Energy Drinks and Their Acute Effects on Heart Rhythm and Electrocardiographic Time Intervals in Healthy Children and Teenagers: A Randomized Trial

Beyond their effect on blood pressure, the effect of energy drinks on heart rate in children and teenagers has not been evaluated until now. Thus, this study aimed to investigate the acute cardiovascular effects of energy drinks in healthy children and teenagers. Twenty-six children and adolescents (mean age 14.49 years) received a commercially available energy drink (ED) and placebo on two consecutive days based on the maximum caffeine dosage as proposed by the European Food Safety Authority. Heart rhythm and electrocardiographic time intervals were assessed in a prospective, randomized, double-blind, placebo-controlled, crossover clinical study design. ED consumption resulted in a significantly increased number of supraventricular extrasystoles (SVES) compared to the placebo, whereas supraventricular tachycardia or malignant ventricular arrhythmias were not observed. The mean heart rate (HR) was significantly lower following consumption of EDs. In contrast, QTc intervals were not affected by EDs. Being the first of its kind, this trial demonstrates the cardiovascular and rhythmological effects of EDs in minors. Interestingly, EDs were associated with adverse effects on heart rhythm. Whether higher dosages or consumption in children with preexisting conditions may cause potentially harmful disorders was beyond the scope of this pilot study and remains to be determined in future trials. Trial Registration Number (DRKS-ID): DRKS00027580

Energy Drinks and Their Acute Effects on Arterial Stiffness in Healthy Children and Teenagers: A Randomized Trial

Adolescents are the main consumer group of energy drinks (ED). Studies suggest that acute ED consumption is associated with increased peripheral blood pressure. Little is known of the ED-induced effects on arterial stiffness. Therefore, this study aimed to investigate the acute effects of ED consumption on arterial stiffness in healthy children and teenagers by conducting a prospective, randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants (n = 27, mean age = 14.53 years) consumed a body-weight-adjusted amount of an ED or a placebo on two consecutive days. Arterial stiffness was evaluated sonographically by two-dimensional speckle tracking of the common carotid artery (CCA) at baseline and up to four hours after beverage consumption. The ED intake led to a significantly decreased peak circumferential strain of the CCA (11.78 +/- 2.70% vs. 12.29 +/- 2.68%, p = 0.043) compared with the placebo. The results of this study indicate that the acute ED consumption might be associated with increased arterial stiffness in healthy children and teenagers. Minors, particularly those with increased cardiovascular morbidity, should be discouraged from ED consumption

Autoantibody Response to Islet Transplantation in Type 1 Diabetes

Islet allotransplantation into patients with autoimmune type 1 diabetes represents a reexposure to autoantigen. Here, measurement of antibodies to GAD and IA-2 autoantigens before and after islet transplantation in 36 patients (33 receiving islet plus kidney grafts with cyclosporin and steroid-based immunosuppression, and 3 receiving solitary islet transplants with mycophenolate but cyclosporin-free immunosuppression) demonstrated marked rises in GAD antibodies within 7 days posttransplantation in 5 patients (3 receiving islet after kidney transplants, and 2 receiving solitary islet transplants) and within 30 days in the third patient receiving solitary islet transplantation. GAD antibodies were of the IgG1 subclass, against major autoantigenic epitopes, and in cases of islet after kidney transplants, the responses were short-lived and not accompanied by HLA antibodies. Two of these patients had subsequent marked rises of IA-2 antibodies, and an additional patient had a marked rise in IgM-GAD antibodies 3 years after transplantation. Insulin independence was not achieved in patients with autoantibody elevations and was significantly less frequent in these patients. These data are consistent with a reactivation of autoimmunity that may be dependent on immunosuppression therapy and is associated with impaired graft function

Routine follow-up transjugular liver biopsy in Fontan patients: technical considerations and safety of an initial case series and literature review

IntroductionPatients with Fontan palliation are susceptible to congestive hepatopathy and Fontan-associated liver disease (FALD) because of hemodynamic changes. The staging of liver fibrosis involves various methods, including invasive biopsy. Transjugular liver biopsy (TJLB) offers a less invasive alternative, enhancing liver disease surveillance in routine cardiac catheterization. We detail the technical aspects, share initial outcomes, and discuss existing literature.Methods/resultsDuring routine follow-up cardiac catheterization indicated by hemodynamic or clinical alterations, four patients aged between 16 and 26 years with univentricular Fontan circulation and three patients with biventricular circulation underwent TJLB during routine surveillance catheterization. The examinations were performed under conscious sedation and local anesthesia without general anesthesia. Jugular access was obtained at the site of liver localization, and a 5 F multipurpose catheter was inserted into the liver veins. After hand angiography to delineate the local hepatic venous anatomy, an exchange wire was used to place the bioptome, and three consecutive biopsies were performed. There were no complications, especially perforation or bleeding. The technical success rate was 100%, with all obtained samples appropriate for histopathological diagnostics. The total additional procedure time was less than 20 min.ConclusionTJLB is an attractive alternative method for obtaining liver specimens in the scope of FALD care. We believe that it should be performed during routine hemodynamic evaluations in Fontan patients and can be performed safely with very low additional time expenditure. As the biopsy site is intravascular, the risk of external bleeding or hematoma is significantly reduced despite the high intrahepatic pressures and the usually impaired coagulation profile in these patients. Based on our initial experience and the lower complication rates compared with other techniques, TJLB should be considered a standard approach in these patients and used more often during the long-term follow-up of Fontan patients. It can be performed in the same setting whenever a hemodynamic assessment of patients with congenital heart defects is required

Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients

WSTĘP. Celem badania była ocena wpływu przewlekłego doustnego stosowania L-argininy, działającej przez normalizację szlaku NO/cykliczny 3’,5’-guanozyno monofosforan (cGMP), na poprawę insulinowrażliwości obwodowej i wątrobowej u 12 szczupłych osób chorych na cukrzycę typu 2. MATERIAŁ I METODY. Badanie, przeprowadzone metodą podwójnie ślepej próby, trwało 3 miesiące. W pierwszym miesiącu chorych leczono typową dietą cukrzycową. Następnie losowo przydzielono ich do dwóch grup. W grupie 1 przez 2 miesiące stosowano typową dietę i placebo (doustnie 3 × d.). W grupie 2 pacjentów leczono przez miesiąc dietą i placebo (doustnie 3 × d.) i następnie przez miesiąc dietą i L-argininą (3 g 3 × d.). Po pierwszymi i drugim miesiącu wykonano badanie za pomocą klamry euglikemiczno-hiperinsulinemicznej z jednoczesnym wlewem dożylnym znakowanej izotopowo glukozy (glukoza 6,6- 2H2). Grupą kontrolną stanowiło 10 zdrowych osób, u których również wykonano badanie za pomocą klamry. WYNIKI. W grupie 1 w czasie badania nie zaobserwowano zmian podstawowego stężenia cGMP, skurczowego ciśnienia tętniczego, przepływu krwi w przedramieniu, wykorzystania glukozy i endogennej produkcji glukozy. W grupie 2 przyjmowanie L-argininy spowodowało normalizację podstawowego stężenia cGMP, poprawę przepływu w przedramieniu o 36%, oraz wykorzystania glukozy w badaniu metodą klamry metabolicznej o 34%, jak również obniżenie skurczowego ciśnienia tętniczego i endogennej produkcji glukozy odpowiednio o 14 i 29%. Pomimo tego w porównaniu z grupą kontrolną podawanie L-argininy nie normalizuje całkowicie metabolizmu glukozy. WNIOSKI. Podawanie L-argininy u chorych na cukrzycę typu 2 znacznie poprawia insulinowrażliwość obwodową i wątrobową, lecz nie normalizuje jej całkowicie.INTRODUCTION. The aim of this study was to evaluate whether long-term administration of L-arginine acting through a normalization of NO/cyclic-guanosine- 3’,5’-cyclic monophosphate (cGMP) pathway was able to ameliorate peripheral and hepatic insulin sensitivity in 12 lean type 2 diabetic patients. MATERIAL AND METHODS. A double-blind study was performed for 3 months. In the first month, patients were treated with their usual diet. Then they were randomly allocated into two groups. In group 1, patients were treated with diet plus placebo (orally three times per day) for 2 months. In group 2 patients were treated for 1 month with diet plus placebo (orally, three times per day) and then for 1 month with diet plus L-arginine (3 g three times per day). At the end of the first and the second month of therapy, patients underwent a euglycemic-hyperinsulinemic clamp combined with [6,6-2H2] glucose infusion. A total of 10 normal subjects underwent the same test as control subjects. RESULTS. In group 1, no changes in basal cGMP levels, systolic blood pressure, forearm blood flow, glucose disposal, and endogenous glucose production were observed throughout. In group 2, L-arginine normalized basal cGMP levels and significantly increased forearm blood flow by 36% and glucose disposal during the clamp by 34%, whereas it decreased systolic blood pressure, and endogenous glucose production by 14 and 29%, respectively. However, compared with normal subjects, L-arginine treatment was not able to completely overcome the defect in glucose disposal. CONCLUSIONS. L-arginine treatment significantly improves but does not completely normalize peripheral and hepatic insulin sensitivity in type 2 diabetic patients

Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication

Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full rep- ertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies. Recently, metabolism has been considered as a relevant player in CSC biology, and indeed, onco- genic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly, the action of metabolic pathways in CSC maintenance might not be merely a conse- quence of genomic alterations. Indeed, certain metabotypic phenotypes may play a causative role in maintaining the stem traits, acting as an orchestrator of stemness. Here, we review the current studies on the metabolic features of CSCs, focusing on the bio- chemical energy pathways involved in CSC maintenance and propagation. We provide a detailed overview of the plastic metabolic behavior of CSCs in response to microenvironment changes, genetic aberrations, and pharmacological stressors. In addition, we describe the potential of comprehensive metabolic approaches to identify and selectively eradicate CSCs, together with the possibility to ‘force’ CSCs within certain metabolic dependences, in order to effectively target such metabolic biochemical inflexibilities. Finally, we focus on targeting mitochondria to halt CSC dissemination and effectively eradicate cancer

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Sodium-lithium countertransport and triglycerides in diabetic nephropathy

Sodium-lithium countertransport and triglycerides in diabetic nephropathy. Elevated erythrocyte sodium-lithium countertransport (SLC) activity is an intermediate phenotype of essential hypertension among Caucasians, and is controversially associated with nephropathy in Type 1 (insulin-dependent) diabetes. Hypertriglyceridemia is a frequent concomitant of elevated SLC in the general population, and may be found in diabetic nephropathy. The present study was designed to investigate the influence of kidney disease, serum triglycerides and blood pressure on the interindividual variability of SLC in Type 1 diabetes. SLC and fasting major serum lipids were studied in 35 Type 1 diabetic patients with persistently elevated urinary albumin excretion and in a group of patients matched for age, sex and duration of diabetes, but with normoalbuminuria. SLC was elevated in patients with clinical nephropathy (N = 10; median: 420 µmol · 1RBC-1 · hr-1) and in patients with microalbuminuria (N = 25; median: 405 µmol · 1RBC-1 · hr-1) compared with normoalbuminuric patients (median: 296 µmol · 1RBC-1 · hr-1; P < 0.01 vs. both groups). Hypertriglyceridemia and hypercholesterolemia were found only among patients with macroalbuminuria. Analysis of covariance indicated that the association of elevated SLC with kidney disease (P < 0.006 in all models) was largely independent of serum triglycerides, but also of total cholesterol, insulin dose and measures of glycemie control. Only diastolic blood pressure was positively associated with SLC (P < 0.02) independently from nephropathy (P < 0.005) also after restricting analysis to the normoalbuminuric patients. Kidney disease and raised blood pressure remain major concomitants of elevated SLC in Type 1 diabetics