Estimating the annual production data of bidi sticks in India using the "back-of-the-envelop-method".

The Indian bidi industry is largely unorganised with poorly implemented regulations along with laxed taxations. The unaccounted production of bidi sticks might potentiate its illicit circulation and therefore, unchecked availability to the minors. Specific production estimates may lead to stricter compliance with the existing regulatory norms. Due to the paucity of evidence and wide variability in production numbers, this estimation of the exact number of bidi sticks produced annually within the country was conducted. The annual number of produced sticks were estimated using the available literature till May 2023, on: a) the quantity of auctioned tendu leaves, b) number of bidi rollers, and c) bidi tobacco cultivated. Around 10 % attritions were considered during each stage of the manufacturing process to arrive at the production estimates. Annual bidi stick production was estimated as a) 319.83 billion, b) 600 billion to 1 trillion, and c) 974 billion to 1.19 trillion. This research provides a crucial estimate of the alarming number of bidi sticks produced and address the significant gap in reliable data of production figures. These insights underscore the urgency for stringent policy measures and regulation of bidi industry to safeguard health and curtail illicit practices.

Eco-friendly and sustainable approaches against aphids management (Myzus persicae) and dissipation studies of imidacloprid in important cash crop capsicum under protected and open condition.

Capsicum is generally infested with many biotic agents mainly sucking insects, among them the major is aphid (Myzus persicae). Chemical management is one of the most common strategies for their management. However, there are no recommended insecticides for insect management in polyhouse. An experiment was designed to assess the bio-potency of four popularly used insecticides (Imidacloprid-17.8SL, Acephate-75SP, Dimethoate-30EC and Buprofezin-25SC), a botanical (Neem oil 10000 ppm) and two entomopathogenic fungi (Metarhizium anisopliae 1.15%WP and Lecanicillium lecanii 1.15%WP) for two consecutive seasons. Most effective and the highest reduction of aphid population (78.14-81.92 %) were found in imidacloprid (17.8SL) treated plots. This effective molecule imidacloprid was further studied for its dissipation pattern under polyhouse and open condition and found that the imidacloprid residues in capsicum fruit dissipated below quantification limit (BQL) within 10days after final spray and the residues in the soil sampled at harvest time were found below the detection level. The half-lives of imidacloprid were 1.88 and 2.61 days under polyhouse and 1.07 and 1.52 days in open field at recommended doses (25 g a.i. ha-1) and double doses (50 g a.i. ha-1) of application respectively. The dietary exposure of imidacloprid on capsicum fruit under both conditions exposed that hazard quotient (HQ) values obtained from the different treatment doses have not exceeded the upper limit of toxicity (HQ < 1) and imidacloprid residues in the fruits were found below the existing MRL (Maximum Residue Limit) values (0.5 mg/kg) at 3 days after its final applications. Thus, imidacloprid may be considered as the effective chemical management option against aphids in capsicum under polyhouse and open field having no harmful effect on human consumption.

Analyzing bacterial detection and transport using redox impact electrochemistry.

Understanding bacterial transport dynamics, particularly at the single-particle level, is crucial across diverse fields from environmental science to biomedical research. In recent times, the emerging impact electrochemistry method offers a transformative approach for detection of bacteria at the single-particle level. The method employs the principle of single-entity electrochemistry to scrutinize electrochemical processes during interaction with the working electrode. In this study, we utilized redox impact electrochemistry to detect bacteria and analyze their transport processes towards the working electrode. Stochastic detection using redox reactions at the ultramicroelectrode enabled the detection of individual bacteria, with collision resulting in a current spike signal due to charge transfer. Notably, the detection of bacteria was demonstrated at an exceptionally low concentration (100 CFU/mL), with recorded current spikes reaching approximately 8.1 nA. Analysis of integrated areas under these spikes unveiled a diverse distribution of charge transfer at the ultramicroelectrode during redox reactions, implying variations in bacterial sizes, collision positions on the electrode surface, and redox activity among bacteria. Remarkably, the average charge transfer per bacterium between E. coli and the electrode was found to be (244 ± 24) pC, underscoring the intrinsic redox activity of the bacteria, equivalent to (2.52 ± 0.25) × 10-15 mol. Additionally, our investigation explored the effects of cell transport mechanisms, including diffusion, migration, convection, and settlement on stochastic interactions of the bacteria at the ultramicroelectrode. Through the collision frequency calculations, we found that migration is the primary factor shaping bacterial transport, with gravitational cell settlement also exerting a significant influence.

Assessment of Psychiatric Illness among Pulmonary Tuberculosis Patients at a Tertiary Care Center in India.

INTRODUCTION: Tuberculosis (TB) is a chronic infectious multisystemic disease caused by Mycobacterium tuberculosis and is one of the leading causes of mortality worldwide. Both common mental disorders (CMD) and TB are global public health problems that have a considerable impact on human health. Moreover, TB and CMDs share common risk factors including poverty, drug addiction, and homelessness and the coexistence of CMD and TB leads to difficult management of TB. MATERIALS AND METHODS: This was a hospital-based longitudinal study, carried out between June 2021 and December 2022. In this study, 147 pulmonary TB patients were included as per inclusion and exclusion criteria, and psychiatric illness was evaluated by the Brief Psychiatric Rating Scale. RESULTS: The mean age of study participants was 37.59 ± 15.37 years, there were 99 (67.3%) were male and 48 (32.7%) were female. Psychiatric illness was found in 77 (52.38%) pulmonary TB patients. Among psychiatric illness, anxiety was found in 33 (22.4%) participants and 21 (14.3%) participants had depression. Mixed anxiety and depression were found in 20 (13.6%) patients and 03 (2%) participants had severe psychosis. The association of psychiatric illness with age group and gender was not significant (P = 0.734, 0.203, respectively). There were 105 (71.40%) patients who had <12 standard education and 42 (28.60%) had >12 standard education and their association with psychiatric illness was statistically significant (P = 0.044). Adverse drug reactions were found among 80 (54.42%) patients and the association between adverse drug reactions and psychiatric illness was significant (P = 0.031). CONCLUSION: Psychiatric illness is one of the important domains to be evaluated in timely manner in TB patients and early intervention is needed for better management of the TB because the severity, social factors, and chronicity of the disease make them susceptible to develop psychiatric illness.

Résumé Introduction:La tuberculose (TB) est une maladie infectieuse multisystémique chronique causée par Mycobacterium tuberculosis et constitue l'une des principales causes de mortalité dans le monde. Les troubles mentaux courants (CMD) et la tuberculose sont des problèmes de santé publique mondiaux qui ont un impact considérable sur la santé humaine. De plus, la tuberculose et les troubles mentaux courants (CMD) partagent des facteurs de risque communs, notamment la pauvreté, la toxicomanie et l'itinérance, et la coexistence des CMD et de la tuberculose rend difficile la gestion de la tuberculoseMéthodes:Il s'agissait d'une étude longitudinale en milieu hospitalier, réalisée entre juin 2021 et décembre 2022. Dans cette étude, 147 patients atteints de tuberculose pulmonaire ont été inclus selon les critères d'inclusion et d'exclusion et la maladie psychiatrique a été évaluée par une brève échelle d'évaluation psychiatrique (BPRS)Résultats:L'âge moyen des participants à l'étude était de 37,59 ± 15,37 ans, il y avait 99 (67,3 %) hommes et 48 (32,7 %) femmes. Une maladie psychiatrique a été trouvée chez 77 (52,38 %) patients atteints de tuberculose pulmonaire. Parmi les maladies psychiatriques, l'anxiété a été constatée chez 33 (22,4 %) participants et 21 (14,3 %) participants souffraient de dépression. Une anxiété et une dépression mixtes ont été trouvées chez 20 (13,6 %) patients et 03 (2 %) participants souffraient d'une psychose sévère. L'association entre la maladie psychiatrique et le groupe d'âge et le sexe n'était pas significative (valeur P = 0,734, 0,203 respectivement). Il y avait 105 (71,40 %) patients ayant <12 niveaux d'éducation standard et 42 (28,60 %) avaient >12 niveaux d'éducation standard et leur association avec une maladie psychiatrique était statistiquement significative (P = 0,044). Des effets indésirables du médicament ont été observés chez 80 (54,42 %) patients et l'association entre l'effet indésirable du médicament et la maladie psychiatrique était significative. (P = 0,031)Conclusion:La maladie psychiatrique est l'un des domaines importants à évaluer en temps opportun chez les patients tuberculeux et une intervention précoce est nécessaire pour une meilleure prise en charge de la tuberculose car la gravité, les facteurs sociaux et la chronicité de la maladie les rendent susceptibles de développer une maladie psychiatrique.

Photoinduced Electron-Transfer-Mediated Differential Recognition of Proteins on Plasmonic Surfaces.

Photoinduced enhanced Raman spectroscopy (PIERS) has emerged as an efficient technique for enhancing the vibrational modes of analyte molecules adsorbed on a plasmonic nanoparticle-semiconductor hybrid material through chemical enhancement governed by electron transfer from the semiconductor to the plasmonic nanoparticles under an additional ultraviolet (UV) preirradiation step. The increase in chemical enhancement is imperative in analyzing and detecting pharmaceutically important moieties, such as amino acids and proteins, with a low Raman scattering cross section, even in complex biological environments. Herein, we demonstrate that UV preirradiation induced the creation of additional oxygen vacancies by introducing a low concentration (≈1%) of Ni as a dopant in the 2D platelike morphology of the BiOCl semiconductor; i.e., defect states in the semiconductor can induce charge transfer from the semiconductor to the plasmonic nanoparticles. This phenomenon facilitates electron transfer to the adsorbed analyte on the plasmonic surface. Additionally, we have shown the usefulness of this method in protein immobilization on the substrate surface, followed by the identification of a specific protein in the mixture of proteins. Proteins containing cysteine residues capture these electrons to form a surface-bound thiol group via a transient disulfide electron adduct radical. This allows differential binding of the protein molecules to the semiconductor plasmonic hybrid depending on the concentration of surface cysteine residues in proteins. Through PIERS and principal component analysis, we demonstrate the possibility of probing and distinguishing biomolecules based on their surface composition and secondary structure components even in their mixtures, thus paving the way for efficient analysis of complex biological systems.

Solvothermally Synthesized Nickel-Doped Marigold-Like SnS2 Microflowers for High-Performance Supercapacitor Electrode Materials.

Two-dimensional transition-metal dichalcogenides (TMDs) have emerged as promising capacitive materials for supercapacitors owing to their layered structure, high specific capacity, and large surface area. Herein, Ni-doped SnS2 microflowers were successfully synthesized via a facile one-step solvothermal approach. The obtained Ni-doped SnS2 microflowers exhibited a high specific capacitances of 459.5 and 77.22 F g-1 at current densities of 2 and 10 A g-1, respectively, in NaClO4 electrolyte, which was found to be higher than that of SnS2-based electrodes in various electrolytes such as KOH, KCl, Na2SO4, NaOH, and NaNO3. Additionally, these microflowers demonstrate a good specific energy density of up to 51.69 Wh kg-1, at a power density of 3204 Wkg-1. Moreover, Ni-doped SnS2 microflowers exhibit a capacity retention of 78.4% even after 5000 cycles. Better electrochemical performance of the prepared electrode may be attributed to some important factors, including the utilization of a highly ionic conductive and less viscous NaClO4 electrolyte, incorporation of Ni as a dopant, and the marigold flower-like morphology of the Ni-doped SnS2. Thus, Ni-doped SnS2 is a promising electrode material in unconventional high-energy storage technologies.

An Investigation of In Vitro Anti-Cancer Efficacy of Dihydroartemisinin-Loaded Bovine Milk Exosomes Against Triple-Negative Breast Cancer.

Repurposing drugs offers several advantages, including reduced time and cost compared to developing new drugs from scratch. It leverages existing knowledge about drug safety, dosage, and pharmacokinetics, expediting the process of clinical trials and regulatory approval. Dihydroartemisinin (DHA) is a semi-synthetic and active metabolite of all artemisinin molecules and is FDA-approved for the treatment of malaria. Apart from having anti-malarial properties, DHA also possesses anticancer properties. However, its pharmacological actions are limited by toxicity and solubility problems. To overcome these challenges and enhance its anticancer effectiveness, we designed an exosomal formulation of DHA. We isolated exosomes from bovine milk using differential ultracentrifugation and loaded DHA using sonication. Scanning and transition electron microscopy revealed a size of roughly 100 nm, with a spherical shape. Furthermore, in pH 7.4 and 5.5, the exosomes exhibited burst release followed by sustained release. Multiple in vitro cell culture tests demonstrated that Exo-DHA exhibited enhanced anticancer activity, including cytotoxicity, cellular uptake, generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, and inhibition of colony formation. Additional evidence supporting Exo-DHA's anti-migration ability came from transwell migration and scratch assays. Based on these results, it was concluded that the anticancer efficacy of DHA was improved when loaded into bovine milk-derived exosomes. While the in vitro results are encouraging, more in vivo testing in suitable animal models and biochemical marker analysis are warranted.

Computational modeling and uncertainty prediction of hyperelastic constitutive responses of damaged brain tissue under different temperature and strain rates.

The effect of strain rate and temperature on the hyperelastic material stress-strain characteristics of the damaged porcine brain tissue is evaluated in this present work. The desired constitutive responses are obtained using the commercially available finite element (FE) tool ABAQUS, utilizing 8-noded brick elements. The model's accuracy has been verified by comparing the results from the previously published literature. Further, the stress-strain behavior of the brain tissue is evaluated by varying the damages at various strain rates and temperatures (13, 20, 27, and 37°C) under compression test. Additionally, the sensitivity analysis of the model is computed to check the effect of input parameters, that is, the temperature, strain rate, and damages on the material properties (shear modulus). The modeling and discussion sections enumerate the inclusive features and model capabilities.

Advances in Nickel-Containing High-Entropy Alloys: From Fundamentals to Additive Manufacturing.

High-entropy alloys (HEAs) are recognized as a class of advanced materials with outstanding mechanical properties and corrosion resistance. Among these, nickel-based HEAs stand out for their impressive strength, ductility, and oxidation resistance. This review delves into the latest advancements in nickel-containing HEAs, covering their fundamental principles, alloy design strategies, and additive manufacturing techniques. We start by introducing HEAs and their unique properties, emphasizing the crucial role of nickel. This review examines the complex relationships between alloy composition, valence electron concentration (VEC), and the resulting crystal structures. This provides insights into design principles for achieving desired microstructures and mechanical properties. Additive manufacturing (AM) techniques like selective laser melting (SLM), electron beam melting (EBM), and laser metal deposition (LMD) are highlighted as powerful methods for fabricating intricate HEA components. The review addresses the challenges of AM processes, such as porosity, fusion defects, and anisotropic mechanical properties, and discusses strategies to mitigate these issues through process optimization and improved powder quality. The mechanical behavior of AM-processed nickel-based HEAs is thoroughly analyzed, focusing on compressive strength, hardness, and ductility. This review underscores the importance of microstructural features, including grain size, phase composition, and deformation mechanisms, in determining the mechanical performance of these alloys. Additionally, the influence of post-processing techniques, such as heat treatment and hot isostatic pressing (HIP) on enhancing mechanical properties is explored. This review also examines the oxidation behavior of nickel-containing HEAs, particularly the formation of protective oxide scales and their dependence on aluminum content. The interplay between composition, VEC, and oxidation resistance is discussed, offering valuable insights for designing corrosion resistant HEAs. Finally, this review outlines the potential applications of nickel-based HEAs in industries such as aerospace, automotive, and energy, and identifies future research directions to address challenges and fully realize the potential of these advanced materials.

Cancer phototherapy by CO releasing terpyridine-based Re(I) tricarbonyl complexes via ROS generation and NADH oxidation.

Here, we have synthesized and characterized three visible light responsive terpyridine based-Re(I)-tricarbonyl complexes; [Re(CO)3(ph-tpy)Cl] (Retp1), [Re(CO)3(an-tpy)Cl] (Retp2), and [Re(CO)3(py-tpy)Cl] (Retp3) where ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine; an-tpy = 4'-anthracenyl-2,2':6',2″-terpyridine, py-tpy = 4'-pyrenyl-2,2':6',2″-terpyridine. The structures of Retp1 and Retp2 were confirmed from the SC-XRD data, indicating distorted octahedral structures. Unlike traditional PDT agents, these complexes generated reactive oxygen species (ROS) via type I and type II pathways and oxidized redox crucial NADH (reduced nicotinamide adenine dinucleotide) upon visible light exposure. Retp3 showed significant mitochondrial localization and demonstrated photoactivated anticancer activity (IC50 ∼ 2 µM) by inducing ROS-mediated cell death in cancer cells selectively (photocytotoxicity Index, PI > 28) upon compromising mitochondrial function in A549 cells. Their diagnostic capabilities were ultimately assessed using clinically relevant 3D multicellular tumor spheroids (MCTs).

A DFT study of the adsorption behavior and sensing properties of CO gas on monolayer MoSe2 in CO2-rich environment.

CONTEXT: Carbon monoxide, also known as the "silent killer," is a colorless, odorless, tasteless, and non-irritable gas that, when inhaled, enters the bloodstream and lungs, binds with the hemoglobin, and blocks oxygen from reaching tissues and cells. In this work, the monolayer MoSe2-based CO gas sensors were designed using density functional theory calculation with several dopants including Al, Au, Pd, Ni, Cu, and P. Here, Cu and P were found to be the best dopants, with adsorption energies of -0.67 eV (Cu) and -0.54 eV (P) and recovery times of 1.66 s and 13.8 ms respectively. Cu conductivity for CO adsorption was found to be 2.74 times that of CO2 adsorption in the 1.0-2.26 eV range. P displayed the highest selectivity, followed by Pd and Ni. The dopants, Pd and Ni, were found suitable for building CO gas scavengers due to their high recovery times of 9.76 × 1020 s and 2.47 × 1011 s. Similarly, the adsorption of CO2 on doped monolayer MoSe2 was also investigated. In this study, it is found that monolayer MoSe2 could be employed to create high-performance CO sensors in a CO2-rich environment. METHOD: The electrical characteristics of all doped MoSe2 monolayers are obtained using a DFT calculation with the PBE-GGA method from the Quantum ESPRESSO package. The self-consistent field (SCF) computations were performed using a 7 × 7 × 1 k-point grid and a norm-conserving pseudo potential (NCPP) file. To determine electrical conductivity, the semi-classical version of Boltzmann transport theory, implemented in the Boltz Trap code, was used.

Photoactivated Anticancer Activity of Cobalt(III) Complexes with Naturally Occurring Flavonoids Chrysin and Silibinin.

Photoactive metal complexes of bioessential transition metal ions with natural chelators are gaining interest as photocytotoxic agents for cancer photodynamic therapy (PDT). We report six new cobalt(III) complexes with a mixed-ligand formulation [Co(B)2(L)](ClO4)2 (Co1-Co6), where B represents a N,N-donor α-diimine ligand, namely, phenanthroline (phen; Co1, Co2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq; Co3, Co4), and dipyrido[3,2-a:2',3'-c]phenazine (dppz; Co5, Co6), and L is the monoanionic form of the naturally occurring flavonoids chrysin (chry; Co1, Co3, Co5) and silibinin (sili; Co2, Co4, Co6). Complexes displayed a d-d absorption band within 500-700 nm and exhibited excellent dark and photostability in solution. Cytotoxicity studies indicated significant activity of Co5 and Co6 against cervical (HeLa) and lung (A549) cancer cells under visible light (400-700 nm) irradiation giving low micromolar IC50 values (2.3-3.4 µM, phototoxicity index~15-30). The complexes demonstrated notably low toxicity against normal HPL1D lung epithelial cells. Flow cytometry assay revealed an apoptotic mode of cell damage triggered by the complexes when irradiated. ROS generation assay indicated the involvement of singlet oxygen species in the cell death mechanism when irradiated with light. Overall, complexes Co5 and Co6 with coordinated dipyridophenazine and flavonoid ligands are potential candidates for cancer PDT applications.

Advancements in Rechargeable Zn-Air Batteries with Transition-Metal Dichalcogenides as Bifunctional Electrocatalyst.

This review covers recent progress on transition metal dichalcogenides (TMDs) as bifunctional electrocatalysts for Zinc-air batteries (ZABs), emphasizing their suitable surface area, electrocatalytic active sites, stability in acidic/basic environments, and tunable electronic properties. It discusses strategies like defect engineering, doping, interface, and structural modifications of TMDs nanostructures for enhancing the performances of ZABs. Zinc-air batteries are promising energy storage devices owing to their high energy density, low cost, and environmental friendliness. However, the development of durable and efficient bifunctional electrocatalysts is a major concern for Zn-air batteries. In this review, we summarize the recent progress on transition metal dichalcogenides (TMDs) as bifunctional electrocatalysts for Zn-air batteries. We discuss the advantages of TMDs, such as high activity, good stability, and tunable electronic structure, as well as the challenges, such as low conductivity, poor durability, and limited active sites. We also highlight the strategies for fine-tuning the properties of TMDs, such as defect engineering, doping, hybridization, and structural engineering, to enhance their catalytic performance and stability. We provide a comprehensive and in-depth analysis of the applications of TMDs in Zn-air batteries, demonstrating their potential as low-cost, abundant, and environmentally friendly alternatives to noble metal catalysts. We also suggest future directions like exploring new TMDs materials and compositions, developing novel synthesis and modification techniques, investigating the interfacial interactions and charge transfer processes, and integrating TMDs with other functional materials. This review aims to illuminate the path forward for the development of efficient and durable Zn-air batteries, aligning with the broader objectives of sustainable energy solutions.

A study to assess the nutritional status and dietary gap among pulmonary tuberculosis patients in Raipur city.

Background: Undernutrition raises the likelihood of progressing from tuberculosis (TB) infection to active TB illness and causes weight loss. Proper food and nutrition are important in the treatment of tuberculosis patients. Active tuberculosis necessitates a substantial energy expenditure. The Tuberculosis treatment guidelines neglect the nutritional supplementation part of Tuberculosis management. The study aims to determine the factors affecting the nutritional status of pulmonary Tuberculosis patients. Material and Methods: A hospital-based cross-sectional study was conducted from December 2021 to January 2022 among the patients newly diagnosed and above 18 years of age coming to DOTS Centre (DMC) of Pt J.N.M. Medical College, Raipur. Total 120 subjects were selected by consecutive sampling method. Data was analyzed using SPSS version 24, and P value <0.05 was considered statistically significant. Result: Among 120 study subjects, malnourished was 54.16% (BMI <18.50 kg/m2), normal was 35% (BMI 18.50-24.99 kg/m2), overweight was 6.67% (BMI 25-29.99 kg/m2), and obese were 4.17% (BMI 30-34.99 kg/m2). Among 120 study subjects, the maximum number of them (96.3%) had a dietary gap in their diets which was equal in two groups of 1-50% calorie deficit and 51-100% calorie deficit. Conclusion: A high proportion of tuberculosis patients were undernourished, and even a very distal factor for undernutrition became proximal for tuberculosis patients. To control tuberculosis and to end the tuberculosis disease, an improvement in the nutritional status of the patient should be our priority. By knowing the importance of nutrition in TB patients, the primary care physicians can decrease the morbidity and mortality in TB patients.

Effect of Aligning Forces by Two Preadjusted Edgewise Techniques on a Buccally Positioned Maxillary Canine at Varying Vertical Displacements: A Finite Element Study.

Objective: To evaluate the effect of continuous arch and piggyback mechanics in a straight wire appliance (SWA) for the alignment of buccal and variably vertically positioned maxillary canines. Methods: A three-dimensional finite element model with near-normal occlusion and buccal and vertically displaced maxillary canines was used. Two groups were created to simulate two commonly used SWAs techniques, continuous archwire (Group 1) and piggyback models (Group 2). Each group had three subgroups with varying vertical displacement of the canine from 2 to 6 mm from the occlusal plane. The displacement and stress distribution were noted in each group. Results: As the vertical displacement increased in Group 1, the concentration of von Mises stress increased progressively at the incisal third (0.36, 0.41 and 0.44 MPa) at 2, 4, and 6 mm, respectively, with decreased maximum occlusal movement in the vertical plane with respect to the canine. Group 2 exhibited a similar pattern but greater occlusal movement of the canine compared with Group 1. Conclusion: A vertical displacement of 4 mm is the optimal level at which continuous arch mechanics should be considered. For displacements beyond 4 mm, the piggyback wire technique is a suitable alternative.

Harnessing the Power of Big Data Analytics-Estimation of Reference Intervals for Neonatal Serum TSH in Pakistan Using RefineR Algorithm.

OBJECTIVE: To estimate the population-specific reference intervals (RIs) for neonatal thyroid stimulating hormone (TSH) in Pakistani neonates, utilising the refineR algorithm. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, Pakistan, from 17th May to 30th November 2023. METHODOLOGY: A data mining analysis was conducted on serum TSH results of neonates (≤1 month) over a period of six years, following approval from the Institutional Ethical Review Committee. Two subgroups were assessed based on the age as 0 - 5 days and 6 - 30 days. The refineR algorithm was implemented using refineR package (version 1.0.0), ensuring accurate analysis and insights. RESULTS: A total of non-duplicate 82,299 neonatal serum TSH tests were retrieved, including 70,788 (88%) aged 0 - 5 days and 11,511 (12%) aged ranging from 6 - 30 days. The estimated RI was from 0.67 µIU/mL (90% CI 0.641 - 0.72) to 15.0 µIU/mL (90% CI 13.2 - 17.3) for the first age group and 0.65 µIU/mL (90% CI 0.6 - 0.84) to 8.6 µIU/mL (90% CI 8.05 - 9.71) for the second age group. CONCLUSION: Reference intervals for neonatal serum TSH of the Pakistani population were estimated, considering the genetic differences of this demographic in comparison to the Western population. Results aligned with global literature, validating the refineR indirect approach's applicability. KEY WORDS: Reference intervals, Neonatal, Thyroid stimulating hormone, RefineR algorithm, Big data, Pakistan.

Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders.

Inherited genetic disorders of the liver pose a significant public health burden. Liver transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive therapy. To overcome these limitations, nucleic acid therapy provides a hopeful alternative that enables gene repair, gene supplementation, and gene silencing with suitable vectors. Though viral vectors are the most efficient and preferred for gene therapy, pre-existing immunity debilitating immune responses limit their use. As a potential alternative, lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms, including pDNA, mRNA, siRNA, and proteins. Herein, we discuss the broader applications of lipid nanoparticles, from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing, as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.

Patterns, outcomes, and preventability of clinically manifest drug-drug interactions in older outpatients: a subgroup analysis from a 6-year-long observational study in North India.

Older adults are vulnerable to adverse drug reactions (ADRs) and drug-drug interactions (DDIs). Evidence on clinically manifest DDIs in older outpatients is scanty. The present study aims to report clinically manifest DDIs, their risk factors, and preventive measures. A subgroup analysis of a 6-year (2015-2021) long prospective study was conducted in a tertiary hospital in North India. Older outpatients with ADRs constituted the study participants. Among 933 ADRs reported in 10,400 patient registrations, clinically manifest DDIs were involved in 199 (21.3%). DDIs accounted for 29.9%, 26.5%, and 21.3% of drug-related metabolic, vascular, and nervous system disorders, respectively. Movement disorders (n = 18), hypotension (n = 16), and hypoglycemia (n = 15) were the most common manifestations. Eighty-six percent of DDIs were of the pharmacodynamic type, and 13.1% were immune-mediated. Around 35% of DDIs resulted in hospitalization, with hyponatremia, movement disorder, and renal impairment as the common reasons. Older adults with Parkinsonism, infection, coronary artery disease, neuropsychiatric disease, and diabetes mellitus, respectively, had 3.28, 2.85, 1.97, 1.76, and 1.80 times higher odds of DDIs. Those receiving ≥ 10 drugs had 5.31 times higher odds of DDIs compared to individuals receiving 1-4 drugs. "Avoiding the causative drug," "optimal monitoring of the patient," and "start-low and go-slow" policy together could prevent 85% of DDIs. In conclusion, every fifth case of ADRs and nearly one third of ADR-related hospitalizations in older adults are related to DDIs. Movement disorder, hypotension, and hypoglycemia are the common manifestations. A holistic approach with drug omission, optimal patient monitoring, and slow titration of therapy can prevent significant DDIs in older adults.

Harnessing Potential of ω-3 Polyunsaturated Fatty Acid with Nanotechnology for Enhanced Breast Cancer Therapy: A Comprehensive Investigation into ALA-Based Liposomal PTX Delivery.

Our hypothesis posited that incorporating alpha-linolenic acid (ALA) into liposomes containing Paclitaxel (PTX) could augment cellular uptake, decrease the therapeutic dosage, and alleviate PTX-related side effects. Our investigation encompassed characterization of the liposomal formulation, encompassing aspects like particle size, surface morphology, chemical structure, drug release kinetics, and stability. Compatibility studies were performed through Fourier transform infrared spectroscopy (FTIR). By utilizing the Box-Behnken design (BBD), we developed ALA-based liposomes with satisfactory particle size and entrapment efficiency. It is noteworthy that ALA incorporation led to a slight increase in particle size but did not notably affect drug entrapment. In vitro drug release assessments unveiled a sustained release pattern, with ALA-PTX liposomes demonstrating release profiles comparable to PTX liposomes. Morphological examinations confirmed the spherical structure of the liposomes, indicating that substituting ALA with phosphatidylcholine did not alter the physicochemical properties. Cellular uptake investigations showcased enhanced uptake of ALA-based liposomes in contrast to PTX liposomes, likely attributed to the heightened fluidity conferred by ALA. Efficacy against MCF-7 cells demonstrated concentration-dependent reductions in cell viability, with ALA-PTX liposomes exhibiting the lowest IC50 value. Morphological analysis confirmed apoptotic changes in cells treated with all formulations, with ALA-PTX liposomes eliciting more pronounced changes, indicative of enhanced anticancer efficacy.