Polymorphisms in vitamin B12 and folate metabolising genes and their association with adverse pregnancy outcome: secondary analysis of a population based case control study.

Vitamin B12 and folate deficiency leads to accumulation of homocysteine that increases the risk of adverse pregnancy outcomes like preterm birth and low birth weight (LBW) of the neonate. We explored the association of genetic variants of key vitamin B12 and folate metabolising enzymes (MTHFR C677T and A1298C, MTR A2756G, TCN-2 C776G) with preterm birth and LBW in South Indian women. MTHFR A1298C heterozygotes (AC) were at higher risk for preterm delivery, whereas TCN-2 C776G heterozygotes (CG) were at higher risk for both preterm delivery and LBW. MTHFR C677T, A1298C and MTR A2756G haplotype CAG was protective for preterm delivery (p=.036, OR = 0.475; 95% CI: 0.233-0.97), whereas, haplotype CCG increasing the risk of preterm birth by 1.8 folds (p=.018, OR = 1.81; 95% CI: 1.09-2.98). These results underscore the significance of vitamin B12 and folate in the pathophysiology of preterm birth and LBW.Impact StatementWhat is already known on this subject? Polymorphisms of vitamin B12 and folate metabolising genes have been reported to influence preterm birth and LBW, but the reports are not consistent.What do the results of this study add? We observed a relationship of MTHFR A1298C and TCN-2 C776G with preterm birth, and significant association of TCN-2 C776G with LBW in infants.What are the implications of these findings for clinical practice and/or further research? Identification of women carrying these polymorphic risk alleles may benefit from early nutritional modifications.

Cross-sectional association between vitamin B12 status and probable postpartum depression in Indian women.

BACKGROUND: Vitamin B12 is an essential micronutrient for neurological function, as it leads to the regeneration of methionine from homocysteine, which is precursor of biologically active molecule S-Adenosyl Methionine (SAM). Pregnancy is a state of increased demand and delayed postpartum repletion of nutrients may predispose women to depression. METHODS: We included women who visited the hospital at 6-weeks postpartum for a regular checkup. Inclusion criteria were age (18-50 years), and willingness to donate venous sample for analysis. Exclusion criteria included previous history of mood disorders or antidepressant medication use, and any systemic illness like hypothyroidism, epilepsy, diabetes, and hypertension. Based on EPDS score of 10 as a cutoff, 217 women with probable postpartum depression (PPD) and equal number of age and BMI matched controls were included. Plasma total vitamin B12, holotranscobalamin (holotc), homocysteine (hcy), methyl malonic acid (MMA), 5-methyl tetrahydrofolate (THF), SAM and serotonin levels were estimated using commercially available ELISA kits. Combined B12 (cB12) score was calculated from study parameters. Multivariate analysis was performed to assess the risk of probable postpartum depression. RESULTS: Total vitamin B12 and combined B12 score were found to be significantly lower (p = 0.001) and MMA (p = 0.002) and 5-methyl THF (p < 0.001) levels were higher in women with probable depression than women without probable PPD. Women in the lowest vitamin B12 quartile had 4.53 times higher likelihood of probable postpartum depression (p < 0.001). Multivariate analysis demonstrated that decreasing vitamin B12 (OR = 0.394; 95% CI: 0.189-0.822) and cB12 (OR = 0.293; 95% CI: 0182-0.470) and increasing MMA (OR = 2.14; 95% CI: 1.63-2.83) and 5-methyl THF levels (OR = 3.29; 95% CI: 1.59-6.83) were significantly associated with the risk of probable PPD. CONCLUSION: Low vitamin B12 may contribute to depressive symptoms in vulnerable postpartum period.

Expression Pattern of Selected Toll-like Receptors (TLR's) in the PBMC's of Severe and Non-severe Dengue Cases.

Objective: The role of TLR's in the pathogenesis of dengue is not explored well. Differential expression of TLR2 and TLR4 was reported in dengue cases. In the present study in order to understand the expression pattern of various TLR's, including TLR2, TLR3, TLR4 and TLR9, mRNA levels were determined in various dengue study groups compared to control groups, at the time of admission and around defervescence using quantitative real-time PCR (RT-PCR).Methods: A total of 88 dengue cases with 32 severe and 56 non-severe cases were involved in the study. Gene expression pattern of the study groups was compared with 31 other febrile illness (OFI) cases and 63 healthy controls. Transcript levels of the target genes were estimated from the peripheral blood mononuclear cells (PBMC) samples collected from cases and controls using quantitative real-time PCR.Results: We have noted a significant alteration in the levels of all TLR's in dengue and OFI cases compared to healthy controls at the time of admission. Interestingly we have noted a significant alteration in the levels of TLR9 in severe and non-severe cases during defervescence. The same was not detected in the OFI group.Conclusion: The present study found a change in TLR's during dengue infection. This suggests us to explore the TLR's as therapeutic candidate for anti-dengue virus strategies. However, in order to ascertain the involvement of TLR's in the disease pathology and its role as biomarkers for prognosis, a complete dynamics of TLR's expression needs to be studied.

Altered Platelet Fatty Acids in Dengue Cases by Gas Chromatography-Mass Spectrometry Analysis.

BACKGROUND: The role of dengue virus in altering the functional properties of platelets remains poorly understood. Few studies have observed that changes in fatty acids are found to have an effect on platelet activation and aggregation. Also, platelet fatty acids have not been extensively studied in dengue so far. So, we aimed to study the fatty acids of platelet membranes in patients with dengue. METHODS: Gas chromatography-mass spectrometry (GC-MS) method was used to analyze fatty acids in the lipid extracts of platelets isolated from the study participants. RESULTS: GC-MS analysis of platelet lipids identified and quantified nearly 23 unique lipid molecules on platelet membrane. We observed significant alterations with some of the fatty acids in patients with dengue compared to controls. Within dengue cases, increase in unsaturated fatty acids in severe dengue was observed compared to non-severe dengue. From baseline to defervescence, no difference in fatty acids was observed in dengue platelets. This indicates that in dengue, platelet physiology remains altered even after the febrile phase. CONCLUSION: To the best of our knowledge, this is the first study characterizing the differential expression of platelet fatty acids in dengue infection. However, further studies are warranted to expound the underlying cause for thrombocytopenia and platelet dysfunction in dengue.

Oxidative stress response in the pathogenesis of dengue virus virulence, disease prognosis and therapeutics: an update.

Dengue virus (DENV) is a mosquito-borne arbovirus that causes febrile illness and can lead to a potentially lethal disease. The mechanism of disease pathogenesis is not completely understood, and there are currently no vaccines or therapeutic drugs available to protect against all four serotypes of DENV. Although many reasons have been suggested for the development of the disease, dengue studies have shown that, during DENV infection, there is an imbalance between oxidants and antioxidants that disrupts homeostasis. An increase in reactive oxygen species (ROS) levels triggers the sudden release of cytokines, which can lead to plasma leakage and other severe symptoms. In the present review, we give an overview of the oxidative stress response and its effect on the progression of dengue disease. We also discuss the role of oxidative-stress-associated molecules in disease prognostic and therapeutics.

Lipid peroxidation, DNA damage, and apoptosis in dengue fever.

Interplay between the apoptosis, DNA damage, and oxidative stress as a host response to dengue viral infections remains unclear. Peripheral blood mononuclear cells (PBMCs) were isolated from 60 dengue infected patients, 20 patients with febrile illness other than dengue (OFI) and 10 non-febrile illness (NFI) patients. DNA damage in the PBMCs was assessed using single cell gel electrophoresis and stages of apoptosis underwent by the PBMCs were studied by Annexin-PI staining using flow cytometry. Plasma levels of malondialdehyde levels were estimated using thiobarbituric acid assay. Dengue infected individuals had showed increased DNA damage than NFI and OFI controls at the time of admission. Annexin-PI staining revealed increased frequency of apoptotic cells in dengue infected PBMCs than controls during the admission time. Similar pattern was observed in samples collected around defervescence. Within the dengue cases, percentage of live cells was higher in non-severe dengue than severe dengue at both the time points. Follow-up samples in dengue showed less number of live cells and higher percentage of apoptotic cells with respect to their baseline and this was reversed in case of OFI. Plasma malondialdehyde levels were found to be relatively higher in dengue cases than controls at admission and around defervescence. Significant positive correlation between DNA damage, apoptosis, and plasma malondialdehyde levels might pave a way for understanding the complex interactions between virus and hosts response thereby aids in identifying plausible immunopathological links contributing to disease pathogenesis. © 2018 IUBMB Life, 70(11):1133-1143, 2018.

Luteinizing hormone-follicle stimulating hormone ratio as biological predictor of post-partum depression.

BACKGROUND: Post-partum depression (PPD) is the common adverse outcome of child bearing which affects the wellbeing of both mother and newborn and has long-term effects. Hence, reliable potential biological tests for early detection of PPD are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were associated with depressive disorders and the present study estimated the levels of serum FSH, LH in postpartum depression and explored them as predictive biomarkers in the development of PPD. METHODS: In this nested case control study done at a tertiary care hospital in South India, 450 postpartum women were screened at 6th week post-delivery for PPD. Socio-demographic and clinical data were recorded and depressive symptoms were assessed using Edinburgh Postnatal Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive symptoms were categorized as cases and 100 controls were selected from the remaining subjects matching for age and BMI with cases. Serum levels of FSH and LH were measured using direct competitive immunoassay by chemiluminescene technology. RESULTS: Serum LH/FSH ratio was found to be significantly (p=0.02) low in PPD women when compared to normal postpartum subjects. We also found a significant negative correlation between LH/FSH ratio and EPDS scores. Based on the receiver operating characteristic curve, the optimal cut-off value for serum of LH/FSH levels in predicting postpartum depression was estimated to be 0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). CONCLUSION: Our study demonstrated that low LH/FSH ratio after delivery was associated with increased risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can be used as a robust biochemical predictor of post-partum depression.

A Study on Gene Expression Profile of Endogenous Antioxidant Enzymes: CAT, MnSOD and GPx in Dengue Patients.

Dengue is an arthropod-borne threat among tropical countries. Currently no effective means to treat the virus or to predict which patient will develop the severe form of the disease. Recently the relationship between oxidative/antioxidative response and dengue pathogenesis was suggested. Based on this the present study has analysed the expression of endogenous antioxidant genes: Catalase (CAT), Superoxide dismutase (MnSOD) and Glutathione peroxidase in patients with dengue compared to other febrile illness (OFI) and healthy controls. The study enrolled 88 dengue confirmed patients comprising 56 were patients with non-severe dengue, and 32 were severe dengue cases, 31 were patients with OFI, and 63 healthy controls were also involved. Peripheral blood mononuclear cells isolated from patients and controls during the day of admission and from the available cases on the day of defervescence were used to estimate the transcript levels by quantitative PCR. The expression levels of all the three genes were found to be down-regulated throughout the course of dengue infection (p < 0.05) and OFI cases compared to healthy controls. Within dengue group, no significant difference was observed in any of the parameters between severe and non-severe cases. Interestingly, a significant down-regulation of MnSOD expression was recorded in secondary dengue infection compared to primary during admission (p < 0.05). It was found that all the down-regulated study genes have positively correlated in all dengue cases during the day of admission (p < 0.01). But during defervescence, the same was found only between CAT and MnSOD. Down-regulated endogenous antioxidant enzymes during dengue infection could be the possible rationale of oxidative stress reported in dengue disease earlier. The present study markers could not distinguish dengue from OFI cases and severe from non-severe dengue cases. Mechanism of down-regulation has to be explored further which will pave the way for the therapeutic target in dengue disease.

Cerebrospinal fluid ferritin and albumin index: potential candidates for scoring system to differentiate between bacterial and viral meningitis in children.

OBJECTIVES: To evaluate the diagnostic role of cerebrospinal fluid (CSF) ferritin and albumin index (AI = CSF albumin/serum albumin × 1000) in differentiating acute bacterial meningitis (ABM) from acute viral meningitis (AVM) in children. METHODS: The study included 42 cases each of ABM and AVM in pediatric age group. Receiver operating characteristic (ROC) analysis was carried out for CSF ferritin and AI. Binary logistic regression was also done. RESULTS: CSF ferritin and AI were found significantly higher in ABM compared to AVM. Model obtained using AI and CSF ferritin along with conventional criteria is better than existing models.

Diagnostic significance of IL-6 and IL-8 in tubal ectopic pregnancy.

As there are no specific non-invasive markers for the diagnosis of tubal ectopic pregnancy, our objective in the present study was to explore the role of inflammatory cytokines IL-6 and IL-8 in the diagnosis of ruptured tubal ectopic pregnancy. Twenty-eight women with tubal ectopic pregnancy, 31 patients with intrauterine abortion and 29 gestational age matched women having normal intrauterine pregnancy were included in the study. Five millilitre of blood was collected at the time of admission, serum was separated and stored at -70 °C for subsequent analysis of ß hCG, IL-6 and IL-8 levels. The level of IL-6 was a significant increase in the women with tubal ectopic pregnancy compared to intrauterine abortion and normal pregnancy. IL-8 levels decrease significantly in the tubal ectopic pregnancy and in intrauterine abortion patients when compared with the normal pregnancy group. At the cutoff of 26.48 pg/ml IL-6 level predicted the tubal ectopic pregnancy with moderate accuracy. Therefore, it can be concluded that measurement of IL-6 may have relevance in the diagnosis of ectopic pregnancy as a novel inflammatory serum biomarkers.

Cardiovascular risk markers and thyroid status in young Indian women with polycystic ovarian syndrome: a case-control study.

AIM: To study thyroid function profile, atherogenic markers and their association in young women with PCOS. METHODS: Thirty women aged 15-30 years with PCOS (married and unmarried) and an equal number of age-matched controls were included in this study. The following parameters were assessed: thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), tetraiodothyronine (FT4), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) homocysteine (HCY), lipoprotein(a) (Lp[a]) levels. RESULTS: Thyroid function tests were within normal ranges in all the cases and controls. The following parameters were significantly elevated in women with PCOS compared to controls: serum TC, TG, LDL,VLDL, HCY and Lp(a). Married women with PCOS had significantly higher levels of TC, TG, VLDL-C, LDL-C, HCY and Lp(a). Among unmarried PCOS cases, HCY levels were found to be significantly higher compared to unmarried controls. In group 1, Lp(a) levels were found to be high. In group 2, TC, TG, LDL-C, VLDL-C, Lp(a) and HCY levels were found to be high. In group 3, TC, VLDL-C and Lp(a) were found to be high. CONCLUSION: Alteration in lipid metabolism and elevated HCY and Lp(a) levels were present in women with PCOS, which were independent of their thyroid status. Unmarried PCOS women are predisposed to develop cardiovascular diseases rather than married PCOS women. Group 2 PCOS women are predisposed to get cardiovascular diseases rather than group 1 and group 3. PCOS women need not have hypothyroidism.

Utility of the Growth Differentiation Factor-15 in the Differential Diagnosis of Follicular-Patterned Lesions of the Thyroid on Cytopathologic and Histopathologic Samples.

Background Follicular-patterned lesions are a major gray zone in thyroid cytopathology. The recently introduced 2022 World Health Organization (WHO) classification emphasizes the importance of genetic alterations in thyroid neoplasms with the introduction of certain newer terminologies that are expected to cause remarkable changes in cytopathologic and histopathologic reporting. Although molecular assays such as the Afirma gene expression classifier and the ThyroSeq are already in use, there has been an ongoing search for further reliable molecular markers. The growth differentiation factor-15 (GDF-15) is one among them. This study aimed to determine the diagnostic utility of GDF-15 mRNA expression in frozen tissue and fine-needle aspiration (FNA) samples from follicular-patterned thyroid lesions and neoplasms. Methodology The real-time quantitative polymerase chain reaction was performed on 75 frozen tissue and FNA samples each from 19 cases of follicular thyroid hyperplasia (FTH), 10 nodular goiters (NGs), 17 follicular thyroid adenomas (FTAs), eight follicular thyroid carcinomas (FTCs), 12 follicular variant of papillary thyroid carcinomas (FVPTCs), and nine classic papillary thyroid carcinomas (CPTCs) that were diagnosed according to the 2017 WHO classification of thyroid neoplasms. The GDF-15 mRNA expression in all these cases was assessed and compared with the control thyroid tissue samples. One-way analysis of variance and the Kruskal-Wallis test were performed using GraphPad Prism 8 software to determine the significance of differences in the GDF-15 mRNA levels among various thyroid lesions. Results A higher GDF-15 mRNA expression was noted in the malignant thyroid neoplasms including FTC, FVPTC, and CPTC in comparison to FTA, with a fold change between the malignant and benign groups being more than 244.18 times. A difference in the fold change was noted between FTH and FTA with an increase in GDF-15 mRNA level in the latter, which was statistically not significant. Conclusions The fact that GDF-15 mRNA was studied both on fine-needle aspiration cytologic and the frozen tissue material and that the majority of the lesions studied were follicular-patterned establishes the GDF-15 as a potential marker not only for diagnosing malignant thyroid neoplasms of the follicular epithelium but also in distinguishing benign and malignant follicular-patterned neoplasms of the thyroid.

Association of VDBP (rs4588 and rs7041) gene polymorphisms with susceptibility to postpartum depression in South Indian population: A cross-sectional study.

Low vitamin D levels have been implicated in postpartum depressive disorders (PPD). Our study aimed to demonstrate the association of Vitamin D Binding Protein (VDBP) genetic variants rs7041 and rs4588 with susceptibility to PPD and to investigate their possible relationship with serum vitamin D and VDBP levels in Indian women with PPD. A cross-sectional study involved 330 cases and 330 controls. Depressive symptoms were assessed using Edinburg Postnatal Depression Scale. Genotyping of SNPs was done by Taqman 5'allelic discrimination assay. Estimation of serum 25 hydroxyvitamin D [25(OH) D] and VDBP levels were done by ELISA. Serum total, free and bioavailable 25(OH) D levels were significantly lower in cases compared to controls, with similar levels of VDBP between the two groups. The study results showed that the VDBP rs4588 variant genotype AA was significantly associated with lower circulating levels of total 25(OH) D in cases. Also, the VDBP rs7041 variant TT genotype demonstrated significantly lower levels of total, free and bioavailable 25(OH) D levels in controls. However, VDBP rs7041 and rs4588 variants were not associated with PPD susceptibility. Also, VDBP haplotypes showed no association with PPD susceptibility. Our results demonstrated that VDBP polymorphisms rs4588 and rs7041 and their haplotypes are not associated with PPD susceptibility in the South Indian population. However, vitamin D levels were found to be influenced by the risk genotypes of VDBP SNPs rs4588 and rs7041.

Reduced Maternal Serum Total, Free and Bioavailable Vitamin D Levels and its Association with the Risk for Postpartum Depressive Symptoms.

BACKGROUND: Low vitamin D levels have been implicated in postpartum depressive disorders. However, studies on bioavailable vitamin D levels in postpartum depression are limited. Our study aimed to assess the serum concentrations of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) levels in women with postpartum depressive symptoms (PPD) and the association between 25(OH)D levels and PPD at 6 week post-delivery. METHODS: In this cross-sectional study, a total of 330 cases and 330 age and BMI matched controls were recruited from the tertiary care hospital in South India. Women with depressive symptoms were assessed using the validated Edinburg Postnatal Depression Scale (EPDS) and cut-off score ≥10 was used. Serum 25(OH)D and VDBP levels were measured using commercially available ELISA kits. RESULTS: Serum total, free and bioavailable 25(OH)D levels were significantly lower in postpartum depressive women compared to non-depressive women (p <0.001, p = 0.01). A significant negative correlation was observed between 25(OH)D, free 25(OH)D and bioavailable 25(OH)D with EPDS score in total study subjects (p <0.001, r = -0.19; p <0.001, r = -0.14 and p <0.001, r = -0.14). Multivariate linear regression analysis further confirmed a significant association between serum total, free and bioavailable 25(OH)D levels and EPDS score (p <0.001∗). CONCLUSIONS: Our study demonstrated that lower serum total, free and bioavailable 25(OH)D levels were associated with postpartum depressive symptoms. Hypovitaminosis D after delivery may be a risk factor for postpartum depression.

Utility of Urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) in Decompensated Cirrhosis.

BACKGROUND AND AIMS: Renal failure occurring in the setting of cirrhosis increases mortality by more than threefold. Serum creatinine, the conventional marker for renal dysfunction has inherent limitations in identifying and categorizing renal dysfunction in patients with chronic liver disease (CLD). Neutrophil gelatinase associated lipocalin (NGAL) is a novel biomarker which gets upregulated as early as 2-6 hours following the insult to renal tubules. In this study, we aim to check the utility of uNGAL to identify the different phenotypes of renal dysfunction in patients with CLD. We also intend to assess the utility of NGAL to predict 90-day transplant-free survival in patients with CLD. METHODS: A total number of 120 adult patients, with cirrhosis of liver were recruited. Those with pre-existing renal parenchymal disease, receiving nephrotoxic medications, spontaneous bacterial peritonitis, septic shock, proteinuria, hematuria, urinary tract infection and anuria were excluded. Urine samples for NGAL was measured at admission and at 48 hours thereafter. Patients were followed up for 90 days post admission. RESULTS: Among the study population, 16 patients (13.3%) had normal kidney function, 43 (35.8%) had prerenal azotemia and 54 (45%) had Hepatorenal Syndrome (HRS - AKI) and 7 (5.8%) had acute tubular necrosis (ATN). Urinary NGAL (uNGAL) levels were considerably lower in patients with normal kidney function and prerenal azotemia. An uNGAL level of 124 ng/ml on admission could distinguish severe forms of renal injury, with a sensitivity of 86% and specificity of 84%. The non survivors had higher uNGAL levels at admission [209.6 ng/ml (118.7-376.8) vs. 123 (33.6-344.3); P = 0.013].The receiver operated curves for uNGAL and serum creatinine at admission did not show any significant difference for predicting 90 day mortality (AUC for uNGAL: 0.632 vs 0.580 for serum creatinine; difference in AUC 0.053, P value 0.17). CONCLUSION: uNGAL levels are elevated in patients with HRS-AKI and ATN. A higher uNGAL level at admission was suggestive of severe renal dysfunction. An elevated uNGAL on admission is associated with inferior survival. However, uNGAL is not superior to serum creatinine in predicting 90-day mortality.

Association of N- terminal Pro Brain Natriuretic Peptide with Echocardiographic Measures of Diastolic Dysfunction in Cirrhosis.

BACKGROUND: Liver cirrhosis is associated with cardiac dysfunction in 40%-60% of the patients. Serum NT-ProBNP is a potential additional marker of cirrhotic cardiomyopathy. MATERIALS AND METHODS: It was a cross-sectional analytical study done in a tertiary care center in South India on 100 patients of cirrhosis of liver. Diastolic function was assessed from mitral inflow parameters as well as tissue Doppler imaging of the left ventricle in 95 patients. Serum NT-ProBNP levels was measured once at the time of inclusion into the study. Cirrhotic cardiomyopathy was diagnosed in those with abnormal echocardiographic parameters and its association with NT-Pro BNP levels was analyzed. Data were analyzed using SPSS version 22. RESULTS: Diastolic dysfunction was found in 40 (42.1%) participants. Twenty-two (23.2%) had Grade I, 16 (16.8%) had Grade II, and 2 (2.1%) had Grade III diastolic dysfunction. The mean NT-Pro-BNP was elevated (107.38 [±66.76] ng/ml) in patients with diastolic dysfunction. NT-ProBNP was higher in Child-Pugh B and C disease when compared to milder disease. NT-ProBNP was not a good screening tool for cardiomyopathy in cirrhotic patients. Area under the curve was 0.517 with 95% confidence interval and the P = 0.77. However, positive correlation was present between the NT-ProBNP value and two echocardiographic parameters of diastolic dysfunction (E/A, E/E'). CONCLUSION: Increased serum NT-ProBNP levels in cirrhosis of liver have a positive correlation with echocardiographic measures of diastolic dysfunction of the heart but it is not a good tool for screening for cirrhotic cardiomyopathy.

Clinical utility of pleural fluid YKL-40 as a marker of malignant pleural effusion.

Pleural effusion is a common presenting feature of malignancy. Malignant pleural effusion is primarily diagnosed by pleural fluid cytology, pleural biopsy, and tumor markers. The glycoprotein YKL-40 is a new tumor marker that has shown to have a good diagnostic accuracy to detect malignant pleural effusion. However, there are only a few studies that have evaluated pleural fluid YKL-40 for detecting malignant pleural effusions. Hence, we conducted this study to evaluate the utility of pleural fluid YKL-40 to detect malignant pleural effusion. This is a cross-sectional study conducted between February 2016 and December 2017 in a tertiary care referral hospital. One hundred and forty-seven consecutive patients with pleural effusion were included in the study. These patients were divided into 3 groups, viz malignant, tuberculous, and parapneumonic pleural effusion, based on clinical features, radiological examination, and pleural fluid analysis. Pleural fluid YKL-40 levels were measured using enzyme-linked immunosorbent assay. Out of the 147 consecutive patients included in the study, 47 patients (31.97%) had malignant pleural effusion, 51 patients (34.69%) had tuberculous pleural effusion, and 49 patients (33.33%) had parapneumonic pleural effusion. The median pleural fluid YKL-40 level was higher in malignant pleural effusion (114.80 ng/mL) compared to tuberculous (93.17 ng/mL) and parapneumonic pleural effusion (89.87 ng/mL; P < 0.05). A diagnostic cut-off for pleural fluid YKL-40 value of 99.76 ng/mL detected malignant pleural effusion with 83% sensitivity, 87% specificity, positive predictive value (PPV) of 75%, negative predictive value (NPV) of 91.58%, and diagnostic accuracy of 85.71%. The level of pleural fluid YKL-40 is significantly elevated in malignant pleural effusion. In lymphocytic pleural effusions presenting with low adenosine deaminase levels and high YKL-40 levels, a thorough diagnostic search for malignancy is warranted.

Gestational impaired glucose tolerance (GIGT)-induced suppression of fetal thyroid secretion: effect on fetal outcome.

INTRODUCTION: Gestational impaired glucose tolerance (GIGT) is a milder form of gestational diabetes mellitus (GDM), which is often poorly managed. Although, GDM is known to be associated with increased incidence of thyroid dysfunction, no study has been done to study the effect of GIGT on thyroid status and its effect on fetal outcome. Here, we carried out a study to assess thyroid function and glycemic status in both maternal and cord blood of the subjects with GIGT, and to find their association with the fetal outcome. MATERIALS AND METHODS: Women who came to the hospital for safe confinement during 37-40th weeks of gestation were recruited in the study. Based on the 2 hours post prandial blood glucose levels with 75 grams OGTT, done at 24-28 weeks of gestation, all the subjects were stratified into two groups: (1) Cases or GIGT group - women with blood glucose levels between 120 and 140 mg/dl and (2) Controls - women with blood glucose levels of less than 120 mg/dl. Three milliliters of venous blood was collected from mothers and 3 ml of cord blood was collected during delivery. New-borns were assessed for birth weight, head circumference, abdominal circumference, thigh circumference, and crown-heel length. Glycated hemoglobin was carried out using immunoturbidimetry (DiaSys Diagnostic Systems GmbH, Holzheim, Germany) and fructosamine was estimated using dye binding method (Biosystems, Spain). Estimation of total T3 (TT3), free T3 (FT3), total T4 (TT4), free T4 (FT4), and TSH was done by chemiluminescence in Siemens Advia Centaur CP using competitive immunoassay. RESULTS: Although within the normal reference range, GIGT mothers had higher concentration of free and total T4 than controls. Cord fructosamine levels were significantly higher in babies of GIGT mothers than controls, indicating the reflection of maternal hyperglycemia. There was a positive correlation between the maternal glycated hemoglobin and cord blood fructosamine in the GIGT group. Statistically significant lower levels of total T3 and T4 with high TSH levels were found in babies with GIGT mothers, indicating the suppressive effect of maternal hyperglycemia on fetal thyroid function. Birth weight, head circumference, and thigh circumference were significantly higher in babies born to mothers with GIGT, which may be a combined effect of maternal hyperglycemia and fetal thyroid suppression. CONCLUSIONS: Maternal hyperglycemia, even in milder form of GIGT may cause suppression of fetal thyroid function. Both these factors may predispose to change in fetal anthropometry, leading to a large baby. Therefore, it is recommended to evaluate maternal and cord thyroid function for timely management strategies.

Serum Total Magnesium Level and its Correlation with Symptom Control in Children with Mild Persistent Asthma.

OBJECTIVES: To determine the prevalence of hypomagnesemia in children with mild persistent asthma and to correlate the serum magnesium levels with symptom control in the above children. METHODS: It was a cross sectional study carried out from 1st April 2015 to 31st July 2016 at the department of Pediatrics, JIPMER Hospital. Participants included six to 12-y-old children with mild persistent asthma registered at childhood asthma clinic. Pulmonary function tests were done in all children using Care fusion Jaeger spirometer. Symptom control was assessed by childhood asthma control test questionnaire and the asthma control test questionnaire (ACT) score. Serum magnesium was measured using photometric method. Proportion of children with well controlled, partially controlled and poorly controlled asthma, serum magnesium levels across the three levels of control and correlation of serum magnesium level with ACT score and pulmonary function tests were studied. RESULTS: The prevalence of hypomagnesemia in children with mild persistent asthma was 5.6%. The median serum magnesium level was 2.0 mg/dl (IQR 1.9-2.1 mg/dL). As assessed by the ACT score, 66% had well controlled, 23% had partially controlled and 11% had poorly controlled asthma. There was no significant difference in the serum magnesium levels in the above three groups. There was no significant correlation between serum magnesium levels and ACT score as well as pulmonary function tests. CONCLUSIONS: The prevalence of hypomagnesemia in the index study is much lower than earlier studies and there seems to be no significant association between serum magnesium levels and asthma symptom control.

Endogenous gene selection for relative quantification PCR and IL6 transcript levels in the PBMC's of severe and non-severe dengue cases.

OBJECTIVES: Dengue viral infection ranges from dengue fever to dengue haemorrhagic fever and lethal dengue shock syndrome. Currently no means are available to monitor the progression of disease. Real time PCR based gene expression analyses are used to find potential molecular markers for effective prediction of dengue clinical outcome. The accuracy of qPCR analysis is strongly dependent on transcript normalization using stably expressed endogenous genes, which if selected imprecisely can lead to misinterpreted results. We aimed to determine the best fit for endogenous gene among six genes namely COX, ACTB, GAPDH, HMBS, HPRT and B2M for dengue viral infection cases. Gene stability was inferred from qPCR data by normalizing with two algorithms geNorm and Normfinder and the rankings generated were validated by gene expression analysis against target gene IL-6. RESULTS: Both the algorithms showed ACTB, HPRT, GAPDH as most stable genes. Normalizing with the stable genes revealed a significant fold change (p < .05) in IL-6 levels of .32, .52, .69, and .62 in non-dengue febrile illness, non severe, severe and All Dengue groups respectively compared to healthy controls. based on our study, we suggest ACTB with HPRT/GAPDH combination for normalization in qPCR for precise quantification of transcripts in dengue infected studies.