Diabete Tipo 1, Tipo 2 e Tipo X

Il muro concettuale secondo il quale il diabete in età pediatrica ha preferibilmente una patogenesi autoimmune sta ormai definitivamente crollando. Il diabete in età infantile e adolescenziale è molto più eterogeneo dal punto di vista eziopatogenetico di quanto si pensasse. In presenza di una qualsiasi iperglicemia è ormai diventato importantissimo chiedersi la patogenesi di questo sintomo utilizzando tutti gli strumenti che abbiamo oggi a disposizione

Alterations in Rev-ERBα/BMAL1 ratio and glycated hemoglobin in rotating shift workers: the EuRhythDia study

Objective: To detect premature gluco-metabolic defects among night shift workers with disturbances in circadian rhythms. Design and methods: We performed a hypothesis-generating, cross-sectional analysis of anthropometric, metabolic, lipid, and inflammation parameters, comparing active (a-NSW, n = 111) and former (f-NSW, n = 98) rotating night shift workers with diurnal workers (controls, n = 69). All participants were hospital nurses. We also evaluated the Pittsburgh Sleep Quality Index (PSQI) and assessed expression of transcription factors REV-ERBα and BMAL1 in peripheral blood mononuclear cells (PBMCs), as indicators of the molecular clock. Results: Both a-NSW and f-NSW participants had significantly higher glycated hemoglobin (HbA1c) and white blood cell counts (WBC) (p < 0.001 for both), PSQI global score (p = 0.001) and diastolic blood pressure levels (p = 0.024) compared with controls. Expression of REV-ERBα/BMAL1 RNA in PBMC was significantly higher in a-NSW (p = 0.05) than in f-NSW or control participants. Multivariate regression analysis showed that working status and PSQI were independent determinants of higher HbA1c levels (p < 0.001). Conclusions: We demonstrated that young, healthy night shift workers show subclinical abnormalities in HbA1c and changes in peripheral clock gene expression

Recognition of zinc transporter 8 and MAP3865c homologous epitopes by new-onset type 1 diabetes children from continental Italy

There are several pieces of evidence indicating that Mycobacterium avium subspecies paratuberculosis (MAP) infection is linked to type 1 diabetes (T1D) in Sardinian patients. An association between MAP and T1D was recently observed in an Italian cohort of pediatric T1D individuals, characterized by a different genetic background. It is interesting to confirm the prevalence of anti-MAP antibodies (Abs) in another pediatric population from continental Italy, looking at several markers of MAP presence. New-onset T1D children, compared to age-matched healthy controls (HCs), were tested by indirect enzyme-linked immunosorbent assay for the presence of Abs toward the immunodominant MAP3865c/ZnT8 homologues epitopes, the recently identified C-terminal MAP3865c281–287 epitope and MAP-specific protein MptD. Abs against MAP and ZnT8 epitopes were more prevalent in the sera of new-onset T1D children compared to HCs. These findings support the view that MAP3865c/ZnT8 cross-reactivity is involved in the pathogenesis of T1D, and addition of Abs against these peptides to the panel of existing T1D biomarkers should be considered. It is important now to investigate the timing of MAP infection during prospective follow-up in at-risk children to elucidate whether Ab-titers against these MAP/ZnT8 epitopes are present before T1D onset and if so if they wane after diagnosis

[Percutaneous treatment of post-acute myocardial infarction mechanical complications: state of the art]

: Left ventricular free wall rupture, ventricular pseudoaneurysm, papillary muscle rupture and ventricular septal rupture are life-threatening mechanical complications of acute myocardial infarction. Despite significant improvements over the last decades in overall mortality for patients with myocardial infarction, the outcome of subjects who develop post-infarction mechanical complications remains poor. Surgical treatment is considered the standard of care. However, percutaneous approaches (such as pericardial fibrin-glue injection for left ventricular free wall rupture, transcatheter edge-to-edge mitral repair for papillary muscle rupture and device closure for ventricular pseudoaneurysm or septal rupture) have been proposed in selected high-risk or inoperable patients, or in subjects with ideal characteristics for feasibility, as therapeutic alternatives to open surgery. The aim of the present review is to provide a comprehensive overview of the percutaneous strategies for the management of post-acute myocardial infarction mechanical complications

Mappatura di inquinanti organici aerodispersi mediante lichene Evernia prunastri in un’area a elevato impatto antropico (Italia centrale)

I composti organici persistenti (Persistent Organic Pollutants, POPs) sono costituiti da un’eterogenea classe di composti di origine prevalentemente antropica che, a causa delle loro caratteristiche di tossicità e resistenza ai processi di degradazione, sono considerati inquinanti pericolosi per la salute umana e ambientale. I POPs comprendono tra gli altri policloro-dibenzop-diossine (polychlorinated dibenzodioxins, PCDDs), policloro-dibenzo-furani (polychlorinated dibenzofurans, PCDFs) e policlorobifenili (polychlorinated biphenyls, PCBs), immessi nell’ambiente prevalentemente a causa di processi di combustione quali riscaldamento domestico, emissioni veicolari e industriali. Ad oggi, dati gli elevati costi dei tradizionali sistemi di monitoraggio, la loro dispersione sul territorio viene stimata tramite modelli matematici che non sono però in grado di rappresentare in maniera esaustiva il complesso sistema atmosferico. Pertanto, negli ultimi anni le ricerche di settore hanno focalizzato l’attenzione sulla capacità di diverse specie licheniche, prelevate in loco oppure trapiantate nei siti di interesse, come strumenti di biomonitoraggio. Lo scopo dello studio è stato valutare l’abilità del lichene trapiantato Evernia (E.) prunastri nel 1) bioaccumulare PCDDs, PCDFs e PCBs e 2) discriminare livelli diversi degli stessi rispetto a diverse sorgenti emissive. A tal fine, è stata scelta la città di Terni, area del centro Italia caratterizzata da numerose sorgenti e da una peculiare geomorfologia che limita la dispersione degli inquinanti. L’indagine ha previsto il monitoraggio di 23 siti in punti strategici nei quali sono stati trapiantati 23 campioni di licheni. Alla fine dei 13 mesi di esposizione, i campionisono stati prelevati e analizzati mediante gas cromatografia accoppiata a spettrometria di massa ad alta risoluzione (GC-HRMS). I risultati ottenuti hanno confermato l’affidabilità dell’utilizzo del lichene E. prunastritrapiantato come strumento di biomonitoraggio per stimare la distribuzione spaziale dei POPs di interesse e per valutare l’impatto delle diverse sorgenti presenti sul territorio

Lichen transplants for high spatial resolution biomonitoring of persistent organic pollutants (POPs) in a multi-source polluted area of Central Italy

The ability of lichen transplant Evernia prunastri (L.) Ach. to reflect air concentration and spatial distribution of 7 polychlorinated dibenzodioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs), and 23 polychlorinated biphenyls (PCBs) was evaluated through the construction of a wide and dense biomonitoring network. For this purpose, 23 lichen transplants were placed in a highly polluted area in Central Italy, characterized by the presence of different local emission sources such as a power plant, a steel plant, vehicular traffic, and domestic heating. The high spatial resolution data obtained from lichens were used to map the spatial distribution of the studied compounds, useful to identify the location and strength of target compounds sources over the territory. The maps showed that the highest concentrations of the pollutants were detected, as expected, in the sites close to the power plant and to the steel plant, confirming their important role as persistent pollutants emission sources. The statistical analysis performed on the spatially resolved data allowed us to identify the steel plant as the main source of PCDD/Fs, while PCBs were emitted by both the steel plant and the power plant. Finally, the efficiency of lichen transplants to reflect PCDD/Fs and PCBs atmospheric concentrations was assessed by comparing lichen data with POPs deposition measured by bulk deposition samplers at sites impacted by intensive emission sources; good results were achieved from the comparison (R2 > 0.79). Lichen transplants have demonstrated to be suitable biomonitors of POPs, allowing to obtain a high spatial monitoring network. The lowcost biomonitoring and experimental approach described in this study can be applied to other monitoring campaigns for identifying localizing emission sources of POPs in areas contaminated by several disaggregated sources

The expression of four pyridoxal kinase (PDXK) human variants in Drosophila impacts on genome integrity

AbstractIn eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B6salvage pathway to produce pyridoxal 5′-phosphate (PLP), the active form of the vitamin, which is implicated in numerous crucial metabolic reactions. In Drosophila, mutations in the dPdxk gene cause chromosome aberrations (CABs) and increase glucose content in larval hemolymph. Both phenotypes are rescued by the expression of the wild type human PDXK counterpart. Here we expressed, in dPdxk1 mutant flies, four PDXK human variants: three (D87H, V128I and H246Q) listed in databases, and one (A243G) found in a genetic screening in patients with diabetes. Differently from human wild type PDXK, none of the variants was able to completely rescue CABs and glucose content elicited by dPdxk1 mutation. Biochemical analysis of D87H, V128I, H246Q and A243G proteins revealed reduced catalytic activity and/or reduced affinity for PLP precursors which justify this behavior. Although these variants are rare in population and carried in heterozygous condition, our findings suggest that in certain metabolic contexts and diseases in which PLP levels are reduced, the presence of these PDXK variants could threaten genome integrity and increase cancer risk.</jats:p

Impact of light therapy on rotating night shift workers: the EuRhythDia study

Aims Disturbances in circadian rhythms may promote cardiometabolic disorders in rotating night shift workers (r-NSWs). We hypothesized that timed light therapy might reverse disrupted circadian rhythms and glucose intolerance observed among r-NSWs). Methods R-NSWs were randomly assigned to a protocol that included 12 weeks on followed by 12 weeks off light therapy (n = 13; 6 men; mean age, 39.5 +/- 7.3 years) or a no-treatment control group (n = 9; 3 men; mean age 41.7 +/- 6.3 years). Experimental and control participants underwent identical metabolic evaluations that included anthropometric, metabolic (including oral glucose tolerance tests), lipid, and inflammation-associated parameters together with an assessment of sleep quality and expression of circadian transcription factors REV-ERB alpha and BMAL1 in peripheral blood mononuclear cells (PBMCs) at baseline, 12 weeks, and 24 weeks of the protocol. Results Twelve weeks of warm white-light exposure (10,000 lx at 35 cm for 30 min per day) had no impact on sleep, metabolic, or inflammation-associated parameters among r-NSWs in the experimental group. However, our findings revealed significant decreases in REV-ERB alpha gene expression (p = 0.048) and increases in the REV-ERB alpha/BMAL1 ratio (p = 0.040) compared to baseline in PBMCs isolated from this cohort. Diminished expression of REV-ERB alpha persisted, although the REV-ERB alpha/BMAL1 ratio returned to baseline levels after the subsequent 12-day wash-out period. Conclusions Our results revealed that intermittent light therapy had no impact on inflammatory parameters or glucose tolerance in a defined cohort of r-NSWs. However, significant changes in the expression of circadian clock genes were detected in PBMCs of these subjects undergoing light therapy