ADVERSE DRUG REACTIONS IN PEDIATRIC PATIENTS IN A TERTIARY CARE HOSPITAL IN KOLLAM

Objective: Adverse drug reactions have not been as thoroughly studied in children as they have in adults. Extrapolation of efficacy, dosing regimens, and ADRs from adult data are inappropriate owing to developmental changes in physiology and drug handling. There is a lack of local data regarding the potential risk of ADRs in pediatric patients. Objective of this study is to identify the adverse drug reaction (ADR) profile in pediatric patients. Methods: In this cross-sectional study, 450 children attending the pediatric inpatient and outpatient department were selected, and the CDSCO reporting form for suspected ADR reporting forms was collected from those who had any adverse events by the consulting pediatrician. Later, this form was analyzed for the details for ADRs and assessed for causality, severity, and preventability using Naranjo’s algorithm, Hartwig and Siegel scale, and modified Schumock and Thornton scale of adverse drug reactions. Results: The cross-sectional study revealed a prevalence of 12.89%. Antibiotics caused more ADRs than any other group of drugs. Dermatological ADRs were the most common. Most ADRs were not preventable and were of moderate severity. The causality assessment showed that most ADRs were possible category. Conclusion: The ADRs are often unrecognized. We need more strict monitoring for early detection, treatment, and more importantly prevention of these events in the future. For that, more awareness programs, CMEs and teamwork are extremely important among the caregivers

Analytical tools for monitoring changes in physical and chemical properties of chromatography resin upon reuse

Protein A resins are often reused for multiple cycles to improve process economy during mAb purification. Significant reduction in binding capacity and product recovery are typically observed due to the presence of unwanted materials (foulants) deposited on the resin upon reuse. In this paper, we have used a wide spectrum of qualitative and quantitative analytical tools (particle size analysis, HPLC, fluorescence, SEM, MS, and FTIR) to compare the strengths and shortcomings of different analytical tools in terms of their capability to detect the fouling of the resin and relate it to chromatographic cycle performance. While each tool offers an insight into this complex phenomena, fluorescence is the only one that can be used for real‐time monitoring of resin fouling. A correlation could be established between fluorescence intensity and the process performance attributes (like yield or binding capacity) impacted upon resin reuse. This demonstration of the application of fluorescence for real‐time monitoring correlated empirically with process performance attributes and the results support its use as a PAT tool as part of a process control strategy. While the focus of this paper is on fouling of protein A chromatography resin, the approach and strategy are pertinent to other modes of chromatography as well

Chronotherapeutics in Ayurveda

In order to maximize health benefits and minimize adverse effects of a treatment, chronotherapeutics is administered to patients according to his/her daily, monthly, seasonal or yearly biological clock. According to Ayurveda observation of the specific features of disease corresponding to season, day and night, age and meal is known as Kaala Aveksha. The Dasha Bheshaja Kaala (ten different time period for the administration of medicine) is one among the Shadaveksha Kaala (Six observatory aspects of time). It is defined according to the biological clock. The medicines at proper Bheshaja Kaala help to attain the equilibrium of Doshas and Dhatus. Here chronotherapeutics can be correlated with Bheshaja Kaala. As it gives importance to the time of administration which can be responsible for variations of drug kinetics. Objective: To conduct an in-depth analysis of the literature in order to identify and evaluate the evidence base for chronotherapy. Data source: A literature search was conducted in classics of Ayurveda and electronic databases. Result: Review shows that the drug administered according to the Bheshaja kaala has more beneficial outcomes than the other methods. Conclusion: The review presents the scope of chronotherapy in drug administration

Discrete wavelet transform de-noising in eukaryotic gene splicing

<p>Abstract</p> <p>Background</p> <p>This paper compares the most common digital signal processing methods of exon prediction in eukaryotes, and also proposes a technique for noise suppression in exon prediction. The specimen used here which has relevance in medical research, has been taken from the public genomic database - GenBank.</p> <p>Methods</p> <p>Here exon prediction has been done using the digital signal processing methods viz. binary method, EIIP (electron-ion interaction psuedopotential) method and filter methods. Under filter method two filter designs, and two approaches using these two designs have been tried. The discrete wavelet transform has been used for de-noising of the exon plots.</p> <p>Results</p> <p>Results of exon prediction based on the methods mentioned above, which give values closest to the ones found in the NCBI database are given here. The exon plot de-noised using discrete wavelet transform is also given.</p> <p>Conclusion</p> <p>Alterations to the proven methods as done by the authors, improves performance of exon prediction algorithms. Also it has been proven that the discrete wavelet transform is an effective tool for de-noising which can be used with exon prediction algorithms.</p

Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis

\ua9 2024 by the authors.Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient’s circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy

Magnetic structure and field-dependent magnetic phase diagram of Ni2In-type PrCuSi

The magnetic structure of the ternary equiatomic intermetallic compound PrCuSi is investigated using neutron powder diffraction experiments in 0 T as well as in external magnetic fields up to 2 T. The PrCuSi compound crystallizes in the hexagonal Ni2In-type structure, in the space group P63/mmc. In this structure, cationic ordering of Cu and Si takes place. The antiferromagnetic phase transition in the Pr sublattice takes place at K in 0 T. Under an external magnetic field of 2 T, a field-induced ferromagnetic phase is observed. Magnetoelastic coupling is evidenced by an increase in the unit cell volume. Clear signatures of a mixed antiferromagnetic and ferromagnetic phase in weak, intermediate fields, 0.4–0.8 T, are obtained from the present study. Using the present set of experimental data, we construct the H  −  T phase diagram of PrCuSi

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

Lawsone Unleashed: A Comprehensive Review on Chemistry, Biosynthesis, and Therapeutic Potentials

Aathira Sujathan Nair,1 Mahendran Sekar,1 Siew Hua Gan,1 Vinoth Kumarasamy,2 Vetriselvan Subramaniyan,3 Yuan Seng Wu,4 Nur Najihah Izzati Mat Rani,5 Subban Ravi,6 Ling Shing Wong7 1School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia; 2Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 4Sunway Microbiome Centre & Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, 47500, Malaysia; 5Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh, Perak, 30450, Malaysia; 6Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India; 7Faculty of Health and Life Sciences, INTI International University, Nilai, 71800, MalaysiaCorrespondence: Mahendran Sekar, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia, Email [email protected] Vinoth Kumarasamy, Department of Parasitology & Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Cheras, Kuala Lumpur, 56000, Malaysia, Email [email protected]: Lawsone, a naturally occurring organic compound also called hennotannic acid, obtained mainly from Lawsonia inermis (Henna). It is a potential drug-like molecule with unique chemical and biological characteristics. Traditionally, henna is used in hair and skin coloring and is also a medicinal herb for various diseases. It is also widely used as a starting material for the synthesis of various drug molecules. In this review, we investigate on the chemistry, biosynthesis, physical and biological properties of lawsone. The results showed that lawsone has potential antioxidant, anti-inflammatory, antimicrobial and antitumor properties. It also induces cell cycle inhibition and programmed cell death in cancer, making it a potential chemotherapeutic agent. Additionally, inhibition of pro-inflammatory cytokine production makes it an essential treatment for inflammatory diseases. Exploration of its biosynthetic pathway can pave the way for its development into targets for new drug development. In future, well-thought-out clinical studies should be made to verify its safety and efficacy. Keywords: lawsone, Lawsonia inermis, henna, antitumor, antioxidant, anti-inflammatory, antimicrobia

Graphene plasmonics

Two rich and vibrant fields of investigation, graphene physics and plasmonics, strongly overlap. Not only does graphene possess intrinsic plasmons that are tunable and adjustable, but a combination of graphene with noble-metal nanostructures promises a variety of exciting applications for conventional plasmonics. The versatility of graphene means that graphene-based plasmonics may enable the manufacture of novel optical devices working in different frequency ranges, from terahertz to the visible, with extremely high speed, low driving voltage, low power consumption and compact sizes. Here we review the field emerging at the intersection of graphene physics and plasmonics.Comment: Review article; 12 pages, 6 figures, 99 references (final version available only at publisher's web site

Arts for the Blues : the development of a new evidence-based creative group psychotherapy for depression

Introduction: Depression affects many adults in the UK, often resulting in referral to primary care mental health services (e.g. Improving Access to Psychological Therapies, IAPT). CBT is the main modality for depression within IAPT, with other approaches offered in a limited capacity. Arts psychotherapies are rarely provided despite their attractiveness to clients. However, the recent drop-out rate of 64% within IAPT suggests that clients’ needs are not being fully met. Therefore, in order to expand clients’ choice we developed a new creative psychological therapy integrating evidence-based approaches with arts psychotherapies. Method: A three-level approach was used: a) thematic synthesis of client-identified helpful factors in evidence-based approaches for depression and in arts psychotherapies; b) studio practice exploring Cochrane Review findings on arts psychotherapies for depression; c) pilot workshops for clients with depression and therapists. Findings and Discussion: Eight key ingredients for positive therapy outcomes were identified: encouraging active engagement, learning skills, developing relationships, expressing emotions, processing at a deeper level, gaining understanding, experimenting with different ways of being, and integrating useful material. These ingredients were brought together as Arts for the Blues for clients with depression: a 12-session evidencebased pluralistic group psychotherapy integrating creative methods as well as talking therapy. Conclusion: The evidence-based foundation, creative content, and pluralistic nature of this new approach aligned with eight client-identified key ingredients for positive therapy outcomes, make it a promising therapy option that can be adapted to individual therapy. Implications include consideration for NICE approval as an additional therapy for depression