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Background From the initial stages of the pandemic in early 2020, COVID-19-related olfactory and gustatory dysfunctions have been widely reported and are emerging as one of the most frequent long-term sequelae of SARS-CoV-2 infection. However, data regarding the long-term recovery of the sense of smell and taste are lacking. This study aimed to characterize the evolution up to one year after the diagnosis of self-reported olfactory and gustatory dysfunctions in COVID-19 cases. Methods Based on the data of the active surveillance platform of the Apulia region, Italy, we selected the residents of Foggia district who were confirmed positive for SARS-CoV-2 from March 1st to June 16th, 2020, and home-quarantined with paucisymptomatic-to-mild clinical presentation. Self-reported olfactory and gustatory dysfunctions were recorded at baseline through a survey of dichotomous questions. The evolution of these symptoms at approximately one year was prospectively assessed via telephone by the validated sino-nasal outcome test 22 (SNOT-22, Italian version). Results Among the 1,175 COVID-19 cases notified in the Foggia district during the first epidemic wave, 488 had paucisymptomatic-to-mild clinical presentation. Of these, 41.2% (n = 201, 95% confidence interval [CI] 36.8–45.7%) reported at least one sensory dysfunction. A total of 178 to 201 (88.5%) patients agreed to participate in the follow-up survey. According to the SNOT-22 results, the persistence of a sensory dysfunction was observed in the 29.8% (n = 53, 95% CI 23.2–37.1%) of them. Particularly, loss of smell persisted in 25.8% (n = 46, 95% CI 19.6–32.9%), loss of taste in 21.3% (n = 38, 95% CI 15.6–28.1%), loss of both in 17.4% (n = 31, 95% CI 12.2–23.8%) of participants in the follow-up. The rates of full recovery increased over time: from 59% at 30 days to 71.9% at 90 days for the sense of smell; from 61.3% at 30 days to 74.7% at 90 days for the sense of taste. Conclusions The persistence of COVID-19-related olfactory and gustatory dysfunctions up to 12 months after the disease onset in a noteworthy proportion (approximately 3 out of 10) of patients with paucisymptomatic-to-mild clinical presentation deserves further investigations due to its possible pathophysiological implications and impact on the quality of life.

Background COVID-19 has been characterised by its global and rapid spread, with high infection, hospitalisation, and mortality rates worldwide. However, the course of the pandemic showed differences in chronology and intensity in different geographical areas and countries, probably due to a multitude of factors. Among these, socio-economic deprivation has been supposed to play a substantial role, although available evidence is not fully in agreement. Our study aimed to assess incidence and fatality rates of COVID-19 across the levels of socio-economic deprivation during the first epidemic wave (March–May 2020) in the Italian Province of Foggia, Apulia Region. Methods Based on the data of the regional active surveillance platform, we performed a retrospective epidemiological study among all COVID-19 confirmed cases that occurred in the Apulian District of Foggia, Italy, from March 1st to May 5th, 2020. Geocoded addresses were linked to the individual Census Tract (CT) of residence. Effects of socio-economic condition were calculated by means of the Socio-Economic and Health-related Deprivation Index (SEHDI) on COVID-19 incidence and fatality. Results Of the 1054 confirmed COVID-19 cases, 537 (50.9%) were men, 682 (64.7%) were 0–64 years old, and 338 (32.1%) had pre-existing comorbidities. COVID-19 incidence was higher in the less deprived areas (p < 0.05), independently on age. The level of socio-economic deprivation did not show a significant impact on the vital status, while a higher fatality was observed in male cases (p < 0.001), cases > 65 years (p < 0.001), cases having a connection with a nursing home (p < 0.05) or having at least 1 comorbidity (p < 0.001). On the other hand, a significant protection for healthcare workers was apparent (p < 0.001). Conclusions Our findings show that deprivation alone does not affect COVID-19 incidence and fatality burden, suggesting that the burden of disease is driven by a complexity of factors not yet fully understood. Better knowledge is needed to identify subgroups at higher risk and implement effective preventive strategies.

The stem cell ability to self-renew and lead regeneration relies on the balance of complex signals in their microenvironment. The identification of modulators of hepatic progenitor cell (HPC) activation is determinant for liver regeneration and may improve cell transplantation for end-stage liver disease. This investigation used different models to point out the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a key regulator of the HPC fate. We initially proved that in vivo models of biliary epithelial cells (BECs)/HPC activation show hepatic oxidative stress, which activates primary BECs/HPCs in vitro. NRF2 downregulation and silencing were associated with morphological, phenotypic, and functional modifications distinctive of differentiated cells. Furthermore, NRF2 activation in the biliary tract repressed the ductular reaction in injured liver. To definitely assess the importance of NRF2 in HPC biology, we applied a xenograft model by inhibiting NRF2 in the human derived HepaRG cell line and transplanting into SCID/beige mice administered with anti-Fas antibody to induce hepatocellular apoptosis; this resulted in effective human hepatocyte repopulation with reduced liver injury. To conclude, NRF2 inhibition leads to the activation and differentiation of liver progenitors. This redox-dependent transcription factor represents a potential target to regulate the commitment of undifferentiated hepatic progenitors into specific lineages.

•Real-world evidence of MMRV clinical protection against varicella is essential.•Data showed effectiveness of two doses MMRV against varicella of any severity of 93%.•Two-dose schedule should be recommended to optimise immunisation programmes worldwide. Priorix-Tetra™ (MMRV GlaxoSmithKline Biologicals’ vaccine) was developed based on the existing measles-mumps-rubella and varicella vaccines. In this study, we aimed to estimate the effectiveness of the combined measles-mumps-rubella-varicella Priorix-Tetra™ vaccine against varicella in real-world conditions. We conducted a post-marketing retrospective case-control study in the Apulia region of Italy in children aged 1–9 years born between January 1, 2008 and December 31, 2016. We assessed the effectiveness against varicella of all grades of severity (including hospitalisation) and against hospitalisation for varicella of a single and two doses of Priorix-Tetra™. Moreover, we also assessed effectiveness of monovalent varicella (monovalent-V) vaccine and any varicella vaccines. Vaccine effectiveness was calculated as (1–OR) x 100. We introduced demographic variables in the model to adjust Vaccine effectiveness (aVE) by potential confounders (sex and year of birth). We recorded 625 varicella cases and matched them with 1,875 controls. Among 625 cases, 198 had received a single MMRV dose, 10 two MMRV doses, 46 a single monovalent-V dose, none two monovalent-V doses; four a monovalent-V as first dose and MMRV as second dose, and one a MMRV as first dose and monovalent-V as second dose; 366 cases were not vaccinated. The aVE against varicella of all grades of severity was 77.0% and 93.0% after a single dose and after two doses of MMRV, respectively. The aVE against varicella of all grades was 72.0% after a single dose of monovalent-V vaccine. The aVE against varicella of all grades of severity was 76.0% after a single dose and 94.0% after two doses of any varicella vaccine. The aVE against varicella hospitalisation was 96% after a single dose of any varicella vaccine. Priorix-Tetra™ showed to be an effective vaccine and the two-dose schedule should be recommended to optimise immunisation programmes. A single dose was able to provide protection against varicella hospitalisation.

•42.4% preterms in Italy receive delayed hexavalent vaccine due to parents’ concerns.•Parents of preterms vaccinated with Hexyon reported systemic adverse effects as rarer.•We aimed at filling hexavalents safety knowledge gaps in pediatric clinical practice. Recommendations in many countries state that preterm infants (PTIs) should receive the same routine immunization schedule and timing as for full-term births, according to their chronological age. Data regarding hexavalent vaccine safety in PTIs are still limited. We conducted a post-marketing surveillance study of the DTaP2-IPV-HB-Hib vaccine administered to PTIs in Apulia region, Italy. We identified PTIs by selecting the hospital discharge records of infants born between January and June 2017 using the DRG and ICD-9-CM codes for preterm birth, and we matched these data with records included in the regional immunization registry. We analyzed coverage and timeliness of vaccination. To investigate adverse events (AEs) after the first dose, we interviewed via phone the parents of PTIs vaccinated with at least one dose of the DTaP2-IPV-HB-Hib vaccine. At the time of our analysis (31.12.2017), 866/936 (92.5%) PTIs received the first dose of hexavalent vaccine and 539/936 (57.6%) were vaccinated by the third month of age, as recommended; 700/866 (80.8%) received the DTaP2-IPV-HB-Hib vaccine. The parents of 339 PTIs vaccinated with the DTaP2-IPV-HB-Hib vaccine reported local pain as the most common reaction (35.7% of the children). Erythema, swelling, induration and nodule were also reported in about 25% of the children. Systemic adverse events were generally rarer than local reactions. No serious AEs were reported. Our findings showed that more than 40% of PTIs received delayed hexavalent vaccination. This study showed a reassuring safety profile of the vaccine in the preterm population and may be considered as a pilot for further real-world studies.

Sustainable Development Goals (SDGs) and 2030 Agenda represent global development programs. Education can widen the acknowledgement of their relevance and their applications. This survey aims to assess awareness, knowledge and attitudes towards SDGs and sustainability among first-year students in nine Italian Universities. A Likert scale-based online questionnaire of 70 items was compiled by students from March to July 2019. It examined knowledge and expectations referred to sustainable development concepts, indicators and documents/models accounting for sociodemographic variables. Statistical analyses performed were Chi-square test, Fisher’s Exact test, Kendall’s W correlation coefficient, univariate and multivariate analysis. The questionnaire was completed by 1676 students. A low percentage referred a good knowledge of SDGs and 2030 Agenda, most of them had never attended related educational activities previously. Better knowledge of SDGs and 2030 Agenda was observed in case of previous specific educational activities (p < 0.001). The expectation towards university guaranteeing an education on SDGs was high, both for personal wisdom and for usefulness in future professional context. A significant difference (p < 0.001) in such expectations was found, as healthcare students were less interested than colleagues of other areas. The results showed low knowledge but interest towards sustainable development. A scheduled implementation of academic initiatives should be considered.

This study assessed the direct costs of using Palivizumab for RSV prevention in the Foggia District, Italy, during the 2023/2024 season, and explored the cost savings coming from reallocating resources to Nirsevimab in a universal RSV program. Switching from Palivizumab to Nirsevimab could protect 57.85 % of newborns per season. Considering also hospitalization expenses, coverage reaches 46.4 % of infants, or 66.2 % if unspecified bronchiolitis is included. These results suggest notable cost savings and greater coverage, supporting a universal RSV initiative. [Display omitted]

BackgroundEnd-stage renal disease (ESRD) is associated with a broad spectrum of morphological and functional thyroid disorders. Recent studies have shown that low free triiodothyronine (fT3) levels are related to inflammatory status and endothelial activation in ESRD patients on haemodialysis (HD). Limited data exist about a possible relationship between dialysis regimen, namely long nocturnal haemodialysis (LNHD), and thyroid function parameters. The aim of this study was to evaluate the relationship between dialysis regimen and thyroid function, and consequently with the main patient outcomes.MethodsTo this purpose, we performed a retrospective, single-centre cohort study including 220 incident chronic HD patients treated during an 8-year period (from January 2010 to December 2017). The main clinical and haematochemical parameters, including thyroid function, were evaluated and related to the main patient outcomes.ResultsPatients with low fT3 levels (<3.05 ng/mL) showed significantly lower survival rates than patients with normal fT3 levels (>3.05 ng/mL) (P < 0.001), although there were no substantial differences in the demographic and clinical characteristics between the two groups. After propensity score 1:3 matching of 25 patients treated with nocturnal HD to 75 patients treated with diurnal HD, LNHD patients showed significantly higher survival rates (88.0% versus 61.3%, P = 0.001) and lower incidence of cardiovascular events than patients on diurnal dialysis (8.0% versus 40.0%, P = 0.001). Moreover, an 8-year time-dependent analysis showed that at any time, except for baseline, the rate of patients with fT3 levels >3.05 ng/mL was significantly higher in LNHD patients than in patients treated with diurnal dialysis.ConclusionsOur data suggest that the application of alternative dialysis regimens, also reducing the frequency of low T3, could ameliorate outcomes and therefore reduce the incidence of cardiovascular events in HD patients.

DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair. Long non-coding RNAs transcribed at DNA damaged sites can play part in DNA damage response. Here the authors reveal that damaged induced lncRNAs can form DNA:RNA hybrids at resected DNA-ends. These hybrids are involved in recruiting HR-mediated repair machinery which, in turn, controls their level at DSBs.

Of the many types of DNA damage, DNA double-strand breaks (DSBs) are probably the most deleterious. Mounting evidence points to an intricate relationship between DSBs and transcription. A cell system in which the impact on transcription can be investigated at precisely mapped genomic DSBs is essential to study this relationship. Here in a human cell line, we map genome-wide and at high resolution the DSBs induced by a restriction enzyme, and we characterize their impact on gene expression by four independent approaches by monitoring steady-state RNA levels, rates of RNA synthesis, transcription initiation and RNA polymerase II elongation. We consistently observe transcriptional repression in proximity to DSBs. Downregulation of transcription depends on ATM kinase activity and on the distance from the DSB. Our study couples for the first time, to the best of our knowledge, high-resolution mapping of DSBs with multilayered transcriptomics to dissect the events shaping gene expression after DSB induction at multiple endogenous sites. DNA double strand breaks (DSBs) are among the most deleterious types of damage and there is strong evidence indicating a relationship between breaks and transcription. Here the authors provide a high-resolution, genome-wide map of induced DSBs and observe ATM-dependent transcriptional repression.