FIT negative clinic as a safety net for low-risk patients with colorectal cancer: impact on endoscopy and radiology utilisation-a retrospective cohort study.

Background: Faecal immunochemical testing (FIT) is recommended by the National Institute for Health and Care Excellence to triage symptomatic primary care patients who have unexplained symptoms but do not meet the criteria for a suspected lower gastrointestinal cancer pathway. During the COVID-19 pandemic, FIT was used to triage patients referred with urgent 2-week wait (2ww) cancer referrals instead of a direct-to-test strategy. FIT-negative patients were assessed and safety netted in a FIT negative clinic. Methods: We reviewed case notes for 622 patients referred on a 2ww pathway and seen in a FIT negative clinic between June 2020 and April 2021 in a tertiary care hospital. We collected information on demographics, indication for referral, dates for referral, clinic visit, investigations and long-term outcomes. Results: The average age of the patients was 71.5 years with 54% female, and a median follow-up of 2.5 years. Indications for referrals included: anaemia (11%), iron deficiency (24%), weight loss (9%), bleeding per rectum (5%) and change in bowel habits (61%). Of the cases, 28% (95% CI 24% to 31%) had endoscopic (15%, 95% CI 12% to 18%) and/or radiological (20%, 95% CI 17% to 23%) investigations requested after clinic review, and among those investigated, malignancy rate was 1.7%, with rectosigmoid neuroendocrine tumour, oesophageal cancer and lung adenocarcinoma. Conclusion: A FIT negative clinic provides a safety net for patients with unexplained symptoms but low risk of colorectal cancer. These real-world data demonstrate significantly reduced demand on endoscopy and radiology services for FIT-negative patients referred via the 2ww pathway.

Treatment of Alzheimer's diseases using donepezil nanoemulsion: an intranasal approach.

Alzheimer disease (AD) is very common among the older people. There are few medications available as oral and suspension dosage forms for the management of AD. Due to the rising cases of AD and the associated risks of the existing line of treatment, oil in water (o/w) nanoemulsion (NE) loaded with donepezil was prepared to explore intranasal route of administration. The NE was prepared using labrasol (10%), cetyl pyridinium chloride (1% in 80% water), and glycerol (10%), with a drug concentration of 1 mg/ml. The developed NE was characterized for particle size, polydispersity index (PDI), and zeta potential. In vitro release studies were conducted to observe the release of drug. Further in vivo studies of developed NE were done on Sprague Dawley rats using technetium pertechnetate (99mTc) labeled formulations to investigate the nose to brain drug delivery pathway. The nanoemulsion showed particle size of 65.36 nm with a PDI of 0.084 and zeta potential of -10.7 mV. In vitro release studies showed maximum release of 99.22% in 4 h in phosphate-buffered saline, 98% in 2 h in artificial cerebrospinal fluid, and 96% in 2 h in simulated nasal fluid. The cytotoxicity and antioxidant activity of the NE showed dose-dependent cytotoxicity and % radical scavenging activity (%RSA). The images of giemsa staining also confirmed that the developed formulation has no impact on the morphology of cells. Scintigrams showed maximum uptake of NE in the brain. The findings suggested that the developed NE loaded with donepezil hydrochloride could serve as a new approach for the treatment of Alzheimer via nose to brain drug delivery. Graphical abstract.

Evaluation of divergent yeast genera for fermentation-associated stresses and identification of a robust sugarcane distillery waste isolate Saccharomyces cerevisiae NGY10 for lignocellulosic ethanol production in SHF and SSF.

BACKGROUND: Lignocellulosic hydrolysates contain a mixture of hexose (C6)/pentose (C5) sugars and pretreatment-generated inhibitors (furans, weak acids and phenolics). Therefore, robust yeast isolates with characteristics of C6/C5 fermentation and tolerance to pretreatment-derived inhibitors are pre-requisite for efficient lignocellulosic material based biorefineries. Moreover, use of thermotolerant yeast isolates will further reduce cooling cost, contamination during fermentation, and required for developing simultaneous saccharification and fermentation (SSF), simultaneous saccharification and co-fermentation (SScF), and consolidated bio-processing (CBP) strategies. RESULTS: In this study, we evaluated thirty-five yeast isolates (belonging to six genera including Saccharomyces, Kluyveromyces, Candida, Scheffersomyces, Ogatea and Wickerhamomyces) for pretreatment-generated inhibitors {furfural, 5-hydroxymethyl furfural (5-HMF) and acetic acid} and thermotolerant phenotypes along with the fermentation performances at 40 °C. Among them, a sugarcane distillery waste isolate, Saccharomyces cerevisiae NGY10 produced maximum 49.77 ± 0.34 g/l and 46.81 ± 21.98 g/l ethanol with the efficiency of 97.39% and 93.54% at 30 °C and 40 °C, respectively, in 24 h using glucose as a carbon source. Furthermore, isolate NGY10 produced 12.25 ± 0.09 g/l and 7.18 ± 0.14 g/l of ethanol with 92.81% and 91.58% efficiency via SHF, and 30.22 g/l and 25.77 g/l ethanol with 86.43% and 73.29% efficiency via SSF using acid- and alkali-pretreated rice straw as carbon sources, respectively, at 40 °C. In addition, isolate NGY10 also produced 92.31 ± 3.39 g/l (11.7% v/v) and 33.66 ± 1.04 g/l (4.26% v/v) ethanol at 40 °C with the yields of 81.49% and 73.87% in the presence of 30% w/v glucose or 4× concentrated acid-pretreated rice straw hydrolysate, respectively. Moreover, isolate NGY10 displayed furfural- (1.5 g/l), 5-HMF (3.0 g/l), acetic acid- (0.2% v/v) and ethanol-(10.0% v/v) tolerant phenotypes. CONCLUSION: A sugarcane distillery waste isolate NGY10 demonstrated high potential for ethanol production, C5 metabolic engineering and developing strategies for SSF, SScF and CBP.

Analysis of BAFF gene polymorphisms in UK Graves' disease patients.

OBJECTIVE: B lymphocyte activating factor (BAFF), a member of the tumour necrosis factor superfamily, is essential for B cell activation, differentiation and survival. Elevated circulating BAFF levels have been found in patients with several autoimmune conditions, including Graves' disease. In addition, BAFF gene variants have been associated with Graves' disease in a Taiwanese cohort, and with several other autoimmune conditions in non-Taiwanese populations. DESIGN AND METHODS: We performed a case-control association study to investigate two BAFF polymorphisms (rs9514828 and rs4000607) in a UK cohort of 444 patients with Graves' disease. Genotype frequencies were compared to those from 447 local controls and more than 5000 healthy controls from the Wellcome Trust case-control consortium (WTCCC2). RESULTS: There was a significant difference in the frequency of the AA genotype at rs4000607 between the Graves' disease cohort and both the local controls (P = 0.045) and the WTCCC2 controls (P = 4.56 × 10-6 ). Furthermore, the frequency of the A allele was found to be increased in the Graves' disease group compared to WTCCC2 controls (P = 0.02, OR 1.20 (95% CI 1.03-1.41). No association was observed at the rs9514828 locus. CONCLUSION: Dysfunction of the humoral immune system is an obligatory pathophysiological component of Graves' disease, hence BAFF is an excellent functional candidate gene. We have demonstrated, for the first time, a significant association of the BAFF polymorphism rs4000607 with Graves' disease in a UK cohort. Further work to elucidate the role of BAFF in the pathogenesis of Graves' disease is now warranted.