Acid alteration of several ignitable liquids of potential use in arsons

Ignitable liquids such as fuels, alcohols and thinners can be used in criminal activities, for instance arsons. Forensic experts require to know their chemical compositions, as well as to understand how different modification effects could impact them, in order to detect, classify and identify them properly in fire debris. The acid alteration/acidification of ignitable liquids is a modification effect that sharply alters the chemical composition, for example, of gasoline and diesel fuel, interfering in the forensic analysis and result interpretation. However, to date there is little information about the consequences of this effect over other accelerants of interests. In this research paper, the alteration by sulfuric acid of several commercial thinners and other accelerants of potential use in arsons is studied in-depth. For that purpose, spectral (by ATR-FTIR) and chromatographic (by GC&-MS) data were obtained from neat and acidified samples. Then, the spectral and chromatographic modifications of each studied ignitable liquid were discussed, proposing several chemical mechanisms that explain the new by-products produced and the gradual disappearance of the initial compounds. Hydrolysis, Fischer esterification and alkylation reactions are involved in the modification of esters, alcohols, ketones and aromatic compounds of the studied ignitable liquids. This information could be crucial for correctly identifying these accelerants. Additionally, an exploratory analysis revealed that some of the most altered ignitable liquid samples might be very similar with each other, which could have impact on casework

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum.

COVID-19 is a systemic infection that exerts significant impact on the metabolism. Yet, there is little information on how SARS-CoV-2 affects metabolism. Using NMR spectroscopy, we measured the metabolomic and lipidomic serum profile from 263 (training cohort)&nbsp;+ 135 (validation cohort) symptomatic patients hospitalized after positive PCR testing for SARS-CoV-2 infection. We also established the profiles of 280 persons collected before the coronavirus pandemic started. Principal-component analysis discriminated both cohorts, highlighting the impact that the infection has on overall metabolism. The lipidomic analysis unraveled a pathogenic redistribution of the lipoprotein particle size and composition to increase the atherosclerotic risk. In turn, metabolomic analysis reveals abnormally high levels of ketone bodies (acetoacetic acid, 3-hydroxybutyric acid, and acetone) and 2-hydroxybutyric acid, a readout of hepatic glutathione synthesis and marker of oxidative stress. Our results are consistent with a model in which SARS-CoV-2 infection induces liver damage associated with dyslipidemia and oxidative stress

Psychological impact of the COVID-19 pandemic on primary care workers: a cross-sectional study

Background: The COVID-19 pandemic has had a major impact on the mental health of healthcare workers, yet studies in primary care workers are scarce. Aim: To investigate the prevalence of and associated factors for psychological distress in primary care workers during the first COVID-19 outbreak. Design and setting: This was a multicentre, cross-sectional, web-based survey conducted in primary healthcare workers in Spain, between May and September 2020. Method: Healthcare workers were invited to complete a survey to evaluate sociodemographic and work-related characteristics, COVID-19 infection status, exposure to patients with COVID-19, and resilience (using the Connor-Davidson Resilience Scale), in addition to being screened for common mental disorders (depression, anxiety disorders, post-traumatic stress disorder, panic attacks, and substance use disorder). Positive screening for any of these disorders was analysed globally using the term 'any current mental disorder'. Results: A total of 2928 primary care professionals participated in the survey. Of them, 43.7% (95% confidence interval [CI] = 41.9 to 45.4) tested positive for a current mental disorder. Female sex (odds ratio [OR] 1.61, 95% CI = 1.25 to 2.06), having previous mental disorders (OR 2.58, 95% CI = 2.15 to 3.10), greater occupational exposure to patients with COVID-19 (OR 2.63, 95% CI = 1.98 to 3.51), having children or dependents (OR 1.35, 95% CI = 1.04 to 1.76 and OR 1.59, 95% CI = 1.20 to 2.11, respectively), or having an administrative job (OR 2.24, 95% CI = 1.66 to 3.03) were associated with a higher risk of any current mental disorder. Personal resilience was shown to be a protective factor. Conclusion: Almost half of primary care workers showed significant psychological distress. Strategies to support the mental health of primary care workers are necessary, including designing psychological support and resilience-building interventions based on risk factors identified