Enhancement of solubility and release profile of simvastatin by co-crystallization with citric acid

Purpose: To enhance the solubility and dissolution profile of simvastatin (SIM) via co-crystallization with varying levels of citric acid using various techniques. Method: Simvastatin-citric acid (SIM-CA) co-crystals were prepared using dry grinding, slurry, liquidassisted grinding, and solvent evaporation techniques, and their various properties were compared. A total of twelve formulations (CC01 to CC12) were prepared. Optimized formulations were selected on the basis of dissolution profiles. Flow properties were evaluated using micromeritic analysis, yielding angle of repose, Carr’s index and Hausner’s ratio. Zeta sizer was employed to evaluate particle size distribution, while surface morphology was determined using scanning electron microscopy (SEM). Melting temperature, stability and physical interaction of simvastatin-citric acid co-crystals were determined by thermal analysis and FTIR. The crystalline nature of the co-crystals was evaluated by powder x-ray diffraction analysis, while solubility and dissolution studies were performed to determine in vitro drug release behavior. Results: Micromeritic analysis revealed good flow properties of SIM-CA co-crystals. Results of Zeta sizer analysis showed that the particle sizes of the co-crystals were in the nanometer range, while SEM revealed that the co-crystals had regular cubical shape. Thermal stability studies with TGA and DSC showed that the co-crystals were stable at temperatures exceeding 400 oC. FTIR results revealed minor shifts in 2956 and 1706 cm-1 peaks. Co-crystal formation was confirmed by PXRD data. The drug release profiles of the optimized formulations (CC02, CC07 and CC11) were 11.36 - 94.46, 12.36 - 95.46 and 13.36 - 96.46 %, respectively. There was significant improvement in solubilities of the optimum formulations, with values of 310.18, 427.21 and 522.02 % for CC02, CC07 and CC11, respectively. Conclusion: Citric acid improves the solubility and dissolution profile of the poorly water-soluble drug, simvastatin, which suggests that co-crystallization can potentially enhance the bioavailability of the drug

Study to assess the patterns of hypertension and factors influencing hypertension in chronic kidney disease

Background: A large proportion of CKD patients have inadequate BP control, and the proportions vary from studies to studies. Clinic BP is considered insufficient to diagnose HTN and monitor overall BP control because it does not correlate well with ambulatory blood pressure monitoring (ABPM), which encompasses white-coat or masked HTN. CKD is associated not only with an abnormal dipping pattern but also with white-coat or masked HTN. Objective of this study was to evaluate the factors influencing the blood pressure in chronic kidney disease patients. Methods: A cross sectional study was conducted at a tertiary hospital in South India from 1st of January 2016 to 31st of July 2017. A total of 124 cases were included in the study. Results: Among subjects with controlled HTN, 31.4% were overweight and 5.7% were Obese. Among Stage 3 CKD subjects, 53.7% had controlled HTN, 12.2% had masked HTN, 12.2% had persistent HTN. We reported that among those with proteinuria 2+, 38.5% had controlled HTN, 11.5% had masked HTN, 19.2% had persistent HTN and 30.8% had white coat HTN. In the study among diabetics, 17.5% had controlled HTN, 36.8% had masked HTN, 43.9% had persistent HTN and 1.8% had white coat HTN. Conclusions: Stage of CKD, diabetes mellitus and proteinuria are determinants of hypertension in CKD patients. ABPM is the best method to monitor BP and hence in the proper management of HTN and in prevention of target organ damage in CKD patients

Vitamin D Deficiency in HCV Antiviral Treatment Responders versus Non-Responders

Background: Hepatitis C virus (HCV) is a major cause of chronic liver disease (CLD). Pakistan has a high burden of infectious diseases, including HCV. Its prevalence varies according to geographic regions in the country from about 2·4% to 6·5%. The objective of the study was to compare the frequency of vitamin D deficiency in responders and non-responders of antiviral treatment for chronic hepatitis C.Material and Methods: This comparative cross-sectional study was conducted in Hepatitis Clinic, Jinnah hospital, Lahore from 20th May to 20th November 2013. After ethical approval, participants were selected by using purposive non-probability sampling, 52 responder patients i.e. who were labeled negative for HCV RNA by PCR after 12 weeks of antiviral treatment and 52 non-responder patients were included in this study. Data was collected by using pretested structured questionnaire. Vitamin D3 levels were measured by ELISA and a cut-off value of below 30ng/ml was labeled as Vitamin D deficiency. SPSS version 21 was used to analyze data with p value less than 0.05 taken as statistically significant.Results: Out of 104 patients (mean age 35±8.1 years), 61.5% were males and 38.5 % were females. There was a significant difference in frequency of vitamin D deficiency in treatment responder group when compared to non-responders (p = 0.016). Mean level of vitamin D was 21.8±10.8ng/ml in responders whereas it was 15.6±7.5 in non-responders with a statistically significant difference (p = 0.001).Conclusion: This study concludes that there is a significant vitamin D deficiency among treatment non-responders as compared to treatment responders in patients with chronic hepatitis C

Mental health conceptualization and resilience factors in the Kalasha youth: An indigenous ethnic and religious minority community in Pakistan

The Kalasha are a religious, ethnic, and linguistic minority community in Pakistan. They are indigenous people living in remote valleys of the Hindu Kush Mountains in northern Pakistan, neighboring Afghanistan. The Kalasha are pastoral, as well as agricultural people to some extent, although they are increasingly facing pressures from globalization and social change, which may be influencing youth and community development. Their traditional world view dichotomizes and emphasizes on the division of the pure (Onjeshta) and the impure (Pragata). There remains a scarcity of literature on mental health and resilience of indigenous communities in South Asia and Pakistan generally, and the polytheistic Kalasha community specifically. Thus, the current study was conducted with the aim to explore the cultural protective factors (resilience) of the Kalasha youth (adolescents and emerging adults) and to explore their perceived etiological understandings and preferred interventions for mental health support systems. The theoretical framework of Bronfenbrenner's (1, 2) ecological systems model was used. Interpretative Phenomenological Analysis (IPA) was conducted, considering the advantage of its idiographic approach and the “double hermeneutic” analytic process. This methodology was consistent with the aim to understand and make sense of mental health and resilience from the Kalasha indigenous perspective. A total of 12 in-depth interviews were conducted with adolescents and emerging adults (5 males, 7 females), along with ethnographic observations. The analysis revealed 3 superordinate themes of mental health perceptions and interventions, each with more specific emergent themes: (1) Psychological Resilience/Cultural Protective Factors Buffering Against Mental Health Problems (Intra-Communal Bonding & Sharing; Kalasha Festivals & Traditions; Purity Concept; Behavioral Practice of Happiness and Cognitive Patterns); (2) Perceived Causes of Mental Health Issues (Biological & Psychosocial; Supernatural & Spiritual; Environmental); and (3) Preferred Interventions [Shamanic Treatment; Ta'awiz (Amulets); Communal Sharing & Problem Solving; Medical Treatment; Herbal Methods]. The overall findings point to the need for developing culturally-sensitive and indigenous measures and therapeutic interventions. The findings highlighted the Kalasha cultural practices which may promote resilience. The findings also call for indigenous sources of knowledge to be considered when collaboratively designing public health program

CYTOCHROME P450 CYP1B1*2 GENE AND ITS ASSOCIATION WITH T2D IN TABUK POPULATION, NORTHWESTERN REGION OF SAUDI ARABIA

Objective: Cytochrome P450 1B1 (CYP1B1) is involved in the activation of procarcinogens and steroid metabolism. Genetic variants of CYP1B1are associated with altered catalytic activity and disease phenotypes. The purpose of this study was to investigate the role of CYP1B1 (rs1056827) polymorphism in inducing T2D.Methods: This cross-sectional study enrolled 113 subjects of T2D and 120 controls. DNA was isolated from blood. Genotyping of the rs1056827 wasdone by allele-specific polymerase chain reaction. The frequency of alleles and genotype distribution was compared in T2D cases and healthy controls.Statistical analysis was performed with SPSS, Chi-square, and Fisher exact test. Hardy-Weinberg equilibrium was tested by a χ2 test. The associations between rs1056827 variant genotypes and T2D were estimated by computing the odds ratios and their 95% confidence intervals (CI) from univariate and multivariate logistic regression analysis.Results: A significant association of rs1056827 was found between T2D cases and controls (p<0.0001). When GG genotype was compared with GT genotype a significant association was found with odd ration (OD)0.24 (95% CI: (0.131–0.452) and risk ratio (RR) 0.45 (0.30–0.67) times the risk of T2D heterozygous with the G/T allele (p≤0.0002). In a comparison of GG homozygous with the TT homozygous, there was no significant association with the OD 0.38 (95% CI: (0.02–6.51) RR 0.55(0.13–2.35), p<0.49. When G allele was compared with the T allele a highly significant association with OD 0.54 (95% [CI]: (0.37–0.80) RR 0.75(0.630–0.897) < p≤0.003 suggesting a possible dominant effect of this polymorphism on T2D risk.Conclusion: This result suggests a significant association between rs1056827G>T polymorphism and T2D. This finding is limited due to the smaller sample size and can be validated by large sample size studies

Comparison of clinical outcomes of conventional hemodialysis and online hemodiafiltration

Background: Several studies have suggested that online hemodiafiltration (OL-HDF) may reduce the risk of mortality and improve quality of life of these patients compared with standard hemodialysis. Methods: Forty stable out patients on dialysis (20 patients on hemodialysis and 20 patients on online hemodiafiltration) above age of 18 years and dialysis vintage of more than 3 months were followed up for 18 months. Clinical, biochemical parameters of these patients along with the SF-36 score at baseline and after 18 months of follow up were assessed. Results: At 18 months, statistically significant difference was found between hemodialysis (HD) and OL- HDF groups in erythropoietin dose (p=0.047), urea reduction ratio (p=0.016), Kt/V (p=0.005), hemoglobin (p=0.043), serum albumin (p=0.002), phosphorus (p=0.024), parathyroid hormone (p=0.007), potassium (p=0.007), β2 microglobulin (p=0.002), high sensitive c-reactive protein (p=0.037), and serum bicarbonate levels (p=0.022). We found statistically significant difference in intradialytic complications namely intradialytic hypotension, muscle cramps, simultaneous hypotension and muscle cramps and stoppage of dialysis. In terms of mortality, the difference was not statistically significant (p=0.052). Conclusions: Patients on OL- HDF were having better quality of life than patients on HD. Better solute clearance, anemia control, improved nutritional and Mineral bone disorder parameters were seen in OL-HDF. Less complications during dialysis were seen with OL-HDF. The difference in mortality rate between the HD group and OL- HDF group was not statistically significant

Latent Embedding Feedback and Discriminative Features for Zero-Shot Classification

Zero-shot learning strives to classify unseen categories for which no data is available during training. In the generalized variant, the test samples can further belong to seen or unseen categories. The state-of-the-art relies on Generative Adversarial Networks that synthesize unseen class features by leveraging class-specific semantic embeddings. During training, they generate semantically consistent features, but discard this constraint during feature synthesis and classification. We propose to enforce semantic consistency at all stages of (generalized) zero-shot learning: training, feature synthesis and classification. We first introduce a feedback loop, from a semantic embedding decoder, that iteratively refines the generated features during both the training and feature synthesis stages. The synthesized features together with their corresponding latent embeddings from the decoder are then transformed into discriminative features and utilized during classification to reduce ambiguities among categories. Experiments on (generalized) zero-shot object and action classification reveal the benefit of semantic consistency and iterative feedback, outperforming existing methods on six zero-shot learning benchmarks. Source code at https://github.com/akshitac8/tfvaegan.Comment: Accepted for publication at ECCV 202

ECCV (22) - Latent Embedding Feedback and Discriminative Features for Zero-Shot Classification

Zero-shot learning strives to classify unseen categories for which no data is available during training. In the generalized variant, the test samples can further belong to seen or unseen categories. The state-of-the-art relies on Generative Adversarial Networks that synthesize unseen class features by leveraging class-specific semantic embeddings. During training, they generate semantically consistent features, but discard this constraint during feature synthesis and classification. We propose to enforce semantic consistency at all stages of (generalized) zero-shot learning: training, feature synthesis and classification. We first introduce a feedback loop, from a semantic embedding decoder, that iteratively refines the generated features during both the training and feature synthesis stages. The synthesized features together with their corresponding latent embeddings from the decoder are then transformed into discriminative features and utilized during classification to reduce ambiguities among categories. Experiments on (generalized) zero-shot object and action classification reveal the benefit of semantic consistency and iterative feedback, outperforming existing methods on six zero-shot learning benchmarks. Source code at https://github.com/akshitac8/tfvaegan.Comment: Accepted for publication at ECCV 202

Pharmacists’ Perception of the Sale of Non-Clinically Proven Health Supplements in Penang, Malaysia

Purpose: To explore community pharmacists’ perception of the sale of non-clinically proven health supplements and over-the-counter (OTC) products available in Penang, Malaysia.Methods: A cross-sectional survey using a self-completed postal questionnaire was conducted in July 2010 among 200 community pharmacists practicing in Penang Island.Results: Fifty six pharmacists participated in the study (response rate, 28.0 %). A total of 10.7 % respondents indicated that the sale of non-clinically proven products result in high profit. Only 25.0 % of the pharmacists believed that non-clinically proven OTC products are effective, while 35.7 % thought that it is not ethical to sell these products. A majority of the respondents (94.7 %) agreed that manufacturers’ advertisement have a huge effect on positive consumers’ behaviour towards such products. Most respondents agreed that manufacturers of these products claim that their products are effective (57.1 %) and have fewor no side effects (60.7 %).Conclusions: Pharmacists who participated in the study have mixed  opinions on the efficacy and effectiveness of non-clinically proven products. There is a need for pharmacists to be well educated on the  evidence-based use of these products in order to be able to offerappropriate advice to those who come to them to purchase the items.Keywords: Perception, Health promotion, Urban poor, Health supplements