Counteranion and Solvent Assistance in Ruthenium-Mediated Alkyne to Vinylidene Isomerizations

The complex [Cp*RuCl(iPr2PNHPy)] (1) reacts with 1-alkynes HC≡CR (R = COOMe, C6H4CF3) in dichloromethane furnishing the corresponding vinylidene complexes [Cp*Ru≡C≡CHR(iPr2PNHPy)]Cl (R = COOMe (2a- Cl), C6H4CF3 (2b-Cl)), whereas reaction of 1 with NaBPh4 in MeOH followed by addition of HC≡CR (R = COOMe, C6H4CF3) yields the metastable π-alkyne complexes [Cp*Ru(η2-HC≡CR)(iPr2PNHPy)][BPh4] (R = COOMe (3a-BPh4), C6H4CF3 (3b-BPh4)). The transformation of 3a-BPh4/3b-BPh4 into their respective vinylidene isomers in dichloromethane is very slow and requires hours to its completion. However, this process is accelerated by addition of LiCl in methanol solution. Reaction of 1 with HC≡CR (R = COOMe, C6H4CF3) in MeOH goes through the intermediacy of the π-alkyne complexes [Cp*Ru(η2-HC≡CR)(iPr2PNHPy)]Cl (R = COOMe (3a-Cl), C6H4CF3 (3b-Cl)), which rearrange to vinylidenes in minutes, i.e., much faster than their counterparts containing the [BPh4]− anion. The kinetics of these isomerizations has been studied in solution by NMR. With the help of DFT studies, these observations have been interpreted in terms of chloride- and methanolassisted hydrogen migrations. Calculations suggest participation of a hydrido−alkynyl intermediate in the process, in which the hydrogen atom can be transferred from the metal to the β-carbon by means of species with weak basic character acting as proton shuttles

Structural Setting of the Trieste Area from Gravity Modelling

Il lavoro riporta un'analisi delle anomlaie gravimtertiche dell'area Nord-Est d'Italia sulla base di dati di nuova acquisizione per la definizione di un modello strutturale dell'are

A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies.

Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have transformed the management of many malignancies. Although rare, immune-mediated myocarditis presents unique clinical challenges due to heterogenous presentation, potential life-threatening consequences, and the time-critical need to differentiate it from other causes of cardiac dysfunction. Increasingly, TKI are being combined with ICI to promote immune modulation and improve efficacy. However, these combinations are associated with more toxicities. This series describes six patients with advanced melanoma who developed immune-mediated myocarditis while receiving an anti-PD-1 antibody or an anti-PD-L1 antibody plus a mitogen-activated protein kinase inhibitor. It provides a review of their heterogenous clinical presentations, investigational findings and treatment outcomes. Presentations ranged from asymptomatic cardiac enzyme elevation to death due to heart failure. We highlight the role of cardiac MRI (CMRI), a sensitive and non-invasive tool for the early detection and subsequent monitoring of myocardial inflammation. Five of the six patients exhibited CMRI changes characteristic of myocarditis, including mid-wall myocardial oedema and late gadolinium enhancement in a non-coronary distribution. Critically, two of these patients had normal findings on echocardiogram. Of the five patients who received immunosuppression, four recovered from myocarditis and one died of cardiac failure. The sixth patient improved with cardiac failure management alone. Three of the four patients responding to ICI derived long-term benefit. Clinical vigilance, prompt multimodal diagnosis and multidisciplinary management are paramount for the treatment of immune-mediated myocarditis

Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes

Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes

Consequences of the COVID-19 pandemic on admissions to general hospital psychiatric wards in Italy: Reduced psychiatric hospitalizations and increased suicidality

Aims: The present investigation aimed at evaluating differences in psychiatric hospitalizations in Italy during and after the lockdown due to the novel coronavirus disease 2019 (COVID-19), compared to the same periods in 2018 and 2019. Methods: We obtained and analyzed anonymized data on psychiatric admissions (n = 4550) from 12 general hospital psychiatric wards (GHPWs) in different Italian regions (catchment area = 3.71 millions of inhabitants). Using a mixed-effects Poisson regression model, we compared admission characteristics across three periods: (a) March 1\u2013June 30, 2018 and 2019; (b) March 1\u2013April 30, 2020 (i.e., lockdown); and (c) May 1\u2013June 30, 2020 (i.e., post-lockdown). Results: During the COVID-19 lockdown, there was a 41% reduction (IRR = 0.59; p 65 years) was observed in the lockdown (40%; IRR = 0.60; 95% CI: 0.44\u20130.82) and post-lockdown (28%; IRR = 0.72; 95% CI: 0.54\u20130.96) periods. Long-stay admissions (>14 days) increased (63%; IRR = 1.63; 95% CI: 1.32\u20132.02) during the lockdown and decreased by 39% thereafter (IRR = 0.61; 95% CI: 0.49\u20130.75). A significant 35% increase in patients reporting suicidal ideation was observed in the post-lockdown period, compared to the rate observed in the 2018 and 2019 control period (IRR = 1.35; 95% CI: 1.01\u20131.79). Conclusion: The COVID-19 lockdown was associated with changes in the number of psychiatric admissions, particularly for older patients and long-stay hospitalizations. Increased admission of patients reporting suicidal ideation in the post-lockdown period merits special attention. Further studies are required to gain insight into the observed phenomena

Consequences of the COVID-19 pandemic on admissions to general hospital psychiatric wards in Italy: Reduced psychiatric hospitalizations and increased suicidality

Aims: The present investigation aimed at evaluating differences in psychiatric hospitalizations in Italy during and after the lockdown due to the novel coronavirus disease 2019 (COVID-19), compared to the same periods in 2018 and 2019. Methods: We obtained and analyzed anonymized data on psychiatric admissions (n = 4550) from 12 general hospital psychiatric wards (GHPWs) in different Italian regions (catchment area = 3.71 millions of inhabitants). Using a mixed-effects Poisson regression model, we compared admission characteristics across three periods: (a) March 1–June 30, 2018 and 2019; (b) March 1–April 30, 2020 (i.e., lockdown); and (c) May 1–June 30, 2020 (i.e., post-lockdown). Results: During the COVID-19 lockdown, there was a 41% reduction (IRR = 0.59; p < 0.001, CI: 0.45–0.79) in psychiatric admissions in the enrolled GHPWs with respect to the 2018 and 2019 control period. Conversely, admission rates in the post-lockdown period were similar to those observed in the control period. Notably, a consistent and significant reduction in psychiatric hospitalizations of older patients (aged >65 years) was observed in the lockdown (40%; IRR = 0.60; 95% CI: 0.44–0.82) and post-lockdown (28%; IRR = 0.72; 95% CI: 0.54–0.96) periods. Long-stay admissions (>14 days) increased (63%; IRR = 1.63; 95% CI: 1.32–2.02) during the lockdown and decreased by 39% thereafter (IRR = 0.61; 95% CI: 0.49–0.75). A significant 35% increase in patients reporting suicidal ideation was observed in the post-lockdown period, compared to the rate observed in the 2018 and 2019 control period (IRR = 1.35; 95% CI: 1.01–1.79). Conclusion: The COVID-19 lockdown was associated with changes in the number of psychiatric admissions, particularly for older patients and long-stay hospitalizations. Increased admission of patients reporting suicidal ideation in the post-lockdown period merits special attention. Further studies are required to gain insight into the observed phenomena