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Chronic hepatitis B is a global health problem and current treatments only suppress hepatitis B virus (HBV) infection, highlighting the need for new curative treatments. Oxygen levels influence HBV replication and we previously reported that hypoxia inducible factors (HIFs) activate the basal core promoter (BCP). Here we show that the hypoxic-dependent increase in BCP-derived transcripts is dependent on N6-methyladenosine (m6A) modifications in the 5' stem loop that regulate RNA half-life. Application of a probe-enriched long-read sequencing method to accurately map the HBV transcriptome showed an increased abundance of pre-genomic RNA under hypoxic conditions. Mapping the transcription start sites of BCP-RNAs identified a role for hypoxia to regulate pre-genomic RNA splicing that is dependent on m6A modification. Bioinformatic analysis of published single cell RNA-seq of murine liver showed an increased expression of the RNA demethylase ALKBH5 in the peri-central low oxygen region. In vitro studies with a human hepatocyte derived HepG2-NTCP cell line showed increased ALKBH5 gene expression under hypoxic conditions and a concomitant reduction in m6A-modified HBV BCP-RNA and host RNAs. Silencing the demethylase reduced the level of BCP-RNAs and host gene (CA9, NDRG1, VEGFA, BNIP3, FUT11, GAP and P4HA1) transcripts and this was mediated via reduced HIFα expression. In summary, our study highlights a previously unrecognized role for ALKBH5 in orchestrating viral and cellular transcriptional responses to low oxygen.

Summary: Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. Our knowledge of the host pathways that define susceptibility to infection and disease severity are limited. Hypoxia inducible factors (HIFs) define metabolic responses to low oxygen and regulate inflammatory responses in the lower respiratory tract. We demonstrate a role for HIFs to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors reduce the expression of the RSV entry receptor nucleolin and inhibit viral cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for this respiratory pathogen.

Summary: Human immunodeficiency virus 1 (HIV-1) causes major health burdens worldwide and still lacks curative therapies and vaccines. Circadian rhythms are endogenous daily oscillations that coordinate an organism’s response to its environment and invading pathogens. Peripheral viral loads of HIV-1 infected patients show diurnal variation; however, the underlying mechanisms remain unknown. Here, we demonstrate a role for the cell-intrinsic clock to regulate rhythmic HIV-1 replication in circadian-synchronized systems. Silencing the circadian activator Bmal1 abolishes this phenotype, and we observe BMAL1 binding to the HIV-1 promoter. Importantly, we show differential binding of the nuclear receptors REV-ERB and ROR to the HIV-long terminal repeat at different circadian times, demonstrating a dynamic interplay in time-of-day regulation of HIV-1 transcription. Bioinformatic analysis shows circadian regulation of host factors that control HIV-1 replication, providing an additional mechanism for rhythmic viral replication. This study increases our understanding of the circadian regulation of HIV-1, which can ultimately inform new therapies.

Sofosbuvir is a common therapy in hepatitis C virus infection, which targets the NS5B polymerase. Here, Smith et al. analyze the association between whole genome HCV polymorphisms and sofosbuvir treatment failure and identify three common polymorphisms present in non-targeted NS2 and NS3 proteins associated with reduced treatment response.

The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the human liver transcriptome but their role in hepatitis B virus infection is largely unknown. Here, Zhuang et al. show that REV-ERB regulates hepatitis B virus entry and BMAL1 directly binds HBV DNA and activates viral genome transcription.

Abstract We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome.

Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge on the infectivity of clinical HCV strains is hampered by the lack of in vitro cell culture systems that support efficient viral replication. We and others have reported that HCV can associate with and infect immune cells and may thereby evade host immune surveillance and elimination. To evaluate whether B cells play a role in HCV transmission, we assessed the ability of B cells and sera from recent (

Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV’s life cycle. We investigated the mechanism(s) behind oestrogen’s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17β-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17β-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17β-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling.

The circadian clock can affect pathogen replication, but underlying molecular mechanisms are unclear. Here the authors demonstrate that the circadian components BMAL1 and REV-ERBα affect entry of hepatitis C virus (HCV) into hepatocytes and genome replication of HCV and related flaviviruses dengue and zika.

Chronic hepatitis B virus (HBV) infection is a global health problem that presents as a spectrum of liver disease, reflecting an interplay between the virus and the host immune system. HBV genomes exist as episomal covalently closed circular DNA (cccDNA) or chromosomal integrants. The relative contribution of these genomes to the viral transcriptome in chronic hepatitis B (CHB) is not well-understood. We developed a qPCR method to estimate the abundance of HBV cccDNA- and integrant-derived viral transcripts and applied this to a cohort of patients diagnosed with CHB in the HBe antigen negative phase of disease. We noted a variable pattern of HBV transcripts from both DNA templates, with preS1/S2 mRNAs predominating and a significant association between increasing age and the expression of integrant-derived mRNAs, but not with inflammatory status. In contrast, cccDNA-derived transcripts were associated with markers of liver inflammation. Analysis of the inflammatory hepatic transcriptome identified 24 genes significantly associated with cccDNA transcriptional activity. Our study uncovers an immune gene signature that associates with HBV cccDNA transcription and increases our understanding of viral persistence.

The phenalenyl-based dysprosium complexes [Dy(PLN)2(HPLN)Cl(EtOH)] (1), [Dy(PLN)3(HPLN)]·[Dy(PLN)3(EtOH)]·2EtOH (2) and [Dy(PLN)3(H2O)2]·H2O (3), HPLN being 9-hydroxy-1H-phenalen-1-one, have been synthesized. All compounds were fully characterized by means of single crystal X-ray analysis, paramagnetic 1H NMR, MALDI-TOF mass spectrometry, UV–vis spectrophotometry and magnetic measurements. Both static (dc) and dynamic (ac) magnetic properties of these complexes have been investigated, showing slow relaxation of magnetization, indicative of single molecule magnet (SMM) behavior. Attempts to synthesize sublimable phenalenyl-based dysprosium complexes have been made by implementing a synthetic strategy under anhydrous conditions. The sublimed species were characterized and their thermal stability was confirmed. This opens up the possibility to deposit phenalenyl-based lanthanides complexes by sublimation onto surfaces, an important prerequisite for ongoing studies in molecular spintronics.

We have studied the electronic properties and the charge carrier mobility of the organic semiconductor tris(1-oxo-1H-phenalen-9-olate)aluminium(III) (Al(Op)3) both experimentally and theoretically. We experimentally estimated the HOMO and LUMO energy levels to be −5.93 and −3.26 eV, respectively, which were close to the corresponding calculated values. Al(Op)3 was successfully evaporated onto quartz substrates and was clearly identified in the absorption spectra of both the solution and the thin film. A structured steady state fluorescence emission was detected in solution, whereas a broad, red-shifted emission was observed in the thin film. This indicates the formation of excimers in the solid state, which is crucial for the transport properties. The incorporation of Al(Op)3 into organic thin film transistors (TFTs) was performed in order to measure the charge carrier mobility. The experimental setup detected no electron mobility, while a hole mobility between 0.6 × 10−6 and 2.1 × 10−6 cm2·V−1·s−1 was measured. Theoretical simulations, on the other hand, predicted an electron mobility of 9.5 × 10−6 cm2·V−1·s−1 and a hole mobility of 1.4 × 10−4 cm2·V−1·s−1. The theoretical simulation for the hole mobility predicted an approximately one order of magnitude higher hole mobility than was observed in the experiment, which is considered to be in good agreement. The result for the electron mobility was, on the other hand, unexpected, as both the calculated electron mobility and chemical common sense (based on the capability of extended aromatic structures to efficiently accept and delocalize additional electrons) suggest more robust electron charge transport properties. This discrepancy is explained by the excimer formation, whose inclusion in the multiscale simulation workflow is expected to bring the theoretical simulation and experiment into agreement.

We have studied the spin-dependent electronic properties of the interface formed between epitaxial Co thin films deposited on Cu(001) and the experimental molecule tris-(9-oxidophenalenone)-aluminum ^(III) (Al(OP) _3 ), created as a variation of the prototypical organic semiconductor Alq _3 to tailor the spin filtering properties by modifying chemisorption with cobalt. The interfaces have been grown under ultra-high vacuum conditions by progressive deposition of 0.5–5 nm Al(OP) _3 on the freshly prepared cobalt substrate. For every growth step we have monitored the energy level alignment at the interface as well as the spin polarization of the occupied manifold by spin-resolved photoemission spectroscopy. We identify two hybrid interface states in the energy window of 2 eV below the Fermi energy. The first is at 0.9 eV below E _F and shows an 8% higher spin polarization than Co, while the second is at 1.6 eV below E _F and shows a spin polarization reduced by 4%.

Abstract Background Delayed discharge from hospital to home or other care institutions is a significant problem and has been investigated in the international scientific literature for many years. Behind this condition is a health care system based on a hospital-centered concept characterized by a lack of territorial health and social welfare services. This phenomenon causes two different problems: an excessive length of hospital stay, resulting in slow turnover of bed utilization; and overcrowding in emergency rooms (ERs). The phenomenon of frequent users assumes particular importance in this context. These patients repeatedly visit the emergency department (ED) in the same year because care needs are not met by primary care services. The authors in this study tried to describe the Frequent users (FUs) population and the variables associated with this condition. Materials and methods A retrospective "single-arm" descriptive study was conducted by analysing all accesses made to the ED of Policlinico Tor Vergata (PTV) from January 1, 2022, to December 31, 2022. FUs were defined as patients who had 4 or more accesses to PTV ER during the year. Results A total of 37,800 accesses occurred during the study period. A total of 31,691 users accessed the PS, with a mean age of 55.8 ± 22.2 years. There were 359 FU patients (approximately 1%) who had a total of 1984 accesses, corresponding to 5.2% of the total accesses. The triage codes for the FU patients were red, 2%; orange, 21%; blue, 45%; green, 26%; white, 5%; and not performed, 1%. Considering the 1984 FU accesses, the most frequently attributed "main problems" in the ED were "other symptoms or disorders" (54%), "psychomotor agitation" (12%), "trauma or burn" (8%), "abdominal pain" (6%), "chest pain" (4%), "dyspnea" (4%) and "urological symptoms or disorders" (4%). Multivariate analysis revealed that the main determinants of FUs were psychomotor agitation (HR = 7,23; CL95%:6,194–8,443), urological disorders (HR = 2,16; CL95%:1,68–2,76) and poor socioeconomic status (HR = 2,40; CL95%:2,213–2,663). Conclusions The FUs phenomenon expresses an area of health and social distress where poverty and lack of territorial services oblige people to refer to the ED. Primary care interventions integrated with social support are crucial for managing access to the ED.

Abstract Mitochondrial dysfunction represents one of the most common molecular hallmarks of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder caused by the selective degeneration and death of motor neurons. The accumulation of misfolded proteins on and within mitochondria, as observed for SOD1 G93A mutant, correlates with a drastic reduction of mitochondrial respiration and the inhibition of metabolites exchanges, including ADP/ATP and NAD+/NADH, across the Voltage-Dependent Anion-selective Channel 1 (VDAC1), the most abundant channel protein of the outer mitochondrial membrane. Here, we show that the AAV-mediated upregulation of VDAC1 in the spinal cord of transgenic mice expressing SOD1 G93A completely rescues the mitochondrial respiratory profile. This correlates with the increased activity and levels of key regulators of mitochondrial functions and maintenance, namely the respiratory chain Complex I and the sirtuins (Sirt), especially Sirt3. Furthermore, the selective increase of these mitochondrial proteins is associated with an increase in Tom20 levels, the receptor subunit of the TOM complex. Overall, our results indicate that the overexpression of VDAC1 has beneficial effects on ALS-affected tissue by stabilizing the Complex I-Sirt3 axis.

Newly licensed physicians (NLPs) are frequently involved in emergencies, requiring a prompt and efficient cardiopulmonary resuscitation, despite poor knowledge about life-support algorithms acquired during academic studies, and low self-confidence levels. This study aims to estimate the influence of guidelines' knowledge on young physicians' self-perceived autonomy in the most common practical scenarios. In this study, 981 young Italian doctors were enrolled (mean age 26.6 years old). The recruiting process was carried out during emergency management training courses. Two self-administered questionnaires have been proposed, respectively, about the knowledge of the algorithms and the self-perceived autonomy in five different scenarios. Young, non-specialized doctors showed low self-confidence, as the average score didn't reach a "passing grade" in any of the questions asked. Only 195 doctors (19.9%) reach the "expertise" group (at least 3 out of 5 scenarios perceived as manageable). The results of the One-Way ANOVA indicate that attending the course has a significant impact on an individual's perceived autonomy. This study suggests the relevance of proper training on the algorithms during and after medical school, to form practically prepared doctors, and to allow the professionals to work safely. [ABSTRACT FROM AUTHOR]

Summary: The voltage-dependent anion-selective channel isoform 1 (VDAC1) is a pivotal component in cellular metabolism and apoptosis with a prominent role in many cancer types, offering a unique therapeutic intervention point. Through an in-silico-to-in-vitro approach we identified a set of VA molecules (VDAC Antagonists) that selectively bind to VDAC1 and display specificity toward cancer cells. Biochemical characterization showed that VA molecules can directly interact with VDAC1 with micromolar affinity by competing with the endogenous ligand NADH for a partially shared binding site. NADH displacement results in mitochondrial distress and reduced cell proliferation, especially when compared to non-cancerous cells. Experiments performed on organoids derived from intrahepatic cholangiocarcinoma patients demonstrated a dose-dependent reduction in cell viability upon treatment with VA molecules with lower impact on healthy cells than conventional treatments like gemcitabine. VA molecules are chemical entities representing promising candidates for further optimization and development as cancer therapy strategies through precise metabolic interventions.

Abstract COVID-19 typically presents with flu-like symptoms due to the viral infection itself. The most severe cases are characterised by lung damage, an important factor in fatal outcome due to alveolar damage. In some cases, patients develop a long COVID with persistent symptoms of chest pain and fatigue. Causes, including organ damage or inflammation, are being investigated. Clinical outcomes are variable and permanent lung damage is not fully understood, while vaccination is effective against severe infection but its effect on respiratory function in mild cases remains uncertain. This retrospective study aims to analyse changes in lung function in HCWs who had COVID-19 between 2020 and 2022, comparing their spirometric test results before and after the pandemic and taking into account their vaccination status. 321 HCWs were included in the study. The study examined spirometric parameters both before and after the pandemic, and all measured outcomes except the FEV1/FVC ratio showed a significant decrease during the study period. We then assessed the association between SARS-CoV-2 infection and changes in lung function parameters, analysing infections in 2020, 2021 and 2022 separately. We found a statistically significant difference in Forced vital capacity (FVC) between infected and non-infected subjects in 2020 and 2021, but not in 2022. To evaluate the protective effect of SARS-CoV-2 vaccination on respiratory function, a linear regression analysis was performed using changes in FVC, Forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio and Peak expiratory flow (PEF) as dependent variables. The analysis showed that the decline in FVC was significantly lower in subjects who had been vaccinated prior to infection. The study concludes that subclinical SARS-CoV-2 infections in 2020 and 2021 worsened respiratory parameters (FVC and FEV1), but vaccination protected against these effects. Even healthy individuals with previous infections showed respiratory changes, with vaccination providing protection, especially for FVC decline. This highlights the importance of vaccinating healthcare workers against COVID-19.

Abstract Mitochondrial dysfunction and the loss of mitophagy, aimed at recycling irreversibly damaged organelles, contribute to the onset of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease affecting spinal cord motor neurons. In this work, we showed that the reduction of mitochondrial respiration, exactly oxygen flows linked to ATP production and maximal capacity, correlates with the appearance of the most common ALS motor symptoms in a transgenic mouse model expressing SOD1 G93A mutant. This is the result of the equal inhibition in the respiration linked to complex I and II of the electron transport chain, but not their protein levels. Since the overall mitochondrial mass was unvaried, we investigated the expression of the Translocator Protein (TSPO), a small mitochondrial protein whose overexpression was recently linked to the loss of mitophagy in a model of Parkinson’s disease. Here we clearly showed that levels of TSPO are significantly increased in ALS mice. Mechanistically, this increase is linked to the overactivation of ERK1/2 pathway and correlates with a decrease in the expression of the mitophagy-related marker Atg12, indicating the occurrence of impairments in the activation of mitophagy. Overall, our work sets out TSPO as a key regulator of mitochondrial homeostasis in ALS.

Mitochondria are key organelles that regulate several functions essential for maintaining cellular homeostasis [...]

Historically, non-cancer diseases have not been considered a health risk following low-dose exposure to ionizing radiation. However, it is now well known that high-dose ionizing radiation causes cardiovascular disease, and emerging epidemiological evidence suggests an excess risk of non-cancer diseases even following exposure to lower doses of ionizing radiation than previously thought. In fact, the evidence is strongest for cardiovascular disease (CVD). The aim of this review was to report the most representative studies and data on the risk of CVD from low-dose radiation in people with occupational exposure. We reported the results of 27 articles selected from a database search of 1151 studies. The results show a complex evidence landscape on the relationship between radiation exposure and cardiovascular disease. In general, published papers show a positive association between ionizing radiation exposure and dermal microcirculation damage, ischemic heart disease, and cerebrovascular disease. Overall, they highlight the need for comprehensive and detailed research to clarify this relationship. Due to limited statistical power, the dose–risk relationship below 0.5 Gy is inconclusive, but if this relationship is found to have no threshold, it could have a significant impact on current estimates of health risks at low doses.

The COVID-19 pandemic has severely affected health systems worldwide and raised the issue of vaccine hesitancy. In 2022, the World Health Organization reported an outbreak of measles infection among people over 20 years of age in the European Region. Previous studies found low rates of measles immunization among Italian healthcare workers (HCWs) and medical students. Vaccine hesitancy is a relevant cause of low immunization rate among HCWs and the general population. We aim to evaluate the measles vaccine uptake among medical students of a large teaching hospital, compared to the pre-pandemic period. This is a retrospective observational study, that evaluated the immune status and the vaccine acceptance rate for measles in medical students at the University of Tor Vergata, Rome, who underwent occupational health surveillance from 1 January to 1 December 2022. We also compared the data with the results of a pre-pandemic survey conducted in 2018. Vaccine uptake among unprotected medical students was 59.5%. The data showed no significant difference in vaccine uptake compared with the pre-COVID-19 period. Conversely, the rate of serologically immune subjects to measles increased from 89.66% in 2018 to 97.45% in 2022 as a result of the recent mandatory vaccination policy. Despite efforts to tackle vaccine hesitancy during the COVID-19 pandemic, measles vaccine uptake is still low among young adults starting their medical training, and their compliance with free workplace vaccination offers is suboptimal. Occupational health services should raise awareness among workers and work together to implement strategies to achieve comprehensive measles vaccination coverage among occupational health workers.

Objective: A troublesome implication of the COVID-19 pandemic has been an increased incidence of antimicrobial resistance. Implementation of containment measures, surveillance and monitoring of multiresistant microorganisms and/or alert organisms (MDROs_AL) should be strengthened. Here, we present the results of our observational study in which the isolation trend of MDROs_AL was compared over several quarters before and during the SARS-CoV-2 pandemic (2019-2020). Results: Although in our hospital the number of hospital admissions decreased significantly during the SARS-CoV-2 pandemic (due to the conversion of our hospital to a COVID hospital), the incidence rate of MDRO_AL infection increased from 18.0–34.6. (incidence rate) Among the MDROs_AL, A. baumannii, carbapenem-resistant enterobacteria, staphylococci/streptococci-MLSB, intermediate/glycopeptide-resistant coagulase-negative staphylococci and vancomycin-resistant enterococci were the most represented.

Mineralization-competent cells, including hypertrophic chondrocytes, mature osteoblasts, and osteogenic-differentiated smooth muscle cells secrete media extracellular vesicles (media vesicles) and extracellular vesicles bound to the extracellular matrix (matrix vesicles). Media vesicles are purified directly from the extracellular medium. On the other hand, matrix vesicles are purified after discarding the extracellular medium and subjecting the cells embedded in the extracellular matrix or bone or cartilage tissues to an enzymatic treatment. Several pieces of experimental evidence indicated that matrix vesicles and media vesicles isolated from the same types of mineralizing cells have distinct lipid and protein composition as well as functions. These findings support the view that matrix vesicles and media vesicles released by mineralizing cells have different functions in mineralized tissues due to their location, which is anchored to the extracellular matrix versus free-floating.

Background: Rubella is a contagious viral infection that occurs most often in children and young adults. Rubella is the leading vaccine-preventable cause of birth defects. Rubella infection in pregnant women may cause fetal death or congenital defects known as congenital rubella syndrome. There is no specific treatment for rubella, but the disease is preventable by vaccination with an efficacy of over 95%. Vaccination coverage is still below the recommended levels and many cases have occurred worldwide. The COVID-19 pandemic has had a negative impact on the immunization programs and the quality of disease surveillance worldwide. Operators of the healthcare setting are at increased risk of infection due to their work duties and should receive preventive vaccination or serologic protection to work in a healthcare setting. Aims: To evaluate the serological evidence of rubella IgG antibodies in female healthcare operators of childbearing age, to assess the risk of a breakthrough infection and the need for an additional dose of vaccine. Methods: We collected age and antibody titers from 449 young female operators aged 11.00 IU/mL. Results: The rate of serologically unprotected subjects was 9.13% (41/449). The mean age of protected subjects was 26.93 years, while the mean age of unprotected subjects was 28.24 years. Age did not correlate with mean titer on statistical analysis (p = 0.10). The acceptance rate among unprotected operators was 31.7%. A positive attitude towards vaccination was found in 11/28 (39.3%) of the unvaccinated subjects, while a negative tendency was found in 2/28 (7.1%) of these subjects; most of the unvaccinated operators 15/28 (53.6%) prefer to postpone the administration of the vaccine. When compared with a similar population from the pre-pandemic period, the actual proportion of immune female subjects was not significantly different from that found in 2019 (90.87% vs. 90.3%). Conclusions: Protection against rubella was suboptimal among female healthcare workers of childbearing age. Acceptance of the rubella vaccine among these operators was low. Most of those who were hesitant intended to postpone the vaccination, while a minority had negative attitudes toward vaccination. A policy of mandatory vaccination policy should overcome the reluctance of operators.

IntroductionHealthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are major public health threats in upper- and lower-middle-income countries. Electronic health records (EHRs) are an invaluable source of data for achieving different goals, including the early detection of HAIs and AMR clusters within healthcare settings; evaluation of attributable incidence, mortality, and disability-adjusted life years (DALYs); and implementation of governance policies. In Italy, the burden of HAIs is estimated to be 702.53 DALYs per 100,000 population, which has the same magnitude as the burden of ischemic heart disease. However, data in EHRs are usually not homogeneous, not properly linked and engineered, or not easily compared with other data. Moreover, without a proper epidemiological approach, the relevant information may not be detected. In this retrospective observational study, we established and engineered a new management system on the basis of the integration of microbiology laboratory data from the university hospital "Policlinico Tor Vergata" (PTV) in Italy with hospital discharge forms (HDFs) and clinical record data. All data are currently available in separate EHRs. We propose an original approach for monitoring alert microorganisms and for consequently estimating HAIs for the entire period of 2018.MethodsData extraction was performed by analyzing HDFs in the databases of the Hospital Information System. Data were compiled using the AREAS-ADT information system and ICD-9-CM codes. Quantitative and qualitative variables and diagnostic-related groups were produced by processing the resulting integrated databases. The results of research requests for HAI microorganisms and AMR profiles sent by the departments of PTV from 01/01/2018 to 31/12/2018 and the date of collection were extracted from the database of the Complex Operational Unit of Microbiology and then integrated.ResultsWe were able to provide a complete and richly detailed profile of the estimated HAIs and to correlate them with the information contained in the HDFs and those available from the microbiology laboratory. We also identified the infection profile of the investigated hospital and estimated the distribution of coinfections by two or more microorganisms of concern. Our data were consistent with those in the literature, particularly the increase in mortality, length of stay, and risk of death associated with infections with Staphylococcus spp, Pseudomonas aeruginosa, Klebsiella pneumoniae, Clostridioides difficile, Candida spp., and Acinetobacter baumannii. Even though less than 10% of the detected HAIs showed at least one infection caused by an antimicrobial resistant bacterium, the contribution of AMR to the overall risk of increased mortality was extremely high.ConclusionsThe increasing availability of health data stored in EHRs represents a unique opportunity for the accurate identification of any factor that contributes to the diffusion of HAIs and AMR and for the prompt implementation of effective corrective measures. That said, artificial intelligence might be the future of health data analysis because it may allow for the early identification of patients who are more exposed to the risk of HAIs and for a more efficient monitoring of HAI sources and outbreaks. However, challenges concerning codification, integration, and standardization of health data recording and analysis still need to be addressed.