An unintended consequence of COVID-19 immunity passports-quasi-experimental evidence of moral hazard observed after implementing the domestic Green Pass policy during the second wave of the COVID-19 pandemic in Italy.

Objectives: Amidst the second wave of the COVID-19 pandemic, Italian policymakers mandated to exhibit evidence of vaccination or immunity (the Green Pass) as a condition to access retail premises and public offices. This study aims to offer evidence, in a quasi-experimental setting, suggesting that an unintended consequence of this policy was the emergence of moral hazard. Methods: Google visit duration data measured the time customers typically spend on retail premises or public offices. A pairwise comparison of median visit time per premise was performed at a six-week interval before and after the introduction of the Green Pass. Results: This study is the first to provide evidence of "ex-post" moral hazard associated with introducing a domestic Green Pass policy. The median visiting time on premises that required digital immunity control significantly increased after introducing the domestic Green Pass policy, contrary to other public premises where access remained free of limitations. The increase in median visit time in premises with faster customer turnaround, such as coffee shops (+49%) and fast-food restaurants (+45%), was lower than the increase observed for fine-dining restaurants (+74%) and pizzerias (+163%). No significant increase in median visit time was observed in premises where the Green Pass was not required, such as food supermarkets, retail non-food shops, post offices, banks, pharmacies, and gas stations. Conclusion: The evidence of moral hazard highlights the critical issue of unintended consequences stemming from public health policies. This discovery is pivotal for policymakers, indicating that unforeseen behavioral adjustments could offset the intended benefits despite the intent to reduce risk through measures like the Green Pass.

SEED Consensus Document on SpyGlass-DS. / Documento de consenso de la Sociedad Española de Endoscopia Digestiva sobre SpyGlass-DS.

Endoscopic retrograde cholangiopancreatography (ERCP) is the technique of choice for the treatment of biliopancreatic pathology. However, fluoroscopic imaging does not always allow an adequate diagnosis. On the other hand, some large stones cannot be removed by the usual methods. In these situations, cholangioscopy has proven to be an essential tool for the diagnosis of biliary strictures and the treatment of large stones. Its role in pancreatic pathology is also increasing. The development of a single-operator, disposable cholangioscope has made it possible to expand the technique to a large number of hospitals that perform ERCP. For this reason, the Spanish Society of Digestive Endoscopy has developed this consensus document on the use of the Spyglass-DS cholangioscope. The document has been prepared by a group of endoscopists with expertise in cholangioscopy, reviewing the scientific evidence on the main current indications for cholangiopancreatoscopy.

From 15 Minutes to 15 Seconds: How the Delta Variant Changed the Risk of Exposure to COVID-19. A Comparative Epidemiological Investigation Using Community Mobility Data From the Metropolitan Area of Genoa, Italy.

The Delta variant became dominant during the second wave of the Covid-19 pandemic due to its competitive advantage, the ability to reduce close contact duration from minutes to seconds, and, consequently, increase the risk of exposure to COVID-19. We used game theory to model the most effective public health response to this new threat. We compared the absolute and relative risk of exposure to COVID-19 before and after the emergence of the Delta variant. The absolute risk of exposure was defined as the product of crowding (people within a six feet distance) and visit duration. Our epidemiological investigation used aggregated and anonymized mobility data from Google Maps to estimate the visit duration for 808 premises in the metropolitan area of Genoa, Italy, in June 2021. The relative risk of exposure was obtained by dividing the risk of exposure of each activity by the lowest value (gas stations = 1). The median absolute risk of exposure to COVID-19 increased by sixty-fold in the first semester of 2021, while the relative risk did not significantly differ from the risk of exposure to the ancestral form of Covid-19 (5.9 in 2021 vs. 2.5 in 2021). The Delta variant represents an evolution of the game against COVID-19, but it is not a game-changer. The best response is to commit to our original strategy based on population-wide vaccination and social distancing. Unilateral deviations from the dominant strategy could offer COVID-19 a fighting chance against humanity.

Risk of Exposure to COVID-19: Visit Duration Data Can Inform Our Daily Activities Choices: An Epidemiological Investigation Using Community Mobility Data from the Metropolitan Area of Genoa, Italy.

COVID-19 spreads mainly among people who are in close contact. Policymakers mostly resorted to normative measures to limit close contacts and impose social distancing. Our study aimed to estimate the risk of exposure to COVID-19 by location and activity in crowded metropolitan areas. The risk of exposure to COVID-19 was defined as the product of crowding (people within a six feet distance) and exposure duration (fraction of 15 min). Our epidemiological investigation used aggregated and anonymized mobility data from Google Maps to estimate the visit duration. We collected visit duration data for 561 premises in the metropolitan area of Genoa, Italy from October 2020 to January 2021. The sample was then clustered into 14 everyday activities, from grocery shopping to the post office. Crowding data by activity were obtained from pre-existing building norms and new government measures to contain the pandemic. The study found significant variance in the risk of exposure to COVID-19 among activities and, for the same activity, among locations. The empirical determination of the risk of exposure to COVID-19 can inform national and local public health policies to contain the pandemic's diffusion. Its simple numerical form can help policymakers effectively communicate difficult decisions affecting our daily lives. Most importantly, risk data by location can help us rethink our daily routine and make informed, responsible choices when we decide to go out.

Cross-regional variations of Covid-19 mortality in Italy: an ecological study.

BACKGROUND: Disparities in cross-regional coronavirus disease 2019 (Covid-19) mortality remain poorly understood. The association between pre-epidemic health and epidemic mortality can inform a policy response to future outbreaks. METHOD: We conducted an ecological study of the association between the cumulative deaths attributed to Covid-19 epidemic in the 20 Italian regions and nine determinants of population health derived from a systematic review of the literature. We used a multiple least square regression to predict the cross-regional variation in mortality observed from the onset of the epidemic to 23 September 2020. RESULTS: Four independent variables best explained the cross-regional differences in the number of deaths attributed to Covid-19: the force of infection, population density, number of elderly living in assisted facilities and the standard rate of diabetes. The semi-partial correlation coefficients suggest that the force of infection and the number of elderly residents in nursing homes were the dominant predictors of the number of deaths attributed to Covid-19. Statistical controls and validation confirmed the generalizability of the predictive model. CONCLUSIONS: Our findings indicate that a significant reduction of social contacts in main metropolitan areas and the timely isolation of elderly and diabetic residents could significantly reduce the death toll of the next wave of Covid-19 infection in Italy.

Evaluation of the relationship between lactacidemia and postoperative complications after surgery for peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery was developed as a treatment for peritoneal carcinomatosis. However, this surgery is associated with important complications. The present study aimed to assess the relationship between lactacidemia and the rate of associated complications during the immediate postoperative period in the intensive care unit (ICU) in patients undergoing cytoreductive surgery. METHODS: This was a retrospective observational study. A total of 57 patients underwent cytoreductive surgery. All patients were admitted to the ICU immediately after the surgery. Data on lactic acid levels at the time of admission and discharge from the ICU were collected. Postsurgical complications that occurred during the ICU stay were recorded according to failure-to-rescue analysis and their severity stratified according to the Clavien-Dindo classification. RESULTS: The lactic acid levels at admission to the ICU were significantly higher in patients who developed complications, with an almost tripled unadjusted relative risk (2.9, 95% CI: 1.6, 5.3), than in those who did not develop complications for the lactacidemia threshold established in the cumulative sum curve graphs. After adjustment for confounding effects, the relative risk became even higher (3.1, 95% CI: 1.8, 3.6). Lactic acid levels were still significantly higher in this group at the time of discharge from the ICU. CONCLUSIONS: Serum lactate level is a risk factor for postoperative complications in patients undergoing cytoreductive surgery for peritoneal carcinomatosis. This study suggests that the risk of developing severe complications almost triples with a lactic acid level of 2.5 mmol/L or higher at the time of admission in the ICU.

Solvatochromism in urea/water and urea-derivative/water solutions.

This work reports the experimental measurements of solvent acidity (SA), basicity (SB), and solvent dipolarity and polarizability (SPP) for water solutions with urea (U) and its molecular derivatives, monomethyl-urea (MU), 1,3-dimethyl-urea (DMU) and tetramethyl-urea (TMU). These solvatochromic parameters are applied to understanding the variation of indexes of refraction and densities and other physico-chemical properties reported for these solutions. These properties are well correlated to the SA, SB, and SPP solvent parameters of these solutions. As a result, from the characterization of the physico-chemical properties, one can infer that urea and its molecular derivatives are mainly modifiers in the structure of liquid water. The solvatochromic parameters indicate the possible existence of different mechanisms in the denaturation process of proteins in these urea/water solutions.

Discovery of novel triazolo[4,3-b]pyridazin-3-yl-quinoline derivatives as PIM inhibitors.

PIM kinase family (PIM-1, PIM-2 and PIM-3) is an appealing target for the discovery and development of selective inhibitors, useful in various disease conditions in which these proteins are highly expressed, such as cancer. The significant effort put, in the recent years, towards the development of small molecules exhibiting inhibitory activity against this protein family has ended up with several molecules entering clinical trials. As part of our ongoing exploration for potential drug candidates that exhibit affinity towards this protein family, we have generated a novel chemical series of triazolo[4,3-b]pyridazine based tricycles by applying a scaffold hopping strategy over our previously reported potent pan-PIM inhibitor ETP-47453 (compound 2). The structure-activity relationship studies presented herein demonstrate a rather selective PIM-1/PIM-3 biochemical profile for this novel series of tricycles, although pan-PIM and PIM-1 inhibitors have also been identified. Selected examples show significant inhibition of the phosphorylation of BAD protein in a cell-based assay. Moreover, optimized and highly selective compounds, such as 42, did not show significant hERG inhibition at 20 µM concentration, and proved its antiproliferative activity and utility in combination with particular antitumoral agents in several tumor cell lines.

Structure-based domain assignment in Leishmania infantum EndoG: characterization of a pH-dependent regulatory switch and a C-terminal extension that largely dictates DNA substrate preferences.

Mitochondrial endonuclease G from Leishmania infantum (LiEndoG) participates in the degradation of double-stranded DNA (dsDNA) during parasite cell death and is catalytically inactive at a pH of 8.0 or above. The presence, in the primary sequence, of an acidic amino acid-rich insertion exclusive to trypanosomatids and its spatial position in a homology-built model of LiEndoG led us to postulate that this peptide stretch might act as a pH sensor for self-inhibition. We found that a LiEndoG variant lacking residues 145-180 is indeed far more active than its wild-type counterpart at pH values >7.0. In addition, we discovered that (i) LiEndoG exists as a homodimer, (ii) replacement of Ser211 in the active-site SRGH motif with the canonical aspartate from the DRGH motif of other nucleases leads to a catalytically deficient enzyme, (iii) the activity of the S211D variant can be restored upon the concomitant replacement of Ala247 with Arg and (iv) a C-terminal extension is responsible for the observed preferential cleavage of single-stranded DNA (ssDNA) and ssDNA-dsDNA junctions. Taken together, our results support the view that LiEndoG is a multidomain molecular machine whose nuclease activity can be subtly modulated or even abrogated through architectural changes brought about by environmental conditions and interaction with other binding partners.

Calidad de vida y competencias sociales: un estudio comparativo entre adolescentes nativos e inmigrantes de España y Portugal / Quality of life and social skills: a comparative study between native and immigrant adolescents in Spain and Portugal

Resumen Esta investigación pretende conocer las relaciones entre las competencias sociales y la calidad de vida (CdV) de los adolescentes nativos e inmigrantes de España y Portugal, para analizar la importancia que tienen estas variables en el desarrollo ajustado adolescente. Para ello, se evaluaron 1151 adolescentes, con edades entre los 12 y 18 años, a través de dos cuestionarios: el KIDSCREEN-52 y Social Skills Rating System (SSRS). Los resultados señalan que los inmigrantes presentan un índice de CdV menor que los nativos en las dimensiones de bienestar psicológico, relación con los padres, recursos económicos y aceptación social. El rendimiento académico correlaciona con las dimensiones de CdV y con las competencias sociales, aunque existen diferencias entre los adolescentes nativos e inmigrantes.

Abstract This research aims to determine the relationship between social skills and quality of life (QoL) in native and immigrant adolescents of Spain and Portugal, in order to understand the importance of these variables in the adolescents' development and adjustment. In order to accomplish this, 1151 adolescents, aged between 12 and 18 years, were assessed through two questionnaires: the KIDSCREEN-52 and the Social Skills Rating System (SSRS). The results indicate that immigrants have a lower QoL index than natives in the dimensions of feelings, relationship with parents, economic resources and social acceptance. Academic performance correlates with the dimensions of QoL and social skills, although there are differences between natives and immigrant adolescents.

IL-6, IL-10 and TNFα do not improve early detection of post-endoscopic retrograde cholangiopancreatography acute pancreatitis: a prospective cohort study.

The most reliable indicators for post-ERCP acute pancreatitis are elevated amylase levels and abdominal pain 24 hours after ERCP. As ERCP is often performed on an outpatient basis, earlier diagnosis is important. We aimed to identify early predictors of post-ERCP pancreatitis. We prospectively analyzed IL-6, IL-10, TNFα, CRP, amylase and lipase before and 4 hours after ERCP, and studied their association with abdominal pain. We included 510 patients. Post-ERCP pancreatitis occurred in 36 patients (7.1%). IL-6, IL-10, TNFα and CRP were not associated with post-ERCP pancreatitis. Levels of amylase and lipase were higher in patients with pancreatitis (522 U/L and 1808 U/L vs. 78 U/L and 61 U/L, respectively; p < 0.001). A cut-off of 218 U/L for amylase (x2.2 ULN) and 355 U/L for lipase (x6 ULN) had a negative predictive value of 99.2% and 99.5%, respectively. Amylase and lipase present a good correlation (Pearson coefficient 0.912). Among 342 (67.1%) patients without abdominal pain at 4 hours, post-ERCP pancreatitis was diagnosed in 8 (2.3%). Only 4 of these patients presented amylase or lipase > 3 ULN. Amylase and lipase were the only markers of post-ERCP pancreatitis 4 hours after the procedure.

Quality of life of Portuguese and Spanish adolescents. A comparative study between natives and immigrants.

The aim of this study was to analyse differences in quality of life (QOL) between Spanish and Portuguese immigrant and native adolescents. In total, 475 native and immigrant adolescents (52% boys) from Algarve (Portugal) and Huelva (Spain), aged between 12 and 17 years old, were assessed with the KIDSCREEN-52. QOL dimensions were not related to most academic variables, with the exception of number of school failures, Financial Resources and Social Support from Peers. Multivariate analysis of variance (MANOVA) was used to examine statistical differences in adolescents QOL. Age differences in QOL levels were not found. Girls reported worse QOL levels on Physical Wellbeing than boys (F = 10.32, p = .001, η2 =.02). Immigrant Portuguese adolescents scored higher on Mood (F = 17.57, p = .000, η2 =.11), and native Portuguese adolescents scored higher on Social Acceptance (F = 4.87, p = .002, η2=.033). Immigrant and native adolescents had similar levels of perceived QOL. Overall, it seems that in both countries, the living contexts for immigrant and native adolescents are fairly homogeneous.

Quality of life of Portuguese and Spanish adolescents. A comparative study between natives and immigrants / Qualidade de Vida nos adolescentes portugueses e espanhóis. Um estudo comparativo entre nativos e imigrantes

Abstract The aim of this study was to analyse differences in quality of life (QOL) between Spanish and Portuguese immigrant and native adolescents. In total, 475 native and immigrant adolescents (52% boys) from Algarve (Portugal) and Huelva (Spain), aged between 12 and 17 years old, were assessed with the KIDSCREEN-52. QOL dimensions were not related to most academic variables, with the exception of number of school failures, Financial Resources and Social Support from Peers. Multivariate analysis of variance (MANOVA) was used to examine statistical differences in adolescents QOL. Age differences in QOL levels were not found. Girls reported worse QOL levels on Physical Wellbeing than boys (F = 10.32, p = .001, η2 =.02). Immigrant Portuguese adolescents scored higher on Mood (F = 17.57, p = .000, η2 =.11), and native Portuguese adolescents scored higher on Social Acceptance (F = 4.87, p = .002, η2=.033). Immigrant and native adolescents had similar levels of perceived QOL. Overall, it seems that in both countries, the living contexts for immigrant and native adolescents are fairly homogeneous.

Resumo Neste estudo são analisadas as diferenças na qualidade de vida (QVD) entre adolescentes imigrantes e nativos de Espanha e Portugal. Avaliou-se a QDV percebida de 475 adolescentes nativos e imigrantes (52% rapazes) entre os 12 e os 17 anos de idade do Algarve (Portugal) e Huelva (Espanha) através do questionário KIDSCREEN-52 e o perfil sociodemográfico. As dimensões da QDV não estavam associadas à maioria das variáveis acadêmicas, excetuando o número de repetições, recursos econômicos e apoio dos pares. Para analisar as diferenças da QVD entre os adolescentes foram realizadas análises de variância multivariada (MANOVA). Não se encontraram diferenças na QDV por idade. As raparigas reportaram piores níveis de QDV no bem-estar físico do que os rapazes (F = 10.32, p = .001, η2 =.02). Os adolescentes portugueses imigrantes mostraram níveis mais elevados no Humor (F = 17.57, p = .000, η2=.11) e os nativos obtiveram pontuações mais altas na Aceitação social (F = 4.87, p = .002, η2 =.033). Os resultados sugerem que os adolescentes imigrantes e nativos têm níveis semelhantes de QDV percebida. Em conjunto, parece que nos dois países os contextos vitais dos adolescentes nativos e imigrantes são bastante homogêneos.

Steady-State Spectroscopy of the 2-(N-methylacetimidoyl)-1-naphthol Molecule.

The steady-state spectroscopy of 2-(N-methylacetimidoyl)-1-naphthol (MAN) reveals composite absorption and emission spectra from 298 to 193 K in hexane. The ground electronic state (So) absorption can be assigned to the sum of three molecular structures: the OH normal tautomer, and two NH proton transfer tautomers. The NH-structures are the most stable ones in equilibrium with the OH tautomer for the S0 state. On photoexcitation of the OH tautomer the excited state intramolecular proton transfer is undergone, and the corresponding NH emission is monitored at 470 nm. On photoexcitation of the NH tautomers the previous emission is monitored in addition to another emission at 600 nm, which is ascribed to intramolecular hydrogen-bonded (IHB) nonplanar NH structures generated from the IHB planar NH tautomers. A Jablonski diagram is introduced which gathers all the experimental evidence as well as the theoretical calculations executed at the DFT-B3LYP and TD-DFT levels. The MAN molecule is compared with other analogs such as 1-hydroxy-2-acetonaphthone (HAN), 2-(1'-hydroxy-2'-naphthyl)benzimidazole and methyl 1-hydroxy-2-naphthoate to validate the theoretical calculations. Photoexcitation of MAN generates two emission bands at longer wavelengths than that of the emission band of HAN. The MAN molecule exhibits a great photostability in hydrocarbon solution which depends on the photophysics of the NH tautomers (keto forms).

Somatostatin for prevention of post-ERCP pancreatitis: a randomized, double-blind trial.

BACKGROUND AND STUDY AIMS: Meta-analyses suggest that an intravenous bolus or a high dose continuous infusion of somatostatin reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). Clinical guidelines, however, do not recommend this prophylaxis. The aim of this randomized, double-blind clinical trial was to evaluate the effect of somatostatin on the incidence of post-ERCP pancreatitis. PATIENTS AND METHODS: Patients undergoing ERCP at a single center were randomized to either intravenous bolus of somatostatin followed by a short (4-hour) continuous infusion, or to a similar placebo regimen. The primary outcome was post-ERCP pancreatitis, defined as abdominal pain with an amylase level at least three times higher than the upper limit of normality 24 hours after the ERCP and requiring admission for at least 2 days. RESULTS: A total of 510 patients were enrolled (255 patients per group) and all completed follow-up. The main indications for ERCP were choledocholithiasis (62 %), and biliary malignant stricture (31 %). Post-ERCP pancreatitis occurred in 19 patients (7.5 %) in the somatostatin group and 17 patients (6.7 %) in the placebo group (relative risk [RR] 1.12, 95 % confidence interval [95 %CI] 0.59 - 2.1; P = 0.73). The number of cases of moderate or severe acute pancreatitis was similar in the somatostatin (2.4 %) and the placebo (3.5 %) groups (RR 0.67, 95 %CI 0.24 - 1.85, P = 0.43). No side effects were observed related to the use of somatostatin. CONCLUSIONS: Administration of an intravenous bolus of somatostatin followed by a short continuous infusion does not reduce the incidence of post-ERCP pancreatitis. Clinical Trials.gov number: NCT01060826.