A Systemic and Severe Infection via Cytomegalovirus and Other Herpesviruses in a Young Apparently Immunocompetent Patient: A Case Report

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Radiation Damage Mechanisms of Chemotherapeutically Active Nitroimidazole Derived Compounds

Photoionization mass spectrometry, photoelectron-photoion coincidence spectroscopic technique, and computational methods have been combined to investigate the fragmentation of two nitroimidazole derived compounds: the metronidazole and misonidazole. These molecules are used in radiotherapy thanks to their capability to sensitize hypoxic tumor cells to radiation by “mimicking” the effects of the presence of oxygen as a damaging agent. Previous investigations of the fragmentation patterns of the nitroimidazole isomers (Bolognesi et al., 2016; Cartoni et al., 2018) have shown their capacity to produce reactive molecular species such as nitric oxide, carbon monoxide or hydrogen cyanide, and their potential impact on the biological system. The results of the present work suggest that different mechanisms are active for the more complex metronidazole and misonidazole molecules. The release of nitric oxide is hampered by the efficient formation of nitrous acid or nitrogen dioxide. Although both metronidazole and misonidazole contain imidazole ring in the backbone, the side branches of these molecules lead to very different bonding mechanisms and properties

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Perspectives of Gas Phase Ion Chemistry: Spectroscopy and Modeling

The study of ions in the gas phase has a long history and has involved both chemists and physicists. The interplay of their competences with the use of very sophisticated commercial and/or homemade instrumentations and theoretical models has improved the knowledge of thermodynamics and kinetics of many chemical reactions, even if still many stages of these processes need to be fully understood. The new technologies and the novel free-electron laser facilities based on plasma acceleration open new opportunities to investigate the chemical reactions in some unrevealed fundamental aspects. The synchrotron light source can be put beside the FELs, and by mass spectrometric techniques and spectroscopies coupled with versatile ion sources it is possible to really change the state of the art of the ion chemistry in different areas such as atmospheric and astro chemistry, plasma chemistry, biophysics, and interstellar medium (ISM). In this manuscript we review the works performed by a joint combination of the experimental studies of ion–molecule reactions with synchrotron radiation and theoretical models adapted and developed to the experimental evidence. The review concludes with the perspectives of ion–molecule reactions by using FEL instrumentations as well as pump probe measurements and the initial attempt in the development of more realistic theoretical models for the prospective improvement of our predictive capability

VUV Photofragmentation of Chloroiodomethane: The Iso-CH2I–Cl and Iso-CH2Cl–I Radical Cation Formation

Dihalomethanes XCH2Y (X and Y= F, Cl, Br and I) are a class of compounds involved in several processes leading to the release of halogen atoms, ozone consumption and aerosol particle formation. Neutral dihalomethanes have been largely studied, but chemical physics properties and processes involving their radical ions, like the pathways of their decomposition, have not been completely investigated. In this work the photodissociation dynamics of the ClCH2I molecule has been explored in the photon energy range 9-21 eV using both VUV rare gas discharge lamps and synchrotron radiation. The experiments show that among the different fragment ions, CH2I+ and CH2Cl+, which correspond to the Cl- and I-losses, respectively, play a dominant role. The experimental ionization energy of ClCH2I and the appearance energies of the CH2I+ and CH2Cl+ ions are in agreement with the theoretical results obtained at the MP2/CCSD(T) level of theory. Computational investigations have been also performed to study the isomerization of geminal [ClCH2I].+ into the iso-chloroiodomethane isomers: [CH2I-Cl].+ and [CH2Cl-I].+

A recurrent, fatal, DRESS syndrome, complicated by sepsis and severe systemic cytomegalovirus reactivation at relapse: a case report

We report a case of recurrent, fatal, DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome induced by allopurinol. A 57-year-old man was admitted to our clinic manifesting a severe skin rash and fever, after following a four-week-long allopurinol therapy. On the basis of clinical, laboratory and instrumental features, the patient was diagnosed with DRESS syndrome, following RegiSCAR and Japanese group’s criteria. The clinical course of the disease was complicated by viral infection, methicillin-resistant Staphylococcus aureus endocarditis, bacterial pneumonia and severe recurrences. Despite allopurinol therapy was suspended and systemic steroids, targeted antibiotics, ganciclovir and immunoglobulins were administered, the clinical course had a fatal outcome. Herpes viruses have shown to have a crucial role in the pathogenesis of severe DRESS syndrome, suggesting that an early use of antiviral therapy, in addition to steroids, could improve the prognosis of DRESS syndrome

Hyperhomocysteinemia is an independent risk factor of atherosclerosis in patients with metabolic syndrome

BACKGROUND: Metabolic syndrome (MetS) is a clinical condition potentially promoting the development of atherosclerotic disease. To date, the clinical impact of elevated serum homocysteine (Hcy) levels in MetS is still under discussion. The aim of this cross sectional study was to evaluate the relationship between MetS and hyperhomocysteinemia and the potential role of Hcy in the pathogenesis of atherosclerotic complications of MetS. METHODS: We recruited 300 outpatients with MetS. All patients underwent a medical history collection, physical examination, blood sampling and carotid ultrasound echo-color Doppler. According to Hcy levels, MetS patients were divided into two groups: "normal" (< 10.7 μmol/l; n = 140, group 1) and "high" Hcy (≥ 10.7 μmol/l; n = 160, group 2). Comparisons between groups were made by Student's t-test or Chi-square test. The effects of potential covariates on group differences were evaluated by general linear models. The relationships between continuous variables were assessed by simple or multiple correlation and by linear regression. Multiple regression models were built to evaluate the effects of Hcy, together with other potential risk factors, on carotid atherosclerosis. RESULTS: Patients with high Hcy were predominantly male and slightly older than group 1 patients. Smokers and non-smokers exhibited similar Hcy levels, nor was a statistical relationship between pack-years and Hcy observed. Group 2 showed lower levels of folic acid, vitamin D, high density lipoprotein (HDL)-cholesterol and glomerular filtration rate (e-GFR) than group 1, but higher levels of C-peptide, uric acid and triglycerides. In all patients, Hcy was positively correlated with C-peptide and uric acid and negatively with folic acid and e-GFR. Intima-media thickness (IMT) and carotid stenosis degree were significantly higher in patients with high Hcy and a positive relationship between Hcy and both IMT and carotid stenosis was detected in all patients. Finally, Hcy atherogenic effects were independent of other well-known atherosclerosis risk factors. CONCLUSIONS: Our results highlight a link between MetS and hyperhomocysteinemia and a direct effect of Hcy on atherogenic process during MetS. Early correction of folic acid levels may contribute to prevent cardiovascular complications in MetS patients

Inner shell photofragmentation of 2Cl-pyrimidine studied by mass spectrometry and electron–ion coincidence experiments

Photoelectron spectroscopy, mass spectrometry and electron–ion coincidence experiments combined with tunable synchrotron radiation have been used to study the decay and fragmentation of 2Cl-pyrimidine after Cl(2p), C(1s) and N(1s) excitations. The goal is to investigate how the state- and site-selected excitation and the chemical environment affect the fragmentation paths of the molecule and to make a comparison with fragmentation induced by direct valence ionization. It has been found that the site-selective inner shell excitation affects the branching ratio of the fragments, while the particular fragmentation channels of the cation are determined by the final state populated in the resonant decay of the core excited states. Effects of nuclear motion in the core excited states and the possible ultrafast molecular dissociation following the Cl(2p → σ*) core excitation are discussed