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The article examines alterations in cardiac output after partial cord occlusion in fetal sheep. Results suggest that the almost simultaneous closure of arterial and venous umbilical vessels altered the flow pattern in the umbilical artery and decreased placental blood perfusion. It did not change the blood flow volume rate through the ductus venosus (DV) and, as a result, the DV shunting rate was increased.

A letter to the editor is presented that describes the control of bleeding in a patient with haemophilia A who underwent supracondylar amputation.

Aim: Calcineurin inhibitors (CNIs) are the backbone for immunosuppression after solid organ transplantation. Although successful in preventing kidney transplant rejection, their nephrotoxic side effects contribute to allograft injury. Renal parenchymal lesions occur for cyclosporine A (CsA) as well as for the currently favored tacrolimus (Tac). We aimed to study whether chronic CsA and Tac exposures, before reaching irreversible nephrotoxic damage, affect renal compartments differentially and whether related pathogenic mechanisms can be identified., Methods: CsA and Tac were administered chronically in wild type Wistar rats using osmotic minipumps over 4 weeks. Functional parameters were controlled. Electron microscopy, confocal, and 3D-structured illumination microscopy were used for histopathology. Clinical translatability was tested in human renal biopsies. Standard biochemical, RNA-seq, and proteomic technologies were applied to identify implicated molecular pathways., Results: Both drugs caused significant albeit differential damage in vasculature and nephron. The glomerular filtration barrier was more affected by Tac than by CsA, showing prominent deteriorations in endothelium and podocytes along with impaired VEGF/VEGFR2 signaling and podocyte-specific gene expression. By contrast, proximal tubule epithelia were more severely affected by CsA than by Tac, revealing lysosomal dysfunction, enhanced apoptosis, impaired proteostasis and oxidative stress. Lesion characteristics were confirmed in human renal biopsies., Conclusion: We conclude that pathogenetic alterations in the renal compartments are specific for either treatment. Considering translation to the clinical setting, CNI choice should reflect individual risk factors for renal vasculature and tubular epithelia. As a step in this direction, we share protein signatures identified from multiomics with potential pathognomonic relevance., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Background: Physical fitness is a health marker in youth and is associated with current and future health., Objective: Present the healthy fitness zone (HFZ) prevalence and age-specific fitness profile of young people from seven European countries., Methods: This study used data from the European Fitness Monitoring System project. The sample comprised 4965 (51.4% boys) youths aged 9 to 18 years. Fitness data were collected by physical education teachers using field-based tests. Raw data from the fitness tests were used to calculate the prevalence and 95% confidence intervals (CI) of participants in the HFZ., Results: The overall prevalence of boys and girls in the HFZ for all tests was 16.6% (95% CI = 14.7, 18.1) and 14.9% (95% CI = 13.2, 16.6), respectively. Boys have a mainly positive HFZ profiles, except for the 9-year-olds in the sit and reach (z-score difference = -1.20) and the 20 m run for boys 13-18-year-olds (z-score difference range: -0.09 to -0.01). Girls have worse HFZ profiles than boys, being out of the HFZ in several tests. Furthermore, a decreasing trend in z-score difference from the HFZ with age was observed in VO 2 peak for boys and girls and sit and reach for girls. Notwithstanding, several country-related, sex and age differences were observed., Conclusions: Boys presented mostly healthy age-specific fitness profiles in several fitness tests and ages. These differences should be considered when promoting youth's health through physical activity and fitness, as different fitness levels may require different approaches to implementing health-enhancing physical activity policies., (© 2023 Wiley Periodicals LLC.)

Background: Cardiac c-Kit+ cells isolated from cardiac explant-derived cells modestly improve cardiac functions after myocardial infarction; however, their full potential has not yet been realized. For instance, the majority of potential candidates for cell therapy suffer from chronic heart failure (CHF), and it is unclear how this disease affects the explant-derived progenitor cells. Therefore, the objective of this study was to determine the effect of CHF on the number and phenotype of cardiac explant c-Kit+ progenitors and elucidate mechanisms of their regulation., Methods and Results: Myocardial infarction was created by left anterior descending coronary artery occlusion. Sham-operated animals were used as a control group. CHF-developed infarcted animals were selected on the basis of left ventricle end-diastolic pressure ≥ 20 mm Hg and scar size ≥ 30%. Here, we found that CHF atrial explants produced less c-Kit+ cells than sham explants. CHF-derived c-Kit+ cells exhibited upregulated transforming growth factor-β (TGF-β) signaling, increased level of epithelial to mesenchymal transition markers, and diminished expression of pluripotency markers compared with shams. We show that intervention with TGF-β signaling by inhibiting TGF-β receptor type I or Smad 2/3 using small-molecule inhibitors improved c-Kit+ cell yield, attenuated epithelial to mesenchymal transition markers, stimulated the pluripotency marker Nanog, and improved efficiency of c-Kit+ cell differentiation toward cardiomyocyte-like cells in vitro., Conclusions: Taken together, our findings suggest that TGF-β inhibition positively modulates c-Kit+ cell phenotype and function in vitro, and this strategy may be considered in optimizing cardiac progenitor function and cell expansion protocols for clinical application.

Objectives: To evaluate serum leptin concentration and its relation to metabolic syndrome (MSy) in non-diabetic patients with myotonic dystrophy type 1 (DM1)., Materials and Methods: This study included 34 DM1 patients, and the same number of healthy subjects matched for age, sex and body mass index (BMI)., Results: DM1 patients had increased BMI and insulin resistance, and increased leptin and insulin concentrations, but the other features of MSy such as diabetes, glucose intolerance and hypertension were not detected in DM1 patients. Serum leptin levels were higher in patients with DM1 than in healthy controls (8.5 +/- 6.6 ng/ml vs 3.6 +/- 2.9 ng/ml in men, and 13.9 +/- 10.0 ng/ml vs 10.9 +/- 6.9 ng/ml in women, respectively). In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) (P < 0.01)., Conclusions: The leptin overproduction correlated with insulin resistance in DM1 patients but the significance of this finding remains unclear.