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Magnetic switchbacks are localised polarity reversals in the radial component of the heliospheric magnetic field. Observations from Parker Solar Probe (PSP) have shown that they are a prevalent feature of the near-Sun solar wind. However, observations of switchbacks at 1 au and beyond are less frequent, suggesting that these structures evolve and potentially erode through yet-to-be identified mechanisms as they propagate away from the Sun. We analyse magnetic field and plasma data from the Magnetometer and Solar Wind Analyser instruments aboard Solar Orbiter between 10 August and 30 August 2021. During this period, the spacecraft was 0.6 to 0.7 au from the Sun. We identify three instances of reconnection occurring at the trailing edge of magnetic switchbacks, with properties consistent with existing models describing reconnection in the solar wind. Using hodographs and Walen analysis methods, we test for rotational discontinuities (RDs) in the magnetic field and reconnection-associated outflows at the boundaries of the identified switchback structures. Based on these observations, we propose a scenario through which reconnection can erode a switchback and we estimate the timescales over which this occurs. For our events, the erosion timescales are much shorter than the expansion timescale and thus, the complete erosion of all three observed switchbacks would occur well before they reach 1 au. Furthermore, we find that the spatial scale of these switchbacks would be considerably larger than is typically observed in the inner heliosphere if the onset of reconnection occurs close to the Sun. Hence, our results suggest that the onset of reconnection must occur during transport in the solar wind in our cases. These results suggest that reconnection can contribute to the erosion of switchbacks and may explain the relative rarity of switchback observations at 1 au., Comment: Accepted for publication in Astronomy & Astrophysics 05/05/2023

The Adriatic Sea is a basin oriented in the NW-SE direction, which represents the result of filling the Apennine and Dinaric-Hellenic chain foredeep. The present surface sediment distribution is controlled by basin evolution, different sediment source areas and processes. The aims of this work were to identify sedimentary facies based on grain-size, geochemical and biogeochemical features and to describe their spatial distribution, to recognize regional patterns of sediment dispersal, geochemical signals for provenance and eventual local features. Grain-size, geochemical (major and trace elements) and biogeochemical (organic carbon) analysis (Droghini, 2017) carried out on 107 samples, collected by box-corer during the PERTRE cruise (Spagnoli, 2016). These data were elaborated with a Q-mode factor analysis to identify the sedimentary facies (Spagnoli et al., 2014). In particular the statistical processing of sediment properties highlighted 5 factors, which allowed characterizing different facies and to evaluate their provenance and surface distribution. In particular were identified: 1) Clayey facies, made up of clayey and clayey-silty sediments, originated from the contribution of the Po River and the Apennine rivers, and that are redistributed by the Adriatic circulation in a SE direction; 2) sandy facies, made up of sandy-silty sediments with silicate minerals and enriched in Magnesium; this facies is more abundant along the Italian coasts; 3) coarse carbonatic facies, made up of sandy-gravel sediments; this facies is more abundant in the outer areas of the Adriatic Basin, coinciding with the depositional areas of the relict sands; 4) silty facies with heavy minerals, characterized by silty sediments enriched in heavy minerals resulting from the action of waves and coastal currents; 5) sediment provenance, useful to identify the origin of sediments. This component shows high values in different areas mainly located offshore of northern Gargano Promontory and is due to sediment features mainly controlled by geochemistry rather than grain-size. The characterization and distribution of the above described facies allowed understanding in more detail the present hydrodynamic, sedimentological, geochemical and biogeochemical processes occurring in the Central and Southern Adriatic Sea, and to identify the main sediment source areas.

Background: Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy. Methods: The European Community Respiratory Health Survey (ECRHS) collected information on prevalent asthma-like symptoms from representative samples of adults aged 20-44 years (29 centres in 13 European countries and Australia) at baseline and 10 and 20 years later (n=7844). Net changes in symptom prevalence were determined using generalised estimating equations (accounting for non-response through inverse probability weighting), followed by meta-analysis of centre level estimates. Findings: Over 20 years the prevalence of ‘wheeze’ and ‘wheeze in the absence of a cold’ decreased (-2.4% 95%CI -3.5 to -1.3%; -1.5% 95%CI -2.4 to -0.6%; respectively) but the prevalence of asthma attacks, use of asthma medication and hayfever/nasal allergies increased (0.6%, 95%CI 0.1 to 1.11; 3.6%, 95%CI 3.0 to 4.2; 2.7% 95%CI 1.7 to 3.7;). Changes were similar in the first ten years compared to the second ten years, except for hayfever/nasal allergies (increase seen in the first ten years only). Decreases in these wheeze-related symptoms were largely seen in the group who gave up smoking, and were seen in those who reported hayfever/nasal allergies at baseline. Interpretation: European adults born between 1946 and 1970 have, over the last 20 years, experienced less wheeze, although they were more likely to report asthma attacks, use of asthma medication and hayfever. Decrease in wheeze is largely attributable to smoking cessation, rather than improved treatment of asthma. It may also be influenced by reductions in atopy with ageing.

Background: Asthma and allergy might influence the choice of keeping pets, leading to apparent protective effects of pets on allergic disease. Objective: We investigated the effects of asthma and allergy on subsequent pet keeping in childhood and adulthood. Methods: Information about asthma and pet keeping at ages 0 to 4, 5 to 15, 20 to 44, and 26 to 56 years was provided by 9812 subjects participating in the 9-year follow-up of the European Community Respiratory Health Survey. Results: In childhood asthma debut at younger than 5 years was associated with less cat keeping at 5 to 15 years (odds ratio [OR], 0.60; 95% CI, 0.44-0.82), an effect only observed when the parents did not have asthma or allergy (P interaction = .045). Childhood asthma did not influence adult pet ownership, unless there were adult symptoms. Adults less often acquired cats at follow-up if they had 3 or more asthma symptoms (OR, 0.78; 95% CI, 0.64-0.95), were taking asthma medication (OR, 0.48; 95% CI, 0.31-0.74), had hay fever (OR, 0.75; 95% CI, 0.62-0.91), had atopy (OR, 0.75; 95% CI, 0.61-0.91), or had specific IgE to cat (OR, 0.57; 95% CI, 0.39-0.82) at baseline. Adults who already had pets usually continued keeping the same type of pet, except that the presence of 3 or more asthma symptoms was associated with less subsequent dog keeping (OR, 0.69; 95% CI, 0.53-0.89). Pet removal between surveys to reduce allergen was reported by 4.7%. Conclusion: Selective avoidance subsequent to asthma or allergy was observed for childhood cat keeping and adult cat acquisition. Avoidance would produce an apparent protective effect of cats on childhood asthma (large OR, 0.83). Avoidance was generally not observed for dogs or birds. Clinical implications: A part of the protective effects of childhood cats on asthma and allergy can be attributed to selective avoidance. © 2006 American Academy of Allergy, Asthma and Immunology.

Sex differences in asthma prevalence and morbidity, assessed with different methods in different populations, have raised several hypotheses about the different susceptibility to asthma in men and women. However, information on the incidence of asthma by age and sex is limited. The aim of this study was to estimate the age- and sex-specific incidence of asthma from birth to 44 yr of age in men and women across several countries, and to evaluate the main factors influencing asthma incidence in young adults. The data of the European Community Respiratory Health Survey, an international, cross-sectional, population-based survey, which were collected in 16 countries from 1991 to 1993 according to a common protocol, and which pertained to 18,659 subjects, were analyzed retrospectively, using the reported age of the first attack as the onset of asthma. During childhood, girls had a significantly lower risk of developing asthma than did boys (relative risk [RR]: 0.74 and 0.56 in the 0- to 5-yr and 5- to 10-yr age classes, respectively). Around puberty, the risk was almost equal in the two sexes (RR = 0.84; 95% confidence interval [CI]: 0.65 to 1.10 in the 10 to 15-yr age class). After puberty, the risk in women was always significantly higher than that in men (RR: 1.38 to 5.91). This pattern was consistent in all of the 16 countries studied, and was not influenced by recall or cohort effects. When the effects of airway caliber and smoking were studied with a case-control design, the results showed that women's greater susceptibility to asthma in early adulthood was at least partly, explained by their smaller airway caliber (the OR decreased from 2. 04 [95% CI: 1.32 to 3.15] to 1.47 [95% CI: 0.89 to 2.44] after controlling for height-adjusted FEV(1)); while smoking did not increase the risk. This analysis strongly confirms that the incidence of asthma shows a sex reversal during puberty, and suggests that airway caliber, in addition to hormonal factors, could play an important role in explaining the different patterns of asthma incidence in men and women.

In this paper we review and present methods and models, based on the maximum likelihood approach, for the study of the pattern of variability of a set of standardized mortality ratios. These methods can be useful in analysing and mapping standardized mortality risks for very rare causes of death., Statistica; Vol 50, No 4 (1990)

MODY2 is the most prevalent monogenic form of diabetes in Italy with an estimated prevalence of about 0.5-1.5%. MODY2 is potentially indistinguishable from other forms of diabetes, however, its identification impacts on patients' quality of life and healthcare resources. Unfortunately, DNA direct sequencing as diagnostic test is not readily accessible and expensive. In addition current guidelines, aiming to establish when the test should be performed, proved a poor detection rate. Aim of this study is to propose a reliable and easy-to-use tool to identify candidate patients for MODY2 genetic testing. We designed and validated a diagnostic flowchart in the attempt to improve the detection rate and to increase the number of properly requested tests. The flowchart, called 7-iF, consists of 7 binary "yes or no" questions and its unequivocal output is an indication for whether testing or not. We tested the 7-iF to estimate its clinical utility in comparison to the clinical suspicion alone. The 7-iF, in a prospective 2-year study (921 diabetic children) showed a precision of about the 76%. Using retrospective data, the 7-iF showed a precision in identifying MODY2 patients of about 80% compared to the 40% of the clinical suspicion. On the other hand, despite a relatively high number of missing MODY2 patients, the 7-iF would not suggest the test for 90% of the non-MODY2 patients, demonstrating that a wide application of this method might 1) help less experienced clinicians in suspecting MODY2 patients and 2) reducing the number of unnecessary tests. With the 7-iF, a clinician can feel confident of identifying a potential case of MODY2 and suggest the molecular test without fear of wasting time and money. A Qaly-type analysis estimated an increase in the patients' quality of life and savings for the health care system of about 9 million euros per year.

Up to now, few cost-of-illness (COI) studies have estimated the cost of adult asthma at an individual level on general population samples. We sought to evaluate the cost of current asthma from the societal perspective in young Italian adults and the determinants of cost variation.In 2000, a COI study was carried out in the frame of the Italian Study on Asthma in Young Adults on 527 current asthmatics (20-44 years) screened out of 15,591 subjects from the general population in seven centres. Detailed information about direct medical expenditures (DMEs) and indirect costs due to asthma was collected at an individual level over the past 12 months.The mean annual cost per patient was EUR 741 (95% CI: 599-884). DMEs represented 42.8% of the total cost, whereas the remaining 57.2% was indirect costs. The largest component of DMEs was medication costs (47.3%; 23.0% was due to hospitalization). The mean annual cost per patient ranged from EUR 379 (95% CI: 216-541)for well-controlled asthmatics to EUR 1,341 (95% CI: 978-1,706) for poorly controlled cases that accounted for 46.2% of the total cost. Poor control, coexisting chronic cough and phlegm, and low socio-economic status were significantly associated with high DMEs and indirect costs.In Italy, asthma-related costs were substantial even in unselected patients and were largely driven by indirect costs. Since about half of the total cost was due to a limited proportion of poorly controlled asthmatics, interventions aimed at these high-cost patients could reduce the economic burden of the disease.

Congesso della Società internazionale di elettrofisiologia della visione (ISCEV).

The most popular way to define asthma based on questionnaires is to use definitions taken from cross-sectional international studies on asthma. These definitions may not, however, be optimal for future studies focusing on risk factors of asthma. The current authors, therefore, compared the performance of different operational definitions of asthma. The European Community Respiratory Health Study I was a cross-sectional study of 21,924 subjects aged between 25-44 yrs in 18 countries. Operational definitions of asthma compared included different combinations of symptoms of asthma and bronchial hyperresponsiveness. A continuous asthma score, ranging from 0-8, was defined as the sum of positive answers to eight main symptom questions. There was no threshold in the associations of asthma symptoms with severity or risk factors of asthma, which would have suggested a dichotomous definition of asthma. Using dichotomous definitions requiring the presence of several asthma symptoms strengthened associations with studied risk factors, and also increased the estimated specificity and positive predictive value. Using a continuous asthma score also improved the power of the analyses. In conclusion, dichotomous definitions of asthma yielding higher odds ratios are achieved by requiring positive responses to several questions on symptoms. However, symptoms of asthma are possibly best analysed as a continuous asthma score.

Monografia della Società Italiana di Oftalmologia (S.O.I.)

Background: Variations in the prevalence of respiratory symptoms according to geo-climatic factors could provide important clues to the knowledge of the aetiology of asthma. Methods: Geo-climatic variations in the prevalence of current asthma, allergic rhinitis and chronic cough, and phlegm were assessed on a random sample of 18 873 subjects (response rate = 72.7%) from different climatic regions of Italy. An ecological analysis, supported by robust statistical methods, was employed to investigate potential trends. Results: The prevalence of all symptoms was significantly heterogeneous throughout the peninsula. Only asthma-like symptoms showed a north–south trend: the prevalence increased at a decreasing latitude [odds ratio (OR) varies from 0.92 to 0.96, P

The knowledge of the natural history of asthma from birth to adulthood could provide important clues for its cause and for the understanding of epidemiologic findings.This study is aimed at assessing the incidence and remission of asthma from birth to the age of 44 years by using data from 18,873 subjects involved in a large, nationally representative, cross-sectional study carried out in Italy from 1998 through 2000.The onset of asthma was defined as the age at the first attack, and remission was considered present when a subject was neither under treatment nor had experienced an asthma attack in the last 24 months. Person-years and survival techniques were used for the analysis.The average annual incidence rate for the 1953 to 2000 period was 2.56/1000 persons per year. Incidence peaked in boys less than 10 years of age (4.38/1000 persons per year) and in women 30 years of age or older (3.1/1000 persons per year) and showed a generational increase (incident rate ratio = 2.63 and 95% CI = 2.20-3.12 for 1974-1979 vs 1953-1958 birth cohort). The overall remission rate was 45.8% (41.6% in women and 49.5% in men, P.001). Asthmatic patients in remission had an earlier age at onset (7.8 vs 15.9 years, P.001) and a shorter duration of the disease (5.6 vs 16.1 years, P.001) than patients with current asthma. The probability of remission was strongly (P.001) and inversely related to the age at onset (62.8% and 15.0% in the10- andor =20-years age-at-onset groups, respectively).With respect to its natural history, asthma presents 2 different forms: early-onset asthma, which occurs early in childhood, affects mainly boys, and has a good prognosis, and late-onset asthma, which generally occurs during or after puberty, mainly affects women, and has a poor prognosis. The minority of patients with early-onset asthma who do not remit represents more than 35% of patients with current asthma in the general young adult population.

Primary productivity in the Ross Sea region is characterized by intense phytoplankton blooms whose temporal and spatial distribution are driven by changes in environmental conditions as well as interactions with the bacterioplankton community. However, the number of studies reporting the simultaneous diversity of the phytoplankton and bacterioplankton in Antarctic waters are limited. Here, we report data on the bacterial diversity in relation to phytoplankton community structure in the surface waters of the Ross Sea during the Austral summer 2017. Our results show partially overlapping bacterioplankton communities between the stations located in the Terra Nova Bay (TNB) coastal waters and the Ross Sea Open Waters (RSOWs), with a dominance of members belonging to the bacterial phyla Bacteroidetes and Proteobacteria. In the TNB coastal area, microbial communities were characterized by a higher abundance of sequences related to heterotrophic bacterial genera such as Polaribacter spp., together with higher phytoplankton biomass and higher relative abundance of diatoms. On the contrary, the phytoplankton biomass in the RSOW were lower, with relatively higher contribution of haptophytes and a higher abundance of sequences related to oligotrophic and mixothrophic bacterial groups like the Oligotrophic Marine Gammaproteobacteria (OMG) group and SAR11. We show that the rate of diversity change between the two locations is influenced by both abiotic (salinity and the nitrogen to phosphorus ratio) and biotic (phytoplankton community structure) factors. Our data provide new insight into the coexistence of the bacterioplankton and phytoplankton in Antarctic waters, suggesting that specific rather than random interaction contribute to the organic matter cycling in the Southern Ocean.

Peptidomimetics containing ( S)- or ( R)-imidazolidin-2-one-4-carboxylate (Imi) have been obtained by the expedient in-peptide cyclization of ( S)- or ( R)-α,β-diaminopropionic acid (Dap) residues. These Imi scaffolds behave as proline analogues characterized by a flat structure and a trans-restricted geometry of the preceding peptide bond and induce well-defined secondary structures in a biomimetic environment. While ( S)-Imi peptides adopted a γ'-turn conformation, ( R)-Imi induced the contemporary formation of a γ-turn and a rare 11-membered H-bonded structure in the 2→4 opposite direction of the sequence, identified as a e-turn. In order to exploit these Imi scaffolds as general promoters of unusual secondary structures, proteinaceous side chains have been introduced at the N1 position of the five-membered ring, potentially mimicking any residues. Finally, the Imi rings have been equipped with unnatural side chains or with functionalized substituents, which can be utilized as linkers to chemoselectively bind the Imi-peptides onto nanoparticles, biomaterials, or diagnostic probes.

Plastic debris in aquatic environments is colonized by microbes, yet factors influencing biofilm development and composition on plastics remain poorly understood. Here, we explored the microbial assemblages associated with different types of plastic debris collected from two coastal sites in the Mediterranean Sea. All plastic samples were heavily colonized by prokaryotes, with abundances up to 1.9×107 cells/cm2. Microbial assemblages on plastics significantly differed between the two geographic areas but not between polymer types, suggesting a major role of the environment as source for the plastisphere composition. Nevertheless, plastic communities differed from those in the surrounding seawater and sediments, indicating a further selection of microbial taxa on the plastic substrates. The presence of potential pathogens on the plastic surface reflected the levels of microbial pollution in the surrounding environment, regardless of the polymer type, and confirmed the role of plastics as carriers for potentially pathogenic microorganisms across the coastal ocean, deserving further investigations.

The rapid and exact identification and quantification of specific biomarkers is a key technology for always achieving more efficient diagnostic methodologies. We present the first application of a nanostructured device constituted of patterned self-assembled monolayers of disk-shaped zeolite L coated with the cyclic integrin ligand c[RGDfK] via isocyanate linker, to the rapid detection of cancer cells. With its high specificity toward HeLa and Glioma cells and fast adhesion ability, this biocompatible monolayer is a promising platform for implementation in diagnostics and personalized therapy formulation devices.

Chiral dehydroamino acid building blocks are versatile starting materials for the preparation of optically active unusual amino acids and other compounds of pharmacological interest. Herein we disclose the expedient preparation of dehydroalanines (ΔAla) equipped with oxazolidin-2-one (Oxd) chiral auxiliaries, Ts-Oxd-ΔAla-OMe. These compounds have been obtained in high yields from dipeptides Ts-Ser/Thr/phenylSer-Ser-OMe by the one-pot cyclization-elimination reaction with N,N-disuccinimidyl carbonate and catalytic DIPEA. To test the efficacy of the chiral auxiliaries in controlling asymmetric transformations, the Friedel-Crafts alkylations of indoles carrying diverse substituents were performed in the presence of Lewis and Brønsted acids. The reactions proceeded with good to excellent diastereomeric ratios giving (S)- or (R)-tryptophan derivatives, isolated very conveniently by simple flash chromatography. To verify the utility of this approach, optically pure (S)-2-methyltryptophan and (S)-5-fluorotryptophan were obtained and utilized to prepare analogues of endogenous opioid peptide endomorphin-1, H-Tyr-Pro-Trp-PheNH2.

The increasing need for large quantities of biologically active peptides for the market strongly raised the problem of the environmental sustainability of their synthesis. In this respect, we describe herein a solid phase procedure in water, using PEG peptide amide resins and NCAs under controlled conditions. This procedure afforded with reasonable yield and purity a short peptide amide, without the need of coupling reagents or protecting groups.

Incidence, predictors and effect of discontinuation of long-acting bronchodilators on the risk of death or hospital admission among adults with Chronic Obstructive Pulmonary Disease (COPD) were assessed in a large population-based prospective study carried out by linking Italian healthcare utilization databases. Specifically, the cohort of 17,490 beneficiaries of the National Health Service in the Italian Region of Lombardy, aged 40 years or older, who started long-acting bronchodilators therapy during 2005–2008 was followed from first dispensation until 2012. During this period, patients who experienced discontinuation of long-acting bronchodilators were identified. Hospitalizations for COPD and deaths for any cause (composite clinical outcome) were also identified during follow-up. A Cox proportional hazards model was fitted to identify predictors of discontinuation. The case-crossover design was used to assess the implications of treatment discontinuation on the clinical outcome risk. Cumulative incidences of discontinuation were, respectively, 67%, 80%, and 92% at 6 months, 1 year, and 5 years since initial treatment. Significant predictors of discontinuation were female gender, younger age, starting treatment with fixed-dose combination of inhaled bronchodilators and corticosteroids, using antibiotics, inhaled long-acting bronchodilators and corticosteroids and not using short-acting bronchodilators, other respiratory drugs and systemic corticosteroids during follow-up. Odds ratios (95% confidence intervals) for the clinical outcome associated with not discontinuing long-acting bronchodilators was 0.64 (0.50 to 0.82). In conclusion, in the real-life setting, discontinuation of inhaled long-acting bronchodilators in adults with COPD is high even after just 6 months, even though persistence to these drugs reduces the risk of severe outcomes.

Background and objective: Real-world evidence suggests that persistence with inhaled corticosteroids (ICS), the mainstay of asthma drug therapy, is generally poor. The effect of persistence with ICS on the risk of asthma exacerbation was addressed in a population-based study. Methods: The cohort of 2335 beneficiaries of the National Health Service provided by the Italian Region of Lombardy, aged 18–40 years and newly treated with ICS during 2005–2008, was followed from their first ICS dispensation until 2010. Discontinuation of treatment with ICS and starting oral corticosteroid therapy during follow-up were respectively regarded as proxies of poor persistence with asthma medication and asthma exacerbation (outcomes). A proportional hazards model was fitted to identify predictors of ICS discontinuation. Case-crossover and case-case-time-control designs and conditional logistic regressions were used to estimate the association between persistence with ICS and asthma exacerbation. Results: Cumulative incidences of discontinuation were 36%, 57% and 78% at 6 months, 1 year and 5 years, respectively. Predictors of poor persistence were female gender, use of antibiotics during follow-up, absence of use of short-acting beta-agonists prior to and after starting treatment with ICS and starting and maintaining ICS monotherapy during follow-up. The odds ratios of asthma exacerbation (and 95% confidence intervals) associated with ICS exposure during the current period, contrasted with exposure during the reference period, were 0.4 (0.2, 0.9) and 0.3 (0.1, 1.0) from case-crossover and case-case-time-control estimates, respectively. Conclusion: Persistence with ICS treatment in adults with asthma reduces the risk of exacerbation in the real-life setting.

Background: Socioeconomic inequalities in smoking habits have stabilized in many Western countries. This study aimed at evaluating whether socioeconomic disparities in smoking habits are still enlarging in Italy and at comparing the impact of education and occupation. Methods: In the frame of the GEIRD study (Gene Environment Interactions in Respiratory Diseases) 10,494 subjects, randomly selected from the general population aged 20–44 years in seven Italian centres, answered a screening questionnaire between 2007 and 2010 (response percentage = 57.2%). In four centres a repeated cross-sectional survey was performed: smoking prevalence recorded in GEIRD was compared with prevalence recorded between 1998 and 2000 in the Italian Study of Asthma in Young Adults (ISAYA). Results: Current smoking was twice as prevalent in people with a primary/secondary school certificate (40-43%) compared with people with an academic degree (20%), and among unemployed and workmen (39%) compared with managers and clerks (20-22%). In multivariable analysis smoking habits were more affected by education level than by occupation. From the first to the second survey the prevalence of ever smokers markedly decreased among housewives, managers, businessmen and free-lancers, while ever smoking became even more common among unemployed (time-occupation interaction: p = 0.047). At variance, the increasing trend in smoking cessation was not modified by occupation. Conclusion: Smoking prevalence has declined in Italy during the last decade among the higher socioeconomic classes, but not among the lower. This enlarging socioeconomic inequality mainly reflects a different trend in smoking initiation.

Contrast sensitivity measurements were obtained from 66 patients with Insulin Dependent Diabetes Mellitus (IDDM) and no visible diabetic retinopathy (Group A, n = 30 prepubescent and pubescent subjects; Group B, n = 36 postpubescent subjects). Contrast thresholds were determined for stationary and 6.87 Hz phase-alternating gratings at eight spatial frequencies from 0.18 to 15.7 c/deg. Data from each group of diabetic patients was compared with data from puberty-matched normal subjects. Mean value of the last four determinations of glycohemoglobin Alc (HbAlc) was used as a index of glycemic control. We found that patients with IDDM and no retinopathy had normal contrast sensitivity and that contrast thresholds were not significantly related to sexual maturity, duration of diabetes and glycemic control.

Small and easy-to-do mimetics of beta-turns are of great interest to interfere with protein-protein recognition events mediated by beta-turn recognition motifs. We propose a straightforward procedure for constraining the conformation of tetrapeptides lacking a pre-formed scaffold. According to the stereochemistry array, N-Ts tetrapeptides including Thr or PhSer (phenylserine) at the positions 2 or 3 gave rise in a single step to the sequences Oxd(2)-Oxd(3) or Delta Abu(2)-Oxd(3) (Oxd, oxazolidin-2-one; Delta Abu, 2,3-dehydro-2-aminobutyric). These pseudo-Pro residues displayed highly constrained phi, psi, and chi dihedral angles, and induced clear beta-turns or inverse turns of type I or II, as determined by extensive spectroscopic and computational analyses

AIM:To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.

none 6 We previously described a novel cyclic endomorphin-1 analog c[Tyr-D-Pro-D-Trp-Phe-Gly] (c[YpwFG]), acting as a mu-opioid receptor (MOR) agonist. This study reports that c[YpwFG] is more lipophilic and resistant to enzymatic hydrolysis than endomorphin-1 and produces preemptive antinociception in a mouse visceral pain model when injected intraperitoneally (i.p.) or subcutaneously (s.c.) before 0.6% acetic acid, employed to evoke abdominal writhing (i.p. ED50 = 1.24 mg/kg; s.c. ED50 = 2.13 mg/kg). This effect is reversed by the selective MOR antagonist β-funaltrexamine and by a high dose of the mu1-opioid receptor-selective antagonist naloxonazine. Conversely, the kappa-opioid receptor antagonist nor-binaltorphimine and the delta-opioid receptor antagonist naltrindole are ineffective. c[YpwFG] produces antinociception when injected i.p. after acetic acid (ED50 = 4.80 mg/kg), and only at a dose of 20 mg/kg did it elicit a moderate antinociceptive response in the mouse, evaluated by the tail flick assay. Administration of a lower dose of c[YpwFG] (10 mg/kg i.p.) apparently produces a considerable part of antinociception on acetic acid-induced writhes through peripheral opioid receptors as this action is fully prevented by i.p. naloxone methiodide, which does not readily cross the blood–brain barrier; whereas this opioid antagonist injected intracerebroventricularly (i.c.v.) is not effective. Antinociception produced by a higher dose of c[YpwFG] (20 mg/kg i.p.) is partially reversed by naloxone methiodide i.c.v. administered. Thus, only at the dose of 20 mg/kg c[YpwFG] can produce antinociception through both peripheral and central opioid receptors. In conclusion, c[YpwFG] displays sufficient metabolic stability to be effective after peripheral administration and demonstrates the therapeutic potential of endomorphin derivatives as novel analgesic agents to control visceral pain. none Bedini A; Baiula M; Gentilucci L; Tolomelli A; De Marco R; Spampinato S. Bedini A; Baiula M; Gentilucci L; Tolomelli A; De Marco R; Spampinato S.

BACKGROUND: To date, Snellen visual acuity and postoperative refraction have been used to evaluate the results of photorefractive keratectomy. However, other parameters, such as contrast sensitivity function and glare, may be affected by refractive surgery and lead to unsatisfactory visual performance. This prospective study is aimed at evaluating the effect of photorefractive keratectomy on contrast sensitivity function and glare. SUBJECTS AND METHODS: Static contrast sensitivity function, dynamic contrast sensitivity function, and glare sensitivity were evaluated in 22 myopic eyes before as well as 1, 3, and 6 months after photorefractive keratectomy. The eyes tested were divided into three groups, according to the amount of myopia: group I, from - 4.00 to - 8.00 diopters (D); group II, from -8.25 to -11.00 D; group ??, from -11.25 to -20.00 D. RESULTS: Both static and dynamic contrast sensitivity function at the intermediate spatial frequencies were altered at 1 month after photorefractive keratectomy, with a trend toward recovery at 3 and 6 months postoperatively. Glare sensitivity was not significantly affected by surgery. CONCLUSIONS: Contrast sensitivity function and glare testing may show abnormalities in the presence of optimal visual and refractive results. These tests may result especially important for the evaluation of new refractive surgical procedures. [J Refract Corneal Surg. 1994;10:129-136.]