Reggio Emilia (Northern Italy) Interdisciplinary Uveitis Clinic: What We Have Learned in the Last 20 Years.

PURPOSE: To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center. METHODS: Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center. RESULTS: Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients (p < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs. CONCLUSIONS: The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay.

COVID-19 post-traumatic stress disorder: the role of ACEs, alexithymia, and attachment in the Italian population.

OBJECTIVE: The COVID-19 pandemic is considered a collective traumatic event. Several studies have highlighted high levels of post-traumatic stress disorder (PTSD) symptoms among the general population during the pandemic. The general aim of this research is to explore the role of adverse childhood experiences (ACEs), alexithymia, and anxiety and avoidance attachment dimensions as risk factors that are making individuals more vulnerable to PTSD-COVID-related symptoms. SUBJECTS AND METHODS: The COVID-19-PTSD Questionnaire, 20-Item Toronto Alexithymia Scale (TAS-20), Adverse Childhood Experiences Questionnaire, and the Experiences in Close Relationships-Revised Form (ECR-R) were administered to 224 participants who were between 18 and 65 years of age, and residents of Italy. Socio-demographic variables were also collected. The data was collected between October 2021 and March 2022. RESULTS: The findings of the Spearman correlation analysis showed several significant associations between alexithymia, attachment dimensions, and PTSD symptoms related to COVID-19 diagnosis and age. A multivariable logistic regression model was performed using the COVID-19-PTSD total scores over/under the clinical cut-off as dependent variables and age, gender, anxiety and avoidance attachment scores, ACEs, and total alexithymia as independent variables, with alexithymia total score (B = .071; p = .001), ECR-R Anxiety (B = .034; p = .001) and ECR-R Avoidance (B = -.033; p = .024) showing to respectively increase and reduce the possibility of reporting clinical symptomatology. CONCLUSIONS: Emotional regulation and attachment have been shown to be risk factors for COVID-19 PTSD symptomatology. Focused intervention programs and emotional education can be useful tools for developing protective factors in the general population.

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro.

PURPOSE: Hypoparathyroidism is a rare endocrine disorder characterized by low or absent secretion of parathyroid hormone (PTH), which leads to decreased calcium and increased phosphorus levels in the serum. The diagnosis of hypoparathyroidism is based on the identification of the aforementioned biochemical abnormalities, which may be accompanied by clinical manifestations. Symptoms of hypoparathyroidism, primarily attributed to hypocalcemia, include muscle cramps or spasms, facial, leg, and foot pain, seizures, and tingling in the lips or fingers. The treatment of hypoparathyroidism depends on the severity of symptoms and the underlying pathology. Over the long term, calcium supplements, active vitamin D analogs, and thiazide diuretics may be needed. In fact, in patient cohorts in which optimal disease control still remains elusive, replacement therapy with recombinant parathyroid hormone analogs may be contemplated. Despite the predominantly neuromuscular symptoms of hypoparathyroidism, further effects of parathyroid hormone deficiency at the muscle cell level remain poorly understood. Thus, the aim of our study was to evaluate the effects of hypocalcemia in combination with hyperphosphatemia on muscle cells differentiation in vitro. METHODS: C2C12 cells, an in vitro model of muscle cells, were differentiated for 2 or 6 days in the presence of hypocalcemia (CaCl2 0.9 mmol/l) and moderate (PO4 1.4 mmol/l) or severe (PO4 2.9 mmol/l) hyperphosphatemia, or combinations of both conditions. Cell differentiation and expression of genes linked to muscle differentiation were evaluated. RESULTS: The combination of hypocalcemia with hyperphosphatemia induced a significant reduction (50%) in differentiation marker levels, such as MyoD (protein 1 for myoblast determination) and myogenin on the 1st day of differentiation, and MHC (myosin heavy chains) after 6 days of differentiation compared to control. Furthermore, this condition induced a statistically significant reduction of insulin-like growth factor-1 (IGF-1) mRNA expression and inhibition of IGF signaling and decrease in ERK phosphorylation compared to control cells. CONCLUSIONS: Our results showed that a condition of hypocalcemia with hyperphosphatemia induced an alteration of muscle cell differentiation in vitro. In particular, we observed the reduction of myogenic differentiation markers, IGF-1 signaling pathway, and ERK phosphorylation in differentiated skeletal myoblasts. These data suggest that this altered extracellular condition might contribute to the mechanisms causing persistence of symptoms in patients affected by hypoparathyroidism.

Non-paraxial design and fabrication of a compact OAM sorter in the telecom infrared.

A novel optical device is designed and fabricated in order to overcome the limits of the traditional sorter based on log-pol optical transformation for the demultiplexing of optical beams carrying orbital angular momentum (OAM). The proposed configuration simplifies the alignment procedure and significantly improves the compactness and miniaturization level of the optical architecture. Since the device requires to operate beyond the paraxial approximation, a rigorous formulation of transformation optics in the non-paraxial regime has been developed and applied. The sample has been fabricated as 256-level phase-only diffractive optics with high-resolution electron-beam lithography, and tested for the demultiplexing of OAM beams at the telecom wavelength of 1310 nm. The designed sorter can find promising applications in next-generation optical platforms for mode-division multiplexing based on OAM modes both for free-space and multi-mode fiber transmission.

Total angular momentum sorting in the telecom infrared with silicon Pancharatnam-Berry transformation optics.

Parallel sorting of orbital angular momentum (OAM) and polarization has recently acquired paramount importance and interest in a wide range of fields ranging from telecommunications to high-dimensional quantum cryptography. Due to their inherently polarization-sensitive optical response, optical elements acting on the geometric phase prove to be useful for processing structured light beams with orthogonal polarization states by means of a single optical platform. In this work, we present the design, fabrication and test of a Pancharatnam-Berry optical element in silicon implementing a log-pol optical transformation at 1310 nm for the realization of an OAM sorter based on the conformal mapping between angular and linear momentum states. The metasurface is realized in the form of continuously variant subwavelength gratings, providing high-resolution in the definition of the phase pattern. A hybrid device is fabricated assembling the metasurface for the geometric-phase control with multi-level diffractive optics for the polarization-independent manipulation of the dynamic phase. The optical characterization confirms the capability to sort orbital angular momentum and circular polarization at the same time.

Knowledge and Attitudes Toward Organ Donation in Health Care Undergraduate Students in Italy.

INTRODUCTION: The number of organ donors in Italy is increasing, but with still disappointing living donation activity and relatively frequent objection by potential deceased donors' relatives to organ recovery. Few studies have assessed health care students' knowledge and attitude on donation. METHODS: We administered a questionnaire to medical (MS) and nursing students (NS) at University of Modena and Reggio Emilia, Italy, and 749 students (406 MS and 343 NS) completed the questionnaire. RESULTS: Although 95% of students were in favor of donation, only 21.9% of NS and 24.9% of MS were registered as donors. One quarter of students reported family disagreement. MS appeared more confident with personnel involved in donation. Overall, 60% of students knew the term donation after brain death but only 40% were aware of the criteria used to define it. Barely 27.1% of NS and 15.3% of MS believed they had received sufficient information in lessons. Backward logistic regression demonstrated that students whose families agree with them and who knew the definition of donation after brain death were more likely to express the disposition of registering, and those who showed distrust in the declaration of brain death were half as likely to register as donors. DISCUSSION: Students expressed a lack of knowledge, controversial attitudes on donation, and strong need for education; increased awareness may help increase donation rates. The majority of educational institutions in Italy do not directly address training on organ donation and transplantation for health care students; an integrated curriculum favoring interpersonal discussion including practical aspects is urgently required.

Safety and efficacy of direct-acting antivirals for the treatment of chronic hepatitis C in a real-world population aged 65 years and older.

The availability of direct-acting antiviral agents (DAA) regimens has expanded the pool of patients eligible for treatment. However, data on the virologic response and tolerability of DAAs in elderly patients are lacking. We evaluated the efficacy and safety of DAAs in patients with advanced fibrosis/cirrhosis in real-life practice with the focus on those aged ≥65 years. Between January and December 2015, all consecutive patients with HCV-related advanced fibrosis/cirrhosis treated with DAA at eleven tertiary referral centres in Emilia Romagna (Italy) were enrolled. Regimen choice was based on viral genotype and stage of disease, according to guidelines. The primary end point was sustained virologic response 12 weeks after the end of treatment (SVR12). Overall, 282 of 556 (50.7%) patients evaluated were elderly, most of them with cirrhosis. Antiviral therapy was stopped prematurely in four (1.4%) patients. Two patients, both with cirrhosis, died during treatment due to worsening of liver/renal function. SVR12 was achieved by 94.7% and was comparable to that obtained in patients aged <65 (P=.074). Similar data were also reported in subgroup of patients aged ≥75 years. All patients with advanced fibrosis achieved virologic response. SVR12 was 80.8% in Child-Pugh-Turcotte (CTP)-B cirrhosis and 95.4% in CTP-A (P=.013). According to genotype, the SVR12 was achieved in 172 of 181 (95%) with genotype 1b cirrhosis and in 44 of 48 (91.7%) with genotype 2 cirrhosis. In conclusions, in a real-world setting, DAAs are safe and effective in elderly patients with HCV-related advanced fibrosis/cirrhosis, but SVR12 is lower with worsening CTP class.

Generation of high-order Laguerre-Gaussian modes by means of spiral phase plates.

Spiral phase plates for the generation of Laguerre-Gaussian (LG) beam with non-null radial index were designed and fabricated by electron beam lithography on polymethylmethacrylate over glass substrates. The optical response of these phase optical elements was theoretically considered and experimentally measured, and the purity of the experimental beams was investigated in terms of LG modes contributions. The far-field intensity pattern was compared with theoretical models and numerical simulations, whereas interferometric analyses confirmed the expected phase features of the generated beams. The high quality of the output beams confirms the applicability of these phase plates for the generation of high-order LG beams.

Extraordinary optical transmission in one-dimensional gold gratings: near- and far-field analysis.

One-dimensional arrays of nanoslits fabricated on silicon nitride membranes show extraordinary optical transmission. Optical characterization techniques have been used to characterize the transmission spectra and the near-field optical configuration. Experimental results have been compared with numerical simulations in order to elucidate the different modes of light propagation. Near- and far-field optical distribution is studied as a function of the polarization of light.

Polarization independence of extraordinary transmission trough 1D metallic gratings.

Extraordinary optical transmission of 1D metallic gratings is studied. Experimental samples are fabricated by means of Electron Beam Lithography. The optical characterization is focused on far field transmission properties and in particular on polarization dependence of the incident light. A peculiar symmetry in transmission spectra at different polarization angles is shown; this symmetry is studied both experimentally, and numerically with FEM method. A comparison between numerical and experimental data is provided.

Altered oxidative stress profile in the cortex of mice fed an enriched branched-chain amino acids diet: possible link with amyotrophic lateral sclerosis?

Branched-chain amino acids (BCAAs), valine, isoleucine, and leucine, are widely used among athletes as dietary integrators. Although the occurrence of untoward effects of BCCA supplementation, with particular regard to neurological disturbances, cannot be excluded, no specific studies have been performed so far. The aim of this work was to evaluate the effects of a diet enriched in BCAAs on the expression of oxidative stress pathway genes in the brain of C57Bl/6J mice. Animals were fed a standard or a BCAA diet for 95 days starting from postnatal day 21 until sacrifice. BCAA treatment, at doses comparable to human usage, significantly down-regulated the expression of some antioxidant genes, while up-regulating the expression of some oxygen transporters. In conclusion, it appears that BCAAs administered by diet could alter some specific oxidative stress pathways in the brain. Caution should thus be exercised in the widespread use of BCAAs as dietary integrators in sports practice.

Early kinetics of innate and adaptive immune responses during hepatitis B virus infection.

BACKGROUND AND AIMS: Innate immunity appears to be silent in acutely hepatitis B virus (HBV)-infected chimpanzees, as shown by microarray analysis of intrahepatic gene expression. Whether this observation also applies to HBV pathogenesis in man remains undefined. The aim of this study was thus to characterise natural killer (NK) and CD56(+) natural T (NT) cell responses early after human HBV infection and their relationship to the induction of adaptive immunity. METHODS: Two HBV-seronegative blood donors who became hepatitis B surface antigen (HBsAg) and HBV DNA positive but had persistently normal alanine aminotransferase (ALT) were followed from a very early stage of HBV infection. The phenotype (CD69 and NKG2D) and function (cytotoxicity and interferon gamma (IFN gamma) production) of NK and NT cells were analysed. CD4- and CD8-mediated responses were studied in parallel with overlapping peptides covering the entire HBV sequence by ex vivo intracellular cytokine staining (ICS) for IFN gamma, interleukin 2 (IL2), IL4 and IL10, and by ex vivo Elispot for IFN gamma. Healthy subjects, and patients with chronic and acute HBV infection were studied for comparison. RESULTS: An early induction of both innate and adaptive responses was observed. NK and NT cells showed faster kinetics than HBV-specific T cells with an earlier peak of activity, while CD4(+) and CD8(+) cell responses were mounted with a similar profile, with higher frequencies of IFN gamma-producing CD8(+) cells at the peak of the response. CONCLUSIONS: The innate immune system is able to sense HBV infection, as shown by the early development of NK and NT cell responses, which probably contribute to contain the HBV infection and to allow timely induction of adaptive responses.

Plasma glucose levels as predictors of diabetes: the Mexico City diabetes study.

AIMS/HYPOTHESIS: The value of diagnostic categories of glucose intolerance for predicting type 2 diabetes is much debated. We therefore sought to estimate relative and population-attributable risk of different definitions based on fasting (impaired fasting glucose [IFG]) or 2 h plasma glucose concentrations (impaired glucose tolerance [IGT]) and to describe the associated clinical phenotypes. METHODS: We prospectively observed a population-based cohort of 1,963 non-diabetic participants (mean age 47 years), in whom an OGTT was performed at baseline and 7 years later. RESULTS: IGT was fivefold more prevalent (13.5%) than IFG. In both categories, participants were older, heavier, hyperinsulinaemic, hyperproinsulinaemic and dyslipidaemic compared with participants with normal glucose tolerance. Relative risk of incident diabetes was similar for IFG and IGT categories (3.73 [95% CI: 2.18-6.39] and 4.01 [95% CI: 3.12-5.14], respectively), but the population-attributable risk was fivefold higher for IGT (29% [95% CI: 26-32]) than for IFG (6% [95% CI: 5-7]). Isolated IFG carried no increase in risk. Lowering the threshold to 5.6 mmol/l raised the population-attributable risk of IFG to 23% (95% CI: 20-25); its contribution to diabetes progression, however, was largely due to co-existent IGT. In multivariate analysis adjusting for sex, age, familial diabetes and BMI, fasting and 2 h glucose were independent predictors. CONCLUSIONS/INTERPRETATION: Fasting and 2 h glucose values are independent predictors of incident diabetes. Isolated IFG is not a high-risk condition; lowering the diagnostic threshold increases the population-attributable risk of IFG fourfold, but performing an OGTT captures additional diabetes progressors compared with the number identified by IFG.

Parvovirus B19 infection in five European countries: seroepidemiology, force of infection and maternal risk of infection.

We conducted a seroprevalence survey in Belgium, Finland, England & Wales, Italy and Poland on 13 449 serum samples broadly representative in terms of geography and age. Samples were tested for the presence of immunoglobulin G antibody using an enzyme immunoassay. The age-specific risk of infection was estimated using parametric and non-parametric statistical modelling. The age-specific risk in all five countries was highest in children aged 7-9 years and lower in adults. The average proportion of women of child-bearing age susceptible to parvovirus B19 infection and the risk of a pregnant women acquiring B19 infection during pregnancy was estimated to be 26% and 0.61% in Belgium, 38% and 0.69% in England & Wales, 43.5% and 1.24% in Finland, 39.9% and 0.92% in Italy and 36.8% and 1.58% in Poland, respectively. Our study indicates substantial epidemiological differences in Europe regarding parvovirus B19 infection.

Epidemiological and virological characterization of a large community-wide outbreak of hepatitis A in southern Italy.

A large outbreak of hepatitis A virus (HAV) infection occurred in 2004 in Campania, a region of southern Italy, with 882 cases reported between 1 January and 1 August. The local public health authorities and the Italian National Institute of Health carried out investigations in order to characterize the agent, identify the source of infection and the route of transmission, and implement appropriate control measures. A web-based reporting system enhanced the flow of information between public health authorities, providing real-time epidemic curves and frequency distributions. The same 1B HAV genotype was found in 90% of sera from a subset of patients with acute disease, suggesting a local common source. A case-control study in the municipality with the highest attack rate showed that raw seafood consumption, in particular if illegally sold in water, was strongly associated with HAV illness. Samples of seafood systematically collected from retailers were found contaminated by HAV.

An Easter outbreak of Salmonella Typhimurium DT 104A associated with traditional pork salami in Italy.

Salmonella enterica is a common cause of gastrointestinal illness in Italy. S. Typhimurium accounts for approximately 40% of isolates, and most of these strains belong to the phage type DT104. We describe the investigation of an outbreak of S. Typhimurium DT104A, a subtype never observed before in Italy, which occurred in Rome during spring 2004.We conducted a matched case control study between 24 July and 9 September 2004. Controls were matched for age and area of residence. Each case had between one and four controls. Odds of exposure to potential risk factors and vehicles for the outbreak were compared between cases and controls. A multivariate analysis was conducted to estimate adjusted Odds Ratios.Sixty-three cases of S. Typhimurium DT 104A infection with onset between 1 April and 5 May 2004 were identified. Sixty-one were residents of Rome and two were residents of a neighbouring region. Twenty-six cases (43%) were enrolled in the study. Their median age was 7.5 years. Fourteen of 26 cases and 16 of 62 controls had eaten pork salami (OR= 25.5; 95% CI 1.6- 416.8). No food samples were available for testing. In northern Italy, two months prior to the outbreak, the veterinary surveillance system identified the first isolation of S. Typhimurium DT104A in a pig isolate. Both human and pig isolates showed indistinguishable PFGE patterns. It was not possible to trace the pig after the sample was taken at slaughter. The epidemiological evidence on the implication of pork salami in this outbreak suggests that pork products can also be a vehicle for salmonella in Italy and underlines the importance of good manufacturing practices for ready-to-eat foods. This investigation highlights the value of laboratory-based surveillance in identifying community-wide outbreaks of uncommon pathogens. It also underlines the need to improve surveillance timeliness, for promptly detecting outbreaks, undergoing field investigation, and implementing control measures. Moreover, our study shows the usefulness of integrated human and animal surveillance in tracing the possible source of infection.

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy.

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C--both symptomatic and asymptomatic--have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment.

Soluble CD30 and lymphocyte activation gene-3 (CD223), as potential serological markers of T helper-type cytokine response induced by acellular pertussis vaccine.

T cell responses are involved in vaccine-induced immunity to pertussis but no easy-to-monitor, serological markers are available to assess these responses. The lymphocyte activation gene-3 (CD223) molecule is present on, and released by, activated T helper (Th) 1 cells, whereas CD30 molecules have been associated with Th2 immune responses. Starting from the recent knowledge of the cytokine profile induced by pertussis vaccination, we examined the levels of soluble (s)CD223 and sCD30 proteins in child recipients of acellular pertussis (aP) and diphtheria-tetanus (DT) vaccines and in children receiving DT vaccine only, as control. The correlation of the two proteins with specific antibody and T cell responses was assessed. The main findings are: i) sCD223 and sCD30 levels are inversely related, suggesting that the two markers are the expression of different and counter-regulated T-cell responses; ii) sCD30 level correlated with induction of T cell proliferation to pertussis vaccine antigens and antibody response to pertussis toxin. Overall, sCD30 and sCD223 levels seem to be promising candidate markers to assess the induction of Th-type responses in vaccine recipients.

Short-term adverse effects from and discontinuation of antiretroviral post-exposure prophylaxis.

OBJECTIVE: To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy. DESIGN: Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP. SETTING: All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs. STUDY POPULATION: Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV. RESULTS: Until October, 2000, 207 individuals receiving two nucleoside reverse transcriptase inhibitors (NRTIs), and 354 receiving two NRTIs plus a protease inhibitor (PI) were enrolled. More individuals experienced side-effects in the 3-drug group (53% and 62%, respectively; OR 0.68, (95% CI 0.48-0.98), p < 0.03). However, the proportion of individuals discontinuing prophylaxis because of side-effects did not differ significantly between the 2 groups (21% and 25% respectively; OR 0.82 (95% CI 0.53-1.26); p=0.4). The 43 individuals in the 2 NRTI group discontinued PEP after a mean of 10.4 days of treatment (median 8, range 1-27), similarly to the 88 discontinuations observed in the 3-drug group (mean duration 10.5 days, median 7.5, range 1-26). Type and incidence of specific adverse effects were similar to those reported in the literature. CONCLUSION: Our study indicates that the difference in the proportion of individuals developing side effects and discontinuing PEP is not significant. The rate of discontinuation because of protease inhibitor side-effects does not justify per se the initial use of a less potent PEP regimen. We suggest initiating PEP with a three-drug regimen and discontinuing the protease inhibitor in the case of adverse effects.