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.

Anterior Segment Optical Coherence Tomography in Uveitis-Glaucoma-Hyphema Syndrome.

PURPOSE: Uveitis-Glaucoma-Hyphema (UGH) syndrome results from contact between the intraocular lens (IOL) and the iris or ciliary body, leading to uveal structure erosion and blood-aqueous barrier breakdown. Treatment involves various drugs, with IOL removal often being necessary. Diagnosis relies on clinical signs, but imaging techniques like ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS-OCT) are crucial. AS-OCT accurately depicts IOL position and potential contact, emerging as a primary alternative to UBM in the diagnosis. Our study aimed to correlate AS-OCT findings with clinically detectable iris atrophy in pseudophakic patients with IOL-iris chafing and UGH syndrome. METHODS: The study retrospectively analyzed patients diagnosed with UGH syndrome presenting at the Ocular Immunology Unit of Reggio Emilia, Italy, from January 2019 to August 2023. Patients' data were collected. Ophthalmological exams and imaging were performed. The peephole sign in AS-OCT images was evaluated. Statistical analyses were conducted, with a significance level of p ≤ 0.05. RESULTS: The study reviewed 22 eyes of 22 patients with UGH syndrome. Four eyes were excluded, leaving 18 patients (8 females, 10 males). Common misdiagnoses included idiopathic anterior uveitis (55.5%) and herpetic anterior uveitis (16.7%). All patients had iris transillumination defects, mostly focal (77.8%). AS-OCT revealed IOL chafing in all the eyes, with peephole sign correlation. More peephole signs occurred with IOL in the sulcus (p-value = 0.08). CONCLUSION: The study recommends AS-OCT for UGH syndrome confirmation and UBM when IOL-iris chafing is not observed on AS-OCT scans.

Epidemiology of Pediatric Uveitis.

Uveitis is uncommon in children and its diagnosis and treatment are challenging. Little is known of the epidemiology of pediatric uveitis. Indeed, population-based studies in the literature are rare. However, there are many tertiary referral center reports that describe the patterns of uveitis in childhood, although few are from developed countries, and their comparison presents some issues. Anterior uveitis is the most frequent entity worldwide, especially in Western countries, where juvenile idiopathic arthritis is diffuse. Most cases of intermediate uveitis do not show any association with infectious or noninfectious systemic diseases. In low- and middle-income countries, posterior uveitis and panuveitis are prevalent due to the higher rates of infectious etiologies and systemic diseases such as Behçet disease and Vogt-Koyanagi-Harada disease. In recent decades, idiopathic uveitis rate has decreased thanks to diagnostic improvements.

Effectiveness of Pegylated Interferon Alpha-2a in Post-Uveitic Macular Edema Previously Responding to Non-Pegylated Interferon.

PURPOSE: To evaluate the efficacy of pegylated interferon (PEG-IFN) alpha-2a to treat post-uveitic relapsing macular edema (ME) after withdrawal of non-PEG IFN alpha-2a or 2b to maintain treatment efficacy. METHODS: This retrospective study investigated subjects with post-uveitic ME who received weekly subcutaneous PEG-IFN alpha-2a injections. Comparisons between baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) and those at all follow-up visits were made. RESULTS: Six patients (nine eyes) were treated and followed up for six months. CMT (mean [standard deviation]) decreased from 375[117] to 283[39] µm after one month (p < 0.001), remaining significantly lower up to the final follow-up visit at six months (275[38] µm, p = 0.008), and BCVA (0.21[0.16] logMAR at baseline) showed an improvement of 0.12[0.11] logMAR (p = 0.026) at six months. Neither recurrences nor any serious adverse events were recorded. CONCLUSIONS: Post-uveitic ME patients were effectively and safely treated with PEG-IFN alpha-2a.

Characterization of the Shells in Layer-By-Layer Nanofunctionalized Particles: A Computational Study.

Drug delivery carriers are considered an encouraging approach for the localized treatment of disease with minimum effect on the surrounding tissue. Particularly, layer-by-layer releasing particles have gained increasing interest for their ability to develop multifunctional systems able to control the release of one or more therapeutical drugs and biomolecules. Although experimental methods can offer the opportunity to establish cause and effect relationships, the data collection can be excessively expensive or/and time-consuming. For a better understanding of the impact of different design conditions on the drug-kinetics and release profile, properly designed mathematical models can be greatly beneficial. In this work, we develop a continuum-scale mathematical model to evaluate the transport and release of a drug from a microparticle based on an inner core covered by a polymeric shell. The present mathematical model includes the dissolution and diffusion of the drug and accounts for a mechanism that takes into consideration the drug biomolecules entrapped into the polymeric shell. We test a sensitivity analysis to evaluate the influence of changing the model conditions on the total system behavior. To prove the effectiveness of this proposed model, we consider the specific application of antibacterial treatment and calibrate the model against the data of the release profile for an antibiotic drug, metronidazole. The results of the numerical simulation show that ∼85% of the drug is released in 230 h, and its release is characterized by two regimes where the drug dissolves, diffuses, and travels the external shell layer at a shorter time, while the drug is released from the shell to the surrounding medium at a longer time. Within the sensitivity analysis, the outer layer diffusivity is more significant than the value of diffusivity in the core, and the increase of the dissolution parameters causes an initial burst release of the drug. Finally, changing the shape of the particle to an ellipse produces an increased percentage of drugs released with an unchanged release time.

Verifying the band gap narrowing in tensile strained Ge nanowires by electrical means.

Group-IV based light sources are one of the missing links towards fully CMOS compatible photonic circuits. Combining both silicon process compatibility and a pseudo-direct band gap, germanium is one of the most viable candidates. To overcome the limitation of the indirect band gap and turning germanium in an efficient light emitting material, the application of strain has been proven as a promising approach. So far the experimental verification of strain induced bandgap modifications were based on optical measurements and restricted to moderate strain levels. In this work, we demonstrate a methodology enabling to apply tunable tensile strain to intrinsic germanium [Formula: see text] nanowires and simultaneously perform in situ optical as well as electrical characterization. Combining I/V measurements and µ-Raman spectroscopy at various strain levels, we determined a decrease of the resistivity by almost three orders of magnitude for strain levels of âˆ¼5%. Thereof, we calculated the strain induced band gap narrowing in remarkable accordance to recently published simulation results for moderate strain levels up to 3.6%. Deviations for ultrahigh strain values are discussed with respect to surface reconfiguration and reduced charge carrier scattering time.

Nodal superconducting exchange coupling.

A superconducting spin valve consists of a thin-film superconductor between two ferromagnetic layers. A change of magnetization alignment shifts the superconducting transition temperature (ΔΤc) due to an interplay between the magnetic exchange energy and the superconducting condensate. The magnitude of ΔΤc scales inversely with the superconductor thickness (dS) and is zero when dS exceeds the superconducting coherence length (ξ). Here, we report a superconducting spin-valve effect involving a different underlying mechanism in which magnetization alignment and ΔΤc are determined by nodal quasiparticle excitation states on the Fermi surface of the d-wave superconductor YBa2Cu3O7-δ sandwiched between insulating layers of ferromagnetic Pr0.8Ca0.2MnO3. We observe ΔΤc values that approach 2 K with the sign of ΔΤc oscillating with dS over a length scale exceeding 100ξ and, for particular values of dS, the superconducting state reinforces an antiparallel magnetization alignment. These results pave the way to all-oxide superconducting memory in which superconductivity modulates the magnetic state.

Chitosan-based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment.

Advanced therapies which combine cells with biomaterial-based carriers are recognized as an emerging and powerful method to treat challenging diseases, such as spinal cord injury (SCI). By enhancing transplanted cell survival and grafting, biomimetic hydrogels can be properly engineered to encapsulate cells and locate them at the injured site in a minimally invasive way. In this work, chitosan (CS) based hydrogels were developed to host mesenchymal stem cells (MSCs), since their paracrine action can therapeutically enhance the SC regeneration, limiting the formation of a glial scar and reducing cell death at the injured site. An injectable and highly permeable CS-based hydrogel was fabricated having a rapid gelation upon temperature increase from 0 to 37 °C. CS was selected as former material both for its high biocompatibility that guarantees the proper environment for MSCs survival and for its ability to provide anti-inflammatory and anti-oxidant cues. MSCs were mixed with the hydrogel solution prior to gelation. MSC viability was not affected by the CS hydrogel and encapsulated MSCs were able to release MSC-vesicles as well as to maintain their anti-oxidant features. Finally, preliminary in vivo tests on SCI mice revealed good handling of the CS solution loading MSCs during implantation and high encapsulated MSCs survival after 7 days.

Lactose-crosslinked fish gelatin-based porous scaffolds embedded with tetrahydrocurcumin for cartilage regeneration.

Tetrahydrocurcumin (THC) is one of the major colourless metabolites of curcumin and shows even greater pharmacological and physiological benefits. The aim of this work was the manufacturing of porous scaffolds as a carrier of THC under physiological conditions. Fish-derived gelatin scaffolds were prepared by freeze-drying by two solutions concentrations (2.5% and 4% w/v), cross-linked via addition of lactose and heat-treated at 105 °C. This cross-linking reaction resulted in more water resistant scaffolds with a water uptake capacity higher than 800%. Along with the cross-linking reaction, the gelatin concentration affected the scaffold morphology, as observed by scanning electron microscopy images, by obtaining a reduced porosity but larger pores sizes when the initial gelatin concentration was increased. These morphological changes led to a scaffold's strength enhancement from 0.92 ±â€¯0.22 MPa to 2.04 ±â€¯0.18 MPa when gelatin concentration was increased. THC release slowed down when gelatin concentration increased from 2.5 to 4% w/v, showing a controlled profile within 96 h. Preliminary in vitro test with chondrocytes on scaffolds with 4% w/v gelatin offered higher metabolic activities and cell survival up to 14 days of incubation. Finally the addition of THC did not influence significantly the cytocompatibility and potential antibacterial properties were demonstrated successfully against Staphylococcus aureus.

Alginate-based hydrogels functionalised at the nanoscale using layer-by-layer assembly for potential cartilage repair.

Injuries to articular cartilage are frequently difficult to repair, in part because of the poor regenerative capacity of this tissue. To date, no successful system for complete regeneration of the most challenging cartilage defects has been demonstrated. The aim of this work was to develop functionalised hydrogels at the nanoscale by Layer-by-Layer (LbL) assembly to promote cartilage healing. Hydrogels, based on sodium alginate (NaAlg) and gelatin (G), were prepared by an external gelation method consisting of CaCl2 diffusion and genipin addition for G crosslinking. Successively, hydrogels were coated with G to obtain a positive charge on the surface, then functionalised by LbL assembly to create 16 nanolayers, based on poly(styrene sulfonate)/poly(allyl amine) (PSS/PAH), including a specific peptide sequence (CTATVHL) and transforming growth factors ß1 (TGF-ß1). Physico-chemical properties were evaluated by XPS, ATR-FTIR and rheological analyses while in vitro cytocompatibility was studied using bovine articular chondrocytes (BAC). XPS spectra showed N1s and S2p peaks, indicating that PAH and PSS have been introduced with success. ATR-FTIR indicated the specific PAH and PSS absorption peaks. Finally, the biomolecule incorporation influenced positively the processes of BAC adhesion and proliferation, and glycosamynoglycan secretion. The functionalised alginate-based hydrogels described here are ideally suited to chondral regeneration in terms of their integrity, stability, and cytocompatibility.

The natural history of prehypertension. A 20-year follow-up.

OBJECTIVE: According to the JNC7 report, prehypertension category includes subjects with systolic blood pressure between 120 and 139 mmHg and/or diastolic blood pressure between 80 and 89 mmHg that would be at risk for developing hypertension and its untoward sequelae as myocardial infarction and cerebrovascular disease. Moreover, ambulatory blood pressure monitoring made it possible to detect subjects with masked hypertension, who are at risk of greater target organ damage than those with normal ambulatory or home blood pressure. The aim of this study was to evaluate the risk of cardiac, cerebral and vascular events in a group of prehypertensive subjects, with and without masked hypertension. PATIENTS AND METHODS: We studied 204 consecutive asymptomatic prehypertensive subjects without history and signs of cardiovascular disease or diabetes. All the subjects underwent clinical evaluation, electrocardiogram, routine laboratory tests and ambulatory blood pressure monitoring. They were followed-up for a maximum of 237 months or until a cardiovascular event occurred. RESULTS: Twenty-seven cardiovascular events (13.2%) occurred, including 4 abdominal aortic aneurysms. Age (p<0.0001), total cholesterol (p=0.004), smoking (p=0.03) and clinically overt hypertension development (p=0.011) were related to cardiovascular events. Prognosis was not related to masked hypertension. CONCLUSIONS: The results of this study suggest that, in subjects with prehypertension, followed for 20 years, traditional cardiovascular risk factors and development of clinically overt hypertension could be more relevant than ambulatory hypertension in the prediction of an adverse outcome.

Preparation and Antibacterial Properties of Silver-Doped Nanoscale Hydroxyapatite Pastes for Bone Repair and Augmentation.

The treatment of deep bone infections remains a significant challenge in orthopaedic and dental surgery. The relatively recent commercial manufacture of nanoscale hydroxyapatite has provided surgeons with an injectable biomaterial that promotes bone tissue regeneration, and with further modification it may be possible to incorporate antimicrobial properties into these devices. Silver-doped nanoscale hydroxyapatite pastes (0, 2, 5 and 10 mol.% silver) were prepared using a rapid mixing method. When the process was modified to prepare a 10 mol.% silver-doped material, silver phosphate was detected in addition to nanoscale hydroxyapatite. Thermal decomposition occurred more readily with greater silver content following calcination at 1000 °C for 2 h. Silver-doped nanoscale hydroxyapatite pastes showed antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa in a dose dependent manner using both agar diffusion assays and suspension cultures. It was concluded that the enhanced antibacterial activity of the silver-doped pastes was due to the action of diffusible silver ions. Based on these results, silver-doped nanoscale hydroxyapatite pastes represent a highly promising new biomaterial system for the prevention and treatment of deep infections in bone tissue.

Uniform phosphorus doping of untapered germanium nanowires.

One of the major challenges in the growth of vapor-liquid-solid (VLS) nanowires is the control of dopant incorporation in the structures. In this work, we study the n-type doping and morphology of nanowires grown by chemical vapor deposition when HCl is introduced. We obtain fully untapered nanowires with a growth temperature up to 410 °C and measure their resistivity using the 4-probe technique to be 2.0 mΩ cm. We perform energy dispersive x-ray measurements showing a concentration of dopants in the (5-7) × 1018 cm-3 range, being radially and axially uniform. The combination of these two measurements shows that the mobility is the same as for bulk germanium, demonstrating that the VLS mechanism has no detrimental effect for the electron transport in these nanowires.

Layer-by-layer assembly for biomedical applications in the last decade.

In the past two decades, the design and manufacture of nanostructured materials has been of tremendous interest to the scientific community for their application in the biomedical field. Among the available techniques, layer-by-layer (LBL) assembly has attracted considerable attention as a convenient method to fabricate functional coatings. Nowadays, more than 1000 scientific papers are published every year, tens of patents have been deposited and some commercial products based on LBL technology have become commercially available. LBL presents several advantages, such as (1): a precise control of the coating properties; (2) environmentally friendly, mild conditions and low-cost manufacturing; (3) versatility for coating all available surfaces; (4) obtainment of homogeneous film with controlled thickness; and (5) incorporation and controlled release of biomolecules/drugs. This paper critically reviews the scientific challenge of the last 10 years--functionalizing biomaterials by LBL to obtain appropriate properties for biomedical applications, in particular in tissue engineering (TE). The analysis of the state-of-the-art highlights the current techniques and the innovative materials for scaffold and medical device preparation that are opening the way for the preparation of LBL-functionalized substrates capable of modifying their surface properties for modulating cell interaction to improve substitution, repair or enhancement of tissue function.

The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: clinical and histomorphometric evaluation.

To investigate the safety and clinical efficacy of AA-PRP injections for pattern hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of the selected patients' scalps with pattern hair loss. The other half was treated with placebo. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair re-growth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 18.0 hairs in the target area, and a mean increase in total hair density of 27.7 ( number of hairs/cm(2)) compared with baseline values. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles two weeks after the last AA-PRP treatment compared to baseline value (P < 0.05). We also observed an increase of Ki67(+) keratinocytes of epidermis and of hair follicular bulge cells and a slight increase of small blood vessels around hair follicles in the treated skin compared to baseline (P < 0.05).

Crosslinked gelatin nanofibres: preparation, characterisation and in vitro studies using glial-like cells.

Gelatin (GL) nanofibrous matrices mimicking the complex biological structure of the natural extracellular matrix (ECM) were prepared from aqueous solutions by electrospinning technique. GL nanofibres with a diameter size of around 300nm were obtained optimising the process and solution parameters. To increase the GL stability in aqueous environment γ-glycidoxypropyltrimethoxysilane (GPTMS) was used as GL crosslinker. GPTMS crosslinking did not modify the nanofibrous matrix morphology: fibre diameter and membrane pores size were 327±45 nm and 1.64±0.37 µm, respectively. The produced GPTMS crosslinked GL nanofibres (GL/GPTMS_NF) were found to support the in vitro adhesion, proliferation and survival of neonatal olfactory bulb ensheating cells (NOBECs).

Platelet-rich plasma and blood components for non-transfusion use: technical and medicolegal aspects.

There are a large number of publications describing the use of platelet-rich plasma (PRP) in multiple fields of application. These illustrate a large number of therapeutic elements with different and specific actions within 'platelet gel' (this term is used in the current regulations to define this product). This term, however, lacks specificity and, depending on the method used in its production is variable both in its blood composition and in platelet concentration, and several publications consider better and easier methods of platelet gel production, which may or may not lead to greater standardization in the product. The authors illustrate the general aspects of PRP and other blood components for non-transfusion use, briefly touching on the history and different fields of application and the rational of for its use. Given the increased use of such preparations, the authors describe critically the regulations in force in Europe and propose a new regulatory framework aimed to simplify and facilitate the use of such material as a therapeutic agent within medicine.

Biomimetic coating on bioactive glass-derived scaffolds mimicking bone tissue.

Bioceramic "shell" scaffolds, with a morphology resembling the cancellous bone microstructure, have been recently obtained by means of a new protocol, developed with the aim to overcome the limits of the conventional foam replication technique. Because of their original microstructure, the new samples combine high porosity, permeability, and manageability. In this study, for the first time, the novel bioactive glass shell scaffolds are provided with a gelatin-based biomimetic coating to realize hybrid implants which mimic the complex morphology and structure of bone tissue. Moreover, the presence of the coating completely preserves the in vitro bioactivity of the bioactive glass samples, whose surfaces are converted into hydroxyapatite after a few days of immersion in a simulated body fluid solution (SBF).

Effect of HCl on the doping and shape control of silicon nanowires.

The introduction of hydrogen chloride during the in situ doping of silicon nanowires (SiNWs) grown using the vapor-liquid-solid (VLS) mechanism was investigated. Compared with non-chlorinated atmospheres, the use of HCl with dopant gases considerably improves the surface morphology of the SiNWs, leading to extremely smooth surfaces and a greatly reduced tapering. Variations in the wire diameter are massively reduced for boron doping, and cannot be measured at 600 °C for phosphorous over several tens of micrometers. This remarkable feature is accompanied by a frozen gold migration from the catalyst, with no noticeable levels of gold clusters observed using scanning electron microscopy. A detailed study of the apparent resistivity of the NWs reveals that the dopant incorporation is effective for both types of doping. A graph linking the apparent resistivity to the dopant to silane dilution ratio is built for both types of doping and discussed in the frame of the previous results.