Eight-Week Creatine-Glucose Supplementation Alleviates Clinical Features of Long COVID.

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η2=0.72; left paracentral grey matter F=19.243, p=0.019; partial η2=0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.

Nutritional Support for Moderate-to-Late-Preterm Infants - A Randomized Trial.

BACKGROUND: Most moderate-to-late-preterm infants need nutritional support until they are feeding exclusively on their mother's breast milk. Evidence to guide nutrition strategies for these infants is lacking. METHODS: We conducted a multicenter, factorial, randomized trial involving infants born at 32 weeks 0 days' to 35 weeks 6 days' gestation who had intravenous access and whose mothers intended to breast-feed. Each infant was assigned to three interventions or their comparators: intravenous amino acid solution (parenteral nutrition) or dextrose solution until full feeding with milk was established; milk supplement given when maternal milk was insufficient or mother's breast milk exclusively with no supplementation; and taste and smell exposure before gastric-tube feeding or no taste and smell exposure. The primary outcome for the parenteral nutrition and the milk supplement interventions was the body-fat percentage at 4 months of corrected gestational age, and the primary outcome for the taste and smell intervention was the time to full enteral feeding (150 ml per kilogram of body weight per day or exclusive breast-feeding). RESULTS: A total of 532 infants (291 boys [55%]) were included in the trial. The mean (±SD) body-fat percentage at 4 months was similar among the infants who received parenteral nutrition and those who received dextrose solution (26.0±5.4% vs. 26.2±5.2%; adjusted mean difference, -0.20; 95% confidence interval [CI], -1.32 to 0.92; P = 0.72) and among the infants who received milk supplement and those who received mother's breast milk exclusively (26.3±5.3% vs. 25.8±5.4%; adjusted mean difference, 0.65; 95% CI, -0.45 to 1.74; P = 0.25). The time to full enteral feeding was similar among the infants who were exposed to taste and smell and those who were not (5.8±1.5 vs. 5.7±1.9 days; P = 0.59). Secondary outcomes were similar across interventions. Serious adverse events occurred in one infant. CONCLUSIONS: This trial of routine nutrition interventions to support moderate-to-late-preterm infants until full nutrition with mother's breast milk was possible did not show any effects on the time to full enteral feeding or on body composition at 4 months of corrected gestational age. (Funded by the Health Research Council of New Zealand and others; DIAMOND Australian New Zealand Clinical Trials Registry number, ACTRN12616001199404.).

Glucagon kinetics assessed by mathematical modelling during oral glucose administration in people spanning from normal glucose tolerance to type 2 diabetes.

Background/Objectives: Glucagon is important in the maintenance of glucose homeostasis, with also effects on lipids. In this study, we aimed to apply a recently developed model of glucagon kinetics to determine the sensitivity of glucagon variations (especially, glucagon inhibition) to insulin levels ("alpha-cell insulin sensitivity"), during oral glucose administration. Subjects/Methods: We studied 50 participants (spanning from normal glucose tolerance to type 2 diabetes) undergoing frequently sampled 5-hr oral glucose tolerance test (OGTT). The alpha-cell insulin sensitivity and the glucagon kinetics were assessed by a mathematical model that we developed previously. Results: The alpha-cell insulin sensitivity parameter (named SGLUCA; "GLUCA": "glucagon") was remarkably variable among participants (CV=221%). SGLUCA was found inversely correlated with the mean glycemic values, as well as with 2-hr glycemia of the OGTT. When stratifying participants into two groups (normal glucose tolerance, NGT, N=28, and impaired glucose regulation/type 2 diabetes, IGR_T2D, N=22), we found that SGLUCA was lower in the latter (1.50 ± 0.50·10-2 vs. 0.26 ± 0.14·10-2 ng·L-1 GLUCA/pmol·L-1 INS, in NGT and IGR_T2D, respectively, p=0.009; "INS": "insulin"). Conclusions: The alpha-cell insulin sensitivity is highly variable among subjects, and it is different in groups at different glucose tolerance. This may be relevant for defining personalized treatment schemes, in terms of dietary prescriptions but also for treatments with glucagon-related agents.

Comparison of modified Del Nido and Custodiol® cardioplegia in minimally invasive mitral valve surgery.

OBJECTIVES: In this study, we evaluated if modified Del Nido cardioplegia delivers comparable cardiac protection in comparison to Custodiol® in patients undergoing isolated minimally invasive mitral valve repair. METHODS: From January 2018 to October 2021, all patients undergoing non-emergent isolated minimally invasive mitral valve repair were included in this study. The cardioplegia was chosen at the surgeons' discretion. The primary end points of this study were peak postoperative cardiac enzyme levels. Secondary end points were in-hospital mortality, hospital stay, occurrence of cardiac arrhythmias, pacemaker implantations, postoperative lactate and sodium levels and postoperative incidence of renal failure requiring dialysis. RESULTS: A total of 355 patients were included in this study. The mean age of patients was 57. After propensity score matching, a total of 156 pairs were identified. There was no difference in cross-clamp time between both groups. Postoperative creatine kinase levels were higher in patients receiving Custodiol on the 1st and 2nd postoperative days. Creatine kinase isoenzyme MB levels were higher in patients receiving Custodiol on the 2nd postoperative day (0.5 ± 0.2 vs 0.4 ± 0.1 µmol/l s; P < 0.001). Postoperative Troponin T concentrations were similar between both groups. Maximum lactate concentrations were higher in patients receiving Custodiol on the day of surgery (2.4 ± 1.9 vs 2.0 ± 1.1 mmol/l; P = 0.04). The overall hospital stay was longer in patients receiving Del Nido cardioplegia (10.6 ± 3.2 vs 8 ± 4.1 days; P < 0.01). CONCLUSIONS: Modified Del Nido cardioplegia based on Ionosteril® solution offers equivalent protection compared to Custodiol for isolated minimally invasive mitral valve repair.

Effect of pacifier and pacifier with dextrose in reducing pain during orogastric tube insertion in newborns: a randomized controlled trial.

OBJECTIVE: This study aimed to assess the efficacy of pacifier use, with and without 25% dextrose, in reducing pain during orogastric tube insertion in newborns. STUDY DESIGN: In a randomized controlled trial involving 60 newborns at a public hospital from April to December 2019, participants were divided into three groups: pacifier (n = 20), pacifier with 25% dextrose (n = 20), and control (n = 20). A pacifier, with and without dextrose, was used for the experimental groups, while the control group performed a routine procedure. Neonatal infant pain scale, crying duration, heart rate (HR), and oxygen saturation (SpO2) were evaluated. RESULTS: Results indicated that the control group experienced significantly higher pain levels, elevated HRs, decreased SpO2, and prolonged crying. Conversely, the pacifier with 25% dextrose group showed a notable reduction in crying duration. CONCLUSION: A pacifier, with and without 25% dextrose, effectively reduces pain and improves physiological and behavioral parameters during orogastric tube insertion. CLINICAL TRIAL NUMBER: NCT05462964 CLINICAL TRIAL REGISTRATION: The protocol for this randomized controlled experimental trial is registered on ClinicalTrials.gov. The clinical trial registration number is https://clinicaltrials.gov ; NCT05462964.

Comparison of an oral mixed meal plus arginine and intravenous glucose, GLP-1 plus arginine to unmask residual islet function in longstanding type 1 diabetes.

Residual beta cells are present in most patients with longstanding type 1 diabetes but it is unknown whether these beta cells react normally to different stimuli. Moreover a defect in proinsulin conversion and abnormal alpha cell response are also part of the islet dysfunction. A three-phase [euglycemia, hyperglycemia, and hyperglycemia + glucagon-like peptide 1 (GLP-1)] clamp was performed in patients with longstanding type 1 diabetes. Intravenous arginine boluses were administered at the end of each phase. On another day, a mixed meal stimulation test with a subsequent intravenous arginine bolus was performed. C-peptide was detectable in a subgroup of subjects at baseline (2/15) or only after stimulation (3/15). When detectable, C-peptide increased 2.9-fold [95% CI: 1.2-7.1] during the hyperglycemia phase and 14.1-fold [95% CI: 3.1-65.2] during the hyperglycemia + GLP-1 phase, and 22.3-fold [95% CI: 5.6-89.1] during hyperglycemia + GLP-1 + arginine phase when compared with baseline. The same subset of patients with a C-peptide response were identified during the mixed meal stimulation test as during the clamp. There was an inhibition of glucagon secretion (0.72-fold, [95% CI: 0.63-0.84]) during the glucose clamp irrespective of the presence of detectable beta cell function. Proinsulin was only present in a subset of subjects with detectable C-peptide (3/15) and proinsulin mimicked the C-peptide response to the different stimuli when detectable. Residual beta cells in longstanding type 1 diabetes respond adequately to different stimuli and could be of clinical benefit.NEW & NOTEWORTHY If beta cell function is detectable, the beta cells react relatively normal to the different stimuli except for the first phase response to intravenous glucose. An oral mixed meal followed by an intravenous arginine bolus can identify residual beta cell function/mass as well as the more commonly used glucose potentiated arginine-induced insulin secretion during a hyperglycemic clamp.

Robust increase in glucagon secretion after oral protein intake, but not after glucose or lipid intake in Japanese people without diabetes.

Few studies in Asian populations have analyzed how glucagon secretion is affected by ingested glucose, proteins or lipids, individually. To investigate the fluctuations of glucagon secretion after the intake of each of these nutrients, 10 healthy volunteers underwent oral loading tests using each of glucose, proteins and lipids, and blood levels of glucose, insulin and glucagon were measured every 30 min for 120 min. Whereas glucagon secretion was suppressed and minimally affected by oral glucose intake and lipid intake, respectively, oral protein intake robustly increased glucagon secretion, as well as insulin secretion. Further studies are needed to elucidate the mechanism by which protein loading increases glucagon secretion.

Inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-fat diet feeding.

G protein-coupled receptor (GPR) 120 is expressed in enteroendocrine cells secreting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP), and cholecystokinin (CCK). Although GPR120 signaling in adipose tissue and macrophages has been reported to ameliorate obesity and insulin resistance in a high long-chain triglyceride (LCT) diet, intestine-specific roles of GPR120 are unclear. To clarify the metabolic effect of GPR120 in the intestine, we generated intestine-specific GPR120-knockout (GPR120int-/-) mice. In comparison with floxed GPR120 (WT) mice, GPR120int-/- mice exhibited reduced GIP secretion and CCK action without change of insulin, GLP-1, or peptide YY (PYY) secretion after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed a mild reduction of body weight and substantial amelioration of insulin resistance and fatty liver. Moreover, liver and white adipose tissue (WAT) of GPR120int-/-mice exhibited increased Akt phosphorylation and reduced gene expression of suppressor of cytokine signaling (SOCS) 3, which inhibits insulin signaling. In addition, gene expression of inflammatory cytokines in WAT and lipogenic molecules in liver were reduced in GPR120int-/- mice. These findings suggest that inhibition of GPR120 signaling in intestine ameliorates insulin resistance and fatty liver under high-LCT diet feeding.NEW & NOTEWORTHY We generated novel intestine-specific GPR120-knockout (GPR120int-/-) mice and investigated the metabolic effect of GPR120 in the intestine. GPR120int-/- mice exhibited a reduction of GIP secretion and CCK action after a single administration of LCT. Under a high-LCT diet, GPR120int-/- mice showed mild improvement in obesity and marked amelioration of insulin resistance and hepatic steatosis. Our results indicate an important role of intestinal GPR120 on insulin resistance and hepatic steatosis.

The Effect of Dextrose or Protein Ingestion on Circulating Growth Differentiation Factor 15 and Appetite in Older Compared to Younger Women.

Growth differentiation factor 15 (GDF15) is a stress signal that can be induced by protein restriction and is associated with reduced food intake. Anorexia of aging, insufficient protein intake as well as high GDF15 concentrations often occur in older age, but it is unknown whether GDF15 concentrations change acutely after meal ingestion and affect appetite in older individuals. After an overnight fast, appetite was assessed in older (n = 20; 73.7 ± 6.30 years) and younger (n = 20; 25.7 ± 4.39 years) women with visual analogue scales, and concentrations of circulating GDF15 and glucagon-like peptide-1 (GLP-1) were quantified before and at 1, 2 and 4 h after ingestion of either dextrose (182 kcal) or a mixed protein-rich meal (450 kcal). In response to dextrose ingestion, appetite increased in both older and younger women, whereas GDF15 concentrations increased only in the older group. In older women, appetite response was negatively correlated with the GDF15 response (rho = -0.802, p = 0.005). Following high-protein ingestion, appetite increased in younger women, but remained low in the old, while GDF15 concentrations did not change significantly in either age group. GLP-1 concentrations did not differ between age groups or test meals. In summary, acute GDF15 response differed between older and younger women. Associations of postprandial appetite and GDF15 following dextrose ingestion in older women suggest a reduced appetite response when the GDF15 response is high, thus supporting the proposed anorectic effects of high GDF15 concentrations.

Paradoxical GH increase during oral glucose load may predict overall remission in acromegalic patients.

BACKGROUND: The nadir growth hormone (nGH) during the oral glucose tolerance test (OGTT) is the gold standard method for diagnosing acromegaly. A paradoxical growth hormone (GH) response to oral glucose (OG) in acromegaly can be observed. The role of the paradoxical GH response on how the patients with acromegaly respond to the treatment has been addressed in few studies. The aim of this study was to investigate the association between glucose-dependent growth hormone results and and the responses of acromegalic patients to surgical and/or medical therapy following surgery. MATERIAL AND METHODS: This retrospective cohort study included patients with acromegaly who underwent surgery (n = 189) or received primary medical treatment (n = 9). The mean age was 50.44 ± 12.81 years (M/F: 84/114). The patients were grouped into paradoxical (GH-P) and non-paradoxical (GH-nP) according to GH response to OG and were compared in terms of clinical and pathological features, pituitary tumor size, invasiveness, biochemical profiles, and how they responded to the treatment. RESULTS: The mean age, gender distribution, and basal tumor diameter were all similar in both groups (p > 0.05). The GH-P group had a higher remission rate in response to medical therapy followed by surgery (83% vs. 55%; p = 0.026). Although a higher surgical remission rate in favor of GH-P was observed, it did not reach statistical significance (63% vs. 48%; p = 0.059). Overall treatment response rates were also higher in the GH-P group compared to the GH-nP group (89% vs. 71%; p = 0.005). CONCLUSION: A paradoxical GH response to OG load may help to predict the response to medical treatment in patients with acromegaly.

Effects of mammalian blood with different glucose levels on reproduction, growth and survival of the southern medicinal leech, Hirudo verbana Carena, 1820.

Medicinal leeches are generally fed using pure mammalian blood. In the present study reproduction, growth and survival of medicinal leeches (Hirudo spp.) fed by mammalian blood with modified glucose level were investigated for the first time. Leeches were fed by cattle blood in a final glucose level of 152 mg/dL (control group; Glucose-free), 200 mg/dL (G200 group), 300 mg/dL (G300 group), 500 mg/dL (G500 group), 750 mg/dL (G750 group), 1000 mg/dL (G1000 group), 2500 mg/dL (G2500 group) and 5000 mg/dL (G5000 group) with the addition of D-Glucose Monohydrate. Greatest growth performance was determined in the G2500 group with a specific growth rate of 2.34% (final body weight: 10.37 ± 3.86 g) (P < 0.05). A quadratic increase was observed in the body weight values of the leeches depending on the glucose dose (Plinear and Pquadratic < 0.05). The greatest survival and gravidity rates were 89% and 38%, respectively, in the G750 group (P < 0.05). The increased glucose level caused a sharp decrease in the survival and gravidity rates of leeches. The glucose level did not significantly effected the cocoon and offspring productivity (P > 0.05). According to the broken line model, optimum glucose levels based on growth, survival rate and gravidity rate were 2461 mg/dL, 750.0 mg/dL and 749.9 mg/dL, respectively. The study showed that, although the optimum growth performance was obtained in the G2500 group, blood with glucose level of 750 mg/dL should be used for profitable medicinal leech culture considering survival and gravidity rates.

Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway.

BACKGROUND: High glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown. METHODS: Osteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red staining and quantitative assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RNA-seq analysis was performed to screen target genes of metformin, and the effects of target genes were confirmed using lentivirus transfection. Western blot analysis was also used to detect the protein level of underlying signaling pathways. RESULTS: We found that osteogenic differentiation of PDLSCs under high glucose was decreased, and metformin addition enhanced this capacity of differentiation. Furthermore, the results of RNA-seq analysis showed that natriuretic peptide receptor 3 (NPR3) was upregulated in PDLSCs under high glucose and downregulated after metformin addition. When the underlying pathways involved were investigated, we found that upregulation of NPR3 can compromise the metformin-enhanced PDLSC osteogenic differentiation and activate the MAPK pathway (especially the p38 MAPK and Erk1/2 pathway), and that inhibition of the NPR3-mediated p38 MAPK or Erk1/2 pathway enhanced the osteogenic differentiation of PDLSCs under high glucose. CONCLUSIONS: The present study suggests that metformin may enhance the osteogenic differentiation of PDLSCs under high glucose via downregulation of NPR3 and inhibition of its downstream MAPK pathway. This is the first report identifying the involvement of NPR3-mediated MAPK pathway in the metformin-enhanced osteogenic differentiation, indicating that NPR3 antagonists, such as metformin, may be feasible therapeutics for periodontal tissue regeneration in diabetic individuals.

El consumo regular de un caldo funcional enriquecido con fosfofructooligosacáridos aumenta los niveles de las hormonas relacionadas con la saciedad en las personas sanas. Ensayo clínico aleatorizado y controlado / Regular consumption of a functional broth enriched with phospho-fructooligosaccharides increases the levels of hormones related to satiety in healthy people. A randomized, controlled clinical trial

Introducción: el exceso de peso representa un problema de salud pública debido a los factores de riesgo asociados. El sedentarismo, una alimentación inadecuada o una disminución de la sensación de saciedad son algunas de sus causas. Objetivos: evaluar las propiedades saciantes del consumo de un caldo ibérico funcional enriquecido con fosfofructooligosacáridos (FOS) en personas sanas a través de la concentración plasmática de las hormonas involucradas en el apetito. Material y métodos: ensayo clínico nutricional, agudo, cruzado, aleatorizado, doble ciego y controlado, llevado a cabo en 18 participantes aleatorizados en dos secuencias de tratamiento (caldo funcional (CF) compuesto de 5,6 g de FOS/100 g y caldo de control (CC), con 0,4 g de maltodextrina/100 g) con 14 días de lavado entre ellas. Se midieron parámetros relacionados con la saciedad (glucosa, insulina, leptina, ghrelina, GLP-1, PYY) y escalas analógicas visuales (EAV). Resultados: el porcentaje de grasa corporal disminuyó en los que tomaron el CF (-0,15 ± 0,32 vs. 0,09 ± 0,52) (p < 0,05). La concentración de leptina fue superior con el CF (p < 0,001), mostrándose dicho aumento en los tiempos -30 (p < 0,001), 0 (p < 0,001), 30 (p = 0,026) y 120 (p = 0,049) con respecto al CC. Las áreas bajo la curva (AUC) de GLP-1 (p = 0,0033) y PYY (p = 0,022) fueron superiores con el CF en comparación con el CC. Conclusión: el consumo de un caldo ibérico enriquecido con FOS mejora la concentración plasmática de las hormonas involucradas en el control de la saciedad y reduce la cantidad de grasa corporal. Dichos resultados podrían tener efectos beneficiosos para la prevención y el tratamiento del exceso de peso corporal (AU)

Introduction: excess weight represents a public health problem due to its associated risk factors. A sedentary lifestyle, an inadequate diet or a decrease in the feeling of satiety are some of the causes. Objetives: to evaluate the satiating properties of the consumption of a functional Iberian broth enriched with phospho-fructooligosaccharides (FOS) in healthy people through the plasma concentration of hormones involved in appetite. Material and methods: acute, crossover, randomized, double-blind and controlled nutritional clinical trial carried out in 18 randomized participants in two treatment sequences (functional broth (CF), composed of 5.6 g POS/100 g and control broth (CC), with 0.4 g of maltodextrin/100 g) with 14 days of washing in between. Satiety-related parameters (glucose, insulin, leptin, ghrelin, GLP-1, PYY) and visual analog scales (VAS) were measured. Results: the percentage of body fat decreased in those who took the CF (-0.15 ± 0.32 vs 0.09 ± 0.52) (p < 0.05). Leptin concentration was higher with CF (p < 0.001), which was shown at time points -30 (p < 0.001), 0 (p < 0.001), 30 (p = 0.026) and 120 (p = 0.049) when compared to CC. The areas under the curve (AUC) for GLP-1 (p = 0.0033) and PYY (p = 0.022) were higher for CF as compared to CC. Conclusion: consumption of an Iberian broth enriched with POS improves the plasma concentration of hormones involved in the control of satiety, and reduces the amount of body fat. This result could have beneficial effects for the prevention and treatment of overweight (AU)

Hsa_circ_0037128 aggravates high glucose-induced podocytes injury in diabetic nephropathy through mediating miR-31-5p/KLF9.

BACKGROUND: Circular RNA is a key regulator involved in the progression of many human diseases including diabetic nephropathy (DN). However, the role and mechanism of hsa_circ_0037128 in the occurrence and development of DN remains to be explored. METHODS: High glucose (HG)-induced podocytes were used to construct in vitro DN models. The expression of hsa_circ_0037128, microRNA (miR)-31-5p, and Kruppel-like factor 9 (KLF9) was determined using quantitative real-time polymerase chain reaction. The viability and apoptosis of podocytes was measured using cell counting kit 8 assay and flow cytometry. Western blot analysis was performed to examine the protein levels of apoptosis markers and KLF9 in podocytes. Inflammation factors were detected by ELISA assay, and oxidative stress markers were assessed by corresponding Assay Kits. In addition, the interaction between miR-31-5p and hsa_circ_0037128 or KLF9 was verified using dual-luciferase reporter assay and RIP assay. RESULTS: Our data suggested that hsa_circ_0037128 was highly expressed in DN patients and HG-induced podocytes. In HG-induced podocytes, hsa_circ_0037128 knockdown could alleviate HG-induced podocytes injury. In the term of mechanism, hsa_circ_0037128 could sponge miR-31-5p to upregulate KLF9. MiR-31-5p inhibitor could reverse the negative regulation of hsa_circ_0037128 silencing on HG-induced podocytes injury. Also, miR-31-5p relieved HG-induced podocytes injury, and this effect also could be reversed by KLF9 overexpression. CONCLUSION: In summary, our data showed that hsa_circ_0037128 could promote HG-induced podocytes injury via regulating miR-31-5p/KLF9 axis, showing that hsa_circ_0037128 might be a target for DN treatment.

Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial.

Importance: Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. Objective: To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. Design, Setting, and Participants: Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. Interventions: Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. Main Outcomes and Measures: The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). Results: Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. Conclusions and Relevance: Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. Trial Registration: anzctr.org.au Identifier: ACTRN12614001263684.

Novel Motor-Sparing Ultrasound-Guided Neural Injection in Severe Carpal Tunnel Syndrome: A Comparison of Four Injectates.

Nerve hydrodissection uses fluid injection under pressure to selectively separate nerves from areas of suspected entrapment; this procedure is increasingly viewed as potentially useful in treating carpal tunnel syndrome (CTS). The usage of normal saline (NS), 5% dextrose water (D5W), platelet-rich plasma (PRP), and hyaluronic acid (HA) as primary injectates for hydrodissection without an anesthetic can limit anesthetic-related toxicity and preserve the motor functions of the median nerve. Here, we describe a novel motor-sparing neural injection and compare the effect of these four injectates for severe CTS. We retrospectively reviewed the outcomes of 61 severe CTS cases after a single neural injection with NS, D5W, PRP, or HA. Outcomes were evaluated on the 1st and 6th months postinjection, including the Boston Carpal Tunnel Questionnaire (BCTQ) scores and the nerve cross-sectional area (CSA). The results revealed that PRP, D5W, and HA were more efficient than NS at all measured time points (p < 0.05), except for CSA at the 1st month between the NS and D5W groups. Single-injections of PRP and D5W seemed more effective than that of HA within 6 months postinjection for symptom and functional improvement (6th-month BCTQ-symptom, D5W vs. HA, p = 0.047; 1st-month BCTQ-symptom, PRP vs. HA, p = 0.018; 1st- and 6th-month BCTQ-function, D5W vs. HA, p = 0.002 and 0.016, respectively; 1st-month BCTQ-function, PRP vs. HA, p < 0.001). For reducing CSA, PRP and HA seemed more effective than D5W (HA > PRP > D5W on the 1st month and HA vs. D5W, p = 0.001; PRP > HA > D5W on the 6th month and PRP vs. D5W, p = 0.012).

Loss of serine/threonine protein kinase 25 in retinal ganglion cells ameliorates high glucose-elicited damage through regulation of the AKT-GSK-3ß/Nrf2 pathway.

Serine/threonine protein kinase 25 (STK25) has critical importance for diabetic complications. However, whether STK25 has a link with diabetic retinopathy is not clearly understood. The damages of retinal ganglion cells (RGCs) caused by high glucose (HG) is a critical determinant for the onset of diabetic retinopathy. Herein, this work focused on assessing the possible role of STK25 in HG-evoked damage to RGCs. An expression abundance of STK25 was occurred in RGCs challenged with HG. STK25 loss lowered the deleterious effects on RGCs, including apoptosis, oxidative stress and inflammation. SKT25 silencing strengthened the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway in HG-challenged RGCs. Moreover, the inhibition of STK25 restored the phosphorylation of AKT and glycogen synthase kinase-3ß (GSK-3ß) in HG-challenged RGCs, whereas limiting AKT decreased the motivating effects of STK25 inhibition on the Nrf2 pathway. Additionally, the beneficial effects of STK25 inhibition on HG injuries were also reversed via the inhibition of Nrf2. Based on these observations, our work suggests that the inhibition of STK25 is protective for RGCs suffering HG injuries, which is achieved by effects on the AKT-GSK-3ß/Nrf2 pathway. STK25 may participate in the onset of diabetic retinopathy by affecting HG-evoked damages of RGCs.

Effect of obstructive sleep apnea on glucose metabolism.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in people with obesity and is a major risk factor for type 2 diabetes (T2D). The effect of OSA on metabolic function and the precise mechanisms (insulin resistance, ß-cell dysfunction, or both) responsible for the increased T2D risk in people with OSA are unknown. DESIGN AND METHODS: We used a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose and palmitate tracer infusions and 18F-fluorodeoxyglucose injection and positron emission tomography to quantify multi-organ insulin action and oral and intravenous tolerance tests to evaluate glucose-stimulated insulin secretion in fifteen people with obesity and OSA and thirteen people with obesity without OSA. RESULTS: OSA was associated with marked insulin resistance of adipose tissue triglyceride lipolysis and glucose uptake into both skeletal muscles and adipose tissue, whereas there was no significant difference between the OSA and control groups in insulin action on endogenous glucose production, basal insulin secretion, and glucose-stimulated insulin secretion during both intravenous and oral glucose tolerance tests. CONCLUSIONS: These data demonstrate that OSA is a key determinant of insulin sensitivity in people with obesity and underscore the importance of taking OSA status into account when evaluating metabolic function in people with obesity. These findings may also have important clinical implications because disease progression and the risk of diabetes-related complications vary by T2D subtype (i.e. severe insulin resistance vs insulin deficiency). People with OSA may benefit most from the targeted treatment of peripheral insulin resistance and early screening for complications associated with peripheral insulin resistance.