Effects of unburned tobacco smoke on inflammatory and oxidative mediators in the rat prefrontal cortex

Although the Food and Drug Administration has authorized the marketing of "heat-not-burn" (HnB) electronic cigarettes as a modified risk tobacco product (MRTP), toxicological effects of HnB smoke exposure on the brain are still unexplored. Here, paramagnetic resonance of the prefrontal cortex (PFC) of HnB-exposed rats shows a dramatic increase in reactive radical species (RRS) yield coupled with an inflammatory response mediated by NF-κB-target genes including TNF-α, IL-1β, and IL-6 and the downregulation of peroxisome proliferator-activated receptor (PPAR) alpha and gamma expression. The PFC shows higher levels of 8-hydroxyguanosine, a marker of DNA oxidative damage, along with the activation of antioxidant machinery and DNA repair systems, including xeroderma pigmentosum group C (XPC) protein complex and 8-oxoguanine DNA glycosylase 1. HnB also induces the expression of drug-metabolizing enzymes such as CYP1A1, CYP2A6, CYP2B6, and CYP2E, particularly involved in the biotransformation of nicotine and several carcinogenic agents such as aldehydes and polycyclic aromatic hydrocarbons here recorded in the HnB stick smoke. Taken together, these effects, from disruption of redox homeostasis, inflammation, PPAR manipulation along with enhanced bioactivation of neurotoxicants, and upregulation of cMYC protooncogene to impairment of primary cellular defense mechanisms, suggest a possible increased risk of brain cancer. Although the HnB device reduces the emission of tobacco toxicants, our findings indicate that its consumption may carry a risk of potential adverse health effects, especially in non-smokers so far. Further studies are needed to fully understand the long-term effects of these devices

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions

BackgroundHeterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services.MethodsUsing a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups.ResultsClustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup.LimitationsNotable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic.ConclusionsConcomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

DETERMINING IN THE EXECUTIVE PROJECT THE DURATION OF WORKS OF A NEW BUILDING

In the execution of public works, the failure of the contractual compliance time is more expensive for the Contracting Authority due to the onset of disputes, the failure to fruition on schedule, etc. Several studies carried out in recent years have found that the actual duration of the works is higher than contract in 90% of cases. In the executive project, not by knowing the actual characteristics of the contracting firm, for estimating the duration of the works, not well certain resources - based only on the labor incidence indicated in the price lists - are assumed. The paper proposes a methodological approach that allows the technician, in executive project phase, the estimation of aduration of the works so-called conventional, setting some parameters according to experimental observations and considering only deemed critical activities. Starting, in fact, from the comparison of the two methods commonly used (calculation of men-day and Circ. n. C/175 Cassa per il Mezzogiorno 02/03/1982), through processing of the parameters contained in them, an algorithm that can be a useful reference for determining the duration of the works has been achieved, even with limitations and by means of further studies

SARS-CoV-2-specific IgG and NCP in vulnerable patients without symptoms

Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS- CoV-2-specific IgG than patients with mild symptoms. In this retrospective study we considered different categories of patients defined as "vulnerable" because affected by other pathologies, such as patients with genetic and cardiovascular diseases; patients with autoimmune dermatological dis- ease; kidney and lung transplant patients, and pregnant women because the prevalence of Covid-19 infection during pregnancy is not known. This study was performed at IRCCS San Matteo Hospital in Pavia, North Italy, a zone considered at high risk during the COVID-19 pandemic from June to December 2020. None of the positive screened patients had symptoms of COVID-19 infection at the time of inclusion in this study

Assessment of the Antioxidant and Hypolipidemic Properties of Salicornia europaea for the Prevention of TAFLD in Rats

Halophyte species represent valuable reservoirs of natural antioxidants, and, among these, Salicornia europaea stands out as a promising edible plant. In this study, young and old S. europaea leaves were compared for the content of bioactive compounds and antioxidant activity to assess changes in different growth phases; then, the potential protective effects against low-dose CCl4-induced toxicant-associated fatty liver disease (TAFLD) were investigated by administering an aqueous suspension of young leaves to rats daily for two weeks. Quantification of total and individual phenolic compounds and in vitro antioxidant activity assays (DPPH, FRAP, and ORAC) showed the highest values in young leaves compared to mature ones. Salicornia treatment mitigated CCl4-induced hepatic oxidative stress, reducing lipid peroxidation and protein carbonyl levels, and preserving the decrease in glutathione levels. Electronic paramagnetic resonance (EPR) spectroscopy confirmed these results in the liver and evidenced free radicals increase prevention in the brain. Salicornia treatment also attenuated enzymatic disruptions in the liver’s drug metabolizing system and Nrf2-dependent antioxidant enzymes. Furthermore, histopathological examination revealed reduced hepatic lipid accumulation and inflammation. Overall, this study highlights Salicornia’s potential as a source of bioactive compounds with effective hepatoprotective properties capable to prevent TAFLD