AimsButyric acid (BUT), a short chain fatty acid produced daily by the gut microbiota, has proven beneficial in models of cardiovascular diseases. With advancements in cancer survival, an increasing number of patients are at risk of anticancer drug cardiotoxicity. Here we assess whether the novel BUT derivative phenylalanine-butyramide (FBA) protects from doxorubicin (DOXO) cardiotoxicity, by decreasing oxidative stress and improving mitochondrial function.In C57BL6 mice, DOXO produced left ventricular dilatation assessed by echocardiography. FBA prevented left ventricular dilatation, fibrosis and cardiomyocyte apoptosis when co-administered with DOXO. DOXO increased atrial natriuretic peptide, brain natriuretic peptide, connective tissue growth factor, and matrix metalloproteinase-2 mRNAs, which were not elevated on co-treatment with FBA. DOXO, but not FBA + DOXO mice, also showed higher nitrotyrosine levels, and increased inducible nitric oxide synthase expression. Accordingly, DOXO hearts showed lower levels of intracellular catalase vs. sham, while pre-treatment with FBA prevented this decrease. We then assessed for reactive oxygen species (ROS) emission: DOXO induced increased activity of mitochondrial superoxide dismutase and higher production of H 2 O 2 , which were blunted by FBA pre-treatment. FBA also ameliorated mitochondrial state 3 and state 4 respiration rates that were compromised by DOXO. Furthermore, in DOXO animals, the mitochondrial degree of coupling was significantly increased vs. sham, while FBA was able to prevent such increase, contributing to limit ROS production, Finally, FBA reduced DOXO damage in human cellular models, and increased the tumour-killing action of DOXO.

The objective of this study was to assess the feasibility of recording pulmonary venous blood flow in the human fetus, and to evaluate its relationship with gestational age. We studied 152 singleton pregnancies between the 19th and 40th weeks of gestation. One hundred and one cases were studied cross-sectionally to gather data on color flow visualization, and 51 were studied longitudinally. The upper right pulmonary vein was interrogated by pulsed wave Doppler to assess pulmonary venous blood flow. On color Doppler, the upper right pulmonary vein could be imaged in 89.6% of cases in the peri-atrial tract and in 75% of cases within the lung. The upper left pulmonary vein could only be imaged in 8% of cases close to the atrium and in 41% of cases within the lung. Reliable velocity waveforms were obtained in 91% of cases. The mean systolic peak velocity was 22.19 +/- 6.39 cm/s and the mean diastolic peak velocity was 22.1 +/- 6.35 cm/s. Both increased significantly with gestational age. Reversed end-diastolic blood flow was present in 18% of cases, regardless of gestational age and fetal heart rate. Expressed as a percentage of the forward flow velocity time integral, its value was 7.65 +/- 5.2%. Our data seem to confirm the presence of pulsatile pulmonary venous blood flow in the second- and third-trimester fetus. Normative data have been established for the second and third trimesters of pregnancy.

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Innovative therapeutic strategies in childhood cancer led to a significant reduction in cancer-related mortality. Cancer survivors are a growing fragile population, at risk of long-term side effects of cancer treatments, thus requiring customized clinical attention. Antineoplastic drugs have a wide toxicity profile that can limit their clinical usage and spoil patients’ life, even years after the end of treatment. The cardiovascular system is a well-known target of antineoplastic treatments, including anthracyclines, chest radiotherapy and new molecules, such as tyrosine kinase inhibitors. We investigated nutritional changes in children with cancer from the diagnosis to the end of treatment and dietary habits in cancer survivors. At diagnosis, children with cancer may present variable degrees of malnutrition, potentially affecting drug tolerability and prognosis. During cancer treatment, the usage of corticosteroids can lead to rapid weight gain, exposing children to overweight and obesity. Moreover, dietary habits and lifestyle often dramatically change in cancer survivors, who acquire sedentary behavior and weak adherence to dietary guidelines. Furthermore, we speculated on the role of nutrition in the primary prevention of cardiac damage, investigating the potential cardioprotective role of diet-derived compounds with antioxidative properties. Finally, we summarized practical advice to improve the dietary habits of cancer survivors and their families.

BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can potentially develop after SARS-CoV-2 infection in children. Gastrointestinal manifestation in MIS-C can mimic acute abdomen, potentially leading to unnecessary surgical treatment. Immune-mediated mechanisms seem to be a determining factor in its pathogenesis, and histological studies can help to shed light on this aspect. We describe three cases of children diagnosed with MIS-C that underwent appendectomy.MethodsWe retrospectively collected the clinical features and histological findings of three previously healthy children who underwent appendectomy for clinical suspicion of acute appendicitis but were later diagnosed with MIS-C.FindingsThe three children presented with prominent abdominal manifestations and fever leading to the suspicion of acute abdomen. Histological findings showed transmural and perivascular inflammation. Notably, CD68+ macrophages were predominant in the child with milder abdominal symptoms without cardiac injury, while CD3+ lymphocytes in the patient presented with more severe abdominal pain and cardiovascular involvement at admission.InterpretationGastrointestinal symptoms of children with MIS-C improve after proper immunomodulatory therapy, conversely showing inadequate response to surgical appendectomy. Histological findings revealed different inflammatory cell infiltration that primarily involved perivisceral fat and vessels, and subsequently mucosal tissue, in contrast to other forms of acute appendicitis. Our findings suggest that this kind of peri-appendicitis in MIS-C could represent a focal sign of systemic inflammation, with different histological patterns compared to other forms of acute appendicitis.

This paper proposes a different point of view to look at the Nelson's derivatives. In particular we relate the Nelson's forward derivative of a function of a diffusion, with certain properties, to the partial differential equation coming from the Feynman-Kac's theorem. We will see that whenever the Nelson forward derivative of functions of a diffusion process, that satisfies a certain stochastic differential equations, is computed at the initial point of the process and whenever we put it equal to zero, we obtain a partial differential equation. The latter is the same equation coming from the Feynman-Kac's theorem. Finally we will see how we could reduce the stochastic derivatives to the forward Nelson's derivative of a certain process by supposing the existence of a new complex processes related to the backward filtration.