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In 2019, the International Consortium for Personalised Medicine (ICPerMed) developed a vision on how the use of personalized medicine (PM) approaches will promote "next-generation" medicine in 2030 more firmly centered on the individual's personal characteristics, leading to improved health outcomes within sustainable healthcare systems through research, development, innovation, and implementation for the benefit of patients, citizens, and society. Nevertheless, there are significant hurdles that healthcare professionals, researchers, policy makers, and patients must overcome to implement PM. The ICPerMed aims to provide recommendations to increase stakeholders' awareness on actionable measures to be implemented for the realization of PM. Starting with best practice examples of PM together with consultation of experts and stakeholders, a careful analysis that underlined hurdles, opportunities, recommendations, and information, aiming at developing knowledge on the requirements for PM implementation in healthcare practices, has been provided. A pragmatic roadmap has been defined for PM integration into healthcare systems, suggesting actions to overcome existing barriers and harness the potential of PM for improved health outcomes. In fact, to facilitate the adoption of PM by diverse stakeholders, it is mandatory to have a comprehensive set of resources tailored to stakeholder needs in critical areas of PM. These include engagement strategies, collaboration frameworks, infrastructure development, education and training programs, ethical considerations, resource allocation guidelines, regulatory compliance, and data management and privacy.
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Background: Ventricular assist device (VAD) implant represents a therapeutic option for pediatric patients with end-stage heart failure (HF). Heart unloading by VAD can modify several molecular pathways underlying cardiac function in HF. Among them, the potential role of microRNA (miRNAs) in response to VAD implant is emerging. This study was aimed at investigating in HF pediatric patients the effect of VAD-modified miRNAs on the adiponectin (ADPN) system, known to exert cardioprotective actions. Methods: ADPN was measured in plasma samples obtained from HF children, before and 1 month after VAD implant, and from healthy control children. miRNA profile and molecules belonging to ADPN system were determined in cardiac biopsies collected at the time of VAD implantation (pre-VAD) and at the moment of heart transplant (post-VAD). An in vitro study using HL-1 cell line was performed to verify the regulatory role of the VAD-modified miRNA on the ADPN system. Results: VAD implant did not affect circulating and cardiac levels of ADPN, but increased the cardiac mRNA expression of ADPN receptors, including AdipoR1, AdipoR2, and T-cad. AdipoR2 and T-cad were inversely related to the VAD-modified miRNA levels. The in vitro study confirmed the regulatory role of miR-1246 and miR-199b-5p on AdipoR2, and of miR-199b-5p on T-cad. Conclusions: These data suggest that VAD treatment could regulate the expression of the cardioprotective ADPN system by epigenetic mediators, suggesting that miRNAs have a potential role as therapeutic targets to improve cardiac function in HF pediatric patients.
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Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been linked to changes in amino acid (AA) levels. The objective of the current study was to examine the relationship between MRI parameters that reflect inflammation and fibrosis and plasma AA concentrations in NAFLD patients. Plasma AA levels of 97 NAFLD patients from the MAST4HEALTH study were quantified with liquid chromatography. Medical, anthropometric and lifestyle characteristics were collected and biochemical parameters, as well as inflammatory and oxidative stress biomarkers, were measured. In total, subjects with a higher MRI-proton density fat fraction (MRI-PDFF) exhibited higher plasma AA levels compared to subjects with lower PDFF. The concentrations of BCAAs (p-Value: 0.03), AAAs (p-Value: 0.039), L-valine (p-Value: 0.029), L-tyrosine (p-Value: 0.039) and L-isoleucine (p-Value: 0.032) were found to be significantly higher in the higher PDFF group compared to lower group. Plasma AA levels varied according to MRI-PDFF. Significant associations were also demonstrated between AAs and MRI-PDFF and MRI-cT1, showing the potential utility of circulating AAs as diagnostic markers of NAFLD.
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Whereas the etiology of non-alcoholic fatty liver disease (NAFLD) is complex, the role of nutrition as a causing and preventive factor is not fully explored. The aim of this study is to associate dietary patterns with magnetic resonance imaging (MRI) parameters in a European population (Greece, Italy, and Serbia) affected by NAFLD. For the first time, iron-corrected T1 (cT1), proton density fat fraction (PDFF), and the liver inflammation fibrosis score (LIF) were examined in relation to diet. A total of 97 obese patients with NAFLD from the MAST4HEALTH study were included in the analysis. A validated semi-quantitative food frequency questionnaire (FFQ) was used to assess the quality of diet and food combinations. Other variables investigated include anthropometric measurements, total type 2 diabetes risk, physical activity level (PAL), and smoking status. Principal component analysis (PCA) was performed to identify dietary patterns. Six dietary patterns were identified, namely "High-Sugar", "Prudent", "Western", "High-Fat and Salt", "Plant-Based", and "Low-Fat Dairy and Poultry". The "Western" pattern was positively associated with cT1 in the unadjusted model (beta: 0.020, p-value: 0.025) and even after adjusting for age, sex, body mass index (BMI), PAL, smoking, the center of the study, and the other five dietary patterns (beta: 0.024, p-value: 0.020). On the contrary, compared with low-intake patients, those with medium intake of the "Low-Fat Dairy and Poultry" pattern were associated with lower values of cT1, PDFF, and LIF. However, patients with a "Low-Fat Dairy and Poultry" dietary pattern were negatively associated with MRI parameters (cT1: beta: -0.052, p-value: 0.046, PDFF: beta: -0.448, p-value: 0.030, LIF: beta: -0.408, p-value: 0.025). Our findings indicate several associations between MRI parameters and dietary patterns in NAFLD patients, highlighting the importance of diet in NAFLD.
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Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Diabetes Mellitus Tipo 2/complicaciones , Fibrosis , Humanos , Inflamación/complicaciones , Hígado/patología , Imagen por Resonancia Magnética/métodos , Enfermedad del Hígado Graso no Alcohólico/epidemiologíaRESUMEN
Cardiac hypertrophy, in its aspects of localized thickening of the interventricular septum and concentric increase of the left ventricle, constitutes a risk factor of heart failure. Myocardial hypertrophy, in the presence of different degree of myocardial fibrosis, is paralleled by significant molecular, cellular, and histological changes inducing alteration of cardiac extracellular matrix composition as well as sarcomeres and cytoskeleton remodeling. Previous studies indicate osteopontin (OPN) and more recently survivin (SURV) overexpression as the hallmarks of heart failure although SURV function in the heart is not completely clarified. In this study, we investigated the involvement of SURV in intracellular signaling of hypertrophic cardiomyocytes and the impact of its transcriptional silencing, laying the foundation for novel target gene therapy in cardiac hypertrophy. Oligonucleotide-based molecules, like theranostic optical nanosensors (molecular beacons) and siRNAs, targeting SURV and OPN mRNAs, were developed. Their diagnostic and therapeutic potential was evaluated in vitro in hypertrophic FGF23-induced human cardiomyocytes and in vivo in transverse aortic constriction hypertrophic mouse model. Engineered erythrocyte was used as shuttle to selectively target and transfer siRNA molecules into unhealthy cardiac cells in vivo. The results highlight how the SURV knockdown could negatively influence the expression of genes involved in myocardial fibrosis in vitro and restores structural, functional, and morphometric features in vivo. Together, these data suggested that SURV is a key factor in inducing cardiomyocytes hypertrophy, and its shutdown is crucial in slowing disease progression as well as reversing cardiac hypertrophy. In the perspective, targeted delivery of siRNAs through engineered erythrocytes can represent a promising therapeutic strategy to treat cardiac hypertrophy. Theranostic SURV molecular beacon (MB-SURV), transfected into FGF23-induced hypertrophic human cardiomyocytes, significantly dampened SURV overexpression. SURV down-regulation determines the tuning down of MMP9, TIMP1 and TIMP4 extracellular matrix remodeling factors while induces the overexpression of the cardioprotective MCAD factor, which counterbalance the absence of pro-survival and anti-apoptotic SURV activity to protect cardiomyocytes from death. In transverse aortic constriction (TAC) mouse model, the SURV silencing restores the LV mass levels to values not different from the sham group and counteracts the progressive decline of EF, maintaining its values always higher with respect to TAC group. These data demonstrate the central role of SURV in the cardiac reverse remodeling and its therapeutic potential to reverse cardiac hypertrophy.
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Cardiomegalia , Insuficiencia Cardíaca , Animales , Cardiomegalia/genética , Cardiomegalia/terapia , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Survivin/genética , Survivin/metabolismo , Survivin/uso terapéutico , Remodelación VentricularRESUMEN
The hyperproduction of oxidative stress and inflammatory biomarkers, which is paralleled by decreased levels of antioxidant and anti-inflammatory mediators, is part of cellular mechanisms that contribute to the disruption of metabolic homeostasis in obesity. Whether gender-specific alterations and gender-restricted associations in these biomarkers underlie the increased cardiometabolic risk in men compared to women is unclear. We enrolled 31 women and 29 men, aged ≥50 and ≤70 years and with body mass index ≥ 30 and <40 kg/m2. We assessed the concentrations of aminothiols (cysteine, homocysteine, and glutathione), expression of oxidant/antioxidant balance, adipomyokines (leptin, adiponectin, myostatin, and interleukin-6), markers of chronic inflammation, and vitamin D, an index of nutritional state, in plasma and serum samples by using HPLC, ELISA, and chemiluminescent immunoassay methods. We measured insulin resistance (IR) by the homeostasis model assessment (HOMA) index. Despite comparable levels of visceral adiposity, IR, and a similar dietary regimen, men showed, with respect to women, higher oxidant concentrations and lower antioxidant levels, which paralleled IR severity. Myostatin levels correlated with prooxidant aminothiols among men only. Gender-specific alterations in aminothiol status and adipomyokine profile and the gender-restricted association between these biomarkers and metabolic derangement are consistent with an increased cardiometabolic risk in men compared to age-matched women with stage I-II obesity. Strict control of redox and inflammatory status, even addressing gender-specific nutritional targets, may be useful to prevent obesity-related metabolic alterations and comorbidities.
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Biomarcadores/sangre , Resistencia a la Insulina/genética , Obesidad/epidemiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Caracteres SexualesRESUMEN
Ventricular Assist Device (VAD) therapy is considered as a part of standard care for end-stage Heart Failure (HF) children unresponsive to medical management, but the potential role of miRNAs in response to VAD therapy on molecular pathways underlying LV remodeling and cardiac function in HF is unknown. The aims of this study were to evaluate the effects of VAD on miRNA expression profile in cardiac tissue obtained from HF children, to determine the putative miRNA targets by an in-silico analysis as well as to verify the changes of predicated miRNA target in the same cardiac samples. The regulatory role of selected miRNAs on predicted targets was evaluated by a dedicated in vitro study. miRNA profile was determined in cardiac samples obtained from 13 HF children [median: 29 months; 19 LVEF%; 9 Kg] by NGS before VAD implant (pre-VAD) and at the moment of heart transplant (Post-VAD). Only hsa-miR-199b-5p, hsa-miR-19a-3p, hsa-miR-1246 were differentially expressed at post-VAD when compared to pre-VAD, and validated by real-time PCR. Putative targets of the selected miRNAs were involved in regulation of sarcomere genes, such as cardiac troponin (cTns) complex. The expression levels of fetal ad adult isoforms of cTns resulted significantly higher after VAD in cardiac tissue of HF pediatric patients when compared with HF adults. An in vitro study confirmed a down-regulatory effect of hsa-miR-19a-3p on cTnC expression. The effect of VAD on sarcomere organization through cTn isoform expression may be epigenetically regulated, suggesting for miRNAs a potential role as therapeutic targets to improve heart function in HF pediatric patients.
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Mastiha is a natural nutritional supplement with known anti-inflammatory properties. Non-alcoholic fatty liver disease (NAFLD) and Inflammatory bowel disease (IBD) are immune mediated inflammatory diseases that share common pathophysiological features. Mastiha has shown beneficial effects in both diseases. MicroRNAs have emerged as key regulators of inflammation and their modulation by phytochemicals have been extensively studied over the last years. Therefore, the aim of this study was to investigate whether a common route exists in the anti-inflammatory activity of Mastiha, specifically through the regulation of miRNA levels. Plasma miR-16, miR-21 and miR-155 were measured by Real-Time PCR before and after two double blinded and placebo-controlled randomized clinical trials with Mastiha. In IBD and particularly in ulcerative colitis patients in relapse, miR-155 increased in the placebo group (p = 0.054) whereas this increase was prevented by Mastiha. The mean changes were different in the two groups even after adjusting for age, sex and BMI (p = 0.024 for IBD and p = 0.042). Although the results were not so prominent in NAFLD, miR-155 displayed a downward trend in the placebo group (p = 0.054) whereas the levels did not changed significantly in the Mastiha group in patients with less advanced fibrosis. Our results propose a regulatory role for Mastiha in circulating levels of miR-155, a critical player in T helper-17 (Th17) differentiation and function.
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Antiinflamatorios/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Resina Mástique/uso terapéutico , MicroARNs/sangre , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antiinflamatorios/farmacología , Método Doble Ciego , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Masculino , Resina Mástique/farmacología , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Adulto JovenRESUMEN
Heart failure (HF) is the main cause of mortality worldwide, particularly in the elderly. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the gold standard biomarker for HF diagnosis and therapy monitoring. It is determined in blood samples by the immunochemical methods generally adopted by most laboratories. Saliva analysis is a powerful tool for clinical applications, mainly due to its non-invasive and less risky sampling. This study describes a validated analytical procedure for NT-proBNP determination in saliva samples using a commercial Enzyme-Linked Immuno-Sorbent Assay. Linearity, matrix effect, sensitivity, recovery and assay-precision were evaluated. The analytical approach showed a linear behaviour of the signal throughout the concentrations tested, with a minimum detectable dose of 1 pg/mL, a satisfactory NT-proBNP recovery (95-110%), and acceptable precision (coefficient of variation ≤ 10%). Short-term (3 weeks) and long-term (5 months) stability of NT-proBNP in saliva samples under the storage conditions most frequently used in clinical laboratories (4, - 20, and - 80 °C) was also investigated and showed that the optimal storage conditions were at - 20 °C for up to 2.5 months. Finally, the method was tested for the determination of NT-proBNP in saliva samples collected from ten hospitalized acute HF patients. Preliminary results indicate a decrease in NT-proBNP in saliva from admission to discharge, thus suggesting that this procedure is an effective saliva-based point-of-care device for HF monitoring.
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Insuficiencia Cardíaca/diagnóstico , Péptido Natriurético Encefálico/análisis , Péptido Natriurético Encefálico/inmunología , Fragmentos de Péptidos/análisis , Fragmentos de Péptidos/inmunología , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Pruebas Diagnósticas de Rutina , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Voluntarios Sanos , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Estabilidad Proteica , Saliva/química , Manejo de Especímenes/métodosRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor-beta-induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03135873.
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Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Suplementos Dietéticos , Resina Mástique/química , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Nutrigenómica , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Biomarcadores , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/etiología , Nutrigenómica/métodos , Estrés Oxidativo/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Increasing evidence links meteorological characteristics and air pollution to physiological responses during sports activities in urban areas with different traffic levels. OBJECTIVE: The main objective of the Smart Healthy ENV (SHE, "Smart Monitoring Integrated System For A Healthy Urban Environment In Smart Cities") project was to identify the specific responses of a group of volunteers during physical activity, by monitoring their heart rates and collecting breath samples, combined with data on meteorological determinants and pollution substances obtained through fixed sensor nodes placed along city routes and remotely connected to a dedicated data acquisition server. METHODS: Monitoring stations were placed along two urban routes in Pisa, each two km long, with one located within the park beside the Arno river (green route) and the other in a crowded traffic zone (red route). Our sample participants were engaged in sports activities (N = 15, with different levels of ability) and were monitored through wearable sensors. They were first asked to walk back and forth (4 km) and then to run the same route. The experimental sessions were conducted over one day per route. A breath sample was also collected before each test. A questionnaire concerning temperature and fatigue perception was administered for all of the steps of the study over the two days. RESULTS: The heart rates of the participants were monitored in the baseline condition, during walking, and while running, and were correlated with meteorological and pollutant data and with breath composition. Changes in the heart rates and breath composition were detected during the experimental sessions. These variations were related to the physical activity and to the meteorological conditions and air pollution levels. CONCLUSIONS: The SHE project can be considered a proof-of-concept study aimed at monitoring physiological and environmental variables during physical activity in urban areas, and can be used in future studies to provide useful information to those involved in sports and the broader community.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Ciudades , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Humanos , Proyectos PilotoRESUMEN
SCOPE: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with poor therapeutic strategies. Mastiha possesses antioxidant/anti-inflammatory and lipid-lowering properties. The authors investigate the effectiveness of Mastiha as a nonpharmacological intervention in NAFLD. METHODS AND RESULTS: Ninety-eight patients with NAFLD in three countries (Greece, Italy, Serbia) are randomly allocated to either Mastiha or Placebo for 6 months, as part of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The authors assess NAFLD severity via magnetic resonance imaging (MRI) scanning and LiverMultiScan technique and evaluate the effectiveness of Mastiha through medical, anthropometric, biochemical, metabolomic, and microbiota assessment. Mastiha is not superior to Placebo on changes in iron-corrected T1 (cT1) and Liver Inflammation Fibrosis score (LIF) in entire patient population; however, after BMI stratification (BMI ≤ 35 kg m-2 and BMI > 35 kg m-2 ), severely obese patients show an improvement in cT1 and LIF in Mastiha versus Placebo. Mastiha increases dissimilarity of gut microbiota, as shown by the Bray-Curtis index, downregulates Flavonifractor, a known inflammatory taxon and decreases Lysophosphatidylcholines-(LysoPC) 18:1, Lysophosphatidylethanolamines-(LysoPE) 18:1, and cholic acid compared to Placebo. CONCLUSION: Mastiha supplementation improves microbiota dysbiosis and lipid metabolite levels in patients with NAFLD, although it reduces parameters of liver inflammation/fibrosis only in severely obese patients.
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Resina Mástique/administración & dosificación , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Adulto , Anciano , Índice de Masa Corporal , Suplementos Dietéticos , Método Doble Ciego , Disbiosis/tratamiento farmacológico , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Grecia , Humanos , Italia , Hígado/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/complicaciones , Placebos , SerbiaRESUMEN
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.
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Disfunción Cognitiva , Envejecimiento Saludable , Telemedicina , Anciano , Humanos , Estilo de Vida , Proyectos PilotoRESUMEN
PURPOSE: This study evaluates among middle-aged subjects with obesity the prevalence of olfactory impairment (OI) with respect to normative values and its correlation with body composition, cognition, sleep quality, and inflammation. METHODS: In 60 (31 women, 29 men) volunteers with a body mass index ≥ 30 to ≤ 40 kg/m2, aged ≥ 50 to ≤ 70 years, we assessed olfaction by the Sniffin' Stick test. We measured anthropometrics, body composition and metabolic profiles and evaluated cognition by the MiniMental State Examination (MMSE) and sleep disturbances by the Insomnia Severity Index (ISI). Patients were classified into two groups according to a total olfactory score (odor Threshold, Discrimination, Identification, TDI) below or above the 25th percentile from age and gender-adjusted normative data. RESULTS: Overall, 25 subjects (42%) had OI (TDI < 25th percentile). The largest differences between subjects with and without OI were observed in discrimination and identification scores, with a large overlap in olfactory threshold. Subjects with an abnormal TDI showed significantly higher fat mass index, ISI scores and urinary neopterin and lower MMSE scores than those without OI. By multivariable logistic regression, MMSE, ISI score and urinary neopterin were significantly associated to OI. CONCLUSIONS: Among middle-aged subjects with stage I and II obesity, OI is highly prevalent and is independently associated with poor self-reported sleep quality, lower cognition scores and higher levels of the inflammatory marker neopterin.
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Trastornos del Olfato , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/epidemiología , Odorantes , Trastornos del Olfato/diagnóstico , Trastornos del Olfato/epidemiología , Trastornos del Olfato/etiología , Umbral Sensorial , OlfatoRESUMEN
Heart Failure (HF) is a progressive clinical syndrome characterized by molecular and structural abnormalities that result in impaired ventricular filling and a reduced blood ejection. In pediatric patients, HF represents an important cause of morbidity and mortality, but underlying cause, presentation and disease course remains unclear in many cases. It is evident that a child is not a "small adult" and findings are not comparable. The adoption of a standardized clinical and surgical tools as well as increased biomolecular research and therapeutic trials targeting pediatric patients with HF would greatly improve the management of this special class of patients. This review examines the most current information about the pathophysiology and molecular mechanisms related to HF in children to identify gaps in our knowledge base to further improve clinical care and outcomes.
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Insuficiencia Cardíaca , Corazón Auxiliar , Adulto , Niño , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Humanos , Transducción de Señal , Resultado del TratamientoRESUMEN
The aim of this study is to ascertain whether the simultaneous measurement of hemoglobin O2 saturation (StO2 ) and dimension of venous leg ulcers (VLU) by near infrared spectroscopy (NIRS) imaging can predict the healing course with protocols employing a conventional treatment alone or in combination with hyperbaric oxygen therapy (HBOT). NIRS 2D images of wound region were obtained in 81 patients with hard-to-heal VLU that had been assigned, in a randomized controlled clinical trial, to the following protocols: 30 HBOT sessions, adjunctive to the conventional therapy, either twice daily over 3 weeks (group A) or once daily over 6 weeks (group B), and conventional therapy without HBOT (group C). Seventy-three patients completed the study with a total of 511 NIRS images being analyzed. At the end of treatment, wound area was significantly smaller in all three groups. However, at the 3-week mark the wound area reduction tended to be less evident in group A than in the other groups. This trend continued up to the 6-week end-point when a significantly greater area reduction was found with group B (65.5%) and group C (56.8%) compared to group A (29.7%) (P < .01). Furthermore, a higher incidence of complete healing was noted with group B (20%) than with group A (4.5%) and group C (3.8%). When using a final wound reduction in excess of 40% to distinguish healing from nonhealing ulcers, it was found that only the former present NIRS StO2 values abating over the study period both at center and edge of lesions. In conclusion, NIRS analysis of StO2 and wound area can predict the healing course of VLU. Adjunctive HBOT significantly facilitates VLU healing compared to the conventional treatment alone. This positive action, however, becomes manifest only with a longer and less intensive treatment schedule.
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Vendajes de Compresión , Hemoglobinas/metabolismo , Oxigenoterapia Hiperbárica/métodos , Espectroscopía Infrarroja Corta/métodos , Úlcera Varicosa/terapia , Cicatrización de Heridas/fisiología , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Consumo de Oxígeno , Resultado del Tratamiento , Úlcera Varicosa/sangreRESUMEN
Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets. c-miRNA profile was determined in serum of HF children by NGS before and one month after VAD-implant. The c-miRNA differentially expressed were analyzed by real time-PCR, before and at 4 hrs,1,3,7,14,30 days after VAD-implant. A miRNA mimic transfection study in HepG2 cells was performed to validate putative miRNA targets selected through miRWalk database. Thirteen c-miRNAs were modified at 30 days after VAD-implant compared to pre-VAD at NSG, and, among them, six c-miRNAs were confirmed by Real-TimePCR. Putative targets of the validated c-miRNAs are involved in the hemostatic process. The in vitro study confirmed a down-regulatory effect of hsa-miR-409-3p towards coagulation factor 7 (F7) and F2. Of note, all patients had thrombotic events requiring pump change. In conclusion, in HF children, the level of six c-miRNAs involved in the regulation of hemostatic events changed after 30 days of VAD-treatment. In particular, the lowering of c-miR-409-3p regulating both F7 and F2 could reflect a pro-thrombotic state after VAD-implant.
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MicroARN Circulante/sangre , Insuficiencia Cardíaca/terapia , Corazón Auxiliar/efectos adversos , Trombosis/diagnóstico , Biomarcadores/sangre , Preescolar , MicroARN Circulante/agonistas , MicroARN Circulante/metabolismo , Biología Computacional , Regulación hacia Abajo , Factor VII/genética , Femenino , Perfilación de la Expresión Génica , Insuficiencia Cardíaca/sangre , Células Hep G2 , Humanos , Lactante , Masculino , MicroARNs/agonistas , MicroARNs/sangre , MicroARNs/metabolismo , Proyectos Piloto , Pronóstico , Protrombina/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Trombosis/sangre , Trombosis/etiologíaRESUMEN
Irisin concentrations are decreased in subjects with overt diabetes and upregulated in those with obesity or impaired fasting glucose. However, gender-balanced data in older populations, in whom risk factors commonly culminate in overt cardiovascular disease, are scarce. We assessed in non-diabetic Caucasian subjects with stage I-II obesity in the early aging range (50 to 70 years), the relationship between irisin, body composition and markers of metabolic derangement by gender. In 60 (31 women, 29 men) non-diabetics with a body mass index ≥30 - ≤40 kg/m2, we measured anthropometrics and body composition (Air Displacement Plethysmography). We assayed lipid and glucose profile by routine methods, plasma irisin by ELISA and measured insulin resistance by the HOMA index. Irisin levels were higher in women than in men (161 [105-198]) vs 83 [33-115] ng/ml, P<0.001), and correlated directly with HOMA index in both (rho 0.735, P<0.001 M, rho 0.452, P = 0.011 F). Sex differences were maintained across insulin resistance severity stages. In men, irisin concentrations correlated directly with body mass index (rho 0.755, P<0.001), waist circumference (rho 0.623, P<0.001), fat mass index (rho 0.762, P<0.001), glucose (rho 0.408, P = 0.028), the fatty liver index (rho 0.705, P<0.001) and FINDRISC score (rho 0.536, P = 0.003). Among non-diabetic Caucasian subjects with obesity in the early stages of aging, irisin levels reflect the amount of body fat and insulin resistance severity, independently of between-gender differences in the adipomyokine concentrations and are associated with markers of visceral adiposity in men but not in women.
Asunto(s)
Envejecimiento/metabolismo , Fibronectinas/metabolismo , Obesidad/metabolismo , Población Blanca , Anciano , Envejecimiento/sangre , Biomarcadores/metabolismo , Ejercicio Físico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/fisiopatología , Caracteres SexualesRESUMEN
OBJECTIVES: Systemic sclerosis (SSc) causes functional and structural microcirculatory dysfunction, affecting also distal extremities. Optical Near-InfraRed Spectroscopy (NIRS) of blood HbO2 saturation (stO2) is able to evaluate O2 delivery/consumption balance in the explored tissue. The NIRS-sensitive camera non-invasively detects stO2 values in superficial tissues, automatically generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand imaging may evaluate peripheral microcirculatory dysfunction and its spatial heterogeneity in SSc patients compared to controls. METHODS: Forty SSc patients (aged 55.1⯱â¯15.6 years) and twenty-one healthy controls (aged 54.3⯱â¯14.5years, pâ¯=â¯0.89) were studied by palmar hand NIRS-2D imaging. A blood pressure cuff was applied to the forearm and 3 min ischemia was induced. Images were acquired at basal conditions and every 10 seconds during 3 minutes of ischemia and 5 minutes of reperfusion. Five regions of interest were positioned on each fingertip, from the second to the fifth finger and one on the thenar eminence. RESULTS: A significant difference was found between controls and SSc patients in basal stO2 (84.3⯱â¯7.5â¯vs. 75.4⯱â¯10.9%, pâ¯<â¯0.001), minimum stO2 (65.2⯱â¯8.0â¯vs. 53.4⯱â¯10.1%, pâ¯<â¯0.001) and time to maximum stO2 during hyperemia (63⯱â¯38â¯vs. 85⯱â¯49â¯s, pâ¯<â¯0.05). Among clinical characteristics, anti-Scl70 antibody positivity, digital ulcers history and smoke exposure affected NIRS parameters, as well as sildenafil and statins therapy. Conversely, no significant differences were found in NIRS-2D values between different nailfold-videocapillaroscopy patterns. CONCLUSION: NIRS-2D imaging is a simple, automated tool to non-invasively detect regional microcirculatory impairment in SSc, which seems to add significant functional information to the morphological picture of nailfold-videocapillaroscopy.