A mechanistic and experimental study of the diethyl ether oxidation

International audienceThis work presents the results of the theoretical investigations on autoxidation process of diethyl ether (DEE), a chemical largely used as solvent in laboratories and considered to be responsible for various accidents. Based on Density Functional Theory (DFT) calculations, the aims of this study were the identification of all the most probable reaction paths involved in DEE oxidation (at ambient temperature and under conditions that reflect normal storage conditions) and the characterization of products and all potential hazardous intermediates, such as peroxides. Results indicate that industrial hazards could be related to hydroperoxide formation and accumulation during the chain propagation step. A detailed kinetics model of DEE oxidation in the gas phase was then developed from all energetic and kinetics parameters collected during the mechanistic study. Outputs of the kinetics model, in terms of time of evolution of product concentrations, have been then compared with the experimentally measured concentration of products (notably hydroperoxides) issued from tests on DEE oxidation conducted under accelerated conditions with autoclaves

Functionalization of a layered oxide with organic moieties: towards hybrid proton conductors

The design of innovative proton conductors for intermediate-temperature fuel cells, closing the gap between PEMFC and SOFC, is a forefront research theme in materials chemistry. [1] Layered perovskites with the Dion-Jacobson structure (ALaNb2O7) have bidimensional lanthanum niobate sheets, separated by a layer of A+ cations. These can be substituted by a variety of molecules with soft chemistry, to yield inorganic-organic hybrids. In particular, the intercalation of amines, alcohols, carboxylic or phosphonic acids, and their covalent binding to the sheets has been demonstrated recently. [2-4]We present preliminary results on the intercalation and covalent bonding of different organic molecules, in order to develop hybrid proton conductors for use in intermediate temperature fuel cells. Smaller molecules (such as alcohols) are intercalated to expand the interlayer space, to form intermediates for the further binding of proton carriers such as imidazoles or sulfonates.The intercalation process is investigated by XRD (to measure the interlayer distance) and TGA (to determine the weight loss upon thermal decomposition). NMR is applied to confirm the covalent bonding between the organic and oxide parts. The intercalation behavior of different functional groups is explained in terms of van der Waals and/or hydrogen bonding between organic chains. The interplay of theory (ab initio and periodic DFT) and experiment allowed us to elucidate the 1H and 13C-NMR spectra, and to investigate the nature of interaction (i.e. ionic or covalent bond) of the organic chains with the interlayer surface

Evaluation of Bronchoscopy and Bronchoalveolar Lavage Findings in Cats With Aelurostrongylus abstrusus in Comparison to Cats With Feline Bronchial Disease

The cat lungworm Aelurostrongylus abstrusus is a cause of lower respiratory tract disease worldwide. Bronchoscopy and bronchoalveolar lavage (BAL) are important tools for diagnosing respiratory diseases in cats. Therefore, the aim of the study was to investigate the usefulness of bronchoscopy and BAL in the diagnosis of A. abstrusus. Findings from bronchoscopic examination and BAL of 24 naturally infected cats were evaluated and compared with those of 12 cats with idiopathic Feline Bronchial Diseases (FBDs). Data were analyzed using Mann-Whitney or Fisher's exact tests. No significant bronchoscopic differences were detected between cats with aelurostrongylosis and FBDs in bronchial mucus, nodular lesions, and airway collapse. On the other hand, airway hyperemia, epithelial irregularities, and bronchial stenosis were observed more frequently in cats affected by FBDs than aelurostrongylosis, while bronchiectasis was found only in cats infected by A. abstrusus. Neutrophilic, eosinophilic, lymphocytic, and mixed inflammation were recorded in both groups. Bacteria or bacterial DNA was identified regardless of the presence or absence of A. abstrusus with no significant differences between groups. Larvae of A. abstrusus were cytologically detected in 5 of the 24 cats (20.8%) with aelurostrongylosis. These results indicate that, although some findings on bronchoscopic examination (i.e., bronchiectasis) can be described more frequently in cats infected by A. abstrusus, bronchial alterations and cytological findings in aelurostrongylosis are not specific unless larvae are observed and overlap with those of other feline airway diseases

Effects of estetrol on migration and invasion inT47-D breast cancer cells through the actin cytoskeleton

Estetrol (E4) is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor (ER) modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17β-estradiol (E2) on T47-D ER+ breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, re-distribution of actin fibers toward the cell membrane was observed. However, when E4 was added to E2, an inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr(558), which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of estrogen receptor-α. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring ER modulator in the breast

Evaluating the effectiveness of neurofeedback in chronic pain management: a narrative review

The prevalence and impact of chronic pain in individuals worldwide necessitate effective management strategies. This narrative review specifically aims to assess the effectiveness of neurofeedback, an emerging non-pharmacological intervention, on the management of chronic pain. The methodology adopted for this review involves a meticulous search across various scientific databases. The search was designed to capture a broad range of studies related to neurofeedback and chronic pain management. To ensure the quality and relevance of the included studies, strict inclusion and exclusion criteria were applied. These criteria focused on the study design, population, intervention type, and reported outcomes. The review synthesizes the findings from a diverse array of studies, including randomized controlled trials, observational studies, and case reports. Key aspects evaluated include the types of neurofeedback used (such as EEG biofeedback), the various chronic pain conditions addressed (like fibromyalgia, neuropathic pain, and migraines), and the methodologies employed in these studies. The review highlights the underlying mechanisms by which neurofeedback may influence pain perception and management, exploring theories related to neural plasticity, pain modulation, and psychological factors. The results of the review reveal a positive correlation between neurofeedback interventions and improved pain management. Several studies report significant reductions on pain intensity, improved quality of life, and decreased reliance on medication following neurofeedback therapy. The review also notes variations in the effectiveness of different neurofeedback protocols and individual responses to treatment. Despite the promising results, the conclusion of the review emphasizes the need for further research. It calls for larger, well-designed clinical trials to validate the findings, to understand the long-term implications of neurofeedback therapy, and to optimize treatment protocols for individual patients

Reasons for initiating long-acting antipsychotics in psychiatric practice: findings from the STAR Network Depot Study

Background: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients.Methods: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient's attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence.Results: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness).Conclusion: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient's engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies

The integrated care pathway for melanoma: the Istituto Dermopatico dell'Immacolata experience in Rome

Introduction: The Integrated Care Pathway (ICP) represents a multidisciplinary outline of anticipated care, placed in an appropriate timeframe, to support patients with specific conditions or symptoms. The aim of this paper is to define the ICP for patients with melanoma referring to the "Istituto Dermopatico dell'Immacolata-IRCCS di Roma e Villa Paola" ("Center"). Methods and results: A multidisciplinary group (oncologists, dermatologists, surgeons, pathologists etc.) was defined as well as a facilitator to act as a link between all experts. The first step of ICP development was a review of current practice for patients with melanoma referring to the Center. This first step had the scope to define the multidisciplinary process map (a "picture" of the care plan) for patients with melanoma. The process map defined: i) the activities performed during delivery of care to the patients, ii) the responsibilities for these activities and iii) potential problem areas or opportunities for improvements. The process map formed the basis of the final ICP document. Conclusion: The adoption of melanoma ICP will allow the multidisciplinary group to ensure that clinical guidelines and available evidence are incorporated into everyday practice. (Oncology, HTA & Market Access

Three vs. Four Cycles of Neoadjuvant Chemotherapy for Localized Muscle Invasive Bladder Cancer Undergoing Radical Cystectomy: A Retrospective Multi-Institutional Analysis

Three or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell