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OBJECTIVE--To determine the efficacy and dose requirements of captopril to reduce functional mitral regurgitation in patients with dilated heart failure. DESIGN--A randomised double blind placebo controlled parallel arm trial. Incremental daily doses of 25 mg, 50 mg and 100 mg captopril used for a four week period each for a total of 12 weeks preceded by a two week placebo washout. Twenty eight ambulatory patients (mean age 72) New York Heart Association (NYHA) class II or III with apparently controlled ischaemic dilated heart failure (ejection fraction 29% (0.04%)) on digoxin, diuretics, and nitrates were randomised. All had at least grade 2/4 functional mitral regurgitation (> 5 cm2 regurgitant area on colour flow Doppler). RESULTS--Twenty three patients completed the study (13 on placebo and 10 on captopril). Significant improvements were confined to the captopril group. Compared with placebo the following improvements were noted in the captopril treated group: mitral regurgitant area decreased from a threshold at 50 mg/day (p < 0.05, mean (95% confidence interval (95% CI)) 3.1 (0.2 to 6.0) cm2), with a further decrease at 100 mg/day (p < 0.01, mean (95% CI) 5.3 (3.1 to 7.5) cm2). Significant improvements in all the other measurements were noted only after 100 mg/day. Stroke volume increased (p < 0.01, mean (95% CI) 11, (1.4 to 21) ml), systemic vascular resistance decreased (p < 0.05, mean (95% CI) 414 (35 to 793) dyn s cm5), left atrial area decreased (p < 0.05, mean (95% CI) 4.3 (0.03 to 8.6) cm2), and deceleration time increased (p < 0.01, mean (95% CI) 52 ms (7 to 98) ms). Left ventricular diameter decreased marginally (p = 0.06, mean (95% CI) 4 (-0.05 to 9 mm). Duke activity index score increased (p < 0.001, median (95% CI) 6.8 (4.5 to 12) points). Heart rate, mean arterial blood pressure, serum creatinine, and serum potassium did not change with either placebo or captopril. No patient was withdrawn directly due to the side effects of captopril. In an open phase nine placebo patients given captopril in rapid increments reaching 100 mg/day in the fourth week showed similar improvements. CONCLUSION--Captopril is efficacious in reducing functional mitral regurgitation in dilated heart failure. Patients require and must tolerate high doses (50-100 mg/day) for additive effects over supervised conventional treatment to occur. [ABSTRACT FROM PUBLISHER]

The research examined the salivary concentrations of various biomarkers, such as OAZ1, SAT, S100P, IL-1β, and IL-8 aiming to detect early-stage oral squamous cell carcinoma (OSCC). These biomarkers show potential as indicators for detecting both pre-cancerous and cancerous states within the oral cavity. Analyzing these specific molecules in saliva could help clinicians enhance diagnostic accuracy and refine early detection methods for OSCC. The research encompassed a cohort of nine OSCC patients, ten with oral submucous fibrosis (OSF), eleven individuals with oral lichen planus (OLP), and ten healthy controls. The study focused on assessing the expression levels of key biomarkers-IL-1β, IL-8, SAT, S100P, and OAZ1 mRNA-in extracellular RNA extracted from saliva samples. This evaluation was conducted using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) with sequence-specific primers. Additionally, receiver operating characteristic curve (ROC) curve analysis was employed to gauge the efficacy of these biomarkers in detecting OSCC. Based on the results we observe, when these five biomarkers are used together, they give a 90% predictive probability for patients with OLP, an 80% predictive probability for OSF, and an impressive 100% predictive probability for patients with OSCC (AUC = 1.000, p = 0.000). This study demonstrates the efficacy of salivary transcriptome diagnostics in detecting OSCC. This novel clinical technique has the potential to be a powerful, efficient, and reliable tool for early detection of cancer. Salivary transcriptomes can be further analyzed to evaluate their effectiveness in other important illness contexts and for regular health monitoring., (© 2024. The Author(s).)

Background: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC., Methods: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC., Results: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023)., Conclusion: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring., (© 2024. The Author(s).)

Plants are a vital ingredient of traditional medicine in Sri Lanka, and the quantity of medicinal plants used as a number differs in literature. Field identification of medicinal plants is carried out based on various plant characteristics. Conventional identification keys are available for plant identification, but it is a complex and time-consuming process that relies on manual observation, introducing inherent errors, particularly among individuals lacking extensive botanical expertise. This may cause uncertainty in the identification of plants due to lack of professional training, morphological similarity and nomenclatural confusion of plants. Such uncertainty may result in misidentifying another plant(s) as intended medicinal plants, which may lead to unsafe consequences. The objectives of the study were accomplished with the following three steps; listing the flowering plants used for medicinal purposes in Sri Lanka using multiple detailed botanical literatures, identifying medicinal plants that are confused with other medicinal or non-medicinal plants using literature and a questionnaire survey, and developing Convolutional Neural Networks (CNN) based technology to distinguish confusing plants. The study prepared a list of 1358 flowering plants cultivated and used in Sri Lanka as medicinal plants. Fifty-three medicinal plants that are confused with 63 medicinal and non-medicinal plant species were identified by two surveys. The CNN solution experimented with five species of the Bauhinia genus with close morphologically similar leaves with a high misidentification possibility. Using CNN EfficientNet-B0 Architecture for classification, four models were tested, and Model 4, which was trained using the augmented dataset with white-coloured background, resulted in a validation accuracy of 96.16%. The current study demonstrated the critical role of CNNs and EfficientNets in addressing misidentification issues in morphologically similar medicinal plants., Competing Interests: Declaration of competing interest I am writing to formally declare that the manuscript entitled "Misidentifications in ayurvedic medicinal plants: Convolutional neural network (CNN) to overcome identification confusions", which I have submitted for publication in your esteemed journal, has not been published previously and is not currently under consideration for publication in any other journal. Furthermore, I confirm that this manuscript adheres to the guidelines of Computers in Biology and Medicine and that all authors have read and approved the final version of the manuscript. There are no conflicts of interest or competing financial interests to disclose. I also declare that any necessary permissions have been obtained for the use of copyrighted material, and ethical guidelines related to the research have been followed in accordance with the policies of the Computers in Biology and Medicine., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cutaneous leishmaniasis (CL) is caused by Leishmania donovani in Sri Lanka. Pentavalent antimonials (e.g., sodium stibogluconate [SSG]) remain first-line drugs for CL with no new effective treatments emerging. We studied whole blood and lesion transcriptomes from Sri Lankan patients with CL at presentation and during SSG treatment. From lesions but not whole blood, we identified differential expression of immune-related genes, including immune checkpoint molecules, after onset of treatment. Using spatial profiling and RNA-FISH, we confirmed reduced expression of programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) proteins on treatment in lesions of a second validation cohort and further demonstrated significantly higher expression of these checkpoint molecules on parasite-infected compared with noninfected lesional CD68+ monocytes and macrophages. Crucially, early reduction in PD-L1 but not IDO1 expression was predictive of rate of clinical cure (HR = 4.88) and occurred in parallel with reduction in parasite load. Our data support a model whereby the initial anti-leishmanial activity of antimonial drugs alleviates checkpoint inhibition on T cells, facilitating immune-drug synergism and clinical cure. Our findings demonstrate that PD-L1 expression can be used as a predictor of rapidity of clinical response to SSG treatment in Sri Lanka and support further evaluation of PD-L1 as a host-directed therapeutic in leishmaniasis.

Objective: The study aimed to compare the usefulness of two staining methods for imprint cytology for diagnosis of Helicobacter pylori infection. Gastric biopsy specimens (from dyspeptic patients attending routine upper gastrointestinal endoscopy) were placed on glass slides to obtain imprints. The imprints were stained with Toluidine blue and Giemsa stains separately and observed under ×400 magnification using a light microscope. Imprinted biopsies were sectioned and stained with H & E stain and Giemsa stain for histological analysis. Diagnosis of H. pylori infection in both imprint and histological sections were confirmed by a consultant pathologist. The sensitivity, specificity, positive predictive value and negative predictive value of each stain were calculated and benchmarked against histological diagnosis., Results: Of the 55 dyspeptic patients enrolled in the study, 5 were positive for H. pylori by Toluidine blue stain and 4 by Giemsa stain. The sensitivity of Toluidine blue stain (57.1%) was higher than Giemsa stain (42.9%) while the specificity of both stains was equal (97.9%). Giemsa stain gave a better discrimination for identification of H. pylori bacteria among the mucosal background. Imprint cytology is a rapid, simple and cost effective diagnosis method that can supplement histological diagnosis.

1. Subpressor calcium infusion for 1 h, which raised calcium levels to the upper limit of normal in normal subjects, increased plasma and urinary levels of atrial natriuretic peptide (ANP). 2. Heart rate fell, presumably due to carotid baroreflex stimulation (supported by the fall in noradrenaline) and the resultant fall in cardiac output prevented the expected rise in blood pressure due to the rise in total peripheral resistance (TPR). Thus the increase in ANP was not explained by an increase in blood pressure or noradrenaline. 3. There was no evidence for increased atrial stretch (no increase in atrial area or early velocity of left ventricular filling) as a mechanism for increased ANP. 4. Isovolumic left ventricular relaxation time increased, early velocity of ventricular filling decreased and TPR increased, consistent with increased tone in left ventricular and arteriolar muscle. 5. This suggests a direct effect of calcium on the atrial myocyte, stimulating ANP either through contractile or secretory mechanisms.

Colour duplex flow imaging is a highly accurate form of non-invasive assessment of the extra-cranial carotid circulation. This method is precise in characterising the degree of carotid stenosis, when compared with intra-arterial digital subtraction angiography. The accuracy of colour duplex in defining mild (1-30%), moderate (31-70%) and severe (71-99%) stenosis was 96%, 95% and 98%, respectively. Sensitivities and specificities were greater than 90% in each category, while positive and negative predictive values ranged from 96% to 100%.

This paper reports a case of fatal perhexiline maleate liver injury. A 62-year-old man had received perhexiline maleate for 18 months before death. Hepatic failure developed after a routine surgical procedure. The clinical course and histological findings are presented.

There is increasing evidence that only hemodynamically significant internal carotid lesions (of more than 50% diameter stenosis or occlusion) rather than minor lesions are the precursors of stroke. A Doppler test combining periorbital and direct audible interpretation of internal carotid Doppler signals was performed on 67 patients (134 internal carotids) and the results were compared with those from conventional biplane angiography. The test was 100% sensitive and had a positive predictive value of 91% for hemodynamically significant lesions. Negative predictive value for normal or less than 50% stenosis was 100%. Carotid bifurcation bruits were heard over only 25% of internal carotids with significant stenosis and nearly 60% of bruits were heard over internal carotids with minor disease. The equipment was portable and relatively inexpensive. The test could be performed by vascular technicians in less than 12 minutes with minimal patient discomfort, thus meeting most of the criteria for an ideal non-invasive screening test.

Identification of lacunar infarction as a cause of stroke is important, as investigation, treatment and outcome differ from those in the other stroke categories. In this study of 121 acute strokes admitted over a period of 12 months, 28 patients (23%) were found to have lacunar infarction and 93% of patients with lacunes had either a past history of hypertension or echocardiographic evidence of left ventricular hypertrophy. The degree of left ventricular hypertrophy tended to be moderate to severe with an average left ventricular mass on echocardiography of 120 g/m2. Pure motor hemiparesis was the commonest clinical presentation and lacunar infarction overall has a low mortality.