Bayesian structural equation modeling for post treatment health related quality of life among tuberculosis patients.

BACKGROUND: The use of Bayesian Structural Equation Model (BSEM) to evaluate the impact of TB on self-reported health related quality of life (HRQoL) of TB patients has been not studied. OBJECTIVE: To identify the factors that contribute to the HRQoL of TB patients using BSEM. METHODS: This is a latent variable modeling with Bayesian approach using secondary data. HRQoL data collected after one year from newly diagnosed 436 TB patients who were registered and successfully completed treatment at Government health facilities in Tiruvallur district, south India under the National TB Elimination Programme (NTEP) were used for this analysis. In this study, the four independent latent variables such as physical well-being (PW = PW1-7), mental well-being (MW = MW1-7), social well-being (SW = SW1-4) and habits were considered. The BSEM was constructed using Markov Chain Monte Carlo algorithm for identifying the factors that contribute to the HRQoL of TB patients who completed treatment. RESULTS: Bayesian estimates were obtained using 46,300 observations after convergence and the standardized structural regression estimate of PW, MW, SW on HRQoL were 0.377 (p<0.001), 0.543 (p<0.001) and 0.208 (p<0.001) respectively. The latent variables PW, MW and SW were significantly associated with HRQoL of TB patients. The age was found to be significantly negatively associated with HRQoL of TB patients. CONCLUSIONS: The current study demonstrated the application of BSEM in evaluating HRQoL. This methodology may be used to study precise estimates of HRQoL of TB patients in different time points.

APOC3 Gene Polymorphism and Antiretroviral Therapy-Induced Dyslipidemia in HIV-Infected Children.

Children exposed to antiretroviral therapy (ART) are at risk of developing metabolic complications. The association between gene polymorphisms and the development of dyslipidemia in children post ART initiation was studied. Children initiating first-line ART were followed for 2 years at the National Institute for Research in Tuberculosis (Chennai, India), and St. John's Medical College Hospital (Bangalore, India). Clinical examination and fasting serum lipid profiles were measured every 6 months. Participants were genotyped for the polymorphisms in the APOC3 gene (rs2854116; rs2854117, and rs5128). Changes in lipid levels from baseline to months 6, 12, and 24, and the difference between the various genotype variants were analyzed using a modified analysis of variance test. Study enrolled 393 ART-naive HIV-infected children (mean age: 7.6 ± 3 years, mean weight: 18 ± 6) of whom 289 (75%) were started on nevirapine (NVP)-based ART and the remaining 96 (25%) were started on efavirenz-based ART. Only children carrying the GG allele of rs5128 genotype showed a decrease in CD4% and serum triglycerides pre-ART. An increasing trend of total cholesterol, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol were seen at 6 months in both EFZ and NVP groups, which subsequently stabilized by 12 months irrespective of genotype variants. Genotype variants of APOC3 (rs2854116 and rs2854117 polymorphism) did not show significant changes in serum lipid levels after 24 months of ART, whereas rs5128 polymorphism with "G" allele showed an association with HDL-c levels when on NVP-based ART. Our results suggest that ART plays a major role in normalizing lipid levels in HIV-infected children and APOC3 polymorphisms may not play a significant role in ART-induced dyslipidemia.

Distribution and growth rate of COVID-19 outbreak in Tamil Nadu: A log-linear regression approach.

BACKGROUND: Most of the countries are affected with the pandemic outbreak of the coronavirus infection. Understanding the severity and distribution in various regions will help in planning the controlling measures. OBJECTIVES: The objective was to assess the distribution and growth rate of COVID-19 infection in Tamil Nadu, India. METHODS: The data on the number of infections of COVID-19 have been obtained from the media reports released by the Government of Tamil Nadu. The data contain information on the incidence of the disease for the first 41 days of the outbreak started on March 7, 2020. Log-linear model has been used to estimate the progression of the COVID-19 infection in Tamil Nadu. Separate models were employed to model the growth rate and decay rate of the disease. Spatial Poisson regression was used to identify the high-risk areas in the state. RESULTS: : The models estimated the doubling time for the number of cases in growth phase as 3.96 (95% confidence interval [CI]: 2.70, 9.42) days and halving time in the decay phase as 12.08 (95% CI: 6.79, 54.78) days. The estimated median reproduction numbers were 1.88 (min = 1.09, max = 2.51) and 0.76 (min = 0.56, max = 0.99) in the growth and decay phases, respectively. The spatial Poisson regression identified 11 districts as high risk. CONCLUSION: The results indicate that the outbreak is showing decay in the number of infections of the disease which highlights the effectiveness of controlling measures.

Glycosmis pentaphylla (Rutaceae): A Natural Candidate for the Isolation of Potential Bioactive Arborine and Skimmianine Compounds for Controlling Multidrug-Resistant Staphylococcus aureus.

Several multidrug-resistant organisms have emerged, which increases the threat to public health around the world and a limited number of therapeutics were available to counteract these issues. Thus, researchers are trying to find out novel antimicrobials to overcome multidrug-resistant issues. The present study aimed to isolate antibacterial principles against the clinical isolates of multidrug-resistant (MDR) Staphylococcus aureus from the ethyl acetate extract of Gycosmis pentaphylla. The isolation and structural characterization of bioactive compounds were carried out using various chromatographic techniques (TLC, column, HPLC, and LC-MS) and spectral studies such as FT-IR, CHNS analysis, 1H-NMR, and 13C-NMR. The antimicrobial potential of isolated compounds was assessed according to the standard methods. The isolated compounds were identified as arborine and skimmianine, which exhibited a significant antibacterial effect with the lowest MIC and MBC values against MDR S. aureus and in vitro kinetic and protein leakage assays supported the antimicrobial activity. Significant morphological changes such as uneven cell surfaces and morphology, cell shrinkage, and cell membrane damages were observed in the MDR S. aureus upon the treatment of arborine and skimmianine. The present investigation concludes that the isolated arborine and skimmianine compounds from G. pentaphylla harbor a strong antibacterial activity against MDR S. aureus and may be used as alternative natural drugs in the treatment of MDR S. aureus.

Antioxidant and Antiproliferative Potential of Bioactive Molecules Ursolic Acid and Thujone Isolated from Memecylon edule and Elaeagnus indica and Their Inhibitory Effect on Topoisomerase II by Molecular Docking Approach.

The present study aimed to evaluate the antioxidant and antiproliferative potential of ursolic acid and thujone isolated from leaves of Elaeagnus indica and Memecylon edule and their inhibitory effect on topoisomerase II using molecular docking study. The isolated ursolic acid and thujone were examined for different types of free radicals scavenging activity, the antiproliferative potential on U-937 and HT-60 cell lines by adopting standard methods. Further, these compounds were docked with the active site of the ATPase region of topoisomerase II. The findings of the research revealed that ursolic acid harbor strong antioxidant and antiproliferative capacity with low IC50 values than the thujone in all tested methods. Moreover, ursolic acid shows significant inhibition effect on topoisomerase II with a considerable docking score (-8.0312) and GLIDE energy (-51.86 kca/mol). The present outcome concludes that ursolic acid possesses significant antioxidant and antiproliferative potential, which can be used in the development of novel antioxidant and antiproliferative agents in the future.

Long-term virological outcome in children receiving first-line antiretroviral therapy.

BACKGROUND: Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. METHODS: Perinatally HIV infected, ART-naive children, between 2 and 12 years of age, initiating NNRTI-based ART during 2010-2015, with at least 12 months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24 weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of > 1000 copies/ml at 48 weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. RESULTS: Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5-5.7) log10 copies/ml] were enrolled into the study. At 48 weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p < 0.001). The immunologic response was good; almost 90% of children showing an increase in their absolute CD4+ T cell count to more than 350 cells/mm3. Immunological failure was noted among 11% (28/261) and virologic failure in 29% (94/328) of children. Of the 94 children with virologic failure at 12 months, 36 children showed immunologic failure while the rest had good immunologic improvement. There was no demonstrable correlation between virologic and immunologic failure. 62% had reported > 90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%-K103N and Y181C being the major NNRTI mutations-observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2-12), specificity 97% (92.4-98.9), PPV 44% (13.7-78.8) and NPV was 72% (65-77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. CONCLUSIONS: Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.

Reversible and unilateral corticospinal tract disease secondary to autoimmune free-T3-thyrotoxicosis.

68-year-old female patient with no significant medical history presents with a 3-month history of progressive neurological symptoms, which began with left eye ptosis, blurred vision and non-painful jaw discomfort, followed by left spastic weakness and hyper-reflexia with positive Babinski and Hoffman signs. An elevated T3 level, a positive peroxidase and an antigraves antibody level led to an ultrasound, which confirmed a sub acute-chronic autoimmune thyroiditis. A nerve conduction studies/electromyogram showed normal motor and sensory velocity conduction with a small amplitude compound motor action potential, indicative of likely axonal damage. Following treatment with carbimazole, the neurological symptoms greatly improved. The authors concluded that the left pyramidal syndrome was secondary to autoimmune free T3-thyrotoxicosis.

Treatment of W. bancrofti (Wb) in HIV/Wb coinfections in South India.

BACKGROUND: The disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coincident infections. METHODOLOGY/PRINCIPAL FINDINGS: To assess the influence of pre-existing Wuchereria bancrofti infection on HIV progression, we performed a case-controlled treatment study of HIV positive individuals with (FIL+) or without (FIL-) W. bancrofti infection. Twenty-eight HIV+/FIL+ and 51 matched HIV+/FIL- subjects were treated with a single dose of diethylcarbamazine and albendazole (DEC/Alb) and followed for a year at regular intervals. Sixteen of the HIV+/FIL+ subjects (54%) and 28 of the HIV+/FIL- controls (57%) were on antiretroviral therapy (ART) during the study. Following treatment, no differences were noted in clinical outcomes between the 2 groups. There also was no significant difference between the groups in the HIV viral load at 12 months as a percentage of baseline viral load (HIV+/FIL+ group had on average 0.97 times the response of the HIV+/FIL- group, 95% CI 0.88, 1.07) between the groups. Furthermore, there were no significant differences found in either the change in viral load at 1, 3, or 6 months or in the change in CD4 count at 3, 6, or 12 months between the 2 groups. CONCLUSIONS/SIGNIFICANCE: We were unable to find a significant effect of W. bancrofti infection or its treatment on HIV clinical course or surrogate markers of HIV disease progression though we recognized that our study was limited by the smaller than predicted sample size and by the use of ART in half of the patients. Treatment of W. bancrofti coinfection in HIV positive subjects (as is usual in mass drug administration campaigns) did not represent an increased risk to the subjects, and should therefore be considered for PLWHA living in W. bancrofti endemic areas. TRIAL REGISTRATION: ClinicalTrials.gov NCT00344279.

KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association.

PURPOSE: We quantified mRNA expression of candidate genes for proliferation (KIF14 and E2F3) in a large retinoblastoma tumor cohort and associated with disease phenotype. METHODS: KIF14 and E2F3 mRNA expression was quantified by real time PCR in 57 retinoblastoma (RB) tumors, 3 RB cell lines, and control samples that included 4 each fetal, age-matched, adult retinas. Immunohistochemistry was done to confirm KIF14 and E2F3 protein expression in tumor cells. The mRNA expression levels were correlated with disease phenotypes including the significance of chemotherapy on tumors. RESULTS: There was statistically significant overexpression of KIF14 and E2F3 mRNA in tumors compared with control retinas (p<0.0001). Further, E2F3 also showed a significant overexpression compared to RB cell lines (p=0.01). Immunohistochemistry confirmed KIF14 and E2F3 protein overexpression in tumor cells. KIF14 had significant mRNA overexpression with older age (p=0.01) in presenting patients and in unilateral RB patients (p=0.04). Chemotherapy-treated tumors showed a significant decrease in KIF14 and E2F3 expression compared to untreated tumors (p<0.01 and 0.001, respectively). CONCLUSIONS: This report confirms significant mRNA overexpression of KIF14 and E2F3 together in a large cohort of RB tumors. The decreased expression in chemotherapy treated cases needs further validation in a large chemotherapy-treated cohort.

Maternal hypothyroidism in early and late gestation: effects on neonatal and obstetric outcome.

BACKGROUND: Maternal hypothyroidism may be associated with a variety of adverse neonatal and obstetric outcomes. Whether these outcomes are affected by maternal thyroid status at initial presentation or in late gestation specifically within a dedicated antenatal endocrine clinic remains unclear. The effects of thyroxine dose requirement during pregnancy and serum concentrations of TSH within such clinic settings are still not known. OBJECTIVES: We investigated these outcomes in patients with hypothyroidism during early and late gestation. TSH levels and thyroxine dose requirement during early and late gestation were also evaluated. METHODS: We performed a retrospective study of data from 167 pregnancies managed in the antenatal endocrine clinic. Analysis of outcomes was linked to TSH at first presentation and in the third trimester. Outcome variables included: rate of caesarean section, pre-eclampsia, neonatal unit admission, neonatal weight and gestational age. Controlled TSH was defined as mothers with TSH between 0.1 and 2 with normal free thyroid hormone levels. RESULTS: The caesarean section (CS) rates were higher in the study cohort (H) compared with the local (C) rate (H = 28.7%, C = 18%). The higher rate in our patient cohort was not due to a higher rate of emergency section nor to a lower threshold for performing elective caesarean section. The infant birthweight (IBW) from mothers with TSH > 5.5 (H1) and mothers with TSH between 0.1 and 5.5 at presentation (H2) was [median (range)] 3.38 (1.73-4.70) vs. 3.45 (1.36-4.76); P = ns. The prevalence of low-birthweight (LBW) infants (< 2.5 g) in groups H1 and H2 was 15% and 4.8%, respectively [odds ratio (OR) = 3.55, 95% confidence interval (95% CI) = 0.96-10.31]. IBW from mothers with TSH > 2 (H3) and mothers with controlled TSH in the third trimester (H4) were similar [3.38 (1.78-4.4) vs. 3.46 (1.36-4.76); P = ns]. The prevalence of LBW in groups H3 and H4 was 9% and 4.9%, respectively (OR = 1.95, 95% CI = 0.52-7.26). The median thyroxine dose (microg) increased significantly during pregnancy (first trimester: 100; second trimester: 125, P < 0.001; and third trimester: 150, P < 0.001) associated with appropriate suppression of TSH levels in the second and third trimesters. Rates of pre-eclampsia or admissions to neonatal units were negligible. CONCLUSION: Thyroxine dose requirement increases during pregnancy and thus close monitoring of thyroid function with appropriate adjustment of thyroxine dose to maintain a normal serum TSH level is necessary throughout gestation. Within a joint endocrine-obstetric clinic, maternal hypothyroidism at presentation and in the third trimester may increase the risk of low birthweight and the likelihood for caesarean section. The latter observation was not due to a higher rate of emergency caesarean section nor to a lower threshold for performing elective caesarean section. A larger study with adjustments made for the various confounders is required to confirm this observation.

Obesity in the elderly: who should we be treating, and why, and how?

PURPOSE OF REVIEW: To investigate emerging data on the relationship between obesity, increased morbidity and mortality, and decreased function in the elderly. To examine what is known about the effectiveness of interventions, and how treatment might be improved. RECENT FINDINGS: Obesity is a common problem in the elderly, although its prevalence decreases in extreme old age. Decreased physical activity and decreased energy expenditure with ageing predispose to fat accumulation and fat redistribution. Reduction in muscle mass (sarcopenic obesity) is an important determinant of physical function and metabolic rate. Chronic inflammation and endocrine changes contribute to the changes in metabolism and body composition that accompany ageing, and are potential therapeutic targets. Body weight and body mass index are imperfect indicators of risk from obesity. The focus of treatment should be on reduction of intra-abdominal fat and preservation of muscle mass and strength. A number of recent studies have confirmed the effectiveness of exercise interventions in the elderly. Progressive resistance training, rather than endurance exercise, may be more effective in many cases. Reduced function and decreased quality of life accompany development of the complications of obesity such as diabetes and vascular disorders. There is considerable scope to impede the development of these complications in the elderly with lifestyle interventions. SUMMARY: Sarcopenic obesity, with accumulation of intra-abdominal fat, is a major determinant of health status in the elderly. As in the younger population, prevention and treatment programmes have the potential to decrease the impact of diabetes, vascular disease, and other complications of obesity.