Healthy aging: the INTECMAN project.

Aging is associated not only with the reduction of psychophysical and sensory capacities but also with different types of neurodegenerative disorders up to dementia manifestations. Aging in health and self-sufficiency is strictly dependent on the prevention and correction of factors that may determine reduction of psychophysical capacities (e.g., cardiovascular, locomotor and neurodegenerative ones). To reach this goal, due to the dynamics of social and family changes and to the aging of the population, health professionals can be supported by technologies which provide noninvasive monitoring of physiologic parameters and rely on telemedicine, both instruments of support and care for better aging in the home setting. The authors, starting from the initial idea of a personalized monitoring of different psychophysical variables, defined a pilot study to assess the role of a 12-month individually tailored lifestyle counseling on parameters of mild cognitive impairment in a group of elderly subjects. Data derived from the applied approach appeared promising and may open the road to the possible implementation of individual counseling, based on multiparametric non-obtrusive technologies which take into consideration both psychological and physical aspects, to be followed in the home environment.

Cardiometabolic risk and subclinical vascular damage assessment in idiopathic inflammatory myopathies: a challenge for the clinician.

OBJECTIVES: A high prevalence of cardiovascular disease (CVD), not fully explained by the prevalence of traditional risk factors only, is reported in patients with idiopathic inflammatory myopathies (IIMs). Thus, we investigated if novel markers of CVD risk, like carotid diameter and advanced glycated end products, can better predict increased CVD risk in IIM patients. METHODS: We studied 43 consecutive patients diagnosed with IIM. All the patients underwent a clinical and laboratory evaluation of cardiovascular risk factors and characterisation of myositis disease activity. Non-invasive instrumental examinations performed included the measurement of carotid parameters (intima-media thickness, IMT and mean arterial diameter, mAD) by ultrasonic techniques, advanced glycation end-product accumulation in the skin by autofluorescence (AF) and body composition by bioelectrical impedance analysis. The parameters were compared to those measured in 29 controls, with similar mean age, BMI, blood pressure and smoking habits. RESULTS: IIM patients showed normal carotid IMT and distensibility, but higher carotid mAD (p=0.012), higher skin AF (p<0.001), lower fat free mass (p=0.036) and increased waist circumference compared to controls. A significant correlation was observed among AF and mAD (rho=0.317 p<0.05), carotid distension (rho=0.391 p=0.036) and IMT (rho=0.627 p<0.001). CONCLUSIONS: Abnormalities of the studied parameters suggest a higher risk of CV disease in IIM patients independent of disease activity. In this population, a thorough assessment of CV risk is recommended also in absence of overt CV disease during the clinical evaluation.

Vocal and motor behaviors as a possible expression of gastrointestinal problems in preschoolers with Autism Spectrum Disorder.

BACKGROUND: Gastrointestinal (GI) problems are one of the most frequent comorbidities in Autism Spectrum Disorder (ASD) but can be under-recognized due to the concomitant communication difficulties of this population. Accordingly, some associated behaviors (AB) such as verbal and motor behaviors (VB and MB, respectively) have been identified as a possible expression of an underlying GI problem and evaluated through an ad hoc questionnaire (the Associated Behaviors Questionnaire -ABQ-). The aims of this study were to investigate the presence and the type of AB in an Italian sample of ASD preschoolers, and to determine their correlations with GI problems. METHODS: We included 85 ASD preschoolers (mean age 4.14 years; SD 1.08) splitted into two groups (GI and No-GI) through the GI Severity Index instrument. AB were evaluated through the ABQ that includes VB, MB and Changes in overall state (C) clusters. Specific tools were administered to evaluate the ASD core ad associated symptoms, as well as the intellective and adaptive functioning. RESULTS: The GI group (N = 30) showed significantly higher scores in all the three ABQ areas (VB, MB and C) than the No-GI group (N = 55), with a positive correlation between GI symptoms and some specific AB as well as ABQ Total score. By dividing the whole sample in verbal and non-verbal individuals, both specific and shared AB emerged in the two groups. CONCLUSIONS: Our results alert clinicians to consider behavioral manifestations as a possible expression of GI problems in ASD subjects. Therefore, the evaluation of AB may be useful to identify the presence of GI problems in the ASD populations, and especially in non-verbal ASD children.

Autonomic Nervous System Response during Light Physical Activity in Adolescents with Anorexia Nervosa Measured by Wearable Devices.

Anorexia nervosa (AN) is associated with a wide range of disturbances of the autonomic nervous system. The aim of the present study was to monitor the heart rate (HR) and the heart rate variability (HRV) during light physical activity in a group of adolescent girls with AN and in age-matched controls using a wearable, minimally obtrusive device. For the study, we enrolled a sample of 23 adolescents with AN and 17 controls. After performing a 12-lead electrocardiogram and echocardiography, we used a wearable device to record a one-lead electrocardiogram for 5 min at baseline for 5 min during light physical exercise (Task) and for 5 min during recovery. From the recording, we extracted HR and HRV indices. Among subjects with AN, the HR increased at task and decreased at recovery, whereas among controls it did not change between the test phases. HRV features showed a different trend between the two groups, with an increased low-to-high frequency ratio (LF/HF) in the AN group due to increased LF and decreased HF, differently from controls that, otherwise, slightly increased their standard deviation of NN intervals (SDNN) and the root mean square of successive differences (RMSSD). The response in the AN group during the task as compared to that of healthy adolescents suggests a possible sympathetic activation or parasympathetic withdrawal, differently from controls. This result could be related to the low energy availability associated to the excessive loss of fat and lean mass in subjects with AN, that could drive to autonomic imbalance even during light physical activity.

The relationship between forearm skin speed-resolved perfusion and oxygen saturation, and finger arterial pulsation amplitudes, as indirect measures of endothelial function.

OBJECTIVE: Endothelial function is important for regulating peripheral blood flow to meet varying metabolic demands and can be measured indirectly during vascular provocations. In this study, we compared the PAT finger response (EndoPAT) after a 5-minutes arterial occlusion to that from forearm skin comprehensive microcirculation analysis (EPOS). METHODS: Measurements in 16 subjects with varying cardiovascular risk factors were carried out concurrently with both methods during arterial occlusion, while forearm skin was also evaluated during local heating. RESULTS: Peak values for EPOS skin Perfconv and speed-resolved total perfusion after the release of the occlusion were significantly correlated to the EndoPAT RHI (ρ = .68, P = .007 and ρ = .60, P = .025, respectively), mainly due to high-speed blood flow. During local heating, EPOS skin oxygen saturation, SO2, was significantly correlated to RHI (ρ = .62, P = .043). This indicates that SO2 may have diagnostic value regarding endothelial function. CONCLUSIONS: We have demonstrated for the first time a significant relationship between forearm skin microcirculatory perfusion and oxygen saturation and finger PAT. Both local heating and reactive hyperemia are useful skin provocations. Further studies are needed to understand the precise regulation mechanisms of blood flow and oxygenation during these tests.

Excessive physical activity in young girls with restrictive-type anorexia nervosa: its role on cardiac structure and performance.

PURPOSE: The aim of this study was to investigate the influence of hyperactivity on left ventricular mass (LVM) in Anorexia Nervosa restricting-type (AN-R) and the correlation between LVM and auxologic parameters/circulating hormones. METHODS: Echocardiography was performed in 44 AN-R girls, subgrouped in 24 hyperactive (ANH+) and 20 non-hyperactive (ANH-), and in 20 controls (HC). LVM indexed to Body Surface Area (LVMi) and LVM indexed to height (LVMh) were calculated. RESULTS: LVMi and LVMh were significantly lower in the AN-R subjects compared to HC. Moreover, both LVMi and LVMh were higher in the ANH+ than in the ANH-. In the HC, LVMi was higher when compared to the ANH- subjects than to the ANH+. Stepwise analysis revealed that in the ANH+ group, fT4 was the only independent predictor of LVMh, while in the ANH- group, height was the only independent predictors of LVMi. CONCLUSIONS: Despite its negative influence on disease severity and outcome, hyperactivity from the standpoint of cardiac function makes the LVM of AN-R young girls more similar to HC. LEVEL OF EVIDENCE: Level III, case-control study.

New cardiac expression of two adenosine-2A receptor isoforms in dysfunctioning minipigs.

PURPOSE: Eight A2AR variants are reported in humans while no A2AR isoforms in pigs. The aim of this study was to evaluate potential isoforms presence in cardiac pig tissue to better define possible involvement of A2AR in the cardiovascular pathophysiology. MATERIALS AND METHODS: In adult male minipigs (n = 4) left ventricular dysfunction (LVD) was induced by pacing at 200 bpm in the right ventricular (RV) apex. In these animals and in sham operated pigs (C-SHAM, n = 4) cardiac tissue was collected from LV-septal wall (LV-SW)-close to pacing site-and from lateral (opposite) site (LV-OSW). A2AR specific primers, derived from Sus scrofa AY772412 sequence, were used for Real-Time PCR. The DNA was sequenced using the Sanger method. Histological analysis was also performed. RESULTS: In LV-SW of LVD minipigs the A2AR melting curves were characterized by a sharp peak between 87 and 91 °C (short isoform, 1-94 bp) on the right of the principal peak corresponding to a long A2AR isoform (GenBank: JQ229674.1) 1-213 bp. As for C-SHAM only one peak was observed in LV-OSW region of LVD animals. The short isoform had an alternative promoter region and a specific translated protein. Histology showed in LVD-LV-SW prominent Purkinje cells compared to LV-OSW and C-SHAM. No difference in A2AR expression was observed between LVD animals and C-SHAM although a slight decrease was observed in LVD-LV-OSW. CONCLUSIONS: The presence of two different isoforms in the myocardium close to the insertion of pacing is suggestive of a differential state-specific expression of A2AR in cardiac tissue.

Adenosine receptors expression in cardiac fibroblasts of patients with left ventricular dysfunction due to valvular disease.

CONTEXT: Adenosine restores tissue homeostasis through the interaction with its membrane receptors (AR) expressed on fibroblasts, endothelial cells, smooth muscle cells and leukocytes, but their modulation is still not fully understood. OBJECTIVE: To evaluate whether changes in the transcriptomic profiling of adenosine receptors (AR) occur in cardiac fibroblasts (CF) of patients (pts) with LV dysfunction due to valvular disease (V). The secondary aim was to compare in the same pts the results obtained at cardiac level with those found in circulating leukocytes. MATERIALS AND METHODS: Auricle fragments were excised from 13 pts during prosthetic implantation while blood samples were collected from pts (n = 9) and from healthy subjects (C, n = 7). In 7 pts cardiac biopsy and blood samples were taken simultaneously. A human CF atrial cell line (cc) was used as control. RESULTS: AR higher levels of mRNA expression were observed with real-time PCR in Vpts compared to C, both at cardiac (overexpression A1R:98%, A2AR:63%, A2BR:87%, A3R:85%, CD39:92%, CD73:93%) and at peripheral level (A1R vs C: p = .0056; A2AR vs C: p = .0173; A2BR vs C: p = .0272; A3R vs C: p = .855; CD39 vs C: p = .0001; CD73 vs C: p = .0091). CONCLUSION: All AR subtypes were overexpressed in CF of Vpts. The same trends in AR expression at cardiac level was assessed on circulating leukocytes, thus opening a new road to minimally invasive studies of the adenosinergic system in cardiac patients.

Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters.

BACKGROUND: A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a "gut-brain axis" disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx®) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. METHODS: A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. DISCUSSION: The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02708901 . Retrospectively registered: March 4, 2016.

Altered expression of connexin 43 and related molecular partners in a pig model of left ventricular dysfunction with and without dipyrydamole therapy.

Gap junctions (GJ) mediate electrical coupling between cardiac myocytes, allowing the spreading of the electrical wave responsible for synchronized contraction. GJ function can be regulated by modulation of connexon densities on membranes, connexin (Cx) phosphorylation, trafficking and degradation. Recent studies have shown that adenosine (A) involves Cx43 turnover in A1 receptor-dependent manner, and dipyridamole increases GJ coupling and amount of Cx43 in endothelial cells. As the abnormalities in GJ organization and regulation have been described in diseased myocardium, the aim of the present study was to assess the regional expression of molecules involved in GJ regulation in a model of left ventricular dysfunction (LVD). For this purpose the distribution and quantitative expression of Cx43, its phosphorylated form pS368-Cx43, PKC phosphorylated substrates, RhoA and A receptors, were investigated in experimental models of right ventricular-pacing induced LVD, undergoing concomitant dipyridamole therapy or placebo, and compared with those obtained in the myocardium from sham-operated minipigs. Results demonstrate that an altered pattern of factors involved in Cx43-made GJ regulation is present in myocardium of a dysfunctioning left ventricle. Furthermore, dipyridamole treatment, which shows a mild protective role on left ventricular function, seems to act through modulating the expression and activation of these factors as confirmed by in vitro experiments on cardiomyoblastic cell line H9c2 cells.

The role of wearable sensors and wireless technologies for the assessment of heart rate variability in anorexia nervosa.

PURPOSE: Bradycardia and abnormal cardiac autonomic function are related to increased mortality in anorexia nervosa (AN). The aim of this study was to assess heart rate (HR) and HR variability of young adolescents with AN as compared to controls by means of wearable sensors and wireless technologies. METHOD: The ECG signal was recorded in 27 AN girls and 15 healthy girls at rest using a wearable chest strap. The tachogram, the mean intervals between R peaks (meanRR), the root mean square of successive differences (RMSSD), the power of low-frequency (LF) and high-frequency (HF) bands and the LF/HF ratio were assessed. RESULTS: All AN girls showed a reduced HR and an increased meanRR and RMSSD. An HF increase, a LF decrease, and a LF/HF reduction indicated a prevalence of the parasympathetic on sympathetic activity. CONCLUSIONS: The instruments used in this pilot study were feasible, unobtrusive and extremely suitable in AN subjects who are burdened by high incidence of cardiovascular mortality; their application could open to new approaches of vital signs monitoring in hospitals as well as in home settings.

Adenosine receptor expression in an experimental animal model of myocardial infarction with preserved left ventricular ejection fraction.

Adenosine, a purine nucleoside and a "retaliatory metabolite" in ischemia, is ubiquitous in the body and increases 100-fold during ischemia. Its biological actions are mediated by four adenosine receptors (ARs): A(1), A(2A), A(2B) and A(3). The aim of this study was to determine possible myocardial alterations in AR expression in an experimental animal model of myocardial infarction (MI) with a preserved left ventricular (LV) ejection fraction. LV tissue was collected from sexually mature male farm pigs with MI (n = 6) induced by permanent surgical ligation of the left anterior descending coronary artery and from five healthy pigs (C). mRNA expression of A(1)R, A(2A)R, A(2B)R, A(3)R and TNF-α was determined by real-time PCR in tissue collected from border (BZ) and remote zones (RZ) of the infarcted area and from LV of C. BZ, RZ and samples of C were stained immunohistochemically to investigate A(3)R immunoreaction. After 4 weeks a different regulation of ARs was observed. A(1)R mRNA expression was significantly lower in the infarct regions than in controls (C = 0.75 ± 0.2, BZ = 0.05 ± 0.2, RZ = 0.07 ± 0.02 p = 0.0025, p = 0.0016, C vs. BZ and RZ, respectively). Conversely A(3)R was higher in infarct areas (C = 0.94 ± 0.2, BZ = 2.85 ± 0.5, RZ = 3.48 ± 1.0, p = 0.048 C vs. RZ). No significant differences were observed for A(2A)R (C = 1.58 ± 0.6, BZ = 0.42 ± 0.1, RZ = 1.37 ± 0.6) and A(2B)R (C = 1.66 ± 0.2, BZ = 1.54 ± 0.5, RZ = 1.25 ± 0.4). A(3)R expression was confirmed by immunohistochemical analysis and was principally localized in cardiomyocytes. TNF-α mRNA results were: C 0.41 ± 0.25; BZ 1.60 ± 0.19; RZ 0.17 ± 0.04. The balance between A(1)R and A(3)R as well as between A(2A)R and A(2B)R was consistent with adaptative retaliatory anti-ischemic adenosinergic changes in the infarcted heart with preserved LV function.

Echo state networks for the recognition of type 1 Brugada syndrome from conventional 12-LEAD ECG.

Artificial Intelligence (AI) applications and Machine Learning (ML) methods have gained much attention in recent years for their ability to automatically detect patterns in data without being explicitly taught rules. Specific features characterise the ECGs of patients with Brugada Syndrome (BrS); however, there is still ambiguity regarding the correct diagnosis of BrS and its differentiation from other pathologies. This work presents an application of Echo State Networks (ESN) in the Recurrent Neural Networks (RNN) class for diagnosing BrS from the ECG time series. 12-lead ECGs were obtained from patients with a definite clinical diagnosis of spontaneous BrS Type 1 pattern (Group A), patients who underwent provocative pharmacological testing to induce BrS type 1 pattern, which resulted in positive (Group B) or negative (Group C), and control subjects (Group D). One extracted beat in the V2 lead was used as input, and the dataset was used to train and evaluate the ESN model using a double cross-validation approach. ESN performance was compared with that of 4 cardiologists trained in electrophysiology. The model performance was assessed in the dataset, with a correct global diagnosis observed in 91.5 % of cases compared to clinicians (88.0 %). High specificity (94.5 %), sensitivity (87.0 %) and AUC (94.7 %) for BrS recognition by ESN were observed in Groups A + B vs. C + D. Our results show that this ML model can discriminate Type 1 BrS ECGs with high accuracy comparable to expert clinicians. Future availability of larger datasets may improve the model performance and increase the potential of the ESN as a clinical support system tool for daily clinical practice.

The role of the adenosinergic system in lung fibrosis.

Adenosine (ADO) is a retaliatory metabolite that is expressed in conditions of injury or stress. During these conditions ATP is released at the extracellular level and is metabolized to adenosine. For this reason, adenosine is defined as a "danger signal" for cells and organs, in addition to its important role as homeostatic regulator. Its physiological functions are mediated through interaction with four specific transmembrane receptors called ADORA1, ADORA2A, ADORA2B and ADORA3. In the lungs of mice and humans all four adenosine receptors are expressed with different roles, having pro- and anti-inflammatory roles, determining bronchoconstriction and regulating lung inflammation and airway remodeling. Adenosine receptors can also promote differentiation of lung fibroblasts into myofibroblasts, typical of the fibrotic event. This last function suggests a potential involvement of adenosine in the fibrotic lung disease processes, which are characterized by different degrees of inflammation and fibrosis. Idiopathic pulmonary fibrosis (IPF) is the pathology with the highest degree of fibrosis and is of unknown etiology and burdened by lack of effective treatments in humans.

Effect of concomitant oral chronic dipyridamole therapy on inflammatory cytokines in heart failure patients.

BACKGROUND: To assess whether dipyridamole therapy exerts a significant anti-inflammatory effect in heart failure patients. METHODS: We performed a retrospective analysis of the stored bio-samples of 3 groups of patients: 1) 25 normal healthy controls (N); 2) 25 heart failure patients (HF) under standard optimal therapy, including aspirin; 3) 17 HF patients with previous stroke and under clinically-driven therapy with A (Aggrenox, long-acting dipyridamole 200 mg + aspirin 25 mg, twice daily) for at least 1 month (HF-A). In all, we evaluated interleukin (IL)-6, adiponectin and C-reactive protein (CRP) as well as NT-proBNP. The same laboratory measurements were performed in the 17 HF patients with recent or previous stroke, both before and 1-month after clinically driven administration of A. RESULTS: All laboratory inflammatory indices were significantly higher in HF patients compared to N: IL-6 (N = 0.68 (0.3 - 12.7) vs. HF = 3.10 (0.5 - 16.7) vs. HF-A = 1.24 (0.3 - 3.3) pg/mL; p < 0.001 N vs. HF, p < 0.01 N vs. HF-A, p = ns HF vs. HF-A); CRP (N = 0.12 (0.01 - 0.45) vs. HF = 0.58 (0.04 - 2.7) vs. HF-A = 0.72 (0.02 - 4.8) mg/dL; p = ns N vs. HF, p = 0.05 N vs. HF-A, p = ns HF vs. HF-A); Adiponectin (N = 8.8 (3.0 - 31.4) vs. HF = 12.16 (4.9 - 27.3) vs. HF-A = 10.0 (4.8 - 15.6) pg/mL; p < 0.05 N vs. HF, p = ns N vs. HF-A p = ns HF vs. HF-A). NT-proBNP was also increased (N = 42.2 (13 - 93) vs. HF = 1907 (18.1 - 8038) vs. HF-A = 497.9 (7.8 - 3686) pg/mL; p < 0.001 N vs. HF, p = 0.01 N vs. HF-A, p = ns HF vs. HF-A). In 17 subjects, the intra-patient assessment (before and 1-month after starting of Aggrenox therapy) did not show a decrease in inflammation markers. CONCLUSIONS: HF patients show an increase in inflammatory indices independently of underlying A therapy.

[Idiopathic pulmonary fibrosis: from experimental approach to clinic]. / La fibrosi polmonare idiopatica: dall'approccio sperimentale alla clinica.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by interstitial lung fibrosis with involvement of alveoli and terminal bronchiole. Its pathogenesis is still unknown, the risk factors involved in this disease are still unclear and its prognosis highly unfavorable. The main clinical presentations, the major and minor diagnostic criteria, the principal hypothesis on the pathogenesis of IPF and the experimental approaches for induction of the disease mostly in the murine model will be discussed together with current available treatments and ongoing clinical studies on drug therapy.

Microplastics: A Matter of the Heart (and Vascular System).

Plastic use dramatically increased over the past few years. Besides obvious benefits, the consequent plastic waste and mismanagement in disposal have caused ecological problems. Plastic abandoned in the environment is prone to segregation, leading to the generation of microplastics (MPs) and nanoplastics (NPs), which can reach aquatic and terrestrial organisms. MPs/NPs in water can access fish's bodies through the gills, triggering an inflammatory response in loco. Furthermore, from the gills, plastic fragments can be transported within the circulatory system altering blood biochemical parameters and hormone levels and leading to compromised immunocompetence and angiogenesis. In addition, it was also possible to observe an unbalanced ROS production, damage in vascular structure, and enhanced thrombosis. MPs/NPs led to cardiotoxicity, pericardial oedema, and impaired heart rate in fish cardiac tissue. MPs/NPs effects on aquatic organisms pose serious health hazards and ecological consequences because they constitute the food chain for humans. Once present in the mammalian body, plastic particles can interact with circulating cells, eliciting an inflammatory response, with genotoxicity and cytotoxicity of immune cells, enhanced haemolysis, and endothelium adhesion. The interaction of MPs/NPs with plasma proteins allows their transport to distant organs, including the heart. As a consequence of plastic fragment internalisation into cardiomyocytes, oxidative stress was increased, and metabolic parameters were altered. In this scenario, myocardial damage, fibrosis and impaired electrophysiological values were observed. In summary, MPs/NPs are an environmental stressor for cardiac function in living organisms, and a risk assessment of their influence on the cardiovascular system certainly merits further analysis.

Expression of miRNAs in Pre-Schoolers with Autism Spectrum Disorders Compared with Typically Developing Peers and Its Effects after Probiotic Supplementation.

Alteration of the microbiota-gut-brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent an important modulating factor. In this contextual framework, we studied the transcriptional profile of specific circulating miRNAs associated with both ASD (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) and GID (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) in a group of pre-schoolers with ASD and in typically developing (TD) peers. In the ASD group, we also assessed the same miRNAs after a 6-month supplementation with probiotics and their correlation with plasma levels of zonulin and lactoferrin. At baseline, the expression of miRNAs involved in ASD were significantly reduced in ASD pre-schoolers vs. TD controls. Regarding the miRNAs involved in GID, the expression levels of miR-320-5p, miR-31-5p, and miR-223-5p were significantly higher in ASD than in TD subjects, whereas miR-21-5p showed significantly reduced expression in the ASD group vs. TD group. Supplementation with probiotics did not significantly change the expression of miRNAs in the ASD population. We found a significative negative correlation between zonulin and miR-197-5p and miR-21-5p at baseline, as well as between lactoferrin and miR-223-5p after 6 months of probiotic supplementation. Our study confirms the presence of an altered profile of the miRNAs investigated in ASD versus TD peers that was not modified by supplementation with probiotics.

A randomized controlled trial into the effects of probiotics on electroencephalography in preschoolers with autism.

LAY ABSTRACT: This study investigates the effects of a probiotic on preschoolers' brain electrical activity with autism spectrum disorder. Autism is a disorder with an increasing prevalence characterized by an enormous individual, family, and social cost. Although the etiology of autism spectrum disorder is unknown, an interaction between genetic and environmental factors is implicated, converging in altered brain synaptogenesis and, therefore, connectivity. Besides deepening the knowledge on the resting brain electrical activity that characterizes this disorder, this study allows analyzing the positive central effects of a 6-month therapy with a probiotic through a randomized, double-blind placebo-controlled study and the correlations between electroencephalography activity and biochemical and clinical parameters. In subjects treated with probiotics, we observed a decrease of power in frontopolar regions in beta and gamma bands, and increased coherence in the same bands together with a shift in frontal asymmetry, which suggests a modification toward a typical brain activity. Electroencephalography measures were significantly correlated with clinical and biochemical measures. These findings support the importance of further investigations on probiotics' benefits in autism spectrum disorder to better elucidate mechanistic links between probiotics supplementation and changes in brain activity.

[Coronary microvascular disease: from experimental models to clinical practice]. / La malattia del microcircolo coronarico nella disfunzione ventricolare sinistra: dai modelli sperimentali alla clinica.

Coronary vascular microcirculation plays a major role in the pathogenesis of left ventricular dysfunction as well as in the development of heart failure. Coronary microcirculation includes all the vessels which contribute to provide resistance to coronary flow. It represents the district where coronary circulation blood flow is regulated to ensure that each structural and functional cardiac component receives the proper amount of oxygen and metabolic substrates through the capillary network. Coronary microcirculation is fundamental for myocardial function which largely depends on the ratio between energetic metabolites received from coronary circulation and their utilization by the myocytes. Alterations in coronary microvascular circulation which limit myocardial perfusion can cause repetitive ischemic events leading to left ventricular dysfunction in several ischemic and non ischemic cardiomyopathies as the idiopathic dilated cardiomyopathy. To date, mechanisms underlying microvascular dysfunction are not completely understood and experimental animal models are employed to study alterations which may cause microcirculation impairment. These animals models are unique tools to identify new therapeutic targets, to test new drug therapies for the treatment of left ventricular dysfunction as well as its progression towards overt heart failure.