Development of a microcantilever-based biosensor for detecting Programmed Death Ligand 1.

The ongoing global concern of cancer worldwide necessitates the development of advanced diagnostic and therapeutic strategies. The majority of recent detection strategies involve the employment of biomarkers. A critical biomarker for cancer immunotherapy efficacy and patient prognosis is Programmed Death Ligand 1 (PD-L1), which is a key immune checkpoint protein. PD-L1 can be particularly linked to cancer progression and therapy response. Current detection methods, such as enzyme-linked immunosorbent assay (ELISA), face limitations like high cost, time consumption, and complexity. This study introduces a microcantilever-based biosensor designed for the detection of soluble PD-L1 (sPD-L1), which has a specific association with PD-L1. The biosensor utilizes anti-PD-L1 as the sensing layer, capitalizing on the specific binding affinity between anti-PD-L1 and sPD-L1. The presence of the sensing layer was confirmed through Atomic Force Microscopy (AFM) and contact angle measurements. Binding between sPD-L1 and anti-PD-L1 induces a shift in the microcantilever's resonance frequency, which is proportional to the PD-L1 concentration. Notably, the resonance frequency shift demonstrates a robust linear relationship with the increasing biomarker concentration, ranging from 0.05 ng/ml to 500 ng/ml. The detection limit of the biosensor was determined to be approximately 10 pg/ml. The biosensor demonstrates excellent performance in detecting PD-L1 with high specificity even in complex biological matrices. This innovative approach not only provides a promising tool for early cancer diagnosis but also holds potential for monitoring immunotherapy efficacy, paving the way for personalized and effective cancer treatments.

Clinical Outcomes With Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Insulin-Naïve and Previously Insulin-Treated Individuals With Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials.

AIMS: The once-weekly insulin icodec, a new basal insulin analog, may positively support a reduction in injection frequency and improve adherence to therapy in type 2 diabetes (T2D). This study aimed to evaluate the safety and efficacy of insulin icodec compared with those of once-daily glargine U100. METHODS: A comprehensive literature search was conducted using PubMed/MEDLINE, Embase and the Cochrane Library from inception till September 2023. Data about clinical outcomes in both groups were extracted. Forest plots were generated using the random-effects model by pooling odds ratios (ORs) and mean differences (MDs). RESULTS: Five randomised controlled trials and 2019 individuals with T2DM were included. In the pooled analysis, time in range was significantly higher (MD = 4.35; 95% CI: 1.65 to 7.05; p = 0.002) in the icodec group than in the once-daily glargine group. The HbA1c levels were significantly reduced (MD = -0.13; 95% CI: -0.24 to -0.03; p = 0.02) in the weekly icodec group compared with those in the once-daily glargine group. The weight gain was significantly less in the glargine group than in the weekly icodec group (MD = 0.41; 95% CI: 0.04 to 0.78; p = 0.03); however, in the subgroup analysis, this change became statistically insignificant in both insulin-naïve and previously insulin-treated individuals. The results were comparable across two groups for fasting plasma glucose levels, hypoglycaemia alert (Level 1), clinically significant (Level 2) or severe hypoglycaemia (Level 3), and adverse events. CONCLUSION: Insulin icodec was associated with a reduction in glycated haemoglobin levels and higher time in range, with a similar safety profile as compared to insulin glargine U100. However, further evidence is still needed to reach a definitive conclusion.

Enhancing WHO Prescription writing guideline adherence through an educational intervention - a quality improvement study of Azad Jammu and Kashmir.

BACKGROUND: Prescription writing is an important component of healthcare delivery and can directly influence patient safety and treatment outcomes. Prescription errors are common in developing countries because of the lack of national guidelines. This two-cycle clinical audit assessed the impact of educational interventions on improving prescription writing practices. METHODS: A cross-sectional prospective clinical audit was conducted in the Out Patients Department (OPD) of the District Head Quarters (DHQ) Hospital in Bhimber, Azad Jammu, and Kashmir. A total of 100 randomly selected prescriptions were reviewed for each cycle from July to August 2023. We recorded compliance with WHO guidelines for prescription writing before and after the educational intervention. Microsoft Excel and SPSS version 25.0 were used for statistical analysis. Categorical variables were analyzed using frequencies and percentages. RESULTS: An improvement in compliance was observed during the 2nd audit cycle, after the educational intervention. The greatest improvement was observed in documenting the allergic status of patients (62%) and the direction of drug administration (40%). We also observed improvements in the treatment duration (>10%), patient weight, physician registration number, diagnosis, and follow-up advice. The legibility of prescriptions also improved during the 2nd audit cycle. CONCLUSION: This study shows that integrating an educational intervention into a clinical audit can improve prescription writing practices and ultimately result in better quality of care for patients.

In-Silico Characterization and in-Vivo Validation of Albiziasaponin-A, Iso-Orientin, and Salvadorin Using a Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia, excessive acetylcholinesterase (AChE) activity, formation of neurotoxic amyloid plaque, and tau protein aggregation. Based on literature survey, we have shortlisted three important target proteins (AChE, COX2, and MMP8) implicated in the pathogenesis of AD and 20 different phytocompounds for molecular docking experiments with these three target proteins. The 3D-structures of AChE, COX2, and MMP8 were predicted by homology modeling by MODELLER and the threading approach by using ITASSER. Structure evaluations were performed using ERRAT, Verify3D, and Rampage softwares. The results based on molecular docking studies confirmed that there were strong interactions of these phytocompounds with AChE, COX2, and MMP8. The top three compounds namely Albiziasaponin-A, Iso-Orientin, and Salvadorin showed least binding energy and highest binding affinity among all the scrutinized compounds. Post-docking analyses showed the following free energy change for Albiziasaponin-A, Salvadorin, and Iso-Orientin (-9.8 to -15.0 kcal/mol) as compared to FDA approved drugs (donepezil, galantamine, and rivastigmine) for AD (-6.6 to -8.2 Kcal/mol) and interact with similar amino acid residues (Pro-266, Asp-344, Trp-563, Pro-568, Tyr-103, Tyr-155, Trp-317, and Tyr-372) with the target proteins. Furthermore, we have investigated the antioxidant and anticholinesterase activity of these top three phytochemicals namely, Albiziasaponin-A, Iso-Orientin, and Salvadorin in colchicine induced rat model of AD. Sprague Dawley (SD) rat model of AD were developed using bilateral intracerebroventricular (ICV) injection of colchicine (15 µg/rat). After the induction of AD, the rats were subjected to treatment with phytochemicals individually or in combination for 3 weeks. The serum samples were further analyzed for biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), matrix metalloproteinase-8 (MMP-8), isoprostanes-2 alpha (isoP-2α), and acetylcholine esterase (AChE) using conventional Enzyme Linked Immunosorbent Assay (ELISA) method. Additionally, the status of lipid peroxidation was estimated calorimetrically by measuring thiobarbituric acid reactive substances (TBARS). Here, we observed a statistically significant reduction (P < 0.05) in the oxidative stress and inflammatory markers in the treatment groups receiving mono and combinational therapies using Albiziasaponin-A, Iso-Orientin, and Salvadorin as compared to colchicine alone group. Besides, the ADMET profiles of these phytocompounds were very promising and, hence, these potential neuroprotective agents may further be taken for preclinical studies either as mono or combinational therapy for AD.