Bioproduction of yeast single cell oil with acute oral toxicity study intended for edible oil application.

Human nutrition and health rely on edible oils. Global demand for edible oils is expanding, necessitating the discovery of new natural oil sources subjected to adequate quality and safety evaluation. However, in contrast to other agricultural products, India's edible oil supply is surprisingly dependent on imports. The microbial oil is generated by fermentation of oleaginous yeast Rhodotorula mucilaginosa IIPL32 MTCC 25056 using biodiesel plant byproduct crude glycerol as a fermentable carbon source. Enriched with monounsaturated fatty acid, nutritional indices mapping based on the fatty acid composition of the yeast SCO, suggested its plausible use as an edible oil blend. In the present study, acute toxicity evaluation of the yeast SCO in C57BL/6 mice has been performed by randomly dividing the animals into 5 groups with 50, 300, 2000, and 5000 mg/Kg yeast SCO dosage, respectively, and predicted the median lethal dose (LD50). Detailed blood biochemistry and kidney and liver histopathology analyses were also reported. The functions of the liver enzymes were also evaluated to check and confirm the anticipated toxicity. To determine cell viability and in vitro biocompatibility, the 3T3-L1 cell line and haemolysis tests were performed. The results suggested the plausible use of yeast SCO as an edible oil blend due to its non-toxic nature in mice models.

Intermittent hypoxia and sleep disruption in obstructive sleep apnea increase serum tau and amyloid-beta levels.

Obstructive sleep apnea is characterized by intermittent hypoxia and sleep disruption, leading to accelerated neurodegenerative changes and cognitive decline. Serum amyloid-beta and tau proteins, which are markers for Alzheimer's disease, have been reported to increase in patients with obstructive sleep apnea. This study compared the serum levels of amyloid-beta proteins and tau proteins in 46 cognitively normal obstructive sleep apnea patients and 30 healthy controls. Sleep parameters and severity of obstructive sleep apnea were determined using overnight polysomnography. Serum levels of Aß40, Aß42, total tau and phosphorylated-tau were determined by enzyme-linked immunosorbent assay. Patients with obstructive sleep apnea had significantly higher median serum levels of Aß40 (121.0 versus 78.3 pg ml-1 ), Aß42 (105.6 versus 18.6 pg ml-1 ) and total tau (168.5 versus 10.9 pg ml-1 ) than controls. Serum levels of phosphorylated-tau did not differ significantly between the two groups. Serum levels of amyloid and tau proteins correlated with parameters of nocturnal oxygen saturation. Rapid eye movement sleep was negatively correlated with total amyloid-beta proteins. We conclude that serum levels of amyloid-beta and total tau are higher in patients with obstructive sleep apnea and hypoxia as well as changes in sleep architecture associated with their increased levels. Patients with obstructive sleep apnea should be closely monitored for the signs of cognitive impairment. Obstructive sleep apnea is a modifiable risk factor, and its treatment may reverse neurodegenerative changes and prevent cognitive impairment.

Reference intervals for reticulocyte parameters (reticulocyte haemoglobin equivalent and immature reticulocyte fraction) in first-trimester pregnancy.

Reticulocyte parameters including reticulocyte haemoglobin equivalent (Ret-He) and immature reticulocyte fraction (IRF) are newly recognised hematological parameters that are being used for diagnosis and follow-up of anaemic patients. Reference intervals of these parameters have been established in different populations, however, the data relating to pregnancy are still lacking. One hundred and fifty-five first-trimester pregnant females were screened and the reference interval was calculated after selecting the patient with fixed criteria. R statistical software was used for statistical calculations. We tried to establish a reference interval of Ret-He content and IRF in first-trimester pregnancy in our study.IMPACT STATEMENTWhat is already known on this subject? Ret-He and IRF have been established as the marker of iron deficiency and iron-deficiency anaemia in different age groups and as a marker of response to iron therapy. However, literature is scarce regarding the reference intervals of these parameters, especially in pregnancy.What do the results of this study add? This study establishes the reference interval of newer reticulocyte parameters in first-trimester pregnancy which is not yet established in the literature. Establishing a reference interval is required for any laboratory parameters to be used in the clinical context.What are the implications of these findings for clinical practice and further research? The results of this study may help in making a clinical decision regarding iron deficiency in early pregnancy which is one of the common clinical problems in pregnancy. This study also serves as a baseline study for further studies of reference intervals for newer reticulocyte parameters in pregnancy. A similar study with a larger study population and follow-up with iron therapy may establish these parameters as one of the important markers of iron deficiency in pregnancy and help institute iron therapy on case-to-case basis.

Molecular characterization of lung carcinomas: A study on diagnostic, predictive, and prognostic markers using immunohistochemical analysis at a Tertiary Care Center in Uttarakhand, India.

INTRODUCTION: Focused studies in different geographic regions would delineate the underlying biological differences and molecular alterations in non-small cell lung cancer (NSCLC) worldwide. Previous studies in literature have documented limited characterization by studying a minimal number of biological markers. This study was done to evaluate expression of multiple immunomarkers including diagnostic, prognostic, and predictive markers in NSCLC for its characterization. MATERIALS AND METHODS: This was an observational study conducted on 60 consecutive cases of NSCLC. Immunomarkers comprising of p63, p40, TTF-1, napsin A, B-Raf, c-Met, phospho-AKT (P-AKT), PTEN, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR) and K-Ras, synaptophysin, chromogranin and pan-cytokeratin were evaluated on paraffin-embedded tissue sections of NSCLC. RESULTS: Age of patients with NSCLC in our study ranged from 35 to 90 years, and 93.3% of them were chronic smokers. 93.3% of cases presented in late stages (Stages III and IV) and 78% of cases were squamous cell carcinoma (SCC). EGFR positivity was noted in 83.3% of cases. ALK was positive in one case while C-Met and PTEN immunopositivity was noted in only two cases. Ten cases showed positivity for K-Ras and 90% of these were SCC. Ten cases were positive for B-Raf and 80% of these were SCC. 30% of cases showed immunopositivity for P-AKT. None of the molecular markers was found to have statistically significant correlation with clinicopathological parameters. CONCLUSION: SCC is the predominant histological subtype of NSCLC in the region of Uttarakhand, India, with a high proportion of cases harboring EGFR mutation. Variable expression of K-Ras, P-AKT, ALK 1, and PTEN in NSCLC signifies that molecular profile of every case is individualistic and independent. We attribute this to ethnicity, influence of implicated substance or metabolite in tobacco, and variable mutations incurred in tumor cells over a period of time.

Short term biological variation of common hematological parameters in healthy subjects in a South Asian population.

There is no rigorous publication on the biological variation of common hematological parameters in South Asians to date. Also, there are few publications worldwide dealing with a variation of Reticulocyte parameters. Therefore, an attempt was made to estimate the short term within-subject and between-subject biological variation of common hematological and reticulocyte parameters. Twenty-eight healthy individuals (fifteen males and thirteen females) were selected after clinical and laboratory examination. Blood was collected in K3-EDTA vials in the morning for six consecutive days and analysed in triplicate on the Sysmex XN-1000 analyzer. Outliers were excluded and the within-subject, between-subject and analytical coefficient of variation calculated after statistical analysis by nested repeated measures ANOVA. The Reference change values (RCV), and estimates for desirable imprecision, bias, total error and index of individuality calculated. The within-subject biological variation for the studied subset belonging to South Asia closely followed published European and American studies and were similar for males and females. The between-subject variation showed differences from the published studies for white blood cells, platelets, red blood cells, hemoglobin, platelet indices and reticulocyte hemoglobin as well as between males and females for hemoglobin, red blood cell count and hematocrit. All the indices of individuality were low. This study supports the contention that the conclusions from within-subject biological variation for common hematological parameters are important and transportable to a South Asian population for short-term serial measurements. For quality specifications dependent on between-subject variation, the lower estimates from European and American studies should be used.

Short-term biological variation of differential count in healthy subjects in a South Asian population.

Estimates of Within-Subject and between subject biological variation for the white blood cell differential count (DC) have not been reported in South Asia. Therefore, we attempted to measure the short-term biological variation estimates for DC. The study was conducted on 28 healthy volunteers (15 males and 13 females). Blood from the volunteers was collected in the morning in K3-EDTA vials and analyzed in triplicate on the Sysmex XN-1000 analyzer, for six consecutive days. The Within subject, between subject and analytical coefficient of variation of the DC was calculated from the results by nested repeated measures ANOVA after outlier exclusion. The Reference change values (RCV) were also calculated. The within-subject variation for eosinophil Count and between subject variation for basophils in our study from South Asia was greater than the published European and American studies. Males and females showed similar biological variation for DC. The within-subject variation of other parameters (Neutrophils, Lymphocytes, Monocytes and Basophils) were similar or showed only mild differences to the published studies. The markedly different within-subject variation for Eosinophil counts suggest that the RCV for DC in South Asians need to be different from the published data in order to have clinical relevance. The Within-subject variation values of the other parameters seem transportable from the published European and American studies, but the small differences found mean that further regional estimates need to be reported for robust evidence of the same.

Diabetes mellitus in the context of blood transfusion.

Diabetes mellitus is one of the commonest medical conditions affecting humans. However, knowledge of diabetes mellitus in the context of blood transfusion is lacking. In this article, the eligibility of people with diabetes as donors, issues faced during blood component transfusion to diabetics and impaired glucose tolerance among chronic blood recipients will be discussed, along with discussion of the present state of evidence.

The Relationship of Grade, Stage and Tobacco Usage in Head and Neck Squamous Cell Carcinoma With p53, PIK3CA and MicroRNA Profiles.

BACKGROUND:  Head and neck squamous cell carcinoma (HNSCC) has multiple epigenetic modifications including post-transcriptional regulation by microRNAs (miRNAs) as well as alterations in molecular pathways due to mutations. Examining these miRNAs and location-specific molecular alterations is essential to understanding the intricacies of HNSCC and directing focused diagnoses and treatments. AIM:  To investigate tobacco-related changes in the expression of miRNAs and proteins with clinicopathological parameters of HNSCC and disease-modifying personal habits like tobacco and alcohol use. METHODOLOGY:  The study concentrated on oropharyngeal cancers using immunohistochemistry and reverse transcription-polymerase chain reaction. Expression of microRNAs mir15a, mir20b, mir21, mir31, mir33b, mir146a, mir155, mir218, mir363 and mir497 and immunohistochemical expression of P53 and PIK3CA were correlated with grade, stage and personal habits like tobacco and alcohol intake. RESULTS:  mir21 and mir15a are under-expressed in higher grades with a trend towards statistical significance (P-value of 0.094 and 0.056 by one-way analysis of variance (ANOVA) on ΔCT values). mir155 and mir146a are overexpressed in stage IV tumours while mir 31 is under-expressed in stage IV tumours but statistical significance was not reached. mir497 showed overexpression in tobacco users, but these results were limited by many tumours not showing any amplification for the miRNA and statistical significance was not reached. There was no statistically significant association found between immunohistochemical expression of p53 and PIK3CA with grade, stage or personal habits. CONCLUSION:  Through the deciphering of complex miRNA patterns and their relationships with clinicopathology, this study attempted to increase our understanding of HNSCC. Some candidate miRNAs showing probable association with grade, stage and personal habits were identified, but larger studies are needed to confirm or refute the importance of these miRNAs.

Systematic Review of Sleep Duration and Development of Myopia.

There is a knowledge gap in the relationship between sleep duration and myopia. Since sleep duration is a modifiable risk factor, its association with the development and progression of myopia has implications for public health. This review was conducted in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The bibliographic databases of PubMed and Scopus were searched for published studies on the association between sleep duration and myopia. These databases were searched in December 2023 with no date or study design limits. The relevant literature was extracted and met the priori determined population (children, adolescents, and adults suffering from myopia with or without corrective glasses), intervention/exposure (sleep), and the outcome (various indicators of sleep especially sleep duration/bedtime/wake time and sleep quality). Data were gathered by gender, age, and refraction technique and standardized to the definition of myopia as refractive error ≥0.50 diopter. The relevant literature was extracted from these electronic databases using the keywords "sleep," "sleep duration," "bedtime," and "myopia." English language articles related to the topic were included. Articles that have discussed the role of risk factors for myopia but did not mention any relation to sleep were excluded. Sixteen studies were included after reviewing the relevant literature, and only six studies have shown a significant relationship between shorter duration of sleep and the development of myopia. This review suggests that apart from other environmental factors, sleep duration may have a role in developing myopia. Thus, increasing awareness about optimum sleep duration has a potential utility to reduce the development and progression of myopia.

Beware it's benign: A unique case of concomitant benign breast pathologies.

Complex sclerosing lesion (CSL)/radial scar of breast is a benign entity that can pose a diagnostic challenge due to resemblance to breast carcinoma on imaging. Hamartoma are uncommon benign tumors, composed of disorganized mixture of glandular, fibrous, and adipose tissues, which can exhibit classical imaging characteristics. Here we describe a case of concomitant CSL and hamartoma in left beast, of which CSL presented as suspicious mass on imaging but was ultimately confirmed to be benign on histopathology with 4 years of documented stability.

A Study of Ki-67 Immunostaining in Prostate Carcinomas and Its Correlation with Gleason's Score and Prognosis: An Experience at a Tertiary Centre in the Himalayan Foothills.

Prostate cancer is a significant cause of cancer-related mortality among men worldwide, necessitating the exploration of prognostic biomarkers to aid in accurate risk assessment and treatment decision-making. This cross-sectional study aimed to comprehensively evaluate the role of Ki-67 as a prognostic marker in prostate cancer by examining its association with clinicopathological parameters. A total of 102 archived cases of prostate core biopsy specimens, histopathologically reported as prostate carcinoma, were included in this study. Histopathological grading was conducted using Gleason's scoring and grading system based on morphology. The statistical software "R" was utilized for data analysis. Kruskal-Wallis test and Fisher's exact test were employed to analyze the association between Ki-67 expression and clinicopathological parameters. The study revealed significant correlations between Ki-67 expression and various clinicopathological parameters in prostate cancer cases. High Ki-67 expression levels were associated with higher Gleason scores, increased incidence of perineural invasion, advanced T stages, lymph node metastasis, presence of distant metastasis, and higher prognostic stage groups. The findings of this cross-sectional study support the potential of Ki-67 as a prognostic marker in prostate cancer. The significant associations observed between Ki-67 expression and clinicopathological parameters indicate its usefulness in risk stratification and treatment decision-making. The incorporation of histopathological grading, including Gleason scoring, and analysis of perineural invasion strengthens the validity of the study. Ki-67, in combination with morphological assessments, provides valuable prognostic information for prostate cancer patients.

EEG based functional connectivity in resting and emotional states may identify major depressive disorder using machine learning.

OBJECTIVE: Disrupted brain network connectivity underlies major depressive disorder (MDD). Altered EEG based Functional connectivity (FC) with Emotional stimuli in major depressive disorder (MDD) in addition to resting state FC may help in improving the diagnostic accuracy of machine learning classification models. We explored the potential of EEG-based FC during resting state and emotional processing, for diagnosing MDD using machine learning approach. METHODS: EEG was recorded during resting state and while watching emotionally contagious happy and sad videos in 24 drug-naïve MDD patients and 25 healthy controls. FC was quantified using the Phase Lag Index. Three Random Forest classifier models were constructed to classify MDD patients and healthy controls, Model-I incorporating FC features from the resting state and Model-II and Model-III incorporating FC features while watching happy and sad videos respectively. RESULTS: Important features distinguishing MDD and healthy controls were from all frequency bands and represent functional connectivity between fronto-temporal, fronto-parietal and fronto occipital regions. The cross-validation accuracies for Model-I, Model-II and Model-III were 92.3%, 94.9% and 89.7% and test accuracies were 60%, 80% and 70% respectively. Incorporating emotionally contagious videos improved the classification accuracies. CONCLUSION: Findings support EEG FC patterns during resting state and emotional processing along with machine learning can be used to diagnose MDD. Future research should focus on replicating and validating these results. SIGNIFICANCE: EEG FC pattern combined with machine learning may be used for assisting in diagnosing MDD.

Comparison of Patient's Procedural Tolerance of EBUS-TBNA Performed Through Nasal Versus Oral Route: The NO-EBUS Randomized Clinical Trial.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly performed procedure by the bronchoscopist for the evaluation of mediastinal lesions. However, evidence directly comparing the nasal and oral routes to guide the choice of an optimal insertion approach is scanty. METHODS: In this prospective, parallel-group, open-label randomized clinical trial, adults posted for a linear EBUS-TBNA examination under conscious sedation were randomized to undergo the procedure via the nasal or oral route. The primary objective was to assess the equivalence of subject-rated tolerance of EBUS-TBNA procedure in the 2 groups. Key secondary objectives were to assess the equivalence of subject-rated overall experience, willingness for a repeat procedure, operator-rated subject's tolerance, and operator-rated ease of performing the procedure. RESULTS: One hundred and eighty subjects were randomized in a 1:1 ratio to the nasal (n=98) or oral (n=82) group. Outcome measures were assessed by both per-protocol (PP) and intention-to-treat (ITT) analysis. Subject-rated procedural tolerance, overall satisfaction and operator's ease of performing the procedure were found to be equivalent in the 2 groups ( P <0.05 in all cases for PP and ITT analysis). The operator-rated subject's tolerance was, however, nonequivalent ( P =0.0596, 0.1286 for PP and ITT, respectively). Subject's willingness to undergo a repeat procedure was similar in both groups [90% CI of difference in proportions: (-0.023, 0.121) in PP and (-0.028, 0.115) in ITT analysis]. CONCLUSION: Nasal route for EBUS-TBNA could be considered where it is feasible and preferable for the patient as well as the operator.

Systematic Review and Meta-Analysis of the Diagnostic Accuracy of the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy in Diagnosing Breast Cancer.

OBJECTIVES: The primary objective is to determine the accuracy of fine-needle aspiration biopsy (FNAB) in breast lesions reported according to the International Academy of Cytology (IAC) Yokohama system for reporting breast FNAB. The participants include any patient presenting with any breast lesion found suitable for FNAB. The target condition was breast cancer. The secondary objective was to study the proportion of inadequate FNAB in the selected studies. METHODS: PubMed/MEDLINE and Embase were searched for studies having all the following key search terms: Breast AND FNAB AND Diagnostic Accuracy published in the time frame of 2017 to May 16, 2022. The Cochrane and PROSPERO databases, citations of selected articles and articles citing the selected articles were also searched. Studies assessing the diagnostic accuracy of breast FNAB in diagnosing breast cancer, which had at least 75 subjects (and at least 20 subjects each in the benign and malignant FNAB groups), were selected. The reference standard was histopathology (or adequate clinical follow-up for benign disease). Studies were screened independently by two researchers, with a consensus reached among the authors in cases of conflict. The risk of bias and applicability were assessed using the QUADAS-2 tool. Sensitivity and specificity at each diagnostic cut-off were assessed by bivariate generalized linear mixed-model meta-analysis. The area under the receiver operating characteristics curve (AUC) and inadequacy rate were assessed by random-effects meta-analysis. The confidence intervals of sensitivity, specificity, and AUC were examined against a value of 0.95. RESULTS: Twenty-two studies, all of which were cross-sectional single-gate studies, were selected with a total of 10,886 subjects with a primary breast lesion having concurrent FNAB and reference standard reports. Sensitivity and specificity, with 95% confidence intervals, were 0.978 [0.968, 0.985] and 0.832 [0.76, 0.886] for the diagnostic cut-off of "Atypical considered positive for malignancy," 0.916 [0.892, 0.935] and 0.983 [0.97, 0.99] for the cut-off of "Suspicious of Malignancy considered positive," and 0.763 [0.706, 0.812] and 0.999 [0.994, 1] for the cut-off of "Malignant considered positive." The overall AUC was 0.975 [0.962, 0.984]. FNAB sampling without imaging guidance was associated with lower inadequacy. DISCUSSION: There is strong evidence that the overall accuracy, sensitivity for "Atypical category considered positive" and specificity when "Suspicious or Malignant categories are considered positive" of FNAB are high when using the categories of the IAC Yokohama Reporting System, demonstrating the usefulness of FNAB in diagnosing breast cancer.

Malignant pleural effusion from a case of squamous-cell carcinoma of the oral cavity: Cytological detection of a rare outcome.

Distant metastases from carcinomas of the oral cavity are rare. Detection of these metastasis are essential for staging and management of the patient. These tumours may metastasize to lung, liver, brain and bone; but pleural involvement by squamous-cell carcinoma is distinctly rare. We present a case of bilateral pleural effusion arising from distant metastasis of squamous-cell carcinoma detected on cytology.