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The preservation of local landraces represents a crucial point in biodiversity maintenance and it necessarily starts from a qualitative and morphological characterization. The 'San Marzano' tomato (Solanum lycopersicum L.) is an elongated fruit cultivar particularly suitable for processing and represents one of the most significant horticultural products for the Italian food industry. Five 'San Marzano' landraces ('SM Bellizzi 1', 'SM Bellizzi 2', 'SM Bellizzi 3', 'SM Montoro Inferiore' and 'SM Sarno') characterized by different fruit shapes (pointed, round and hollow) were compared in terms of yield, nutritional and functional quality. The fruit dry matter percentage as well as the juice EC ranged from 4.94 to 7.10% and from 3.04 to 3.80 dS m-1, respectively, with the lowest values observed in 'SM Montoro Inferiore'. The highest total soluble solids content was recorded in both 'SM Montoro Inferiore' and 'SM Sarbo', followed by 'SM Bellizzi 1' and 'SM Bellizzi 3', whereas the lowest values were observed in both 'SM Bellizzi 2' and 'SM Bellizzi 3'. Among the three macronutrients analyzed K was the most abundant macro-mineral, followed by phosphorus and finally nitrate. 'SM Bellizzi 1' was richer in P and K compared to the rest of the landraces tested. The highest levels of hydrophilic and lipophilic antioxidant activities were recorded in 'SM Sarno' and 'SM Bellizzi 3', respectively. Our findings will contribute toward the documentation of nutritional and functional quality profiles of an important collection of niche products such as the SM tomato.

Sweet basil (Ocimum basilicum L.) is one of the most common aromatic herbs cultivated all over the world. It is widely used for its aromatic and culinary purposes. Consumer demand for fresh sweet basil has been on the rise and many farmers of leafy vegetables and aromatic herbs have oriented their production schemes to include basil. The genetic material is a key preharvest factor and the major determinant of variation in yield and quality of leafy vegetables. Another important preharvest factor that may modulate yield and nutritional quality of sweet basil could be the growing medium. The aim of this research was to assess in a multi-factorial approach the effects of two sweet basil cultivars (Napoletano and Genovese) and two substrates (rockwool and an innovative inert substrate, SISAL fiber) on plant growth, marketable yield, nitrogen content and nutritional quality. The plant growth parameters, yield and especially the bioactive compounds were mostly affected by the growing media and to a lesser extent by the genetic material. When averaged over growing media, the highest leaf number was observed in 'Genovese' while an opposite trend was recorded for the leaf area. Irrespective of the sweet basil cultivar, plants grown on rockwool exhibited a higher leaf area, leaf fresh weight and dry biomass compared to those grown on SISAL fiber substrate. Contrarily to crop productivity, sweet basil grown on SISAL was characterized by high levels of lipophilic antioxidant activity, total chlorophyll and carotenoids, whereas no significant effect among treatments were recorded on total phenols. Although the yield reduction with SISAL was quite significant, the basil plants grown on this innovative substrate produced leaves with high concentrations of bioactive compounds. Additional researches should focus on elucidating the Genotype × Substrate interaction in order to select the best combinations.

In many irrigated regions of Mediterranean areas, vegetable farmers are forced to use low quality water (often with elevated salinity) for their crops with important losses in productivity. Sweet basil (Ocimum basilicum L.) is one of the most important aromatic herbs cultivated in Italy under both open-field and protected conditions. The application of endophytic fungi such as mycorrhizal fungi and Trichoderma could be an efficient tool to mitigate the detrimental effect of salinity. A greenhouse experiment was carried out to assess the influence of co-inoculation of endophytic fungi and plant growth promoting rhizobacteria on yield and quality traits under non-saline (1 mM NaCl) and saline (40 mM NaCl) conditions. Increasing the NaCl concentration in the nutrient solution in both inoculated and non-inoculated plants decreased the yield and growth parameters but increased the quality traits in particular the hydrophilic and lipophilic antioxidant activities and total phenols. The microbial-based biostimulant markedly enhanced the marketable fresh yield by 17.0% compared to control plants. The better crop performance of inoculated basil has been attributed to a better pigment biosynthesis (i.e., higher SPAD index). On the other hand, the nitrate content in microbial biostimulant basil plants was significantly reduced by 16.1%, whereas the total phenols increased by 7.7% compared to untreated plants. Overall, the use of beneficial microorganisms could be adopted as a sustainable tool in vegetable cropping systems to mitigate the detrimental effect of saline water.

Since the beginning of the COVID-19 pandemic it has been recommended that chemical disinfectants are used to protect surfaces. This study aimed to determine whether the number of exposure calls related to household disinfectants (HD) received between January 30, 2020 to May 18, 2020 varied from the same time period in the previous year.A retrospective review of the poison control center database from the Fondazione Universitario Policlinico Agostino Gemelli IRCCS, Rome, Italy, was conducted. Calls from Italian citizens, hospitals, and general practitioners received during the same time period in 2019 and 2020 were compared.The center received 1972 exposure calls during the study period. A 5% increase in calls regarding exposure to HDs was noted from 2019 to 2020 (9.8% to 15.2%, p0.001). The majority of enquiries regarded bleach-containing products, hand sanitizers, ethanol, and hydrogen peroxide. Most calls were received from patients in their homes (n, 259; prevalence, 86%; increase, 107%) and concerned accidental exposure (n, 280; prevalence, 93%; increase, 76%), while cases of intentional exposure decreased (n, 14; prevalence, 5%; decrease, 33%). The main route of exposure was ingestion (n, 170; prevalence, 57%; increase, 45%), but the highest increase was observed in inhalation cases (n, 82; prevalence, 27%; increase, 122%).As the incidence of enquiries regarding products that can represent an important health hazard, when improperly used, increased in 2020 suggests that the COVID-19 public health messaging on the proper use of HDs should be improved.

Background and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. Introduction Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. Material and methods We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Results Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. Conclusion We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Azotobacter chroococcum 67B, A. chroococcum 17-1 and A. chroococcum 76A, isolated from compost, were previously selected for their plant growth promoting activities and high NaCl tolerance. The performances of these strains to increase plants' salinity tolerance were tested on tomato plants ('Microtom') in a greenhouse experiment. Plants substrate was inoculated with A. chroococcum 67B, A. chroococcum 76A, alone or with a combination of strains 67B and 17-1. Plants inoculated with commercial product of PGPR and non-inoculated plants were used as controls. Inoculated plants and their relative controls were exposed to 3 salinization levels (0, 5, 10 g L-1 NaCl) and 3 fertilization regimes [Basic nutrient Solution (BS), BS + 0.5 g L-1 NH4NO3 and BS + 1 g L-1NH4NO3]. Preliminary analysis revealed that all the bacterial strains did not have a significant impact onthe total fresh biomass and fruits fresh weight of tomato under NaCl stress. Further investigations, including shoot vs. root development, profiling of ions uptake and distribution and fruits quality parameters will be necessary to assess the complete performance of these strains and their value in agricultural applications.

Botulinum toxin is considered as first-line therapy for cervical dystonia, but few papers have addressed these issues in the long term. Aim of this study was to investigate the long-term efficacy and safety of abobotulinumtoxin A (A/Abo) in patients with primary cervical dystonia. Consecutive patients who received at least six injections with A/Abo were included. Safety was assessed on patients' self-reports. Efficacy was assessed by recording the total duration of benefit, duration of maximum efficacy, disease severity measured by means of the Tsui score, and pain intensity evaluated by means of the visual analog scale (VAS). Thirty-nine patients with PCD were included. The mean dose injected was 701.5 ± 280.6 U. The mean duration of the clinical improvement was 93.0 ± 30.7 days, while the mean duration of the maximum clinical improvement was 77.1 ± 27.1 days. The mean VAS before and 4 weeks after injection was 4.4 ± 1.8 and 1.8 ± 1.6, respectively. The mean Tsui score before and 4 weeks after treatment was 5.7 ± 1.8 and 3.5 ± 1.5, respectively. Doses of A/Abo and duration of the maximum clinical improvement significantly increased over time, while the Tsui score and VAS displayed a tendency to decrease along time. Side effects occurred in 19.6% of all the treatments but were severe in only four injections. The results of our study confirm the effectiveness and safety profile of A/Abo for the long-term treatment of primary cervical dystonia.

Monoclonal plasma cell proliferative disorders comprise a wide spectrum of diseases associated to clonal B-cell expansion. Serum protein electrophoretic profile (SPEP) and circulating free light chains (FLCs) levels are the mainstay of diseases management. Recently, soluble (s) Syndecan-1 (SDC1, CD138) produced by myeloma plasma cells has been suggested in the monitoring and follow-up of patients with myeloma. The aim of our study is to evaluate sCD138 in addition with FLCs and SPEP for the screening of patients with different evolutive disease pathways.Sera from 73 patients with monoclonal gammopathy of undetermined significance (MGUS), 120 smoldering and 42 multiple myeloma (SMM and MM, respectively), 70 HCV-related mixed cryoglobulinemia (MC), 35 B-cell non-Hodgkin's lymphoma (B-NHL) and sera from 50 healthy donors (HD), were tested for sCD138, FLCs (assessed by means of ELISA and turbidimetric assay, respectively) and electrophoresis pattern (performed on Capillarys system) for the generation of a novel biomarker score (BS).Our results were grouped according to the two main lines of disease progression (vs. MM or B-NHL): in one group we found BS mean values of 0.2, 3.4, 5.3, 7.1 for HD, MGUS, SMM and MM, respectively; in the other group of 0.2, 4.4, 6.7 for HD, MC and B-NHL.We showed that BS mean values follow the ingravescence disease status towards the two main lines of progression to cancerous conditions; it could represent an additional useful tool in the management of screening and/or follow-up.

Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity.Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function.LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure.Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 ± 24 mL at baseline to 8 ± 8 mL 12 months after treatment (P.001). Mean nodule volume reduction was 72% ± 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% ± 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P.001) and evidence of cosmetic signs from 86% to 8% of cases (P.001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed.Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

Obesity and gestational diabetes mellitus (GDM) are rising worldwide. This study retrospectively evaluated the role of excessive gestational weight gain (eGWG) in women with GDM and different pre-pregnancy body mass indices (BMIs).Optimal glycaemic control was defined as achieving glucose target thresholds in more than 80% of measurements. 283 women with GDM were categorized as underweight, normal weight, overweight or obese based on WHO's classification scheme. eGWG was defined as18.0 kilograms for women who were underweight,15.8 kilograms for those who were normal weight,11.3 kilograms for those who were overweight and9.0 kilograms for those who were obese. For the analysis, women were divided into two groups: normal and excessive GWG. The main outcomes measured were incidences of large/small for gestational age (LGA/SGA), macrosomia, preterm delivery, hypertensive disorders and caesarean sections (CS).Excessive GWG was associated with higher birth weight and percentile (p0.001), and with a higher prevalence of LGA (p0.001), macrosomia (p=0.002) and hypertensive disorders (p=0.036). No statistical differences were found for the week of delivery, or prevalence of CS and SGA. The multivariate analysis highlighted both pre-pregnant BMI and eGWG as independent risk factors for LGA and macrosomia. Women with a pre-pregnant BMI of at least 25 and eGWG have a 5.43-fold greater risk of developing LGA (p=0.005).When combined with an inadequate pre-pregnant BMI, eGWG acts as a "synergic risk factor" for a poor outcome. When obesity or GDM occur, an optimal GWG can guarantee a better pregnancy outcome.

Basil (Ocimum basilicum L.) is one of the most common aromatic herbs cultivated all over the world. It is widely used for aromatic and culinary purposes. Two greenhouse experiments were carried out to determine the effects of increasing the level of salinity in the nutrient solution (1 or 40 mM NaCl) during two consecutive growing seasons (summer and autumn) on growth, yield and leaf-quality traits of green sweet basil 'Mammolo' grown in an open-loop system. Increased salinity in the nutrient solution from 1 to 40 mM decreased fresh yield and final leaf area, with a more detrimental effect during the warm season. The percentage reductions in yield and leaf area in comparison with the non-saline control were respectively 30 and 42% in the summer cropping season and 20 and 16% in the autumn season. Increasing the NaCl concentration in the nutrient solution from 1 to 40 mM increased the hydrophilic antioxidant activity (HAA) and total phenolics (TP) by 87 and 17%, respectively, and reduced the nitrate content by 84%. When averaged over salinity level, TP increased and the nitrate content decreased in plants grown in summer compared with the autumn growing season.

Background: The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure. Patients: Two hundred consecutive patients were randomly assigned to a single LAT session (group 1, 101 cases) or to follow-up (group 2, 99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid nodule with volume of 6–17 mL, repeat benign cytological findings, normal thyroid function, no autoimmunity, and no thyroid gland treatment. Methods: Group 1: LAT was performed in a single session with two optical fibers, a 1064 nm Nd-YAG laser source, and an output power of 3 W. Volume and local symptom changes were evaluated 1, 6, 12, 24, and 36 months after LAT. Side effects and tolerability of treatment were registered. Group 2: Follow-up with no treatment. Results: One patient was lost to follow-up in each group. Group 1: Volume decrease after LAT was −49 ± 22%, −59 ± 22%, −60 ± 24%, and −57 ± 25% at 6, 12, 24, and 36 months, respectively (P < .001 vs baseline). LAT resulted in a nodule reduction of >50% in 67.3% of cases (P < .001). Local symptoms decreased from 38 to 8% of cases (P = .002) and cosmetic signs from 72 to 16% of cases (P = .001). Baseline size, presence of goiter (P = .55), or US findings (fluid component ≤ 20% [P = .84], halo [P = .46], vascularization [P = .98], and calcifications [P = .06]) were not predictive factors of a volume decrease > 50%. The procedure was well tolerated in most (92%) cases. No changes in thyroid function or autoimmunity were observed. In group 2, nodule volume increased at 36 months (25 ± 42%; P = .04). The efficacy and tolerability of the procedure were similar in different centers. Conclusions: A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.

The scarcity of good quality water frequently led to the use of saline water for the irrigation of ornamental shrubs. Therefore, their salt tolerance needs to be investigated, along with the possibility to counteract the effect of salinity exposure on plant growth and ornamental quality, possibly due to reduced growth, and nutritional imbalances. Under salt stress conditions, plants can activate mechanisms helping to withstand it, such as the production of several organic solutes that play a role in the osmotic adjustment. Aiming to this extent the exogenous application of osmolytes, such as glycine betaine (GB) and L-proline (L-P), has been tested on potted plants of Viburnum lucidum L. grown under saline irrigation. The experiment was designed as a factorial combination of two nutrient solutions (non-salt control, or 200 mM NaCl) and three osmoprotectant treatments (untreated, GB 2.5 mM, or L-P 5 mM application). Shoot and root biomass were negatively affected by salinity (-37 and -29%, respectively), but not the shoot/root ratio. A significant and positive effect of osmolytes application was found on the shoot biomass of plants treated with GB (+46%). Lateral sprouting total length per plant was also reduced by saline irrigation (-60%), but the GB application resulted in a significant increase (+102%). A positive effect of GB application was also found on the total leaf area (LA) per plant that was increased by 182% under saline conditions. Root/shoot ratio did not change with salinity. L-P application resulted in a significant increase of both shoot and root biomass per unit of LA (+40 and +85%, respectively) in comparison with the untreated control and GB.

The aim of this study is to verify whether degeneration of skin receptors or intradermal nerve endings by topical application of capsaicin modifies the double peak response obtained by submaximal anodal stimulation. Five healthy volunteers topically applied capsaicin to the finger-tip of digit III (on the distal phalanx) four times daily for 4-5 weeks. Before and after local capsaicin applications, we studied the following electrophysiological findings: compound sensory action potential (CSAP), double peak response, sensory threshold and double peak stimulus intensity. Local capsaicin application causes disappearance or decrease of the second component of the double peak, which gradually increases after the suspension of capsaicin. Conversely, no significant differences were observed for CSAP, sensory threshold and double peak stimulus intensity. This study suggests that the second component of the double peak may be a diagnostic tool suitable to show an impairment of the extreme segments of sensory nerve fibres in distal sensory axonopathy in the early stages of damage, when receptors or skin nerve endings are impaired but undetectable by standard nerve conduction studies.

Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serum Chit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis. Mammalian chitinases exert important biological roles in the monocyte lineage and chronic inflammatory diseases. In particular, Chit seems to promote bone resorption in vitro. No in vivo studies have been performed to confirm this finding. We aim to evaluate Chit activity in postmenopausal women affected by severe osteoporosis. In this cross-sectional study, 91 postmenopausal women affected by osteoporosis and 61 with either osteopenia or normal BMD were screened. All subjects were assessed by dual-energy X-ray absorptiometry (DXA) and X-ray vertebral morphometry. Osteoporotic subjects were considered eligible if they were affected by at least one vertebral osteoporotic fracture (group A = 57 subjects). Osteopenic or healthy subjects were free from osteoporotic fractures (group B = 51 subjects). Enzymatic Chit and serum β-CrossLaps (CTX) were measured in the whole population. Group A showed higher serum levels of beta-CTX compared to group B (0.40 ± 0.26 ng/mL vs 0.29 ± 0.2 ng/mL, p = 0.022). Chit was significantly higher in group A than in group B (1042 ± 613 nmol/mL/h vs 472 ± 313 nmol/mL/h, p

Cryoimmunoglobulins are pathological antibodies characterized by a temperature-dependent reversible insolubility. Rheumatoid factors (RF) are immunoglobulins possessing anti-immunoglobulin activity and usually consist of an IgM antibody that recognizes IgG as antigen. These proteins are present in sera of patients affected by a large variety of different pathologies, such as HCV infection, neoplastic and autoimmune diseases. Aggregation and precipitation of cryoimmunoglobulins, leading to vasculiti, are physical phenomena behind such pathologies. A deep knowledge of the physico-chemical mechanisms regulating such phenomena plays a fundamental role in biological and clinical applications. In this work, a preliminary investigation of the aggregation kinetics and of the final macromolecular structure of the aggregates is presented. Through static light scattering techniques, the gyration radius Rg and the fractal dimension Dm of the growing clusters have been determined. However, while the initial aggregation mechanism could be described using the universal reaction-limited cluster–cluster aggregation (RLCCA) theory, at longest times from the beginning of the process, the RLCCA theory fails and a restructuring of clusters is observed together with an increase of the cluster fractal dimension Dm up to a value Dm∼3. The time tn, at which the restructuring takes place, and the final cluster size can be modulated by varying the quenching temperature.

Cardiovascular changes during laparoscopic surgery have been described in several studies. Pneumoperitoneum effects on cardiac performance instead have not been much investigated and are less known. The carbon dioxide insufflation necessary in order to perform laparoscopic procedures represents a higher force against which the myocardial fibers must shorten during ventricular contraction. Hypothesis of this study is that the intra-abdominal pressure at 12 mmHg could acutely affect the left ventricular wall stress and work. Aim of the study was to evaluate the impact of relationship pneumoperitoneum on the echocardiographic measures of left ventricular contractile function.We studied 20 healthy, ASA I women, undergoing laparoscopic hysterectomy. Transthoracic echocardiography was performed preoperatively, after induction of anaesthesia, 15' after pneumoperitoneum, 15' after Trendelenburg positioning and 15' after the end of surgery. Left ventricular end-systolic wall stress, stroke work, left ventricular ejection time and mean velocity of fiber shortening were registered.Carbon dioxide insufflation caused a consistent increase in left ventricular end-systolic wall stress and left ventricular ejection time, while the mean velocity of fiber shortening decreased. The Trendelenburg position did not produce any other signficant effects. These changes were transient with a return to preinsufflation values at the last measurement. Pneumoperitoneum adversely affects left ventricular performance during laparoscopy, leading to an increase of left ventricular end-systolic wall stress and reducing the mean velocity of circumferential fiber shortening. These cardiac consequences appear to be reversible since all the echocardiographic parameters normalized at the end of surgery.Our results suggest that there is an adaptation of the cardiac systolic contractile status to the pressure overload during laparoscopy.

No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group (p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months (p

The aim of this study was to investigate the severity of coronary artery disease (CAD) and the plaque composition in neuropathic type 2 diabetic subjects with and without Charcot neuroarthropathy (CN) undergoing multidetector computed tomography coronary angiography (MDCT-CA). The study was a single-center, observational, with unmatched case–control design. We selected 17 CN patients and 18 patients with diabetic neuropathy (DN) without CN. In all the patients, multidetector computed tomography was performed to assess the coronary artery calcium score (CACS) and degree of coronary artery stenosis. Patients were classified as positive in the presence of significant CAD if there was at least one stenosis >50 % on MDCT-CA. The invasive coronary angiography was performed in case of significant stenosis detected with MDCT-CA, both as reference to standard and eventually as treatment. Groups were matched for age, sex, and traditional CAD risk factors. As compared to DN individuals, CN exhibited higher rates of significant coronary stenoses (p = 0.027; OR 7.7 [1.3–43.5]). However, no significant differences were observed in the CACS, which reflects plaque burden, in the two groups (p = 0.759). No significant differences were observed comparing CACS distribution in all subjects for stenosis higher/equal or lower than 50 % (p = 0.320). Finally, no significant differences were observed comparing CACS distribution in CN and DN subjects for coronary stenoses higher/equal or lower than 50 %. Our results suggest that CN patients have a higher prevalence of severe coronary plaques compared to DN patients. Nevertheless, coronary plaques in CN patients did not exhibit an increased degree of calcification.

Shear stress triggers conformational stretching of von Willebrand factor (VWF), which is responsible for its self-association and binding to the platelet receptor glycoprotein (GP)Ibα. This phenomenon supports primary hemostasis under flow. Type 2B VWF natural mutants are considered to have increased affinity for platelet GPIbα.To assess the mechanism responsible for the enhanced interaction of the p.R1306W VWF mutant with the platelet receptor.The interaction of GPIbα with wild-type (WT) and p.R1306W VWF multimers and A1-A2-A3 constructs was investigated with surface plasmon resonance spectroscopy. Analysis of the static VWF conformation in solution was performed with dynamic light scattering spectroscopy. The shear stress-induced self-association of VWF multimers was investigated with atomic force microscopy (AFM) over a 0-60 dyn cm(-2) range.WT VWF did not interact with GPIbα under static conditions, whereas the mutant at ~ 2 μg mL(-1) already bound to the receptor. By contrast, the WT and p.R1306W-A1-A2-A3 constructs showed comparable affinities for GPIbα (Kd ~ 20 nm). The hydrodynamic diameter of resting R1306W VWF multimers was significantly greater than that of the wild type (210 ± 60 nm vs. 87 ± 22 nm). At shear forces of 14 dyn cm(-2) , the p.R1306W multimers rapidly changed conformation, entering a regime of self-aggregation, which, in contrast, was induced for WT VWF by shear forces of 30 dyn cm(-2) . Mechanical stretching AFM experiments showed that p.R1306W multimers needed less energy per length unit (~ 10 pN) to be stretched than the WT protein.The increased affinity of p.R1306W VWF for GPIbα arises mostly from higher sensitivity to shear stress, which facilitates exposure of GPIbα binding sites.

Purpose: Leptin deficiency in mice (LepOb/Ob) triggers high caloric intake leading to obesity/insulin resistance and activates several reactive oxygen species (ROS) generating pathways. Recent evidence suggest that mitochondrial adaptor p66Shc is a crucial player in ROS-mediated vascular damage. The present study investigates p66Shc role in obesity-driven vascular dysfunction. Methods: Three groups of male mice were studied (C57/B6, 4-6 months old, n=14 per group): 1) wild-type (WT), 2) leptin-deficient (p66Shc-LepOb/Ob), 3) double-mutant (p66Shc-/-/LepOb/Ob;). Plasma 8-iso-prostaglandin-F2α (8-iso-PGF2α was measured as a systemic marker of oxidative stress. mRNA and protein expression were assessed by real-time PCR and immunoblotting. ESR spectroscopy assessment of superoxide anion (O2-) levels and mitochondrial swelling were performed in mitochondria isolated from mouse aortas. The interaction between p66Shc and cytochrome c was investigated by pull-down assays. Organ chamber experiments were performed to assess endothelium-dependent relaxations to acetylcholine (Ach, 10-9-10-6 mol/L). NF-kB activity was determined as p65 nuclear translocation. Results: Plasma 8-iso-PGF2α as well as mitochondrial O2- levels were significantly higher in LepOb/Ob than WT. This increase was abolished in p66Shc-/-LepOb/Ob mice. Oxidative stress in LepOb/Ob mice was associated with p66Shc upregulation, mitochondrial translocation and swelling. Consistently, co-immunoprecipitation of p66Shc with cytochrome c and impaired Ach-induced relaxations were observed in the aortas of LepOb/Ob but not in WT mice. By contrast, in p66Shc-/-/LepOb/Ob mice endothelial dysfunction and mitochondrial swelling did not occur. In agreement with these findings, a preserved activation of Akt/eNOS pathway was observed. Genetic disruption of p66Shc in obese mice also prevented vascular activation of NF-kB signalling and upregulation of VCAM-.1, ICAM-1, IL-6, IL-8 and MCP-1 mRNAs. Conclusions: Our results suggest that p66Shc is critically involved in obesity-induced oxidative stress and vascular dysfunction. A better understanding of the molecular mechanism responsible for ROS production may provide a novel target to reduce cardiovascular health burden in this setting.

Hunger sensation (HS) in humans physiologically shows intraday (circadian) and within-day (ultradian) recursivity. This intrinsic periodicity was investigated by applying the cosinor method and spectral analysis to the 24-hour profile of HS (orexigram) derived by a self-rating score (from 1 to 10 hunger units [HU]) recorded every half-hour. The study of circadian and ultradian recursivity on the orexigram was performed in 30 diabetic obese patients ([DOPs], 14 men and 16 women aged 22 to 62 years; body weight, 77 to 130 kg; body mass index, 31–47). The control group consisted of 30 clinically healthy subjects ([CHS], 15 men and 15 women aged 21 to 60 years; body weight, 65 to 72 kg; body mass index, 23 to 25). DOPs showed two types of orexigrams in which hunger was felt with limitation to the diurnal part of the day or with extension to the night, respectively. The type 1 orexigram was characterized by a normal spectrum and circadian rhythm. The type 2 orexigram was characterized by subsidiary ultradian components associated with an abnormal elevation of the circadian mesor and a significant delay of the circadian phase, as the spectral analysis was indicative of a structural difference in the frequencies that sustain the intraday and within-day recursivity of the HS. Accordingly, DOPs can be recognized by their orexigram as “eurectic” or “hyperrectic” to indicate subjects with a normal or an exaggerated HS, respectively, during the 24-hour span.

Ketorolac tromethanime is a non steroidal anti inflammatory drug and its efficacy on acute pain control after abdominal surgery has been well documented. It has a rapid onset and it can be given both for intra operative and for post operative pain management.In this study we aimed to evaluate if there were any differences in relieving post operative pain when Ketorolac was administered with continuous infusion or if it was given at prearranged times.80 ASA I patients, scheduled for major gynecological surgery, were randomly assigned to 2 groups: group A patients were connected after surgical incision with a 24h analgesic infusor (2 ml/h) containing morphine (0.02 mg/kg/h) and Ketorolac (90 mg). Group B patients were connected after surgical incision with a 24h analgesic infusor (2 ml/h) containing morphine (0.02 mg/kg/h) at first and Ketorolac was then given in bolus after surgical incision and then every 8 hours for the first 24 hours. Post-operative pain scores were assessed using the Visual Analogue Scale (VAS) every 8 hours for 24 h. For a VAS value greater than 6, patients received Tramadol 100 mg.Post-operative pain scores showed a better pain relief for patients in the group B. Furthermore, the requirements of rescue analgesic were less in the group B [Tramadol was used for only 8 patients] than in the group A [Tramadol was used for 31 patients]. No adverse effects were registered in both groups.strong/strongFor post-operative pain Ketorolac administration at prearranged times, every 8 hours, offers greater benefits in respect to its continuous infusion.

We recently demonstrated that pneumoperitoneum affects diastolic echocardiographic findings in healthy women scheduled for gynaecologic laparoscopy. No reports have been conducted in order to assess the echocardiographic consequences in hypertensive subjects during laparoscopic procedures.The aim of this study was to evaluate Left Ventricular filling pressures in hypertensive women with and without diastolic dysfunction, combining the tissue Doppler imaging technique and the plasmatic levels of amino terminal proBNP.Doppler recordings of mitral inflow, tissue Doppler imaging of mitral annulus and N-terminal-proBNP plasmatic levels were obtained in 40 hypertensive women with or without diastolic dysfunction. Measurements were executed in awake patients (T0), after the induction of anesthesia (T1), 10 and 20 minutes after the creation of the pneumoperitoneum (T2 and T3, respectively) and at the end of the surgery (T4). Furthermore, we collected the last blood sample after 12 hours (T5).The E/Ea ratio for the evaluation of left ventricular filling pressures were higher in the diastolic dysfunction group than in the non diastolic dysfunction and significantly increased after pneumoperitoneum. Pneumoperitoneum increased the plasmatic levels of natriuretic peptide in both groups. At the end of the procedure we did not observe any further significant alteration.Pneumoperitoneum produces a consistent increase of ventricular filling pressures in a population of hypertensive patients with and without diastolic dysfunction. Moreover, there is a significant but transient rise in NT-proBNP after gas insufflation in both groups, most accentuated in the diastolic dysfunction group.

Previous studies have shown a high cardiovascular risk in patients with autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Conversely, few data are available about patients with celiac disease (CD). The aim of our study was to assess carotid intima-media thickness (c-IMT), in patients with T1DM, CD or both (T1DM+CD) as compared with age- and sex-matched healthy individuals (H).We enrolled 120 patients, 30 with T1DM, 30 with CD, 30 with T1DM+CD and 30 H. Clinical, metabolic and anthropometric data were collected. All T1DM patients were on insulin while all CD patients were on a gluten-free diet. c-IMT was evaluated by high frequency linear digital ultrasound.c-IMT was significantly greater in patients with T1DM+CD than in patients with T1DM or CD (P0.001 for both), while no difference was found between T1DM and CD. Moreover, c-IMT was greater in CD than in H (P0.001). Glycemic control and disease duration were similar between T1DM+CD and T1DM. Lipid and anthropometric parameters were similar among groups. Furthermore, in a pooled multivariate analysis, only age and disease type were significantly correlated with c-IMT (P0.001 for both).Our study demonstrates that celiac patients have greater c-IMT as compared with healthy individuals. Thus, non-invasive monitoring of c-IMT in CD might be useful in preventing cardiovascular disease. Moreover, patients with T1DM+CD show more severe subclinical atherosclerosis as compared with those presenting T1DM or CD only, suggesting that the association of these autoimmune diseases might accelerate the atherosclerotic process.

In the PREdiction of DIabetes from CApillary blood glucose (PREDICA) study, we propose a novel approach based on multiple capillary blood glucose (CBG) measurements, assuming that weekly measurements performed for 2 months may be an efficient strategy to screen for diabetes. We studied 538 Caucasian subjects (247 men and 291 women) without a history of diabetes, consecutively recruited by 50 GPs from the Italian provinces of Rome and Frosinone. Subjects were asked to perform 8 fasting glucose and 8 post-prandial glucose measurements during a frame time of 2 months (Glucometer Accu-chek AVIVA Roche Diagnostics). Study subjects were 55 ± 9 years old (range 22-77 years of age), 50% were overweight and 16% obese. Fifty-eight percent of subjects have performed 13 to 16 CBG measurements during the study, 68% of subjects have performed at least 5 out of 8, both fasting and post-prandial measurements. Among 492 subjects who had at least two fasting measurements, 63.6% had normal glucose levels, 25.4% showed IFG, and 11.0% were diabetic. Considering post-prandial measurements, 74.2% had normal glucose levels, 23.0% had IGT, and 2.8% were diabetic. Combined IFG + IGT was detected in 7% of study subjects, while in 0.8% diagnosis of diabetes was confirmed with both fasting and post-prandial measurements. In this study, we found a high adherence to a novel screening strategy based on self-glucose monitoring in the general population. Our results show that multiple CBG measurements may represent a simple and efficient method for diabetes screening.

Patency of the ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) development represent severe affections for premature newborns, therefore the research of early markers for these two conditions is really important. The aim of this study is to analyze epithelial lining fluid (ELF) Neutrophil-gelatinase-associated lipocalin (NGAL) levels for prediction of lung injury or possible involvement of this molecule in PDA. Only scarce and contrasting results have previously been published in this field. In contrast, this molecule, included in a large macromolecular complex together with matrix metalloproteinase-9 (MMP-9), is considered an acceptable marker of infectious/inflammatory processes, cancer monitoring and induction of apoptotic pathway. NGAL was detected in 28 pre-term newborns by means of a commercially available kit in bronchoalveolar lavage fluid (BALF). The results have been corrected to ELF levels, by the urea method, to eliminate bias due to BALF collection. ELF NGAL levels were found significantly increased both in infants developing BPD or in those affected by PDA. By means of multivariate logistic regression analysis the significances were confirmed after adjusting for possible interfering variables such as gestational age and concomitant presence of both PDA and BPD. Our results stress the involvement of NGAL in the mechanisms leading to BPD and also suggest a possible association with PDA, which is often linked to prematurity and BPD development, probably due to the involvement of inflammatory and angiogenetic processes in both pathologies.

Summary Background Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. Objectives The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. Methods One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. Results All cases and controls were in Hardy–Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0·02) along with Breslow thickness (P = 0·001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. Conclusions Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.

Background: Vitamin D receptor (VDR) mediates the effects of vitamin D. Our paper evaluates the FokI and BsmI VDR genotypes in 246 Caucasian (Italian from Lazio Region) T1DM patients compared with 246 Caucasian healthy controls, sharing age and gender and regional provenience with the patients. In addition, T1DM patients without complications were compared with those carrying three complications. Methods: Genotyping has been obtained by RFLP-PCR technique. Results: A slight significant association of T1DM with FokI homozygous “ f ” genotype was observed. No association was observed with the presence of multiple complications by a multivariate analysis. Conclusion: T1DM patients showed slightly increased prevalence of “ ff ” VDR genotype.

Amyloid beta-peptide (AbetaP), the central constituent of senile plaques in Alzheimer's disease (AD) brain, has been shown to be a source of free radical oxidative stress that may lead to neurodegeneration. In particular, it is well known that oxidation of methionine 35, is strongly related to the pathogenesis of AD, since it represents the residue in AbetaP most susceptible to oxidation in vivo. In the present study, we used the fragment 31-35 of AbetaP, which has a single methionine at residue 35, in order to investigate the influence of the oxidation state of methionine-35 on the toxic and pro-apoptotic effects induced by Abeta(31-35) on isolated brain mitochondria. The obtained results show that exposure of isolated mitochondria from rat brain to AbetaP(31-35) determines (i) a large release of cytochrome c (ii) a significant reduction in mitochondrial respiration and (iii) a slight drop in the mitochondrial membrane potential (DeltaPsi). In contrast, the amplitude of these events resulted attenuated or completely abrogated in isolated brain mitochondria exposed to the AbetaP(31-35)Met35(OX), in which methionine 35 was oxidized to methionine sulfoxide. We have further characterized the action of AbetaP(31-35) and Abeta(31-35)Met35(OX) peptide on PC12 cells. Although these two peptides, compromised mitochondrial function at a different extent as assessed by MTT reduction, neither one of them decreased cell viability as measured by Trypan Blue exclusion assay. The results obtained in this study support the hypothesis that the oxidative state of Met-35 may play a critical role in the mechanisms responsible of neurotoxicity exerted by this peptide.

Histatin-5 is a peptide secreted in the human saliva, which possesses powerful antifungal activity. Previous studies have shown that this peptide exerts its candidacidal activity, through the inhibition of both mitochondrial respiration and the formation of reactive oxygen species. The purpose of the present study was to investigate the biological consequences of histatin-5 action on mammalian mitochondria to verify if the toxic mechanism exerted on mitochondria from Candida albicans is an exclusive for fungal cells. Moreover, hypothesising that the damage exerted on mitochondria may induce programmed cellular death pathways, we evaluated two main markers of apoptosis: the mitochondrial membrane potential (DeltaPsi) and the release of cytochrome c. The results obtained show that exposure of isolated mammalian mitochondria to histatin-5 determines: (i) a large inhibition of the respiratory chain at the level of complex I, (ii) a slight decrease in the mitochondrial membrane potential, and (iii) no release of cytochrome c.

Two brothers presented with late-onset cerebellar ataxia and severe dysphonia. Brain MRI showed vermian and hemispheric cerebellar atrophy. Laringofiberscopy revealed laryngeal abductor paralysis in both patients. Neurophysiologic studies showed a pure motor neuropathy. The combined findings and the molecular analysis suggest a new familial disorder. Inheritance is most likely autosomal recessive, but X-linked transmission is also possible.

We evaluated whether type of response to the migraine-induction test with a nitroglycerin ointment applied to the frontotemporal head region could predict the efficacy of antimigraine therapy. Forty-two patients with migraine without aura underwent the test before and 2 months after antimigraine therapy. Two and 4 months after treatment withdrawal, most subjects with a negative response to the post-treatment test maintained treatment benefit, whereas benefit was lost in patients with an early onset migraine response.

We have compared the migraine-inducing effect of nitroglycerin ointment applied to the frontotemporal region of the head, which is innervated by the ophthalmic and maxillary divisions of the trigeminal nerve, with that of nitroglycerin applied to the chin (innervated by the mandibular division), the posterolateral region of the neck (innervated by the second and third cervical roots), the lateral surface of the proximal third of the forearm (innervated by the sixth cervical root), and the medial surface of the upper-arm region (second dorsal root). One hundred patients suffering from migraine without aura were randomly divided into five equal groups. Each group received an application of 5 mg nitroglycerin in 2% ointment on a preselected body area for 2 hours. Frontotemporal nitroglycerin induced a significantly greater number of early onset migraine attacks with respect to the arm and forearm regions. In all cases, nitroglycerin applied to the frontotemporal region resulted in subsequent migraine, whereas there was a significant number of negative trials with nitroglycerin applied to the neck, arm, and forearm vs the frontotemporal area. It, therefore, appears that the trigeminal nerve endings in the affected frontotemporal region are particularly sensitive to the migraine-inducing effect of the nitrate. This suggests a peripheral neurogenic hypothesis of migraine genesis.

In human beings, hunger is a proprioceptive signal that shows intraday (circadian components) and within-day (ultradian components) recursivity. Both periodic components can be investigated by chronobiometric procedures by combining the Cosinor method with spectral analysis. A 24-hour profile of hunger sensation (HS) can be plotted on a 1-to-10 scale of intensity using self-rated scores performed every half-hour of the day. Circadian and ultradian components were studied in 60 patients affected by essential obesity (20 men and 40 women; mean age, 38.4 years; mean body weight, 101 kg) before and after treatment with dexfenfluramine (Isomeride®; Servier, Orleans, France) 15 mg orally twice daily, for 30 days. The control group consisted of 30 clinically healthy subjects (15 men and 15 women; mean age, 37.5 years; mean body weight, 69 kg). Chronobiometric analysis shows three patterns in obese patients, which suggests that HS may be normal (eurectic obesity), exaggerated (hyperrectic obesity), or diminished (hyporectic obesity). After dexfenfluramine administration, HS was showed a substantial decrease in the daily mean level. The spectrum of resolution in circadian and ultradian components was found to be maintained in eurectic obesity and partially readjusted in hyperrectic and hyporectic obesities. This demonstrates that dexfenfluramine acts not only as an anorectic but also as a chronizer by interfering with the recursive components of HS. The anorectic and chronizing effects suggest that dexfenfluramine is a “chronoanorectic drug” that interacts with the chronobiologic properties of the serotoninergic system.

The hypothesis that alpha-adrenergic receptor blockade accounts for the ability of ergotamine to stop migraine attacks was tested, in migraine patients, in an experimental migraine model based on nitroderivative- induced attacks. In a preliminary single blind, placebo controlled study, thymoxamine, a prevalently post-synaptic alpha adrenergic receptor antagonist, was able to abort migraine attack in 9 out of 10 patients, as opposed to 2 out of 10 by placebo (p0.005 Fisher's exact test). In a subsequent randomized, crossover, placebo controlled double blind study, the ability of a selective alpha-1 adrenergic receptor agonist, methoxamine, to block ergotamine antimigraine effect was studied. In 26 patients migraine was induced in two separate tests and then ergotamine was administered once after methoxamine pretreatment and once after placebo; methoxamine was significantly more effective than placebo in blocking antimigraine effect of ergotamine (p = 0.0055 Fisher's exact test). These results support the hypothesis that ergotamine alpha-1 adrenolytic properties may account for its antimigraine effect suggesting that this action takes place outside the blood-brain barrier, since methoxamine can cross it very poorly. Ergotamine target structure could be the trigeminal innervation of the extracranial and/or dural vessels.