venous thrombosis. This evidence has the potential to change the advice of healthcare professionals to ensure they stress the importance of adequate hydration with the use of workout supplements. [ABSTRACT FROM AUTHOR]