Variables Associated with 30-Day Mortality in Very Elderly COVID-19 Patients.

Background: Advanced age increases the risk for severe COVID-19. However, the risk factors for mortality from COVID-19 in very elderly patients (≥80-years-old) are unknown. Objective: Investigate the relationship of mortality with the clinical characteristics of very elderly COVID-19 patients. Materials and Methods: Very elderly patients who were hospitalized with COVID-19 from December 3, 2022 to January 1, 2023 were retrospectively examined. Sociodemographic and clinical variables were recorded and survival was recorded after 30 days. Results: We examined 181 patients (median age: 90.84 years; 114 older than 90 years). The median Barthel index was 30.69, and 55.8% of patients had severe or critical COVID-19 pneumonia. Forty-two patients (33.2%) received a high-flow nasal cannula or non-invasive ventilation, and only 4.4% received mechanical ventilation. The overall mortality was 35.9%, and there was no significant difference in mortality for the 80 to 90-year-old group and the over 90-year-old group (37.7% vs 32.8%, P=0.508). A multivariate analysis showed that the Barthel index (OR, 0.975; 95% CI, 0.962-0.989), serum creatinine (SCr) level (OR, 1.003; 95% CI, 1.000-1.006), white blood cell (WBC) count (OR, 1.160; 95% CI, 1.056-1.276), D-dimer level (OR, 1.060; 95% CI, 1.009-1.113), and corticosteroid use (OR, 0.268; 95% CI, 0.124-0.582) were significantly and independently related to 30-day mortality. A binary classification model based on the multivariate analysis had good predictive value (area under the curve, 0.794). Conclusion: Very elderly COVID-19 patients have a high risk for mortality. The Barthel index, SCr, WBC count, D-dimer level, and corticosteroid use were independently associated with mortality.

Relationship Between Sclerostin Levels and Coronary Artery Calcification and Plaque Composition.

OBJECTIVE: The primary function of sclerostin is the regulation of bone metabolism. Research investigating the cardiovascular effects of sclerostin had conflicting results. We aimed to study serum sclerostin levels in coronary artery plaque types. METHODS: Coronary calcium scores of 175 patients were evaluated. Patients with normal coronary arteries and calcium score of greater than zero constituted control (n = 47) and study groups (n = 83), respectively. Patients' plaques were further categorized as non-calcified plaque, calcified plaque, or mixed plaque (n = 45, n = 40, and n = 43, respectively). RESULTS: The study group had increased serum sclerostin levels than that of controls. Moreover, sclerostin levels were significantly higher in patients with calcified or mixed plaques compared to those without plaque or non-calcified plaque (median 248.5, 60.7-790.4) pg/mL and 1085.8 (185.8-3902.2) pg/mL versus 68.7 (34.0-141.3) pg/mL, and 67.7 (48.6-94.9) pg/mL, P < 0.001, respectively). Sclerostin showed a high correlation with coronary calcium scores (r = 0.95, P < 0.001). Serum sclerostin concentration of 106.27 pg/mL had 97.5% sensitivity and 67.4% specificity for the prediction of calcific plaque, whereas the level of 308.55 pg/mL had 95.3% sensitivity and 90.9% specificity for the prediction of mixed plaque. Coronary calcium scores, serum sclerostin, and C-reactive protein levels were significant predictors of 1-year major adverse cardiac events. CONCLUSIONS: Increased serum sclerostin level is a marker of coronary atherosclerosis burden and has a value for the prediction of 1-year major adverse cardiac events.

Evaluation of risk factors associated with first episode febrile seizure.

OBJECTIVE: Febrile convulsion (FC) is one of the most common neurological findings in children. This study was aimed to investigate the difference in laboratory parameters between Febrile Seizure and control groups. PATIENTS AND METHODS: In this study, 169 children admitted to the pediatric emergency department with their first episode of FS and 189 control groups were retrospectively analyzed. The demographic characteristics and laboratory parameters of children were obtained from their files. RESULTS: Upper respiratory tract infection (URTI) was determined the most common disease (81.6%) in the FC group followed by acute gastroenteritis (AGE) (15.4%) and urinary tract infection (UTI) (3%), respectively. Similarly, URTI was detected as the most common disease (81.8%) in control groups. It was determined that there was no statistically significant difference between the two groups in terms of diseases. The leukocyte and neutrophil counts of the children with FC were significantly higher but the mean corpuscular volume of lenfosit and lenfosit/neutrophil ratio was significantly lower than the control groups (p= 0.009, <0.001, 0.001, <0.001, <0.001, respectively). Children with FC had significantly higher blood glucose, urea, creatinine, creatine kinase, alkaline phosphatase and albumin levels compared with the control groups (p<0.001, in all parameters). On the other hand, the potassium, sodium and chlorine levels of the Children with FCs were significantly lower than control groups (p=0.017, <0.001, p <0.001, respectively). CONCLUSIONS: To conclude, febrile patients with high leukocyte counts, high neutrophil counts, and several biochemical parameters should be carefully monitored for FCs due to the increasing seizure risk.

The effect of branched-chain amino acid on muscle damage markers and performance following strenuous exercise: a systematic review and meta-analysis.

This systematic review and meta-analysis determined whether the ergogenic effects of branched-chain amino acids (BCAA) ameliorated markers of muscle damage and performance following strenuous exercise. In total, 25 studies were included, consisting of 479 participants (age 24.3 ± 8.3 years, height 1.73 ± 0.06 m, body mass 70.8 ± 9.5 kg, females 26.3%). These studies were rated as fair to excellent following the PEDro scale. The outcome measures were compared between the BCAA and placebo conditions at 24 and 48 hours following muscle-damaging exercises, using standardised mean differences and associated p-values via forest plots. Our meta-analysis demonstrated significantly lower levels of indirect muscle damage markers (creatine kinase, lactate dehydrogenase and myoglobin) at 48 hours post-exercise (standardised mean difference [SMD] = -0.41; p < 0.05) for the BCAA than placebo conditions, whilst muscle soreness was significant at 24 hours post-exercise (SMD = -0.28 ≤ d ≤ -0.61; p < 0.05) and 48 hours post-exercise (SMD = -0.41 ≤ d≤ -0.92; p < 0.01). However, no significant differences were identified between the BCAA and placebo conditions for muscle performance at 24 or 48 hours post-exercise (SMD = 0.08 ≤ d ≤ 0.21; p > 0.05). Overall, BCAA reduced the level of muscle damage biomarkers and muscle soreness following muscle-damaging exercises. However, the potential benefits of BCAA for muscle performance recovery is questionable and warrants further investigation to determine the practicality of BCAA for ameliorating muscle damage symptoms in diverse populations. PROSPERO registration number: CRD42020191248. Novelty: BCAA reduces the level of creatine kinase and muscle soreness following strenuous exercise with a dose-response relationship. BCAA does not accelerate recovery for muscle performance.

Laboratory Tests in the Patient with Abdominal Pain.

Abdominal pain is one of the most common presenting complaints to the emergency department (ED). More often than not, some degree of laboratory testing is used to narrow the differential diagnosis based on the patient's history and examination. Ordering practices are often guided by evidence, habit, consulting services, and institutional/regional culture. This review highlights relevant laboratory studies that may be ordered in the ED, as well as commentary on indications and diagnostic value of these tests.

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Divergence between serum creatine and cystatin C in estimating glomerular filtration rate of critically ill COVID-19 patients.

BACKGROUND: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. METHODS: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. RESULTS: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m2) was associated with death (HR = 1.939, 95%CI 1.078-3.489, p = 0.027). CONCLUSIONS: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.

Contribution of monocarboxylate transporter 12 to blood supply of creatine on the sinusoidal membrane of the hepatocytes.

Creatine (Cr)/phosphocreatine has the ability to buffer the high-energy phosphate, thereby contributing to intracellular energy homeostasis. As Cr biosynthetic enzyme deficiency is reported to increase susceptibility to colitis under conditions of inflammatory stress, Cr is critical for maintaining intestinal homeostasis under inflammatory stress. Cr is mainly produced in the hepatocytes and then distributed to other organs of the body by the circulatory system. Since monocarboxylate transporter 9 (MCT9) and monocarboxylate transporter 12 (MCT12) have been reported to accept Cr as a substrate, these transporters are proposed as candidates for Cr efflux transporter in the liver. The aim of this study was to elucidate the transport mechanism on Cr supply from the hepatocytes. Immunohistochemical staining of the rat liver sections revealed that both MCT9 and MCT12 were localized on the sinusoidal membrane of the hepatocytes. In the transport studies using Xenopus laevis oocyte expression system, [14C]Cr efflux from MCT9- or MCT12-expressing oocytes was significantly greater than that from water-injected oocytes. [14C]Cr efflux from primary cultured hepatocytes was significantly decreased following MCT12 mRNA knockdown, whereas this efflux was not decreased after mRNA knockdown of MCT9. Based on the extent of MCT12 protein downregulation and Cr efflux after knockdown of MCT12 in primary cultured rat hepatocytes, the contribution ratio of MCT12 in Cr efflux was calculated as 76.4%. Our study suggests that MCT12 substantially contributes to the efflux of Cr at the sinusoidal membrane of the hepatocytes.NEW & NOTEWORTHY Our study is the first to identify the role of monocarboxylate transporter 12 (MCT12) as a transporter of creatine (Cr) in the liver. MCT12 was found to significantly contribute to the efflux of Cr on the sinusoidal membrane of the hepatocytes. Since hepatocytes are known to be involved in creatine biosynthesis, the present findings can be beneficial for the regulation of Cr biosynthesis and supply.

Plasma metabolomic profiles as affected by diet and stress in Spanish goats.

The effects of high-condensed tannin (CT) diet combined with preslaughter stress have not been studied at the metabolome level in goats. This study was conducted to determine the effects of feeding sericea lespedeza (SL; Lespedeza cuneata), a high-CT legume, and transportation stress on plasma metabolome in goats. Uncastrated male Spanish goats (age = 8 months; BW = 26.0 ± 0.48 kg) were either fed ground 'Serala' SL hay (SER), bermudagrass (Cynodon dactylon) hay (BG), or bermudagrass hay-dewormed goats (BG-DW; Control) at 75% of intake, with a corn-based supplementation (25%) for 8 weeks (n = 12/Diet). At the end of the trial, goats were subjected to one of two stress treatments (ST): transported for 90 min to impose stress (TS) or held in pens (NTS) before slaughtering, in two replicates. Live and carcass weights, and blood samples were collected at 0, 30, 60 and 90 min of transportation or holding time (Time). The data were analyzed using MIXED procedures in SAS and metabolomics data were analyzed using the R software. When measured after ST, SER group had the lowest body weight (P < 0.05) among the three diet groups. Carcass weights were high in the BG-DW, low in SER, and intermediate in BG group. Plasma creatine concentrations decreased over Time (P < 0.01) in the TS goats in all diet groups. Meat crude protein percentages were higher (P < 0.05) in SER (22.5 ± 0.22) and BG-DW (22.3 ± 0.22) groups compared to the BG group (21.6 ± 0.22). At the metabolome level, SER group had the lowest (P < 0.05) glycine, alanine, threonine, taurine, trans-hydroxyproline, methionine, and histidine concentrations and highest (P < 0.01) lysine and citrulline concentrations among the Diet groups. Butyric acid, concentration was higher (P < 0.05) in the SER group compared to BG group. Eight medium- and long-chained acylcarnitines were higher (P < 0.05) in the BG-DW group than SER or BG groups. In general, amino acid levels decreased and acylcarnitine increased with Time (P < 0.05) in all groups. Sericea diet can be beneficial in enhancing stress coping abilities in goats due to elevated butyrate, lysine, and citrulline levels; however, SER resulted in lower energy level in goats compared to BG or BG-DW groups. Fatty acid metabolism is the main energy pathway in all groups during prolonged stress. Inclusion of certain varieties of SL in the diet must be carefully controlled to prevent possible negative effect.

Routine Postoperative Chemistry Panels Are Not Necessary for Most Total Joint Arthroplasty Patients.

BACKGROUND: The routine use of traditional chemistry-7 (chem-7) laboratory tests following total joint arthroplasty (TJA) has been called into question with the advent of short-stay procedures. Our objective was to determine the incidence, risk factors, and clinical interventions associated with inpatient abnormal routine postoperative chem-7 panels. METHODS: From 2015 to 2017, 3,162 patients underwent a total of 3,721 TJA procedures, including primary total hip arthroplasty (THA) (n = 1,939; 52.1%) or primary total knee arthroplasty (TKA) (n = 1,782; 47.9%). Patients underwent routine preoperative and postoperative chem-7 testing. Clinical interventions were identified. With use of mixed-effects multivariate logistic regression, potential risk factors for abnormal chemistry panel values (including preoperative chem-7 results, type of surgery, age, sex, race, comorbidities, American Society of Anesthesiologists [ASA] score, and medications) were analyzed. RESULTS: The rates of abnormal preoperative laboratory results were 3.4% for sodium (Na+), 7.4% for potassium (K+), 15.8% for blood urea nitrogen (BUN), and 26.4% for creatinine (Cr). The incidence of abnormal postoperative results was low for K+ (9.7%) and higher for Na+ (25.6%), BUN (55.6%), and Cr (27.9%). Preoperative abnormal laboratory results were a significant predictor of a postoperative abnormality for Na+ (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.82 to 2.54), K+ (OR = 4.22; 95% CI = 3.03 to 5.88), and Cr (OR = 3.00; 95% CI = 2.45 to 3.68). Bilateral TJA was associated with increased odds of abnormal postoperative Na+ (OR = 1.56; 95% CI = 1.44 to 1.68). Renal disease was associated with increased odds of abnormal postoperative Cr (OR = 15.21; 95% CI = 5.67 to 40.77). Patients taking loop diuretics had increased odds of abnormal postoperative K+ (OR = 2.10; 95% CI = 1.42 to 3.11) and Cr (OR = 2.28; 95% CI = 1.56 to 3.33). Regarding intervention, 6.7% of hypokalemic patients received potassium chloride (KCl) fluid/tablets. Forty percent of hyponatremic patients received sodium chloride (NaCl) fluid/tablets. The electrolyte-related medicine consultation rate was 0.3% (13 of 3,721). CONCLUSIONS: On the basis of our findings, we recommend postoperative chem-7 testing for patients with an abnormal preoperative laboratory result (Na+, K+, BUN, Cr), preexisting renal disease, bilateral TJA, and prescribed angiotensin-converting enzyme inhibitors (ACE), angiotensin II receptor blockers (ARB), and diuretics. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The first knock-in rat model for glutaric aciduria type I allows further insights into pathophysiology in brain and periphery.

Glutaric aciduria type I (GA-I, OMIM # 231670) is an inborn error of metabolism caused by a deficiency of glutaryl-CoA dehydrogenase (GCDH). Patients develop acute encephalopathic crises (AEC) with striatal injury most often triggered by catabolic stress. The pathophysiology of GA-I, particularly in brain, is still not fully understood. We generated the first knock-in rat model for GA-I by introduction of the mutation p.R411W, the rat sequence homologue of the most common Caucasian mutation p.R402W, into the Gcdh gene of Sprague Dawley rats by CRISPR/CAS9 technology. Homozygous Gcdhki/ki rats revealed a high excretor phenotype, but did not present any signs of AEC under normal diet (ND). Exposure to a high lysine diet (HLD, 4.7%) after weaning resulted in clinical and biochemical signs of AEC. A significant increase of plasmatic ammonium concentrations was found in Gcdhki/ki rats under HLD, accompanied by a decrease of urea concentrations and a concomitant increase of arginine excretion. This might indicate an inhibition of the urea cycle. Gcdhki/ki rats exposed to HLD showed highly diminished food intake resulting in severely decreased weight gain and moderate reduction of body mass index (BMI). This constellation suggests a loss of appetite. Under HLD, pipecolic acid increased significantly in cerebral and extra-cerebral liquids and tissues of Gcdhki/ki rats, but not in WT rats. It seems that Gcdhki/ki rats under HLD activate the pipecolate pathway for lysine degradation. Gcdhki/ki rat brains revealed depletion of free carnitine, microglial activation, astroglyosis, astrocytic death by apoptosis, increased vacuole numbers, impaired OXPHOS activities and neuronal damage. Under HLD, Gcdhki/ki rats showed imbalance of intra- and extracellular creatine concentrations and indirect signs of an intracerebral ammonium accumulation. We successfully created the first rat model for GA-I. Characterization of this Gcdhki/ki strain confirmed that it is a suitable model not only for the study of pathophysiological processes, but also for the development of new therapeutic interventions. We further brought up interesting new insights into the pathophysiology of GA-I in brain and periphery.

5-aminolevulinic acid combined with sodium ferrous citrate ameliorated lupus nephritis in a mouse chronic graft-versus-host disease model.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the abnormal activation of immune cells and hypersecretion of autoantibodies and causes irreversible chronic damage, such as lupus nephritis. Chronic graft-versus-host-disease (cGvHD) in mice induced by the injection of parental mouse lymphocytes into F1 hybrids leads to a disease similar to SLE. 5-aminolevulinic acid (5-ALA) is a key progenitor of heme, and its combination with sodium ferrous citrate (SFC) can up-regulate the heme oxygenase (HO-1) expression, resulting in an anti-inflammatory effect. While HO-1 had been reported to be involved in T cell activation and can limit immune-based tissue damage through Treg suppression, which promotes effector response. Thus, we hypothesized that treatment with 5-ALA/SFC could ameliorate lupus nephritis in a mouse cGvHD model. Our results showed that 5-ALA/SFC-treatment significantly decreased the anti-double-stranded DNA (ds-DNA) autoantibodies, blood urea nitrogen (BUN) and creatinine (Cre) levels, reduced kidney inflammatory dendritic cells (DCs) and B cell activation, and increased the regulatory T cells (Tregs) at nine weeks. Furthermore, 5-ALA/SFC suppressed mRNA expression of TNF-α, IL-1ß, IFN-γ and markers on DCs. In addition, we also found that 5-ALA/SFC treatment increased the HO-1 expression on donor-derived DCs and Tregs concurrently, increased the number of Tregs, and reduced the population of activated DCs, B cells and CD8+ T cells at three weeks (early stage of the disease). We thus identified a novel role of 5-ALA/SFC for therapeutically improving the symptoms of lupus nephritis in a mouse cGvHD model and expanded the current understanding of how this immunoregulatory agent can be used to generate beneficial immune responses and treat autoimmune disease.

Role of Creatine in the Heart: Health and Disease.

Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines.

SERUM BIOCHEMISTRY AND SELECT MINERAL PARAMETERS OF PRE-RELEASE SUNDA PANGOLINS (MANIS JAVANICA) FOLLOWING REHABILITATION IN VIETNAM.

Native to Southeast Asia, the Sunda pangolin (Manis javanica) is critically endangered largely because of poorly regulated wildlife trade, consumptive practices, and use in traditional Chinese medicine. Efforts to rescue and rehabilitate animals confiscated from the illegal trade are complicated by a general lack of knowledge surrounding the normal health and disease processes unique to the species. To provide clinical reference intervals for normal health states of Sunda pangolins, biochemical parameters were determined from rescued individuals in Vietnam that had undergone a 14-day observation period and met a set of criteria for release back into the wild. Blood samples were collected from 42 apparently healthy Sunda pangolins while anesthetized or awake. Packed cell volume (PCV) and total solids (TS) were determined manually, and serum biochemistry values were determined in-house with a benchtop analyzer. Additional biochemical and mineral parameters not included in the primary panel were determined from a subset of 10 pangolins through an external diagnostic laboratory. Overall reference intervals were calculated for PCV and TS (n = 29) and for standard serum biochemistry parameters (n = 42). Females and males demonstrated significant variation with respect to body mass, potassium (K+), and phosphorus, whereas age was a significant source of variation in alkaline phosphatase. Seasonal variation in glucose (GLU), creatinine (CRE), total proteins, sodium, calcium, and K+ was also observed. Comparisons between anesthetized and awake pangolins demonstrated significant variation in GLU, CRE, and K+. The parameters determined in this study can serve as a clinical reference for ex situ Sunda pangolin conservation efforts. In the context of wildlife rehabilitation, serial bloodwork allows for continued monitoring of patient health and should inform decision making regarding release readiness and timing.

Resistance exercise training ameliorates chronic kidney disease outcomes in a 5/6 nephrectomy model.

Chronic kidney disease (CKD) is defined by decreased glomerular filtration rate (GFR) or increased albumin excretion leading to renal injury. However, exercise training is an important non-pharmacological intervention that ameliorates and protects against Diabetes Mellitus, cardiovascular disease, and CKD. AIM: Our aim was to evaluate the capability of resistance exercise training (RET) to improve CKD outcomes and the contribution of the renal and muscular Akt/mTOR signaling pathway for RET beneficial effects on a CKD model. MAIN METHODS: Male Wistar rats were subjected to RET, followed for 10 weeks, and randomly divided into 5 groups: Sham: Sham-operated; sedentary and nephrectomy (5/6Nx) (SNS); exercising post-5/6Nx (SNE); exercising pre-5/6Nx (ENS); exercising pre- and post-5/6Nx (ENE). The systolic blood pressure (BP) was measured. Creatinine, proteinuria, and blood urea nitrogen (BUN) were evaluated. After euthanasia Renal and muscular Akt/mTOR signaling pathways were analyzed. KEY FINDING: Our study showed that the SNS presented renal injury, hypertension, weight and muscular mass loss and a higher mortality rate. SNS group also decreased renal IL-10 and increased TNF-alfa and TGF-Beta. Renal AKT, mTOR, and rpS6 pathway were increased, PTEN was decreased on SNS. And muscular Akt and mTOR were decreased on SNS. SIGNIFICANCE: The RET before and after the 5/6Nx ameliorates all these parameters mentioned above, suggesting that RET is a good non-pharmacological approach to diminish complications frequently found in CKD. We also suggest that the AKT-m-TOR pathway can play an important role in these beneficial outcomes of RET on the CKD animal model.

Possible Protective Effect of Remote Ischemic Preconditioning on Acute Kidney Injury Following Elective Percutaneous Coronary Intervention: Secondary Analysis of a Multicenter, Randomized Study.

Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI.

Blood plasma metabolomics of children and adolescents with sickle cell anaemia treated with hydroxycarbamide: a new tool for uncovering biochemical alterations.

Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long-term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non-SCA individuals. Fifty-three metabolites were identified by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and 1 H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least-squares discriminant analysis (PLS-DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients' metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands' cycle and increased synthesis of sphingosine 1-phosphate. Putative novel biomarkers are suggested.

Estimation of the hemoglobin glycation rate constant.

In a previous study, a method of obtaining mean erythrocyte age ([Formula: see text]) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant ([Formula: see text] dL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of deriving [Formula: see text] from erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate of [Formula: see text]. One hundred and seven subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, and [Formula: see text] using HbA1c, AG and the newly-derived constant, [Formula: see text] were compared to [Formula: see text] using traditional [Formula: see text] in three patients whose data were taken from previous case studies. A value of [Formula: see text] dL/mg/day was determined for [Formula: see text]. [Formula: see text] using HbA1c, AG and [Formula: see text] were found to no be significantly different (paired t-test, [Formula: see text]) to [Formula: see text] using traditional [Formula: see text]. [Formula: see text] enables the estimation of [Formula: see text] from HbA1c and AG.

A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism.

Creatine is an organic compound used as fast phosphate energy buffer to recycle ATP, important in tissues with high energy demand such as muscle or brain. Creatine is taken from the diet or endogenously synthetized by the enzymes AGAT and GAMT, and specifically taken up by the transporter SLC6A8. Deficit in the endogenous synthesis or in the transport leads to Cerebral Creatine Deficiency Syndromes (CCDS). CCDS are characterized by brain creatine deficiency, intellectual disability with severe speech delay, behavioral troubles such as attention deficits and/or autistic features, and epilepsy. Among CCDS, the X-linked creatine transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different mouse models of CTD were generated by doing long deletions in the Slc6a8 gene showing reduced brain creatine and cognitive deficiencies or impaired motor function. We present a new knock-in (KI) rat model of CTD holding an identical point mutation found in patients with reported lack of transporter activity. KI males showed brain creatine deficiency, increased urinary creatine/creatinine ratio, cognitive deficits and autistic-like traits. The Slc6a8Y389C KI rat fairly enriches the spectrum of CTD models and provides new data about the pathology, being the first animal model of CTD carrying a point mutation.

Quantification of serum C-mannosyl tryptophan by novel assay to evaluate renal function and vascular complications in patients with type 2 diabetes.

C-Mannosyl tryptophan (CMW) is a unique glycosylated amino acid, and a candidate novel biomarker of renal function. In type 2 diabetes (T2D), a combination of metabolites including CMW has recently been the focus of novel biomarkers for the evaluation of renal function and prediction of its decline. However, previous quantification methods for serum CMW have several limitations. We recently established a novel assay for quantifying serum CMW. Serum CMW from 99 Japanese patients with T2D was quantified by this assay using hydrophilic interaction liquid chromatography. The serum CMW levels were cross-sectionally characterized in relation to clinical features, including renal function and vascular complications. Serum CMW level was more strongly correlated with serum creatinine and cystatin C levels and with eGFR than with albumin urea level. The ROC curve to detect eGFR < 60 ml/min/1.73 m2 revealed that the cutoff serum CMW level was 337.5 nM (AUC 0.883). Serum CMW levels were higher in patients with a history of macroangiopathy than in those without history. They correlated with ankle-brachial pressure index, whereas cystatin C did not. Serum CMW levels quantified by the novel assay could be useful in evaluation of glomerular filtration of renal function and peripheral arterial disease in T2D.