Specific miRNAs Change After 3 Months of GH treatment and Contribute to Explain the Growth Response After 12 Months

Context: There is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role. Objective: The aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response. Design and methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response. Results: Sixteen miRNAs were upregulated and 2 were downregulated at t+3 months. MiR-199a-5p (p = 0.020), miR-335-5p (p = 0.001), and miR-494-3p (p = 0.026) were confirmed to be upregulated at t+3. Changes were independent of GH peak values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters. Conclusions: MiR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months of GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response.Context: There is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role. Objective: The aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response. Design and methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response. Results: Sixteen miRNAs were upregulated and 2 were downregulated at t+3 months. MiR-199a-5p (p = 0.020), miR-335-5p (p = 0.001), and miR-494-3p (p = 0.026) were confirmed to be upregulated at t+3. Changes were independent of GH peak values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters. Conclusions: MiR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months of GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response

Polar organic marker compounds in atmospheric aerosol in the PoValley during the Supersito campaigns. Part 1: Low molecular weight carboxylic acids in cold seasons

In the framework of the“Supersito”project, three intensive experimental campaigns were conducted in the Po Valley (Northern Italy) in cold seasons, such as late autumn, pre-winter and deep-winter, over three years from 2011 to 2013. As a part of a study on polar marker compounds, including carboxylic acids, sugar derivatives and lignin phenols, the present study reports a detailed discussion on the at-mospheric concentrations of 14 low molecular weight carboxylic acids, mainly dicarboxylic and oxo-hydroxy carboxylic acids, as relevant markers of primary and secondary organic aerosols. PM2.5samples were collected in two monitoring sites, representing urban and rural background sta-tions. The high acid concentrations can be explained by the large human emission sources in the urbanized region, combined with the stagnant atmospheric conditions during the cold seasons that accumulate the organic precursors and accelerate the secondary atmospheric reactions. The distribution profiles of the investigated markers suggest the dominant contributions of primary anthropogenic sources, such as traffic, domestic heating and biomass burning. These results are confirmed by comparison with additional emission tracers, such as anhydro-saccharides for biomass burning and fatty acids originated from different anthropogenic sources. In addition, some secondary constituents were detected in both sites, as produced by in situ photo-chemical reactions from both biogenic (e.g. pinonic acid) and anthropogenic precursors (e.g. phthalic and adipic acids). The impact of different sources from human activities was elucidated by investigating theweek pattern of carboxylic and fattyacid concentrations. Theweekly trends of analytes during the warmer campaign may be related to emissions from motor vehicle traffic and industrial activities. Otherwise, the random pattern of the markers suggests the prevalent contribution of primary emissions from residential heating in the colder deep-winter

Drug-induced renal injury in neonates: challenges in clinical practice and perspectives in drug development

Acute kidney injury (AKI) is frequently diagnosed in the neonatal population, especially in those admitted to intensive care units, and poses several challenges for clinicians mainly because of difficulties in timely identification of renal impairment and the need to administer drugs with potential nephrotoxicity. In this context, research on biomarkers is growing for their implication in the early detection of renal damage and their higher sensitivity in monitoring renal activity, but also as an important tool for drug development. Areas covered: We described the tools currently used to detect renal damage in neonatal settings, their limits and applicability, as well as the role of drugs on renal toxicity occurrence. Subsequently, we discuss current knowledge on new biomarkers for the detection of kidney injury and drug-induced kidney injury in neonates, and the qualification programs developed by regulatory agencies for biomarkers intended as tools in drug development. Expert opinion: Some molecules are emerging as potential biomarkers for early detection of AKI: promising data has demonstrated higher sensitivity and accuracy compared with tools currently used in the clinical setting. In addition, novel techniques (e.g. high power magnetic resonance imaging) to assess long-term consequences of AKI in neonates are in early steps of development

PROGETTO SUPERSITO

The project is focused on a detailed study of some chemical, physical and toxicological parameters and on health, epidemiological and environmental assessment by interpretative models, in the atmosphere of Emilia-Romagna (Italy). The project rises from the necessity to improve  knowledge about environmental and health aspects of fine and ultrafine particles, in primary and secondary components, in the atmosphere. The project, structured in 7 workpackages, is organized in two measurement programmes: the routine one that has a mainly daily time resolution, and the intensive one with high time resolution and a higher chemical speciation than the routine one. The sampling sites are five: three in urban areas (Bologna, Parma and Rimini), one in a rural area (San Pietro Capofiume) and one in a remote area (Monte Cimone). Parallel to outdoor studies, a workpackage  is planned for indoor studies and chemical composition analysis with the  outdoor/indoor ratio for characterizing indoor human exposure to outdoor pollution.Le projet consiste en une étude détaillée des paramètres chimiques, physiques et météorologiques et une évaluation sanitaire, épidémiologique et l’environnementale (grâce à des modèles), dans l’atmosphère de la région Emilie-Romagne. L’objectif du projet est le progrès des connaissances sur les aspects environnementaux et sanitaires des particules fines et ultra-fines en composants primaires et/ou secondaires dans l’ atmosphère. Le projet, articulé en 7 lignes directrices,  est organisé en deux programmes de mesures: un programme de routine avec une fréquence temporelle surtout quotidienne et un programme intensif avec une fréquence temporelle èlevée et un éventail plus large de l'analyse.  Les sites de mesure sont au nombre de cinq:  trois dans la zone urbaine (Bologne, Parme et Rimini), un dans la zone rurale (San Pietro Capofiume) et un dans une région reculée (Monte Cimone). Parallèlement, une ligne directrice se concentre sur l’étude du rapport intérieur/extérieur des composants  de la qualité de l’air dans les bâtiments, pour caractériser l'exposition humaine à la pollution extérieure lorsque les sujets son à l’intérieur.Lo scopo del progetto è la realizzazione di uno studio integrato dell’inquinamento dell’atmosfera in Emilia-Romagna attraverso misure di parametri chimici, fisici, tossicologici e valutazioni sanitarie, epidemiologiche ed ambientali mediante modelli interpretativi. Il progetto nasce dalla necessità di migliorare le conoscenze relativamente agli aspetti ambientali e sanitari del particolato fine ed ultrafine, nelle componenti e/o secondarie, presente in atmosfera. Il progetto, strutturato in 7 linee progettuali, è organizzato in due programmi di misure: uno routinario in cui sono previsti campionamenti giornalieri ed uno intensivo in cui è prevista una speciazione più dettagliata con maggiore risoluzione temporale. I siti di campionamento sono 5: 3 in area urbana (Bologna, Parma e Rimini), 1 in  area rurale (San Pietro Capofiume) e 1 in area remota (Monte Cimone). Contestualmente agli studi outdoor è prevista una linea progettuale che si occupa dello studio del particolato, della sua composizione chimica nel rapporto qualità dell’aria outdoor/indoor e della caratterizzazione dell’esposizione della popolazione in ambienti indoor agli inquinanti tipici dell’ambiente outdoor

EFFICACIA E SICUREZZA DI DEGLUDEC NEI BAMBINI ED ADOLESCENTI CON DIABETE DI TIPO 1

OBIETTIVI L’insulina Degludec (IDeg) è un nuovo analogo lento basale che negli adulti con diabete di tipo 1 (DM1) ha permesso di ottenere valori glicemici più bassi ed un minor numero di episodi di ipoglicemia rispetto all’insulina Glargine (IGlar). Gli studi pubblicati in letteratura sugli effetti di IDeg nei soggetti in età evolutiva sono pochi. Scopo di questo studio è stato quello di valutare effi cacia e sicurezza di IDeg in bambini ed adolescenti con DM1. METODI Sono stati reclutati 20 pazienti con DM1 (15.1±4.0 anni; 9 maschi, 7 prepuberi; durata DM1 7.2±3.7 anni; IGlar ≥1 anno) in cui è stato cambiato l’analogo lento basale, passando dall’iniezione giornaliera di IGlar a quella di IDeg. BMI-SDS, HbA1c, FPG, numero di episodi di ipoglicemia grave, e dose di insulina (UI/kg/die) [IGlar o IDeg più analogo rapido/rapida] sono stati raccolti al momento dello switch da IGlar a IDeg (T0), a 3 (T1) e 6 mesi (T2) dall’inizio di IDeg. RISULTATI Abbiamo dimostrato, longitudinalmente, una riduzione statisticamente signifi cativa della dose di insulina basal-bolus (χ2=13.1; p=0.004), di quella prima dei pasti (χ2=8.68; p=0.033) e di IDeg (χ2=10.1; p=0.018). La riduzione della dose di insulina basal-bolus è risultata essere determinata dal calo della dose di insulina prima dei pasti (-9.63% a T2), piuttosto che da quello di IDeg (-2.96% a T1). I livelli di HbA1c non sono migliorati (χ2=1.66; p=0.435), tuttavia, rispetto a T0, abbiamo riscontrato una riduzione del valore di 0.35% punti al T1 e di 0.20% punti al T2. FPG è risultato signifi cativamente diminuito al T1 (-18.6±34.1 mg/dl, p=0.05). Il passaggio da IGlar ad IDeg non ha determinato signifi cative modifi che del BMI-SDS ovvero nessun episodio di ipoglicemia grave. CONCLUSIONI Rispetto a quanto riscontrato in età adulta, i nostri dati suggeriscono che in età evolutiva il passaggio da IGlar ad IDeg dovrebbe prevedere una riduzione del 5% della dose di analogo lento basale e del 10% della dose di insulina ai pasti. IDeg sembra migliorare il controllo glicemico, riducendo sia la glicemia a digiuno che l’HbA1c in assenza di complicanze acute. IDeg può essere considerata utile e ben tollerata anche nei bambini ed adolescenti con DM1