Project description:The bis(pyridylimino)isoindoline (BPI) ligand is a tridentate chelate that binds to metals via a meridional coordination mode. However, when this ligand forms a complex with Re(CO)3, an almost exclusively facial moiety, the BPI ligand deforms to coordinate in a facial mode. We have in-vestigated this deformation via structural and theoretical means, and the non-planar binding mode of the ligand bathochromically shifts the metal to ligand charge transfer (MLCT) transition.
Project description:BackgroundCOVID-19 associated acute respiratory distress syndrome (CARDS) is a severe form of SARS CoV-2 infection and affects about 15-30% of hospitalized patients with a high mortality rate. Growing research and data suggest several available drugs with appropriate pharmacological effects to treat COVID-19.Main bodyProstacyclin analogues are regiments for pulmonary artery hypertension. Prostacyclin analogues are expected to be beneficial in treating CARDS based on at least four rationales: (1) inhaled prostacyclin analogues improve oxygenation, V/Q mismatch, and act as an ARDS therapy alternative; (2) it alleviates direct SARS-CoV-2-related coagulopathy; (3) increases nitric oxide production; and (4) possible anti-inflammatory effect. Prostacyclin analogues are available in oral, intravenous, and inhaled forms. The inhaled form has the advantage over other forms, such as parenteral administration risks. Previously, a meta-analysis demonstrated the beneficial effects of inhaled prostaglandins for ARDS treatment, such as improved PaO2/FiO2 and PaO2 along with reduced pulmonary artery pressure. Currently, two ongoing randomized controlled trials are evaluating inhaled epoprostenol (VPCOVID [NCT04452669]) and iloprost (ILOCOVID [NCT04445246]) for severe COVID-19 patients.ConclusionsInhaled prostacyclin could be considered in patients with refractory, life-threatening hypoxia despite standard management.
Project description:The coronavirus disease 2019 (COVID-19) pandemic has caused respiratory failure and associated mortality in numbers that have overwhelmed global health systems. Thrombotic coagulopathy is present in nearly three quarters of patients with COVID-19 admitted to the intensive care unit, and both the clinical picture and pathologic findings are consistent with microvascular occlusive phenomena being a major contributor to their unique form of respiratory failure. Numerous studies are ongoing focusing on anticytokine therapies, antibiotics, and antiviral agents, but none to date have focused on treating the underlying thrombotic coagulopathy in an effort to improve respiratory failure in COVID-19. There are animal data and a previous human trial demonstrating a survival advantage with fibrinolytic therapy to treat acute respiratory distress syndrome. Here, we review the extant and emerging literature on the relationship between thrombotic coagulopathy and pulmonary failure in the context of COVID-19 and present the scientific rationale for consideration of targeting the coagulation and fibrinolytic systems to improve pulmonary function in these patients.
Project description:BackgroundComorbidity of musculoskeletal (MSK) and mental health (MH) problems is common but challenging to treat using conventional approaches. Integration of conventional with complementary approaches (CAM) might help address this challenge. Integration can aim to transform biomedicine into a new health paradigm or to selectively incorporate CAM in addition to conventional care. This study explored professionals' experiences and views of CAM for comorbid patients and the potential for integration into UK primary care.MethodsWe ran focus groups with GPs and CAM practitioners at three sites across England and focus groups and interviews with healthcare commissioners. Topics included experience of co-morbid MSK-MH and CAM/integration, evidence, knowledge and barriers to integration. Sampling was purposive. A framework analysis used frequency, specificity, intensity of data, and disconfirming evidence.ResultsWe recruited 36 CAM practitioners (4 focus groups), 20 GPs (3 focus groups) and 8 commissioners (1 focus group, 5 interviews). GPs described challenges treating MSK-MH comorbidity and agreed CAM might have a role. Exercise- or self-care-based CAMs were most acceptable to GPs. CAM practitioners were generally pro-integration. A prominent theme was different understandings of health between CAM and general practitioners, which was likely to impede integration. Another concern was that integration might fundamentally change the care provided by both professional groups. For CAM practitioners, NHS structural barriers were a major issue. For GPs, their lack of CAM knowledge and the pressures on general practice were barriers to integration, and some felt integrating CAM was beyond their capabilities. Facilitators of integration were evidence of effectiveness and cost effectiveness (particularly for CAM practitioners). Governance was the least important barrier for all groups. There was little consensus on the ideal integration model, particularly in terms of financing. Commissioners suggested CAM could be part of social prescribing.ConclusionsCAM has the potential to help the NHS in treating the burden of MSK-MH comorbidity. Given the challenges of integration, selective incorporation using traditional referral from primary care to CAM may be the most feasible model. However, cost implications would need to be addressed, possibly through models such as social prescribing or an extension of integrated personal commissioning.
Project description:The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary oedema, hypoxaemia and the need for mechanical ventilation. ARDS occurs most often in the setting of pneumonia, sepsis, aspiration of gastric contents or severe trauma and is present in ~10% of all patients in intensive care units worldwide. Despite some improvements, mortality remains high at 30-40% in most studies. Pathological specimens from patients with ARDS frequently reveal diffuse alveolar damage, and laboratory studies have demonstrated both alveolar epithelial and lung endothelial injury, resulting in accumulation of protein-rich inflammatory oedematous fluid in the alveolar space. Diagnosis is based on consensus syndromic criteria, with modifications for under-resourced settings and in paediatric patients. Treatment focuses on lung-protective ventilation; no specific pharmacotherapies have been identified. Long-term outcomes of patients with ARDS are increasingly recognized as important research targets, as many patients survive ARDS only to have ongoing functional and/or psychological sequelae. Future directions include efforts to facilitate earlier recognition of ARDS, identifying responsive subsets of patients and ongoing efforts to understand fundamental mechanisms of lung injury to design specific treatments.
Project description:Acute respiratory distress syndrome (ARDS) is an acute respiratory illness characterised by bilateral chest radiographical opacities with severe hypoxaemia due to non-cardiogenic pulmonary oedema. The COVID-19 pandemic has caused an increase in ARDS and highlighted challenges associated with this syndrome, including its unacceptably high mortality and the lack of effective pharmacotherapy. In this Seminar, we summarise current knowledge regarding ARDS epidemiology and risk factors, differential diagnosis, and evidence-based clinical management of both mechanical ventilation and supportive care, and discuss areas of controversy and ongoing research. Although the Seminar focuses on ARDS due to any cause, we also consider commonalities and distinctions of COVID-19-associated ARDS compared with ARDS from other causes.
Project description:Rat model of ARDS was induced by saline lavage and mechanical ventilation. Total RNA from rat lungs were used for dual color DNA microarray hybridization with 3DNA 50 kit version 2. Two-condition experiment, CON vs. ARDS lung tissues. replicates: 5 control, 7 ARDS. One replicate per array.