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Microbial colonization on plastic polymers has been extensively explored, however the temporal dynamics of biofilm community in Antarctic environments are almost unknown. As a contribute to fill this knowledge gap, the structural characteristics and microbial diversity of the biofilm associated with polyvinyl chloride (PVC) and polyethylene (PE) panels submerged at 5 m of depth and collected after 3, 9 and 12 months were investigated in four coastal sites of the Ross Sea. Additional panels placed at 5 and 20 m were retrieved after 12 months. Chemical characterization was performed by FTIR-ATR and Raman (through Surface-Enhanced Raman Scattering, SERS) spectroscopy. Bacterial community composition was quantified at a single cell level by Catalyzed Reporter Deposition Fluorescence In Situ Hybridization (CARD-FISH) and Confocal Laser Scanning Microscopy (CLSM); microbial diversity was assessed by 16S rRNA gene sequencing. This multidisciplinary approach has provided new insights into microbial community dynamics during biofouling process, shedding light on the biofilm diversity and temporal succession on plastic substrates in the Ross Sea. Significant differences between free-living and microbial biofilm communities were found, with a more consolidated and structured community composition on PVC compared to PE. Spectral features ascribable to tyrosine, polysaccharides, nucleic acids and lipids characterized the PVC-associated biofilms. Pseudomonadota (among Gamma-proteobacteria) and Alpha-proteobacteria dominated the microbial biofilm community. Interestingly, in Road Bay, close to the Italian "Mario Zucchelli" research station, the biofilm growth - already observed during summer season, after 3 months of submersion - continued afterwards leading to a massive microbial abundance at the end of winter (after 12 months). After 3 months, higher percentages of Gamma-proteobacteria in Road Bay than in the not-impacted site were found. These observations lead us to hypothesize that in this site microbial fouling developed during the first 3 months could serve as a starter pioneering community stimulating the successive growth during winter., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This research article has not been submitted previously, it is not under consideration for publication elsewhere, its publication is approved by all authors and, if accepted, it will not be published elsewhere in the same form in English or in any other language, including electronically, without the written consent of the copyright-holder. No generative artificial intelligence (AI) and AI-assisted technologies were used in the writing process., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypersensitivity reactions represent one of the most common causes of hesitancy for adherence to national vaccination programs. The majority of hypersensitivity reactions after vaccination are mild, and anaphylaxis is reported to be rare, although it remains challenging to estimate the frequency attributed to each single vaccine, either because of the lower number of administered doses of less common vaccines, or the administration of simultaneous vaccine in most of the vaccination programs. Although literature remains scattered, international consensus guides clinicians in identifying patients who might need the administration of vaccines in protected environments due to demonstrated hypersensitivity to vaccine components or adjuvants. Here we provide the current guidance on hypersensitivity reactions to vaccines and on vaccination of children with allergy disorders., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: Comparing the effect of standard trabeculectomy with direct sutures versus trabeculectomy with compression and everting sutures., Methods: Mono-centric randomized prospective comparative study on 38 glaucomatous eyes undergoing trabeculectomy: 19 with standard fixed sutures (group A) and 19 withremovable regulating sutures (group B). Preoperatively and at day-7, 1-month, 2-months, 3-months and 6-months after surgery, we recorded best-corrected visual acuity (BCVA), intraocular pressure (IOP) and possible complications. Complete, partial success and failure rates were recorded at the end of the study., Results: In group B, we pulled everting sutures with the "horse bridle" technique at the 14 th day, and successively removed all sutures between the 14 th -30 th post-operative day. At month-1, we recorded a significant IOP reduction in both groups (mean reduction of 11.5 mmHg for group A and of 14.4 mmHg for Group B, p = 0.001 and p < 0.0001, respectively). Furthermore, group B showed a significantly lower IOP than group A (-4.2 mmHg, 95% confidence interval [CI] -7.0 to -0.5 mmHg for group B, p = 0.01). At 2, 3 and 6-months, no significant IOP differences were reported between the two groups (all p > 0.05), but failure rate was higher for group A (21%) than for group B (11%). No differences in visual outcomes at any timepoints were noted., Conclusions: Trabeculectomy with removable regulating sutures showed a good safety profile, comparable to standard trabeculectomy. Moreover, we reported a lower IOP one month postoperatively, suggesting this technique may optimize early management of trabeculectomy., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child's pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement., Methods: This study includes a sample of 127 youth (66.1% female) with mixed etiology chronic pain, ranging in age from 8 to 17 (M = 12.24; SD = 1.598), and their parent. Data was collected at an interdisciplinary pediatric pain clinic and online peer support groups. Measures of demographic, pain intensity, and functioning were collected., Results: Means of parent-proxy reports were significantly lower than child self-reports on the PROMIS (p < 0.05). A statistically significant association between child's pain intensity (β = 0.953, P < 0.05) and the difference between child self-reported and parent-proxy reported PROMIS functional interference scores was found., Conclusion: Parents underestimated pain-related functional disability relative to children's self-reports. The difference between the paired child self-report and parent-proxy report of functional disability was significantly associated with greater child self-reported pain intensity. Although parent-proxy reports in pediatric chronic pain is often used in research and practice, findings underscore the importance of incorporating child and adolescent self-report, when possible, to comprehensively capture the child's pain experience and best inform clinical interventions., (© 2024. The Author(s).)

Purpose: To report a case of a patient with perifoveal exudative vascular anomalous complex (PEVAC) and to analyze morphological and vascular changes by OCT and OCTA before and after treatment., Materials and Methods: In this case we reported a case which received multiple treatment for unresponsive effect to Repeated Aflibercept intravitreal injections, subthreshold micropulse laser therapy (SMPL) duty cycle 5%. At last the focal fully dose yellow laser was performed., Results: A 57-year-old male patient presented with best corrected visual acuity (BCVA) of 20/50 in his right eye (RE) The fundoscopic evaluation, structural optical coherence tomography (OCT) and OCT angiography (OCTA) deposed for a diagnosis of PEVAC. The patient underwent three Aflibercept intravitreal injections in the RE. Since no changes were detected, we opted for multiple sessions of yellow subthreshold micropulse laser therapy (SMPL) duty cycle 5%, however no signs of regression were registered. Only after a fully dose yellow laser, signs of edema regression were observed. Stuctural OCT B-scan showed complete restitutio of retinal profile, in absence of any intraretinal or subretinal fluid and PEVAC lesion, while the OCTA showed a slight flow deficit at the previous lesion site., Conclusions: and Importance: The PEVAC treatment is still unknown. In our experience, we reported a case of multiple treatments for unresponsive effect to: Aflibercept intravitreal injections, subthreshold micropulse laser therapy (SMPL) duty cycle 5%. At list the focal fully dose yellow laser was the only effective in our patient. We proposed our management to share the heterogeneous response at PEVAC entity., Competing Interests: Conflicts of Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study, we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections among the pathophysiology of each disease. The significantly changed metabolites in the untargeted urine metabolomic profiles of 21 patients (seven MMA, seven PA, seven cblC) were identified through statistical analysis ( p < 0.05; log2FC > |1|) and then used for annotation. Annotated features were associated with different metabolic pathways potentially involved in the disease's development. Comparative statistics showed markedly different metabolomic profiles between MMA, PA, and cblC, highlighting the characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (all diseases), amino acids (all diseases), and glycine and its conjugates (in PA); the transsulfuration pathway; oxidative processes; and neurosteroid hormones (in cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast in the cblC profile compared to MMA and PA. Some new biomarkers were proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration.

Purpose: To examine whether the extension of retinal pigment epithelium (RPE) and outer retinal atrophy (RORA) and various other morphofunctional parameters correlate with the genetic assessment and severity of retinitis pigmentosa (RP)., Methods: Thirty-eight patients (76 eyes) with RP were prospectively enrolled and underwent full ophthalmic examination, including visual field testing, full-field electroretinography (ERG), and optical coherence tomography angiography. The severity of the disease was calculated using the RP stage scoring system, and the area of RORA was assessed using the automatically calculated area of sub-RPE illumination. Blood or saliva samples were collected from subjects, and DNA extraction was performed to evaluate genetic mutations and nucleotide and amino acid variations., Results: There was a statistically significant correlation between the extent of RORA and patient age, best-corrected visual acuity, ellipsoid zone extension, and disease severity in both eyes (each, P < 0.05). In contrast, RORA did not correlate with either the visual field or the ERG amplitude. Cumulative score and grade severity were both significantly correlated with superficial and deep capillary plexus density (both, P < 0.001) in both eyes. Evaluating RORA, we found genes with an overall less severe phenotype, such as EYS, PCDH15, and PRPF31, and those with a worse phenotype, such as RPGR., Conclusions: The correlation of RORA with structural, functional, and genetic assessment in RP disease leads us to consider RORA as a potential biomarker for prediction of disease stage. Multicenter studies are needed to confirm our findings., Translational Relevance: The morphofunctional and genetic correlations suggest a role for RORA in RP diagnosis and follow-up.

Purpose: To understand whether the preoperative morphology of the posterior corneal surface influences the rate of re-bubbling after Descemet membrane endothelial keratoplasty (DMEK)., Methods: After retrospectively analyzing the medical records of patients undergoing DMEK, in this multicentric cross-sectional study, we performed a binomial logistic regression analysis to assess significant predictors of re-bubbling and re-transplantation after surgery. Analyzed parameters included the preoperative diagnosis, anterior and posterior surface K1/K2, central corneal thickness, posterior Q value, and other posterior corneal surface parameters evaluated on the elevation maps produced by anterior segment optical coherence tomography. Results were stratified based on the surgeons' experience., Results: We included 202 eyes of 202 patients with a mean age of 69.5 ± 12.4 years; 154 eyes were operated by a high-volume surgeon and 48 by one with less experience; 48 eyes (23.8%) underwent ≥ 1 re-bubbling and 14(6.9%) ≥ 1 re-transplantation. The presence of positive/less-negative posterior corneal irregularities and irregularities with greater absolute height had a significantly higher risk of re-bubbling in both the expert and less expert group (OR = 2.85 and 1.42, OR = 3.22 and 3.01, respectively, p < 0.05), whereas more negative posterior K1 and K2 were significant risk factors only in the former group (OR = 0.67 and 0.55, respectively, p < 0.05). Endothelial decompensation other than Fuchs and pseudophakic bullous keratopathy, more negative posterior Q values and smaller distances between center, and the highest/lowest posterior corneal surface irregularity correlated with an increased risk of graft failure (OR 1.23, 1.21, and 1.29, respectively, p < 0.05)., Conclusion: Posterior corneal surface morphology significantly influences the risk of re-bubbling after DMEK., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea., Methods: Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients' group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol., Results: SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes (p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH., Conclusion: When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular "compaction" could be a first phase of hypoestrogenism adaptation., (© 2024. The Author(s).)

Background: Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among US infants. A child's calendar birth month determines their age at first exposure(s) to RSV. We estimated birth month-specific risk of medically attended (MA) RSV lower respiratory tract infection (LRTI) among infants during their first RSV season and first year of life (FYOL)., Methods: We analyzed infants born in the USA between July 2016 and February 2020 using three insurance claims databases (two commercial, one Medicaid). We classified infants' first MA RSV LRTI episode by the highest level of care incurred (outpatient, emergency department, or inpatient), employing specific and sensitive diagnostic coding algorithms to define index RSV diagnoses. In our main analysis, we focused on infants' first RSV season. In our secondary analysis, we compared the risk of MA RSV LRTI during infants' first RSV season to that of their FYOL., Results: Infants born from May through September generally had the highest risk of first-season MA RSV LRTI-approximately 6-10% under the specific RSV index diagnosis definition and 16-26% under the sensitive. Infants born between October and December had the highest risk of RSV-related hospitalization during their first season. The proportion of MA RSV LRTI events classified as inpatient ranged from 9% to 54% (specific) and 5% to 33% (sensitive) across birth month and comorbidity group. Through the FYOL, the overall risk of MA RSV LRTI is comparable across birth months within each claims database (6-11% under the specific definition, 17-30% under the sensitive), with additional cases progressing to care at outpatient or ED settings., Conclusions: Our data support recent national recommendations for the use of nirsevimab in the USA. For infants born at the tail end of an RSV season who do not receive nirsevimab, a dose administered prior to the onset of their second RSV season could reduce the incidence of outpatient- and ED-related events., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Purpose: To evaluate ophthalmological, neurological, radiological, and laboratory data in patients with multiple sclerosis (MS) and to identify new ophthalmological factors that could be helpful as biomarkers of the disease, potentially leading to an earlier prediction of disease course and disability progression., Design: Retrospective, cross-sectional-study., Methods: Best-corrected visual acuity (BCVA), ophthalmological biomicroscopy of the anterior segment and fundus, structural optical coherence tomography (OCT) with retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC), and OCT angiography (OCTA) with vascular density (VD) were performed. The following clinical and neuro-radiological features were assessed: MS phenotype, disease duration, clinical severity, type of treatment, and T2-weighted lesion and T1-weighted Gd+ enhancing lesion number on the brain and spinal cord MRI., Results: One hundred and six patients (212 eyes) were analyzed. Sixty-six of them (62.2%) had MS and 40 (37.8%) were matched healthy controls (HCs). patients with MS showed lower RNFL, GCC, and VD in the radial peripapillary capillary plexus than controls in both eyes (P < .05). By Performing a logistic regression with a distinct MS outcome for both eyes, we were able to demonstrate that the value that was most predictive of MS was the average GCC thickness (P = .009). Regression analysis demonstrated that patients with a higher T2-weighted lesions showed a lower RNFL thickness value and reduced GCC and VD values than those with a low lesion load (P < .01 and P < .05, respectively). Similarly, relapsing MS patients showed lower RNFL values (P < .05)., Conclusions: Several OCT and OCTA-optic nerve parameters could be useful prognostic biomarkers for the MS disease course in clinical practice. However, it is necessary to do additional research with larger sample sizes in order to validate these findings., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: This study investigates the association between parental attitudes towards mandatory and recommended vaccines in the National Immunization Plan (NIP) of Italy and their acceptance of the COVID-19 vaccine in children aged 5-11 years., Methods: Using data from approximately 42,000 children in Southern Italy, parental attitudes towards previous vaccinations were examined. Mandatory and recommended vaccinations were considered for the analysis, with the first shot of each schedule being considered relevant, regardless of when it was administered or whether the recommended number of doses was administered. A multivariate logistic regression was performed to analyze associations between the covariates of age, sex, adherence to mandatory vaccinations, number of recommended vaccinations, and COVID-19 vaccination., Results: The COVID-19 vaccine acceptance rate was 50.7% in our sample. We revealed a strong association between parental attitudes towards previous vaccinations and the acceptance of the COVID-19 vaccine. Mandatory vaccinations under the NIP showed the highest acceptance rates, and among non-mandatory vaccines, the pneumococcal conjugate vaccine had the highest acceptance rate, potentially due to its co-administration with the hexavalent vaccine. The study identified a trend of lower COVID-19 vaccine coverage in younger children., Conclusions: The study underscores the importance of co-administration approaches and well-planned vaccination schedules in enhancing vaccine coverage. It suggests that integrating newer vaccines, like the COVID-19 vaccine, into established vaccination schedules could potentially increase acceptance and coverage. The findings highlight the urgency of addressing vaccine hesitancy, particularly in the pediatric population, to ensure high vaccination coverage and effective disease control. Further research is needed to explore the potential strategies to increase vaccine acceptance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luigi De Angelis reports a relationship with Moderna Inc that includes: travel reimbursement. Alberto Fedele reports a relationship with Seqirus Vaccines Ltd that includes: board membership. Francesco Baglivo reports a relationship with Moderna Inc that includes: travel reimbursement. Francesco Baglivo reports a relationship with AstraZeneca that includes: educational grant. Caterina Rizzo reports a relationship with Seqirus Vaccines Ltd that includes: board membership. Caterina Rizzo reports a relationship with MSD that includes: board membership. Caterina Rizzo reports a relationship with GlaxoSmithKline (GSK) that includes: board membership. Caterina Rizzo reports a relationship with Sanofi that includes: board membership. Caterina Rizzo reports a relationship with AstraZeneca that includes: board membership., (Copyright © 2024 Elsevier India Pvt Ltd. Published by Elsevier Ltd.. All rights reserved.)

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery., (© 2024. The Author(s).)

Background: To evaluate, in patients undergoing macula-off rhegmatogenous retinal detachment surgery (RRD), the correlation between preoperative optical coherence tomography (OCT) morphological features and postoperative visual acuity., Methods: Retrospective interventional non-randomised clinical trial on 89 eyes of 89 patients undergoing pars plana vitrectomy for macula-off primary RRD at Policlinico Universitario Agostino Gemelli from 2020 to 2023. Preoperative 6×6 mm OCT B scans with Nidek Mirante (Nidek, Gamagori, Japan) were performed, collecting the following features: foveal involvement (fovea-on vs fovea-off), subretinal hyper-reflective points (HRPs), outer retinal corrugations (ORCs) and intraretinal cystic spaces (ICS) in the outer nuclear layer. The patients were followed in a 6-month follow-up to evaluate best-corrected visual acuity (BCVA) outcomes., Results: Preoperative mean BCVA was 0.15±0.22 and improved to 0.29±0.3 decimals at 6 months (p<0.001). The presence of subretinal HRPs showed a significant negative impact on BCVA improvement in the univariate regression analysis (r=-0.264, p=0.024), as well as the presence of foveal detachment (r=-0.355, p=0.012). The other OCT features did not show a significant correlation with BCVA improvement: ORCs (r=0.072, p=0.257) and ICS (r=-0.020, p=0.734). In the multivariate regression analysis, the negative impact of foveal detachment was confirmed (r=-0.199, p=0.05) while the statistical significance of subretinal HRPs was lost (r=-0.135, p=0.105)., Conclusions: The negative impact of foveal involvement in a macula-off RRD was confirmed. Moreover, the presence of subretinal HRPs, as a possible indirect marker of inflammatory response extent, may act as a negative predictor for postoperative visual recover., Trial Registration Number: NCT05747144., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This explorative study was aimed at first characterizing the sponge Spongilla lacustris (Linnaeus, 1759) from the sub-Arctic Pasvik River (Northern Fennoscandia), in terms of associated microbial communities and pollutant accumulation. Persistent organic pollutants were determined in sponge mesohyl tissues, along with the estimation of the microbial enzymatic activity rates, prokaryotic abundance and morphometric traits, and the analysis of the taxonomic bacterial diversity by next-generation sequencing techniques. The main bacterial groups associated with S. lacustris were Alphaproteobacteria and Gammaproteobacteria, followed by Chloroflexi and Acidobacteria. The structure of the S. lacustris-associated bacterial communities was in sharp contrast to those of the bacterioplankton, being statistically close to those found in sediments. Dieldrin was measured at higher concentrations in the sponge tissues (3.1 ± 0.4 ng/g) compared to sediment of the same site (0.04 ± 0.03 ng/g). Some taxonomic groups were possibly related to the occurrence of certain contaminants, as was the case of Patescibacteria and dieldrin. Obtained results substantially contribute to the still scarce knowledge of bacterial community diversity, activities, and ecology in freshwater sponges. PRACTITIONER POINTS: Microbial community associated with Spongilla lacustris is probably shaped by the occurrence of certain contaminants, mainly dieldrin and heavy metals. A higher accumulation of dieldrin in the sponge mesohyl tissues than in sediment was determined. S. lacustris is suggested as sponge species to be used as a sentinel of pesticide pollution in the Pasvik River. S. lacustris, living in tight contact with soft substrates, harbored communities more similar to sediment than water communities., (© 2024 Water Environment Federation.)

Objectives: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients., Methods: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events., Results: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported., Conclusions: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Synthesis of heterocyclic compounds is fundamental for all the research area in chemistry, from drug synthesis to material science. In this framework, catalysed synthetic methods are of great interest to effective reach such important building blocks. In this review, we will report on some selected examples from the last five years, of the major improvement in the field, focusing on the most important conventional catalytic systems, such as transition metals, organocatalysts, to more sustainable ones such as photocatalysts, iodine-catalysed reaction, electrochemical reactions and green innovative methods., (© 2023 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Background: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season., Methods: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations., Results: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration., Conclusions: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures., (© 2024. The Author(s).)

Introduction: Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in primary care settings is still little studied., Methods: During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community-based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow-up questionnaires completed by the parents of positive children on Days 14 and 30., Results: RSV laboratory-confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV-positive swabs. RSV-positive children were younger than RSV-negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV-A positive patients required more additional pediatric examinations than RSV-B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs., Conclusions: Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Circumscribed choroidal hemangioma is a rare vascular hamartoma of the choroid, presenting as a red-orange mass at the posterior pole on fundoscopic examination. Despite its benign origin, associated complications such as subretinal fluid, serous retinal detachment, retinoschisis and neovascular glaucoma may lead to serious visual impairment in more than half patients. Because of its similarity to amelanotic choroidal melanoma and choroidal metastasis, differential diagnosis is still challenging for specialists. Multimodal imaging such as ultrasonography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography guides the clinician to the correct diagnosis and the proper follow-up. Treatment is indicated in symptomatic cases in order to resolve exudation and improve visual acuity. Treatment options include photocoagulation, transpupillary thermotherapy, radiation therapy, photodynamic therapy and anti-vascular endothelial growth factor therapy. Currently, photodynamic therapy is the treatment of choice due to its effectiveness and safety. The purpose of this review is to describe the latest knowledge in the etiopathogenesis of the circumscribed choroidal hemangioma, the most recent multimodal imaging findings, and the available treatment options., (© 2023. The Author(s).)

This comprehensive retrospective data-linkage study aimed at evaluating the impact of Direct-Acting Antivirals (DAAs) on Hepatitis C Virus (HCV) testing, treatment trends, and access to care in Tuscany over six years following their introduction. Utilizing administrative healthcare records, our work reveals a substantial increase in HCV tests in 2017, attributed to the decision to provide universal access to treatment. However, despite efforts to eradicate chronic HCV through a government-led plan, the target of treating 6,221 patients annually was not met, and services contracted after 2018, exacerbated by the COVID-19 pandemic. Key findings indicate a higher prevalence of HCV screening among females in the 33-53 age group, influenced by pregnancy-related recommendations, while diagnostic tests and treatment uptake were more common among males. Problematic substance users constituted a significant proportion of those tested and treated, emphasizing their priority in HCV screening. Our paper underscores the need for decentralized HCV models and alternative testing strategies, such as point-of-care assays, especially in populations accessing harm reduction services, communities, and prisons. The study acknowledges limitations in relying solely on administrative records, advocating for improved data access and timely linkages to accurately monitor HCV care cascades and inform regional plans. Despite challenges, the paper demonstrates the value of administrative record linkages in understanding the access to care pathway for hard-to-reach populations. The findings emphasize the importance of the national HCV elimination strategy and the need for enhanced data collection to assess progress accurately, providing insights for future regional and national interventions., (© 2024. The Author(s).)

Purpose: To analyze differences in refractive outcome Δ (difference between postoperative and expected refractive error) and in anterior segment changes between cataract surgery patients and combined phacovitrectomy patients. We also aimed to provide a corrective formula allowing to minimise the refractive outcome Δ in combined surgery patients., Methods: Candidates for phacoemulsification and combined phacovitrectomy (respectively PHACO and COMBINED groups) were prospectively enrolled in two specialised centres. Patients underwent best corrected visual acuity (BCVA) assessment, ultra-high speed anterior segment optical coherence tomography (OCT), gonioscopy, retinal OCT, slit lamp examination and biometry at baseline, 6 weeks postoperatively and 3 months postoperatively., Results: No differences in refractive Δ, refractive error and anterior segment parameters were noted between PHACO and COMBINED group (109 and 110 patients respectively) at 6 weeks. At 3 months, COMBINED group showed a spherical equivalent of -0.29 ± 0.10 D versus -0.03 ± 0.15 D in PHACO group (p = 0.023). COMBINED group showed a significantly higher Crystalline Lens Rise (CLR), angle-to-angle (ATA) and anterior chamber width (ACW) and a significantly lower anterior chamber depth (ACD) and refractive Δ with all 4 considered formulas at 3 months. For IOL power lower than 15, a hyperopic shift was observed instead., Conclusions: Anterior segment OCT suggests anterior displacement of the effective lens position in patients undergoing phacovitrectomy. A corrective formula can be applied to IOL power calculation to minimize undesired refractive error., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Recent evidence suggests that innate lymphoid cells (ILCs) might be involved in rheumatoid arthritis (RA) pathogenesis and individuals at risk of RA exhibited an increased frequency of ILC1. JAK3 participates in ILC1 and ILC3 differentiation. Tofacitinib and the Janus Kinase (JAK) 3 inhibitor, PF-06651600, impair the ability of human intraepithelial ILC1 (iILC1) to produce IFN-γ and the proliferation of ILC1 and ILC3. Our study aims to evaluate the ex vivo effects of tofacitinib in RA patients and to investigate if ILC1s and ILC3s are specific targets of tofacitinib in RA., Methods: Twenty RA patients starting tofacitinib and 10 RA patients starting anti-TNFα were enrolled. Peripheral blood mononuclear cells (PBMCs) from RA patients, collected before and three months after therapy, were cultured to evaluate ILC1 and ILC3 frequencies and the respective production of IFN-γ and IL-17 by flow cytometry analysis. PBMCs of RA patients were in vitro cultured with tofacitinib to evaluate the dose effects on ILC frequencies., Results: RA patients showed a significant expansion of ILC1 but not ILC3. Unlike anti-TNFα treated patients, in whom no reduction in ILCs was reported, after three months of tofacitinib therapy the overall ILC frequency was reduced, as well as the ILC1 ability to release IFN-γ. In vitro treatment of PBMCs with tofacitinib demonstrated a dose-dependent reduction in the frequency of ILCs compared to untreated cells., Conclusions: Our preliminary results demonstrate that tofacitinib modulates the innate immune response by reducing the frequency of ILC1 cells and their production of IFN-γ.

Purpose: To review the literature focusing on the clinical outcomes of KeraKlear (KK) (KeraMed), a foldable intrastromal keratoprosthesis., Methods: We searched 6 databases using 4 keywords: KeraKlear, Foldable Keratoprosthesis, Intrastromal Keratoprosthesis, and Non-penetrating Keratoprosthesis. Included studies had to be conducted in vivo on humans, published until January 3, 2023, and had to investigate the implantation of the KK. Eyes were considered at high risk of keratoprosthesis retention failure whenever there was an active inflammatory ocular surface disorder or in case of previous KK failure. We aimed at recording the postoperative complications, rate of prosthesis retention, and mean improvements in visual acuity., Results: We identified 144 publications, 6 of which (38 eyes) met the inclusion criteria. No randomized controlled trials were found, and some studies had significant limitations regarding sample size and follow-up duration. With a mean follow-up of 28 ± 18.8 months, postoperative complications of any kind occurred between 0% and 50% and 24% had an implant extrusion/needed a reoperation. The mean postoperative visual acuity improvement on the last follow-up was -0.83 ± 0.27 LogMAR, that is, -0.57 ± 0.3 for high-risk and -1.03 ± 0.25 for low-risk eyes, whereas 1 year after implantation, 50% of the prostheses were retained in the former and 81% in the latter group. None of the eyes developed glaucoma, endophthalmitis, or expulsive hemorrhages; none had to be eviscerated/enucleated., Conclusions: Despite the limited quality and quantity of evidence, the available literature seems to suggest the KK to be a valuable tool in the treatment of complicated corneal disorders. Because in many parts of the world, the access to corneal transplantation is limited, this prosthesis could represent a valid alternative., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality and trainees' expectations., Methods: Active or remission rheumatoid arthritis patients were enrolled. Nine trainees joined the 4-month programme in a centre experienced in performing US-guided ST biopsies consisting of four sequential phases: (1) observation, (2) performance of guided step-by-step phases, (3) execution of the whole procedure on paired joints (knees or wrists) of the same patient in parallel with the trainer and (4) performance of the procedure autonomously. Sample representativity was assessed by histology, and procedure-related adverse events were recorded. Before and after the programme, trainees' expectations and perceptions were collected., Results: 328 ST biopsy procedures were included. The rate of trainees' informative samples was: (1) comparable to the trainers in active and remission knees, but lower in active wrists (70% for trainees vs 100% for trainers, p=0.06) in phase 3; (2) excellent on active knees and wrists (91.9% and 90.9% respectively) but lower (77.6%, p=0.0089) on remission knees in phase 4. Procedures performed by trainees did not affect patient tolerability. Trainees' expectations about procedure-related invasiveness and pain infliction decreased while the difficulty of procedure execution on active wrists and remission knees remained perceived as moderately difficult., Conclusions: This intensive training programme develops advanced skills in the performance of US-guided ST biopsy on knees and wrists, yielding high-quality specimens available for basic and translational studies on inflammatory joint diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Antarctic Porifera have gained increasing interest as hosts of diversified associated microbial communities that could provide interesting insights on the holobiome system and its relation with environmental parameters., Methods: The Antarctic demosponge species Haliclona dancoi and Haliclona scotti were targeted for the determination of persistent organic pollutant (i. e., polychlorobiphenyls, PCBs, and polycyclic aromatic hydrocarbons, PAHs) and trace metal concentrations, along with the characterization of the associated prokaryotic communities by the 16S rRNA next generation sequencing, to evaluate possible relationships between pollutant accumulation (e.g., as a stress factor) and prokaryotic community composition in Antarctic sponges. To the best of our knowledge, this approach has been never applied before., Results: Notably, both chemical and microbiological data on H. scotti (a quite rare species in the Ross Sea) are here reported for the first time, as well as the determination of PAHs in Antarctic Porifera. Both sponge species generally contained higher amounts of pollutants than the surrounding sediment and seawater, thus demonstrating their accumulation capability. The structure of the associated prokaryotic communities, even if differing at order and genus levels between the two sponge species, was dominated by Proteobacteria and Bacteroidota (with Archaea abundances that were negligible) and appeared in sharp contrast to communities inhabiting the bulk environment., Discussions: Results suggested that some bacterial groups associated with H. dancoi and H. scotti were significantly (positively or negatively) correlated to the occurrence of certain contaminants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Papale, Giannarelli, Azzaro di Rosamarina, Ghezzi, Lo Giudice and Rizzo.)

Objectives: We studied high-resolution impedance manometry (HRiM) findings in dermatomyositis (DM) to detect oesophageal dysmotility, even in asymptomatic patients, and correlated the alterations to clinical and serological disease domains., Methods: We performed a cross-sectional study of DM patients, enrolled between December 2021 and December 2022. All patients underwent rheumatological, laboratory and HRiM assessment. HRiM findings were compared with different clinical and serological profiles., Results: The study population consisted of 15 DM patients (13 women and 2 men, age 54±15.2 years). The mean disease duration was 6.6 years. According to HRiM findings, three different groups of oesophageal disease severity were identified (in order of severity G0, G1 and G>1, 5 patients per group). G>1 group was significantly associated with MDA5 antibodies (80% vs. 20%, p<0.05). Interstitial lung disease (ILD) did not show any significant association with HRiM findings. However, a diffusing lung capacity for carbon oxide (DLCO) < 80% was present in 100% of G>1 (p<0.05). No associations between dysphagia, creatine kinase (CK) level, muscle weakness, skin, articular involvement and treatment were found., Conclusions: Oesophageal involvement is frequent and should be evaluated in the comprehensive work-up of DM. We used for the first time HRiM in DM, which proved to be an accurate and objective technique in assessing oesophageal disease, even in the subclinical stage. Interestingly, the MDA5-positive group had a higher burden of HRiM pathological findings, suggesting a greater severity of oesophageal involvement, often asymptomatic.

Large-vessel vasculitis (LVV) are autoimmune and autoinflammatory diseases focused on vascular inflammation. The central core of the intricate immunological and molecular network resides in the disruption of the "privileged immune state" of the arterial wall. The outbreak, initially primed by dendritic cells (DC), is then continuously powered in a feed-forward loop by the intimate cooperation between innate and adaptive immunity. If the role of adaptive immunity has been largely elucidated, knowledge of the critical function of innate immunity in LVV is still fragile. A growing body of evidence has strengthened the active role of innate immunity players and their key signaling pathways in orchestrating the complex pathomechanisms underlying LVV. Besides DC, macrophages are crucial culprits in LVV development and participate across all phases of vascular inflammation, culminating in vessel wall remodeling. In recent years, the variety of potential pathogenic actors has expanded to include neutrophils, mast cells, and soluble mediators, including the complement system. Interestingly, new insights have recently linked the inflammasome to vascular inflammation, paving the way for its potential pathogenic role in LVV. Overall, these observations encourage a new conceptual approach that includes a more in-depth study of innate immunity pathways in LVV to guide future targeted therapies.

Purpose: To evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD)., Design: Interventional, open-label study started in January 2021 with follow-up at 12 months (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov NCT04636853 ) ., Participants: Thirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months., Intervention: All 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-gauge needle., Main Outcomes and Measures: Best-corrected visual acuity ( BCVA) with ETDRS letters, central macular thickness using OCT, and atrophic area measured on en face OCT images were assessed at baseline, 1, 3, 6, and 12 months., Results: The BCVA in the treated group was 34.46 ± 20.8 ETDRS at baseline, 40.84 ± 20.52 at 1 month, 40.07 ± 20.34 at 3 months, 39.38 ± 19.84 at 6 months, and 35.84 ± 18.38 at 12 months. In the untreated group , the BCVA was 53 ± 21.1 ETDRS letters at baseline, 51.54 ± 20.99 at 1 month, 46.62 ± 19.47 at 3 months, 46.85 ± 18.58 at 6 months, and 43.92 ± 17.97 at 12 months (2-way analysis of variance: interaction of treatment by eye or time, P = 0.084). Central macular thickness did not show a significant intereye difference at 12 months ( P = 0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months ( P < 0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up., Conclusions: Subretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed to understand whether the CB-PRP could have a role in the GA treatment., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Artificial intelligence (AI)- and deep learning (DL)-based systems have shown significant progress in the field of macular disorders, demonstrating high performance in detecting retinal fluid and assessing anatomical changes during disease progression. This study aimed to validate an AI algorithm for identifying and quantifying prognostic factors in visual recovery after macular hole (MH) surgery by analyzing major optical coherence tomography (OCT) biomarkers. This study included 20 patients who underwent vitrectomy for a full-thickness macular hole (FTMH). The mean diameter of the FTMH was measured at 285.36 ± 97.4 μm. The preoperative best-corrected visual acuity (BCVA) was 0.76 ± 0.06 logMAR, improving to 0.38 ± 0.16 postoperatively, with a statistically significant difference ( p = 0.001). AI software was utilized to assess biomarkers, such as intraretinal fluid (IRF) and subretinal fluid (SRF) volume, external limiting membrane (ELM) and ellipsoid zone (EZ) integrity, and retinal hyperreflective foci (HRF). The AI analysis showed a significant decrease in IRF volume, from 0.08 ± 0.12 mm 3 preoperatively to 0.01 ± 0.01 mm 3 postoperatively. ELM interruption improved from 79% ± 18% to 34% ± 37% after surgery ( p = 0.006), whereas EZ interruption improved from 80% ± 22% to 40% ± 36% ( p = 0.007) postoperatively. Additionally, the study revealed a negative correlation between preoperative IRF volume and postoperative BCVA recovery, suggesting that greater preoperative fluid volumes may hinder visual improvement. The integrity of the ELM and EZ was found to be essential for postoperative visual acuity improvement, with their disruption negatively impacting visual recovery. The study highlights the potential of AI in quantifying OCT biomarkers for managing MHs and improving patient care.

Healthcare-associated infections (HAIs) pose significant challenges in healthcare systems, with preventable surveillance playing a crucial role. Traditional surveillance, although effective, is resource-intensive. The development of new technologies, such as artificial intelligence (AI), can support traditional surveillance in analysing an increasing amount of health data or meeting patient needs. We conducted a scoping review, following the PRISMA-ScR guideline, searching for studies of new digital technologies applied to the surveillance, control, and prevention of HAIs in hospitals and LTCFs published from 2018 to 4 November 2023. The literature search yielded 1292 articles. After title/abstract screening and full-text screening, 43 articles were included. The mean study duration was 43.7 months. Surgical site infections (SSIs) were the most-investigated HAI and machine learning was the most-applied technology. Three main themes emerged from the thematic analysis: patient empowerment, workload reduction and cost reduction, and improved sensitivity and personalization. Comparative analysis between new technologies and traditional methods showed different population types, with machine learning methods examining larger populations for AI algorithm training. While digital tools show promise in HAI surveillance, especially for SSIs, challenges persist in resource distribution and interdisciplinary integration in healthcare settings, highlighting the need for ongoing development and implementation strategies.

Desmosterolosis is a rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, severe developmental delay, progressive epileptic encephalopathy, and elevated levels of desmosterol caused by biallelic mutations of DHCR24 encoding 3-β-hydroxysterol Δ-24-reductase. DHCR24 is regarded as the key enzyme of cholesterol synthesis in the metabolism of brain cholesterol as it catalyzes the reduction of the Δ-24 double bond of sterol intermediates during cholesterol biosynthesis. To date, 15 DHCR24 variants, detected in 2 related and 14 unrelated patients, have been associated with the desmosterolosis disorder. Here, we describe a proband harboring the never-described DHCR24 homozygous missense variant NM&#95;014762.4:c.506T>C, NP&#95;055577.1:p.M169T, whose functional validation was confirmed through biochemical assay. By using molecular dynamics simulation techniques, we investigated the impact of this variant on the protein stability and interaction network with the flavin adenine dinucleotide cofactor, thereby providing a preliminary assessment of its mechanistic role in comparison to all known pathogenic variants, the wild-type protein, and a known benign DHCR24 variant. This report expands the clinical and molecular spectra of the DHCR24-related disorder, reports on a novel DHCR24 deleterious variant associated with desmosterolosis, and gives new insights into genotype-phenotype correlations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cocciadiferro, Mazza, Vecchio, Biagini, Petrizzelli, Agolini, Villani, Minervino, Martinelli, Rizzo, Boenzi, Panfili, Buonuomo, Macchiaiolo, Bartuli and Novelli.)

Background: The question of whether influenza vaccine effectiveness (VE) wanes over the winter season is still open and some contradictory findings have been reported. This study investigated the possible decline in protection provided by the available influenza vaccines., Research Design and Methods: An individual-level pooled analysis of six test-negative case-control studies conducted in Italy between the 2018/2019 and 2022/2023 seasons was performed. Multivariable logistic regression analyses were performed to estimate weekly change in the odds of testing positive for influenza 14 days after vaccination., Results: Of 6490 patients included, 1633 tested positive for influenza. Each week that had elapsed since vaccination was associated with an increase in the odds of testing positive for any influenza (4.9%; 95% CI: 2.0-8.0%) and for A(H3N2) (6.5%; 95% CI: 2.9-10.3%). This decline in VE was, however, significant only in children and older adults. A similar increase in the odds of testing positive was seen when the dataset was restricted to vaccinees only. Conversely, VE waning was less evident for A(H1N1)pdm09 or B strains., Conclusions: Significant waning of VE, especially against influenza A(H3N2), may be one of the factors associated with suboptimal end-of-season VE. Next-generation vaccines should provide more durable protection against A(H3N2).

Background: Protection provided by seasonal influenza vaccination (SIV) may be measured against numerous outcomes, and their heterogeneity may hamper decision-making. The aim of this study was to explore outcomes used for estimation of SIV efficacy/effectiveness (VE) and obtain expert consensus on their importance., Research Design and Methods: An umbrella review was first conducted to collect and map outcomes considered in systematic reviews of SIV VE. A Delphi study was then performed to reach expert convergence on the importance of single outcomes, measured on a 9-point Likert scale, in principal target groups, namely children, working-age adults, older adults, subjects with co-morbidities and pregnant women., Results: The literature review identified 489 outcomes. Following data reduction, 20 outcomes were selected for the Delphi process. After two Delphi rounds and a final consensus meeting, convergence was reached. All 20 outcomes were judged to be important or critically important. More severe outcomes, such as influenza-related hospital encounters and mortality with or without laboratory confirmation, were generally top-ranked across all target groups (median scores ≥8 out of 9)., Conclusions: Rather than focusing on laboratory-confirmed infection per se, experimental and observational VE studies should include more severe influenza-related outcomes because they are expected to exercise a greater impact on decision-making.

Microbial communities first respond to changes of external environmental conditions. Observing the microbial responses to environmental changes in terms of taxonomic and functional biodiversity is therefore of great interest, particularly in extreme environments, where the already extreme conditions can become even harsher. In this study, sediment samples from three different shallow hydrothermal vents in Levante Bay (Vulcano Island, Aeolian Islands, Italy) were used to set up microcosm experiments with the aim to explore the microbial dynamics under changing conditions of pH and redox potential over a 90-days period. The leading hypothesis was to establish under microcosm conditions whether the starting microbial communities of the sediments evolved differently depending on their origin. To profile the dynamics of microbial populations over time, biodiversity, enzymatic profile, total cell abundance estimations, total/respiring cell ratio were estimated by using different approaches. An evident change in the microbial community structure was observed, mainly in the microcosm containing the sediment from the most acidified site, which was characterized by a highly diversified microbial community (in prevalence composed of Thermotoga, Desulfobacterota, Planctomycetota, Synergistota and Deferribacterota). An increase in microbial resistant forms (e.g., spore-forming species) with anaerobic metabolism was detected in all experimental conditions. Differential physiological responses characterized the sedimentary microbial communities. Proteolytic activity appeared to be stimulated under microcosm conditions, whereas the alkaline phosphatase activity was significantly depressed at low pH values, like those that were measured at the station showing intermediate pH-conditions. The results confirmed a differential response of microbial communities depending on the starting environmental conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

One of the main causes of mortality in humans continues to be infectious diseases. Scientists are searching for new alternatives due to the fast increase in resistance of some harmful bacteria to the frontline antibiotics. To effectively treat pathogenic infections, it is crucial to design antibiotics that can prevent the development of pathogenic resistance. For this purpose, a set of 39 quaternary pyridinium and bis-pyridinium salts with different lengths of side alkyl or fluorinated chains, heterocyclic spacers, and counter ions were tested on diverse reference bacterial ATCC (American Type Culture Collection) strains, such as S. aureus and E. coli . Subsequently, 6 out of the 39 pyridinium salts showing relevant MIC (Minimum Inhibitory Concentration) values were tested on clinically isolated, resistant strains of S. aureus , S. epidermids , S. haemolyticus , K. pneumoniae , A. baumannii , and P. aeruginosa . Additional tests have been performed to assess if the minimum concentration detected through MIC assay may limit the growth of biofilms.

Freshwater sponges (Spongillida: Demospongiae), including more than 240 described species, are globally distributed in continental waters (except for Antarctica), where they cover both natural and artificial surfaces. However, fragmentary studies have targeted their microbiome, making it difficult to test hypotheses about sponge-microbe specificity and metabolic relationships, along with the environmental factors playing key roles in structuring the associated microbial communities. To date, particular attention has been paid to sponges (family Lubomirskiidae ) that are endemic to Lake Baikal. Few other freshwater sponge species (e.g., Ephydatia spp., Eunapius spp., and Spongilla lacustris ), from lakes and rivers spanning from Europe to South and North America, have been targeted for microbiological studies. Representatives of the phyla Proteobacteria , Bacteroidetes , and Actinobacteria largely predominated, and high differences were reported between the microbiome of freshwater and marine sponges. Several bacterial strains isolated from freshwater sponges can produce bioactive compounds, mainly showing antibiotic activities, with potential application in biotechnology. Understanding the roles played by sponge microbiomes in freshwater ecosystems is still in its infancy and has yet to be clarified to disentangle the ecological and evolutionary significance of these largely under-investigated microbial communities. This review was aimed at providing the main available information on the composition and biotechnological potential of prokaryotic communities associated with healthy freshwater sponges, as a neglected component of the global sponge microbiome, to stimulate researchers interested in the field.

The decline in children's vaccination coverage and the resurgence of preventable infectious diseases draw attention to parents' vaccine hesitancy. Our study introduces two validated tools to independently assess vaccine hesitancy and health literacy among parents with school-age children. We developed a Vaccine Confidence Index (VCI) from 10 Likert items, exploring their relationships through exploratory and confirmatory factor analyses. We modified the IMETER (Italian medical term recognition test) to measure health literacy. We assessed the internal consistency of the modified IMETER and the 10 Likert items using Cronbach's alpha test (α) and McDonald's omega total coefficient (ω) with good results (ω = 0.92, α = 0.90; ω = 0.87, α = 0.82 respectively). We used these tools within a questionnaire conducted on 743 parents recruited from pediatric clinic waiting rooms in Italy, collecting demographic data, information sources on vaccines and vaccine-preventable diseases knowledge. The VCI resulting from factor analyses consisted of six items on a ten-point Likert scale, reflecting the ratio of positive to negative items. The survey revealed significant variations in the VCI according to individual features such as education, use of social networks, or Health institutions as sources of information. Multivariate logistic regression identified an association between vaccine intention and the VCI. Health literacy was functional for 91.2% of participants, but knowledge about vaccine-preventable diseases was generally low. The VCI showed no significant association with health literacy and vaccine-preventable diseases knowledge. The VCI and the modified IMETER effectively assess vaccination attitude and health literacy, offering valuable public health tools for tailoring vaccination campaigns to hesitant population subgroups.

Different marine sponge species from Tethys Bay, Antarctica, were analyzed for contamination by polyester and polyamide microplastics (MPs). The PISA (Polymer Identification and Specific Analysis) procedure was adopted as it provides, through depolymerization and HPLC analysis, highly sensitive mass-based quantitative data. The study focused on three analytes resulting from the hydrolytic depolymerization of polyesters and polyamides: terephthalic acid (TPA), 6-aminohexanoic acid (AHA), and 1-6-hexanediamine (HMDA). TPA is a comonomer found in the polyesters poly(ethylene terephthalate) (PET) and poly(butylene adipate co terephthalate) (PBAT), and in polyamides such as poly(1,4-p-phenylene terephthalamide) (Kevlar™ and Twaron™ fibers) and poly(hexamethylene terephthalamide) (nylon 6 T). AHA is the monomer of nylon 6. HMDA is a comonomer of the aliphatic nylon 6,6 (HMDA-co-adipic acid) and of semi-aromatic polyamides such as, again, nylon 6 T (HMDA-co-TPA). Except for the biodegradable PBAT, these polymers exhibit high to extreme mechanical, thermal and chemical resistance. Indeed, they are used as technofibers in protective clothing able to withstand extreme conditions as those typical of Antarctica. Of the two amine monomers, only HMDA was found above the limit of quantification, and only in specimens of Haliclona (Rhizoniera) scotti, at a concentration equivalent to 27 μg/kg of nylon 6,6 in the fresh sponge. Comparatively higher concentrations, corresponding to 2.5-4.1 mg/kg of either PBAT or PPTA, were calculated from the concentration of TPA detected in all sponge species. Unexpectedly, TPA did not originate from PET (the most common textile fiber) as it was detected in the acid hydrolysate, whereas the PISA procedure results in effective PET depolymerization only under alkaline conditions. The obtained results showed that sponges, by capturing and concentrating MPs from large volumes of filtered marine waters, may be considered as effective indicators of the level and type of pollution by MPs and provide early warnings of increasing levels of pollution even in remote areas., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefania Giannarelli reports financial support was provided by Government of Italy Ministry of Education University and Research., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

In the frame of the circular economy, bioplastics are considered a good alternative to conventional plastic materials. Until recently, only a few studies have focused on the occurrence and impact of bio-microplastics (bio-MPs) in aquatic environments, and there is a lack of a methodological approach to measure their amount in marine compartments. This research aimed to identify and validate a method for bio-MPs extraction from biota. A chemical digestion protocol suitable for conventional MPs, using potassium hydroxide (KOH), was applied for the detection, in mussels, of MPs made with Mater-Bi (MBi) from socks used in mussel farming. This method was tested on virgin MBi (VMBi) and aged (AMBi) MPs, ranging from 200 to 1000 μm in presence and absence of mussel tissues. Samples were analysed in pre- and post-digestion steps to assess the recovery rate, potential visual and size changes and polymer alteration in different bio-MPs size ranges. Results showed that MBi seems to be affected by KOH under pre-production conditions (VMBi), whereas in the AMBi treatment, which represents the environmentally realistic condition, the presence of fouling due to deployment at sea preserves MBi from the action of the alkaline agent. This approach allowed the recovery of small MPs, generally difficult to extract from biota, in an optimal visual condition and without polymer alteration. Despite the fraction of organic material in the MBi, these results suggested the suitability of this method and provided the assessment of the KOH effects on MBi-MPs under different environmental conditions. Finally, validation tests proved that the KOH protocol represents a reliable approach for detecting bio-MPs in marine organisms. This study is an important starting point for assessing the impact of the bio-MPs on the marine environment and suggests future studies to improve these issues in order to fill the gaps in the field of bioplastics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We assessed fungal diversity in water and sediment samples obtained from five Arctic lakes in Ny-Ålesund (Svalbard Islands, High Arctic) and five Antarctic lakes on Livingston and Deception Islands (South Shetland Islands), using DNA metabarcoding. A total of 1,639,074 fungal DNA reads were detected and assigned to 5980 ASVs amplicon sequence variants (ASVs), with only 102 (1.7%) that were shared between the two Polar regions. For Arctic lakes, unknown fungal taxa dominated the sequence assemblages, suggesting the dominance of possibly undescribed fungi. The phylum Chytridiomycota was the most represented in the majority of Arctic and Antarctic samples, followed by Rozellomycota , Ascomycota , Basidiomycota , and the less frequent Monoblepharomycota , Aphelidiomycota , Mortierellomycota , Mucoromycota, and Neocallimastigomycota . At the genus level, the most abundant genera included psychrotolerant and cosmopolitan cold-adapted fungi including Alternaria , Cladosporium , Cadophora , Ulvella (Ascomycota), Leucosporidium, Vishniacozyma ( Basidiomycota ), and Betamyces ( Chytridiomycota ). The assemblages displayed high diversity and richness. The assigned diversity was composed mainly of taxa recognized as saprophytic fungi, followed by pathogenic and symbiotic fungi.

Background: Artificial intelligence (AI) is a rapidly developing field with the potential to transform various aspects of health care and public health, including medical training. During the "Hygiene and Public Health" course for fifth-year medical students, a practical training session was conducted on vaccination using AI chatbots as an educational supportive tool. Before receiving specific training on vaccination, the students were given a web-based test extracted from the Italian National Medical Residency Test. After completing the test, a critical correction of each question was performed assisted by AI chatbots., Objective: The main aim of this study was to identify whether AI chatbots can be considered educational support tools for training in public health. The secondary objective was to assess the performance of different AI chatbots on complex multiple-choice medical questions in the Italian language., Methods: A test composed of 15 multiple-choice questions on vaccination was extracted from the Italian National Medical Residency Test using targeted keywords and administered to medical students via Google Forms and to different AI chatbot models (Bing Chat, ChatGPT, Chatsonic, Google Bard, and YouChat). The correction of the test was conducted in the classroom, focusing on the critical evaluation of the explanations provided by the chatbot. A Mann-Whitney U test was conducted to compare the performances of medical students and AI chatbots. Student feedback was collected anonymously at the end of the training experience., Results: In total, 36 medical students and 5 AI chatbot models completed the test. The students achieved an average score of 8.22 (SD 2.65) out of 15, while the AI chatbots scored an average of 12.22 (SD 2.77). The results indicated a statistically significant difference in performance between the 2 groups (U=49.5, P<.001), with a large effect size (r=0.69). When divided by question type (direct, scenario-based, and negative), significant differences were observed in direct (P<.001) and scenario-based (P<.001) questions, but not in negative questions (P=.48). The students reported a high level of satisfaction (7.9/10) with the educational experience, expressing a strong desire to repeat the experience (7.6/10)., Conclusions: This study demonstrated the efficacy of AI chatbots in answering complex medical questions related to vaccination and providing valuable educational support. Their performance significantly surpassed that of medical students in direct and scenario-based questions. The responsible and critical use of AI chatbots can enhance medical education, making it an essential aspect to integrate into the educational system., (©Francesco Baglivo, Luigi De Angelis, Virginia Casigliani, Guglielmo Arzilli, Gaetano Pierpaolo Privitera, Caterina Rizzo. Originally published in JMIR Medical Education (https://mededu.jmir.org), 01.11.2023.)

Background: To describe the efficacy and safety of the adjustable system eyeWatch in vitrectomized glacomatous eyes., Methods: Prospective, non-comparative, small case series of 2 patients who underwent glaucoma drainage device implant with the eyeWatch system. Intraocular pressure, number of medications and early and late complications were evaluated., Results: None of the operated eyes developed early or late complications. After 1 week post operatively, the IOP raised at 28 mmHg in the first eye and 25 mmHg in the second one. The eyeWatch Pen was used to open and set the device into position 3 (that means implant half opened) After waiting for 30 min, IOP was 15 mmHg and 11 mmHg, respectively. Thirty days after surgery we set the EyeWatch into position 0 (that means implant full opened) even though the IOP was under control. A new IOP measurement was done and we registered that IOP was 14 mmHg and 10 mmHg respectively, and it remained stable after six months of follow up., Conclusion: In conclusion, in our case series the use of eyeWatch adjustable system allows a safe and gradual regulation of the flow during post-operative management also in vitrectomized eyes. Considering the percentage of hypotony related complications in vitrectomized eyes this system is an effective and safe technique to handle glaucoma in post vitreoretinal surgery eyes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Local anesthesia is commonly adopted in vitreoretinal surgery to reach painless and akinesia surgical condition. Currently, peribulbar anesthesia (PBA) and subtenon injection (STN) are the most widely used methods. We propose a transcaruncular double injection peribulbar technique (TRS) and aim to compare it with both standard PBA and STN injections., Methods: A total of 105 patients underwent TRS, PBA, or STN. A numerical rating scale was used to assess preoperative, postoperative, and intraoperative pain. Best akinesia score and onset and duration of akinesia were evaluated by two independent graders. The need for supplementary injection was also registered., Results: TRS group was characterized by a lower intraoperative numerical rating scale variation and absolute numerical rating scale score both at the beginning of surgery ( P 0.046), after 30 minutes ( P 0.032), and at the end of surgery ( P 0.002) compared with the other groups. The TRS group also showed better akinesia score ( P 0.004), fastest onset ( P 0.002), and longer duration ( P 0.042) compared with both PBA and STN. No injection-related complications were reported in the three groups., Conclusion: The newly proposed transcaruncular PBA provided superior pain control and akinesia level with no additional adverse events.

Jellyfish envenomation is a common problem in coastal areas all over the world; usually symptoms are self-limited with no long-lasting complications. Despite that, some jellyfish species, mainly populating the Indian Ocean, are renown to be potentially lethal and in some cases may cause severe myopathy. We report the first case of rhabdomyolysis following a jellyfish sting in the Mediterranean Sea. A 17-year-old patient was admitted to the intensive care unit of our hospital in life-threatening conditions. He was dyspnoeic and dysphagic with pain and functional impairment of upper and lower limbs. The evidence of a red mark in his face and the clinical presentation, coupled with the diagnostic test performed, allowed the diagnosis of toxidrome from jellyfish venom. Treatment with hydration, ventilatory support and steroids led to a progressive improvement of patient conditions. Our case report stresses the importance of prompt identification and treatment of potential rhabdomyolysis determined by jellyfish and rises awareness on the presence of such venomous species in the Mediterranean Sea., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)