A critical evaluation of pictogram based patient information leaflet on hypothyroidism patients with metabolic syndrome: a visual approach to enhance health literacy.

INTRODUCTION: Hypothyroidism is a condition with an underactive thyroid gland. Since thyroid hormones play a significant role in metabolism, hypothyroidism is often associated with metabolic syndrome. Thus, the patient's awareness regarding metabolic syndrome is crucial. OBJECTIVES: To develop and evaluate a Pictogram-based Patient Information Leaflet (P-PIL) for hypothyroidism with metabolic syndrome. MATERIALS AND METHODS: This is a quasi-experimental study without a control group. The P-PIL was developed and validated using the Lawshe Method, translated, and evaluated with 72 patients (24 patients each for English and regional languages, Kannada and Malayalam). RESULTS: The leaflet's Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL) scores were 62.0 and 7.1, respectively. The Baker Able Leaflet Design (BALD) index of English, Kannada, and Malayalam versions of the P-PIL were 28, 27, and 27, respectively. The user testing of the P-PIL was assessed in 72 patients. The overall mean knowledge assessment scores significantly improved from 52.92 ± 6.90 to 77.92 ± 9.31. The majority of patients, precisely 84.72%, expressed a positive opinion regarding the design and layout of the P-PIL. CONCLUSION: The evaluation results strongly suggest that this P-PIL can be an effective educational tool for hypothyroidism patients with metabolic syndrome.

Detection of phosphatidylserine-positive exosomes for the diagnosis of early-stage malignancies.

BACKGROUND: There has been increasing interest in the detection of tumour exosomes in blood for cancer diagnostics. Most studies have focussed on miRNA and protein signatures that are surrogate markers for specific tumour types. Because tumour cells and tumour-derived exosomes display phosphatidylserine (PS) in their outer membrane leaflet, we developed a highly sensitive ELISA-based system that detects picogram amounts of exosomal phospholipid in plasma as a cancer biomarker. METHODS: This report describes the development of a highly specific and sensitive ELISA for the capture of PS-expressing tumour exosomes in the blood of tumour-bearing mice. To monitor the relationship between tumour burden and tumour exosome plasma concentrations, plasma from one transplantable breast cancer model (MDA-MB-231) and three genetic mouse models (MMTV-PyMT; breast and KIC and KPC; pancreatic) were screened for captured exosomal phospholipid. RESULTS: We show that quantitative assessment of PS-expressing tumour exosomes detected very early-stage malignancies before clinical evidence of disease in all four model systems. Tumour exosome levels showed significant increases by day 7 after tumour implantation in the MDA-MB-231 model while palpable tumours appeared only after day 27. For the MMTV-PyMT and KIC models, tumour exosome levels increased significantly by day 49 (P⩽0.0002) and day 21 (P⩽0.001) while tumours developed only after days 60 and 40, respectively. For the KPC model, a significant increase in blood exosome levels was detected by day 70 (P=0.023) when only preinvasive lesions are microscopically detectable. CONCLUSIONS: These data indicate that blood PS exosome levels is a specific indicator of cancer and suggest that blood PS is a biomarker for early-stage malignancies.

Metabolic and Cardiovascular Ageing Indices in Relation to Glycated Haemoglobin in Healthy and Diabetic Subjects.

BACKGROUND: Ageing is a natural phenomenon that has tremendous amount of control over normal physiological functions. Diabetes mellitus and ageing share common symptoms like stiffness and loss of functioning of tissues due to cross-liked proteins and free radicals. Glycated Haemoglobin (HbA1c) is often used as a stable cumulative index of glycemic control and has shown that even in non-diabetic adults, there is a steady increase in HbA1c levels with age. Aim of the study is to evaluate the strength of association of HbA1c with metabolic and cardiovascular ageing indices in subjects between the age group of 40 to 60 yrs. METHOD: A total of 220 subjects, with (n=110) and without (n=110) diabetes were assessed for the metabolic and cardiovascular ageing indices. BMI, waist hip ratio, fat percentage, Fasting blood sugar and HbA1c were assessed as metabolic ageing indices. The cardiovascular ageing indices measured were resting heart rate, blood pressure and heart rate variability. RESULTS: Ageing indices were compared between subjects with and without diabetes using independent' t' test and showed that the T2DM group exhibit significant accelerated ageing as compared to that of the controls. Pearson's and partial correlation coefficient was used to assess the association of HbA1c with the ageing indices without and with controlling for chronological age, indicated that, strength of association of levels of HBA1c with cardiovascular and other metabolic indices of ageing is statistically significant. CONCLUSION: The study concludes that the tightness of glycemic control has a significant impact on the biological ageing process.

Detection of phosphatidylserine-positive exosomes as a diagnostic marker for ovarian malignancies: a proof of concept study.

There are no suitable screening modalities for ovarian carcinomas (OC) and repeated imaging and CA-125 levels are often needed to triage equivocal ovarian masses. Definitive diagnosis of malignancy, however, can only be established by histologic confirmation. Thus, the ability to detect OC at early stages is low, and most cases are diagnosed as advanced disease. Since tumor cells expose phosphatidylserine (PS) on their plasma membrane, we predicted that tumors might secrete PS-positive exosomes into the bloodstream that could be a surrogate biomarker for cancer. To address this, we developed a highly stringent ELISA that detects picogram quantities of PS in patient plasma. Blinded plasma from 34 suspect ovarian cancer patients and 10 healthy subjects were analyzed for the presence of PS-expressing vesicles. The nonparametric Wilcoxon rank sum test showed the malignant group had significantly higher PS values than the benign group (median 0.237 vs. -0.027, p=0.0001) and the malignant and benign groups had significantly higher PS values than the healthy group (median 0.237 vs -0.158, p<0.0001 and -0.027 vs -0.158, p=0.0002, respectively). ROC analysis of the predictive accuracy of PS-expressing exosomes/vesicles in predicting malignant against normal, benign against normal and malignant against benign revealed AUCs of 1.0, 0.95 and 0.911, respectively. This study provides proof-of-concept data that supports the high diagnostic power of PS detection in the blood of women with suspect ovarian malignancies.

Effect of very early mobilisation on functional status in patients with acute stroke: a single-blind, randomized controlled trail.

OBJECTIVE: To evaluate the effect of very early mobilisation on functional status following acute stroke. DESIGN: Single blind, randomized controlled trial. SETTING: University hospital. SUBJECTS: Eighty-six patients with acute stroke (42 men and 38 women) aged 30-80 years were randomized to an Intervention group and a Standard care group. INTERVENTIONS: All participants received 45 minutes standard care once a day for seven days. In addition, the intervention group (n=43) performed very early mobilisation consisting of early and frequent out of bed activities which started within 24 hours of stroke onset for 5 to 30 minutes at least twice a day, for seven days. OUTCOME MEASURES: Functional status was measured with Barthel ADL Index on admission, discharge and three months follow up. RESULTS: Intervention group showed a significant improvement in Barthel Index change scores (discharge - admission) (median=35, IQR=30-38.75 versus median=17.50, IQR=10-30) than the standard care group. Intervention group showed a significant improvement in Barthel Index change scores (three month follow up - admission) (median=42.50, IQR=35-55) versus (median=30, IQR=20-35) than the standard care group. The Intervention group reported statistically significant improvement in functional status at discharge (P<0.001) and at three months follow up (P<0.001) compared with the Standard care group. CONCLUSIONS: The results indicate that very early mobilisation in addition to the standard care may be effective in improving the functional status following acute stroke.

Putative bioactive motif of tritrpticin revealed by an antibody with biological receptor-like properties.

Antimicrobial peptides represent one of the most promising future strategies for combating infections and microbial drug resistance. Tritrpticin is a 13mer tryptophan-rich cationic antimicrobial peptide with a broad spectrum of activity whose application in antimicrobial therapy has been hampered by ambiguity about its biological target and consequently the molecular interactions necessary for its antimicrobial activity. The present study provides clues about the mechanism of action of tritripticin by using a unique monoclonal antibody (mAb) as a 'physiological' structural scaffold. A pool of mAbs were generated against tritrpticin and based on its high affinity and ability to bind tritrpticin analogs, mAb 6C6D7 was selected and characterized further. In a screening of phage displayed random peptides, this antibody was able to identify a novel antimicrobial peptide with low sequence homology to tritrpticin, suggesting that the mAb possessed the physico-chemical characteristics mimicking the natural receptor. Subsequently, thermodynamics and molecular modeling identified a core group of hydrophobic residues in tritrpticin arranged in a distorted's' shaped conformation as critical for antibody binding. Comparison of the mAb induced conformation with the micelle bound structure of tritrpticin reveals how a common motif may be able to interact with multiple classes of biomolecules thus extending the target range of this innate immune peptide. Based on the concurrence between thermodynamic and structural data our results reveal a template that can be used to design novel antimicrobial pharmacophores while simultaneously demonstrating at a more fundamental level the potential of mAbs to act as receptor surrogates.