A BODIPY derivative for selective fluorescent chemosensing of iron (III)

A BODIPY derivative functionalized with a phenyl group at the meso-position was synthesized and characterized through 1H NMR and UV–Vis absorption/emission spectroscopies. The compound showed an absorption band at 497 nm and a fluorescence band at 513 nm, with a ΦF = 0.68 in acetonitrile. The evaluation of the chemosensing ability of the BODIPY was investigated in the presence of several ions with environmental and biomedical relevance. A highly selective fluorimetric response was observed for Fe3+ through fluorescence quenching upon successive additions of this cation.The authors acknowledge Fundação para a Ciência e Tecnologia—FCT (Portugal) for funding through CQUM (UID/QUI/00686/2020) and a PhD grant to R.C.R. Gonçalves (SFRH/BD/05278/2020). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT

Investigation of an integrated standardised pain assessment and management tool in addition to usual care versus usual care alone in oncology outpatient clinics for adults with pain: the CAPTURE cluster randomised pilot trial protocol. ISRCRN86926298

Background Each year in the UK approximately 367,000 people are diagnosed with cancer of whom half will experience moderate to severe chronic pain and a third are undertreated for their pain. Most people with cancer are cared for at oncology outpatient services where there are no standardised approaches for managing pain. As a result, cancer patients are at risk of receiving inadequate care for pain. There is a need for a standardised approach to pain management within oncology outpatient services. Methods/design The aim of this pilot trial is to establish the feasibility of conducting a multi-centre clustered-randomised trial of an integrated standardised pain assessment and management programme integrated within routine care at oncology outpatient services in the United Kingdom National Health Service (NHS). We will conduct a two-arm pilot cluster randomised trial with nested process evaluation to evaluate the feasibility and acceptability of trial processes, establish fidelity of intervention implementation, estimate variability in outcomes and feasibility of future economic evaluation. Twelve outpatient services (clusters) from at least two NHS tertiary oncology referral centres (sites), in the North of England will be randomised (1:1) to deliver a pain management programme plus usual care or usual care alone and will recruit a total sample of 180 participants. Adults attending a participating outpatient service who self-report a score of ≥ 3 on the 0–10 Numerical Rating Scale (NRS) for worst pain in the past 72 h in any part of their body, and will be available for 1-week follow-up will be eligible. Participant self-reported questionnaires will be collected at baseline, 1-week, 1-month, and 2-months with medical record review at 1-month and 2-months. Progression to a future trial will be based on pre-defined criteria associated with eligibility and consent rates, follow-up and intervention delivery and acceptability. Discussion Little research has described optimal ways to implement a standardised pain assessment and management programme into oncology outpatient services. The strengths of the pilot trial are its sample size, number of clusters, and planned evaluation of trial processes and intervention fidelity to provide robust trial evidence to fully inform a future definitive phase III multi-centre cluster randomised trial within the UK NHS. Trial registration The CAPTURE pilot trial is registered on the ISRCTN registry (86,926,298)

Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment

The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

The Cholecystectomy As A Day Case (CAAD) score: a validated score of preoperative predictors of successful day-case cholecystectomy using the CholeS data set

Background: Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods: Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results: Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions: The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Lynch syndrome (hereditary non-polyposis colorectal cancer): current concepts and approaches to management

Colorectal cancer is among the most frequent causes of cancer death worldwide. An inherited predisposition to cancer of the colon and other organs, Lynch syndrome-- also called hereditary non-polyposis colorectal cancer--is probably the most frequent cause of hereditary cancer and is often found in a colon cancer patient and traced through other family members. However, this syndrome is not only characterized by the early onset of colon cancers but also by a predisposition to a constellation of extraintestinal cancers that tend to be misdiagnosed. With new diagnostic technologies, the incidence of familial/inherited versus sporadic cases may appear to increase, due to the recognition of cancers in families that do not fulfill clinical guidelines developed prior to knowledge of the genetic basis of this disease. We now have the ability and the responsibility to detect and prevent this disease, and equally important, to direct patients to specifically targeted treatment. Specialists should be aware of the significance of inherited colon cancer and should become familiar with the molecular diagnostic tests now widely available