Iron homeostasis is particularly important in pathogenic bacteria, which need to compete with the host for this essential cofactor. In Helicobacter pylori, a causative agent of several gastric pathologies, iron uptake and storage genes are regulated at the transcriptional level by the ferric uptake regulator Fur. The regulatory circuit of Fur has recently come under focus because of an intimate interlink with a broader regulatory network governing metal homeostasis, acidic response, and virulence. To dissect the Fur regulatory circuit and identify in vivo targets of regulation, we developed a genome-wide location analysis protocol which allowed the identification of 200 genomic loci bound by Fur as well as the investigation of the binding efficiency of the protein to these loci in response to iron. Comparative analysis with transcriptomes of wild-type and fur deletion mutant strains allowed the distinction between targets associated with Fur regulation and genes indirectly influenced by the fur mutation. The Fur regulon includes 59 genes, 25 of which appear to be positively regulated. A case study conducted by primer extension analysis of two oppositely regulated genes, hpn2 and flaB, suggests that negative regulation as well as positive regulation occurs at the transcriptional level. Furthermore, the results revealed the existence of 13 Fur targeted loci within polycistronic operons, which were associated with transcript deregulation in the fur mutant strain. This study provides a systematic insight of Fur regulation at the genome-wide level in H. pylori and points to regulatory functions extending beyond the classical Fur repression paradigm.

Background: Health-related quality of life (HRQoL) impairment is often reported among COVID-19 ICU survivors, and little is known about their long-term outcomes. We evaluated the HRQoL trajectories between 3 months and 1 year after ICU discharge, the factors influencing these trajectories and the presence of clusters of HRQoL profiles in a population of COVID-19 patients who underwent invasive mechanical ventilation (IMV). Moreover, pathophysiological correlations of residual dyspnea were tested. Methods: We followed up 178 survivors from 16 Italian ICUs up to one year after ICU discharge. HRQoL was investigated through the 15D instrument. Available pulmonary function tests (PFTs) and chest CT scans at 1 year were also collected. A linear mixed-effects model was adopted to identify factors associated with different HRQoL trajectories and a two-step cluster analysis was performed to identify HRQoL clusters. Results: We found that HRQoL increased during the study period, especially for the significant increase of the physical dimensions, while the mental dimensions and dyspnea remained substantially unchanged. Four main 15D profiles were identified: full recovery (47.2%), bad recovery (5.1%) and two partial recovery clusters with mostly physical (9.6%) or mental (38.2%) dimensions affected. Gender, duration of IMV and number of comorbidities significantly influenced HRQoL trajectories. Persistent dyspnea was reported in 58.4% of patients, and weakly, but significantly, correlated with both DLCO and length of IMV. Conclusions: HRQoL impairment is frequent 1 year after ICU discharge, and the lowest recovery is found in the mental dimensions. Persistent dyspnea is often reported and weakly correlated with PFTs alterations. Trial registration: NCT04411459. 15D score 3 months -mean ± SD 0.857 ± 0.133 0.927 ± 0.061 0.800 ± 0.135 0.853 ± 0.114 0.637 ± 0.204 < 0.001 15D score 1 year -mean ± SD 0.880 ± 0.115 0.964 ± 0.033 0.820 ± 0.068 0.866 ± 0.088 0.572 ± 0.112 < 0.001 Mobility -mean ± SD 0.876 ± 0.207 0.963 ± 0.104 0.828 ± 0.191 0.901 ± 0.166 0.375 ± 0.298 < 0.001 Vision -mean ± SD 0.953 ± 0.119 0.992 ± 0.040 0.942 ± 0.108 0.949 ± 0.094 0.681 ± 0.280 < 0.001 Hearing -mean ± SD 0.968 ± 0.098 1.000 ± 0.000 1.000 ± 0.000 0.745 ± 0.135 0.857 ± 0.192 < 0.001 Breathing -mean ± SD 0.746 ± 0.238 0.879 ± 0.154 0.620 ± 0.227 0.753 ± 0.223 0.438 ± 0.238 < 0.001 Sleeping -mean ± SD 0.838 ± 0.238 0.940 ± 0.135 0.716 ± 0.274 0.929 ± 0.142 0.632 ± 0.312 < 0.001 Eating -mean ± SD 0.979 ± 0.102 1.000 ± 0.000 1 .000 ± 0.000 1.000 ± 0.000 0.587 ± 0.221 < 0.001 Speech -mean ± SD 0.980 ± 0.090 0.996 ± 0.032 0.996 ± 0.036 0.948 ± 0.117 0.777 ± 0.276 < 0.001 Excretion -mean ± SD 0.974 ± 0.110 1.000 ± 0.000 1.000 ± 0.000 0.872 ± 0.191 0.720 ± 0.292

Background A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation. The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. Methods This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. Results Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications. ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. Conclusions Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. Trial registration NCT04411459

Purpose The onset of the coronavirus disease 19 (COVID-19) pandemic in Italy induced a dramatic increase in the need for intensive care unit (ICU) beds for a large proportion of patients affected by COVID-19-related acute respiratory distress syndrome (ARDS). The aim of the present study was to describe the health-related quality of life (HRQoL) at 90 days after ICU discharge in a cohort of COVID-19 patients undergoing invasive mechanical ventilation and to compare it with an age and sex-matched sample from the general Italian and Finnish populations. Moreover, the possible associations between clinical, demographic, social factors, and HRQoL were investigated. Methods COVID-19 ARDS survivors from 16 participating ICUs were followed up until 90 days after ICU discharge and the HRQoL was evaluated with the 15D instrument. A parallel cohort of age and sex-matched Italian population from the same geographic areas was interviewed and a third group of matched Finnish population was extracted from the Finnish 2011 National Health survey. A linear regression analysis was performed to evaluate potential associations between the evaluated factors and HRQoL. Results 205 patients answered to the questionnaire. HRQoL of the COVID-19 ARDS patients was significantly lower than the matched populations in both physical and mental dimensions. Age, sex, number of comorbidities, ARDS class, duration of invasive mechanical ventilation, and occupational status were found to be significant determinants of the 90 days HRQoL. Clinical severity at ICU admission was poorly correlated to HRQoL. Conclusion COVID-19-related ARDS survivors at 90 days after ICU discharge present a significant reduction both on physical and psychological dimensions of HRQoL measured with the 15D instrument. Trial Registration: NCT04411459. Supplementary Information The online version contains supplementary material available at 10.1007/s11136-021-02865-7.

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