First Measurement of Near-Threshold J/ψ Exclusive Photoproduction off the Proton.

We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8 GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39 GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).

Italian Titration Approach Study (ITAS) with insulin glargine 300 U/mL in insulin-naïve type 2 diabetes: Design and population.

BACKGROUND AND AIMS: Fostering patient's self-managing of basal insulin therapy could improve glucose control, by removing patient's and physician's barriers to basal insulin initiation, titration and glucose monitoring. The Italian Titration Approaches Study (ITAS) aims at demonstrating non-inferiority (<0.3% margin) in efficacy of glucose control (change in glycated hemoglobin [HbA1c] after 24 weeks) by the same titration algorithm of insulin glargine 300 U/mL (Gla-300), managed by the (nurse assisted) patient versus the physician, in insulin naïve patients with Type 2 Diabetes Mellitus (T2DM), uncontrolled with previous treatments. METHODS AND RESULTS: ITAS is a phase IV, 24-week, national, multicenter, open label, randomized (1:1) parallel group study. 458 patients were enrolled, 359 randomized, and 339 completed the study, in 46 Italian centers. Baseline characteristics and previous medications of the ITT population (N = 355) are reported. Mean ± SD age, T2DM duration, HbA1c, FPG and BMI were 64.0 ± 9.8 years, 11.6 ± 7.6 years, 8.79 ± 0.65%, 170.9 ± 42.3 mg/dL, and 30.3 ± 5.6 kg/m2, respectively. Vascular and metabolic disorders were most frequent (73.8% and 58.3%, respectively). More than 90% of patients were on metformin. CONCLUSION: ITAS is the first study to compare two different managers (nurse-assisted patient vs physician) of the same titration algorithm of Gla-300 in insulin naïve patients with T2DM in unsatisfactory glucose control. This study might provide novel evidence on the efficacy/effectiveness of patient-managed titration algorithm of Gla-300 in a pragmatic setting and may reduce barriers to basal insulin initiation and its titration.

Intensive lifestyle intervention is particularly advantageous in poorly controlled type 2 diabetes.

BACKGROUND AND AIMS: It is unknown whether lifestyle change is effective in people with type 2 diabetes with inadequate glucose control. The aim of this study was to asses, in a group of people with type 2 diabetes, the impact of baseline values of glycosylated haemoglobin (HbA1c) on the effects of an intensive lifestyle intervention on metabolic, clinical and strength parameters. METHODS AND RESULTS: 222 people with type 2 diabetes with mean ± standard deviation baseline HBA1c of 7.50% ± 1.27 (range 5.1-12.7%), were enrolled in a 3-month structured multidisciplinary lifestyle intervention. Anthropometric, biochemical, clinical and fitness measurements were collected at baseline, at the end of the lifestyle intervention program and at two-year follow-up visit. Significant improvements in glycometabolic control (HbA1c: p ≤ 0.0001); anthropometric parameters (BMI p ≤ 0.0001; waist circumference: p ≤ 0.0001); and systemic blood pressure (p ≤ 0.0001) were observed both at the end of the three month intensive lifestyle program and at the two-year follow up visit. In addition, defined daily doses of hypoglycaemic treatment significantly decreased (p = 0.001). Fitness measures exhibited significant increments in the whole sample at the end of the intensive intervention program (p ≤ 0.0001). When patients were divided into tertiles considering the baseline value of HbA1c, the most marked improvements in HbA1c, blood glucose and triglycerides were observed in the group with inadequate glucose control (Hba1c ≥ 7.71%), both at the three-month and two-year follow-ups. CONCLUSION: These results demonstrate that an intensive lifestyle intervention should be recommended for people with type 2 diabetes, particularly those with the most inadequate glycaemic control. REGISTRATION NUMBER: CURIAMO trial was registered in the Australian New Zealand Clinical Trials Registry, (ACTRN12611000255987).

Polarization Transfer in Wide-Angle Compton Scattering and Single-Pion Photoproduction from the Proton.

Wide-angle exclusive Compton scattering and single-pion photoproduction from the proton have been investigated via measurement of the polarization transfer from a circularly polarized photon beam to the recoil proton. The wide-angle Compton scattering polarization transfer was analyzed at an incident photon energy of 3.7 GeV at a proton scattering angle of θ_{cm}^{p}=70°. The longitudinal transfer K_{LL}, measured to be 0.645±0.059±0.048, where the first error is statistical and the second is systematic, has the same sign as predicted for the reaction mechanism in which the photon interacts with a single quark carrying the spin of the proton. However, the observed value is ~3 times larger than predicted by the generalized-parton-distribution-based calculations, which indicates a significant unknown contribution to the scattering amplitude.

Glargine metabolism over 24 h following its subcutaneous injection in patients with type 2 diabetes mellitus: a dose-response study.

BACKGROUND AND AIMS: After subcutaneous injection insulin glargine is rapidly metabolized to M1 and M2. In vitro, both M1 and M2 have metabolic effects and bind to IGF-1R similarly to human insulin, whereas glargine exhibits a higher affinity for the IGF-1R and greater mitogenetic effects. The present study was specifically designed to establish the dose-response metabolism of glargine over 24 h following s.c. injection in T2DM subjects on long-term use of glargine. METHODS AND RESULTS: Ten subjects with T2DM were studied during 24 h after s.c. injection of 0.4 (therapeutic) and 0.8 (high dose) U/kg of glargine on two separate occasions during euglycaemic clamps (cross-over design). Glargine, M1 and M2 over 24 h period were determined in appropriately processed plasma samples by a specific liquid chromatography-tandem mass spectrometry assay. Plasma M1 concentration (AUC0-24 h) was detected in all subjects and increased by increasing the glargine dose from therapeutic to high dose (p = 0.008). Glargine was detectable in 6 (therapeutic dose) and 9 (high dose) out of the 10 subjects and also increased by increasing the dose (p = 0.031). However, glargine concentration (AUC0-24 h--high dose) represented at most only 9.7% (4.6-15%) of the total amount of insulin measured in the blood. M2 was not detected at all. CONCLUSION: In T2DM people on long-term use of insulin glargine, even with higher doses (0.8 U/kg), glargine is nearly totally metabolized to the active metabolite M1. Glargine is often detectable in plasma, but its concentration remains well below that needed in vitro to potentiate IGF-1R binding and mitogenesis.

Diagnosis of hepatic steatosis and steatohepatitis in people with new-onset type 2 diabetes: a multidisciplinary approach.

AIMS: Non-Alcoholic-Fatty-Liver-Disease (NAFLD) is the most common cause of chronic liver disease in Western countries; closely linked to obesity and type 2 diabetes (T2DM), it is an additional cardiovascular risk factor. The aim of this study is to investigate the prevalence of NAFLD at T2DM onset. METHODS: 122 newly diagnosed T2DM patients were enroled; NAFLD was diagnosed using ultrasound and fibrosis risk calculated with an FIB4-score. Intermediate and high-risk patients were referred to a hepatologist and underwent transient elastography (TE). RESULTS: At T2DM diagnosis, 25% of patients were overweight, 47% were obese; ultrasound steatosis was present in 79% of patients; the average FIB-4 score was 1.4 (0.7). The NAFLD population was characterised by higher presence of obesity (60%, p 0.06); hypertension (56%, p 0.00); AST (26.3 (23.6) UI/L; p 0.00); ALT (49.3(41.0) UI/L p 0.00); FIB-4 score (1.6 (0.8); p 0.00). Among patients referred to a hepatologist, at TE, 65% had severe steatosis, 22% significant fibrosis and 25% advanced fibrosis. CONCLUSION: This is the first proposal of a NAFLD screening model at T2DM diagnosis. The high prevalence of fibrosis found at the early stage T2DM confirms the compelling need for early management of NAFLD through cost-effective screening and long-term monitoring algorithms.

The current and future off-label uses of dalbavancin: a narrative review.

Dalbavancin is a novel long-acting semi-synthetic lipoglycopeptide. It is licensed for acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. Many studies on dalbavancin alternative use in clinical practice have been published recently, including osteomyelitis, prosthetic joint infections (PJIs), and infective endocarditis (IE). Thus, we conducted a narrative review on dalbavancin efficacy in difficult-to-treat infections, such as osteomyelitis, PJIs, and IE. We performed a comprehensive literature search through electronic databases (PubMed-MEDLINE) and search engines (Google Scholar). We included peer-reviewed publications (articles and reviews), and grey literature on dalbavancin use in osteomyelitis, PJIs, and IE. No time or language restrictions have been established. Despite the great interest in clinical practice, only observational studies and case series on the use of dalbavancin in infections other than ABSSSI are available. The reported success rate was extremely variable between studies, ranging from 44% to 100%. A low success rate has been reported for osteomyelitis and joint infections, while in endocarditis, the success rate was higher than 70% in all studies. However, there is no literature agreement about the correct regimen of dalbavancin for this type of infection heretofore. Dalbavancin showed great efficacy and a good safety profile, not only in patients with ABSSSI but also in those with osteomyelitis, PJIs, and endocarditis. Further randomized clinical trials are needed to assess the optimal dosing schedule depending on the site of infection. Implementing therapeutic drug monitoring for dalbavancin may represent the future step to achieving optimal pharmacokinetic/pharmacodynamic target attainment.

Effects of losartan, in monotherapy or in association with hydrochlorothiazide, in chronic nephropathy resulting from losartan treatment during lactation.

We recently standardized a model (L(Lact)) of severe chronic kidney disease based on impaired nephrogenesis by suppression of angiotensin II activity during lactation (Machado FG, Poppi EP, Fanelli C, Malheiros DM, Zatz R, Fujihara CK. Am J Physiol Renal Physiol 294: F1345-F1353, 2008). In this new study of the L(Lact) model, we sought to gain further insight into renal injury mechanisms associated with this model and to verify whether the renoprotection obtained with the association of the angiotensin II receptor blocker losartan (L) and hydrochlorothiazide (H), which arrested renal injury in the remnant kidney model, would provide similar renoprotection. Twenty Munich-Wistar dams, each nursing six pups, were divided into control, untreated, and L(Lact) groups, given losartan (L; 250 mg·kg(-1)·day(-1)) until weaning. The male L(Lact) offspring remained untreated until 7 mo of age, when renal functional and structural parameters were studied in 17 of them, used as pretreatment control (L(Lact)Pre), and followed no further. The remaining rats were then divided among groups L(Lact)+V, untreated; L(Lact)+L, given L (50 mg·kg(-1)·day(-1)) now as a therapy; L(Lact)+H, given H (6 mg·kg(-1)·day(-1)); and L(Lact)+LH, given L and H. All parameters were reassessed 3 mo later in these groups and in age-matched controls. At this time, L(Lact) rats exhibited hypertension, severe albuminuria, glomerular damage, marked interstitial expansion/inflammation, enhanced cell proliferation, myofibroblast infiltration, and creatinine retention. L monotherapy normalized albuminuria and prevented hypertension and the progression of renal injury, inflammation, and myofibroblast infiltration. In contrast to the remnant model, the LH combination promoted only slight additional renoprotection, perhaps because of a limited tendency to retain sodium in L(Lact) rats.

Aflatoxins are natural scavengers of reactive oxygen species.

The role of aflatoxins (AFs) in the biology of producing strains, Aspergillus sect. Flavi, is still a matter of debate. Over recent years, research has pointed to how environmental factors altering the redox balance in the fungal cell can switch on the synthesis of AF. Notably, it has been known for decades that oxidants promote AF synthesis. More recent evidence has indicated that AF synthesis is controlled at the transcriptional level: reactive species that accumulate in fungal cells in the stationary growth phase modulate the expression of aflR, the main regulator of AF synthesis-through the oxidative stress related transcription factor AP-1. Thus, AFs are largely synthesized and secreted when (i) the fungus has exploited most nutritional resources; (ii) the hyphal density is high; and (iii) reactive species are abundant in the environment. In this study, we show that AFs efficiently scavenge peroxides and extend the lifespan of E. coli grown under oxidative stress conditions. We hypothesize a novel role for AF as an antioxidant and suggest its biological purpose is to extend the lifespan of AFs-producing strains of Aspergillus sect. Flavi under highly oxidizing conditions such as when substrate resources are depleted, or within a host.

Does Angiotensin II receptor blockers increase the risk of SARS-CoV-2 infection? A real-life experience.

OBJECTIVE: Since the start of the COVID-19 pandemic, millions of people have been infected with thousands of deaths. Few data regarding factors that increase the risk of infection are available. Our study aimed to evaluate all people living in retirement homes (PLRNH) and identify factors that could increase infection risk in a close community. MATERIALS AND METHODS: We conducted a retrospective study enrolling all PLRNH, where at least one SARS-CoV-2 infected person was present. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on the infection. RESULTS: We included 452 PLRNH; 144 (31.7%) were male, with a mean age of 82.2±8.6 years. People with a positive swab for SARS-CoV-2 were 306 (67.4%). A significant difference between SARS-CoV-2 infected and not infected was observed in the percentage of those receiving chronic treatment with Angiotensin II receptor blockers (ARBs) (18.6% vs. 9.5%, p=0.012). On the contrary, there was no difference in the proportion of those receiving ACE inhibitors (ACE-I) (21.2% vs. 23.6%, p=0.562). At multivariate analysis, people with mental illness and cancer had an increased risk of being infected. Furthermore, receiving ARBs as a chronic treatment was an independent predictor of infection risk [OR 1.95 (95% CI 1.03-3.72) p=0.041]. CONCLUSIONS: Our data suggest that, in close communities, such as retirement nursing homes, the receipt of ARBs increased the risk of acquiring SARS-CoV-2 infection. However, before changing an important chronic treatment in a fragile population, such as the elderly living in retirement nursing homes, clinicians should carefully evaluate the risk-benefit ratio.

Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS.

AIMS: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. METHODS: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. RESULTS: HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00-pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05). CONCLUSIONS: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. CLINICAL TRIAL REGISTRATION: EudraCT 2015-001167-39.

On the incorrect use and interpretation of the model for colloidal, spherical crystal growth.

HYPOTHESIS: The standard model for diffusion and surface kinetics driven growth of a single spherical particle in solution is applied incorrectly throughout the literature. This leads to inaccurate values for parameter values, such as the diffusion and surface kinetics coefficients. The model cannot even distinguish between diffusion or surface kinetics driven growth. FINDINGS: It is shown that crystal growth occurs in two distinct stages. The standard model only holds during the late time. Fitting to experimental data, including the early time, leads to incorrect values for the coefficients. It is shown that diffusion and surface kinetics are interchangeable in the model and so indistinguishable. The growth is controlled by a single non-dimensional group. Previous studies, where more independent parameters are calculated have redundancy. The Gibbs-Thomson relation plays an important role but, in the cases studied here, this is only noticeable during the first growth stage where the model does not hold. For the first time an explicit relation for the variation of the radius with time is given. Excellent agreement with experimental data on CdSe growth is shown.

Clinical relevance of pharmacokinetic and pharmacodynamic profiles of insulin degludec (100, 200 U/mL) and insulin glargine (100, 300 U/mL) - a review of evidence and clinical interpretation.

AIM: Second-generation basal insulin analogues (e.g. insulin degludec, insulin glargine 300 U/mL), were designed to further extend the duration of insulin action and reduce within-day and day-to-day variability, and consequently hypoglycaemia risk, versus earlier long-acting basal insulins. This review examines the pharmacokinetic/pharmacodynamic characteristics of insulin degludec (100, 200 U/mL) and insulin glargine (100, 300 U/mL), and their influence on clinical outcomes. METHODS: Available pharmacokinetic/pharmacodynamic publications comparing insulin degludec and insulin glargine were reviewed. RESULTS: Both insulin degludec and insulin glargine 300 U/mL have more prolonged and stable pharmacokinetic/pharmacodynamic profiles than the earlier basal insulin analogue, insulin glargine 100 U/mL. Insulin glargine 300 U/mL (0.4 U/kg, morning) showed a more stable pharmacodynamic profile (20% lower within-day variability [P = 0.047]) and more even 24-h distribution (over each 6-h quartile) than insulin degludec 100 U/mL, whereas the supratherapeutic 0.6 U/kg dose demonstrated a similar, albeit non-significant, trend. In contrast, a second clamp study indicated lower day-to-day variability in the 24-h glucose-lowering effect (variance ratio 3.70, P < 0.0001), and more even dosing over each 6-h quartile, with insulin degludec 200 U/mL versus insulin glargine 300 U/mL (0.4 U/kg, evening). Methodological differences and differences in bioequivalence that may explain these discrepancies are discussed. CONCLUSIONS: Compared with earlier insulin analogues, second-generation basal insulins have improved pharmacokinetic/pharmacodynamic profiles that translate into clinical benefits, primarily reduced nocturnal-hypoglycaemia risk. Additional head-to-head comparisons of insulin degludec and insulin glargine 300 U/mL at bioequivalent doses, utilising continuous glucose monitoring and/or real-world evidence, are required to elucidate the differences in their pharmacological and clinical profiles.

Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes.

AIMS: This study measured the insulin concentration (Ins[C]) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). METHODS: Measurements included Ins[C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. RESULTS: In vials of NPH(R+) (assumed to be 100%), Ins[C] in the clear phase of NPH(R-) was<1%, but 230±41% and 234±54% in the cloudy phases of Novo Nordisk and Eli Lilly NPH, respectively. Likewise, in pen cartridges, Ins[C] in the clear phase of NPH(R-) was<1%, but 182±33%, 204±22% and 229±62% in the cloudy phases of Novo, Lilly and Sanofi NPH. Time needed to resuspend NPH (spent in tipping) in vials was brief with both Novo (5±1s) and Lilly NPH (6±1s), but longer with all pen cartridges (50±8s, 40±6s and 30±4s from Novo, Lilly and Sanofi, respectively; P=0.022). Time required for 50% separation into cloudy and clear parts of NPH was longer with Novo (60±7min) vs. Lilly (18±3min) in vials (P=0.021), and affected by temperature, but not by the different diameter sizes of the vials. With pen cartridges, separation into clear and cloudy parts was significantly faster than in vials (P<0.01). CONCLUSION: Ins[C] in NPH preparations varies depending on their resuspension or not. Thus, subcutaneous injection of the same number of units of NPH in patients with diabetes may deliver different amounts of insulin depending on its prior NPH resuspension.

Adrenergic mechanisms contribute to the late phase of hypoglycemic glucose counterregulation in humans by stimulating lipolysis.

Three studies were performed on nine normal volunteers to assess whether catecholamine-mediated lipolysis contributes to counterregulation to hypoglycemia. In these three studies, insulin was intravenously infused for 8 h (0.30 mU.kg-1.min-1 from 0 to 180 min, and 0.40 mU.kg-1.min-1 until 480 min). In study I (control study), only insulin was infused; in study II (direct + indirect effects of catecholamines), propranolol and phentolamine were superimposed to insulin and exogenous glucose was infused to reproduce the same plasma glucose (PG) concentration of study I. Study III (indirect effect of catecholamines) was the same as study II, except heparin (0.2 U.kg-1.min-1 after 80 min), 10% Intralipid (1 ml.min-1 after 160 min) and variable glucose to match PG of study II, were also infused. Glucose production (HGO), glucose utilization (Rd) [3-3H]glucose, and glucose oxidation and lipid oxidation (LO) (indirect calorimetry) were determined. In all three studies, PG decreased from approximately 4.8 to approximately 2.9 mmol/liter (P = NS between studies), and plasma glycerol and FFA decreased to a nadir at 120 min. Afterwards, in study I plasma glycerol and FFA increased by approximately 75% at 480 min, but in study II they remained approximately 40% lower than in study I, whereas in study III they rebounded as in study I (P = NS). In study II, LO was lower than in study I (1.69 +/- 0.13 vs. 3.53 +/- 0.19 mumol.kg-1.min-1, P less than 0.05); HGO was also lower between 60 and 480 min (7.48 +/- 0.57 vs. 11.6 +/- 0.35 mumol.kg-1.min-1, P less than 0.05), whereas Rd was greater between 210 and 480 min (19 +/- 0.38 vs. 11.4 +/- 0.34 mumol.kg-1.min-1, respectively, P less than 0.05). In study III, LO increased to the values of study I; between 4 and 8 h, HGO increased by approximately 2.5 mumol.kg-1.min-1, and Rd decreased by approximately 7 mumol.kg-1.min-1 vs. study II. We conclude that, in a late phase of hypoglycemia, the indirect effects of catecholamines (lipolysis mediated) account for at least approximately 50% of the adrenergic contribution to increased HGO, and approximately 85% of suppressed Rd.

Demonstration of a critical role for free fatty acids in mediating counterregulatory stimulation of gluconeogenesis and suppression of glucose utilization in humans.

In vitro studies indicate that FFA compete with glucose as an oxidative fuel in muscle and, in addition, stimulate gluconeogenesis in liver. During counterregulation of hypoglycemia, plasma FFA increase and this is associated with an increase in glucose production and a suppression of glucose utilization. To test the hypothesis that FFA mediate changes in glucose metabolism that occur during counterregulation, we examined the effects of acipimox, an inhibitor of lipolysis, on glucose production and utilization ([3-3H]glucose), and incorporation of [U-14C]-alanine into glucose during insulin-induced hypoglycemia. Eight normal volunteers were infused with insulin for 8 h to produce modest hypoglycemia (approximately 3 mM) on two occasions, first without acipimox (control) and then with acipimox administration (250 mg per os at 60 and 240 min). Despite identical plasma insulin concentrations, glucose had to be infused in the acipimox experiments (glucose-clamp technique) to maintain plasma glucose concentrations identical to those in control experiments. Acipimox completely prevented counterregulatory increases in lipolysis so that during the last 4 h plasma FFA were below baseline values and averaged 67 +/- 13 vs. 725 +/- 65 microM in control experiments, P < 0.001. Concomitantly, overall glucose production was reduced by 40% (5.5 +/- 11 vs. 9.3 +/- 0.7 mumol/kg per min, P < 0.001), and gluconeogenesis from alanine was reduced by nearly 70% (0.32 +/- 0.09 vs. 1.00 +/- 0.18 mumol/kg per min, P < 0.001), while glucose utilization increased by 15% (10.8 +/- 1.4 vs. 9.3 +/- 0.7 mumol/kg per min). We conclude that FFA play a critical role in mediating changes in glucose metabolism during counterregulation, and that under these conditions, FFA exert a much more profound effect on hepatic glucose production than on glucose utilization.

[Professional exposure to natural ultraviolet radiation: risk assessment and management and preventing strategies]. / Esposizione professionale a radiazione ultravioletta (UV) naturale: valutazione, controllo del rischio e strategie di prevenzione.

The aim of our study was to verify the impact of work risk factor in causing cutaneous neoplasia on a group of patients and to assess the risk of exposure to UV on outdoor workers. The survey was divided in three phases: a) Questionnaire, b) Dermatological clinical examination. c) Exposure measurement by spectral radiance method (mW/cm2). 248 subjects were enrolled, 100 of which affected by basal cellular carcinoma (BCC) (68% M and 32% F: mean age 70 +/- 11.93 y) 130 by melanoma (42% M and 58% F; mean age 53 +/- 17.35 y) and 18 by squamous cellular carcinoma (33% F and 67% M: mean age 78 +/- 11.41 y). In addiction 22 healthy male subjects exposed to UV were examined (mean age 38.59 +/- 13.65 y; specific working age 11.88 +/- 10.92 y). The assessment of UV exposure was performed over a 24 days timeframe during summer 2007, all over the working day. Furthermore, maximum allowed exposure time (t(max)) without protection was calculated according to ACGIH guidelines in order to prevent cutaneous alterations. It turned out that the UV exposure, both in working and spare time, is the root cause for squamous cellular cancer developing. Furthermore our results proved that also BCC is related to the overall UV exposure. No clear link to the UV exposure was found for cutaneous melanoma. No precancerous lesions were observed on shortly exposed subjects. The measurements performed revealed, as expected, lower exposure during first and last hours of the day without any particular constrain on t(max), and maximum exposure in the timeframe between 10:00 AM and 4:00 PM. Therefore, it is necessary to pay higher attention to the UV exposure and related consequences on employees health in order to provide with the most suitable preventing measures such the usage of protections depending from the requested exposure time.

[Risk assessment in upper limb overload]. / Studio del sovraccarico biomeccanico dell'arto superiore attraverso l'applicazione di quattro diversi metodi di valutazione del rischio.

One of the most important factors of the work-related musculoskeletal disorders of the upper extremities (WMSDs) is the biomechanical overload. The purpose of this study is to evaluate the possibility to predict the upper limb repetitive stress, according to risk assessment procedures. In order to this aim, we gathered clinical-anamnestic data and risk assessment considerations of a cohort of workers in a car industry.

[Occupational risk stress in shift workers]. / Valutazione del rischio da stress occupazionale in una popolazione di lavoratori a turni.

Aim of our study was to assess the stress risk at work in a group of nurses. 197 workers (nurses, auxiliary, physiotherapists, midwives and technicians of laboratory) were enrolled divided in two sets respectively of 100 people (subset A) with daily and nightly shifts and 97 (subset B) only daily workers. The mean age was 43.29 years (DS +/- 8.13) in subset A and 46.85 years (DS +/- 7.48) in subset B. For the survey S-90, a questionnaire composed by 90 items faces to frame some of the possible factors of risk has been used and the relative effects on health's state induced by the occupational stress were analyzed. The results show a possible greater risk of daily sleepiness in workers with nightly job. The majority of hypertension workers in subgroup B could depend more on the elevated mean age of this sample. Although a greater perception of the psychological load has been found, statistically meaningful association between the insurgence of gastrointestinal symptoms and shift was not showed.