Explore the vast range of titles available.

Kramers–Kronig theory points to a new way of designing perfect anti-reflection surfaces. When a planar dielectric medium has a permittivity profile that is an analytic function in the upper or lower half of the complex position plane x  =  x ′ + i x ″ then the real and imaginary parts of its permittivity are related by the spatial Kramers–Kronig relations. We find that such a medium will not reflect radiation incident from one side, whatever the angle of incidence. Using the spatial Kramers–Kronig relations, one can derive a real part of a permittivity profile from some given imaginary part (or vice versa) such that the reflection is guaranteed to be zero. This result is valid for both scalar and vector wave theories and may have relevance for designing materials that efficiently absorb radiation or for the creation of a new type of anti-reflection surface.

We present an improved version of the superatom (SA) model to examine the slow-light dynamics of a few-photons signal field in cold Rydberg atoms with van der Waals (vdW) interactions. A main feature of this version is that it promises consistent estimations on total Rydberg excitations based on dynamic equations of SAs or atoms. We consider two specific cases in which the incident signal field contains more photons with a smaller detuning or less photons with a larger detuning so as to realize the single-photon-level light storage. It is found that vdW interactions play a significant role even for the slow-light dynamics of a single-photon signal field as distributed Rydberg excitations are inevitable in the picture of dark-state polariton. Moreover, the stored (retrieved) signal field exhibits a clearly asymmetric (more symmetric) profile because its leading and trailing edges undergo different (identical) traveling journeys, and higher storage/retrieval efficiencies with well preserved profiles apply only to weaker and well detuned signal fields. These findings are crucial to understand the nontrivial interplay of single-photon-level light storage and distributed Rydberg excitations.

Pain remains one of the main reasons for medical consultation worldwide: moderate- to severe-intensity pain occurs in 19% of adult Europeans, seriously affecting the quality of their social and working lives. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for long-term use and a careful surveillance to monitor for toxicity and efficacy is critical. This study aims to assess: 1) the pattern of use of NSAIDs and opioids in a population covered by a cloud-based pharmacovigilance surveillance system; and 2) potential inappropriate use. A retrospective 18-months systematic analysis on patients' pain treatment was performed. The primary endpoint was evaluating the prevalence of NSAIDs and opioids use and the duration of therapy regimen. The secondary endpoint was to investigate the prevalence of NSAIDs taken for >21 consecutive days concomitant with drugs for peptic ulcer and gastroesophageal reflux disease (GORD) or antiplatelet drugs. The yearly cost for individual users of concomitant NSAIDs for more than 21 consecutive days and of GORD medications has been estimated. A total of 3,050 subjects with chronic pain were enrolled; 97% of them took NSAIDs for >21 consecutive days; about one-fourth of these users also received drugs for peptic ulcer and GORD (Anatomical Therapeutic Chemical code A02B). The yearly cost foran individual who uses NSAIDs for >21 consecutive days as well as concomitant GORD medications is 61.23 euros. In total, 238 subjects (8%) using NSAIDs for >21 days also received one antiplatelet agent. About 11% of subjects received opioids at least once and only 2% of them carried on the therapy for more than 90 consecutive days. In evaluating the escalation in dosage as a proxy of dependence risk, this study shows no dosage escalation in our cohort of chronic pain population - that is to say we show no risk of dependence.

Background:Last-generation ultra-high-frequency ultrasound (UHFUS) transducers are highly sensitive tools potentially able to visualize the echo structure abnormalities of labial salivary glands (LSG) with a good diagnostic accuracy in differentiating patients with Sjögren’s disease (SD) from no-SD sicca. Little is known about the correspondence between LSG-UHFUS, LSG histology and anti-Ro/SSA and anti-La/SSB antibodies levels and specificities.Objectives:1. to assess the association between UHFUS scoring and LSG histology in patients with established SD; 2. to explore the association between LSG-UHFUS scoring and anti-Ro/SSA and anti-La/SSB antibodies specificities and titers. 3. To explore whether pathological UHFUS (grade 3 and 2) may allow the identification of different phenotypes of SD.Methods:Out of a cohort of consecutive patients undergoing a UHFUS guided LSG biopsy for suspected SD (Jan 2018-Nov 2022), SD patients who fulfilled the ACR/EULAR classification criteria and had available the quantitative titer of anti-Ro/SSA and anti-La/SSB antibodies at baseline were included. Patients’ clinical, serological, and histological features were collected. UHFUS of LSG was performed by using VEVO MD, equipped with a 70 MHz probe, evaluating parenchymal inhomogeneity (grade 0-3, with grade 2 and 3 defined as pathological, Figure 1). For each of the LSG specimens’ number of foci, focus score (FS) and ectopic lymphoid structures (ELS) were assessed. Serum from each patient was tested for anti-Ro52, anti-Ro60, and anti-SSB/La antibodies with commercially available immunoblot (EUROIMMUN srl), analyzing the quantitative titer of the autoantibodies with band densitometry. The positive control value of the immunoblot strips, obtained in an automatized way, was used to normalize the value of each autoantigen tested. With the formula value of the autoantigen/ (positive control value/100) we calculated a ratio that was used for the analysis. Descriptive statistics and logistic regression were performed with SPSS software.Results:We included a total of 117 SD patients, 107 (91.5%) were female, median age was 57 years (IQR 48.5-66)). UHFUS grade 0 was detected in 3/117 (2.6%) patients, grade 1 in 52/117 (44.4%), grade 2 in 30/117 (25.6%) and grade 3 in 32 (27.4%). We found a significant positive correlation between UHFUS scoring and LSG histology parameters (number of foci, FS and ELS) (p<0.001) Patients presenting a pathological UHFUS (grade 2 and 3) had a higher FS (2 (1.7-2.5) vs 1(0.7-1.1)), number of foci (4.5(4.5-6.5) vs 2(1.5-2.5)) and number of ELS (2 (2-4) vs 1(0-1) compared to patients with milder UHFUS (grade 0 and 1) (p<0.01). Similarly, when compared to the latter, the former presented more frequently a combined positivity for anti-Ro52 and anti-Ro60 or a triple positivity for anti-Ro52 and anti-Ro60 and anti-La/SSB (p=0.004). Moreover, titers of anti-Ro52 (p=0.01), anti-Ro60 (p<0.001) and anti-La/SSB (p<0.001) were significantly higher in patients with UHFUS grade 2 and 3 than in patients with UHFUS score 0 and 1. Finally, patients with UHFUS grade 2 and 3had a significantly higher ESSDAI score. Age at inclusion, anti-Ro60 titer and FS were independent factors associated with pathological UHFUS scores.Conclusion:UHFUS of LSG appeared significantly associated with serological and histological findings in SD. Pathological UHFUS grading may have a role in patients’ stratification.Figure 1.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Literature data regarding clinical characteristics and outcome of primary Sjögren’s syndrome-related Interstitial Lung Disease (pSS-ILD) are often conflicting, possibly due to the existence of heterogeneous pSS-ILD phenotypes that still need appropriate stratification. Preliminary findings suggest that patients diagnosed with ILD during pSS course (ILD-incident) may present significant differences compared to those with ILD diagnosis preceding or accompanying pSS diagnosis (ILD-onset).Objectives:To describe the clinical features and long-term outcome of distinct pSS-ILD phenotypes.Methods:Demographic, clinical, laboratory and imaging data of consecutive pSS patients (2016 ACR/EULAR classification criteria) attending our center from Jan 2016 to Sep 2023 were retrospectively analyzed. All enrolled pSS patients were screened for ILD by clinical examination and at least one among Chest X-Ray, Pulmonary Function Tests and HRCT. All pSS-ILD diagnosis were confirmed based on clinical history, pulmonary function tests (PFT) and HRCT scans, reviewed by an expert thoracic radiologist. She also defined ILD radiologic pattern according to ATS/ERS definitions and ILD extension and severity by Warrick score.Results:Out of 474 pSS patients, 43 were classified as pSS-ILD (M:F=6:37, mean age 64 years), accounting for an overall ILD prevalence of 9.1%. 19 subjects presented ILD as the first manifestation of pSS (ILD-onset), while 24 developed ILD after pSS diagnosis (ILD-incident). Most pSS-ILD patients were symptomatic for exertional dyspnea (81.4%) and chronic cough (74.4%), with a median FVC at baseline of 87% (IQ 77-101) and median DLCO of 66% (IQ 60-76). ILD pattern on HRCT was defined as NSIP in 17 (39.5%), UIP in 8 (18.6%), OP in 2 (4.7%), LIP in 6 (14%), NSIP+OP in 8 (18.6%) and Not classifiable in 2 (4.7%) cases. 8/43 (65%) patients were treated with steroids and 20/43 (46%) received at least one immunosuppressive agent, none was treated with antifibrotics. After a median FU of 7 yrs (IQ 4-15), 8/43 (18.6%) patients necessitated long term oxygen supplementation (LTOT), while 3/43 (7%) died because of progression of the pulmonary disease. UIP patients were the oldest both at pSS diagnosis (mean age 66.3 ±10.6 yrs, p=.001) and at ILD diagnosis (mean age 70.3 ±5.4 yrs, p=.002) and exhibited the highest Warrick score (mean 21.7 ±5.5, p=.044). In contrast, compared to other ILD patients, LIP patients were the youngest at the time of pSS diagnosis (mean age 39.2±21 yrs, p=.008) and presented significantly more often constitutional symptoms (p=.017), purpura (p=.014), hypergammaglobulinemia (p=.023), triple positivity for anti-Ro60/52/SSB (p=.028) and positive RF (p=.006). Moreover, mean latency between onset of respiratory symptoms and ILD diagnosis was significantly longer for LIP patients (p=.02). Compared to ILD-onset, ILD-incident patients presented more often pSS-related hematologic abnormalities (p=.012), cutaneous involvement (p=.027), inflammatory arthralgias (p=.026), C4 hypocomplementemia (p=.012) and positive RF (p=.031). On the contrary ILD-onset patients tended to be more frequently of male sex (26.3% vs 4.2%, p=.07), were significantly older at pSS diagnosis (p=.008) and presented more severe fibrosis on HRCT (mean Warrick score 17.9±7.1 vs 11±5.2, p=.008). In the survival analysis male gender (p=.049) and age older than 60yrs (p=.05) at diagnosis were risk factors for mortality, while UIP pattern and ILD-onset of pSS were the only independent risk factors for LTOT.Conclusion:PSS-ILD patients are heterogeneous for clinical course and outcome. A UIP pattern and ILD-onset represent risk factors for pSS-ILD progression despite management with immunosuppressive drugs and identify a subset of patients that may benefit from additional treatment with antifibrotics. A LIP pattern seems associated with a specific phenotype of pSS, characterized by younger age at diagnosis, high systemic disease activity and serologic biomarkers of lymphocytic hyperactivation, which may represent a promising therapeutic target. Phenotypic stratification of pSS-ILD patients is crucial both for research purposes and clinical practice.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by lymphocytic inflammation and dysfunction of the exocrine glands, particularly the salivary and lacrimal glands. Ultrasonography of Major Salivary Glands (SGUS) is a well-established tool for the identification of the salivary glands’ abnormalities in SjD. Recently, a growing interest has arisen in the assessment of the other exocrine glands including lacrimal glands ultrasound (LGUS). However, few studies are available on the employment of ultra-high frequency ultrasound for lacrimal gland evaluation.Objectives:i) To evaluate the diagnostic accuracy of lacrimal gland ultra-high frequency ultrasound (LGUHFUS) examination for the diagnosis of SjD and the prediction of LSG biopsy results. ii) To explore possible associations between LGUHFUS, labial histology disease clinico-serological, features.Methods:Consecutive patients with suspected SD, undergoing labial salivary gland (LSG) biopsy, were included from Dec 2022 to Dec 2023. Patients were positioned supine with closed eyelids and lacrimal glands were examined using a 48 MHz probe. The following parameters were assessed: dimension, glandular inhomogeneity (Score 0-3), presence of multiple very hypoechoic areas and high perilesional Doppler. Demographic, histological, and clinical features were collected. Serum from each patient was tested for anti-Ro52, anti-Ro60, and anti-SSB/La abs, evaluating the quantitative titer of the autoantibodies with band densitometry. Receiver operating characteristic analysis was calculated to assess the accuracy of UHFUS to predict LSG histology and SjD diagnosis.Results:A total of 71 subjects (10 males and 61 females, mean age 53.04±2.03) were evaluated. Out of them, 28 met the ACR/EULAR 2016 criteria for SjD. No demographic differences were observed between SjD patients and no-SjD sicca controls. ROC curve analysis indicated that LGUHFUS greyscale, at the optimal cut-off value of 2, identified SjD and sicca controls with a sensitivity of 89.3 % and a specificity of 82.4% (AUC=0.836, 95%CI: 0.702-0.970). LSG biopsy of subjects with a LGUHFUS Score≥2 showed a higher Focus Score (FS) (0.48 vs 1.71, p<0.0001), a higher number of foci (1.38 vs 5.57, p<0.0001), and of ectopic lymphoid structures (0.38 vs 3.02, p<0.0001). Moreover, LGUHFUS can predict a FS≥1 at the LSG biopsy with a sensitivity of 88.2% and a specificity of 74.7% (AUC= 0.809, 95% CI: 0.700-0.918). Autoantibodies titer was higher in subjects with LGUHFUS Score≥2 (Ro-52/SSA 9.02 vs 59.49, p<0.05; Ro-60/SSA 5.38 vs 48.32, p<0.0001; SSB 2.1 vs 24.86, p<0.05). A trend was observed between the positivity of LGUHFUS and ocular tests abnormalities results (p=0.089). Lacrimal glands with multiple very hypoechoic areas were more frequently enlarged (p<0.001) and characterised by a high perilesional Doppler. Patients with this pattern presented higher antibody titer (IgG 2224 vs 1453, p< 0.05; IgA 208 vs 339, p< 0.05; IgM 136 vs 234, p< 0.05) and higher systemic disease activity measured according to the ESSDAI (4.43 vs 10.25, p<0.12).Conclusion:LGUHFUS shows a good diagnostic accuracy for SjD and is associated with both tissue infiltrate in LSG and serological biomarkers. Patients with multiple very hypoechoic areas in their lacrimal glands presented a more severe phenotype characterised by high immunoglobulin levels and clinical activity.Figure 1.Lacrimal gland with very hypoechoic areas (a) and high perilesional Doppler (b) compared to lacrimal gland with hypoechoic areas (c) and moderate Doppler signal increase.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

Chondropathies are increasing worldwide, but effective treatments are currently lacking. Mesenchymal stromal cell (MSCs) transplantation represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Umbilical cord- (UC-) MSCs gained increasing interest due to their multilineage differentiation potential, immunomodulatory, and anti-inflammatory properties as well as higher proliferation rates, abundant supply along with no risks for the donor compared to adult MSCs. In addition, UC-MSCs are physiologically adapted to survive in an ischemic and nutrient-poor environment as well as to produce an extracellular matrix (ECM) similar to that of the cartilage. All these characteristics make UC-MSCs a pivotal source for a stem cell-based treatment of chondropathies. In this review, the regenerative potential of UC-MSCs for the treatment of cartilage diseases will be discussed focusing on in vitro, in vivo, and clinical studies.

In optical experiments one-sided reflectionless ( ORL ) and coherent perfect absorption ( CPA ) are unusual scattering properties yet fascinating for their fundamental aspects and for their practical interest. Although these two concepts have so far remained separated from each other, we prove that the two phenomena are indeed strictly connected. We show that a CPA – ORL connection exists between pairs of points lying along lines close to each other in the 3D space-parameters of a realistic lossy atomic photonic crystal. The connection is expected to be a generic feature of wave scattering in non-Hermitian optical media encompassing, as a particular case, wave scattering in parity-time ( PT ) symmetric media.

Matrix metalloproteinases, in particular the gelatinases MMP-2 and MMP-9, have received great attention in recent years as putative tumour markers for clinical applications. The main reason for the observed interest is their easy detection in body fluids. Moreover, recent evidence has shown multiple functions of MMPs, rather than simply degrading ECM, which include the mobilisation of growth factors and processing of surface molecules. Several authors have reported increased levels of MMPs in a number of cancers, but clinical correlations in breast cancer are still fragmentary. Thus, the aim of the present research was to investigate the activity levels of circulating gelatinases in the sera of breast cancer patients by means of zymographic analysis, and correlate data with clinicopathological parameters. In all, 80 patients and 22 healthy volunteers were involved in this study. Sera were obtained prior to surgery. The clinical variables were: grading of tumours, tumour size, lymph node involvement, tumour staging, oestrogen and progesterone receptor levels (76 out of 80 cases), and c-erbB-2 levels (46 cases). The densitometric measures of MMP-2 and MMP-9 activity levels indicated that the average values of both gelatinase activities were significantly higher in breast cancers than in control sera ( P <0.0001). In addition, our analysis showed for the first time that elevated activity levels of both gelatinases correlated only with c-erbB-2 overexpression ( P =0.0273 for MMP-2 and P =0.0075 for MMP-9). An inverse correlation was observed with regard to oestrogen receptor expression ( P =0.0075 for MMP-2 and P =0.0273 for MMP-9). Moreover, a borderline inverse correlation was observed between the activity levels of both enzymes and nuclear grade ( P =0.0511 for MMP-2 and P =0.0794 for MMP-9). In conclusion, the present data suggest that serum measures of MMP's activity may have diagnostic value for discriminating subgroups of breast cancer patients and support the hypothesis that ERBB2 amplification and/or overexpression enhance signalling pathways that may lead to increased production of gelatinases in c-erbB-2 positive breast cancers with higher metastatic potentialities.

The umbilical cord (UC) is a perinatal tissue from which it is possible to isolate mesenchymal stromal cells (MSCs) with a higher proliferation rate and a higher differentiation capacity compared to their adult counterparts. Wharton's jelly (WJ) is a rich source of multipotent and hypoimmunogenic MSCs (WJ-MSCs), which are considered promising candidates for cell therapy of many conditions, including liver diseases. Preterm umbilical cord (birth before 37 weeks of gestation) is generally considered a waste product, so its use does not affect ethical issues. Similarly to the full-term UC, it can be considered a valid source of WJ-MSCs, although little is known about their phenotype and differentiation capacity. We aim to show that WJ-MSCs derived from preterm umbilical cords exhibit comparable characteristics to their mature counterparts and, in particular, show a similar ability to differentiate into hepatocyte-like cells and retain hypoimmunogenicity features. Both these aspects may be key in the prospective application of these cells in regenerative medicine. Here, we isolated WJ-MSCs from seven prematurely harvested umbilical cords (pWJ-MSCs). We assessed a mesenchymal phenotype and differentiation potential by flow cytometry, immunocytochemistry, and immunofluorescence. A standardized liver differentiation protocol was performed, and the acquisition of the hepatic phenotype was assessed by characterization of hepatic protein expression and functional assays. We demonstrated that pWJ-MSCs exhibited mesenchymal characteristics, acquired phenotypical and functional features of hepatocytes when induced to differentiate in a specific medium, and maintained the expression of immunomodulatory molecules. This study showed that even if pregnancy has been interrupted before the 22nd week, p-WJ-MSCs had the same differentiative ability as the counterpart derived from the full-term UC, that we have previously demonstrated, and can be considered a valid cellular population for liver cell therapy.