Notes

Detection of a Fresh Allosteric Web site on the M5 Muscarinic Acetylcholine Receptor.
Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. Selleck mTOR inhibitor With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.Organic-inorganic perovskite single crystals are promising in the field of optoelectronics due to their excellent optoelectronic properties. However, the ion transport of perovskite precursor is poor in confined spaces, which results in difficulty in the preparation of perovskite single-crystal films. Herein, MAPbBr3 films consisting of square grains were fabricated by the surface-confined process using the organic molecule PEAI (phenethylammonium iodide). Under the effect of oversaturation gradient, PEA+ is combined with the surface of perovskite grain from top to side, which constrains the lateral growth of grains and induces a downward growth of perovskite, leading to the formation of square grains. With the improvement of concentration PEAI, the perovskite film exhibits a decreased side length of grains (from 0.98 to 12.96 μm) and increased grain number and coverage, as well as crystallinity. The perovskite single crystalline grain films with PEAI showed double photoluminescence (PL) emission peaks due to the existence of iodine-rich perovskite. This work may provide a practical way to fabricate high-quality perovskite films for perovskite photoelectronic devices.One of the most severe effects of coronavirus disease 2019 (COVID-19) is lung disorders such as acute respiratory distress syndrome. In the absence of effective treatments, it is necessary to search for new therapies and therapeutic targets. Platelets play a fundamental role in respiratory disorders resulting from viral infections, being the first line of defense against viruses and essential in maintaining lung function. The direct application of platelet lysate (PL) obtained from the platelet-rich plasma of healthy donors could help in the improvement of the patient due its anti-inflammatory, immunomodulatory, antifibrotic, and repairing effects. This work evaluates PL nebulization by analyzing its levels of growth factors and its biological activity on lung fibroblast cell cultures, besides describing a scientific basis for its use in this kind of pathology. The data of the work suggest that the molecular levels and biological activity of the PL are maintained after nebulization. Airway administration would allow acting directly on the lung tissue modulating inflammation and stimulating reparative processes on key structures such as the alveolocapillary barrier, improving the disease and sequels. The protocol developed in this work is a first step for the study of nebulized PL both in animal experimentation and in clinical trials.Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 11 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively; p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004; treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission.The decentralization of the Brazilian health system required that municipalities took responsibility for the local Pharmaceutical Policy and Services (PPS) system. This article presents and analyses an innovative experience of diagnosis of municipal PPS as a sociotechnical system. We adopted a multi-methods approach and various data sources. Sociotechnical theory was the framework of the methodology of evaluation and design of systems, analyzing the External System (health system, stakeholders, financing) and Internal System (goals, management, workforce, infrastructure, processes, technology and culture). The "objective" component of the PPS system was identified as the central element. The lack of a unified objective and of a central coordination and unmanaged pharmaceutical services prevented integrated internal planning and planning with other sectors. Stakeholders and documents referred only to technical elements of the system Infrastructure, technical process, and technology. The social components of the workforce and culture were not mentioned.
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