GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according to gender (NIRAD study 6).

CONTEXT: Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. OBJECTIVE: The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects. METHODS: Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. RESULTS: High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001). CONCLUSIONS: In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender

fracture toughness of structural adhesives for the automotive industry

Abstract Adhesive bonding is currently employed by automotive manufacturers to complement (or replace) welding in joining dissimilar materials. In order to reduce the impact on the existing manufacturing infrastructures, structural adhesives are deployed in the body shop but hardening is accomplished in the paint cure oven. Various adhesive formulations have been specifically developed for the implementation in the automotive manufacturing chain. However, it is very important to assess the mechanical behaviour of the joints which results from the peculiar curing strategy. In the present work, automotive grade single component epoxy and two component epoxy modified acrylic adhesives were evaluated. T-joints were fabricated using a cold rolled galvanized steel (FeP04) employed in the production of car body parts. The fracture toughness of the joints was determined using the test protocol proposed by the European Structural Integrity Society (ESIS). Optical microscopy was employed to ascertain the mechanisms of failure. The results indicated that both adhesives were able to provide a fairly good mechanical response with minimum preparation of the mating substrates. Moreover, the obtained values of fracture toughness were shown to be essentially independent of the adhesive layer thickness

Independent association of atherogenic dyslipidaemia with all-cause mortality in individuals with type 2 diabetes and modifying effect of gender. a prospective cohort study

Atherogenic dyslipidaemia has been implicated in the residual risk for cardiovascular morbidity and mortality, which remains despite attainment of LDL cholesterol goals especially in individuals with type 2 diabetes. However, its relationship with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of increased triglycerides and triglyceride:HDL cholesterol ratio (TG:HDL) and decreased HDL cholesterol with total mortality and the possible modifying effect of gender in a large cohort of patients with type 2 diabetes

Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes

Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 patients with T2D from the "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes". Measurements of serum vitamin D were centralised. Genotypes were obtained by Eco™ Real-Time PCR. Data were adjusted for gender, age, BMI, HbA1c, T2D therapy and sampling season. DHCR7 rs12785878 (p = 1 x 10-4) and GC rs4588 (p = 1 x 10-6) but not CYP2R1 rs10741657 (p = 0.31) were significantly associated with vitamin D levels. One unit of a weighted genotype risk score (GRS) was strongly associated with vitamin D levels (p = 1.1 x 10-11) and insufficiency (&lt;30 ng/ml) (OR, 95%CI = 1.28, 1.16-1.41, p = 1.1 x 10-7). In conclusion, DHCR7 rs12785878 and GC rs4588, but not CYP2R1 rs10741657, are significantly associated with vitamin D levels. When the 3 variants were considered together as GRS, a strong association with vitamin D levels and vitamin D insufficiency was observed, thus providing robust evidence that genes involved in vitamin D metabolism modulate serum vitamin D in T2D

Quality Performances of Sweet Pepper under Farming Management

Conventional management of sweet pepper is based on farming practices characterized by the use of chemicals with harmful environmental impact. In order to investigate innovative production, research was carried out in order to assess the effects of two pepper cultivars ('Brillant' and 'Yolo Wonder') in combination with four farming systems (Conventional control-C; Conventional with microorganism-enriched fertilization-CMF; Organic control-O; Organic with microorganism-enriched fertilization-OMF) on plant physiological parameters, yield and fruit quality. Conventionally grown plants showed higher values of assimilatory pigments and of photosynthetic rate compared to the Organically ones. The CMF resulted in the highest early and total yield, followed by the OMF, due to higher fruit number. Higher values of carotenoids, ascorbic acid and α-tocopherol were recorded in 'Yolo Wonder' red fruits compared to 'Brillant' yellow berries. The highest total polyphenols concentration was recorded under the CMF, whereas OMF resulted in the highest flavonoids concentration and antioxidant activity

Industrial processing affects product yield and quality of diced tomato

The tomato industry has been searching for new genotypes with improved fruit production, both in the field and industrially processed, together with high-quality performance under sustainable management conditions. This research was carried out in Southern Italy with the aim of assessing the effects of industrial processing on the yield and quality of four tomato hybrids grown according to organic farming methods and addressed at dicing. MAX 14111 and HMX 4228 showed the highest values of field and processing yield as well as reduced sugars and fructose. MAX 14111 had the highest values of total solids and soluble solids, titratable acidity, fiber, energetic value, polyphenols, and also rutin, though not significantly different from Impact. HMX 4228 performed best in terms of sugar ratio, color and naringenin. Concerning the diced products, the sensorial qualities of the four hybrids differed significantly. Total polyphenols, naringenin and rutin in the tomato fruits were higher in the processed than in the raw product. The appreciable fruit yield and quality resulting from both field and processing phase represent a promising perspective for identifying improved tomato genotypes addressed at dicing

The mechanism of action of a novel neuroprotective low molecular weight dextran sulphate : new platform therapy for neurodegenerative diseases like Amyotrophic Lateral Sclerosis

Background: Acute and chronic neurodegenerative diseases represent an immense socioeconomic burden that drives the need for new disease modifying drugs. Common pathogenic mechanisms in these diseases are evident, suggesting that a platform neuroprotective therapy may offer effective treatments. Here we present evidence for the mode of pharmacological action of a novel neuroprotective low molecular weight dextran sulphate drug called ILB®. The working hypothesis was that ILB® acts via the activation of heparin-binding growth factors (HBGF). Methods: Pre-clinical and clinical (healthy people and patients with ALS) in vitro and in vivo studies evaluated the mode of action of ILB®. In vitro binding studies, functional assays and gene expression analyses were followed by the assessment of the drug effects in an animal model of severe traumatic brain injury (sTBI) using gene expression studies followed by functional analysis. Clinical data, to assess the hypothesized mode of action, are also presented from early phase clinical trials. Results: ILB® lengthened APTT time, acted as a competitive inhibitor for HGF-Glypican-3 binding, effected pulse release of heparin-binding growth factors (HBGF) into the circulation and modulated growth factor signaling pathways. Gene expression analysis demonstrated substantial similarities in the functional dysregulation induced by sTBI and various human neurodegenerative conditions and supported a cascading effect of ILB® on growth factor activation, followed by gene expression changes with profound beneficial effect on molecular and cellular functions affected by these diseases. The transcriptional signature of ILB® relevant to cell survival, inflammation, glutamate signaling, metabolism and synaptogenesis, are consistent with the activation of neuroprotective growth factors as was the ability of ILB® to elevate circulating levels of HGF in animal models and humans. Conclusion: ILB® releases, redistributes and modulates the bioactivity of HBGF that target disease compromised nervous tissues to initiate a cascade of transcriptional, metabolic and immunological effects that control glutamate toxicity, normalize tissue bioenergetics, and resolve inflammation to improve tissue function. This unique mechanism of action mobilizes and modulates naturally occurring tissue repair mechanisms to restore cellular homeostasis and function. The identified pharmacological impact of ILB® supports the potential to treat various acute and chronic neurodegenerative disease, including sTBI and ALS

IL TRATTAMENTO DELLE DISLIPIDEMIE NELLA PREVENZIONE PRIMARIA DELLE MALATTIE CARDIOVASCOLARI: LE INDICAZIONI PER LA PRATICA CLINICA

Le dislipidemie rappresentano uno dei più importanti fattori causali della arteriosclerosi e delle sue complicanze d’organo, come l’infarto del miocardico, l’ictus e la vasculopatia periferica. Il loro appropriato trattamento rappresenta la base degli interventi di prevenzione primaria delle malattie cardiovascolari su base ischemica. In generale, per dislipidemia si intende una condizione clinica nella quale sono presenti alterazioni qualitative e/o quantitative dei lipidi e delle lipoproteine plasmatiche

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study

Introduction In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and &gt;= 3 (late add-on) prior antiseizure medications. Results A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p &lt; 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p &lt; 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p &lt; 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively. Conclusion Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy