Assessing the mental health needs of Yazidi adolescents and young adults in an Iraqi Kurdi IDP Camp: a focus group study.

BACKGROUND: Internally displaced people (IDP) in Iraq are 1.2 million (as March 2023). Protracted refugee status endangers the mental health, especially of minorities who survived persecution and conflict, such as the Yazidis. This study aims to identify the mental health needs of Yazidi adolescents and young adults (AYA) in the IDP camp of Bajed Kandala (Iraqi Kurdistan). METHODS: A focus group discussion (FGD) study was conducted between April and August 2022. The FGDs involved AYAs, as well as the staff of the clinic of the Bajed Kandala camp. An inductive approach was adopted referring to the 'theme' as the unit of content analysis of the text. All FGDs were recorded and transcribed. The analysis was carried out independently by two researchers. The inter-rater agreement was assessed through the Cohen's k. RESULTS: A total of 6 FGDs were conducted. The participants were 34 of whom 21 (61.8%) females with a median age of 18.5 years (IQR 17.0-21.0). A total of 156 themes were found as relevant to the objective of this study. Four main areas and twelve subareas of needs in mental health were identified. The interrater agreement over the main area and subareas was good (κ = 0.78 [0.95CI 0.69-0.88], κ = 0.82 [0.95CI 0.73-0.91], respectively). The four areas had a similar frequency: Activities (28.2%), Individual (27.6%), Social relationships (22.4%) and Places/setting (21.8%). The subareas 'community' and 'internal resources' were labelled as negative 85.7% and 61.9% of the time, respectively. These sub-areas referred to stigma and self-stigma towards mental health. The subarea 'female condition' was always considered as negative, as well as the subareas 'camp' and 'tent' referring to housing as an important social determinant of mental health. CONCLUSIONS: Community stigma and self-stigma are two still important factors preventing the achievement of mental well-being. Alongside these, a gender gap in mental health was identified in the FGDs. These factors should be taken into account in order to guide future mental health interventions in refugee camps.

The use of 12-item General Health Questionnaire (GHQ-12) in Ukrainian refugees: translation and validation study of the Ukrainian version.

Following the Russian-Ukrainian conflict, the well-being of millions of Ukrainians has been jeopardised. This study aims to translate and test the psychometric features of the Ukrainian version of the General Health Questionnaire 12 (GHQ-12). The study included Ukrainian refugees housed in Verona (Italy) between November/2022 and February/2023. The Ukrainian translation was obtained through a 'forward-backward' translation. Questionnaire was completed by 141 refugees (females: 78.7%). Median age was 36 years (IQR 23-43). Individuals with a score suggestive of psychological distress were 97 (68.8%). Cronbach's coefficient was 0.84 (0.95CI 0.80-0.88). According to confirmatory factor analysis, both single- (modelB1) and two-factor (model B2) structures with bimodal scoring method fitted the data satisfactorily. The two factors of model B2 had a 0.88 correlation. Pearson coefficient showed a positive significant correlation between the GHQ-12 and International Trauma Questionnaire scores (ρ = 0.53, 0.95CI 0.40-0.64, p < 0.001). The GHQ-12 Ukrainian translation showed good psychometric features being a reliable and valid instrument to assess Ukrainian refugees' general well-being.

Assessing the resilience of HIV healthcare services provided to adolescents and young adults after the COVID-19 pandemic in the city of Beira (Mozambique): an interrupted time series analysis.

BACKGROUND: The COVID-19 pandemic has put the provision of health services globally at risk. In Sub-Saharan Africa, it had a major impact on HIV services. However, there is a lack of data on the post-pandemic period. This study aims to evaluate the resumption of HIV services and retention in care for adolescents and young people in the period following the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted using interrupted time series analysis. Three periods were considered: pre-pandemic (form June 2019 to March 2020), pandemic (form April 2020 to March 2022) post-pandemic (from April 2022 to March 2023). Six outcome measures were considered: number of outpatient visits, HIV tests, HIV positivity ratio, the antiretroviral treatment (ART) non-adherence ratio, recall ratio, and the return ratio for adolescent and young adults on ART. RESULTS: During the study period, 447,515 outpatient visits and 126,096 HIV tests were recorded. After a reduction at the beginning of the pandemic period, both visits and tests increased during the pandemic (p < 0.05) and decreased in the post-pandemic (p < 0.05), recovering the pre-pandemic trends. The HIV positivity ratio slightly decreased from 3.3% to 1.7% during the study period (p < 0.05). The ART non-adherence ratio decreased from 23.4% to 2.4% throughout the study period (p < 0.05), with a drop at the beginning of the post-pandemic period (p < 0.05). The recall ratio increased during the study period (p < 0.05) with a drop at the beginning of the pandemic and post-pandemic periods (p < 0.05). The return ratio decreased at the beginning of the pandemic (p < 0.05) but returned to the pre-pandemic ratio in the post-pandemic period. CONCLUSIONS: The post-pandemic values of the investigated outcomes were comparable to pre-pandemic period, or even improved. Differently from other services, such as the community activities, that have been severely affected by COVID-19 pandemic, the HIV service system has shown resilience following emergency situation.

SARS-CoV-2 seroprevalence and associated factors, based on HIV serostatus, in young people in Sofala province, Mozambique.

INTRODUCTION: In Sofala province (Mozambique), young people living with HIV (YPLHIV) are estimated at 7% among people aged 15-24 years. Even though the COVID-19 pandemic threatened HIV health services, data on the impact of COVID-19 on YPLHIV people are lacking. This study aimed at exploring the seroprevalence of SARS-CoV-2 and associated factors among young people based on their HIV status. METHODS: A cross-sectional study was conducted, including people aged 18-24 attending a visit at one of the adolescent-friendly health services in Sofala province between October and November 2022. People vaccinated against SARS-COV-2 or YPLHIV with WHO stage III-IV were excluded. A SARS-CoV-2 antibodies qualitative test and a questionnaire investigating socio-demographic and clinical characteristics were proposed. SARS-CoV-2 seroprevalence was calculated with Clopper-Pearson method. The odds ratio (OR) of a positive SARS-CoV-2 antibodies test was estimated through multivariable binomial logistic regression. RESULTS: In total, 540 young people including 65.8% women and 16.7% YPLHIV participated in the survey.. The mean age was 20.2 years (SD 2.0). Almost all the sample (96.1%) reported adopting at least one preventive measure for COVID-19. The weighted seroprevalence of SARS-CoV-2 in the whole sample was 46.8% (95%CI 42.6-51.2) and 35.9% (95%CI 25.3-47.5) in YPLHIV. The adjusted OR of testing positive at the SARS-CoV-2 antibodies test was higher in students compared to workers (aOR:2.02[0.95CI 1.01-4.21]) and in those with symptoms (aOR:1.52[0.95CI 1.01-2.30]). There were no differences based on HIV status(aOR:0.663[95%CI 0.406-1.069]). Overall, COVID-19 symptoms were reported by 68 (28.2%) people with a positive serological SARS-CoV-2 test and by 7 (21.7%) YPLHIV (p = 0.527). No one required hospitalization. CONCLUSIONS: SARS-CoV-2 seroprevalence was 46.8% without differences in risk of infection or clinical presentation based on HIV status. This result may be influenced by the exclusion of YPLHIV with advanced disease. The higher risk among students suggests the schools' role in spreading the virus. It's important to continue monitoring the impact of COVID-19 on YPLHIV to better understand its effect on screening and adherence to treatment.

Impact and burden of sickle cell disease in critically ill obstetric patients in a high dependency unit in Sierra Leone-a registry based evaluation.

INTRODUCTION: Sickle cell disease (SCD) in pregnancy is associated with worse maternal and neonatal outcomes. There is limited available data describing the burden and outcomes of critically ill obstetric patients affected by SCD in low-income settings. OBJECTIVES: We aimed to define SCD burden and impact on mortality in critically-ill obstetric patients admitted to an urban referral hospital in Sierra Leone. We hypothesized that SCD burden is high and independently associated with increased mortality. METHODS: We performed a registry-based cross-sectional study from March 2020 to December 2021 in the high-dependency unit (HDU) of Princess Christian Maternity Hospital PCMH, Freetown. Primary endpoints were the proportion of patients identified in the SCD group and HDU mortality. Secondary endpoints included frequency of maternal direct obstetric complications (MDOCs) and the maternal early obstetric warning score (MEOWS). RESULTS: Out of a total of 497 patients, 25 (5.5%) qualified to be included in the SCD group. MEOWS on admission was not different between patients with and without SCD and SCD patients had also less frequently reported MDOCs. Yet, crude HDU mortality in the SCD group was 36%, compared to 9.5% in the non SCD group (P < 0.01), with an independent association between SCD group exposure and mortality when accounting for severity on admission (hazard ratio 3.40; 95%CI 1.57-7.39; P = 0.002). Patients with SCD had a tendency to longer HDU length of stay. CONCLUSIONS: One out of twenty patients accessing a HDU in Sierra Leone fulfilled criteria for SCD. Despite comparable severity on admission, mortality in SCD patients was four times higher than patients without SCD. Optimization of intermediate and intensive care for this group of patients should be prioritized in low-resource settings with high maternal mortality.

Comparing swab- and different symptoms-based strategies to ascertain COVID-19 recovery in healthcare workers: a cost-effectiveness analysis.

OBJECTIVE: Given the human and economic cost of the COVID-19 pandemic, protecting healthcare workers (HCW) and ensuring continuity of care is critical. The aim of this study is to evaluate the cost-effectiveness of different strategies to ascertain COVID-19 recovery in HCWs. METHODS: Data were collected from the hospital health surveillance program on HCWs at the University Hospital of Verona between 29/02/2020 and 14/04/2021. The diagnosis of SARS-CoV-2 infection and the assessment of the recovery were made through RT-PCR on oro-nasopharyngeal swab-sample. Recovery time and probability were estimated through Kaplan-Meier estimate. For each recovery assessment strategy costs (laboratory diagnostics and human resources), expressed in local currency (euro-€), and working days saved (WDS-effectiveness) were estimated. A decision-tree was created where each knot was a time point scheduled by the different recovery assessment strategies. A Monte Carlo simulation method was used, and probabilistic sensitivity analysis assessed the effect of input uncertainty. RESULTS: In the study period 916 (9.9%) HCWs tested positive. Recovery time through symptom-based strategy (21 days 0.95 CI 16-24) was significantly lower compared to swab-based one (25 days 0.95 CI 23-28, p < 0.001). The swab-based strategy was dominated by all symptoms-based ones. Symptoms-based with a swab on days 14 and 17 had an ICER of 2 €/WDS and 27 €/WDS compared to the one scheduled on days 10 and 17 and with only one swab on the 17th day. CONCLUSIONS: Scheduling swabs on days 14 and 17 in a symptom-based strategy was the most cost-effective, saving 7.5 more working days than the standard one with swabs on days 10 and 17.

Refining the structure-activity relationships of 2-phenylcyclopropane carboxylic acids as inhibitors of O-acetylserine sulfhydrylase isoforms.

The lack of efficacy of current antibacterials to treat multidrug resistant bacteria poses a life-threatening alarm. In order to develop enhancers of the antibacterial activity, we carried out a medicinal chemistry campaign aiming to develop inhibitors of enzymes that synthesise cysteine and belong to the reductive sulphur assimilation pathway, absent in mammals. Previous studies have provided a novel series of inhibitors for O-acetylsulfhydrylase - a key enzyme involved in cysteine biosynthesis. Despite displaying nanomolar affinity, the most active representative of the series was not able to interfere with bacterial growth, likely due to poor permeability. Therefore, we rationally modified the structure of the hit compound with the aim of promoting their passage through the outer cell membrane porins. The new series was evaluated on the recombinant enzyme from Salmonella enterica serovar Typhimurium, with several compounds able to keep nanomolar binding affinity despite the extent of chemical manipulation.

Combination of SAXS and Protein Painting Discloses the Three-Dimensional Organization of the Bacterial Cysteine Synthase Complex, a Potential Target for Enhancers of Antibiotic Action.

The formation of multienzymatic complexes allows for the fine tuning of many aspects of enzymatic functions, such as efficiency, localization, stability, and moonlighting. Here, we investigated, in solution, the structure of bacterial cysteine synthase (CS) complex. CS is formed by serine acetyltransferase (CysE) and O-acetylserine sulfhydrylase isozyme A (CysK), the enzymes that catalyze the last two steps of cysteine biosynthesis in bacteria. CysK and CysE have been proposed as potential targets for antibiotics, since cysteine and related metabolites are intimately linked to protection of bacterial cells against redox damage and to antibiotic resistance. We applied a combined approach of small-angle X-ray scattering (SAXS) spectroscopy and protein painting to obtain a model for the solution structure of CS. Protein painting allowed the identification of protein-protein interaction hotspots that were then used as constrains to model the CS quaternary assembly inside the SAXS envelope. We demonstrate that the active site entrance of CysK is involved in complex formation, as suggested by site-directed mutagenesis and functional studies. Furthermore, complex formation involves a conformational change in one CysK subunit that is likely transmitted through the dimer interface to the other subunit, with a regulatory effect. Finally, SAXS data indicate that only one active site of CysK is involved in direct interaction with CysE and unambiguously unveil the quaternary arrangement of CS.

Moonlighting O-acetylserine sulfhydrylase: New functions for an old protein.

O-acetylserine sulfhydrylase A (CysK) is the pyridoxal 5'-phosphate-dependent enzyme that catalyzes the final reaction of cysteine biosynthesis in bacteria. CysK was initially identified in a complex with serine acetyltransferase (CysE), which catalyzes the penultimate reaction in the synthetic pathway. This "cysteine synthase" complex is stabilized by insertion of the CysE C-terminus into the active-site of CysK. Remarkably, the CysK/CysE binding interaction is conserved in most bacterial and plant systems. For the past 40years, CysK was thought to function exclusively in cysteine biosynthesis, but recent studies have revealed a repertoire of additional "moonlighting" activities for this enzyme. CysK and its paralogs influence transcription in both Gram-positive bacteria and the nematode Caenorhabditis elegans. CysK also activates an antibacterial nuclease toxin produced by uropathogenic Escherichia coli. Intriguingly, each moonlighting activity requires a binding partner that invariably mimics the C-terminus of CysE to interact with the CysK active site. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation of O-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR.

Cysteine is a building block for many biomolecules that are crucial for living organisms. O-Acetylserine sulfhydrylase (OASS), present in bacteria and plants but absent in mammals, catalyzes the last step of cysteine biosynthesis. This enzyme has been deeply investigated because, beside the biosynthesis of cysteine, it exerts a series of "moonlighting" activities in bacteria. We have previously reported a series of molecules capable of inhibiting Salmonella typhimurium (S. typhymurium) OASS isoforms at nanomolar concentrations, using a combination of computational and spectroscopic approaches. The cyclopropane-1,2-dicarboxylic acids presented herein provide further insights into the binding mode of small molecules to OASS enzymes. Saturation transfer difference NMR (STD-NMR) was used to characterize the molecule/enzyme interactions for both OASS-A and B. Most of the compounds induce a several fold increase in fluorescence emission of the pyridoxal 5'-phosphate (PLP) coenzyme upon binding to either OASS-A or OASS-B, making these compounds excellent tools for the development of competition-binding experiments.

Effectiveness of the Hypertension Screening Corner in Enhancing the Cascade of Care at Primary Healthcare Center Level: Evidence from Zambezia, Mozambique.

Background: Hypertension is the leading cause of cardiovascular disease, whose death burden is dramatically increasing in sub-Saharan Africa. To curb its effects, early diagnosis and effective follow-up are essential. Therefore, this study aims to evaluate the impact of a hypertension screening corner on the hypertension care cascade at the primary healthcare level. Methods: A prospective cohort study was conducted between October 2022 and March 2023 in two PHCCs in Zambezia (Mozambique). The study involved a demographic and socioeconomic status (SES) questionnaire for those screened. Patients with blood pressure (BP) > 140/90 mmHg were given a follow-up questionnaire regarding the care cascade. The four cascade steps were: medical visit, diagnosis confirmation, follow-up visit, and recalling the follow-up appointment. The odds ratio (OR) of reaching each step of the cascade was assessed by binomial logistic regression. Results: Patients with BP > 140/90 mmHg were 454, and 370 (86.0%) completed both study phases. Individuals attending the medical visit were 225 (60.8%). Those with low SES had a higher probability of visit attendance than those with middle (OR = 0.46, 0.95CI[0.23-0.88] p = 0.020) and high (OR = 0.21 0.95CI[0.10-0.42], p < 0.001). Hypertension diagnosis was confirmed in 181 (80.4%), with higher probability in the low SES group compared to the middle (OR = 0.24 IC95[0.08-0.66], p = 0.007) and high (OR = 0.23, IC95[0.07-0.74], p = 0.016) groups. The OR to complete step 1 and step 2 were higher for older age groups. A follow-up appointment was received and recalled by 166 (91.7%) and 162 (97.6%) patients, respectively. Conclusions: The hypertension corner proved to be a useful tool for effective screening of hypertension with satisfactory retention in care, especially for people with lower socio-economic status.

Assessing the impact of a community-based psychodrama intervention on mental health promotion of adolescents and young adults in Mozambique: A mixed-methods study.

Background: While mental health is an emerging issue in low-income countries, its promotion remains poor, with little context-oriented evidence available. Here we aimed to assess the impact and acceptability/feasibility of a community-based psychodrama intervention involving both adolescents and young adults (AYA) living with HIV (AYALHIV) and without HIV (AYAHIV-). Methods: We used a mixed-methods approach, where the quantitative part was based on pre/post questionnaires and the qualitative one on content analysis of semi-structured interviews. Trained community health care workers delivered psychodrama sessions involving AYAs aged 15-24 years once a week between July and August 2023 in Beira, Mozambique. The baseline assessment involved a sociodemographic and three mental health questionnaires: the Mental Health Knowledge Schedule (MAKS), Community Attitudes toward People with Mental Illness (CAMI27), and the Toronto Alexithymia Scale (TAS). We repeated all questionnaires after the intervention and conducted semi-structured interviews. Results: We enrolled 354 AYAs (50.8% female, 45.5% AYALHIV) at baseline; 315 (89.0%) attended the sessions, with a mean participation rate of 94.4%. Overall, 281 (89.2%) completed the post-intervention assessment. MAKS score improved from 44.5 (95% confidence interval (CI) = 44.0-45.0) to 47.1 (95% CI = 46.4-47.7, P < 0.001). Total CAMI27 score showed no significant variation (P = 0.855). Total TAS score decreased from 57.3 (95% CI = 56.1-58.5) to 54.3 (95% CI = 53.0-55.6, P < 0.001). We found no statistically significant interactions between time and sex, age, or HIV serostatus in all questionnaires. For the qualitative part of the study, we analysed 37 semi-structured interviews (43.2% with females, 40.5% with AYALHIV). We identified four areas of intervention impact: peer-to-peer support (30.3%), social empowerment (24.7%), resilience (23.0%), and emotional skills (21.9%). Regarding acceptability/feasibility, perceived scalability (37.2%) and affective attitude (34.5%) were the sub-areas most frequently retrieved in the SSIs. Conclusions: The community-based psychodrama intervention proved to be an effective tool in AYAs' mental health promotion, increasing knowledge and improving emotional awareness through group experience and interpersonal learning. The intervention also showed good acceptability and feasibility in the context of our study.

Adverse events following Measles-Mumps-Rubella and varicella immunization: A safety profile analysis and comparison of different vaccination schedules based on the Italian Pharmacovigilance Network in the Veneto Region.

Objective: The vaccines for measles, mumps, rubella and varicella (MMR and V) have been mandatory in Italy since 2017. Two different vaccination strategies are suggested for the first dose: trivalent MMR and a separate V vaccine or the tetravalent MMRV vaccine. Our aim is to compare the safety profile of MMRV and MMR-V vaccines through the passive adverse event reporting system in the Veneto region and to perform a case-by-case review of a few conditions of interest (febrile and afebrile seizures, ataxia, encephalitis, Guillain-Barré Syndrome, thrombocytopenia, neutropenia and Henoch-Schönlein Purpura). Age and sex differences were also explored. Methods: We identified all reports following MMRV or MMR-V vaccination in the Veneto Region and received into the National Pharmacovigilance Network between 2007 and April 30, 2022. Results: 9,510 reports were retrieved, of which 5,662 (59.5 %) were related to MMRV and 3,848 (40.5 %) to MMR-V. No safety signals were detected supporting the evidence that MMRV and MMR-V vaccinations have a good safety profile. The reporting rate (RR) for serious events between 2007 and 2022 resulted in 13.67 per 10,000 administered doses for MMRV and 10.90 for MMR-V. Conclusion: Passive surveillance data show a significantly higher rate of serious events for males 0-2 years old, both overall and stratified per vaccination strategy. Further studies are needed to confirm this observation. The analyses suggest that retrieved differences do not have a significant impact on the overall safety of both formulations.

Safety profile assessment of HPV4 and HPV9 vaccines through the passive surveillance system of the Veneto Region (Italy) between 2008 and 2022: A 15-year retrospective observational study.

In Veneto Region, HPV vaccine has been actively offered to 12 year-old females since 2008, and to 12 year-old males since 2015. The study aims to analyze the safety profile of HPV4v and HPV9v vaccines and perform a case-by-case review of conditions of interest. Spontaneous reports related to HPV uploaded to the database of the Regional Pharmacovigilance Center between 2008-2022 were included. HPV vaccine doses administered until April 2022 in the Veneto Region were considered to calculate the reporting rate (RR). Potential "safety concerns" examined as conditions of interest were included through Standardized MedDRA or preferred terms searching queries. The level of diagnostic certainty was evaluated as per the Brighton Collaboration case definition criteria. A total of 637 reports and 1316 Adverse Events Following Immunizations (AEFI) were retrieved: 469 for HPV4v (73.6 %) and 168 for HPV9v (26.4 %). Serious reports were 71 (11.1 %): 49 (10.4 %) for HPV4v and 22 (13.1 %) for HPV9v. The RR for serious events between 2008-2022 was 6.9/100,000 administered doses, with no differences by vaccine type. Females and adults showed higher overall RR compared to males and to children and adolescents (p < 0.001), this result was confirmed by stratifying analysis by vaccine type. One case of Guillain Barré syndrome, anaphylactic shock, thrombocytopenia, Henoch Schoenlein purpura and four generalized seizures were reviewed. Vaccinovigilance data from the Veneto Region reaffirm a good safety profile for HPV vaccination and found no vaccine-related unexpected events. Such a detailed analysis may assist healthcare providers to advocate properly for HPV vaccination.

HIV-1 Infection Reduces NAD Capping of Host Cell snRNA and snoRNA.

Nicotinamide adenine dinucleotide (NAD) is a critical component of the cellular metabolism and also serves as an alternative 5' cap on various RNAs. However, the function of the NAD RNA cap is still under investigation. We studied NAD capping of RNAs in HIV-1-infected cells because HIV-1 is responsible for the depletion of the NAD/NADH cellular pool and causing intracellular pellagra. By applying the NAD captureSeq protocol to HIV-1-infected and uninfected cells, we revealed that four snRNAs (e.g., U1) and four snoRNAs lost their NAD cap when infected with HIV-1. Here, we provide evidence that the presence of the NAD cap decreases the stability of the U1/HIV-1 pre-mRNA duplex. Additionally, we demonstrate that reducing the quantity of NAD-capped RNA by overexpressing the NAD RNA decapping enzyme DXO results in an increase in HIV-1 infectivity. This suggests that NAD capping is unfavorable for HIV-1 and plays a role in its infectivity.

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective.

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation.

Disparities in access to COVID-19 vaccine in Verona, Italy: a cohort study using local health immunization data.

Introduction: Migrant populations worldwide were disproportionately impacted by the COVID-19 pandemic. Although substantial resources have been invested in scaling COVID-19 vaccination campaigns, globally vaccine rate and uptake remained low among migrants from across many countries. This study aimed to explore the country of birth as a factor influencing access to the COVID-19 vaccine. Methods: This retrospective cohort study included adults vaccinated against SARS-CoV-2 receiving at least one dose in the Verona province between 27 December 2020 and 31 December 2021. Time-to-vaccination was estimated as the difference between the actual date of each person's first dose of COVID-19 vaccination and the date in which the local health authorities opened vaccination reservations for the corresponding age group. The birth country was classified based on both the World Health Organization regions and the World Bank country-level economic classification. Results were reported as the average marginal effect (AME) with corresponding 0.95 confidence intervals (CI). Results: During the study period, 7,54,004 first doses were administered and 5,06,734 (F = 2,46,399, 48.6%) were included after applying the exclusion criteria, with a mean age of 51.2 years (SD 19.4). Migrants were 85,989 (17.0%, F = 40,277, 46.8%), with a mean age of 42.4 years (SD 13.3). The mean time-to-vaccination for the whole sample was 46.9 days (SD 45.9), 41.8 days (SD 43.5) in the Italian population, and 71.6 days (SD 49.1) in the migrant one (p < 0.001). The AME of the time-to-vaccination compared to the Italian population was higher by 27.6 [0.95 CI 25.4-29.8], 24.5 [0.95 CI 24.0-24.9], 30.5 [0.95 CI 30.1-31.0] and 7.3 [0.95 CI 6.2-8.3] days for migrants from low-, low-middle-, upper-middle- and high-income countries, respectively. Considering the WHO region, the AME of the time-to-vaccination compared to the Italian group was higher by 31.5 [0.95 CI 30.6-32.5], 31.1 [0.95 CI 30.6-31.5], and 29.2 [0.95 CI 28.5-29.9] days for migrants from African, European, and East-Mediterranean regions, respectively. Overall, time-to-vaccination decreased with increasing age (p < 0.001). Although both migrants and Italians mainly used hub centers (>90%), migrants also used pharmacies and local health units as alternative sites (2.9% and 1.5%, respectively), while Italians (3.3%) and migrants from the European region (4.2%) relied more on family doctors. Conclusion: The birth country of migrants influenced access to COVID-19 vaccine both in terms of time-to-vaccination and vaccination points used, especially for the LIC migrant group. Public health authorities should take socio-cultural and economic factors into consideration for tailored communication to people from migrant communities and for planning a mass vaccination campaign.

Exploring the use of cluster analysis to assess antibiotic stewardship in critically-ill neonates in a low resource setting.

BACKGROUND: Sepsis is the third leading cause of neonatal death in low and middle-income countries, accounting for one third of all deaths in Ethiopia. A concerning issue is the increasing number of multidrug-resistant microorganisms facilitated by suboptimal antibiotic stewardship. The study aims to identify clusters of newborns switching antibiotic lines for sepsis in a neonatal intensive care unit (NICU) in Ethiopia, and to explore their potential association with sepsis outcomes. METHODS: A retrospective cohort study was conducted including all newborns discharged with a diagnosis of probable neonatal sepsis from the St. Luke Catholic Hospital NICU between April and July 2021. The antibiotic management protocol included two lines according to WHO guidelines and a third line based on internal hospital guidelines. In the cluster analysis, the Gower distance was estimated based on the antibiotics employed in the different lines and the duration of each line. Mortality and respiratory distress (RD) were the response variables. RESULTS: In the study period, 456 newborns were admitted to the NICU and 196 (42.8%) had probable neonatal sepsis. Four antibiotic management clusters were identified. Cluster 1 (n = 145, 74.4%) had no antibiotic switches, using only the first line. Cluster 2 (n = 26, 13.3%) had one switch from the first to the second line. Cluster 4 (n = 9, 4.6%) had two switches: from first to second and then to third line. In cluster 3 (n = 15, 7.7%), newborns were switched from ceftriaxone/cloxacillin as second line to off-protocol antibiotics. There were no differences in sex, age, weight on admission or crude mortality between clusters. Cluster 3 included a higher frequency of infants who did not breathe at birth (53.3%, p = 0.011) and that necessitated bag ventilation (46.7%, p = 0.039) compared to the other clusters. CONCLUSIONS: The first antibiotic line failed in one out of four newborns with probable sepsis while third-generation cephalosporins were insufficient in one in ten patients. Cluster analysis can provide valuable insights into antibiotic treatment patterns and their potential implications. This approach may support antibiotic stewardship and aid in contrasting antimicrobial resistance in limited resource settings.

Arabidopsis thaliana NudiXes have RNA-decapping activity.

Recent discoveries of various noncanonical RNA caps, such as dinucleoside polyphosphates (Np n N), coenzyme A (CoA), and nicotinamide adenine dinucleotide (NAD) in all domains of life have led to a revision of views on RNA cap function and metabolism. Enzymes from the NudiX family capable of hydrolyzing a polyphosphate backbone attached to a nucleoside are the strongest candidates for degradation of noncanonically capped RNA. The model plant organism Arabidopsis thaliana encodes as many as 28 NudiX enzymes. For most of them, only in vitro substrates in the form of small molecules are known. In our study, we focused on four A. thaliana NudiX enzymes (AtNUDT6, AtNUDT7, AtNUDT19 and AtNUDT27), and we studied whether these enzymes can cleave RNA capped with Np n Ns (Ap2-5A, Gp3-4G, Ap3-5G, m7Gp3G, m7Gp3A), CoA, ADP-ribose, or NAD(H). While AtNUDT19 preferred NADH-RNA over other types of capped RNA, AtNUDT6 and AtNUDT7 preferentially cleaved Ap4A-RNA. The most powerful decapping enzyme was AtNUDT27, which cleaved almost all types of capped RNA at a tenfold lower concentration than the other enzymes. We also compared cleavage efficiency of each enzyme on free small molecules with RNA capped with corresponding molecules. We found that AtNUDT6 prefers free Ap4A, while AtNUDT7 preferentially cleaved Ap4A-RNA. These findings show that NudiX enzymes may act as RNA-decapping enzymes in A. thaliana and that other noncanonical RNA caps such as Ap4A and NADH should be searched for in plant RNA.

Low-dose anti-IL 5 treatment in idiopathic hypereosinophilic syndrome: towards a precision medicine approach for remission maintenance.

Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. According to the available real-life evidence mepolizumab 300 mg and 100 mg, licensed for severe eosinophilic asthma, are comparable in terms of drug efficacy. However, the clinical rationale for selecting one dose or the other has not been explored. We investigated the efficacy and safety of mepolizumab 100 mg in idiopathic HES (I-HES) patients as a steroid sparing strategy for disease remission maintenance by assessing clinical conditions, blood eosinophil count (BEC) and adverse events at baseline and at 3-6-12 months follow-up. Overall, 11 patients were enrolled (females 4-36%) with a median age of 62 years (IQR 55.0-72.0). At 3-month visit both prednisone daily dose and BEC significantly decreased from baseline, whilst a substantial improvement of Brief fatigue inventory score (BFI) was not recorded before the 6 months assessment. More than 70% of patients completely stopped prednisone at 12-months follow-up, without any flare in terms of BEC and BFI. No adverse event was registered. Although larger studies are needed, our report firstly describes that in a well-defined population, diagnosed with I-HES and in disease remission, low dose mepolizumab is a safe and effective steroid-sparing option for remission maintenance. It suggests that a personalized treatment dose might be explored according to the disease classification and activity at the time of biologic treatment start.