Insoluble electrospun membranes for analyte pre-concentration in saliva

Insoluble electrospun membrane based on poly acrylic acid (PAA) crosslinked with ethylene glycol (EG) was prepared. The surface of the crosslinked PAA fibers was then grafted with polyethylenimine (PEI), octyl amine (OA) and EG using carbodiimide or thermal crosslinking to obtain insoluble membranes having anionic, cationic, hydrophobic and neutral characteristics for filtration of biomolecules from saliva. The resulting surface chemistries were confirmed by their respective ATR-FTIR spectra. Differences in fiber morphology and diameters were observed between the membranes. All the membrane variants were tested for their efficacy as solid phase extraction (SPE) matrices in the pre-concentration of ethanol in synthetic saliva, using a microfluidic chip. Gas chromatography assays showed no statistical difference for ethanol in eluents through each of the tested insoluble electrospun membrane variants versus their corresponding controls. Further studies would include the testing of these membranes in the pre-concentration of clinical biomolecules, including drugs of abuse (e.g., cocaine, THC), nutrients (e.g., glucose), proteins (e.g., albumin, HbA1C) and nucleic acids for sample preparation within point of care devices

Chemically roughened solid silver: A simple, robust and broadband SERS substrate

Surface-enhanced Raman spectroscopy (SERS) substrates manufactured using complex nano-patterning techniques have become the norm. However, their cost of manufacture makes them unaffordable to incorporate into most biosensors. The technique shown in this paper is low-cost, reliable and highly sensitive. Chemical etching of solid Ag metal was used to produce simple, yet robust SERS substrates with broadband characteristics. Etching with ammonium hydroxide (NH4OH) and nitric acid (HNO3) helped obtain roughened Ag SERS substrates. Scanning electron microscopy (SEM) and interferometry were used to visualize and quantify surface roughness. Flattened Ag wires had inherent, but non-uniform roughness having peaks and valleys in the microscale. NH4OH treatment removed dirt and smoothened the surface, while HNO3 treatment produced a flake-like morphology with visibly more surface roughness features on Ag metal. SERS efficacy was tested using 4-methylbenzenethiol (MBT). The best SERS enhancement for 1 mM MBT was observed for Ag metal etched for 30 s in NH4OH followed by 10 s in HNO3. Further, MBT could be quantified with detection limits of 1 pM and 100 µM, respectively, using 514 nm and 1064 nm Raman spectrometers. Thus, a rapid and less energy intensive method for producing solid Ag SERS substrate and its efficacy in analyte sensing was demonstrated.This work was financially supported by Home Office UK through the SBRI programme of Innovate UK, Grant No. SBRI_HO_202_007 (HOS/14/003). S. Wijesuriya acknowledges the fellowship for her Ph.D. from Brunel Institute for Bioengineering, Brunel University. We also acknowledge the support from Brunel University—RCUK fund for open access publishing

The Hybrid Motor Prototype: Design Details and Demonstration Results

A novel hybrid rotary motor incorporating piezoelectric and magnetostrictive actuators has been designed and demonstrated. The novelty of this motor was the creation of an electrical resonant circuit, whereby reactive power requirement on the power source is reduced. It was envisioned that the motor would be suitable for low output speed, high torque applications because of its design. This report presents the constructional details of this motor and the results of the demonstration

DIABRISK - SL Prevention of cardio-metabolic disease with life style modification in young urban Sri Lankan's - study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Urban South-Asian's are predisposed to early onset of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There is an urgent need for country specific primary prevention strategies to address the growing burden of cardio-metabolic disease in this population. The aim of this clinical trial is to evaluate whether intensive (3-monthly) lifestyle modification advice is superior to a less-intensive (12 monthly; control group) lifestyle modification advice on a primary composite cardio-metabolic end point in 'at risk' urban subjects aged between 5-40 years.</p> <p>Methods/Design</p> <p>This is an open randomised controlled parallel group clinical trial performed at a single centre in Colombo, Sri-Lanka. A cluster sampling strategy was used to select a large representative sample of subjects aged between 5-40 years at high risk of T2DM and CVD for the intervention study. We have screened 23,298 (males 47% females 53%) healthy subjects for four risk factors: obesity, elevated waist circumference, family history of diabetes and physical inactivity, using a questionnaire and anthropometry. Those with two or more risk-factors were recruited to the intervention trial. We aim to recruit 4600 subjects for the intervention trial. The primary composite cardio-metabolic end point is; new onset T2DM, impaired glucose tolerance, impaired fasting glycaemia, new onset hypertension and albuminuria, following 5 years of intervention. The effect of the intervention on pre-specified secondary endpoints will also be evaluated. The study will be conducted according to good clinical and ethical practice, data analysis and reporting guidelines.</p> <p>Discussion</p> <p>DIABRISK-SL is a large population based trial to evaluate the prevalence of diabetes, pre-diabetes and cardio-metabolic risk factors among young urban Sri-Lankans and the effect of a primary prevention strategy on cardio-metabolic disease end points. This work will enable country specific and regional cardio-metabolic risk scores to be derived. Further if the proposed intervention is successful the results of this study can be translated and implemented as a low-cost primary prevention tool in Sri-Lanka and other low/middle income developing countries.</p> <p>Trial registration</p> <p>The trial is registered with the World Health Organisation and Sri-Lanka clinical trial registry number SLCTR/2008/003</p

Should I Take Aspirin? (SITA): RCT of a decision aid for cancer chemoprevention.

Background Australian guidelines recommend that all people aged 50-70 years old consider taking low-dose aspirin to reduce the risk of colorectal cancer (CRC). Aim To determine the effect of a consultation with a researcher in general practice using a decision aid about taking low-dose aspirin to prevent CRC on informed decision-making and low-dose aspirin uptake compared to a general CRC prevention brochure. Design and Setting Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021. Method Patients aged 50-70 years attending a general practitioner (GP) were recruited consecutively. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk; control consultations discussed reducing CRC risk generally. The self-reported co-primary outcomes were informed choices about taking aspirin at one month and low-dose aspirin uptake at six months. Results 261 participants (86% of eligible patients) were randomised into trial arms (129 intervention, 132 control). 17.7% (20/113) of intervention and 7.6% (9/118) control participants reported making an informed choice at one month, an estimated 9.1% (95% CI 0.29% to 18.5) between-arm difference in proportions [odds ratio (OR) 2.47 (97.5% CI:0.94 to 6.52) p=0.074]. The proportions of individuals who reported using aspirin at six months were: 10.2% (12/118) intervention vs 13.8% (16/116) control (estimated between-arm difference: -4.0% (95% CI: -13.5 to 5.5); [OR= 0.68 (97.5% CI:0.27 to 1.70), p= 0.692]. Conclusion The decision aid improved informed decision-making; but has little effect on long-term regular use of aspirin to reduce CRC risk

Sorsby's fundus dystrophy in the British Isles: demonstration of a striking founder effect by microsatellite-generated haplotypes

Sorsby's fundus dystrophy (SFD) has been mapped to a genetic interval of 8 cM between loci D22S275 and D22S278. A total of 15 families, unrelated on the basis of genealogy and expressing the SFD phenotype were identified from a large data base of genetic eye disease families originating from diverse parts of the British Isles. The identification of the same Ser181Cys mutation cosegregating with disease in each family led us to consider the hypothesis of a founder effect being present. In all families studied, the same relatively infrequent allele (occurring in just 11% of the control group) was associated with disease at marker locus D22S280. A highly significant disease-associated haplotype, spanning across 3 cM of the SFD locus, was conserved in 11 of the 15 families (68% of all affected chromosomes); a further extended haplotype spanning up to 7 cM, was identified in 5 families (27% of SFD-associated chromosomes) and possibly represents the ancestral haplotype. This haplotype analysis has refined the TIMP3 gene localization to a 1- to 3-cM interval between marker loci D22S273 and D22S281 and provides strong evidence for a single mutational event being responsible for the majority of SFD identified in the British Isles

Stage II/III rectal cancer with intermediate response to preoperative radiochemotherapy: Do we have indications for individual risk stratification?

<p>Abstract</p> <p>Background</p> <p>Response to preoperative radiochemotherapy (RCT) in patients with locally advanced rectal cancer is very heterogeneous. Pathologic complete response (pCR) is accompanied by a favorable outcome. However, most patients show incomplete response. The aim of this investigation was to find indications for risk stratification in the group of intermediate responders to RCT.</p> <p>Methods</p> <p>From a prospective database of 496 patients with rectal adenocarcinoma, 107 patients with stage II/III cancers and intermediate response to preoperative 5-FU based RCT (ypT2/3 and TRG 2/3), treated within the German Rectal Cancer Trials were studied. Surgical treatment comprised curative (R0) total mesorectal excision (TME) in all cases. In 95 patients available for statistical analyses, residual transmural infiltration of the mesorectal compartment, nodal involvement and histolologic tumor grading were investigated for their prognostic impact on disease-free (DFS) and overall survival (OS).</p> <p>Results</p> <p>Residual tumor transgression into the mesorectal compartment (ypT3) did not influence DFS and OS rates (p = 0.619, p = 0.602, respectively). Nodal involvement after preoperative RCT (ypN1/2) turned out to be a valid prognostic factor with decreased DFS and OS (p = 0.0463, p = 0.0236, respectively). Persistent tumor infiltration of the mesorectum (ypT3) and histologic tumor grading of residual tumor cell clusters were strongly correlated with lymph node metastases after neoadjuvant treatment (p < 0.001).</p> <p>Conclusions</p> <p>Advanced transmural tumor invasion after RCT does not affect prognosis when curative (R0) resection is achievable. Residual nodal status is the most important predictor of individual outcome in intermediate responders to preoperative RCT. Furthermore, ypT stage and tumor grading turn out to be additional auxiliary factors. Future clinical trials for risk-adapted adjuvant therapy should be based on a synopsis of clinicopathologic parameters.</p

Structure-Based Analysis of Five Novel Disease-Causing Mutations in 21-Hydroxylase-Deficient Patients

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most frequent inborn error of metabolism, and accounts for 90–95% of CAH cases. The affected enzyme, P450C21, is encoded by the CYP21A2 gene, located together with a 98% nucleotide sequence identity CYP21A1P pseudogene, on chromosome 6p21.3. Even though most patients carry CYP21A1P-derived mutations, an increasing number of novel and rare mutations in disease causing alleles were found in the last years. In the present work, we describe five CYP21A2 novel mutations, p.R132C, p.149C, p.M283V, p.E431K and a frameshift g.2511_2512delGG, in four non-classical and one salt wasting patients from Argentina. All novel point mutations are located in CYP21 protein residues that are conserved throughout mammalian species, and none of them were found in control individuals. The putative pathogenic mechanisms of the novel variants were analyzed in silico. A three-dimensional CYP21 structure was generated by homology modeling and the protein design algorithm FoldX was used to calculate changes in stability of CYP21A2 protein. Our analysis revealed changes in protein stability or in the surface charge of the mutant enzymes, which could be related to the clinical manifestation found in patients