Epidemiology, Clinical Profile, Intensive Care Needs and Outcome in Children with SARS-CoV-2 Infection Admitted to a Tertiary Hospital During the First and Second Waves of the COVID-19 Pandemic in India

Objectives To compare the epidemiological, clinical profle, intensive care needs and outcome of children hospitalized with SARS-CoV-2 infection during the frst and second waves of the pandemic. Methods This was a retrospective study of all children between 1 mo and 14 y, admitted to a dedicated COVID-19 hospital (DCH) during the frst (1st June to 31st December 2020) and second waves (1st March to 30th June 2021). Results Of 217 children, 104 (48%) and 113 (52%) were admitted during the frst and second waves respectively. One hundred ffty-two (70%) had incidentally detected SARS-CoV-2 infection, while 65 (30%) had symptomatic COVID-19. Comorbidities were noted in 137 (63%) children. Fifty-nine (27%) and 66 (30%) children required high-dependency unit (HDU) and ICU care respectively. Severity of infection and ICU needs were similar during both waves. High-fow oxygen (n=5, 2%), noninvasive ventilation [CPAP (n=34, 16%) and BiPAP (n=8, 5%)] and invasive ventilation (n=45, 21%) were respiratory support therapies needed. NIV use was more during the second wave (26% vs. 13%; p=0.02). The median (IQR) length (days) of DCH stay among survivors was longer during the frst wave [8 (6–10) vs. 5.5 (3–8); p=0.0001]. Conclusions Disease severity, associated comorbidities, PICU and organ support need and mortality were similar in the frst and second waves of the pandemic. Children admitted during the second wave were younger, had higher proportion of NIV use and shorter length of COVID-19 hospital stay.

Network pharmacology and molecular docking study of the active ingredients in Saptasaram kashayam for the treatment of Polycystic ovary syndrome-Supplemenntary data

Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.

Network pharmacology and molecular docking study of the active ingredients in Saptasaram kashayam for the treatment of Polycystic ovary syndrome

Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.

Comparison of prevention of parent-to-child HIV transmission programme & national biennial HIV sentinel surveillance data for tracking HIV epidemic in India

Background & objectives: HIV sentinel surveillance (HSS) among antenatal women in India has been used to track the epidemic for many years. However, reliable tracking at the local level is not possible as ANC sentinel sites are limited in number and cover a smaller sample size at each site. Prevention of parent-to-child-transmission (PPTCT) programme data has a potential advantage due to better geographical coverage, which could provide more precise HIV case estimates; therefore, we compared HSS ANC data with PPTCT programme data for HIV tracking. Methods: Out of the 499 surveillance sites, where HSS and PPTCT programme was being conducted in 2015, 210 sites (140 urban and 70 rural) were selected using a stratified random sampling method. HSS (n=72,981) and PPTCT (n=112,832) data records were linked confidentially. The sociodemographic characteristics of HSS and PPTCT attendees were compared. HIV prevalence from HSS ANC was compared with the PPTCT programme data using Chi-square test. State- and site-level correlation of HIV prevalence was also done. Concordance between HSS and PPTCT HIV positivity was estimated using kappa statistics. Results: The age distribution of HSS and PPTCT attendees was similar (range: 23 to 27 yr); however, HSS ANC participants were better educated, whereas PPTCT recorded a higher proportion of homemakers. The correlation of HIV prevalence between HSS and PPTCT was high (r=0.9) at the State level and moderate at the site level (r=0.7). The HIV positivity agreement between HSS ANC and PPTCT was good (kappa=0.633). A similar prevalence was reported across 26 States, whereas PPTCT had a significantly lower prevalence than HSS in three States where PPTCT coverage was low. Overall HIV prevalence was 0.31 per cent in HSS and 0.22 per cent in PPTCT (P<0.001). Interpretation & conclusions: High-quality PPTCT programme data can provide reliable HIV trends in India. An operational framework for PPTCT-based surveillance should be pilot-tested in a phased manner before replacing HSS with PPTCT.

Symptoms and psychosocial effects following hospitalization for Covid-19: A sequential, mixed-methods study from northern India

BACKGROUND It is reported that patients who have recovered from Covid-19 continue to experience various symptoms and adverse outcomes. However, this aspect has not been studied well. We aimed to evaluate these variables and the perceived impact of Covid-19 among patients discharged from a Covid hospital in northern India. METHODS We conducted this study among patients discharged from a Covid-19 hospital in northern India in June 2020. As per the official policy at that time, patients detected to have Covid-19 (symptomatically or via contact tracing) were mandatorily admitted. A sequential, mixed-methods design was followed. Patients discharged from the hospital were contacted telephonically, and the cross-sectional prevalence of symptoms, the prevalence of depression and anxiety and the social consequences of admission were assessed. A subgroup of patients was interviewed for qualitative assessment of their experience. RESULTS A total of 274 patients provided consent and were assessed, of which 8 patients underwent detailed interviews. The prevalence of somatic symptoms was 3.4%; 36.2% of the patients had depressive and 12% of the patients had anxiety symptoms. A majority of patients experienced adverse social and economic consequences of hospitalization for Covid-19. These themes were reinforced by a qualitative analysis of in-depth interviews. CONCLUSIONS Our study population experienced a high prevalence of adverse psychosocial consequences of Covid-19. These included depression and anxiety symptoms, stigma and economic and occupational consequences. These deserve more recognition and study.

Association of Birth Weight with Risk Factors of Cardiovascular Diseases: A Birth Cohort Analysis from a Rural Area of Northern India

Background: Fetal origin of cardiovascular diseases (CVD) hypothesis has been explored mostly in retrospective studies. Objectives: A prospective study was conducted to find the association of birth weight with CVD risk factors. Methods: A cohort of 243 babies born in 1992–1993 in ten villages of Raipur Rani Block in India, were followed?up in 2016–2017. WHO STEPS methods were used to assess the risk factors of CVDs. A total of 213 (87.8%) participants were examined; blood samples were collected from 207. Multivariable regression analysis was done to adjust for the confounding variables. Results: Study participants were 22–24 year old, 27.7% were exposed to tobacco and 24.8% consumed alcohol, 3.3% were taking >5 servings of fruits and vegetables per day, 35.7% were physically inactive, 28.6% were overweight (body mass index [BMI] ?23 kg/m2 ), 12.2% had hypertension, 16% had high cholesterol (?200 mg/dl), 16.4% had insulin resistance (IR) (Homeostatic Model Assessment?IR >3), and 20.7% were born with low birth weight (<2.5 kg). Multivariable regression analysis revealed inverse relationship between birth weight and systolic blood pressure (regression coefficient ?3.72 mmHg, 95% confidence interval ?7.249; ?0.183, P < 0.05). Conclusion: Birth weight has inverse relationship with blood pressure. Effect of birth weight on CVDs should also be studied in future follow?ups.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Cost of National Vector Borne Disease Control Programme in North India

Background & objectives: Despite significant resources being spent on National Vector Borne Disease Control Programme (NVBDCP), there are meagre published data on health system cost upon its implementation. Hence, the present study estimated the annual and unit cost of different services delivered under NVBDCP in North India. Methodology: Economic cost of implementing NVBDCP was estimated based on data collected from three North Indian States, i.e. Punjab, Haryana and Himachal Pradesh. Multistage stratified random sampling was used for selecting health facilities across each level [i.e. subcentres (SCs), Primary Health Centres (PHCs), community health centres (CHCs) and district malaria office (DMO)] from the selected States. Data on annual consumption of both capital and recurrent resources were assessed from each of the selected facilities following bottom-up costing approach. Capital items (equipment, vehicles and furniture) were annualized over average life span using a discount rate of 3 per cent. The mean annual cost of implementation of NVBDCP was estimated for each level along with unit cost. Results: The mean annual cost of implementing NVBDCP at the level of SC, PHC and CHC and DMO was ? 230,420 (199,523-264,901), 686,962 (482,637-886,313), 1.2 million (0.9-1.5 million) and 9.1 million (4.6-13.5 million), respectively. Per capita cost for the provision of complete package of services under NVBDCP was ? 45 (37-54), 48 (29-73), 10 (6-14) and 47 (31-62) at the level of SC, PHC, CHC and DMO level, respectively. The per capita cost was higher in Himachal Pradesh (HP) at SC [? 69 (52-85)] and CHC [? 20.8 (20.7-20.8)] level and in Punjab at PHC level [? 89 (49-132)] as compared to other States. Interpretation & conclusions: The evidence on cost of NVBDCP can be used to undertake future economic evaluations which could serve as a basis for allocating resources efficiently, policy development as well as future planning for scale up of services.

Cytotoxic effect of transdermal invasomal anastrozole gel on MCF-7 breast cancer cell line

Introduction: Anastrozole is an anti-cancer drug, an effective aromatase inhibitor for the treatment of breast cancerin post-menopausal women. As it undergoes extensive first-pass metabolism and has many side effects related to oraluse, it has been envisaged to develop anastrozole invasomes in the form of transdermal gel.Objective: The objective of this work was to prepare, characterize, and evaluate invasomal gel of anastrozole.Materials and Methods: Invasomes were prepared by thin layer film hydration method using Phospholipon 80H,fenchone (terpene), and ethanol. The optimized invasomes were incorporated into sodium carboxy methyl cellulosegel. Prepared formulations were evaluated and cytotoxic study on Michigan cancer foundation (MCF)-7 cancer cellline was studied.Results and Discussion: The scanning electron microscope results of the optimized formulation showed sphericalshaped vesicles.The ex vivo permeation of invasomes and the skin deposition (73%) were studied on male Wistar ratskin. Cell line studies on MCF-7 cells showed cytotoxic effect of optimized formulation at 5 µl/ml.Conclusion: It was concluded that the developed anastrozole invasomes enhanced the transdermal flux and theresults obtained encouraged the use of the anastrozole invasomal gel for the potential treatment of breast cancer inpost-menopausal women.

Cytotoxic effect of transdermal invasomal anastrozole gel on MCF-7 breast cancer cell line

Introduction: Anastrozole is an anti-cancer drug, an effective aromatase inhibitor for the treatment of breast cancerin post-menopausal women. As it undergoes extensive first-pass metabolism and has many side effects related to oraluse, it has been envisaged to develop anastrozole invasomes in the form of transdermal gel.Objective: The objective of this work was to prepare, characterize, and evaluate invasomal gel of anastrozole.Materials and Methods: Invasomes were prepared by thin layer film hydration method using Phospholipon 80H,fenchone (terpene), and ethanol. The optimized invasomes were incorporated into sodium carboxy methyl cellulosegel. Prepared formulations were evaluated and cytotoxic study on Michigan cancer foundation (MCF)-7 cancer cellline was studied.Results and Discussion: The scanning electron microscope results of the optimized formulation showed sphericalshaped vesicles.The ex vivo permeation of invasomes and the skin deposition (73%) were studied on male Wistar ratskin. Cell line studies on MCF-7 cells showed cytotoxic effect of optimized formulation at 5 µl/ml.Conclusion: It was concluded that the developed anastrozole invasomes enhanced the transdermal flux and theresults obtained encouraged the use of the anastrozole invasomal gel for the potential treatment of breast cancer inpost-menopausal women

Social capital as a mediator of the influence of socioeconomic position on health: Findings from a population-based cross-sectional study in Chandigarh, India

Background: Social capital has been recognized as part of the WHO's Social Determinants of Health model given that social connections and relationships may serve as resources of information and tangible support. While the association between socioeconomic position and health is relatively well established, scant empirical research has been conducted in developing countries on the association between social capital and health. Objective: Based on the WHO's Social Determinants of Health framework, we tested whether social capital mediates the effect of socioeconomic position on mental and physical health. Methods: A population-based study was conducted among a representative sample (n = 1563) of men and women in Chandigarh, India. We used standardized scales for measuring social capital (mediator variable) and self-rated mental and physical health (outcome variable). Results: A socioeconomic position index (independent variable) was computed from education, occupation, and caste categories. Mediation model was tested using path analysis in IBM SPSS-Amos. Participants' mean age was 40.1 years. About half of the participants were women (49.3%), and most were relatively well educated. The results showed that socioeconomic position was a significant predictor of physical and mental health. Social capital was a significant mediator of the effect of socioeconomic position on mental health but not physical health. Conclusion: Besides removing socioeconomic barriers through poverty alleviation programs, interventions to improve social capital, especially in economically disadvantaged communities, may help in improving population health.

Novel core in cup (In-lay) tablets of lamotrigine for mucoadhesive drug delivery system.

Lamotrigine a BCS class II drug used in treatment of epilepsy has several disadvantages when taken orally (first pass metabolism and increased Cmax). The aim of the study is to design core in cup (In lay) buccoadhesive tablets which aims for controlled, unidirectional release, increased patient compliance and decreased side effects. The present study involves the preparation of core in cup tablets containing release retarding polymers like sodium alginate, xanthan gum and HPMC E 15LV in core and HPMC K 15M in cup for mucoadhesion. L9 orthogonal array Taguchi design was constructed for the study. The dependent variable studied for L9 orthogonal array Taguchi runs include % drug release from which the formulation with highest S/N ratio was optimized. All the runs were evaluated for physical parameters, drug release, mucoadhesive studies and assay. L1, L2, L4 and L8 formulations showed controlled release for up-to 8 hours with good assay values. The model dependent kinetics showed zero order kinetics with super case II transport and Hixson Crowell mechanism which indicates unidirectional drug release.

Design and Optimization of Hydrodynamically Balanced Oral In situ Gel of Glipizide.

Objective: The purpose of the present investigation was to formulate hydrodynamically balanced oral In situ gel of glipizide inorder to increase the gastric residence time and to modulate the release behavior of the drug. Material and method: In situgel formulations were prepared by using different concentrations of sodium alginate, calcium carbonate, trisodium citrate and release retardant polymers. pH triggered ionic gelation is the mechanism involved in the present study. Taguchi L9 OA experimental design was employed for the optimization of formulations. All the formulations were subjected to various evaluation parameters. Results: Formulation F9 containing 3% of sodium alginate, 1.0 % of CaCO3, 0.2% of trisodium citrate and 0.5% of HPMC-K100M was selected as optimized batch based on Q12 58.26%, floating time 47.76 sec and drug content 98.2%. The release pattern of drug was found to follow first order. The value of ‘n’ from Korsemeyer equation was found to be 1.00 indicating the drug release by supercase II. The DSC study revealed that there was no incompatibility. Gastroretentive X-ray imaging study on Albino rabbit demonstrated that it was able to float in the stomach for more than 8hrs. Pharmacodynamic study on Wistar rats demonstrated significant hypoglycaemic activity of the optimized formulation. Conclusion: It was concluded that the hydrodynamically balanced oral In situ gel of glipizide could be an effective dosage form which remains buoyant and sustain the drug release for 24hrs.

Bacterial profile of blood stream infections and their antibiograms.

Background: Blood culture provides essential information for the evaluation of a variety of diseases like endocarditis, pneumonia, and pyrexia of unknown origin particularly, in patients with suspected sepsis. Septicaemia is one of the leading causes of neonatal mortality along with perinatal hypoxia. Objectives: To study the bacterial flora of blood stream infections in adults & pediatric patients including neonates. To study the risk factors and duration of incubation for obtaining positive cultures. To study their antibiotic resistant pattern and compare results with those of other investigators in this field. Methods: This prospective study was conducted in the department of microbiology, Narayana medical college and hospital, Nellore over a period of six months, from March 2014 to September 2014. During the six months period, 200 samples received from various departments were processed and relevant findings were noted. Results: Out of 200 blood samples growth was obtained in 34 samples (17%). Among them Gram positive bacteria were 11 (5.5%). Gram negative bacilli were 23 (11.6%). Among the gram positive bacteria maximum resistance was seen with methicillin and imipenum. No resistance was seen with vancomycin and erythromycin. Most of gram negative bacilli were multidrug resistant. Maximum resistance was seen with piperacillin, amikacin, ceftizoxime and amoxyclav. Conclusion: Early diagnosis & appropriate treatment of bacterial infections can make difference between life & death. It would reduce mortality from septicaemia, reduce time & improve patient management.

Effect of synthetic super disintegrants and natural polymers in the preparation of donepezil hydrochloride fast disintegration films.

The main aim of the present research was to develop a fast dissolving oral polymeric film with good mechanical properties, faster disintegration and dissolution when placed on tongue. Donepezil hydrochloride (DPH) is prescribed in the treatment of mild to moderate Alzheimer’s disease (AD). The polymers selected for preparing films were sodium alginate (SA), poly vinyl alcohol (PVA) and guar gum (GG). Three batches of films were prepared by solvent casting method with sodium alginate, sodium alginate & PVA and with the combination of sodium alginate & guar gum. From these three batches, three optimized film formulations S3, SP7 and SG8 were selected based on disintegration time. To these three selected film formulations, superdisintegrants sodium starch glycolate (SSG), cross carmellose sodium (CCS) and cross povidone (CP) were added at a concentration of 4% w/w of polymer to improve the disintegration time. The films prepared with or without superdisintegrants were compared for fast releasing properties. Based on DT and in vitro dissolution data, S3CP was selected as the best formulation among the all formulations.

Reproducibility and validity of a quantitative food frequency questionnaire in an urban and rural area of northern India.

Background. Food frequency questionnaires (FFQs) have been used in epidemiological studies across the world to capture the usual food intake of individuals. As food habits vary in different population groups, FFQs should be validated before use. Hence, we determined the reproducibility and validity of FFQs designed for urban and rural populations of northern India. Methods. Separate FFQs, designed for urban and rural populations using standard methods, were administered to a sample of 200 subjects (100 urban and 100 rural) in the age group of 35–70 years in the beginning (baseline FFQ) of the study and after an interval of 1 year (1-year FFQ) to assess their reproducibility. Six 24-hour dietary-recalls, taken at an interval of 2 months over a period of 1 year, were used as a reference method to test the validity. Crude and energyadjusted nutrient intakes estimated from FFQs and 24-hour dietary-recalls were compared using Pearson correlation coefficients. Bland and Altman plots were also used to test the agreement between the two methods. Results. Nutrient intakes were found to be similar at the baseline and 1-year FFQs in urban and rural areas. The unadjusted Pearson correlation between 24-hour dietaryrecalls and 1-year FFQ ranged from 0.22 for vitamin C to 0.63 for iron in the urban area. It ranged from 0.06 for vitamin C to 0.74 for energy in the rural area. The correlations lowered after adjusting for energy and there was a minimal increase after de-attenuation. Conclusion. The FFQs were reproducible and valid for assessing nutrient intakes except for some micronutrients.

Effect of synthetic super disintegrants and natural polymers in the preparation of donepezil hydrochloride fast disintegration films.

The main aim of the present research was to develop a fast dissolving oral polymeric film with good mechanical properties, faster disintegration and dissolution when placed on tongue. Donepezil hydrochloride (DPH) is prescribed in the treatment of mild to moderate Alzheimer’s disease (AD). The polymers selected for preparing films were sodium alginate (SA), poly vinyl alcohol (PVA) and guar gum (GG). Three batches of films were prepared by solvent casting method with sodium alginate, sodium alginate & PVA and with the combination of sodium alginate & guar gum. From these three batches, three optimized film formulations S3, SP7 and SG8 were selected based on disintegration time. To these three selected film formulations, superdisintegrants sodium starch glycolate (SSG), cross carmellose sodium (CCS) and cross povidone (CP) were added at a concentration of 4% w/w of polymer to improve the disintegration time. The films prepared with or without superdisintegrants were compared for fast releasing properties. Based on DT and in vitro dissolution data, S3CP was selected as the best formulation among the all formulations.

Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

Purpose The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT) transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24) was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2). Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5%) and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1) was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder. .

Development of ethosomes with taguchi robust design-based studies for transdermal delivery of alfuzosin hydrochloride.

In the present investigation efficiency of ethosomes as novel lipid carriers for transdermal delivery of Alfuzosin Hydrochloride (AH) has been evaluated. Taguchi robust design method was used for optimization of ethosomal formulations. Phospholipid type, concentration of phospholipid and concentration of ethanol was selected as independent variables and their effect on the dependent variables (entrapment efficiency and flux) was studied. Ethosomal formulation (EA8) with soya phosphatidylcholine (3%) and ethanol 20% were optimized. Vesicles were spherical, unilamellar with smooth surface. The optimized formulation exhibited vesicle size (6.85 ± 1.35μm), zeta potential (-8.14 ± 0.62mv), entrapment efficiency (91.86 ± 3.25%), flux (27.42 ± 0.04μg/cm2/hr), lag time (0.26±0.20hr) and skin deposition (298.01 ± 15.4μg/g). Transdermal flux was enhanced by 6.92 times over drug solution. Vesicle skin interaction studies showed fatty change in the dermis. The formulations were stable at 4°C for 120 days. Results suggested ethosomes as efficient carriers for AH transdermal delivery.

Correlation of p53 and KI-67 expression with grade and subtype of ependymoma.

Introduction: The morphological criteria for grading ependymomas were always felt subjective. Recently some studies have showed that Ki-67 and p53 immunolabeling are important prognostic markers in ependymomas. Materials and Methods: All the cases of ependymomas diagnosed from 2005 to 2010 were graded according to WHO classification for central nervous system (CNS) tumors 2007. Two tissue microarray (TMA) blocks were prepared. Immunohistochemical analysis with glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), Ki-67 and p53 was performed. The difference in expression of p53 and Ki-67 in various tumor grades and subtypes was evaluated using Student's t test. Results: There were 54 cases with a M: F ratio of 1.34 : 1, age ranging from 7 years to 65 years (mean 29.35 years). There were 33 intracranial and 21 spinal cases. There were 9 grade I ependymomas, 32 grade II ependymomas and 13 grade III ependymomas. GFAP immunopositivity was seen in all the cases and EMA was positive in 49% cases. The mean p53 indices were higher in grade III and grade II tumors (26.26% and 26.08%) as compared to subependymomas (7.25%). But these values did not show statistical significance (P = 0.2). The Ki-67 labeling index increased from grade I to grade III tumors. The difference was highly significant between grade II and grade III (0.5% vs. 2.75, P = 0.016). Conclusion: Ki-67 labeling index correlates with grade of ependymoma (P = 0.016). There is no correlation between p53 expression and grade of ependymomas.