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.

Inter-rater reliability of classification systems of scapular dyskinesis.

Prevalence of scapular dyskinesis varies across records, with overhead athletes being more frequently affected than non-overhead athletes A number of methods have been described to evaluate scapular kinematics and scapular dyskinesis. The "yes/no" and the "4-type" classification systems are widely accepted and diffusely used among orthopaedics and physical therapists. The inter-rater reliability for both the "yes/no" and the "4-type" classification systems may be different. Moreover, differences between physical therapists and orthopaedic surgeons may exist. Seven examiners (2 orthopaedic surgeons and 5 physical therapists) were asked to evaluate a mixed sequence of video recordings of healthy subjects and patients affected by shoulder, scapular or clavicular disorders and to assess scapular dyskinesis using the "yes/no" and the "4-type" classification systems. Cohen's kappa coefficient (κ) and weighted kappa were used to measure inter-rater reliability. Twenty-four subjects were enrolled. In general, the "4- type" system has higher κ values than ''yes/no'' classification system and orthopaedic surgeons achieve higher reliability than physical therapists for both systems. The clinical evaluation of active shoulder movements permits reproducible assessment and classification of scapular dyskinesis, in particular for the "4-type" classification system. The "4-type" classification system can be used to assess and classify scapular dyskinesis, especially among orthopaedic surgeons.

Transthoracic cholecystectomy following biliary pancreatitis arising from a thoracic herniated gallbladder.

Asymptomatic right diaphragmatic rupture with liver and gallbladder herniation and secondary Budd-Chiari syndrome is a rare complication of abdominal trauma. In this setting, the management of gallbladder stones remains poorly described and may require a thoracic approach.

Thermal decomposition of FC(O)OCH3 and FC(O)OCH2CH3.

The thermal decomposition of methyl and ethyl formates has been extensively studied due to their importance in the oxidation of several fuels, pesticidal properties and their presence in interstellar space. We hitherto present the study of the thermal decomposition of methyl and ethyl fluoroformates, which could help in the elucidation of the reaction mechanisms. The reaction mechanisms were studied using FTIR spectroscopy in the temperature range of 453-733 K in the presence of different pressures of N2 as bath gas. For FC(O)OCH3 two different channels were observed; the unimolecular decomposition which is favored at higher temperatures and has a rate constant kFC(O)OCH3 = (5.3 ± 0.5) × 1015 exp[-(246 ± 10 kJ mol-1/RT)] (in units of s-1) and a bimolecular channel with a rate constant kFC(O)OCH3 = (1.6 ± 0.5) × 1011 exp[-(148 ± 10 kJ mol-1/RT)] (in units of s-1 (mol L)-1). However for ethyl formate, only direct elimination of CO2, HF and ethylene operates. The rate constants of the homogeneous first-order process fit the Arrhenius equation kFC(O)OCH2CH3 = (2.06 ± 0.09) × 1013 exp[-(169 ± 6 kJ mol-1/RT)] (in units of s-1). The difference between the mechanisms of the two fluoroformates relies on the stabilization of a six-centered transition state that only exists for ethyl formate. First principles calculations for the different channels were carried out to understand the dynamics of the decomposition.

The impact of drugs on male fertility: a review.

Beside cytotoxic drugs, other drugs can impact men's fertility through various mechanisms. Via the modification of the hypothalamic-pituitary-gonadal axis hormones or by non-hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed.

Conformational Change in the Mechanism of Inclusion of Ketoprofen in ß-Cyclodextrin: NMR Spectroscopy, Ab Initio Calculations, Molecular Dynamics Simulations, and Photoreactivity.

Inclusion of drugs in cyclodextrins (CDs) is a recognized tool for modifying several properties such as solubility, stability, bioavailability, and so on. The photoreactive behavior of the ß-CD/ketoprofen (KP) complex upon UV exposure showed a significant increase in photodecarboxylation, whereas the secondary degradation products by hydroxylation of the benzophenone moiety were inhibited. The results may account for an improvement of KP photophysical properties upon inclusion, thus better fostering its topical use. To correlate the structural details of the inclusion with these results, an NMR spectroscopic study of KP upon inclusion in ß-CD was performed. Effects of the magnetically anisotropic centers of KP, changing their orientations upon inclusion and giving chemical shift variations, were specifically correlated with the results of the molecular dynamic simulations and ab initio calculations. In the large variety of papers focusing on the structural analysis of ß-CD complexes, this work represents one of the few examples in which a detailed analysis of these simultaneous upfield-downfield NMR shifts of the same aromatic molecule upon inclusion is reported. Interestingly, the results demonstrate that the observed upfield and downfield shifts upon inclusion are not related to any direct magnetic role of ß-CD. The conformational change of KP upon the inclusion process consists of a slight reduction in the angle between the two phenyl rings and in a remarkable reduction in the mobility of the carboxyl group, the latter being one of the main contributions to the NMR resonance shifts. These structural details help in understanding the features of the inclusion complex and, eventually, the driving force for its formation.

Mechanism of Action of Thymosinα1: Does It Interact with Membrane by Recognition of Exposed Phosphatidylserine on Cell Surface? A Structural Approach.

Thymosinα1 is a peptidic hormone with pleiotropic activity, which is used in the therapy of several diseases. It is unstructured in water solution and interacts with negative regions of micelles and vesicles assuming two tracts of helical conformation with a structural flexible break in between. The studies of the interaction of Thymosinα1 with micelles of mixed dipalmitoylphosphatidylcholine and sodium dodecylsulfate and vesicles with mixed dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylserine, the latter the negative component of the membranes, by (1)H and natural abundance (15)N NMR are herewith reported, reviewed, and discussed. The results indicate that the preferred interactions are those where the surface is negatively charged due to sodium dodecylsulfate or due to the presence of dipalmitoylphosphatidylserine exposed on the surface. In fact the unbalance of dipalmitoylphosphatidylserine on the cellular surface is an important phenomenon present in pathological conditions of cells. Moreover, the direct interaction of Thymosinα1 with K562 cells presenting an overexposure of phosphatidylserine as a consequence of resveratrol-induced apoptosis was carried out.

Intra-Operative Contrast Cholangiography in Living Donor Liver Transplantation: The ISMETT Experience.

BACKGROUND: We evaluated the clinical impact of donor biliary anatomy discrepancies (DBAD) achieved by comparing pre-operative evaluation obtained with magnetic resonance (MR)/magnetic resonance cholangiopancreatography (MRCP) imaging, with intra-operative cholangiography (IOC) on the living related liver donor (LDLT) and recipient. METHODS: This single-center, retrospective study included 97 consecutive adult-to-adult (A2A) LDLT performed in our hospital in the last 12 years. Donor sex and age, living donors with biliary and/or vascular anomalies, recipient age, sex, primary etiology, re-transplantation, Model of End-Stage Liver Disease score, co-morbidities, arterial and biliary recipient complications assessed on the basis of clinical follow-up were collected and analyzed for significance through the use of a multivariate linear regression model. RESULTS: Biliary complications in the donor (DBC) were detected in 8 (8.2%) cases. Biliary complications in the recipients (RBC) were detected in 38 (39%) cases. DBADs were found in 32 (33%) cases and resulted strictly related to RBC (P = .05). CONCLUSIONS: After adjusting for co-variables, results of the linear regression analysis confirmed that DBAD is an independent predictor of RBC, but it is not significantly associated with vascular complications or patient survival. We showed that RBCs after LDLT were influenced by DBAD.

Human induced pluripotent stem cell-derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block.

BACKGROUND AND PURPOSE: Two new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and in silico human adult ventricular cardiomyocyte (hAdultV-CM) models. Their combination was recently proposed as a potential replacement for the present hERG-based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC-CM and hAdultV-CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies. EXPERIMENTAL APPROACH: In silico AP models of ventricular-like and atrial-like hiPSC-CMs and hAdultV-CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents. KEY RESULTS: Qualitatively, hiPSC-CM and hAdultV-CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC-CMs were more sensitive to block of (i) L-type Ca(2+) currents due to the overexpression of the Na(+) /Ca(2+) exchanger (leading to shorter APs) and (ii) the inward rectifier K(+) current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure). CONCLUSIONS AND IMPLICATIONS: In silico hiPSC-CMs and hAdultV-CMs exhibit a similar response to selective current blocks. However, overall hiPSC-CMs show greater sensitivity to block, which may facilitate in vitro identification of drug-induced effects. Extrapolation of drug effects from hiPSC-CM to hAdultV-CM and pro-arrhythmic risk assessment can be facilitated by in silico predictions using biophysically-based computational models.

An experimental and theoretical study of the photoisomerization and thermal reversion on 5-arylmethylene-2-thioxoimidazolidin-4-one.

Unraveling the photochemical behaviour of the green fluorescent protein chromophore has lately attracted widespread attention among scientists. In this paper we present the study of the photochemical isomerization Z → E and the back reaction of the chromophore analog, 5-arylmethylene-2- thioxoimidazolidin-4-one. Experimental results are supported with ab initio calculations at the DFT, (B3LYP/6-31+g(d,p)), TD-DFT (B3LYP/6-311++g(3df,3pd)) and CASSCF levels. A first excitation to the S2 state, where the isomerization occurs, is proposed followed by two conical intersections to S1 and S0 respectively. Three different mechanisms were analyzed for thermal reversion, concluding that the preferred channel involves an intersystem crossing between the S0 and T1 states with the formation of a biradical.

[Elective single embryo transfer policy at 48/72 h: which results after fresh transfers and frozen/thawed transfers?]. / Politique de transfert électif d'un embryon à 48/72h: quels résultats après transferts frais et transferts d'embryons congelés ?

OBJECTIVES: To evaluate our elective single embryo transfer policy performed at 48/72h and define predictive factors of pregnancy after frozen/thawed embryo transfer. METHODS: Analysis of 289 elective single embryo transfers (eSET) performed in a selected population in the ART center of Marseille University Hospital from January 2005 to December 2011, as well as the 325 following frozen/thawed embryo transfers performed in this population between May 2005 and December 2012. RESULTS: Cumulative pregnancy rate/oocyte retrieval was of 62.6%; 45% of the couples obtained the birth of at least one child. During this studied period, cumulative pregnancy and delivery rates in the whole population remained stable while multiple delivery rate/delivery clearly decreased. Elective single embryo after frozen/thawed transfer gave satisfying results (24.6% pregnancy/transfer) only in the lack of lysis or in case of mild lysis (1-25%) of the transferred embryo. CONCLUSION: The implementation of an eSET policy gives satisfying results, depending largely on embryo quality. By proposing eSET to a well-targeted population, chosen both on clinical and biological criteria, a clear reduction of cumulative multiple delivery rate/delivery was obtained in our center over this period, without any global decrease of cumulative pregnancy rate/attempt. Embryo quality is a major factor of success, especially in frozen/thawed cycles. The elective single embryo frozen/thawed transfer should be carried out only if embryo lysis after thawing does not exceed 25%.

Determination of the presence of hyaluronic acid in preparations containing amino acids: the molecular weight characterization.

Several pharmaceutical preparations contain hyaluronic acid in the presence of a large variety of low molecular weight charged molecules like amino acids. In these mixtures, it is particularly difficult to determine the concentration and the molecular weight of the hyaluronic acid fragments. In fact zwitterionic compounds in high concentration behave by masking the hyaluronic acid due to the electrostatic interactions between amino acids and hyaluronic acid. In such conditions the common colorimetric test of the hyaluronic acid determination appears ineffective and in the (1)H NMR spectra the peaks of the polymer disappear completely. By a simple separation procedure the presence of hyaluronic acid was revealed by the DMAB test and (1)H NMR while its average molecular weight in the final product was determined by DOSY NMR spectroscopy alone. The latter determination is very important due to the healthy effects of some sizes of this polymer's fragments.

Diagnostic pitfalls in the preoperative 18F-FDG PET/CT evaluation of a case of giant malignant solitary fibrous tumor of the pleura.

Solitary fibrous tumor of the pleura (SFTP) is an uncommon entity, generally with an indolent behavior. Nevertheless, some malignant forms have been rarely reported. These, often have an aggressive biological behavior with pathological findings of invasiveness. The preoperative diagnosis and evaluation of the grade of malignancy are extremely challenging. Herein we report a case of a 64-year-old man who presented with a left giant intra-thoracic mass imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG/PET-CT) and sampled via fine-needle aspiration biopsy (FNAB). Imaging and FNAB findings showed suspicion of a benign form of SFTP. Surgical radical resection of the giant mass was performed. The definitive histological diagnosis showed a malignant SFTP. Based on this report, we take the opportunity to briefly discuss the insidious pitfalls concerning the radiological and (18)F-FDG/PET-CT features as well as cyto/histological findings in the pre-operative diagnostic work-up examination of this rare entity.

Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology.

This study aimed at challenging pulmonary large cell carcinoma (LLC) as tumor entity and defining different subgroups according to immunohistochemical and molecular features. Expression of markers specific for glandular (TTF-1, napsin A, cytokeratin 7), squamous cell (p40, p63, cytokeratins 5/6, desmocollin-3), and neuroendocrine (chromogranin, synaptophysin, CD56) differentiation was studied in 121 LCC across their entire histological spectrum also using direct sequencing for epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and FISH analysis for ALK gene translocation. Survival was not investigated. All 47 large cell neuroendocrine carcinomas demonstrated a true neuroendocrine cell lineage, whereas all 24 basaloid and both 2 lymphoepithelioma-like carcinomas showed squamous cell markers. Eighteen out of 22 clear cell carcinomas had glandular differentiation, with KRAS mutations being present in 39 % of cases, whereas squamous cell differentiation was present in four cases. Eighteen out of 20 large cell carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenocarcinoma. All six LCC of rhabdoid type expressed TTF-1 and/or CK7, three of which also harbored KRAS mutations. When positive and negative immunohistochemical staining for these markers was combined, three subsets of LCC emerged exhibiting glandular, squamous, and neuroendocrine differentiation. Molecular alterations were restricted to tumors classified as adenocarcinoma. Stratifying LCC into specific categories using immunohistochemistry and molecular analysis may significantly impact on the choice of therapy.

Saliva metabolomics by NMR for the evaluation of sport performance.

The paper reports preliminary results of a study in order to verify that saliva is a bio-fluid sensitive to metabolite variations due to stress and fatigue in soccer athletes, and possibly, to identify potential markers of test of performance. Saliva samples of fourteen professional soccer players were collected before and after the stressful physical activity of the level 1 Yo-Yo intermittent recovery test and, also, physiological parameters were evaluated. The NMR spectra of saliva offer a metabolites profiling which was analyzed by Principal Component Analysis as a blind test. The results of NMR pre and post test shows that it was possible to cluster the best and the worst performing athletes and that the role of the actual player may be diagnosed by a different cluster of metabolites profile. Thus saliva can be considered a biofluid metabolically sensitive to the induced physical stress and, in the future, deeper investigated to monitor the performances in athletes.

Bovine rod rhodopsin. 1. Bleaching by luminescence in vitro by recombination of radicals from polyunsaturated fatty acids.

Rod outer segments of photoreceptors are characterized by rhodopsin, a membrane protein surrounded by phospholipids containing a very high concentration of polyunsaturated fatty acids. These fatty acids can propagate free radicals, initiated by peroxidation, whose recombination is eventually associated with light emission as chemiluminescence. The results reported here indicate that this effect produces an isomerization of the retinal (bleaching effect) of the rhodopsin, similar to that induced by light in normal vision. In vitro experiments on detergent-suspended rod outer segments (RdOS) from bovine eyes, using an enzymatic source of radicals, xanthine/xanthine oxidase, were carried out. The results indicate that the proposed mechanism is likely, because they can show the bleaching of rhodopsin in RdOS, owing to its extraordinary sensitivity. Thus this mechanism is, also, a possible explanation for anomalous visual effects such as light flashes (phosphene-like) perceived by humans. The functionality of the rhodopsin in the RdOS was first tested by visible light. Rhodopsin reactivation after bleaching was obtained by adding cis-retinal to the suspension, demonstrating the reversibility of the bleaching process. A special experimental system was developed to observe the bleaching from luminescence by radical recombination, avoiding physical contact between the rod outer segment suspension and the radicals to prevent radical-induced damage and modifications of the delicate structure of the rod outer segment.

Outcomes from ischemic stroke subtypes classified by the Oxfordshire Community Stroke Project: a systematic review.

BACKGROUND: Stroke is a highly heterogeneous disorder with distinct subtypes, each presenting specific clinical aspects. Information on prognosis of ischemic stroke subtypes help to improve clinical management and rehabilitation treatments. AIM: Summarize findings of studies on outcome in stroke subtypes categorized by use of the Oxfordshire Community Stroke Project (OCSP) classification. DESIGN: Systematic review. SETTING: Not applicable. POPULATION: Adult post-stroke patients. METHODS: Systematic literature research of five databases was undertaken to identify relevant studies. Outcomes were examined in terms of impairment, activity restriction and participation restriction. Quality of Life and mortality was also examined for each study. RESULTS: Sixteen studies met inclusion criteria. Most studies measure outcome in terms of activity limitations and participation restriction. Only one study measures impairment. TACI group have poor outcomes in comparison with other groups. Outcomes of LACI, PACI and POCI groups are controversial. CONCLUSION: Stroke subtype is a factor influencing outcome. However, differences among groups, overall in terms of impairment, should be further investigated. CLINICAL REHABILITATION IMPACT: Different prognosis of stroke subtypes may imply different rehabilitation managements.