Studying GGDEF Domain in the Act: Minimize Conformational Frustration to Prevent Artefacts

GGDEF-containing proteins respond to different environmental cues to finely modulate cyclic diguanylate (c-di-GMP) levels in time and space, making the allosteric control a distinctive trait of the corresponding proteins. The diguanylate cyclase mechanism is emblematic of this control: two GGDEF domains, each binding one GTP molecule, must dimerize to enter catalysis and yield c-di-GMP. The need for dimerization makes the GGDEF domain an ideal conformational switch in multidomain proteins. A re-evaluation of the kinetic profile of previously characterized GGDEF domains indicated that they are also able to convert GTP to GMP: this unexpected reactivity occurs when conformational issues hamper the cyclase activity. These results create new questions regarding the characterization and engineering of these proteins for in solution or structural studies

Cohort profile: the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS), a multicentre cohort for socioeconomic inequalities in health monitoring.

PURPOSE: The Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS) is a system of integrated data on health outcomes, demographic and socioeconomic information, and represents a powerful tool to study health inequalities. PARTICIPANTS: IN-LiMeS is a multicentre and multipurpose pool of metropolitan population cohorts enrolled in nine Italian cities: Turin, Venice, Reggio Emilia, Modena, Bologna, Florence, Leghorn, Prato and Rome. Data come from record linkage of municipal population registries, the 2001 population census, mortality registers and hospital discharge archives. Depending on the source of enrolment, cohorts can be closed or open. The census-based closed cohort design includes subjects resident in any of the nine cities at the 2001 census day; 4 466 655 individuals were enrolled in 2001 in the nine closed cohorts. The open cohort design includes subjects resident in 2001 or subsequently registered by birth or immigration until the latest available follow-up (currently 31 December 2013). The open cohort design is available for Turin, Venice, Reggio Emilia, Modena, Bologna, Prato and Rome. Detailed socioeconomic data are available for subjects enrolled in the census-based cohorts; information on demographic characteristics, education and citizenship is available from population registries. FINDINGS TO DATE: The first IN-LiMeS application was the study of differentials in mortality between immigrants and Italians. Either using a closed cohort design (nine cities) or an open one (Turin and Reggio Emilia), individuals from high migration pressure countries generally showed a lower mortality risk. However, a certain heterogeneity between the nine cities was noted, especially among men, and an excess mortality risk was reported for some macroareas of origin and specific causes of death. FUTURE PLANS: We are currently working on the linkage of the 2011 population census data, the expansion of geographical coverage and the implementation of the open design in all the participating cohorts

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Geografia e centri di responsabilità: un’applicazione di analisi dei raggruppamenti nel contesto piemontese

L’articolo presenta i risultati di un’applicazione finalizzata a valutare la possibilità di individuare all’interno del territorio regionale piemontese macroaree omogenee per caratteristiche di bisogno,domanda e offerta di servizi sanitari. A tal fine sono state effettuate in successione un’analisi fattoriale e un’analisi dei cluster sui 1.206 comuni della regione Piemonte, tenendo conto di un set molto esteso di indicatori di bisogno (mortalità, parametri socioeconomici), domanda (ospedalizzazione: intensità, appropriatezza, mobilità, efficienza, efficacia; assistenza specialistica ambulatoriale; ricorso al pronto soccorso), offerta (posti letto, n. branche di erogazione di assistenza specialistica, distanza dal punto di offerta). L’analisi fattoriale ha spiegato circa il 60% della variabilità complessiva. I risultati dell’analisi dei cluster mostrano la presenza di 5 raggruppamenti geografici di comuni, ben caratterizzabili da dicotomie di eccesso-difetto rispetto a sottoinsiemi di macroindicatori, che ne evidenziano specificità e criticità assistenziali. Queste aree sub-regionali sono caratterizzate da contiguità territoriale, che potrebbe delineare possibili confini di area vasta, come opzione verso scelte di programmazione regionale che deleghino la composizione di bisogno, domanda e offerta a piani orientati in tal senso. Inoltre, nell’ambito dei processi riorganizzativi, esercizi di questa natura potrebbero essere finalizzati al miglioramento del governo dei percorsi assistenziali organizzati in rete per l’identificazione dei relativi poli

Socioeconomic inequalities in coronary heart disease in Italy: A multilevel population-based study

This longitudinal study evaluates the role of individual and contextual socioeconomic determinants in the socioeconomic inequalities in incidence and mortality for coronary events in Turin, Italy, using hierarchical models. All residents aged 35-74 at the start of 1997 were included in the study population. We considered as outcomes all incident cases and deaths that occurred in the study population in the period 1997-2002. The socioeconomic indicators were educational level, job status and median income per census tract. A neighbourhood deprivation index was also used, which combines, in an aggregated measure, a series of poor individual socioeconomic conditions. The analyses were performed using hierarchical Poisson models, with individuals (n=523,755) considered as level I units and neighbourhoods (n=23) as level II units. Among men, we observed an inverse gradient in incidence by educational level and an excess risk for persons who were not actively employed. More marked excesses were found for mortality (RR: 1.63; 95% CI: 1.05-2.55, for unemployed persons compared to employed persons). Among women, greater socioeconomic differences were observed for both incidence and mortality; all of the individual indicators contributed to these differences. The differentials in mortality were particularly great for the retired and for housewives (RR: 1.98; 95% CI: 1.40-2.81). Slight excesses in incidence were observed among men for the most deprived areas. The results of this study reveal that job status is the most important individual factor explaining socioeconomic inequalities for coronary events, whereas context seems to play a marginal role.Coronary events Socioeconomic inequalities Contextual effects Hierarchical models Italy Gender

The variation in the health status of immigrants and Italians during the global crisis and the role of socioeconomic factors

Abstract Background The effects of the recent global economic and financial crisis especially affected the most vulnerable social groups. Objective of the study was to investigate variation of self-perceived health status in Italians and immigrants during the economic global crisis, focusing on demographic and socioeconomic factors. Methods Through a cross-sectional design we analyzed the national sample of multipurpose surveys “Health conditions and use of health services” (2005 and 2013) conducted by the Italian National Institute of Statistics (ISTAT). Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, derived from SF-12 questionnaire, were assumed as study outcome, dichotomizing variables distribution at 1st quartile. Prevalence rate ratios (PRR) were estimated through log-binomial regression models, stratified by citizenship and gender, evaluating the association between PCS and MCS with surveys’ year, adjusting for age, educational level, employment status, self-perceived economic resources, smoking habits, body mass index. Results From 2005 to 2013 the proportion of people not employed or reporting scarce/insufficient economic resources increased, especially among men, in particular immigrants. Compared with 2005 we observed in 2013 among Italians a significant lower probability of worse PCS (PRR = 0.96 both for males and females), while no differences were observed among immigrants; a higher probability of worse MCS was observed, particularly among men (Italians: PRR = 1.26;95%CI:1.22–1.29; immigrants: PRR = 1.19;95%CI:1.03–1.38). Self-perceived scarce/insufficient economic resources were strongly and significantly associated with worse PCS and MCS for all subgroups. Lower educational level was strongly associated with worse PCS in Italians and slightly associated with worse MCS for all subgroups. Being not employed was associated with worse health status, especially mental health among men. Conclusions Our findings support the hypothesis that economic global crisis could have negatively affected health status, particularly mental health, of Italians and immigrants. Furthermore, results suggest socioeconomic inequalities increase, in economic resources availability dimension. In a context of public health resources’ limitation due to financial crisis, policy decision makers and health service managers must face the challenge of equity in health

The 2008 Financial Crisis and Changes in Lifestyle-Related Behaviors in Italy, Greece, Spain, and Portugal: A Systematic Review

Italy, Greece, Spain, and Portugal have all been strongly affected by the 2008 financial crisis, which has had a negative impact on health. We systematically evaluated the effects of the crisis on lifestyle and socioeconomic inequalities. We conducted a literature search using MEDLINE, Embase, the Cochrane Library, and health economics databases for studies reporting quantitative comparisons before and after (or during) the crisis on the following risk behaviors: alcohol consumption, smoking habit, healthy diet, physical activity, and psychotropic drugs and substance abuse, without setting any age restrictions. We selected 34 original articles published between 2011 and 2020. During/after the crisis, alcohol consumption and substance abuse decreased, while psychotropic drug use increased. We also observed a deterioration in healthy eating behavior, with a reduction in fruit and vegetable consumption. Smoking habit and physical activity showed a more complex, controversial trend. Socioeconomic inequalities were affected by the recession, and the negative effects on unhealthy lifestyle tended to be more pronounced among the disadvantaged. These results suggest the need to implement health policies and interventions aimed at monitoring risk behaviors, with special regard to disadvantaged people, and considering the potential additional impact of the COVID-19 pandemic