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Background: Mucopolysaccharidosis type VI (MPS VI) is due to a deficiency of the lysosomal enzyme arylsulfatase B (ARSB) that results in multi-organ accumulation of glycosaminoglycans (GAGs). Limitations of current treatments prompted the development of a liver-directed gene therapy clinical trial for MPS VI., Methods: We report the long-term follow-up of patients with MPS VI who discontinued enzyme replacement therapy (ERT) and received a single intravenous infusion of high-dose (6 × 10 12 genome copies/kg) recombinant adeno-associated virus serotype 8 (AAV8) vector expressing ARSB under the control of a liver-specific promoter (ClinicalTrials.gov: NCT03173521). Primary outcomes were safety and urinary GAG excretion. Secondary outcomes were endurance and respiratory function., Findings: Median follow-up time was 45 months (n = 4, three females and one male; age range: 5-10 years). No late-emergent safety events were observed. Patients showed sustained serum ARSB activity (38%-67% of mean healthy reference values), a modest increase in urinary GAG concentrations, and no relevant changes in endurance, cardiac, or pulmonary function. In one of the four patients, ERT was restarted because of elevated urinary GAGs without decreased serum ARSB activity up to about 2.5 years after gene transfer. Liver and spleen size remained within the reference ranges., Conclusions: A single intravenous administration of AAV8.TBG.hARSB was safe and resulted in sustained ARSB expression and a modest increase in urinary GAGs in most patients, thus supporting liver-directed gene therapy for MPS VI., Funding: This study was sponsored by the Telethon Foundation ETS, the European Union, the Isaac Foundation, and the Italian Ministry of University and Research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study examined psychiatric hospitalisation patterns in San Salvatore Hospital in L' Aquila (Italy), during two major crises: the 2009 earthquake and the COVID-19 pandemic lockdown. The investigation spans two four-year periods, from 2008 to 2011 and from 2019 to 2022, with a focus on the trimester around the earthquake and the first wave/lockdown of the pandemic., Methods: We analysed weekly psychiatric unit admissions of adults diagnosed with schizophrenia spectrum disorder, major depression, bipolar disorder, and alcohol/substance use disorder. Four-year periods around the Earthquake and COVID-19 Lockdown were divided into sixteen trimesters, and Generalised linear models were used to analyse the relationship between weekly hospitalisation frequency and trimesters by diagnosis using a Poisson distribution., Results: A total of 1195 and 1085 patients were admitted to the psychiatric ward in the 2008-2011 and 2019-2022 periods, respectively. Weekly hospitalisations in the earthquake trimester were lower than during the previous one for all diagnoses (schizophrenia spectrum: -41.9%, p = 0.040; major depression: -56.7%, p = 0.046; bipolar disorder: -69.1%, p = 0.011; alcohol/substance use disorder: -92.3%, p = 0.013). This reduction persisted for 21, 18, and 33 months after the earthquake for schizophrenia spectrum, bipolar, and alcohol/substance use disorders, respectively. Contrarily, patterns of weekly admissions around the COVID-19 lockdown remained substantially stable in the short term. However, a consistent long-term hospitalisation increase for all diagnoses characterised the first half of 2022 (the cessation of anti-COVID-19 measures; schizophrenia spectrum: +68.6%, p = 0.014; major depression: +133.3%, p = 0.033; bipolar disorder: +180.0%, p = 0.034; alcohol/substance use disorder: +475.0%, p = 0.001)., Conclusions: The present study indicated that exposure to major health crises can have both short- and long-term effects on psychiatric ward admission, holding significant implications for current and future major health emergency management strategies., (© 2024. The Author(s).)

Background: Adverse life occurrences (e.g., severe accidents, violence/abuse, organic disorders such as COVID-19) can elicit traumatic responses that heighten fear, anxiety, and depression. However, scientific research has shown that certain variables, such as self-esteem, based on theories like terror management theory (TMT) and the anxiety-buffering hypothesis (ABH), can mitigate the negative effects of trauma. This study aimed to test the ABH by assessing the buffering role of self-esteem in the relationships among the impact of traumatic experiences, fear, anxiety, and depression., Method: An observational research design was used. This study involved 321 participants who experienced COVID-19 as a traumatic experience. A sequential multiple-mediation model with observed variables (path analysis) was used to test the impact of the traumatic experience on fear, anxiety, and depression, examining the protective role of self-esteem., Results: A path analysis revealed that fear and anxiety mediated the relationship between the impact of the traumatic experience of COVID-19 and depression. Additionally, in line with the ABH, self-esteem was found to mediate the relationship between the predictors and their adverse psychological consequences. This suggests that self-esteem played a buffering role, mitigating the negative impact of traumatic experiences on mental health outcomes., Conclusions: These findings underscore the central mediating role of self-esteem, as well as fear and anxiety, in the pathway from trauma-related factors to depression. These insights advocate for evidence-based interventions aimed at alleviating the psychological suffering associated with traumatic experiences, fostering adaptation, and supporting psychological health.

Adverse life events (e.g., severe accidents, violence/abuse, organic disorders) can elicit traumatic responses characterized by intrusive thoughts, hyperarousal, and avoidance-highlighting the need for sound assessment tools. Also, these traumatic components could heighten anxiety and depression symptoms. This study aims included to: (1) assessing the psychometric properties of the Post-Traumatic Symptom Questionnaire (PTSQ) and delineating clinical cut-offs; (2) investigating how distinct trauma components contribute to anxiety and depression symptoms. Involving 761 participants who experienced a traumatic event, Part I tested the PTSQ psychometric properties, defining clinical cut-offs. Part II tested the impact of traumatic components on anxiety and depression symptoms, using a multiple multivariate latent regression model. PTSQ exhibited exemplary fit indices and robust psychometric properties. Clinically relevant cut-offs were identified. The differential contributions of intrusion, avoidance, and hyperarousal to anxiety and depression symptoms were evaluated, elucidating the strength and nature of these relationships. This study reaffirms the PTSQ as a psychometrically sound and reliable instrument. It underscores the effects of intrusion, avoidance, and hyperarousal on anxiety and depression symptoms in individuals with traumatic experiences. These insights advocate for evidence-based interventions aimed at alleviating the psychological suffering associated with trauma components, fostering adaptation and supporting psychological health., (© 2024. The Author(s).)

Candida auris is considered a nosocomial pathogen of high concern and is currently spreading across the United States. Infection control measures for C. auris focus mainly on healthcare facilities, yet transmission levels may already be significant in the community before outbreaks are detected in healthcare settings. Wastewater-based epidemiology (culture, quantitative PCR, and whole-genome sequencing) can potentially gauge pathogen transmission in the general population and lead to early detection of C. auris before it is detected in clinical cases. To learn more about the sensitivity and limitations of wastewater-based surveillance, we used wastewater-based methods to detect C. auris in a southern Utah jurisdiction with no known clinical cases before and after the documented transfer of colonized patients from bordering Nevada. Our study illustrates the potential of wastewater-based surveillance for being sufficiently sensitive to detect C. auris transmission during the early stages of introduction into a community.

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, (FC) 2.2, P < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, P < 0.0001), and ceramide (FC 2.4, P < 0.0001) levels and bile acid (FC 0.7, P < 0.001), acylcarnitines (FC 0.7, P < 0.001), and cholesterol esters (FC 1.0, P < 0.001) than those of healthy controls, and higher di- (FC 1.1, P < 0.0001; FC 0.9, P < 0.01) and triacylglycerol (FC 6.3, P < 0.0001; FC 3.9, P < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol and triglyceride values correlated with Cer (d16:1/22:0), Cer (d18:1/20:0), Cer (d18:1/20:0(OH)), Cer (d18:1/22:0), Cer (d18:1/23:0), Cer (d18:1/24:1), Cer (d18:2/22:0), Cer (d18:2/24:1). Total cholesterol also correlated with Cer (d18:1/24:0), Cer (d18:2/20:0), HexCer (d16:1/22:0), HexCer (d18:1/18:0), and Hex2Cer (d18:1/20:0). Triglyceridelevels correlated with Cer (d18:0/24:1). Alanine aminotransferase values correlated with Cer (d18:0/22:0), insulin with Cer (d18:1/22:1) and Cer (d18:1/24:1), and HDL with hexosylceramide (HexCer) (d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: COPD management and therapy have been periodically revised to support a more patient-specific approach. Several concerns remain in primary care, such as the proper choice of initial treatment, medication adherence, and missing values for spirometry investigations. These concerns may be exacerbated by inconsistencies between the GOLD23 report and reimbursement criteria, as per the Italian NOTA99, especially for what concerns the assessment of disease severity and related treatment choice. We therefore examined the perception and knowledge of general practitioners (GPs) on COPD management and treatment., Methods: We conducted an exploratory e-Delphi study among 600 GPs. The study examined the COPD-related GP's access to spirometry evaluations in primary care clinics; knowledge on early recognition of COPD and related clinical concerns; perception of the clinical application of the NOTA99; the place in therapy of the triple LABA/LAMA/ICS combination., Results: Among 466 participating GPs (response rate: 70.3%; mean age 52, SD: 14.2; mean years of experience: 21.3, SD: 15) had a good level of knowledge about the GOLD 2023 document and the reimbursement criteria for COPD medications. Nevertheless, a low (34%) direct access to spirometry was reported, along with absence of consensus on the proper choice of initial treatment (especially of use of LABA/LAMA combination), and the re-evaluation of free-triple therapy LABA/LAMA/ICS through specialist's referral., Conclusions: This study captured the domains on which further training for GPs might be implemented to improve the management and treatment of COPD. An extension of this e-Delphi to a larger GPs' panel might further confirm these findings.

Background: Increasing attention to the early stages of psychosis and the identification of symptomatic prodromal states have led to the development of a growing number of screening tools. The 16-item version of the Prodromal Questionnaire (PQ-16) is a worldwide used self-administered tool for this purpose. However, to date, fundamental psychometric properties of PQ-16 were not thoroughly investigated. This study aimed to examine the structural validity, measurement invariance, reliability and other psychometrical properties of the Italian version of the PQ-16 (iPQ-16) in help-seeking individuals and in the general population., Methods: The iPQ-16 was administered to 449 young outpatients attending six community mental health services and to 318 control participants enrolled in educational environment. Confirmatory factor analyses (CFAs), measurement invariance (MI) between the help-seeking group and the general population sample, convergent validity, test-retest reliability, internal consistency, and prevalence analyses were performed. Lastly, the validity of the adopted PQ-16 cut-offs through Receiver Operating Characteristic (ROC) curves plotted against CAARMS diagnoses was also tested., Results: CFAs confirmed the single-factor structure for the iPQ-16 and scalar MI was reached. The iPQ-16 showed high internal consistency, test-retest reliability, convergent validity, and acceptable diagnostic accuracy. ROC analysis suggested a score of ≥4 as best cut-off., Conclusions: The iPQ-16 represents a valid and reliable questionnaire for the assessment of high mental risk in both Italian outpatients and general student population. It has good psychometric properties and is easy to implement as UHR screening for clinical as well as research purposes., (© 2024 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a validated assessment designed to screen cognitive functions and behavioral disorders in amyotrophic lateral sclerosis (ALS). Objective of this study is to determine the factors associated with ECAS impairment in a cohort of ALS patients without a co-morbid diagnosis of dementia, at the time of diagnosis., Methods: We enrolled 71 non-demented ALS patient. We collected clinical and demographic data, ALS familiarity, analysis of the most commonly mutated genes in ALS, ALS Milano Torino Staging System and ALS Functional Rate Scale revised scores, progression rate; finally, we recorded whether symptoms onset involved spinal or bulbar area. The alteration of the ECAS was estimated based on age and education-adjusted-validated cut off for each of the items included in ECAS. A multivariable regression analysis was done., Results: The significant determinants of ECAS alterations were: bulbar onset in both ALS-specific test and total ECAS score; bulbar onset and familiarity in ALS-non-specific test; finally, familiarity and diagnosis delay in ALS-behavioral test. All the subjects carrying C9orf72 mutations had alteration of both total ECAS score and ALS-specific tests., Discussion: At diagnosis, bulbar-onset ALS, family history, diagnosis delay and C9orf72 hexanucleotide repeat expansion may contribute to impairment of ECAS., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Schizophrenia is a severe psychiatric disorder, associated with a reduction in life expectancy of 15-20 years. Available treatments are at least partially effective in most affected individuals, and personal resources such as resilience (successful adaptation despite adversity) and coping abilities (strategies used to deal with stressful or threatening situations), are important determinants of disease outcomes and long-term sustained recovery. Published findings support the existence of a genetic background underlying resilience and coping, with variable heritability estimates. However, genome-wide analyses concerning the genetic determinants of these personal resources, especially in the context of schizophrenia, are lacking. Here, we performed a genome-wide association study coupled with accessory analyses to investigate potential genetic determinants of resilience, coping and self-esteem in 490 schizophrenia patients. Results revealed a complex genetic background partly overlapping with that of neuroticism, worry and schizophrenia itself and support the importance of social aspects in shapingthese psychological constructs. Hippocampal neurogenesis and lipid metabolism appear to be potentially relevant biological underpinnings, and specific miRNAs such as miR-124 and miR-137 may warrant further studies as potential biomarkers. In conclusion, this study represents an important first step in the identification of genetic and biological correlates shaping resilience, coping resources and self-esteem in schizophrenia., 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 © 2024. Published by Elsevier B.V.)

Objective: To develop and validate a score to predict the 90-day risk of hospitalization/death in patients with low respiratory tract infections (LRTIs) with the aim to support clinical decision making on vaccine (co)-administration., Methods: We formed a cohort of patients aged 18 years or older being diagnosed with LRTIs in the period between January 1, 2012 and December 31, 2022. Each patient was followed until occurrence of respiratory-related hospitalization/death up to the end of the study period (December 31, 2022). Along with age and sex, forty determinants were adopted to assemble the respiratory tract infection (RTI)-Health Search (HS) core using the development sub-cohort. The prediction accuracy of the score was therefore assessed in the validation sub-cohort., Results: We identified 252,319 patients being diagnosed with LRTIs (females: 54.7 %; mean age: 60 (SD:18.1)). When the risk of LRTIs-related hospitalizations/deaths was estimated via RTI-HScore, its predicted value was equal to 1.4 % over a 90-day event horizon. The score showed explained variation and discrimination accuracy were equal to 45 % (95 % CI: 44-47 %) and 81 % (95 % CI: 79-84 %), respectively. The calibration slope did not significantly differ from the unit (p = 0.8314)., Conclusions: The RTI-HScore was featured by good accuracy for prediction of LRTIs-related complications over a 90-day follow-up. Such a tool might therefore support general practitioners to enhance patients' care by facilitating approaches for (co)-administration of vaccines for respiratory infections through a score-based decision support system., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FL, EM and IC provided consulting for protocol preparation for epidemiological studies and data analyses for GSK, Pfizer, Moderna, Sanofi, MSD and Seqirus. AR and CC provided clinical consulting for GSK, Pfizer, Moderna, Sanofi, MSD and Seqirus. AD provided consultancies and received speaker fees from CSL Seqirus, GSK and SD Biosensor. GI provided consultancies and/or received grants for conducting experimental and/or observational studies for GSK, Sanofi, MSD, CSL Seqirus and Pfizer. IC is an employee at Genomedics SRL., (Copyright © 2024. Published by Elsevier Ltd.)

This paper presents a comprehensive study of hydrogenated amorphous silicon (a-Si)-based detectors, utilizing electrical characterization, Raman spectroscopy, photoemission, and inverse photoemission techniques. The unique properties of a-Si have sparked interest in its application for radiation detection in both physics and medicine. Although amorphous silicon (a-Si) is inherently a highly defective material, hydrogenation significantly reduces defect density, enabling its use in radiation detector devices. Spectroscopic measurements provide insights into the intricate relationship between the structure and electronic properties of a-Si, enhancing our understanding of how specific configurations, such as the choice of substrate, can markedly influence detector performance. In this study, we compare the performance of a-Si detectors deposited on two different substrates: crystalline silicon (c-Si) and flexible Kapton. Our findings suggest that detectors deposited on Kapton exhibit reduced sensitivity, despite having comparable noise and leakage current levels to those on crystalline silicon. We hypothesize that this discrepancy may be attributed to the substrate material, differences in film morphology, and/or the alignment of energy levels. Further measurements are planned to substantiate these hypotheses.

Objective: To identify differentially expressed genes in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA) with different histological patterns of inflammation: transmural inflammation (TMI) and inflammation limited to adventitia (ILA), compared with normal TABs from patients without GCA., Methods: Expression of 770 immune-related genes was profiled with the NanoString nCounter PanCancer Immune Profiling Panel on formalin-fixed paraffin-embedded TABs from 42 GCA patients with TMI, 7 GCA patients with ILA and 7 non-GCA controls., Results: Unsupervised clustering of the samples revealed two distinct groups: normal TABs and TABs with ILA in one group, 41/42 TABs with TMI in the other one. TABs with TMI showed 31 downregulated and 256 upregulated genes compared with normal TABs; they displayed 26 downregulated and 187 upregulated genes compared with TABs with ILA (>2.0 fold changes and adjusted p values <0.05). Gene expression in TABs with ILA resembled normal TABs although 38 genes exhibited >2.0 fold changes, but these changes lost statistical significance after Benjamini-Yekutieli correction. Genes encoding TNF superfamily members, immune checkpoints, chemokine and chemokine receptors, toll-like receptors, complement molecules, Fc receptors for IgG antibodies, signalling lymphocytic activation molecules, JAK3, STAT1 and STAT4 resulted upregulated in TMI., Conclusions: TABs with TMI had a distinct transcriptome compared with normal TABs and TABs with ILA. The few genes potentially deregulated in ILA were also deregulated in TMI. Gene profiling allowed to deepen the knowledge of GCA pathogenesis., 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.)

A considerable proportion of patients with schizophrenia perform below population norms on standardized neuropsychological tests, and the performance of those performing within normal range is lower than predicted based on parental education. Cognitive impairment predates the onset of psychosis, is observed during symptom remission and in non-affected first-degree relatives of patients. At the present time, cognitive deficits are regarded as key features of schizophrenia, important determinants of poor psychosocial outcome and targets for both pharmacological and non-pharmacological treatment strategies. A group of eight key opinion leaders reviewed and discussed latest advances in scientific research and current good clinical practices on assessment, management, and treatment of CIAS. In the present paper they summarize the current evidence, identify main gaps between current knowledge and mental health services clinical practice, and provide practical recommendations to reduce the gap., Competing Interests: SB received advisory board, lecture, or consulting fees, outside the present work, from: Angelini, Janssen Pharmaceuticals, Lundbeck, Otsuka. RC received advisory board fees from Boehringer and was a speaker for Rovi. SG reports consulting fees from Gedeon Richter; honoraria from Angelini, Boehringer Ingelheim, Gedeon Richter, Janssen, Lundbeck, Otsuka, Recordati, Rovi; and participation on data safety monitoring boards with Angelini, Boehringer Ingelheim, Janssen, and Rovi. AM received advisory board or consultant fees from the following drug companies: Angelini, Rovi and Boehringer Ingelheim outside the submitted work. MR has received compensation as speaker/consultant from Angelini, Lundbeck, Otzuka, Sumitomo Pharma, and Sunovion, and he has received research grants from Sumitomo Pharma. PR has received honoraria as consultant for lectures from Angelini, Janssen, Lundbeck, and Otsuka. Furthermore, she is in the advisory board of Angelini. AV received advisory board, lecture, or consulting fees, outside the present work, from: Angelini, Innova Pharma-Recordati, Janssen Pharmaceuticals, Lundbeck, Otsuka, and Pfizer. The remaining author declares 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 Vita, Barlati, Cavallaro, Mucci, Riva, Rocca, Rossi and Galderisi.)

(1) Background: Experiencing intimate partner violence (IPV) can greatly impact victims' physical and mental health, often leading to post-traumatic stress disorder (PTSD). Emotion regulation has been identified in the literature as a factor that contributes to the manifestation of PTSD. Consequently, this study aims to investigate the relationship among the increase in IPV victimization (i.e., physical, psychological, sexual, and economic violence), emotion dysregulation, and PTSD symptoms. It has been hypothesized that emotion dysregulation may mediate the increase in IPV occurrence and PTSD symptoms. (2) Methods: 284 women (M age = 40.92) exposed to IPV were recruited in Italy. IPV experience was screened using the Revised Conflict Tactic Scale questionnaire. A mediational analysis was performed using Rstudio. (3) Results: The findings corroborated the mediating role of emotion dysregulation: the relationship between the increase in IPV and PTSD symptoms appears to be mediated by emotion dysregulation. (4) Conclusions: These findings bolster the existing literature regarding the association between emotion dysregulation and PTSD, underscoring the important role of emotion dysregulation in trauma symptoms. This highlights the significance of prioritizing the treatment of emotion dysregulation as a focal point for intervention and support for those who have experienced IPV.

Lysosomal storage disorders (LSDs) are multisystemic progressive disorders caused by defects in proteins involved in lysosomal function. Different gene therapy strategies are under clinical investigation in several LSDs to overcome the limitations of available treatments. However, LSDs are slowly progressive diseases that require long-term studies to establish the efficacy of experimental treatments. Biomarkers can be reliable substitutes for clinical responses and improve the efficiency of clinical trials, especially when long-term disease interventions are evaluated. In this review, we summarize both available and future biomarkers for LSDs and discuss their strengths and weaknesses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background : In recent years, Europe has experienced a significant increase in pertussis cases. One reason behind this rise is the decline in diphtheria-tetanus-pertussis (dTap) booster coverage among adults. Currently, Italy lacks a reliable monitoring system to track pertussis infections and vaccine coverage among adults. We therefore evaluated the reliability of a primary care framework to respond to this need. Methods : Using an Italian primary care database for individuals aged 15 or above, we determined the pertussis infection notification rate and dTap vaccine/booster coverage for the timeframe of 2009-2022. Results : In the overall population, we obtained a lifetime occurrence rate of pertussis infections of 7.52 per 10,000 individuals. The annual incidence rates of pertussis infections ranged from 0.008 to 0.001 per 10,000 person-years between 2009 and 2022. A rising trend in dTap vaccine coverage rate (ranging from 8.72 to 16.54 vaccines per 10,000 individuals) was observed during the same period. Notably, those aged 65 or older, smokers, and/or individuals with immunodeficiencies were more likely to receive the dTap vaccine compared to the general population. Conclusions : Given the organization of the Italian public health system, this primary care network might act as a reliable epidemiological monitoring system to keep track of pertussis infections and dTap vaccine coverage in adults. Pertussis cases were underreported, and there was a low uptake of vaccines and boosters. Therefore, it is crucial to closely monitor pertussis notifications and dTap administrations and develop intervention strategies at the national level to enhance vaccine-related prevention.

Background: Cohort data on continuous glucose monitoring (CGM) metrics are scarce for liver glycogen storage diseases (GSDs) and idiopathic ketotic hypoglycemia (IKH). The aim of this study was to retrospectively describe CGM metrics for people with liver GSDs and IKH., Patients and Methods: CGM metrics (descriptive, glycemic variation and glycemic control parameters) were calculated for 47 liver GSD and 14 IKH patients, categorized in cohorts by disease subtype, age and treatment status, and compared to published age-matched CGM metrics from healthy individuals. Glycemic control was assessed as time-in-range (TIR; ≥3.9 - ≤7.8 and ≥3.9 - ≤10.0 mmol/L), time-below-range (TBR; <3.0 mmol/L and ≥3.0 - ≤3.9 mmol/L), and time-above-range (TAR; >7.8 and >10.0 mmol/L)., Results: Despite all patients receiving dietary treatment, GSD cohorts displayed significantly different CGM metrics compared to healthy individuals. Decreased TIR together with increased TAR were noted in GSD I, GSD III, and GSD XI (Fanconi-Bickel syndrome) cohorts (all p < 0.05). In addition, all GSD I cohorts showed increased TBR (all p < 0.05). In GSD IV an increased TBR (p < 0.05) and decreased TAR were noted (p < 0.05). In GSD IX only increased TAR was observed (p < 0.05). IKH patient cohorts, both with and without treatment, presented CGM metrics similar to healthy individuals., Conclusion: Despite dietary treatment, most liver GSD cohorts do not achieve CGM metrics comparable to healthy individuals. International recommendations on the use of CGM and clinical targets for CGM metrics in liver GSD patients are warranted, both for patient care and clinical trials., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest related to the content of this manuscript. R.J.O.: There are confidentiality agreements with third parties. There is a consultation agreement (with Ultragenyx Pharmaceutical Inc). For all private-public relationships, all contracts are via UMCG Contract Research Desk and all payments are to UMCG. A.V., C.M.A.L.: No conflicts of interest. M.J.F.W., F.D.B., A.B.S.: There are confidentiality agreements with third parties. For all private-public relationships, all contracts are via UMCG Contract Research Desk and all payments are to UMCG. A.R.: There are confidentiality agreements with third parties. In the past 36 months there have been consultation agreements or honoraria for lectures or presentations with Nestlé, Danone and Ultragenyx Pharmaceutical Inc. T.G.J.D.: There are confidentiality agreements with third parties. In the past 36 months, there have been consultation agreements (with Danone, Ultragenyx Pharmaceutical Inc, ModernaTX Inc., and Beam Therapeutics), contracts for financial research support for investigator-initiated research (NCT04311307) and sponsor-initiated research (NCT03517085, NCT03970278, NCT05139316, and NCT05196165), honoraria for lectures or presentations (by MEDTalks, Prelum, and Danone), and participations in a Data Safety Monitoring Board (NCT05095727) and Advisory Boards (Ultragenyx Pharmaceutical Inc, ModernaTX Inc., and Beam Therapeutics). For all private-public relationships, all contracts are via UMCG Contract Research Desk and all payments are to UMCG., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Testing serum C-reactive protein (CRP) levels can help determine whether there is a need for antibiotics and can limit prescribing of antibiotics for illnesses that are likely viral or non-infectious in origin. Using Health Search, an Italian primary care database, we identified all patients, aged 15 years or older, being registered in the period between 1 January 2000 and 31 December 2019 and newly diagnosed with upper respiratory tract infections (URTIs) or COPD- or asthma-related exacerbations. From the date of these diagnoses, patients were followed up until occurrence of antibiotic prescription (for these indications) up to 31 December 2019. The association between the CRP testing and the outcome was investigated using a nested case-control analysis. In a cohort of 469 684 patients being diagnosed for URTI (83%), COPD- (11%) and asthma (7%)-related exacerbations, 28 688 (6.11%) were prescribed with antibiotics because of the aforementioned indications. Of note, 98% of cases, nominally those prescribed with antibiotics, were not tested with CRP. However, those receiving antibiotics were more likely to have been previously tested for CRP than controls who did not receive antibiotics (833/28 601 [3%] and 4128/277 968 [1.5%]; OR 2.0 [95% CI: 1.8-2.1]). Our findings indicate that most of the antibiotic prescriptions for the investigated conditions were given without any prior CRP testing. A small minority of GPs did properly use CRP to determine whether antibiotics were needed. Further guidance is needed in Italy on the use of CRP in guiding antibiotic prescribing in primary care., (© 2024 British Pharmacological Society.)

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative., (© 2023. The Author(s).)

Background: Colorectal cancer currently presents the third-highest incidence of cancers worldwide, making secondary prevention through screening programs for colorectal cancer, usually by Fecal Occult Blood Testing, an essential preventive medicine intervention. First-degree relatives of colorectal cancer patients are a particularly at-risk group, with indications to consider direct screening by full colonoscopy. Colonoscopy is considered the gold standard for diagnosing colorectal cancer, as it has high sensitivity and specificity, and is both a diagnostic and therapeutic tool. However, it requires significant organizational and financial resources, and has a small but relatively higher risk of complications as opposed to fecal occult blood testing. The present study aimed to assess the appropriateness of a screening program without age restrictions of CRC by full colonoscopy in asymptomatic, first-degree adult relatives of patients with colorectal cancer, aiming both to actively increase screening coverage and to determine the detection rate of precancerous lesions and colorectal cancer in this population., Study Design: Uncontrolled interventional study - colorectal cancer screening by full colonoscopy for at-risk population., Methods: The Italian League for the Fight against Cancer started a colorectal cancer screening program by full colonoscopy for first-degree relatives of colorectal cancer patients in 1998 in the province of Latina, Lazio Region, Italy. The program was expanded to the provinces of Rieti, Lazio Region, and Sassari, Sardinia Region, in 2014 and 2016 respectively, and was concluded in 2018. Subjects were actively and voluntarily recruited by the study's working group. Subjects that had already been subjected to a full colonoscopy in the preceding 5 years were excluded from this study. Identified neoplastic lesions were treated either directly or referred to the Day Hospital setting, and histologically diagnosed following World Health Organization guidelines., Results: In total, 2,288 subjects (age range 15-88, mean 52.3 yrs, M/F = 946/1,204) were screened by colonoscopy, of which 103 (4.5%) were incomplete and 2,173 (95.0%) complete, with data on colonoscopy performance missing for 12 participants. Out of 468 positive outcomes on colonoscopy, diagnosis for 422 (204M/173F), 19.4% of total subjects, was adenomatous polyps and 46 (20M/20F), 2.1% of total subjects, was colorectal cancer. Female sex was a protective factor against a positive test outcome, with a 35% reduction compared to male sex, with OR=0.64 95%CI (0.52-0.80). On the other hand, being over 50 years of age was found to be a risk factor, making a positive outcome more than twice as likely, with OR=2.3 95%CI (1.8-2.9). Subjects over 50 also had significantly more instances of multiple adenomas being found, however the size distribution of found adenomas was not significantly different between subjects under and over 50, despite size being a predictor of risk of neoplastic progression., Conclusions: Given the high detection rate of precancerous lesions and colorectal cancer in the studied population, it is our opinion that guidelines should continue to recommend earlier and more frequent screening in first-degree relatives of patients with colorectal cancer, and, barring the introduction of more cost-effective and/or lower risk procedures with a similar efficacy profile, maintain the use of colonoscopy as the main screening option.

Background: Seasonal influenza vaccination coverage in Italian older adults is insufficient and well below the minimum target of 75%. In Italy, most influenza vaccine doses are administered by general practitioners (GPs), whose number has been declining. In parallel, the number of patients per GP and GP workload increased dramatically, which theoretically may impair vaccination counselling. In this ecological study, we aimed to assess whether influenza vaccination coverage in older adults is associated with the density of GPs having high number of patients., Methods: The study outcome was the influenza vaccination coverage rate in adults aged ≥ 65 years and registered in 20 Italian regions over the last 23 years. The independent variable of interest was the proportion of GPs with more than 1,500 adult patients, which is an imposed normative ceiling. This latter variable was considered as a proxy of GP overload. By adopting a panel regression approach, different specifications of fixed- and random-effects models were run to assess the association of interest, when adjusted for several social structural, economic and healthcare-related variables., Results: Over the last two decades, most regions showed a negative association between influenza vaccination coverage rates and the density of GPs with a high number of patients. This latter negative association was confirmed (P < 0.05) in different panel model specifications. In particular, in the fully adjusted two-way fixed-effects model, each 10% increase in the number of GPs with more than 1,500 patients was associated with a 1.7% decrease in influenza vaccination coverage. However, this association was present only in region-years where at least 18% of GPs were deemed overloaded., Conclusions: In the upcoming years, the number of Italian GPs is projected to decline further. At the same time, the aging Italian population will determine an even greater workload for GPs. This study demonstrated that increased GP workload may partially explain the spatiotemporal variation in influenza vaccination uptake in the Italian elderly. With the imperative of increasing or at least maintaining influenza vaccination coverage rates, several short- and mid-term initiatives should be implemented in order to optimize GP workload during seasonal immunization campaigns., (© 2024. The Author(s).)

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). It is approved as a coprimary measure of performance-based instruments, such as the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Recent research highlights negative symptoms, social cognition, and functional capacity as mediators of cognitive impairment's impact on functioning. This study compared mediation analysis outcomes using CAI or MCCB scores, providing insights into the utility of interview-based tools in research and clinical practice. The study included 618 individuals diagnosed with schizophrenia, recruited from 24 Italian psychiatric clinics. Neurocognitive assessments utilized both CAI and MCCB. Mediation analyses explored negative symptoms, social cognition, and functional capacity as mediators of the impact of neurocognition on real-life functioning domains. The study's results extend the validation of the CAI as a coprimary measure that provides valid information on the impact of cognitive impairment on real-life functioning and its possible mediators, complementing the information obtained using the MCCB. Interview-based cognitive assessment might be essential for understanding schizophrenia complexity and its impact on various cognitive and functional domains for clinicians, patients, and caregivers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Background: The development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain resting-state (rs)-activity with disease-related features., Methods: Sixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables., Results: Attention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity., Conclusion: Neurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes., 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 Giuliani, Pezzella, Giordano, Fazio, Mucci, Perrottelli, Blasi, Amore, Rocca, Rossi, Bertolino, Galderisi and Maj.)

Hepatic glycogen storage diseases constitute a group of disorders due to defects in the enzymes and transporters involved in glycogen breakdown and synthesis in the liver. Although hypoglycemia and hepatomegaly are the primary manifestations of (most of) hepatic GSDs, involvement of the endocrine system has been reported at multiple levels in individuals with hepatic GSDs. While some endocrine abnormalities (e.g., hypothalamic‑pituitary axis dysfunction in GSD I) can be direct consequence of the genetic defect itself, others (e.g., osteopenia in GSD Ib, insulin-resistance in GSD I and GSD III) may be triggered by the (dietary/medical) treatment. Being aware of the endocrine abnormalities occurring in hepatic GSDs is essential (1) to provide optimized medical care to this group of individuals and (2) to drive research aiming at understanding the disease pathophysiology. In this review, a thorough description of the endocrine manifestations in individuals with hepatic GSDs is presented, including pathophysiological and clinical implications., (© 2024. The Author(s).)

Introduction: Income inequality, a pivotal determinant of general and mental health, operates through intricate mechanisms at various geographical scales. While established at country or region levels, the impact of lower-level (municipal or neighborhood) inequality remains inconsistent. This study explores the influence of regional- and municipal-level income inequality on individual psychological distress during the COVID-19 pandemic in Italy, employing a multilevel data analysis., Materials and Methods: In a post hoc analysis of data from the first wave of the pandemic (March to April 2020), three hierarchical levels were considered: individual participants, municipalities, and regions. Depressive and anxiety symptoms were measured using the PHQ-9 and GAD-7 scales, while the Gini coefficient gauged income inequality at municipal and regional levels. The analysis incorporated demographic variables as potential confounders., Results: The study encompassed 21 regions, 3,900 municipalities, and 21,477 subjects. Income inequality at both regional and municipal levels exhibited associations with distress scores, suggesting independent effects. Notably, higher distress scores were identified in southern regions with elevated inequality, despite a more substantial COVID-19 impact in the north., Discussion: Findings contribute to existing literature by emphasizing the independent impact of lower-level (municipal) and higher-level (regional) income inequality on population psychopathology. The study supports theories suggesting diverse pathways through which inequality at different levels influences health, such as potential associations with healthcare system dysfunction at the regional level and welfare dysfunction at the municipal level. The observed north-south gradient in distress scores highlights the need for psychosocial interventions to alleviate income inequality, especially in historically disadvantaged southern regions. Future research should explore the nuanced interplay between income inequality and various ecological variables to provide a comprehensive understanding of its health impact.

Images collected during NASA's Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters. Didymos' moon, Dimorphos, possesses an intimate mixture of boulders, several asteroid-wide lineaments, and a handful of craters. The surfaces of both asteroids include boulders that are large relative to their host body, suggesting that both asteroids are rubble piles. Based on these observations, our models indicate that Didymos has a surface cohesion ≤ 1 Pa and an interior cohesion of ∼10 Pa, while Dimorphos has a surface cohesion of <0.9 Pa. Crater size-frequency analyzes indicate the surface age of Didymos is 40-130 times older than Dimorphos, with likely absolute ages of ~ 12.5 Myr and <0.3 Myr, respectively. Solar radiation could have increased Didymos' spin rate leading to internal deformation and surface mass shedding, which likely created Dimorphos., (© 2024. The Author(s).)

Aims: Cardiac resynchronization therapy (CRT) may induce left ventricular (LV) reverse remodelling (=LV response) in patients with heart failure. Intraventricular pressure gradients can be quantified using echocardiography-derived haemodynamic forces (HDF). The aim was to evaluate the association between baseline HDF and LV response and to compare the change of HDF after CRT between LV responders and LV non-responders., Methods and Results: The following HDF parameters were assessed: 1)apical-basal (AB) strength, 2)lateral-septal strength, 3)force vector angle, 4)systolic AB impulse, 5)systolic force vector angle. LV response was defined as a reduction of LV end-systolic volume ≥15% at six months. One hundred ninety-six patients were included (64±11 years, 122(62%) men), 136(69%) showed LV response. On multivariable logistic regression analysis, the force vector angle in the complete heart cycle (OR 1.083 (95%CI 1.018, 1.153), p=0.012) and the systolic force vector angle (OR 1.089 (95%CI 1.021, 1.161), p=0.009), both included in separate models, were independently associated with LV response. Six months after CRT, LV responders had greater AB strength, AB impulse and higher force vector angles, while LV non-responders only showed improvement in the force vector angle in the complete heart cycle., Conclusion: The orientation of HDF at baseline is associated with LV response to CRT. Six months after CRT, the orientation of HDF improves in LV responders and LV non-responders, while the magnitude of AB HDF only improves in LV responders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

3-methylcrotonyl-CoA carboxylase deficiency (3MCCD) is a hereditary disorder of leucine catabolism caused by pathogenetic variants in the MCCC1 or MCCC2 genes. Typically diagnosed through newborn screening (NBS), 3MCCD is characterized by elevation of 3-hydroxyisovalerylcarnitine (C5OH) in blood as well as increased excretion of 3-methylcrotonylglycine (3-MCG) in urine. While most diagnosed children remain asymptomatic, data on adults are scarce. To date, only 39 molecularly confirmed adult individuals have been reported, all being mothers diagnosed subsequent to their child NBS results. Herein, we present a 36-year-old asymptomatic man who was incidentally diagnosed with 3MCCD following his son NBS recall. Molecular analysis revealed compound heterozygosity for two pathogenic variants in the MCCC1 gene. This is the first molecularly confirmed adult man with 3MCCD reported. This case highlights the need for additional longitudinal follow-up data on individuals with 3MCCD to clarify the clinical significance of this condition and guide clinical practice, including NBS strategy., Competing Interests: The authors declare that there is no potential conflict of interest related to this work., (© 2024 The Authors. Published by Elsevier Inc.)

Empagliflozin has been successfully repurposed for treating neutropenia and neutrophil dysfunction in patients with glycogen storage disease type 1b (GSD 1b), however, data in infants are missing. We report on efficacy and safety of empagliflozin in infants with GSD 1b. This is an international retrospective case series on 21 GSD 1b infants treated with empagliflozin (total treatment time 20.6 years). Before starting empagliflozin (at a median age of 8.1 months with a median dose of 0.3 mg/kg/day) 12 patients had clinical signs and symptoms of neutrophil dysfunction. Six of these previously symptomatic patients had no further neutropenia/neutrophil dysfunction-associated findings on empagliflozin. Eight patients had no signs and symptoms of neutropenia/neutrophil dysfunction before start and during empagliflozin treatment. One previously asymptomatic individual with a horseshoe kidney developed a central line infection with pyelonephritis and urosepsis during empagliflozin treatment. Of the 10 patients who were treated with G-CSF before starting empagliflozin, this was stopped in four and decreased in another four. Eleven individuals were never treated with G-CSF. While in 17 patients glucose homeostasis remained stable on empagliflozin, four showed glucose homeostasis instability in the introductory phase. In 17 patients, no other side effects were reported, while genital (n = 2) or oral (n = 1) candidiasis and skin infection (n = 1) were reported in the remaining four. Empagliflozin had a good effect on neutropenia/neutrophil dysfunction-related signs and symptoms and a favourable safety profile in infants with GSD 1b and therefore qualifies for further exploration as first line treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Deficits in social cognition (SC) interfere with recovery in schizophrenia (SZ) and may be related to resting state brain connectivity. This study aimed at assessing the alterations in the relationship between resting state functional connectivity and the social-cognitive abilities of patients with SZ compared to healthy subjects. We divided the brain into 246 regions of interest (ROI) following the Human Healthy Volunteers Brainnetome Atlas. For each participant, we calculated the resting-state functional connectivity (rsFC) in terms of degree centrality (DC), which evaluates the total strength of the most powerful coactivations of every ROI with all other ROIs during rest. The rs-DC of the ROIs was correlated with five measures of SC assessing emotion processing and mentalizing in 45 healthy volunteers (HVs) chosen as a normative sample. Then, controlling for symptoms severity, we verified whether these significant associations were altered, i.e., absent or of opposite sign, in 55 patients with SZ. We found five significant differences between SZ patients and HVs: in the patients' group, the correlations between emotion recognition tasks and rsFC of the right entorhinal cortex (R-EC), left superior parietal lobule (L-SPL), right caudal hippocampus (R-c-Hipp), and the right caudal (R-c) and left rostral (L-r) middle temporal gyri (MTG) were lost. An altered resting state functional connectivity of the L-SPL, R-EC, R-c-Hipp, and bilateral MTG in patients with SZ may be associated with impaired emotion recognition. If confirmed, these results may enhance the development of non-invasive brain stimulation interventions targeting those cerebral regions to reduce SC deficit in SZ., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Patients with cancer can be immunocompromised because of their disease and/or due to anticancer therapy. In this population, severe influenza virus infections are associated with an elevated risk of morbidity and mortality. Influenza vaccination is therefore highly recommended in cancer patients, including those receiving anticancer therapy. However, vaccination coverage remains far below the recommended target for vulnerable subjects. Six specialists in oncology, hematology, immunology, and public health/vaccinology convened with the objective of developing strategies, based on evidence and clinical experience, for improving influenza vaccination coverage in cancer patients. This viewpoint provides an overview of current influenza vaccination recommendations in cancer patients, discusses barriers to vaccination coverage, and presents strategies for overcoming said barriers. New immunization issues raised by the COVID-19 pandemic are also addressed. Future directions include improving public education on influenza vaccination, providing the media with accurate information, improving knowledge among healthcare professionals, improving access to vaccines for cancer patients, co-administration of the influenza and COVID-19 vaccines, increased collaboration between oncologists and other health professionals, increased accessibility of digital vaccination registries to specialists, shared information platforms, and promoting immunization campaigns by healthcare systems with the support of scientific societies.

Background: Viral infections are the main original cause of recurrent respiratory tract infections (RRTIs), but their complications and recurrences are due to bacteria as well. While some operational definitions and epidemiology of RRTIs are reported in paediatrics, no similar definitions have been proposed for adults., Aim: To assess the epidemiology and characteristics of RRTIs in the adult population., Design and Setting: Cohort study in the primary care setting., Methods: Using the Health Search Database, we selected a cohort of patients aged 18 years or older between 2002 and 2022. Yearly, we counted upper and lower respiratory tract infections (RTIs) per patient. We investigated 2 cut-offs defining RRTIs, nominally 3+ RRTIs/patient/year or greater than the mean value of RTIs/patient/year. The associations between these two event definitions and the correlates defining the patients' vulnerability were assessed by estimating a logistic regression model., Results: Over the study years, the mean number of RTIs/patient/year ranged from 0.07-0.16 or 1.10-1.13 events, when the denominator was formed by the overall population or those diagnosed with RTIs, respectively. When the analysis was focussed on 2022, we obtained 0.2% (1.3% among those with RTIs) or 13% (11.3% among those with RTIs) cases of RRTIs, using a cut-off of 3+ or >=0.16 events (mean value/patient), respectively. Consistent associations were found for these two operational definitions and the investigated clinical correlates., Conclusion: We provided evidence on the epidemiology and concurrent/predisposing factors of RRTIs in adults. These data should support health authorities and general practitioners for the application of the most appropriate preventive and/or treatment strategies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Breast cancer (BC) treatment has recently been revolutionized by the introduction of newer targeted agents, that helped tailoring therapies around the single patient. Along with increased survival rates, a careful evaluation of diet, lifestyle habits, physical activity, emotional and psychological experiences linked to the treatment journey, is now mandatory. However, a true proposal for an omnicomprehensive and "integrative" approach is still lacking in literature., Methods: A scientific board of internationally recognized specialists throughout different disciplines designed a shared proposal of holistic approach for BC patients., Results: A narrative review, containing information on BC treatment, endocrinological and diet aspects, physical activity, rehabilitation, integrative medicine, and digital narrative medicine, was developed., Conclusions: In the context of a patient-centered care, BC treatment cannot be separated from a patient's long-term follow-up and care, and an organized interdisciplinary collaboration is the future in this disease's cure, to make sure that our patients will live longer and better., Trial Registration: NCT05893368: New Model for Integrating Person-based Care (PbC) in the Treatment of Advanced HER2-negative Breast Cancer (PERGIQUAL). Registration date: 29th May 2023., (© 2024. The Author(s).)

Objectives: The aim of this study was to investigate the shape of the time-varying relationship between herpes zoster infection, nominally shingles, and the occurrence of stroke., Study Design: Retrospective cohort study., Methods: Using the Italian Health Search Database, a cohort of patients aged ≥18 years who were registered between 2002 and 2021 was selected. In this cohort, a nested case-control analysis was used to model the time-varying distance (in months) between the dates of shingles and post-herpetic stroke, using a regression cubic spline, based on the odds of the occurrence of stroke compared with those without shingles., Results: The dataset comprised 42,513 cases (51.1% males; mean age [stanndard deviation {SD}]: 71.0 [11.8] years) and 425,124 related controls (51.1% males; mean age [SD]: 70.9 [12] years). In the first 12 months following shingles diagnosis, a rapid increase in the risk of stroke was observed, reaching an odds ratio of 1.31 (95% confidence interval: 1.21-1.41); subsequently, there was some risk reduction and a new symmetric increase within the first 4.2 years of follow-up, thus shaping a bimodal distribution. Then, a new increase in the stroke risk was reported, although less steep, which was followed by a regular risk reduction (still 10% higher compared with those without shingles), resulting in a right-skewed relationship between the time from the shingles diagnosis and the occurrence of stroke. This association was no longer statistically significant 13.1 years after shingles diagnosis., Conclusions: This study demonstrated that the risk of post-herpetic stroke has a short- and long-term association according to a risk continuum relationship. These findings confirm the relevance of vaccination coverage for herpes zoster., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Giant cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries. MiRNAs are small, non-coding RNAs that inhibit gene expression at post-transcriptional level. Several miRNAs have been shown to be dysregulated in temporal artery biopsies (TABs) from GCA patients, but their role is unknown. The aims of the present work were: to gain insight into the link between inflammation and miRNA up-regulation in GCA; to identify the role of miR-146a and miR-146b. Primary cultures from TABs were treated with IL-1β, IL-6, soluble IL-6R (sIL6R), IL-17, IL-22, IFNγ, LPS and PolyIC. Correlations between cytokine mRNA and miRNA levels were determined in inflamed TABs. Primary cultures from TABs, human aortic endothelial and smooth muscle cells and ex-vivo TAB sections were transfected with synthetic miR-146a and miR-146b to mimic miRNA activities. Cell viability, target gene expression, cytokine levels in culture supernatants were assayed. Treatment of primary cultures from TABs with IL-1β and IL-17 increased miR-146a expression while IL-1β, IL-6+sIL6R and IFNγ increased miR-146b expression. IFNγ and IL-1β mRNA levels correlated with miR-146a/b levels. Following transfection, cell viability decreased only in primary cultures from TABs. Moreover, transfection of miR-146a/b mimics increased ICAM-1 gene expression and production of the soluble form of ICAM-1 by primary cultures from TABs and by ex-vivo TABs. ICAM-1 expression was higher in inflamed than normal TABs and ICAM-1 levels correlated with miR-146a/b levels. Expression of miR-146a and miR-146b in GCA appeared to be driven by inflammatory cytokines (e.g. IL-1β, IFNγ). miR-146a and miR-146b seem responsible for the increase of soluble ICAM-1., Competing Interests: Declaration of 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective and Design: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients., Material or Subjects: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled., Methods: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann-Whitney U test, the Kruskal-Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses., Results: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1., Conclusion: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Among the dysfunctional eating behaviors associated with excessive food intake, a construct that is gaining increasing attention is grazing-the constant, continuous, compulsive, and repetitive consumption of small/moderate amounts of food. Furthermore, in some cases, grazing seems to indicate a dependence on food and/or eating. Currently, the Repetitive Eating Questionnaire (Rep(Eat)-Q) appears to be the only questionnaire that comprehensively measures grazing, including its repetitive and compulsive eating component. Therefore, in a sample of individuals with severe obesity, the objective of this study was twofold: (A) to evaluate the psychometric properties of the Italian version of the Rep(Eat)-Q, and (B) to analyze the association between grazing and food addiction (FA)., Method: A cross-sectional research design was used. A total of 402 inpatients with severe obesity (BMI > 35) were recruited. Participants underwent a series of questionnaires to investigate structural validity and convergent validity and association with FA criteria., Results: The factorial structure of the Rep(Eat)-Q is robust and showed fit indexes: CFI = 0.973; RMSEA = 0.074; 90%CI [0.056-0.091]; and SRMR = 0.029. Also, it exhibited good internal consistency and convergent validity. Furthermore, logistic regression analysis highlights a specific association between certain FA criteria and grazing., Conclusions: The Rep(Eat)-Q can be considered to be a concise, robust, reliable, and statistically sound tool to assess repetitive eating, specifically grazing. Its strong psychometric properties offer significant advantages for both research and clinical applications. Furthermore, in a sample of individuals with severe obesity, the results suggest that individuals with problematic grazing exhibit a typical behavioral profile of subjects with FA, indicating that FA can manifest through problematic grazing as well.

Background : There are algorithms to predict the risk of SARS-CoV-2-related complications. Given the spread of anti-COVID vaccination, which sensibly modified the burden of risk of the infection, these tools need to be re-calibrated. Therefore, we updated our vulnerability index, namely, the Health Search (HS)-CoVulnerabiltyIndex (VI)d (HS-CoVId), to predict the risk of SARS-CoV-2-related hospitalization/death in the primary care setting. Methods : We formed a cohort of individuals aged ≥15 years and diagnosed with COVID-19 between 1 January and 31 December 2021 in the HSD. The date of COVID-19 diagnosis was the study index date. These patients were eligible if they had received an anti-COVID vaccine at least 15 days before the index date. Patients were followed up from the index date until one of the following events, whichever came first: COVID-19-related hospitalization/death (event date), end of registration with their GPs, and end of the study period (31 December 2022). To calculate the incidence rate of COVID-19-related hospitalization/death, a patient-specific score was derived through linear combination of the coefficients stemming from a multivariate Cox regression model. Its prediction performance was evaluated by obtaining explained variation, discrimination, and calibration measures. Results : We identified 2192 patients who had received an anti-COVID vaccine from 1 January to 31 December 2021. With this cohort, we re-calibrated the HS-CoVId by calculating optimism-corrected pseudo-R 2 , AUC, and calibration slope. The final model reported a good predictive performance by explaining 58% (95% CI: 48-71%) of variation in the occurrence of hospitalizations/deaths, the AUC was 83 (95% CI: 77-93%), and the calibration slope did not reject the equivalence hypothesis ( p -value = 0.904). Conclusions : Two versions of HS-CoVId need to be differentially adopted to assess the risk of COVID-19-related complications among vaccinated and unvaccinated subjects. Therefore, this functionality should be operationalized in related patient- and population-based informatic tools intended for general practitioners.

The lateralization of the inferior alveolar nerve, or LIAN procedure, may be a surgical consideration for implant-prosthetic rehabilitation in the edentulous mandibular posterior region. This technique can be advantageous in that it does not require a donor site and allows for the immediate placement of an implant, potentially leading to reduced morbidity, healing time, and costs. Although such risks as altered sensory nerve function and weakening of the mandibular body are associated with the LIAN procedure, it is a viable alternative to various regenerative techniques to rehabilitate a patient with an implant-supported fixed prosthesis.

Glycogen storage disease type Ib (GSD Ib, biallelic variants in SLC37A4) is a rare disorder of glycogen metabolism complicated by neutropenia/neutrophil dysfunction. Since 2019, the SGLT2-inhibitor empagliflozin has provided a mechanism-based treatment option for the symptoms caused by neutropenia/neutrophil dysfunction (e.g. mucosal lesions, inflammatory bowel disease). Because of the rarity of GSD Ib, the published evidence on safety and efficacy of empagliflozin is still limited and does not allow to develop evidence-based guidelines. Here, an international group of experts provides 14 best practice consensus treatment recommendations based on expert practice and review of the published evidence. We recommend to start empagliflozin in all GSD Ib individuals with clinical or laboratory signs related to neutropenia/neutrophil dysfunction with a dose of 0.3-0.4 mg/kg/d given as a single dose in the morning. Treatment can be started in an outpatient setting. The dose should be adapted to the weight and in case of inadequate clinical treatment response or side effects. We strongly recommend to pause empagliflozin immediately in case of threatening dehydration and before planned longer surgeries. Discontinuation of G-CSF therapy should be attempted in all individuals. If available, 1,5-AG should be monitored. Individuals who have previously not tolerated starches should be encouraged to make a new attempt to introduce starch in their diet after initiation of empagliflozin treatment. We advise to monitor certain safety and efficacy parameters and recommend continuous, alternatively frequent glucose measurements during the introduction of empagliflozin. We provide specific recommendations for special circumstances like pregnancy and liver transplantation., Competing Interests: Declaration of competing interest All authors with exception of ELC, JlF, PH and SKU received accommodation support by Sophie's Hope Foundation. All authors report no conflict of interest related to this study. TGJD declares that he has confidentiality agreements with third parties. In the past 36 months, there have been consultation agreements (with Danone, Ultragenyx Pharmaceutical Inc, ModernaTX Inc., and Beam Therapeutics), contracts for financial research support for investigator-initiated research (NCT04311307) and sponsor-initiated research (NCT03517085, NCT03970278, NCT05139316, and NCT05196165), honoraria for lectures or presentations (by MEDTalks, Prelum, and Danone), and participations in a Data Safety Monitoring Board (NCT05095727) and Advisory Boards (Ultragenyx Pharmaceutical Inc, ModernaTX Inc., and Beam Therapeutics). For all private-public relationships, all contracts are via UMCG Contract Research Desk and all payments are to UMCG. ND declares that he is a director and minority shareholder in SpOtOn Clinical Diagnostics Ltd. KMS declares that in the last 36 months there were consultancy agreements with BioMarin, Chiesi, Takeda, Sanofi, Amicus and Immusoft Corporation. SCG declares that over the last 3 years in the area of inherited metabolic diseases she has received accommodation support from Nutricia Metabolics, honoraria for lectures from Vitaflo and Ultragenyx, and that she is an advisory board member of Ultragenyx. JL and BS declare no conflict of interest. Funding to Sophie's Hope Foundation and curegsd1b.org is by individual donors, rather than pharmaceutical or medical food industry. ELC declares no conflict of interest. C.D. Nina la Guerrera (www.ninalaguerrera.org) is a small size non-for-profit platform, whose main sources of funding are by individual donors from sectors that have no interest in biomedical research. HM declares that over the last 3 years in the area of inherited metabolic diseases she has received accommodation support from Vitaflo. honoraria for lectures from Vitaflo and Nutricia and served as a paid consultant for Ultragenyx. SBW declares that over the last 3 years in the area of inherited metabolic diseases she has received accommodation support from Nutricia Metabolics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The Raise Awareness of Influenza Strategies in Europe (RAISE) group gathered information about the healthcare burden of influenza (hospitalizations, intensive care unit [ICU] admissions, and excess deaths), surveillance systems, and the vaccine coverage rate (VCR) in older adults in 18 European countries and Israel., Areas Covered: Published medical literature and official medical documentation on the influenza disease burden in the participating countries were reviewed from 2010/11 until the 2022/23 influenza seasons. Information on the framework for monitoring the disease burden and the provision for ensuring older adults had access to vaccination in their respective countries was provided. Data on influenza VCR in older adults were collected for the 2019/20 to 2022/23 influenza seasons. Data are reported descriptively., Expert Opinion: Influenza presents a significant healthcare burden in older adults. Reporting outcomes across participating countries is heterogeneous, highlighting the need for standardized approaches. Although older adults receive free influenza vaccination, vaccine uptake is highly variable among countries. Moreover, hospitalization rates remain high even in countries reporting a high VCR. Increased awareness and education on the burden of disease and the broader use of improved influenza vaccines for older adults may help reduce the disease burden on this population.

Background: Gaining knowledge of the various reasons behind people's consumption of highly processed foods has the potential to enhance obesity prevention initiatives and open avenues to tailor treatment approaches for obesity and binge eating at a more personalized level. This contribution aimed to test the psychometric properties and factor structure of the Palatable Eating Motives Scale (PEMS-IT) in a community sample of Italian adults., Methods: A confirmatory factor analysis was performed to test the factor structure of the Italian version of the PEMS (PEMS-IT) on a total of 616 respondents. Furthermore, the reliability and convergent validity analysis of the tool were evaluated., Results: The analysis confirmed the four-factor structure of PEMS-IT [(YBχ 2 (164) = 537.901; p < 0.001, the CFI = 0.918, RMSEA = 0.072; 90%CI [0.065-0.078]; p (RMSEA < 0.05) < 0.001, and SRMR = 0.080] and satisfactory reliability on its subscales (Cronbach's α: 0.745-0.917). Positive correlations were also found with food addiction and binge-eating symptoms, compulsive eating behavior, and uncontrolled and emotional eating., Conclusions: The PEMS-IT appears to be an instrument with promising psychometric properties and potential applications in clinical settings. However, it also has some limitations, and future studies could focus on improving the semantic content of the elements to increase the overall utility and precision of the instrument.

Background: The Three Factor Eating Questionnaire-Revised 18 (TFEQ-R-18) is an extensively used questionnaire to measure three transdiagnostic features of eating behavior: cognitive restraint, uncontrolled eating, and emotional eating., Objective: This research aims to investigate the psychometric properties of the Italian version of the TFEQ-R-18 in three large community samples., Method: Cross-sectional research designs were employed. In Study 1 (N = 537), an exploratory graph analysis (EGA) was used to examine item clustering within the TFEQ-R-18. In Study 2 (N = 645), a confirmatory factor analysis (CFA) was conducted to test its structural validity. In Study 3 (N = 346), a MANOVA was employed assessing mean differences across eating disorders (e.g., anorexia nervosa, bulimia nervosa, binge eating disorder)., Results: In Study 1, the EGA accurately identified the three original dimensions of the TFEQ-R-18. Study 2 showed that the Italian TFEQ-R-18 has good fit indexes (CFI = 0.989, RMSEA = 0.064; 90% CI [0.058, 0.070], SRMR = 0.062), and possesses robust psychometric properties. Study 3 reveals distinct, statistically significant differences among eating disorders., Conclusion: The TFEQ-R-18 proves to be a concise and precise tool for measuring transdiagnostic eating behaviors. Its applicability in the Italian context, supported by robust psychometric properties, suggests its utility for both research and clinical purposes. The findings affirm its potential to inform interventions aimed at enhancing psychological health., Level of Evidence: Level V, descriptive study., (© 2024. The Author(s).)

Background: The ever-increasing spread of Internet-based systems for common mental disorders has generated the need for brief online screening methods. This study aims to test the psychometric properties of the Web Screening Questionnaire (WSQ) to examine its suitability for screening for common mental health problems among a community sample of Italian adults., Methods: A total of 1282 subjects (F = 819; mean age = 42.05) answered the WSQ. Its discriminant characteristics were examined with other validated selected scales for measuring mental health widely used in the Italian population using sensitivity, specificity, and area under the curve (AUC), as well as positive (PPV) and negative predictive values (NPV)., Results: Most of the WSQ subscales exhibited moderate to high specificity values. Specifically, the scales of 'agoraphobia' (0.947; 95%CI [0.934, 0.960]), 'anxiety' (0.959; 95%CI [0.946, 0.970]), and 'panic disorder' (0.973; 95%CI [0.964, 0.981]) showed the highest values whilst the 'obsessive-compulsive' dimension had the lowest value at 0.838, 95%CI [0.815, 0.861]. With exceptions observed for 'depression' (0.716; 95%CI [642, 798]) and 'alcohol abuse' (0.760; 95%CI [560, 920]), instead, the WSQ demonstrated critical sensitivity values (<0.6) in all dimensions., Conclusions: The WSQ was appropriate for discriminating between people with and without a psychiatric condition, as it helps to confirm the absence of disorders. However, further diagnostic procedures are required, in case of a positive WSQ screening result.

Self-esteem and emotion dysregulation appear to be important factors in the psychological well-being of trauma survivors. On the one hand, self-esteem may act as a shield against the psychological consequences of traumatic experiences; on the other hand, emotion regulation can affect the way individuals deal with post-traumatic affects (e.g., fear, terror, shame, and guilt). Consequently, the objective of this study was to investigate the role that emotion dysregulation and self-esteem play in the well-being of a sample of women after the traumatic experience of intimate partner violence (IPV). This study involved 282 women (mean age  = 41.55, SD = 10.52) who experienced IPV in the last year. Conditional process analyses and Johnson-Neyman analysis for regions of significance were performed. The results showed that emotion dysregulation mediated the relationship between post-trauma affectivity (i.e., fear, terror, shame and guilt) and survivors' well-being. Furthermore, self-esteem negatively predicted lack of well-being and acted as a moderator of the relationship between emotion dysregulation and lack of well-being. In this regard, through the Johnson-Neyman analysis for regions of significance, it was possible to identify a cut-off value above which the relationship between emotion dysregulation and lack of well-being became non-statistically significant. This study contributed to understanding the role that emotion dysregulation and self-esteem play in the well-being of IPV survivors. In this regard, clinical implications will be presented., (© 2024 Family Process Institute.)

Annual influenza vaccination is one of the main public health measures able to drastically reduce the burden of this infectious disease. Some evidence suggests 'trained immunity' triggered by influenza vaccine might reduce the risk of SARS-CoV-2 infection. Adjuvanted influenza vaccines are known to induce a broader cross-reactive immunity. No studies investigated the effect of adjuvanted vs. non-adjuvanted influenza vaccines on the risk of symptomatic SARS-CoV-2 infection. A case-control analysis nested in a cohort of subjects aged ≥65 years and immunized with adjuvanted or non-adjuvanted influenza vaccines was conducted. Although no statistically significant (OR = 0.87; P = .082) difference between the two vaccine types was observed for the 9-month follow-up period, a 17% (OR = 0.83; P = .042) reduction in the odds of COVID-19 was observed for adjuvanted vaccines with a 6-month follow-up. Further evidence is needed, but these results might have implications given the complexity of the upcoming winter seasons, in which the co-occurrence of influenza, SARS-CoV-2 and other respiratory infections (e.g., syncytial virus) might be unpredictable., (© 2023 British Pharmacological Society.)