Evaluation of chemiluminescence immunoassay as a screening test for syphilis on blood donor samples.

BACKGROUND AND OBJECTIVE: Global re-emergence of syphilis among blood donors necessitates novel diagnostic and prevention approaches that encourage timely intervention. Thus, the present study was planned to evaluate the efficiency of Chemiluminescence immunoassay (CLIA) as a screening test for syphilis. MATERIAL AND METHODS: This prospective cross-sectional observational study was conducted from October 2021 to September 2022. A total of 344 donors were enrolled by purposive sampling method, including additional 16 donors who were reactive by the Rapid plasma reagin test (RPR) during the study period. Data from three screening tests - RPR test, Treponema pallidum haemagglutination assay (TPHA) and CLIA for 360 blood donors were analysed. TPHA was considered the gold standard test. RESULTS: Of the total 360 samples tested, 21 (5.8 %) were reactive by the RPR test. Of these 21 RPR reactive samples, 19 (90.5 %) were reactive by both TPHA and CLIA, while 2 (9.5 %) RPR reactive samples were non-reactive by both TPHA and CLIA. Of the remaining 339 RPR non-reactive samples, 1 (0.3 %) sample was reactive by both TPHA and CLIA, and 1 (0.3 %) was reactive by CLIA alone. CLIA was found to have sensitivity and specificity of 100 % and 99.7 % and positive predictive value (PPV) and negative predictive values (NPV) of 95.2 % and 100 % respectively, while it was 95 %, 99.4 %, 90 %, and 99.7 %, respectively, with the RPR test. CONCLUSION: CLIA was found to have a higher sensitivity, specificity, PPV and NPV than the RPR test. Thus, CLIA can be an acceptable alternative for syphilis screening in blood donors.

Role of cerebrospinal fluid tau protein levels as a biomarker of brain injury in pediatric status epilepticus.

BACKGROUND: Various biomarkers have been studied for predicting etiology and outcome in status epilepticus (SE); cerebrospinal fluid (CSF) total tau (t-tau) protein levels is foremost among them. Only handful of studies are available regarding role of t-tau in childhood SE. METHODOLOGY: This prospective study was conducted in a tertiary care center of Northern India in children 6 months -12 years of age. The Cases were patients with convulsive status epilepticus (CSE) whereas Controls were patients without SE and normal CSF. The t-tau levels were done in CSF of both the groups. The outcome was assessed by GOS-E Peds score. RESULTS: A total of 50 (62% males) cases and 15 (67% males) controls were enrolled in the study. SE was generalized in 78% cases whereas 14% had refractory SE. Most common etiology of CSE was acute symptomatic (52%), followed by prolonged febrile seizure (24%), remote symptomatic group (14%), unknown etiology (8%) and progressive disorder (2%). Case fatality rate was 10%. Poor outcome was seen in 30% cases. Median (IQR) CSF t-tau levels was significantly lower 2.6 × 103 (0.5-9.4 × 103) pg/ml in cases vs 10.6 × 103 (6.0-14.2 × 103) pg/ml in controls (p = 0.004). There was no significant correlation seen between type, duration, etiology and response to antiepileptic drugs of SE with CSF t-tau levels. Also, no significant correlation of poor sensorium, outcome of SE and critical care needs with CSF t-tau levels was noted. CONCLUSION: CSF t-tau is not a useful diagnostic or prognostic biomarker in pediatric SE.

Does ensuring optimum vitamin D levels result in early resolution of neurocysticercosis?

BACKGROUND: Neurocysticercosis is a leading cause of acquired epilepsy. Calcified granulomas are known to cause seizure recurrence. Researchers have reported that vitamin D deficiency is associated with brain calcification and reduction in calcification occurs with vitamin D receptor agonist calcitriol through upregulation of SLC20A2. Based on these observations, a hypothesis was proposed that the occurrence of calcification could be reduced by optimizing vitamin D levels, resulting in early resolution of neurocysticercosis. METHODOLOGY: A case-control (retrospective and prospective) study on 60 children with solitary intraparenchymal neurocysticercosis, 20 new cases prior to starting cysticidal therapy and other 40 resolved cases was carried out. Among new cases, children deficient in vitamin D were given megadose of vitamin D and vitamin D levels were rechecked after 30 days. Children having normal vitamin D were taken as cases and the deficient ones were taken as controls. Standard treatment for neurocysticercosis was given. Three monthly MRI scans were done. Outcome was evaluated as resolution/persistence of neurocysticercosis at 3, 6, 9 and 12 months. STATISTICS AND RESULTS: Pearson chi square/Fisher's exact test was used along with Kaplan Meier and log rank test. Of 60 patients, at 6 months 3 cases and 4 controls (p value 0.43), at 9 months 2 cases and 6 controls (p value 0.037) and at 12 months 3 cases and 6 controls (p value 0.029) had complete resolution of NCC. CONCLUSION: The results do not show that adequate vitamin D levels result in early resolution of neurocysticercosis.

Systemic biomarkers of retinopathy of prematurity in preterm babies.

PURPOSE: Retinopathy of prematurity (ROP) progression is an inter-play of various perinatal and neonatal angiogenic and inflammatory cytokines. A small subset of ROP progresses to ROP requiring treatment. The present study was conducted with the aim to determine whether levels of IL-6, IL-8 and VEGF in serum and urine at the time of first ROP screening visit could be a biomarker for the prediction of development of treatable ROP. METHOD: Prospective single-center observational study of preterm babies screened for ROP. Blood and urine samples were collected as a part of routine sampling at initial ROP screening visit and stored at -80 °C for further processing. The babies were followed up and grouped into 'Group A' comprising of 35 babies who developed treatable ROP and 'Group B' comprising of 36 babies with regressed ROP or no ROP. The evaluation of blood and urine samples was done for IL6, IL8 and VEGF by solid-phase sandwich RayBio® Human ELISA kit. RESULTS: The median serum values for IL-6, IL-8 and VEGF in Group A and Group B were 5.8 pg/ml (IQR 1.5,128.5) and 8.7 pg/ml (IQR 1.5,30.5), 55.9 pg/ml (IQR 28.0, 392.9) and 27.0 pg/ml (IQR 20.5,444.9) and 26.6 pg/ml (IQR 6.3, 39.4) and 30.0 pg/ml (IQR9.2,70.3), respectively. Group A had significantly increased levels of IL-8 (p < 0.05). However, AUROC curve for serum IL-8 demonstrated suboptimal discriminating ability. CONCLUSION: Babies developing ROP requiring treatment had significantly increased levels of IL-8 in the serum at the time of initial screening. However, it could not serve as predictor for treatable ROP.

Early diagnosis of kidney injury in a paediatric population: a prospective cohort study (E-DRIP STUDY).

BACKGROUND: Renal Angina Index (RAI) is a bedside tool for risk stratification of patients to predict acute kidney injury (AKI). Kidney biomarkers are better indicators of real-time injury and give us lead time for diagnosing impending AKI. METHODS: We enrolled consecutive children aged 2 months-14 years admitted to a tertiary hospital in northern India over 2 years. RAI was calculated on day 0 (D0) and urinary (u) and plasma (p) neutrophil gelatinase-associated lipocalin (NGAL) were measured within 6 h of admission. Children were followed for the development of severe AKI on day 3 (D3) using Kidney Disease Improving Global Outcomes criteria to define and stage AKI. RESULTS: Of the 253 children enrolled and analysed, 44 (17.4%) developed D3-AKI (stage 1 in 52.2%, stage 2 in 20.5% and stage 3 in 27.3%). Renal angina (RAI ≥ 8) on D0 was present in 66.7% children who developed stage 2/3 D3-AKI vs. 43.5% in children who did not develop D3-AKI /stage 1 AKI (p = 0.065). Area under ROC (AUROC) curve for D0-RAI to predict D3-severe-AKI was 0.66 (95% CI, 0.55-0.77). AUROC curve for uNGAL and pNGAL to predict D3-severe-AKI was 0.62 (95% CI, 0.50-0.74) and 0.48 (95% CI, 0.35-0.61), respectively. The severe AKI group had greater requirement of ventilation and inotropic support with mortality being thrice higher compared to the non-AKI group. CONCLUSION: RAI ≥ 8 and uNGAL had a high negative predictive value but low sensitivity for predicting D3-severe-AKI. pNGAL had a poor predictive value for D3-severe-AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effect of fetal growth restriction on urinary podocalyxin levels at birth in preterm neonates.

BACKGROUND: Small-for-gestational-age (SGA) neonates are at a higher risk of adult-onset metabolic disorders because of fetal programming in the presence of growth restriction. Nephrogenesis may also be affected in fetal growth restriction. This study hypothesized that urinary podocalyxin levels, a marker of nephrogenesis, would be lower among preterm SGA neonates as compared to appropriate-for-gestational-age (AGA) controls. METHODS: This cross-sectional study enrolled gestation-matched SGA (n = 90) and AGA (n = 45) neonates born at 260-366 weeks of gestation. The SGA group comprised of 45 neonates with birth weight between 3rd and 10th centile and 45 neonates with birth weight <3rd centile. The primary outcome of the study was the difference in urinary podocalyxin levels between SGA and AGA neonates. Glomerular and tubular functions were also assessed. RESULTS: Urinary podocalyxin levels were similar in SGA and AGA neonates (ng/mg of creatinine; median [interquartile range]: 28.7 [4.8-70.2] vs. 18.7 [3.1-55.9]), P value 0.14). No correlation was observed between birth weight centile and urinary podocalyxin levels (r: -0.06). Glomerular filtration rate, fractional excretion of sodium, and serum ß-2-microglobulin levels were comparable across the study groups. CONCLUSIONS: Glomerular development as assessed by urinary podocalyxin levels and renal functions are comparable in SGA and AGA preterm neonates. IMPACT: Neonates born with fetal growth restriction are at a higher risk of adult-onset metabolic disorders because of fetal programming. This cross-sectional study investigated the effect of presence and severity of fetal growth restriction on glomerular development by measuring urinary podocalyxin levels in preterm infants. This study did not observe any effect of the presence or severity of fetal growth restriction on urinary podocalyxin levels and other markers of glomerular and renal tubular functions.

Role of interleukin-6 and insulin resistance as screening markers for metabolic syndrome in patients of chronic obstructive pulmonary disease. A hospital-based cross-sectional study.

Chronic obstructive pulmonary disease (COPD) is usually associated with various extra-pulmonary manifestations. Metabolic syndrome (MetS) is one such entity that has been scarcely studied in Indian patients. The availability of a good screening marker may help in the timely detection of this co-morbidity in COPD patients. We conducted a cross-sectional study to evaluate the prevalence of MetS among COPD patients and the role of Interleukin-6 and insulin resistance (as measured by HOMA-IR) as screening markers for MetS in COPD. One hundred stable COPD patients were evaluated for MetS using US National Cholesterol Education Program Adult Treatment Panel III (2005) guidelines. Interleukin-6 and HOMA-IR (for insulin resistance) were measured and compared between COPD patients with and without MetS. ROC analysis was done to find both the molecules' best cut-off value and sensitivity and specificity in detecting MetS. In the results, the mean age of the study cohort was 59.9±8.7yrs (males=93). Forty-five COPD patients (45%) fulfilled the criteria for MetS. Patients with MetS were comparatively younger (57.9+9.5 v/s 61.6+7.8 years; p=0.037) but had a longer duration of preceding COPD (9.9±2.8 v/s 6.0±2.2 years; p<0.001) as compared to those without MetS. Both IL-6 and HOMA index were statistically higher (p<0.05) in COPD-MetS patients compared to the other group. A cutoff value of 36.3 pg/ml for IL-6 and 1.61 for HOMA index, IL-6 and HOMA-IR had sensitivity of 91.1% and 82.2%, respectively in detecting MetS among COPD patients. To conclude, metabolic syndrome is common comorbidity seen in COPD patients. Interleukin-6 has a better sensitivity than HOMA-IR in screening MetS among COPD patients.

Vitamin D levels of anesthesiologists working in tertiary care hospital of South Asian country: An observational study.

BACKGROUND AND AIMS: Vitamin D deficiency is now emerging as a major global health problem. Doctors spend most of their time indoors and hence, have very low sun exposure. With limited studies on vitamin D levels of anesthesiologists and no published study from South Asian countries, we planned to determine vitamin D levels in anesthesiologists. MATERIAL AND METHODS: One hundred twenty anesthesiologists, working in two tertiary care hospitals, were enrolled in this study. The participants were asked to complete the questionnaire and blood samples were drawn at the same sitting for measuring serum 25(OH) D and serum calcium levels. A subgroup analysis of anesthesiologists was done based on vitamin D status levels defined as per Endocrine society clinical practice guidelines 2011 on vitamin D deficiency. Vitamin D deficiency: 25(OH) D <20 ng/ml (<50 nmol/l), Vitamin D insufficiency: 25(OH) D of 21-29 ng/ml (52.5-72.5 nmol/l), Vitamin D sufficiency: 25(OH) D of ≥30 ng/ml (≥75 nmol/l). RESULTS: The mean working hours in a day [mean ± standard deviation (SD)] were 10.70 ± 1.56 hours with a range of 8-15 hours. The mean ± SD level of vitamin D in anesthesiologists was 14.56 ± 9.39 ng/ml with a range of 5.30-58.00 ng/ml. Out of 120 anesthesiologists, 101 (84.2%) anesthesiologists had deficient levels of vitamin D, 10 (8.3%) had insufficient levels, and 9 (7.5%) anesthesiologists had sufficient levels of vitamin D. Majority of the anesthesiologists had normal serum calcium levels. A total of 91.5% of doctors had vitamin D deficiency who were not taking vitamin D supplement groups as compared to 28.6% in doctors who had taken vitamin D supplements in the past. CONCLUSION: Prevalence of vitamin D deficiency/insufficiency was high among anesthesiologists. However, levels were optimal in professionals taking vitamin D supplements.

Rv0646c, an esterase from M. tuberculosis, up-regulates the host immune response in THP-1 macrophages cells.

The genome sequence of Mycobacterium tuberculosis revealed the presence of several hydrolases involved in lipid metabolism including the members of Lip gene family. Rv0646c (LipG) is one of them. It is annotated as putative esterase/lipase because of the presence of consensus sequence 'GXSXG.' The gene was cloned, expressed, and purified in E. coli. It showed 22 U/mg specific activity with pNP-butyrate as a preferred substrate. However, it actively worked on substrates with short chain. The enzyme was optimally active at 50 °C/pH 8.0 and also stable up to 50 °C and in a lower pH range (pH 6-8). The Km, Vmax, and catalytic efficiency of the enzyme were calculated to be 500 µM, 58.82 µmoles/min/ml, and 3.92 µM/min, respectively. Homology modeling of Rv0646c revealed the presence of a canonical putative catalytic triad (Ser123, His279, and Asp251). The esterase activity was abolished in the presence of serine hydrolase inhibitors, THL and PMSF. Various antigenic epitopes were predicted in Rv0646c. The protein mounted significantly high antibody response against the sera of extrapulmonary and MDR-TB patients. Rv0646c up-regulated the production of various pro-inflammatory cytokines (TNF-α and IFN-γ), chemokine (IL-8), and nitric oxide in THP-1-derived macrophages. The secretion of IL-6 from macrophages was also found to be elevated in response to Rv0646c. The treatment resulted in the increased level of reactive oxygen species. Conclusively, Rv0646c could be classified as esterase having vast immunogenic property by eliciting strong humoral response as well as cell-mediated immunity.

High Methotrexate Triglutamate Level Is an Independent Predictor of Adverse Effects in Asian Indian Rheumatoid Arthritis Patients-A Preliminary Study.

BACKGROUND: It is unclear whether erythrocyte methotrexate polyglutamate levels (MTX-glun) are associated with response or adverse effects to methotrexate in rheumatoid arthritis. This preliminary study evaluated their utility in Asian Indian patients over 24 weeks. METHODS: Rheumatoid arthritis patients were started on oral methotrexate at a dose of 15 mg/wk, which was escalated to 25 mg by 12 weeks and continued till 24 weeks. Erythrocyte (RBC) MTX-glu1 to MTX-glu5 levels (nmol/L RBC) were determined at 4, 8, 16, and 24 weeks by using reverse-phase high-performance liquid chromatography. Area under the concentration curve (AUC) of MTX-glu1-5, MTX-glu3-5, and MTX-glu3 levels was compared between groups with regards to response and adverse effects. RESULTS: This study included 117 patients with mean (SD) age of 42.7 (±11.9) years and disease duration of 2.0 (1.7) years. Mean (SD) RBC MTX-glu1-5 levels at 4, 8, 16, and 24 weeks were 93 (±29), 129 (±46), 143 (±49), and 159 (±65) nmol/L RBC; the highest individual polyglutamate was MTX-glu3 (40%). There was significant correlation between MTX-glu1-5 (r = 0.38, P < 0.001) and MTX-glu3 (r = 0.49, P < 0.001) with methotrexate dose. There was no significant difference of AUC MTX-glun between responders and nonresponders. However, AUC MTX-glu3 was significantly (P = 0.03) higher in patients with adverse effects. On logistic regression, AUC of MTX-glu3 [odds ratio = 1.004 (95% confidence interval 1.002-1.007)] and methotrexate dose at 24 weeks were independent predictors of adverse effects. CONCLUSIONS: In this preliminary study, higher levels of RBC MTX-glu3 were found to be the independent predictors for adverse effects in rheumatoid arthritis patients.

Safety and efficacy of low dose intramuscular magnesium sulphate (MgSO4) compared to intravenous regimen for treatment of eclampsia.

AIM: This study was performed to compare the safety and efficacy of low dose intramuscular magnesium sulphate (MgSO4) (Dhaka regimen) and intravenous (IV) MgSO4 (Zuspan regimen) for the prevention of eclampsia recurrence and to compare serum magnesium concentration. METHODS: Forty one eligible patients with eclampsia were randomly divided into two groups: group I patients received IV MgSO4 according to the Zuspan regime, while group II patients received intramuscular (IM) MgSO4 according to the Dhaka regimen (i.e. low dose MgSO4). The total dose MgSo4 requirements per patient were calculated and serum MgSo4 level was measured. Maternal and fetal outcomes were compared between the groups. RESULTS: The mean total dose of MgSO4 required for the treatment of eclampsia was higher in group I compared to group II (32 ± 6.8 g vs 25.4 ± 8.8 g, respectively; P < 0.5). The mean serum MgSO4 levels were significantly higher (P < 0.003) in group I compared to group II, although there were no significant differences in seizure recurrence. Statistically, more patients in group I experienced a loss of knee jerk reaction and required dose deferral compared to group II. There was a significantly higher number of babies with poor Apgar scores in group I. Overall the maternal and fetal outcomes were comparable between the groups. CONCLUSIONS: A low dose IM regimen (Dhaka regimen) of MgSo4 is equally efficacious and safe compared to an IV regimen (Zuspan regimen) for the control and prevention of seizures in patients with eclampsia.

Assessment of changes in plasma hemoglobin and potassium levels in red cell units during processing and storage.

Red cell units undergo changes during storage and processing. The study was planned to assess plasma potassium, plasma hemoglobin, percentage hemolysis during storage and to determine the effects of outdoor blood collection and processing on those parameters. Blood collection in three types of blood storage bags was done - single CPDA bag (40 outdoor and 40 in-house collection), triple CPD + SAGM bag (40 in-house collection) and quadruple CPD + SAGM bag with integral leukoreduction filter (40 in-house collection). All bags were sampled on day 0 (day of collection), day 1 (after processing), day 7, day 14 and day 28 for measurement of percentage hemolysis and potassium levels in the plasma of bag contents. There was significant increase in percentage hemolysis, plasma hemoglobin and plasma potassium level in all the groups during storage (p < 0.001). No significant difference was found between any parameter analyzed for outdoor and in-house collected single CPDA red cell units. There was significant lower percentage hemolysis (p < 0.001) and potassium (day 7 to day 14 - p < 0.05 and day 14 to day 28 - p < 0.001) in red cell units from day 7 onward until day 28 of storage in the leukoreduced quadruple bag as compared to the triple bag. The in-house single CPDA red cell units showed significantly more hemolysis (p < 0.001) as compared to the triple bags with SAGM additive solution after 28 days of storage. There is gradual increase in plasma hemoglobin and plasma potassium levels during the storage of red blood cells. Blood collection can be safely undertaken in outdoor blood donation camps even in hot summer months in monitored blood transport boxes. SAGM additive solution decreases the red cell hemolysis and allows extended storage of red cells. Prestorage leukoreduction decreases the red cell hemolysis and improves the quality of blood.

Salivary lactate dehydrogenase levels can provide early diagnosis of hypoxic-ischaemic encephalopathy in neonates with birth asphyxia.

AIM: Timely detection of hypoxic-ischaemic encephalopathy (HIE) is crucial for selecting neonates who are likely to benefit from neuroprotective therapy. This study evaluated the efficacy of salivary lactate dehydrogenase (LDH) in the early diagnosis of HIE among neonates with perinatal asphyxia. METHODS: We prospectively enrolled 30 neonates who needed resuscitation at birth or had a history of delayed cry into the HIE group if they developed HIE within 12 h of birth. The control group comprised 30 neonates who had no evidence of HIE, but had intrapartum foetal distress or needed resuscitation at birth. LDH was measured using saliva samples collected within 12 h of birth. RESULTS: Salivary LDH was significantly higher in the HIE group, with a median of 2578 and an interquartile range (IQR) of 1379-3408 international units per litre (IU/L), than in the control group (median 558.5, IQR: 348-924 IU/L, p < 0.001). The test demonstrated excellent discriminating ability: the area under the curve was 0.92 and the levels of 893 IU/L showed a sensitivity of 90% and a specificity of 73.3%. CONCLUSION: Measuring salivary LDH among neonates with birth asphyxia provided an early and accurate diagnosis of HIE and could be used as a triage tool.

Cell wall and immune modulation by Rv1800 (PPE28) helps M. smegmatis to evade intracellular killing.

Rv1800 is predicted as PPE family protein found in pathogenic mycobacteria only. Under acidic stress, the rv1800 gene was expressed in M. tuberculosis H37Ra. In-silico study showed lipase/esterase activity in C-terminus PE-PPE domain having pentapeptide motif with catalytic Ser-Asp-His residue. Full-length Rv1800 and C-terminus PE-PPE domain proteins showed esterase activity with pNP-C4 at the optimum temperature of 40 °C and pH 8.0. However, the N-terminus PPE domain showed no esterase activity, but involved in thermostability of Rv1800 full-length protein. M. smegmatis expressing rv1800 (MS_Rv1800) showed altered colony morphology and a significant resistance to numerous environmental stresses, antibiotics and higher lipid content. In extracellular and membrane fraction, Rv1800 protein was detected, while C terminus PE-PPE was present in cytoplasm, suggesting the role of N-terminus PPE domain in transportation of protein. MS_Rv1800 infected macrophage showed higher intracellular survival and low production of ROS, NO and expression levels of iNOS and pro-inflammatory cytokines, while induced expression of the anti-inflammatory cytokines. The Rv1800, PPE and PE-PPE showed antibody-mediated immunity in MDR-TB and PTB patients. Overall, these results confirmed the esterase activity in the C-terminus and function of N-terminus in thermostabilization and transportation; predicting the role of Rv1800 in immune/lipid modulation to support intracellular mycobacterium survival.

N-terminal PPE domain plays an integral role in extracellular transportation and stability of the immunomodulatory Rv3539 protein of the Mycobacterium tuberculosis.

Multigene PE/PPE family is exclusively present in mycobacterium species. Only few selected genes of this family have been characterized till date. Rv3539 was annotated as PPE63 with conserved PPE domain at N-terminal and PE-PPE at C-terminal. An α/ß hydrolase structural fold, characteristic of lipase/esterase, was present in the PE-PPE domain. To assign the biochemical function to Rv3539, the corresponding gene was cloned in pET-32a (+) as full-length, PPE, and PE-PPE domains individually, followed by expression in E. Coli C41 (DE3). All three proteins demonstrated esterase activity. However, the enzyme activity in the N-terminal PPE domain was very low. The enzyme activity of Rv3539 and PE-PPE proteins was approximately same with the pNP-C4 as optimum substrate at 40 °C and pH 8.0. The loss of enzyme activity after mutating the predicted catalytic triad (Ser296Ala, Asp369Ala, and His395Ala) found only in the PE-PPE domain, confirmed the candidature of the bioinformatically predicted active site residue. The optimal activity and thermostability of the Rv3539 protein was altered by removing the PPE domain. CD-spectroscopy analysis confirmed the role of PPE domain to the thermostability of Rv3539 by maintaining the structural integrity at higher temperatures. The presence of the N-terminal PPE domain directed the Rv3539 protein to the cell membrane/wall and the extracellular compartment. The Rv3539 protein could generate humoral response in TB patients. Therefore, results demonstrated that Rv3539 demonstrated esterase activity. PE-PPE domain of Rv3539 is functionally automated, however, N-terminus domain played a role in protein stabilization and its transportation. Both domains participated in immunomodulation.

Prevalence, associated risk factors and effects of hypothyroidism in pregnancy: a study from north India.

BACKGROUND AND OBJECTIVE: There is a controversy regarding universal versus targeted screening for hypothyroidism during pregnancy. We studied the prevalence and the associated risk factors of hypothyroidism. The secondary objective of the study was to compare the maternal and perinatal outcomes in overt and subclinical hypothyroidism. METHODS: We screened 1,005 antenatal patients for hypothyroidism with a thyrotropin assay. Patients diagnosed with hypothyroidism were further tested for anti-thyroid peroxidase antibodies and free thyroxin to determine the cause and type (overt or subclinical) of hypothyroidism. Maternal and perinatal outcomes were compared in the overt, subclinical and euthyroid groups. RESULTS: The overall prevalence of hypothyroidism was 6.3% (overt 2.9% and subclinical 3.4%). Thirty-four (3.4%) new hypothyroid cases could be detected by universal screening. The risk factors for thyroid dysfunction were not significantly different in the screen-positive versus screen-negative patients except for excessive weight gain (p = 0.00). Targeted screening could have missed one third of subclinical hypothyroid cases. Gestational hypertension was significantly greater in the overt hypothyroid group (p = 0.007), and more patients required induction in this group (p = 0.013) but other maternal complications and perinatal outcomes were similar. CONCLUSION: We recommend universal screening for hypothyroidism in pregnancy in our population, as the prevalence of hypothyroidism is high.

Osteopontin as a Tumor Marker in Ovarian Cancer.

Introduction: Ovarian cancer is associated with high morbidity and mortality. This is due to the nonspecific symptoms and no effective screening methods. Currently, carbohydrate antigen-125 (CA125) is used as a tumor biomarker for the diagnosis of ovarian cancer, but it has its own limitations. Hence, there is a need for other tumor biomarkers for the diagnosis of ovarian cancer. Objective of the study was to evaluate the diagnostic test characteristics of plasma osteopontin (OPN) in detecting ovarian malignancy and comparing its performance with CA125. Materials and Methods: This is a prospective cross-sectional diagnostic test evaluation. Women with adnexal mass detected by clinical or radiological examination were enrolled as suspected cases. Women who presented with other gynecological conditions were enrolled as controls. OPN and CA125 levels were measured in all enrolled subjects. Results: Among 106 women enrolled, 26 were ovarian cancer, 31 had benign ovarian masses, and 49 were controls. Median plasma CA125 levels were higher in subjects with ovarian cancer (298 U/ml; interquartile range [IQR]: 84-1082 U/ml vs. 37.5U/ml; IQR: 17.6-82.9U/ml; P < 0.001). CA125 sensitivity, specificity, positive, and negative likelihood ratios were 88.5%, 61.3%, 2.10, and 0.19, respectively. Median plasma OPN levels were higher in subjects with ovarian cancer (63.1 ng/ml; IQR: 39.3-137 ng/ml vs. 27 ng/ml; IQR: 20-52 ng/ml; P = 0.001). Sensitivity, specificity, positive, and negative likelihood ratios of OPN were 50%, 87%, 2.58, and 0.62, respectively. Conclusion: OPN levels were higher in ovarian cancer than in the benign ovarian mass and had better specificity than CA125. OPN can better differentiate between benign and malignant ovarian mass as compared to CA125.

Mean platelet volume and glycaemic control in patients with new-onset Type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with vascular complications that are attributable to dysregulated platelet reactivity as measured by mean platelet volume (MPV). This study aimed at determining a relationship between MPV and glycaemic control in new-onset T2DM. METHODS: This was a prospective study conducted on 236 new-onset T2DM patients divided in two groups as group A, glycosylated haemoglobin A1c (HbA1c < 7.9%; n = 70) and group B, HbA1c ⩾ 8% (n = 107) who were followed up for 6 months for change in platelet and glycaemic parameters. RESULTS: At 6-month follow-up, there was a significant decrease in HbA1c and MPV (group A (HbA1c: 7.40 ± 0.40 vs 7.03 ± 0.23%, p < 0.03; MPV: 9.65 fl ± 0.74 vs 9.46 fl ± 0.71, p < 0.001) and group B (HbA1c: 10.59 ± 1.89% vs 9.29 ± 1.50%, p < 0.001; MPV: 10.89 fL ± 1.29 vs. 10.23 fL ± 1.40, p< 0.001)). The percentage decline in HbA1c was more in group B (11.81 ± 5.87 vs 4.76 ± 4.58, p < 0.01). There was a positive correlation between ΔMPV and ΔHbA1c in group B; however, we did not observe significant correlation for group A. CONCLUSION: We interpret that in people with diabetes with baseline HbA1c ⩾ 8%, with improvement in glycaemic control, there is a significant decrease in MPV. We propose that a routine MPV testing can be used as a potential marker for glycaemic control in T2DM.

Reference Levels for TSH in Iodine-Sufficient Low-Risk Pregnant Women.

BACKGROUND: Recent evidence suggests that thyrotropin (TSH) levels are population specific because of differences in ethnicity. As a result, the 2017 ATA guidelines state that treatment may be tailored as per the laboratory-specific reference ranges of TSH for the local population instead of using a fixed upper limit of 2.5 mIU/L during pregnancy. METHODOLOGY: This was a cross-sectional study in which we collected detailed clinical data of 604 pregnant women along with their TSH and spot urinary iodine excretion levels. Reflex testing for thyroid peroxidase antibodies (TPOAb) was done in women with TSH levels > 2.5 mIU/L in 1st trimester and 3.0 mIU/L in 2nd and 3rd trimester. After excluding 295 women who had high risk factors as per ATA 2017 guidelines and those who were TPOAb positive, we calculated the reference range for TSH in an iodine-sufficient low-risk cohort of 309 women. RESULTS: With median urinary Iodine of 255 µg/l, our population had more than required iodine levels. The 5th and 95th percentiles of TSH in our study cohort of 604 women were 0.64 and 7.81 mIU/L, respectively, while the 5th and 95th percentiles of TSH for the low-risk cohort of 309 women were 0.59 and 4.48 mIU/L, respectively. CONCLUSION: An upper limit of 4.5 mIU/L for TSH level during pregnancy can be used to guide management decisions for low-risk North Indian women.