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   Table of Contents - Current issue
Coverpage
January-March 2021
Volume 11 | Issue 1
Page Nos. 1-93

Online since Friday, February 12, 2021

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EDITORIAL  

Trends and Determinants of Mental Health During COVID-19 Pandemic: Implications and Strategies to Overcome the Mental Health Issues - A Rapid Review from 2019-2020 p. 1
Golden Catherine Thangaswamy, Judie Arulappan, Sudhakar Anumanthan, Sathish Kumar Jayapal
DOI:10.4103/ijnpnd.ijnpnd_86_20  
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REVIEW ARTICLES Top

Biosimilars: An Update p. 7
Saravanan Bhojaraj, Thirumoorthy Durai Ananda Kumar, Abhinav Raj Ghosh, BS Sushmitha, Srinivasan Ramamurthy, Thirunavukkarasu Velusamy, Thiyagarajan Ramesh, MK Jayanthi, Musthafa Mohamed Essa, Saravana Babu Chidambaram, M. Walid Qoronfleh
DOI:10.4103/ijnpnd.ijnpnd_96_20  
Biologics are medicines primarily derived from living systems and produced through recombinant DNA (rDNA) and monoclonal technologies. Generic version of biologics with improved efficacy and safety is called biosimilar. Patent and copyright expiration of biological products permits the entry of biosimilars. Synthesis of biosimilars involves two main processes, such as monoclonal antibodies and rDNA technology, and characterized by various methods such as posttranslational modification, mass spectrometry, peptide mapping, three-dimensional (high-order) structure, X-ray crystallography, ion mobility spectrometry, and hydrogen deuterium exchange mass spectrometry. Though both generic and biosimilar products follow the same regulatory approval, the requirements are not the same due to the variability in composition and instability. Hence, it is essential to develop pharmacokinetic and pharmacodynamic data to support the efficacy and safety data on biosimilars. This review summarizes the recent updates on biosimilars, synthesis, characterization, and current market status. Brief information on the role of biosimilars in multiple sclerosis is also provided in the review.
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Sleep and Gonadotrophin Hormones p. 17
Sushmitha Basavapattana Shivalingaiah, Sunanda Tuladhar, Arehally M Mahalakshmi, Prathibha Muthukumar, Sudheer Kumar Yannam, Luay Rashan, Musthafa Mohamed Essa, Surapaneni Krishna Mohan, Vishnu Priya Veeraraghavan, Srinivasa Rao Bolla, Saravana Babu Chidambaram, M. Walid Qoronfleh
DOI:10.4103/ijnpnd.ijnpnd_97_20  
Sleep plays a key role in neuroendocrine functioning and glucose metabolism. Currently existing data reveal that restriction of sleep duration results in adverse health effects. Sleep plays an imperative role in endocrine systems. Sleep causes the episodic secretion of gonadotrophin through modulation of neurotransmitters activity. Research on the significance of sex and gonadotrophic hormone in causing sleep disparities and its effects on cognition among men and women is gaining increased awareness. Epidemiologic, preclinical, and clinical studies have reported that sleep deprivation causes alteration of metabolic endocrine functions, including reduced glucose tolerance, insulin sensitivity, and leptin levels with increased cortisol and ghrelin levels. Men with lesser levels of testosterone and women with elevated levels of progesterone are more susceptible to the effects of sleep restriction on cognition and emotion processing tasks. The present integrative review highlights the effects of sleep deprivation on sex and gonadotrophin hormones and its link to cognitive function.
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COVID-19: A Review of Clinical Trials and Repurposed Drugs p. 27
A Ruckmani, KR Ilamathi, R Arun Kumar, PM Umesh Kumar
DOI:10.4103/ijnpnd.ijnpnd_90_20  
This review was undertaken to synthesize data from various databases on therapeutic clinical trials conducted on COVID- 19 in order to find out the trial details and outcome of the completed trials as well as the rationale for selecting the different trial drugs. The data were obtained from articles published December 2019 to September 4, 2020. The analysis of the data has shown that Corona Virus Disease-19 (COVID-19) is the only disease for which more than 2100 clinical trials have been registered. In these trials many existing drugs like Hydroxychloroquine (HCQ), Remdesivir, Tocilizumab, Sarilumab, Lopinavir/Ritonavir, Favipiravir, Glucocorticoids, COVID-19 convalescent plasma, Mesenchymal stem cells, Interferons, Azithromycin, Ivermectin, traditional medicines and many others are being tested globally for their efficacy in COVID-19. 225 trials have been completed as of September 4, 2020 and the results are available only for a few trials. Out of these results, two have shown favorable outcome for Favipiravir, one for HCQ alone, and one for HCQ + Azithromycin and one for Meplazumab. Topline data of two trials have resulted in the emergency use authorization (EUA) for Remdesivir on May 1, 2020. The available results of NIAD, WHO’s SOLIDARITY, Gilead and RECOVERY trials have not shown the anticipated outcome. The results of the rest of the completed trials are awaited to draw conclusion regarding the definite therapy of COVID-19. The new drug development for COVID-19 is still in its preliminary stage. Identification of potential drug candidates which could selectively inhibit Severe Acute Respiratory Syndrome-Corona Virus 2 (SARS-CoV2) protease (Mpro) and SARS CoV2 S protein is in progress.
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Epigenetic Modifications Due to Childhood Trauma Causative of Potential Mental and Physical Disorders p. 41
J. Megala, Diveyaa Sivakumar, Divya Jha, Soumyadyuti Kundu, Khyati Arora, V. Gayathri
DOI:10.4103/ijnpnd.ijnpnd_74_20  
The early years of life are when brain and behavioral development are most impacted by the environment. Children need to be in a nurturing environment with responsive and sensitive caretakers to ensure normal development. Findings have shown that traumatic events that occur during these stages tend to have lasting effects that extend to adulthood. Epigenetic modifications of the genes and receptors involved in the hypothalamic-pituitary-adrenal (HPA) axis have been shown to be the link between early life adversities (ELAs) and the increased risk of disease in adulthood. In this review, we have discussed the effect of ELAs on child development and its associated disorders in later life. We have also highlighted certain prominent genes involved in the stress response that have been reported to be epigenetically regulated in response to ELAs. As the detrimental mental and physical health consequences of ELAs have been well documented, we have also included reports that validate the hypothesis that ELAs increase the risk of depression and cardiovascular diseases (CVDs) in adulthood. Learning how these epigenetic modifications could occur in early stages, can help us in discovering new therapeutic interventions to reverse these effects by expressing or inhibiting the genes. Also, studying the interrelation between biological and psychological systems will provide an opportunity to improve treatment outcomes.
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ORIGINAL ARTICLES Top

A Novel Herbal Combination Decreased Lipid Droplets Accumulation and Cytokines Levels During Adipogenesis by Regulating Leptin, PPARγ and SREBP1c Genes Expression in 3T3L1 Cells p. 50
Vasavi Rakesh Gorantla, Srinivasa Rao Bolla, Sunanda Tuladhar, Muhammed Bishir, Arehally M Mahalakshmi
DOI:10.4103/ijnpnd.ijnpnd_88_20  
The present study aims at demonstrating the anti-adipogenesis and anti-inflammatory of combination of extracts of commiphora wightti, curcuma longa, and tinospora cordifolia using mouse 3T3-L1 cells. Herbal formula (CCT) significantly suppressed the mRNA of PPARγ, leptin, and SREBP1c expression, which is reveals its significant anti-adipogenesis activity. In addition, CCT down-regulated TNFα and iNOS expression, this is an added advantage and helps to alleviate the inflammatory reactions during adipogenesis. These findings encourage for further studies using in vivo models of obesity and associated complications.
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Machine Learning Approaches for Prognostication of Newly Diagnosed Glioblastoma p. 57
Thara Tunthanathip, Thakul Oearsakul
DOI:10.4103/ijnpnd.ijnpnd_93_20  
Background: Glioblastoma (GBM) is the poorest prognosis in glioma. Although Temozolomide (TMZ) with radiotherapy following tumor resection is currently the standard treatment, the high cost has become an economic burden in a limited-resource setting. In an era of disruptive innovation, machine learning (ML) has been recently performed to be the clinical prediction tool for prognostication, especially GBM. The aim of the study was to assess the predictability of ML algorithms for 2-year survival in patients with GBM. Methods: A retrospective cohort study was performed in patients with GBM. Various clinical, radiological, and treatment variables were collected, and the outcome was a 2-year living status as bi-classifiers. The candidate variables, which had a P<0.1, were performed to train the ML model. For training the ML model, random forest (RF), logistic regression (LR), and support vector machines were used for training the model and testing the predictive performance. Results: There were 190 GBM patients in the cohort. Four candidate variables were used for building the ML model and testing the performance of each algorithm. The LR and RF algorithms had an acceptable performance for predicting a 2-year survival with an area under the receiver operating characteristic curve at 0.82 and 0.81, respectively. Conclusion: ML-based algorithms had an acceptable performance for the prognostication of 2-year survival in GBM patients that could be implicated in real-world practice for selecting patients with a favorable prognosis and developing treatment strategies for resource allocation in a limited-resource setting.
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Dietary Omega-6 to Omega-3 Fatty Acids Ratio is Correlated with High Molecular Weight Adiponectin Level in Indonesian Office Workers p. 64
Helena Fabiani, Ninik Mudjihartini, Wiji Lestari
DOI:10.4103/ijnpnd.ijnpnd_89_20  
Context: Adiponectin is an adipokine that is secreted by adipocytes and acts to prevent obesity and obesity-related disorders. The high ratio of omega-6 to omega-3 fatty acids in modern dietary habits in working-age populations, urban areas in particular, is known to play a role in adiponectin secretion. However, previous studies showed inconclusive results. Aim: The study aims to determine the association of the dietary omega-6 to omega-3 fatty acids ratio with adiponectin levels in office workers in Jakarta, Indonesia. Settings and Design: This cross-sectional study included 55 office workers in East Jakarta, Indonesia. Methods: Data were collected via questionnaire, 3-day food record, anthropometric measurement, and serum collection. Statistical analysis used: Independent t test was applied to assess the relationship between subjects characteristics and dietary intake with high molecular weight adiponectin levels. Association of dietary omega-6/omega-3 fatty acids ratio and adiponectin were evaluated using Pearson correlation test (P < 0.05). Results: There is no statistically significant difference in adiponectin levels based on waist circumference category, as well as categories of physical activity, household income levels, total energy, and total fat intake. Conversely, in female subjects (P = 0.000), subjects with normal body mass index (P = 0.000), higher education levels (P = 0.031), and nonsmoking subjects (P = 0.019), significantly higher adiponectin levels are obtained. The ratio of dietary omega-6/omega-3 fatty acids is negatively correlated with adiponectin (P = 0.004, r = –0.383). Conclusions: The decrease in the ratio of omega-6/omega-3 fatty acids is inversely related to higher level of adiponectin, indicating that dietary changes may potentially play a role in prevention strategies for obesity and obesity-related diseases.
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Antioxidant and Antitumor Properties of Wild Blueberry (Sideroxylon mascatense): Effects of Drying Methods p. 71
Shaima Al Hasani, Zahir Humaid Al-Attabi, Mostafa Waly, Mohammad Shafiur Rahman, Yahya Tamimi
DOI:10.4103/ijnpnd.ijnpnd_76_20  
Background: Sideroxylon mascatense is a wild blueberry plant that traditionally known as “boot” in Oman. Studies on health beneficial effects of this fruit are very limited. Aims and Objectives: This study aimed to evaluate the antioxidant and antitumor properties of Sideroxylon mascatense under different drying methods. Materials and Methods: Freeze (−20°C) and air drying (60 and 90°C) methods were used. The antioxidant potential properties were evaluated using DPPH and ABTS assay. Moreover, the antitumor activities of blueberry extracts were determined using Alamar blue assay. Results: The results of this study revealed that a blueberry extract at 20 mg powder/mL provided the maximum amount of vitamin C, reaching a value of 19.45 mg/100 g dry-basis in the flesh dried at 60°C and 14.24 mg/100 g dry-basis in seed dried at 90°C. The freeze-dried blueberry exhibited the highest percentage of free radical scavenging activity (DPPH) from both fruit flesh (50.8%) and seeds (39.4%) at a concentration of 20 mg/mL indicating a higher antioxidant activity. There was no significant difference in the ability of blueberry extracts to scavenge radical cations (ABTS+) at various concentrations of extracts. However, there was a 40% reduction of ABTS+ radical formation in blueberry flesh extracts obtained from freeze-dried berry at a concentration of 20 mg/mL. On the other hand, blueberry seeds showed variation in the scavenging activity of the ABTS+ radical of 38% after different processing methods. Breast MCF7 and ovarian Ov2008 tumor cell lines were the most sensitive to the dried blueberry. The 50% growth inhibition (IC50) of the freeze-dried blueberry extract at both cell lines was 64 and 69 μg/mL, respectively. Conclusion: Our findings indicated a potent antioxidant activity of Sideroxylon mascatense, but further research is required to isolate the active compounds in the fruit and test their effects in an experimental animal model.
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HHOM-051608 A Whey Protein Formulation Fortified with Herbal Actives Improves Exercise Performance and Muscle Strength: A Preclinical Study p. 80
Kamlesh K Vishwakarma, Madan M Narendra, Mohammed M Azeemuddin, Poornima Shankar, Prathibha Babshet, Mohamed Rafiq, Uddagiri V Babu
DOI:10.4103/ijnpnd.ijnpnd_50_20  
Context: The lifestyle of individuals is changing rapidly in today’s world and physical fitness is an essential requirement to keep oneself fit and healthy. Nutritional supplements could improve physical fitness by modulating energy metabolism, oxidative processes, and perceived fatigue. Aim: This study aimed to evaluate the effects of HHOM-051608, which is a first-of-its-kind whey protein supplement, packed with naturally rich essential amino acids and herbal ingredients to improve the exercise performance, energy metabolism, and physical endurance. Setting and study design: Thirty-two male Wistar rats were divided into four groups of eight each. Group 1 served as sedentary control; group 2 was sedentary rats treated with HHOM-051608 (2 g/kg b.w.); group 3 was exercise training control, and group 4 was exercise training rat treated with HHOM-051608 (2g/kg b.w.). Methods: The exercise training rats were trained on a motorized rat treadmill at a constant speed for 8 weeks. After 8 weeks, all animals were subjected to a grip strength test followed by a treadmill endurance test. Statistical analysis: The results were statistically analyzed by one-way analysis of variance followed by Tukey comparison test, using Prism GraphPad 6.07 (GraphPad Software Inc, San Diego, CA, USA). A P value < 0.05 was considered statistically significant. Results: HHOM-051608 supplemented animals showed a significant increase in grip strength and run time on the treadmill. Conclusion: HHOM-051608 has improved the exercise performance, muscle strength, and muscle glycogen. Thus can be recommended to enhance exercise performance, build muscle mass and decrease muscle soreness.
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Biochemical Assessment of Hyperhomocysteinemia-Mediated Oxidative Stress in Coronary Artery Disease Patients: A Hospital-Based Cross-Sectional Study p. 88
Kouthar Sulaiman Saif Al-Alawi, Mostafa I Waly, Muhammad Athar Sadiq, Ruqaiya Moosa Al Balushi, Amanat Ali
DOI:10.4103/ijnpnd.ijnpnd_71_20  
This study aimed to assess the status of B-vitamins (folate, vitamin B6, and B12) and homocysteine (HCY) in the sera of Omani coronary artery disease (CAD) patients. Sixteen Omani patients (10 males and 6 females) gave consent for blood sampling and were enrolled in the study on voluntary basis. All patients were evaluated for their anthropometric and biochemical measurements of B-vitamins, glutathione (reduced and oxidized), HCY, and quantification of N-homocysteinylated albumin protein. It was observed that both male and female patients had a comparable age (57.64 ±9.86, 56.5 ±10.04 years, respectively) with no significant difference, P = 0.69 and both genders were obese based on their body mass index (31.22 ± 8.17 kg/m2 for males and 30.26 ± 4.70 kg/m2for females). Serum levels of folate, vitamins B6, and B12 were lower than the normal reference values in all the study participants. There was depletion in glutathione levels (higher level of oxidized glutathione versus lower level of reduced glutathione) in the sera of all study participants. High serum HCY levels in both males and females (75.81±9.21 and 68.66±8.1 μmol/L, respectively) suggest that both males and females had hyperhomocysteinemia. Correlation coefficient analysis revealed that the serum HCY levels were negatively correlated with serum reduced glutathione, folic acid, vitamins B6, and B12 levels in both male and female study participants. The serum HCY level was positively correlated with age, body mass index, and serum oxidized glutathione. Proteomic measurements of N-homocysteinylation in serum albumin revealed that N-homocysteinylated albumin was present in all the assayed serum samples of study participants. The results suggest that low serum status of B-vitamins might act as a metabolic trigger for the observed hyperhomocysteinemia, oxidative stress, and pathological formation of N-homocysteinylated albumin protein, which collectively aggravates the CAD risk in the studied Omani patients.
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