Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) continues to be a major concern in clinical practice, thus necessitating a need for novel therapeutic approaches to alleviate its impact on hepatic function. This review investigates the therapeutic potential of nutraceuticals against DILI, focusing on examining the underlying molecular mechanisms and cellular pathways. In preclinical and clinical studies, nutraceuticals, such as silymarin, curcumin, and N-acetylcysteine, have demonstrated remarkable efficacy in attenuating liver injury induced by diverse pharmaceutical agents. The molecular mechanisms underlying these hepatoprotective effects involve modulation of oxidative stress, inflammation, and apoptotic pathways. Furthermore, this review examines cellular routes affected by these nutritional components focusing on their influence on hepatocytes, Kupffer cells, and stellate cells. Key evidence highlights that autophagy modulation as well as unfolded protein response are essential cellular processes through which nutraceuticals exert their cytoprotective functions. In conclusion, nutraceuticals are emerging as promising therapeutic agents for mitigating DILI, by targeting different molecular pathways along with cell processes involved in it concurrently.

Unveiling the Aggressiveness of Cholesteatoma: Associating MERI with miRNA-21 & IL-6 Expression.

BACKGROUND: Cholesteatoma, a destructive middle ear condition, poses challenges due to its variable clinical presentation and propensity for recurrence. Understanding its molecular underpinnings could enhance prognostication and guide therapeutic interventions. This study investigates the association between cholesteatoma aggressiveness, as assessed by the Middle Ear Risk Index (MERI), and the expression of miRNA-21 and IL-6 genes. METHODS: A cross-sectional observational study involving 30 patients with cholesteatoma undergoing tympanomastoid exploration was conducted. MERI scores were calculated preoperatively, and cholesteatoma tissue was analyzed for miRNA-21 and IL-6 gene expression using RT-PCR. Statistical analysis was performed to correlate MERI scores with gene expression levels. RESULTS: The majority (80%) of patients exhibited severe MERI scores, correlating with extensive middle ear pathology and necessitating canal wall-down (CWD) mastoidectomy. Higher miRNA-21 and IL-6 gene expression levels were observed in cholesteatoma tissues, indicating local aggressiveness and inflammatory activity. Significant moderate correlations were found between MERI scores and miRNA-21 (Pearson correlation = 0.579, p = 0.001) and IL-6 gene expression (Pearson correlation = 0.388, p = 0.034). Patients with severe MERI scores had elevated miRNA-21 and IL-6 levels, suggesting a more aggressive disease phenotype. CONCLUSION: MERI scores demonstrated utility in predicting cholesteatoma aggressiveness, with higher scores correlating with elevated miRNA-21 and IL-6 expression. These findings suggest a potential role for MERI in guiding surgical decision-making and prognostication. Future research on targeted therapies based on molecular mechanisms holds promise for improving cholesteatoma management. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Dependability and Prognostic Value of Biomarkers in COVID-19 Associated Rhino-Orbito- Cerebral Mucormycosis- A Long Term Ambispective Study.

COVID-19 pandemic, which has exhibited a wide clinical spectrum and an unexpected surge in mucormycosis cases, understanding various biomarkers' roles becomes pivotal. As mucormycosis leads to clinical morbidity and mortality through angioinvasion and thromboembolism, unveiling the correlation between these markers and disease progression can shed light on the reasons behind mucormycosis's emergence as an epidemic, especially following the second wave of COVID-19. This long term ambispective observational study, conducted from May 2020 to July 2023, aimed to assess specific biomarkers as predictors of severity in COVID-19-associated mucormycosis (CAM). Biomarkers measured included ESR, CRP, D-dimer, IL-8, PCT, serum ferritin, and neutrophil-lymphocyte ratio (NLR) at different time points. Data analysis employed descriptive statistics, repeated measure ANOVA, Spearman correlations, ROC curve analysis, and logistic regression. Of 290 patients, 198 completed the 2-year follow-up. Elevated baseline biomarker levels significantly decreased with treatment initiation. CRP and NLR emerged as significant predictors of severe CAM, with odds ratio 2.926 (95% CI 1.466-4.360) and 2.203 (95% CI 0.863-1.040) respectively. Factors influencing CAM progression included age, CRP, and NLR, while all biomarkers independently predicted mortality. A death prediction model using CRP, PCT, D-dimer, NLR, and IL-8 demonstrated exceptional performance, with a sensitivity of 83.1% and specificity of 100%. Elevated inflammatory markers in CAM patients showed a decline with treatment, with NLR and CRP proving crucial for predicting severity. Serial monitoring of IL-8, CRP, PCT, NLR, D-dimer, and ferritin provides insights into disease progression and prognosis. The study underscores the importance of biomarker assessment in managing CAM, especially in the context of the unpredictable clinical spectrum of COVID-19 and the subsequent mucormycosis surge. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04921-3.

Beyond the basics: Sigma scores in laboratory medicine with variable total allowable errors (TEa).

BACKGROUND: To diagnose diseases, track the effectiveness of treatments and make well-informed clinical decisions, doctors rely on results from laboratories. Accurate and precise results minimize the necessity for additional testing, saving time and money while enhancing patient satisfaction.. Internal quality control and an external quality assurance scheme(EQAS) are metrics used to evaluate a clinical laboratory's performance. One of the numerous quality indicators that can be used to gauge the amount of errors is sigma metrics. To calculate the sigma scores bias%, CV%, and Total Error Allowable (TEa) are needed. Total Error allowable(TEa) is a crucial benchmark that establishes allowed limits on the degree of deviation from the target value for a certain analyte. Nevertheless, a proper consensus for establishing a TEa goal has not been reached and the impact of this limiting factor in standard laboratory practice and sigma calculation has not been sufficiently established. Choosing the right Total Error allowable(TEa) goal is one of the greatest challenges when employing sigma metrics as depending on the source, several measurands of TEa values may exhibit alteration. MATERIAL AND METHODS: Our study aims to determine the sigma scores of 20 routine chemistry parameters using six different TEa sources: Clinical Laboratory Improvement Amendment (CLIA 88'), CLIA(Clinical Laboratory Improvement Amendment) 24, BDV (Biological Variation Desirable), RCPA(Royal College of Pathologists of Australasia), RiliBak(Guideline of the German Medical Association for Quality Assurance of Laboratory Medical Examinations), and EMC/Spain(Measurement and Control Scheme) over a 12-month period using the bias percent from the External Quality Assessment Scheme (EQAS) and coefficient of variation (CV) from the Internal Quality Control (IQC). Detection system was automated, multi-channel, selective analyzer, the Beckman Coulter AU680 which works on the principle of spectrophotometry. To compute the Sigma metrics, formula used was Sigma = (TEa - Bias%) / CV%. By comparing the sigma values from the different TEa sources, TEa variance on the evaluation of the sigma metric was ascertained after which an internal quality control plan and QGI(Quality Goal Index) for underperforming parameters were devised. RESULTS: The study discovered that the sigma values of common chemical parameters varied significantly based on the TEa sources used. Maximum parameters in the above three-sigma zone were TBil, HDL, CK, ALP, amylase and uric acid in CLIA'88 while RCPA and Biological variation were determined to be the most severe, with the highest performing parameters falling below three sigma zones. Rilibaek was the most liberal, with only sodium in the lower three sigma zones along with CLIA'88. The findings indicate that there is the substantial influence of various Total Error Allowable (TEa) sources on the sigma metric evaluation. A quality control plan was devised depending on different sigma scores of the analytes using biorad unity 2.0 software(westgard sigma multirules). The origins of errors that resulted in low sigma ratings liked enhanced cleaning of electrodes, electrode replacement, ageing of reagents, instrument maintainence were pinpointed and addressed. CONCLUSION: The study highlights the necessity of harmonizing and standardizing sigma metrics, stressing the significance of choosing suitable total error allowable goals (TEa). The creation of worldwide standards and recommendations for total error allowable (TEa) can lead to its harmonization. Establishing a consensus on the acceptable levels of error for various laboratory tests would necessitate the cooperation of specialists from many nations and organizations in order to set such guidelines and standards.

Assessing Performance of Martins's and Sampson's Formulae for Calculation of LDL-C in Indian Population: A Single Center Retrospective Study.

Various formulae had been derived to calculate the LDL-C from other lipid profile parameters to supplant the need for direct estimation. Martin's, Sampson's, and Cordova's formulae are recently derived formulae for calculating LDL-C. However, no study has been undertaken till now to verify the newer formulae viz. Martins's and Sampson's in Indian population. The retrospective cross-sectional study was carried out after obtaining approval from the Institutional Ethics Committee on human subject research. The lipid profile data were collected for a period of 17 months from January 2020 to May 2021. The formulae proposed by Friedewald, Cordova, Anandaraja, Martin, and Sampson were used to assess calculated LDL-C. Intraclass correlations were performed to assess the effectiveness of each formula when compared with direct estimation. In our study, we observed that LDL-C calculated using Martin was observed to be closer to that of direct estimation. The bias observed was lowest for Martin's formulae, followed by Sampson's. Intraclass correlation analysis for absolute agreement demonstrated Cordova, Martin, and Sampson to have an average ICC > 0.9, with Martin, and Sampson having a p value < 0.05. Martin fared superior to other formulae in intraclass correlation in patients with LDL > 70. In patients with TG below 200 mg/dL, Martin, and Sampson had a significant correlation with comparable average ICC. However, in patients with TG > 300 mg/dL, Cordova appears to fare better than all other formulae. Our study demonstrated a distinctly superior performance of Martin's formula over Friedewald's formula in the Indian patient population.

Correlation Between Severity of Schizophrenia with Certain Trace Elements and TNF-α Gene Expression and Its Circulatory Level in the Population of Western India.

This cross-sectional study aimed to assess serum trace element (TE) concentrations, TNF-α gene expression, protein levels in schizophrenia (SZ) patients, and their correlation with disease severity measured by Positive and Negative Syndrome Scale (PANSS) scores. Forty SZ cases and 40 healthy controls aged 18-60 were recruited. Forty (n = 40) cases who meet ICD-10 criteria for SZ and 40 (n = 40) healthy individuals (controls) between 18 and 60 years of age were recruited in the study. Sandwich enzyme-linked immunosorbent assay (ELISA) and RT-qPCR (quantitative real-time PCR) were used to estimate pro-inflammatory cytokine TNF-α protein and gene expression. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) and graphite furnace atomic absorption spectroscopy (GFAAS) were used to assess serum levels of trace elements (TEs): Fe, Zn, Cu, Mg, and Se. Compared to healthy controls, cases had significantly higher levels of TNF-α protein, as well as Fe, Cu, and Se (p < 0.05). Cu correlated positively with TNF-α protein level (rho = 0.234; p = 0.048) and gene expression (rho = 0.333; p = 0.041) and with PANSS negative (rho = 0.531), general (rho = 0.643), and total (rho = 0.541) scores. Additionally, Zn negatively correlated with serum Mg (rho = - 0.426, p < 0.01) and positively with serum Se (rho = 0.343, p < 0.05). In conclusion, elevated Cu levels could potentially contribute to the development of SZ. Elevated Cu levels in cases and their correlation with the TNF-α gene and protein and PANSS score indicate Cu's potential role in exacerbating SZ severity through inflammatory cytokines. This suggests the involvement of metals and cytokines in the pathophysiology of SZ.

Seasonal variation and Vitamin-D status in ostensibly healthy Indian population: An experience from a tertiary care institute.

Background: 25-hydroxy vitamin-D (25(OH)D) deficiency is prevalent worldwide including India. Earlier some cross-sectional studies have discussed 25(OH)D deficiency and its prevalence. The correlation of 25(OH)D with seasonal variation has been reported rarely in India. To determine the 25(OH)D levels and seasonal changes of 25(OH)D status at a tertiary care hospital in North-western India. Materials and methods: 25(OH)D assessments performed in laboratories between 2018 and 2020 was acquired using hospital records. A total of 11,428 assays of serum 25(OH)D were analyzed in the study. Subjects were divided into three groups based on the International Endocrine Society's recommendation for serum 25(OH)D level. The 25(OH)D deficiency <20 ng/ml, insufficiency 20-29 ng/mL and sufficiency ≥30 ng/mL was defined. The months have been separated into the following seasons to analyze seasonal trends: Summer/monsoon (April-September), and winter/spring (October-March). Results: The median 25(OH)D was 17.2 ng/mL. We observed the prevalence of 60 %, 24.1 % & 15.9 % of 25(OH)D deficiency, 25(OH)D insufficiency, and sufficiency respectively in the total number of individuals tested. 56 % male and 63 % females were 25(OH)D deficient. Notably, the lowest median 25(OH)D value was found in the 21-30 age group (14.8 ng/mL). A significant difference in 25(OH)D levels between the summer (18.7 ng/mL) and winter (15.8 ng/mL) seasons has been noticed. Discussion: Current study revealing that 25(OH)D deficiency is common in all age groups and genders, according to our findings. Surprisingly, the lowest levels were reported in young adults. Seasonal variation has an impact on 25(OH)D status, however in all seasons 25(OH)D levels are lower than reference intervals. These findings suggest that the criteria for determining the state of 25(OH)D insufficiency and deficiency in the Indian population should be reconsidered.

TET3 downregulation and low 5-hydroxymethylcytosine are epigenetic signatures of head and neck carcinoma.

BACKGROUND: Ten-eleven translocases (TETs) are enzymes responsible for demethylation processes, playing a crucial role in maintaining the body's methylation balance. Dysregulation of TET expression can lead to abnormal methylation levels. Isocitrate dehydrogenases (IDH) are upstream genes involved in Kreb cycle responsible for production of α-ketoglutarate (α-KG). α-KG and vitamin C are cofactors of TET3 enzyme. There is limited data on the relationship between TET3 and its cofactor Vitamin C in head and neck carcinoma (H&NC). METHODS AND RESULTS: In this study, we have investigated the expression of the TET3 gene along with IDH1/2 genes involved in the Krebs cycle in the peripheral blood of 32 H&NC patients compared to 32 healthy controls. We estimated serum levels of TET3 protein and vitamin C and 5-hydroxymethylcytosine (5-hmC) percentage in DNA isolated from EDTA blood samples. Our findings revealed that TET3 and IDH1/2 were downregulated in H&NC patients compared to healthy controls. Serum levels of TET3 and Vitamin C were low in H&NC patients compared to healthy controls. Diminished levels of percentage 5-hmC were detected in EDTA blood samples of H&NC patients compared to controls. Spearman correlation analysis revealed a significant positive correlation between TET3 levels, vitamin C levels and 5-hmC percentage. CONCLUSION: The low levels of Vitamin C are believed to contribute to decreased activity of the TET3 gene and less conversion of 5-methylcytosine (5-mC) to 5-hmC. Dietary supplementation of Vitamin C may increase TET3 activity.

GALNT6, GALNT14, and Gal-3 in association with GDF-15 promotes drug resistance and stemness of breast cancer via ß-catenin axis.

N-acetylgalactosaminyltransferases (GALNTs) are a polypeptide responsible for aberrant glycosylation in breast cancer (BC), but the mechanism is unclear. In this study, expression levels of GALNT6, GALNT14, and Gal-3 were assessed in BC, and their association with GDF-15, ß-catenin, stemness (SOX2 and OCT4), and drug resistance marker (ABCC5) was evaluated. Gene expression of GALNT6, GALNT14, Gal-3, GDF-15, OCT4, SOX2, ABCC5, and ß-catenin in tumor and adjacent non-tumor tissues (n = 30) was determined. The same was compared with GEO-microarray datasets. A significant increase in the expression of candidate genes was observed in BC tumor compared to adjacent non-tumor tissue; and in pre-therapeutic patients compared to post-therapeutic. GALNT6, GALNT14, Gal-3, and GDF-15 showed positive association with ß-catenin, SOX2, OCT4, and ABCC5 and were significantly associated with poor Overall Survival. Our findings were also validated via in silico analysis. Our study suggests that GALNT6, GALNT14, and Gal-3 in association with GDF-15 promote stemness and intrinsic drug resistance in BC, possibly by ß-catenin signaling pathway.

Gallbladder perforation: Diagnostic accuracy of new CT difficulty score in predicting complicated laparoscopic cholecystectomy.

PURPOSE: To formulate and evaluate the diagnostic performance and utility of a new CT difficulty score in predicting difficult laparoscopic surgery in cases of gallbladder (GB) perforation. METHODS: This prospective single centre study included a total of 48 diagnosed cases of GB perforation on CT between December 2021 and June 2023, out of which 24 patients were operated. A new 6-point CT difficulty scoring system was devised to predict difficult laparoscopic approach, based on patterns of inflammation around the perforated GB that were found to be surgically relevant. The pre-operative imaging findings on CT were studied in detail and correlation coefficients of various imaging findings were calculated to predict difficult surgery. RESULTS: On CECT, the type of perforation, according to the revised Niemeier's classification could be exactly delineated in all 48 patients. A CT difficulty score of ≥ 3 was found to a good predictor difficult laparoscopic approach, with statistical significance (p = 0.001), sensitivity of 94.44%, specificity of 83.33%, PPV of 94.44% and NPV of 83.33%. Inflammatory changes around duodenum showed maximum correlation coefficient of 0.744 (p = 0.0001), around colon showed a correlation coefficient of 0.657 (p = 0.0005), and in the omentum had a correlation coefficient of 0.5 (p = 0.013)). Inter-observer agreement was also calculated for various findings and it was found to have moderate to strong agreement (κ value 0.5-1.0). CONCLUSION: The CT difficulty scoring system can be an effective tool in predicting difficult laparoscopic surgery in cases of GB perforation in an emergency setting which can help in decision making and improved patient outcome.

GALNT14 in association with GDF-15 promotes stemness and drug resistance through ß-catenin signalling pathway in breast cancer.

BACKGROUND: Altered glycosylation plays a role in carcinogenesis. GALNT14 promotes cancer stem-like properties and drug resistance. GDF-15 is known to induces drug resistance and stemness markers for maintenance of breast cancer (BC) stem-like cell state. Currently there is lack of data on association of GDF-15 and GALNTs. In this study, the expression and interaction of GALNT14 and GDF-15 with stemness (OCT4 and SOX2) and drug resistance (ABCC5) markers were evaluated in BC. METHODS: We investigated tumour tissue from 30 BC patients and adjacent non-tumour tissues. Expression of serum GALNT14 from BC patients and matched healthy controls was evaluated. Expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and ß-catenin in BC tissue was determined by RT-PCR. Knockdown of GALNT14 and GDF-15 in the MCF-7 cell line was done through siRNA, gene expression and protein expression of ß-catenin by western blot were determined. RESULTS: A significant increase in the expression of GALNT14, GDF-15, OCT4, SOX2, ABCC5, and ß-catenin was observed in BC tumour tissues compared to adjacent non-tumour tissues. The serum level of GALNT14 was significantly high in BC patients (80.7 ± 65.3 pg/ml) compared to healthy controls (12.2 ± 9.12 pg/ml) (p < 0.000). To further analyse the signalling pathway involved in BC stemness and drug resistance, GALNT14 and GDF-15 were knocked down in the MCF-7 cell line, and it was observed that after knockdown, the expression level of OCT4, SOX2, ABCC5, and ß-catenin was decreased, and co-knockdown with GALNT14 and GDF-15 further decreased the expression of genes. CONCLUSION: It can be concluded that GALNT14, in association with GDF-15, promotes stemness and intrinsic drug resistance in BC, possibly through the ß-catenin signalling pathway.

Expression of stem cell markers as predictors of therapeutic response in metastatic prostate cancer patients.

BACKGROUND: Cancer stem cells (CSCs) have been implicated in prostate cancer (PCA) progression and therapeutic resistance. This study aimed to compare the expression levels of CSC CD (CD 44, CD 133, and CD 24) markers in treatment-naive patients with metastatic PCA before and after treatment. METHODS: The study included 60 treatment-naïve patients with metastatic PCA who received androgen deprivation therapy (ADT) alone (n = 30) and ADT plus chemotherapy (n = 30). The level of CD44, CD133, and CD24 were obtained by flow cytometric analysis before and after treatment. Baseline characteristics were also assessed, including age, pretreatment testosterone levels, and pretreatment prostate-specific antigen (PSA) levels. RESULTS: The baseline characteristics analysis showed no significant difference in pre-treatment testosterone levels between the ADT+ chemotherapy and ADT-alone groups. In the flow cytometric analysis, no significant difference was observed in pre-treatment CD44+ and CD133+ levels between the 2 treatment groups, although a trend towards higher pretreatment CD24- levels was observed in the ADT+ chemotherapy group. After treatment, significant reductions in testosterone and PSA levels were observed in both treatment arms. The ADT+ chemotherapy group showed a greater reduction in CD44+ and CD133+ levels compared to the ADT-alone group. Bioinformatic analysis using the UALCAN TCGA database also showed a similar trend of CD 44, CD 24, and CD 133 gene expression patterns. CONCLUSION: Combination therapy involving chemotherapy and ADT appears to have a greater impact on suppressing CSCs compared to ADT alone. These findings highlight the potential of targeting CSCs as a prognostic and predictive marker therapeutic strategy in metastatic PCA.

Safety and Efficacy of Resveratrol in Healing of Maxillofacial Fractures: A Randomized Controlled Study.

Objectives: To assess the efficacy of resveratrol in improving functional outcomes following open reduction and internal fixation of maxillofacial fractures. Study Design: A single-center, randomized, parallel group, prospective, double-blind clinical trial was conducted on 40 patients between the age 20 and 60 years, requiring open reduction and internal fixation of maxillofacial fractures. The selected patients were randomly divided into two groups, Group 1 (placebo) and Group 2 (resveratrol) where tablets resveratrol 500 mg were given twice daily for 1 month following open reduction and internal fixation of fractured segments. Bite force was calculated pre-operatively and on the 1st, 4th, 8th and 12th week postoperatively. Serum markers osteocalcin and alkaline phosphate were calculated pre-operatively and at 4th and 12th week postoperatively. Results: Bite force (690.55 ± 262.00) in the resveratrol group was higher than the placebo group (553.27 ± 300.08) at 12th week postoperatively. However, the difference was non-significant statistically (p = 0.132). Resveratrol group (116.80 ± 55.25) showed better maintenance of serum ALP level as compared to placebo group (107.90 ± 42.99) at 12th week postoperatively, but again it lacked statistical significance (p = 0.573). Resveratrol group after initial reduction at 4th week showed serum osteocalcin levels nearly equal to the preoperative values at 12th week, while the placebo group showed a decline both at 4th and 12th week postoperatively. However, these results were not statistically significant (p = 0.065). Conclusion: There was no statistically significant difference in bite force, serum ALP level and serum osteocalcin levels between placebo group and resveratrol group. Though not statistically significant but early increased level of serum osteogenic markers, better restoration of bite force in group 2 (tab. Resveratrol) indicates toward its possible optimistic role in maxillofacial fracture healing. More studies with larger sample sizes are needed in order to confirm the efficacy of this drug in maxillofacial fracture.

Effectiveness of ayurvedic formulation, NAOQ19 along with standard care in the treatment of mild-moderate COVID-19 patients: A double blind, randomized, placebo-controlled, multicentric trial.

BACKGROUND: Medicines in indigenous systems such as Ayurveda have strong antimicrobial activity but double-blind randomized control trials are infrequent in this system of medicine. The efficacy of a new ayurvedic formulation was evaluated during the pandemic. METHODS: 150 mild-moderate COVID-19 patients were enrolled and randomized in 1:1 to NAOQ19 and placebo group. RT-PCR was done on Day 3, 5 and 7. CBC, CRP, LFT, and KFT were assessed at baseline and exit. Duration of hospital stay was noted and clinical assessment was also performed. RESULT: The results demonstrated more people turning RT-PCR negative in the NAOQ19 group compared to the placebo group on day 3 (p-value = 0.033). The mean time duration to turn RT-PCR negative was significantly lower in the NAOQ19 group (4.6 days) compared to placebo group (5.2 days) (p-value = 0.018). There was significant reduction in hospital stay among patients in the NAOQ19 arm who were discharged earlier (5.6 days) compared to placebo group (6.4 days) (p-value = 0.046). Patients in NAOQ19 arm did not show any adverse life-threatening events. CONCLUSION: The ayurvedic preparation given along with standard of care therapy reduced the duration of hospital stay and there was earlier conversion to RT-PCR negative.The integrated approach can help to reduce patient workload in the hospitals as well as limit the transmission of the virus in the community. STUDY REGISTRATION: CTRI/2021/05/033790.

Clinical Utility of Bronchoalveolar Lavage Neutrophilia and Biomarkers for Evaluating Severity of Chronic Fibrosing Interstitial Lung Diseases.

Introduction It is hypothesized that bronchoalveolar lavage (BAL) neutrophilia, Krebs von den Lungen-6 (KL-6), and C-reactive protein (CRP) predict the severity of chronic fibrosing interstitial lung diseases (CF-ILDs). Methods This cross-sectional study enrolled 30 CF-ILD patients. Using Pearson's correlation analysis, BAL neutrophils, KL-6, and CRP were correlated with forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), six-minute walk distance (6MWD), partial pressure of oxygen (PaO2), computed tomography fibrosis score (CTFS), and pulmonary artery systolic pressure (PASP). Using the receiver operator characteristic (ROC) curve, BAL KL-6 and CRP were evaluated against FVC% and DLCO% in isolation and combination with BAL neutrophilia for predicting the severity of CF-ILDs. Results BAL neutrophilia significantly correlated only with FVC% (r = -0.38, P = 0.04) and DLCO% (r = -0.43, P = 0.03). BAL KL-6 showed a good correlation with FVC% (r = -0.44, P < 0.05) and DLCO% (r = -0.50, P = 0.02), while BAL CRP poorly correlated with all parameters (r = 0.0-0.2). Subset analysis of BAL CRP in patients with CTFS ≤ 15 showed a better association with FVC% (r = -0.28, P = 0.05) and DLCO% (r = -0.36, P = 0.04). BAL KL-6 cut-off ≥ 72.32 U/ml and BAL CRP ≥ 14.55 mg/L predicted severe disease with area under the curve (AUC) values of 0.77 and 0.71, respectively. The combination of BAL neutrophilia, KL-6, and CRP predicted severity with an AUC value of 0.89. Conclusion The combination of BAL neutrophilia, KL-6, and CRP facilitates the severity stratification of CF-ILDs complementing existing severity parameters.

Relationship of Serum Periostin With Asthma Control in Children: Single Center Experience.

OBJECTIVE: To determine the association between serum periostin levels and asthma control in children. METHODS: Children aged 6-17 years with physician-diagnosed asthma were enrolled in the study. Age-matched (±2 years) control children, who visited our outpatient department with non-respiratory complaints, were also enrolled. RESULTS: A total of 90 children (60 with asthma and 30 control subjects) with a mean (SD) age of 12.1 (2.77) years were enrolled. Children with asthma had significantly higher median (IQR) periostin levels than the controls [23.5 (22,26) vs 22 (19.4, 22.96); P= 0.04]. On multivariable logistic regression analysis, serum periostin levels were associated with poor asthma control in children [OR (95% CI), 1.12 (1.01-1.24); P= 0.02]. Age, body mass index, IgE levels, eosinophil count, forced expiratory volume in first minute (FEV1) and presence of allergic rhinitis did not have any association with asthma control. CONCLUSION: Asthmatic children have a high serum periostin level, and its higher levels are associated with poor asthma control.

Genetic and Epigenetic Basis of Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) is a rare but severe adverse drug reaction seen in pharmacotherapy and a major cause of postmarketing drug withdrawals. Advances in genome-wide studies indicate that genetic and epigenetic diversity can lead to inter-individual differences in drug response and toxicity. It is necessary to identify how the genetic variations, in the presence of environmental factors, can contribute to development and progression of DILI. Studies on microRNA, histone modification, DNA methylation, and single nucleotide polymorphisms related to DILI were retrieved from databases and were analyzed for the current research and updated to develop this narrative review. We have compiled some of the major genetic, epigenetic, and pharmacogenetic factors leading to DILI. Many validated genetic risk factors of DILI, such as variants of drug-metabolizing enzymes, HLA alleles, and some transporters were identified. In conclusion, these studies provide useful information in risk alleles identification and on implementation of personalized medicine.

Smouldering Myeloma: Chasing a Hyperviscous Sample.

Serum hyperviscosity is a rare laboratory finding. Amongst several causes of serum hyperviscosity, malignant disorders are quite common. Monoclonal gammopathy is a family of disorders in which monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma are the asymptomatic variants whereas multiple myeloma is the malignant variant showing different signs and symptoms related to bone lesions, renal failure and anemia. Initially during sample preparation, pipetting of a serum sample was found to be cumbersome. This sample during routine analysis in the automated analyser flagged repeated alarms for clot detection indicating a possibility of a hyper viscous sample. Serum was subjected to fibrinogen and D- dimer test. The D-Dimer levels were found to be normal and fibrinogen levels were mildly elevated. Routine biochemistry investigations were normal except grossly reversed A/G ratio. Due to gross reversal of A/G ratio, the possibility of Multiple myeloma was entertained. Physician's were alerted on telephone. Serum was sent for electrophoresis which showeda M spike. Bone marrow aspirate showed 13% plasma cells. Considering the above lab results the diagnosis of monoclonal gammopathy of smoldering type was considered. The sample was traced to a 77 years old male, who presented to Medicine OPD with the chief complaints of generalised weakness for two months without any history of fever. On physical examination pallor was evident but there was no icterus, cyanosis, clubbing, lymphadenopathy or edema. On haematological evaluation patient was found to be anemic. Careful tracking of hyperviscous patient's serum followed up by thorough investigation led us to the final conclusion that the case mentioned is a rare case of Smoldering type of multiple myeloma.

In silico analysis of differentially expressed-aberrantly methylated genes in breast cancer for prognostic and therapeutic targets.

Breast cancer (BC) is the leading cause of death among women across the globe. Abnormal gene expression plays a crucial role in tumour progression, carcinogenesis and metastasis of BC. The alteration of gene expression may be through aberrant gene methylation. In the present study, differentially expressed genes which may be regulated by DNA methylation and their pathways associated with BC have been identified. Expression microarray datasets GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724 and one DNA methylation profile dataset GSE20713 were downloaded from Gene Expression Omnibus database (GEO). Differentially expressed-aberrantly methylated genes were identified using online Venn diagram tool. Based on fold change expression of differentially expressed-aberrantly methylated genes were chosen through heat map. Protein-protein interaction (PPI) network of the hub genes was constructed by Search Tool for the Retrieval of Interacting Genes (STRING). Gene expression and DNA methylation level of the hub genes were validated through UALCAN. Overall survival analysis of the hub genes was analysed through Kaplan-Meier plotter database for BC. A total of 72 upregulated-hypomethylated genes and 92 downregulated-hypermethylated genes were obtained from GSE10780, GSE10797, GSE21422, GSE42568, GSE61304, GSE61724, and GSE20713 datasets by GEO2R and Venn diagram tool. PPI network of the upregulated-hypomethylated hub genes (MRGBP, MANF, ARF3, HIST1H3D, GSK3B, HJURP, GPSM2, MATN3, KDELR2, CEP55, GSPT1, COL11A1, and COL1A1) and downregulated-hypermethylated hub genes were constructed (APOD, DMD, RBPMS, NR3C2, HOXA9, AMKY2, KCTD9, and EDN1). All the differentially expressed hub genes expression was validated in UALCAN database. 4 in 13 upregulated-hypomethylated and 5 in 8 downregulated-hypermethylated hub genes to be significantly hypomethylated or hypermethylated in BC were confirmed using UALCAN database (p < 0.05). MANF, HIST1H3D, HJURP, GSK3B, GPSM2, MATN3, KDELR2, CEP55, COL1A1, APOD, RBPMS, NR3C2, HOXA9, ANKMY2, and EDN1 were significantly (p < 0.05) associated with poor overall survival (OS). The identified aberrantly methylated-differentially expressed genes and their related pathways and function in BC can serve as novel diagnostic and prognostic biomarkers and therapeutic targets.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 4 Given name: [Jeewan Ram] Last name [Vishnoi]. Also, kindly confirm the details in the metadata are correct.It is correct.