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.

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.

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.

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.

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.

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.

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.

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.

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.

Pre-operative Joint Inflammation has no Bearing on Outcome of Arthroscopic Anterior Cruciate Ligament Reconstruction at 1-Year Follow-Up; a Prospective Study.

BACKGROUND: To study the effect of pre-operative joint inflammation on clinical outcome at 1 year follow-up following ACL reconstruction surgery. METHODS: Male patients, aged 18-40 years, suffering from isolated ACL injury were included. All patients were randomly divided into two groups based on the type of graft used: Group A: semitendinosus gracilis graft with preserved insertions (STG-PI), Group B: bone-patellar tendon-bone graft (BPTB). Patients were categorised based on the time of presentation after injury: (a) within 6 weeks of injury, (b) between 6 and 12 weeks of injury, (c) after 12 weeks of injury. Synovial fluid levels of Interlukin-1, Interlukin-6 and TNF-α were measured in all the ACL deficient knees by taking a joint fluid sample intra-operatively. RESULTS: The total number of patients in the study was 59; 23 in group A (STG-PI) and 36 in group B (BPTB). Mean age of patients was 26 ± 5.146 years. 14 out of 59 (23.7%) patients presented within 6 weeks of injury, 16 (27.11%) patients presented between 6 and 12 weeks after injury and 29 (49.1%) patients presented after 12 weeks of injury. IL-6 levels were significantly high in group with < 6 weeks of injury than in group with > 12 weeks since injury. IL-6 had significant correlation with VAS scores, KT 1000, Lysholm knee scores and Tegner level of activity. There was no difference in outcome (pain scores, mechanical stability, Lysholm knee score and Tegner level of activity) at 1 year follow-up when patients with different time intervals since injury were compared. CONCLUSION: The clinical outcome in terms of pain score, mechanical stability, functional scores and return to sporting activity is comparable, irrespective of the time since injury, at short term follow-up.

One-Hour Postload Plasma Glucose in Obese Indian Adults with Nonalcoholic Fatty Liver Disease: An Observational Study from North India.

Background: Metabolic perturbations and hyperglycemia are increasingly identified as causal factors for nonalcoholic fatty liver disease (NAFLD). Insulin resistance, an indirect marker for initiation of NAFLD can be promptly diagnosed with standard oral glucose tolerance test (OGTT). One-hour postOGTT plasma glucose measurement can have a significant impact on early identification of dysglycemia with NAFLD and may be superior to fasting and 2-hour plasma glucose. Objective: To assess 1-hour post OGTT plasma glucose levels and presence of NAFLD in obese adults. Materials and Methods: In this observational study, we included 101 consecutive obese (body mass index >25 kg/m2) participants of age 20-50 years without known illness of diabetes mellitus. Their anthropometric and laboratory characteristics were recorded and a standard OGTT was performed. Plasma glucose (PG) levels were measured during fasting, 1-hour (1-hour-PPG), and 2-hour (2-hour-PPG) intervals. All participants underwent ultrasound of the abdomen by a single, experienced observer for fatty liver (FL) grade assessment. Comparison of the PG and FL was done by the Chi-square test and a P value <0.05 was considered statistically significant with a 95% confidence interval. Data analysis was done using SPSS version 24.0 (IBM® SPSS Statistics Inc., Chicago, Illinois, USA). Results: The result demonstrated that 53 adults had 1-hour-PPG values above the cutoff (≥155 mg/dl), whereas only 20 individuals had raised PG at 2 hours (≥140 mg/dl). All study subjects (100%) had an evidence of FL disease on ultrasound scan. Among these, 33 had grade I and 68 participants had grade II or III FL. About 41.6% of individuals had deranged 1-hour-PPG levels and higher FL grades as compared to 11.9% individuals with raised 2-hour-PPG values and FL of same grades. The relationship between 1-hour-PPG and FL grades was also statistically significant (P value <0.05). Conclusions: 1-hour-PPG levels were more deranged in obese adults without diabetes, and had more consistent and significant relationship with higher FL grades than the 2-hour-PPG levels.

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.

Dihydrotestosterone in Amyotrophic lateral sclerosis-The missing link?

OBJECTIVE: Testosterone has been postulated to be involved in ALS causation. MATERIALS AND METHODS: CSF levels of free testosterone and dihydrotestosterone were measured in 13 ALS patients [7 males, 6 females] and 22 controls [12 males, 10 females]. RESULTS: CSF free testosterone levels did not show any significant differences but CSF dihydrotestosterone levels were significantly decreased in all male and female ALS patients. CONCLUSIONS: DHT is probably integral to survival of motor neurons. In patients predisposed to develop ALS, there is possibly a sort of "testosterone resistance" at level of blood-brain barrier [BBB] existing right from birth and is likely the result of dysfunctional transport protein involved in testosterone transfer across the BBB. In these patients, lesser amount of testosterone is able to breach the BBB and enter the central neural axis. Lesser amount of testosterone is available to 5 α reductase in the anterior pituitary to be converted to DHT and lesser amount of DHT is generated. There is inadequate negative feedback suppression of LH at the level of anterior pituitary by DHT. As a result of higher LH levels, testosterone levels rise in the peripheral testosterone fraction [the fraction outside the BBB] and this explains the various physical attributes of ALS patients like lower Ratio of the index and ring finger lengths (2D:4D ratio), increased incidence of early onset alopecia etc. This deficiency of DHT leads to motor neuron death causing ALS.

Rv2037c, a stress induced conserved hypothetical protein of Mycobacterium tuberculosis, is a phospholipase: Role in cell wall modulation and intracellular survival.

The genome of Mycobacterium tuberculosis encode for several hypothetical proteins that needed to be characterized. Rv2037c, a hypothetical protein, was 25 and 4 folds upregulated under acidic and nutritive stress, respectively in M. tuberculosis H37Ra. The protein demonstrated lipolytic activity with pNP-decanoate with optimum pH 8.0 and temperature 40 °C. In addition, the protein demonstrated phospholipase activity. To understand the effect of rv2037c on mycobacterium physiology, the gene was cloned and expressed in M. smegmatis. The protein was found in membrane and extracellular fraction. The expression of rv2037c in M. smegmatis (MS_Rv2037c) altered colony morphology and cell surface features like enhanced biofilm and pellicle formation. MS_Rv2037c decreased cell-wall permeability, enhanced TDM content, resistance against various stresses and antibiotics. MS_Rv2037c demonstrated better infection and intracellular survival capability in infected THP-1 macrophage. Macrophages treated with Rv2037c demonstrated irregular cell membrane. Mice infected with MS_Rv2037c had higher bacterial load in lung, liver and spleen compared to control. Rv2037c induced the production of pro-inflammatory cytokines TNFα and IL12, suggesting its role in immune-modulation. Recombinant protein also generated humoral response in EPTB and MDR-TB patients. The results pointed towards the crucial role of this enzyme in cell-wall modulation, infection and intracellular survival of mycobacterium.

Hormonal changes and reproductive health issues in females with tuberculosis.

BACKGROUND/AIMS: The association between tuberculosis (TB) and female reproductive health issues usually remains unaddressed. TB is considered as one of the major causes of infertility in India. Because of the associated stigma, the suffering females do not discuss the problems they are facing. This may lead to disturbances in serum hormone levels also. Hence, a study was planned to find abnormalities in menstrual patterns and fertility in women in childbearing age, who were suffering from TB, and evaluate disturbances in serum hormone levels of LH, FSH, Prolactin and testosterone, if any. It also aimed to evaluate if hormone levels, or some early disturbances in menstrual cycle, can serve as a predictor for infertility in future lives. MATERIALS AND METHODS: 25 female patients each of child bearing age group from OPD/IPD: of pulmonary TB (PTB), extra pulmonary non genital TB (EPTB), extra pulmonary genital TB (GTB) and healthy controls were enrolled. Thus, a total of 75 patients with TB and 25 healthy controls were taken into the study. Patients were questioned for any abnormalities of menstrual cycle. If married, fertility status, total number of live children, abortions etc and previous history of any reproductive health issues was asked. Serum FSH, LH, Prolactin and testosterone levels on the 3rd day of the menstrual cycle were done. Data so obtained was tabulated and statistically analyzed. RESULTS: TB patients (75/100) and healthy controls (25/100) were matched with respect to age, marital status and rural/urban background. Menstrual abnormalities, infertility and adverse events related to pregnancy were higher in patients with TB than healthy controls (p = 0.176, 0.571 and 0.005 respectively). TB patients had significantly higher levels of Testosterone and significantly lower levels of Prolactin than healthy controls (p=<0.001). Levels of FSH and LH were lower in TB patients than healthy controls (p = 0.428 and 0.274 respectively). On categorization into different types of TB, the sub-groups were matched with respect to rural/urban background. GTB was significantly higher in patients who were married (p = 0.020). Significantly higher GTB patients (10/25) reported menstrual abnormalities (p < 0.001). All the 3 infertile patients reported in the study belonged to GTB sub-group (p = 0.044). GTB had higher number of adverse events related to pregnancy followed by EPTB and PTB. Levels of FSH, LH, Testosterone and Prolactin in the three sub-groups of TB patients did not show any significant difference (p = 0.683, 0.817, 0.781, and 0.187). Since the total number of infertile patients in our study was only 3, relationship of menstrual abnormalities or serum hormone levels as a predictor of infertility could not be assessed. CONCLUSION: Females suffering from TB experience significantly higher adverse events related to pregnancy than healthy controls. Menstrual abnormalities, infertility and adverse events related to pregnancy were more pronounced in females suffering from GTB than PTB/EPTB. Female patients suffering from any form of TB need to be comprehensively managed. Because of highly sensitive issues related to infertility and reproductive health in today's era, it is imperative that any future complications of the same are kept into consideration in female patients with TB.