This cohort study examines the rate of SARS-CoV-2 reinfection among people in Lombardy, Italy, who previously recovered from COVID-19.

The high incidence and poor prognosis of heart failure (HF) patients affected with diabetes (DM) is in part related to a specific cardiac remodeling currently recognized as diabetic cardiomyopathy (DCM). This cardiac frame occurs regardless of the presence of coronary artery diseases (CAD) and it can account for 15–20% of the total diabetic population. The pathogenesis of DCM remains controversial, and several molecular and cellular alterations including myocardial hypertrophy, interstitial fibrosis, oxidative stress and vascular inflammation, have been postulated. The main cardio-vascular alterations associated with hyperglycemia comprise endothelial dysfunction, adverse effects of circulating free fatty acids (FFA) and increased systemic inflammation. High glucose concentrations lead to a loss of mitochondrial networks, increased reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS) activation and a reduction in cGMP production related to protein kinase G (PKG) activity. Current mechanisms enhance the collagen deposition with subsequent increased myocardial stiffness. Several concerns regarding the exact role of DCM in HF development such as having an appearance as either dilated or as a concentric phenotype and whether diabetes could be considered a causal factor or a comorbidity in HF, remain to be clarified. In this review, we sought to explain the different DCM subtypes and the underlying pathophysiological mechanisms. Therefore, the traditional and new molecular and signal alterations and their relationship with macroscopic structural abnormalities are described.

BackgroundDNA methylation is an epigenetic mechanism for regulating the transcription of many genes and has been linked to the development of various diseases. A promising gene to investigate is methylenetetrahydrofolate reductase (MTHFR), since the enzyme methylenetetrahydrofolate reductase (MTHFR) promotes methyl radical synthesis in the homocysteine cycle and can provide methyl groups for DNA methylation. In addition, several studies have correlated gene polymorphisms of this enzyme with a greater risk of diabetes, but little is known regarding the relationship between epigenetic changes in this gene and diabetes and its complications. The aim of this study was to investigate the relationship between methylation profile in the MTHFR gene promoter and biochemical, inflammatory and oxidative stress markers in individuals with type 2 diabetes (T2DM) who have been diagnosed for 5–10 years with or without diabetic retinopathy (DR) and nephropathy (DN).MethodsSpecific PCR for methylation (MSP) was used to analyze MTHFR methylation profile in leucocytes DNA. Biochemical markers (glycemia, glycated hemoglobin, total cholesterol, LDL, HDL, triglycerides, serum creatinine), inflammatory markers (C-reactive protein and alpha-1 acid glycoprotein) and oxidative stress (total antioxidant and malonaldehyde) were determined in peripheric blood samples and microalbuminuria in 24 h urine samples. The X2 and Mann–Whitney statistical tests were performed and p < 0.05 were considered significant.ResultsThe hypermethylated profile was most frequently observed in individuals with retinopathy (p < 0.01) and was associated with higher total cholesterol and LDL levels (p = 0.0046, 0.0267, respectively). Individuals with DN and hypermethylated profiles had higher levels of alpha-1 acid glycoprotein (p = 0.0080) and total antioxidant capacity (p = 0.0169) compared to subjects without complications.ConclusionsHypermethylation in the promoter of the MTHFR gene is associated with the occurrence of DR and with biochemical, inflammatory and oxidative stress parameters in the context of chronic complications

No abstract

Although myocarditis can be a severe cardiac complication of COVID-19 patients, few data are available in the literature about the incidence and clinical significance in patients affected by SARS-CoV-2. This study aims to describe the prevalence and the clinical features of suspected myocarditis in 3 cohorts of patients hospitalized for COVID-19. We retrospectively evaluated all the consecutive patients admitted for COVID-19 without exclusion criteria. Suspect myocarditis was defined according to current guidelines. Age, sex, in-hospital death, length of stay, comorbidities, serum cardiac markers, interleukin-6, electrocardiogram, echocardiogram, and therapy were recorded. Between March 4 to May 20, 2020, 1169 patients with COVID-19 were admitted in 3 Italian Medicine wards. 12 patients (1%) had suspected acute myocarditis; 5 (41.7%) were men, mean age was 76 (SD 11.34; median 78.5 years); length of stay was 38 days on average (SD 8, median value 37.5); 3 (25%) patients died. 8 (66.7%) had a history of cardiac disease; 7 (58.33%) patients had other comorbidities like diabetes, chronic obstructive pulmonary disease, or renal insufficiency. Myocarditis patients had no difference in sex prevalence, rate of death, comorbidities, elevations in serum cardiac markers as compared with patients without myocardial involvement. Otherwise, there was a significantly higher need for oxygen-support and a higher prevalence of cardiac disease in the myocarditis group. Patients with suspected myocarditis were older, had a higher frequency of previous cardiac disease, and significantly more prolonged hospitalization and a lower value of interleukin-6 than other COVID-19 patients. Further studies, specifically designed on this issue, are warranted.

SUMMARYBecause abnormalities in redox balance cluster in type I diabetes families and the intracellular thiol redox status seems to modulate immune function, we aimed to investigate the relationship between oxidative stress and immunological features. We measured oxidative markers, serum proinflammatory cytokines, soluble cytokine receptors and subsets of peripheral blood lymphocytes (by varying combinations of CD4, CD8, CD23 or low-affinity IgE receptor, and CD25 or IL-2 receptor) from 38 type I patients, 76 low-risk (i.e. without underlying islet autoimmunity) non-diabetic first-degree relatives of diabetic patients, and 95 healthy subjects. In type I diabetes families, protein and lipid oxidation was confirmed by the presence of reduced sulphhydryl groups, increased advanced oxidation protein products, and increased plasma and erythrocyte malondialdehyde. Relatives had decreased counts of monocytes, of cells co-expressing CD23 and CD25 and of CD25 + cells in peripheral blood. Patients with TIDM had similar defects and, in addition, showed decreased counts of peripheral CD4 + CD8+ lymphocytes and increased serum levels of soluble receptors for interleukin (IL)-6 and IL-2. Abnormal indicators of oxidative stress were related in part to immune abnormalities. In the whole study group, we found a correlation (multiple R 0·5, P < 0·001) of CD23 + CD25+ cells with blood counts of monocytes, CD4 + CD8 + cells, CD25 + cells, basal haemolysis and plasma levels of thiols. In type I diabetics, anti-GAD65 antibody levels were associated (multiple R 0·6, P = 0·01) positively with sIL-6R, negatively with duration of diabetes and CD23 + CD25 + counts; plasma creatinine correlated positively (multiple R 0·6, P < 0·001) with both sIL-2R and tumour necrosis factor (TNF)-a concentration. Our study reports the first evidence that the oxidative stress observed in type I families is related to immunological hallmarks (decreased peripheral numbers of monocytes as well as cells bearing a CD4 + CD8 + , CD23 + CD25 + and CD25 + phenotype) from which the involvement of some immunoregulatory mechanisms could be suspected. It remains to be elucidated the course of events culminating in the loss of physiological immune homeostasis and disease pathology.

BackgroundPolymorphisms in the gene encoding methylenetetrahydrofolate reductase (MTHFR) have been investigated as risk factors for microvascular complications of diabetes; however, simultaneous analysis of these polymorphisms and the methylation pattern of the gene has never been conducted. The objective of the present study was to evaluate the simultaneous relationship between MTHFR methylation and MTHFR C6TT7 and A1298C polymorphisms with metabolic, inflammatory and oxidative stress parameters related to microvascular complications, diabetic retinopathy (DR) and diabetic nephropathy (DN) in diabetic patients.MethodsA total of 107 patients who were diagnosed in the previous 5 to 10 years were recruited and divided into groups with complications (DR and/or DN) or without complications. Methylation analysis of the gene promoter was conducted using the MSP technique, and analysis of the A1298C and C677T polymorphisms was conducted using the restriction fragment length polymorphism (RFLP) assay. Microalbuminuria was determined using urine samples, and other analytes of interest were determined in blood samples using commercial kits. The Mann–Whitney and Chi square statistical tests were used with significance considered at p < 0.05.ResultsSubjects with a hypermethylated profile and the 1298AA genotype showed the highest levels of blood glucose (p = 0.03), total cholesterol (p = 0.0001) and LDL cholesterol (p = 0.0006). The same profile was associated with higher levels of HbA1c (p = 0.025), glycemia (p = 0.04) and total cholesterol (0.004) in the control group and total cholesterol (p = 0.005) and LDL cholesterol (p = 0.002) in the complications group. Serum creatinine was higher in subjects in the hypermethylated group with the genotype 677CC only in the control group (p = 0.0020). The methylated profile in presence of 677CC + 1298AA and the 677CT/TT +1298AA haplotypes showed higher levels of total cholesterol (p = 0.0024; 0.0031) and LDL cholesterol (p = 0.0060; 0.0125) than 1298AC/CC carriers. The fasting glycemia was higher in hypermethylated profile in the presence of 677CC/1298AA haplotype (p = 0.0077).ConclusionThe hypermethylated methylation profile associated with the 1298AA genotype appeared to be connected to higher values of glycemia, total cholesterol and LDL cholesterol.

Objective: Nutritional status and lifestyle can have profound effects on health. To analyse behaviour patterns in population subgroups of public health importance, we compared lifestyle, dietary intake of energy and selected nutrients, and nutritional biomarkers of type 1 diabetes (T1DM) patients and nondiabetic first-degree relatives against control subjects with no family history of T1DM. Design: A cross-sectional study. Setting: Department of Internal Medicine, University of Pisa, Italy. Subjects: A total of 209 individuals including 38 type 1 patients, 76 relatives, and 95 healthy subjects. Interventions: We used the European Prospective Investigation of Cancer and Nutrition questionnaires to assess dietary intake and lifestyle. Anthropometric indices and nutritional biomarkers (such as plasma levels of albumin, iron, lipids, homocysteine, vitamin B 9 and vitamin B 12 as well as urinary outputs of nitrogen, sodium and potassium) were evaluated. Results: Emerging health issues: (1) In total, 45% of controls were overweight. Increasing age was associated with increasing body mass and decreasing activity in sport in front of an unchanged energy intake.(2) The distribution of energy sources was incorrect. The proportion of caloric intake derived from total fat and cholesterol did not match general guidelines. Total dietary fibre consumption was assessed to be adequate (25 g/day) in only 27% of all the participants. (3) Estimated daily intakes of water-soluble vitamin B 9 and fat-soluble vitamin D and vitamin E were deficient in comparison with dietary reference intakes. (4) The prevalence of adoption and maintenance of healthful eating and physical activity habits was higher in women and T1DM patients (probably as a consequence of the medical educational intervention). On the contrary, supportiveness of the family in term of changing the undesirable behaviours at home seemed to fail. Conclusions: This study provides first evidence indicating unhealthy dietary behaviours, which could even predispose to the development of diabetes and cardiovascular complications, in subjects living in Pisa. The combination of vitamin B 9 and vitamin E deprivation could be deleterious for endothelial function, since these antioxidants have been implicated in the modulation of nitric oxide and eicosanoid signalling.