eFluorination of Activated Alcohols Using Collidinium Tetrafluoroborate.

Tertiary C-F bonds are important structural designs; however, they suffer from challenging synthesis. Current methodologies use corrosive amine-HF salts or expensive and hazardous catalysts and reagents. Our group recently introduced collidinium tetrafluoroborate as an efficient fluorinating agent for anodic decarboxyfluorination reactions. Nevertheless, tertiary carboxylic acids are less readily available and more challenging to prepare than their alcohol analogues. Herein we report a practical, mild, and cheap electrochemical method to achieve deoxyfluorination of hindered carbon centers.

Systematic review of physiological and psychological outcomes of surgery for pectus excavatum supporting commissioning of service in the UK.

BACKGROUND: Pectus excavatum (PEx) is the most common congenital chest wall abnormality affecting 1 in 400 births in the UK. PEx is associated with significant physiological and psychological impairment. While readily surgically correctable, the benefits that surgery can bring have been debated and proven difficult to objectively measure. In the UK, this has led to the decommissioning of PEx surgery. The aim of this review is to conduct a systematic search of the literature on PEx surgery to assess physiological and psychological outcomes. METHODS: A systematic review of the MEDLINE (PubMed), Embase and Cochrane databases was performed. Articles were sought which included patients undergoing surgery for PEx and reported on changes in cardiopulmonary measures, symptoms, quality of life and psychological assessments before and after surgical repair. Last search was performed in July 2022 and relevant findings were synthesised by narrative review. RESULTS: Fifty-one articles were included in qualitative synthesis, with 34 studies relating to physiological outcomes and 17 studies relating to psychological and quality of life measures. Twenty-one studies investigated pulmonary function at rest. There was no change in forced vital capacity or forced expiratory volume in 1 second following open repair and transient reductions followed closed repair. In the 11 studies investigating echocardiography, transthoracic rarely demonstrated cardiac compression; however, transoesophageal demonstrated intraoperative relief in cardiac compression in severe cases. Sixteen studies investigated exercise testing (cardiopulmonary exercise testing, CPET), 12 of which demonstrated significant improvement following surgery, both in maximal oxygen consumption and oxygen pulse. Seventeen studies investigated quality of life, all but one of which showed improvement following repair of PEx. All papers that reported on patient satisfaction following surgery found high rates, between 80% and 97%. DISCUSSION: While the majority of studies to date have been small and data heterogeneous, the literature shows that for many patients with PEx, there exists a cardiopulmonary limitation that while difficult to objectify, is likely to improve with surgical repair. Resting parameters offer little yield in aiding this except in the most severe cases. CPET therefore offers a better option for dynamic assessment of this limitation and improvements following repair. Surgery significantly improves psychological well-being and quality of life for patients with PEx.

eHydrogenation: Hydrogen-free Electrochemical Hydrogenation.

Hydrogenation reactions are staple transformations commonly used across scientific fields to synthesise pharmaceuticals, natural products, and various functional materials. However, the vast majority of these reactions require the use of a toxic and costly catalyst leading to unpractical, hazardous and often functionally limited conditions. Herein, we report a new, general, practical, efficient, mild and high-yielding hydrogen-free electrochemical method for the reduction of alkene, alkyne, nitro and azido groups. Finally, this method has been applied to deuterium labelling.

Transcriptional Profiling of a Patient-Matched Cohort of Glioblastoma (IDH-Wildtype) for Therapeutic Target and Repurposing Drug Identification.

Glioblastoma (GBM) is the most prevalent and aggressive adult brain tumor. Despite multi-modal therapies, GBM recurs, and patients have poor survival (~14 months). Resistance to therapy may originate from a subpopulation of tumor cells identified as glioma-stem cells (GSC), and new treatments are urgently needed to target these. The biology underpinning GBM recurrence was investigated using whole transcriptome profiling of patient-matched initial and recurrent GBM (recGBM). Differential expression analysis identified 147 significant probes. In total, 24 genes were validated using expression data from four public cohorts and the literature. Functional analyses revealed that transcriptional changes to recGBM were dominated by angiogenesis and immune-related processes. The role of MHC class II proteins in antigen presentation and the differentiation, proliferation, and infiltration of immune cells was enriched. These results suggest recGBM would benefit from immunotherapies. The altered gene signature was further analyzed in a connectivity mapping analysis with QUADrATiC software to identify FDA-approved repurposing drugs. Top-ranking target compounds that may be effective against GSC and GBM recurrence were rosiglitazone, nizatidine, pantoprazole, and tolmetin. Our translational bioinformatics pipeline provides an approach to identify target compounds for repurposing that may add clinical benefit in addition to standard therapies against resistant cancers such as GBM.

eFluorination Using Cheap and Readily Available Tetrafluoroborate Salts.

A practical electrochemical method for the rapid, safer, and mild synthesis of tertiary hindered alkyl fluorides from carboxylic acids has been developed without the need for hydrofluoric acid salts or non-glass reactors. In this anodic fluorination, collidinium tetrafluoroborate acts as both the supporting electrolyte and fluoride donor. A wide range of functional groups has been shown to be compatible, and the possibility of scale-up using flow electrochemistry has also been demonstrated.

Electrochemical Isothiocyanation of Primary Amines.

Isothiocyanates are ubiquitous building blocks used across the fields. Nevertheless, their classical syntheses very often rely on the use of toxic and expensive reagents. Herein, we report a new practical, mild, high-yielding, and supporting-electrolyte-free electrochemical method for the preparation of aliphatic and aromatic isothiocyanates from amine and carbon disulfide.

Electrosynthesis of Stabilized Diazo Compounds from Hydrazones.

An electrochemical synthesis of diazo compounds from hydrazones in yields as high as 99% was performed. This method was elaborated as a useful synthetic method and demonstrated on various diazo compounds (24 examples). Apart from exhibiting an efficiency that matched that of commonly used harsh and toxic chemical oxidants, this reaction is practically simple to set up, requires mild conditions, and is highly electron efficient (3 F/mol).

Early Interleukin-22 and Neutrophil Proteins Are Correlated to Future Lung Damage in Children With Cystic Fibrosis.

Cystic Fibrosis (CF) lung damage begins early in life. Lung function decline is associated with pulmonary infections, neutrophil infiltration and inflammation. In CF, neutrophils have an altered phenotype. In this pilot study, we aimed to determine if signals of dysfunctional neutrophil responses were evident early in life and whether these signals may be associated with lung damage in later childhood. We examined the pulmonary protein profiles of 14 clinical stable infants and pre-school children with CF employing the aptamer-based affinity platform, SOMAscan®. High resolution computed tomography (HRCT) was performed on all children after age 6 years and Brody score calculated. A Spearman's rank order correlation analysis and Benjamini-Hochberg adjustment was used to correlate protein concentrations in early life to Brody scores in later childhood. Early life concentrations of azurocidin and myeloperoxidase, were positively correlated with Brody score after age 6 (p = 0.0041 and p = 0.0182, respectively). Four other neutrophil associated proteins; Complement C3 (p = 0.0026), X-ray repair CCP 6 (p = 0.0059), C3a anaphylatoxin des Arginine (p = 0.0129) and cytokine receptor common subunit gamma (p = 0.0214) were all negatively correlated with Brody scores. Interestingly, patients with more severe lung damage after age 6 had significantly lower levels of IL-22 in early years of life (p = 0.0243). IL-22 has scarcely been reported to have implications in CF. Identification of early biomarkers that may predict more severe disease progression is particularly important for the future development of early therapeutic interventions in CF disease. We recommend further corroboration of these findings in prospective validation studies.

Improving the use of treatment escalation plans: a quality-improvement study.

OBJECTIVES: Treatment escalation plans (TEPs) are vital in communicating a ceiling of care. However, many patients still deteriorate and die without a pre-established ceiling of care for attending clinicians to rely on. We aimed to increase the proportion of suitable patients that have TEPs in place in a rural district general hospital. METHODS: We undertook three 'Plan-Do-Study-Act' (PDSA) cycles between 1 December 2016 and 9 June 2017. These cycles aimed to assess the problem, implement a solution and monitor its sustainability. We sampled all acute medical admissions at different time points, focusing on the acute medical unit. We identified patients requiring TEP forms using SupportiveandPalliative Care Indicators Tool. Stakeholders were surveyed during the project, and a process communication map was developed to understand the human interfaces that occur when producing a TEP. RESULTS: We sampled a total of 323 patients (PDSA 1, n=128; PDSA 2, n=95; PDSA 3, n=100). Following implementation of a 'talking to your doctor about treatment' leaflet, the proportion of patients who did not have a TEP but required one fell from 43% (n=38, PDSA 1) to 27% (n=20, PDSA 3) then to 23% (n=77, PDSA 3) (CI 0.6631 to 39.917, p=0.028). CONCLUSIONS: This study highlights the challenges of TEP form completion. The impact of our intervention appeared to raise awareness of advanced care planning. The information contained in our leaflet could be distributed in more innovative ways to ensure patients unable to access textual information are able to receive this message.

Changing EMS dispatcher CPR instructions to 400 compressions before mouth-to-mouth improved bystander CPR rates.

BACKGROUND: To examine the impact of changing dispatcher CPR instructions (400 compressions: 2 breaths, followed by 100:2 ratio) on rates of bystander CPR and survival in adults with presumed cardiac out-of-hospital arrest (OHCA) in Melbourne, Australia. METHODS: The Victorian Ambulance Cardiac Arrest Registry (VACAR) was searched for OHCA where Emergency Medical Services (EMS) attempted CPR between August 2006 and August 2009. OHCA included were: (1) patients aged ≥18 years old; (2) presumed cardiac etiology; and (3) not witnessed by EMS. RESULTS: For the pre- and post-study periods, 1021 and 2101 OHCAs met inclusion criteria, respectively. Rates of bystander CPR increased overall (45-55%, p<0.001) and by initial rhythm (shockable 55-70%, p<0.001 and non-shockable 40-46%, p=0.01). In VF/VT OHCA, there were improvements in the number of patients arriving at hospital with a return of spontaneous circulation (ROSC) (48-56%, p=0.02) and in survival to hospital discharge (21-29%, p=0.002), with improved outcomes restricted to patients receiving bystander CPR. After adjusting for factors associated with survival, the period of time following the change in CPR instructions was a significant predictor of survival to hospital discharge in VF/VT patients (OR 1.57, 95% CI: 1.15-2.20, p=0.005). CONCLUSION: Following changes to dispatcher CPR instructions, significant increases were seen in rates of bystander CPR and improvements were seen in survival in VF/VT patients who received bystander CPR, after adjusting for factors associated with survival.