Emerging Natural Therapies for the Treatment of Inflammatory Bowel Disease.

The term "inflammatory bowel disease," which includes Crohn's disease (CD) and ulcerative colitis (UC), refers to a chronic inflammatory condition of the digestive system. There are many different treatment options, such as corticosteroids, biologics, 5-aminosalicylate, and immune-suppressants, but none of them can maintain the disease remission for a longer period, which is the ultimate goal of treatment. Furthermore, they have numerous serious side effects like nephrotoxicity, infertility, congestive heart failure, myopathy, etc. So, in order to treat these conditions, researchers are concentrating more on natural medicine that is less expensive and has fewer side effects. The current analysis includes a list of plants showing promising activity against IBD. These include Cannabis sativa, Aloe vera, Boswellia serrata, Withania somnifera, Curcuma longa, Triticum aestivum, and many others. These plants need to be further investigated in terms of preclinical and clinical studies to obtain the safety and efficacy data necessary for their commercialisation. Global regulatory norms will facilitate simple commercialisation. Also, more investigation is required to pinpoint the precise mechanism of action to confirm clinical success.

Nanoemulsions a Delivery System in the Making for Tumor Targeting Therapeutics: Evaluation and Characterization to Meet Clinical Challenges.

Cancer is a complex disease characterized by the uncontrolled and unregulated growth of cells followed by invasion and proliferation from the site of origin to other sites of the body. Conventional chemotherapy largely kills rapidly expanding and dividing cancer cells by impairing DNA synthesis and mitosis. It is associated with various types of adverse effects ranging from simple nausea and appetite loss to serious ones like bone marrow depression and compromised immunity etc., due to their non-selectivity and inability to differentiate. The ideal feature of a delivery system is delivering the drug to the target place to achieve the most therapeutic impact while having the least toxicity. With the advent of novel drug delivery systems, it has been easier to deliver the drug to the target site. Utilizing new techniques and technology makes it a feasible approach to target cancer cells. Nanoemulsions are isotropic mixtures of transparent or translucent oil globules dispersed in an aqueous phase that is kinetically stable and supported by an interfacial coating of surfactant and co-surfactant molecules with droplet sizes in the nanometre range. Nanoemulsions are the delivery system of choice in case of cancer because of certain key attributes, including biodegradability, biocompatibility, large surface area nonimmunogenicity, and release behavior control. At the same time, nanoemulsions have been engineered for various reasons, including enhanced biological half-life, target-specific binding ability, and imaging capability at different therapy levels by modifying the characteristics of nanoemulsions. This review focuses on current cancer treatment challenges and the role of nanoemulsions in treating cancer with their production methods, characterization methods, application, and quality attributes, which would help them make it to the clinics where cancer treatment is going on.

Burden of Chronic Nonhealing Wounds: An Overview of the Worldwide Humanistic and Economic Burden to the Healthcare System.

Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary, leading to inconsistent estimates. The definition of a wound is a loss of epithelial continuity caused by damage to the tissue. The following conditions can cause chronic wounds: panniculitis, pyoderma gangrenosum, traumatic, neurological, metabolic, hematologic, neoplastic, or infection-related. The growing global incidence of diabetes and the aging population necessitate greater attention to chronic wounds. Regrettably, it is sad that significant healthcare institutions have overlooked wound research. The study of health-related illnesses and occurrences in particular populations, including their distribution, frequency, and determinants, and the application of this research to control health problems.

Carbon-Sulfur Bond Cleavage in Methanesulfonate on Diorganotin Quinaldate Platform - Synthesis and Characterization of [(n-Bu2SnL)2SO4].

The synthesis of mixed ligand di-n-butyltin complexes, [(n-Bu2SnL1-3)2SO4], 2-4 (HL1-3=2-quinoline/ 1-isoquinoline/ 4-methoxy-2-quinoline carboxylic acid) has been realized by reacting n-Bu2Sn(OMe)OSO2Me, 1 a with the corresponding quinaldic acid under solvothermal conditions. The observed transformation of methane sulfonate to sulfate anion represents a rare example of C-S bond cleavage on the organotin scaffolds, n-Bu2Sn(L1-3)OSO2Me, which have been identified as en route intermediates by NMR and X-ray crystallography. Analogous reaction when extended with Me2Sn(OMe)OSO2Me, 1 b and HL2 yields [(Me2Sn)2(L2)3(OSO2Me)], 5 as partially disproportionated product of Me2Sn(L2)OSO2Me. The solid-state structures of 2-5 reveal variable modes of coordination of the ligands to afford molecular and polymeric motifs.

Stimuli responsiveness of recent biomacromolecular systems (concept to market): A review.

Stimuli responsive delivery systems, also known as smart/intelligent drug delivery systems, are specialized delivery vehicles designed to provide spatiotemporal control over drug release at target sites in various diseased conditions, including tumor, inflammation and many others. Recent advances in the design and development of a wide variety of stimuli-responsive (pH, redox, enzyme, temperature) materials have resulted in their widespread use in drug delivery and tissue engineering. The aim of this review is to provide an insight of recent nanoparticulate drug delivery systems including polymeric nanoparticles, dendrimers, lipid-based nanoparticles and the design of new polymer-drug conjugates (PDCs), with a major emphasis on natural along with synthetic commercial polymers used in their construction. Special focus has been placed on stimuli-responsive polymeric materials, their preparation methods, and the design of novel single and multiple stimuli-responsive materials that can provide controlled drug release in response a specific stimulus. These stimuli-sensitive drug nanoparticulate systems have exhibited varying degrees of substitution with enhanced in vitro/in vivo release. However, in an attempt to further increase drug release, new dual and multi-stimuli based natural polymeric nanocarriers have been investigated which respond to a mixture of two or more signals and are awaiting clinical trials. The translation of biopolymeric directed stimuli-sensitive drug delivery systems in clinic demands a thorough knowledge of its mechanism and drug release pattern in order to produce affordable and patient friendly products.

Assessing caregiver burden in advanced kidney disease: protocol for a systematic review of the measurement properties of instruments and tools.

INTRODUCTION: Caregiver burden is a significant issue in the care of patients with advanced kidney disease. Its assessment is crucial for evaluating the needs of caregivers and for the development of interventions to support them. Several instruments have been developed to measure caregiver burden in these patients. However, the measurement properties of these instruments have not been systematically reviewed. METHODS AND ANALYSIS: This systematic review will include a comprehensive search of databases including PubMed, CINAHL, Embase, Cochrane Library, SCOPUS and Web of Science by using keywords and MeSH terms to identify relevant studies starting from each database inception to 1 January 2024 and covering papers in English. The search strategy will combine relevant keywords and database-specific subject headings related to the following concepts: (1) caregivers, (2) burden, stress, distress, (3) chronic kidney disease, end-stage kidney disease, dialysis. Reference lists of eligible articles will also be hand searched. We will include quantitative and qualitative studies evaluating measurement properties of instruments assessing caregiver burden in caregivers of adult patients (aged ≥18 years). Data will be extracted from the selected studies and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist as the study quality assessment tool. Subsequently, the van der Vleuten utility index will be used to critique and categorise the instruments. A narrative that synthesises the utility of all instruments will be presented along with recommendations for the selection of instruments depending on specific clinical contexts. This systematic review will provide an overview of the measurement properties of available instruments, including discussion on reliability, validity and responsiveness. Results from the review may give rise to the subsequent development of most appropriate instrument that could be applied to the assessment of caregiver burden in advanced kidney disease. ETHICS AND DISSEMINATION: Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023433906.

Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101).

4-Chlorokynurenine (4-Cl-KYN, AV-101) is a prodrug of a NMDA receptor antagonist and is in clinical development for potential CNS indications. We sought to further understand the distribution and metabolism of 4-Cl-KYN, as this information might provide a strategy to enhance the clinical development of this drug. We used excretion studies in rats, in vitro transporter assays, and pharmacogenetic analysis of clinical trial data to determine how 4-Cl-KYN and metabolites are distributed. Our data indicated that a novel acetylated metabolite (N-acetyl-4-Cl-KYN) did not affect the uptake of 4-Cl-KYN across the blood-brain barrier via LAT1. 4-Cl-KYN and its metabolites were found to be renally excreted in rodents. In addition, we found that N-acetyl-4-Cl-KYN inhibited renal and hepatic transporters involved in excretion. Thus, this metabolite has the potential to limit the excretion of a range of compounds. Our pharmacogenetic analysis found that a SNP in N-acetyltransferase 8 (NAT8, rs13538) was linked to levels of N-acetyl-4-Cl-KYN relative to 4-Cl-KYN found in the plasma and that a SNP in SLC7A5 (rs28582913) was associated with the plasma levels of the active metabolite, 7-Cl-KYNA. Thus, we have a pharmacogenetics-based association for plasma drug level that could aid in the drug development of 4-Cl-KYN and have investigated the interaction of a novel metabolite with drug transporters.

Randomized Controlled Trial on the Effect of the Neonatal Nurse Navigator Program on Maternal Stress and Neonatal Cortisol Levels.

OBJECTIVE: To assess the effect of the Neonatal Nurse Navigator Program (NNNP) compared to usual care on maternal stress and neonatal salivary cortisol level (SCL) in the NICU. DESIGN: Randomized control trial. SETTING: NICU in a tertiary health care hospital in Manipal, Udupi District, Karnataka, India. PARTICIPANTS: Neonates between 34 and 36 weeks gestation and their mothers (N = 120 dyads). METHODS: We used block randomization to assign dyads to the intervention or control group. We measured maternal stress using the Parental Stress Scale: Neonatal Intensive Care Unit, and we estimated neonatal stress by measuring SCLs within 24 hours of NICU admission and before discharge from the unit. We conducted a descriptive analysis on participant characteristics and reported maternal stress levels using means and standard deviations. We used the analysis of covariance change score test to determine the difference in maternal and neonatal stress levels between the intervention and control groups. RESULTS: The NNNP group exhibited significantly lower maternal stress scores before discharge than the control group, and we observed reductions across all three subscales of the Parental Stress Scale: Neonatal Intensive Care Unit. Mean neonatal salivary cortisol levels were significantly lower in the interventional group than in the control group, F(1.117) = 24.03, 95% confidence interval [7.9, 18.6], p < .001. CONCLUSION: Use of the NNNP reduced maternal stress SCLs in high-risk neonates by actively engaging mothers in the care of their neonates in the NICU. We recommend adoption of the NNNP model as a standard care policy in NICUs throughout India.

Living with COPD: understanding patient experiences through the lens of photovoice.

BACKGROUND: Conventional quantitative or qualitative methodologies may not encompass the wide array of experiences of individuals living with Chronic Obstructive Pulmonary Disease (COPD). We used a novel approach - photovoice-to understand the impact of COPD on activities of daily living (ADLs) in a multicultural Asian country. METHODS: We recruited a purposive sample of eight patients from the outpatient clinics of the National University Health System, Singapore, between December 2020 and August 2021. We adopted a photovoice approach for data collection; participants were invited to take photos of how ADLs were impacted by COPD and attend a follow-up interview. An Interpretative Phenomenological Analysis method was used to analyze the data. Data saturation was reached by the seventh patient. RESULTS: COPD and the resulting breathlessness had a profound and diverse impact on our participants' lives. Living with COPD required substantial changes to how everyday tasks are performed, and participants learnt new strategies to deal with such tasks. A mixture of active and passive coping styles was evident. Feelings of frustration, anxiety and a sense of isolation were also reported. Contextual factors impacting ADLs included challenging climatic conditions and the local popularity of traditional or alternative medicine. CONCLUSION: The photovoice technique improved our understanding of the lived experiences of COPD patients and can benefit those who struggle to articulate their views by offering a different way to communicate beyond conventional interviewing.

Energy and exergo-environmental (3E) analysis of wheat seeds drying using indirect solar dryer.

Food insecurity is becoming a big problem due to the continuous increase in the population, for which there is a requirement of effective drying method for the storage of agricultural items which can solve this problem at global level. Hence, the present study deals with the evaluation of energy, exergy, and environmental parameters of low-cost indirect solar dryer with paraffin wax as energy storage material in rural areas for drying of wheat seeds to check its thermodynamic as well as environmental feasibility. The wheat seeds were dried in solar dryer from initial moisture of 20.2% in 6 h to achieve recommended moisture content which took lesser drying time as compared to open sun drying. The maximum value of collector exergy efficiency, exergy efficiency of drying chamber and pick-up efficiency are 1.5%, 72.62%, and 30.4% respectively. Environmental impacts assessment has revealed that the energy payback, CO2 mitigation, CO2 emission per year and carbon credit earned (at $80 per carbon credit) with present system are 1.35 years, 6.67 tons, 7.32 kg and $533.7, respectively considering the lifetime of solar dryer as 25 years. The performed study shows that the indirect solar dryer with paraffin wax is suitable for the households of rural areas with enhanced performance, lesser waste, sustainable, and lesser adverse effect on environment. This system can also be preferred for drying of other agricultural crops for a particular household.

Bimetal-oxide (Fe/Co) modified bagasse-waste carbon coated on lead oxide-battery electrode for metronidazole removal.

Current study covers the preparation and application of a commercial modified lead oxide battery electrode (LBE) in electrochemical oxidation (ECO) of metronidazole (MNZ) in an aqueous phase. Modified electrode is prepared by doping of bimetal-oxide (Fe and Zn) nanoparticles (NPs) & single metal-oxide (Fe/Zn) on bagasse-waste carbon (bwc) which is further coated on LBE. The modified LBE electrode surface was examined for metal-oxide NPs through X-ray diffraction analysis (XRD). Different electrodes are prepared by varying combinations of two metal-oxide based on molar ratio and tested for electrochemical characterization and MNZ removal test. Based on large oxygen evolution potential in a linear sweep volumetry (LSV) analysis and high MNZ removal rate, the best electrode has been represented as Fe1:Co2-bwc/LBE which contains Fe & Co molar ratio of 1:2. Moreover, equilibrium attained at faster rate in degradation process of MNZ, where pseudo first order kinetics of 2.29 × 10-2 min-1 was obtained under optimized condition of (MNZ:100 mg/L, pH:7, CD: 30 mA/cm2 and electrolyte: 0.05 M Na2SO4). Maximum MNZ removal, total organic carbon removal (TOC), mineralization current efficiency (MCE) & energy consumption (EC) of 98.7%, 85.3%, 62.2% & 96.143 kW h/kg-TOC removed are found in 180 min of treatment time for Fe1:Co2-bwc/LBE electrode. Accelerated service life test confirms that the stability of modified electrode is enhanced by 1.5 times compared to pristine LBE. Repeatability test confirms that modified LBE (Fe1:Co2-bwc/LBE) can be utilized up to 3 times.

Sustainable solid waste management system using technology-enabled end-of-pipe strategies.

Ever Increasing accumulation of solid waste, attributed to population growth and rapid urbanization, is a serious issue for all nations. This creates hindrance in implementing sustainable solid waste management systems (SWMS), which contribute to socio-economic-environmental-operational (SEEO) benefits for the nations and their citizens. Limited understanding of various solid waste management (SWM) practices, their operational sequence, and other system constraints pose numerous challenges for the concerned authorities and policymakers. This paper provides a framework depicting three broad categories of strategies for managing solid waste: preventive, end-of-pipe (EOP), and environmental restoration. Among these, the research emphasizes on EOP strategies, being suitable alternative as per current requirements, to deal with massive amounts of generated waste. It further adopts Grey-DEMATEL approach to models the causal relationship among EOP strategies to identify the most influential strategy, which influences other ones. The model suggests waste segregation to be the major enabler for other EOP strategies, as it has maximum overall significance value (R + C) between 1.18 and 1.41 and it is the only one with positive value in "net-effect" computation (R-C), compared to other strategies with negative (R-C) values. This would enable concerned authorities to understand and follow the sequence of actions. Finally, a comprehensive framework is proposed for effective, efficient, and sustainable methods of handling different types of solid waste using technology-enabled EOP strategies. A case study is performed to demonstrate the significance of waste segregation towards SEEO benefits. It indicates that technology-based solutions at decentralized depots and establishment of biogas plant in the vicinity of garbage collection point leads to reduction in transportation cost and energy saving in efficient manner. The ground level implementation of our research in an Indian city resulted in the reduction of daily vehicle requirement from 25 to 20 vehicles, leading to approx. 25% savings in overall transportation costs thereby cutting exchequer's bill by up to $ 2820/month. It also reveals that mechanized and decentralized solutions were not effective for inert waste, its disposal to landfill was more suited alternative.

Synthesis and site selective C-H functionalization of imidazo-[1,2-a]pyridines.

Imidazo[1,2-a]pyridine has attracted much interest in drug development because of its potent medicinal properties, therefore the discovery of novel methods for its synthesis and functionalization continues to be an exciting area of research. Although transition metal catalysis has fuelled the most significant developments, extremely beneficial metal-free approaches have also been identified. Even though pertinent reviews focused on imidazo[1,2-a]pyridine synthesis, properties (physicochemical and medicinal), and functionalization at the C3 position have been published, none of these reviews has focused on the outcomes obtained in the field of global ring functionalization. We wish here to describe a brief synthesis and an overview of all the functionalization reactions at each carbon atom, viz, C2, C3, C5, C6, C7 and C8 of this scaffold, divided into sections based on site-selectivity and the type of functionalization methods used.

Youth focused life skills training and counselling services program-An inter-sectoral initiative in India: Program development and preliminary analysis of factors affecting life skills.

OBJECTIVES: This paper describes the methodology of developing and implementation of a youth focused life skills training and counselling services programme (LSTCP) and assessment of factors associated with life skills of participants pre-training. DESIGN: Development of all aspects of LSTCP (modules, methods and evaluation) was through a consultative process. Experiential learning based facilitation was decided as the approach for training participants. A quasi-experimental design with pre, post and follow-up assessment post-training was finalised. Data collection was done using specifically developed semi-structured self-administered questionnaire. RESULTS: Multivariable logistic regression with life skills as outcome and various exposure variables was performed. About 2/3rd of participants had high level of life skills (68%). Increased score of extraversion (AOR = 1.57,95% CI = 1.32-1.85), agreeableness (AOR = 1.42,95% CI = 1.16-1.73), conscientiousness (AOR = 1.9,95% CI = 1.55-2.33), physical (AOR = 1.03,95% CI = 1.01-1.04), environmental (AOR = 1.02,95% CI = 1.004-1.03) and social quality of life (AOR = 1.01,95% CI = 1.006-1.02) were associated with high life skills score. Higher score of neuroticism (AOR = 0.66,95% CI = 0.53-0.79) was associated with low life skills score. CONCLUSION: The results presented provide an opportunity to understand the evolution of factors affecting life skills during the follow-up of this study. This study throws light on development of LSTCP for apparently healthy population in a setting like India and its states.

Morphological, phytochemical, and transcriptome analyses provide insights into the biosynthesis of monoterpenes in Monarda citriodora.

MAIN CONCLUSION: Morphological, phytochemical, and transcriptome analyses revealed candidate genes involved in the biosynthesis of volatile monoterpenes and development of glandular trichomes in Monarda citriodora. Monarda citriodora Cerv. ex Lag. is a valuable aromatic plant due to the presence of monoterpenes as major constituents in its essential oil (EO). Thus, it is of sheer importance to gain knowledge about the site of the biosynthesis of these terpenoid compounds in M. citriodora, as well as the genes involved in their biosynthesis. In this study, we studied different types of trichomes and their relative densities in three different developmental stages of leaves, early stage of leaf development (L1), mid-stage of leaf development (L2), and later stage of leaf development (L3) and the histochemistry of trichomes for the presence of lipid and terpenoid compounds. Further, the phytochemical analysis of this plant through GC-MS indicated a higher content of monoterpenes (thymol, thymoquinone, γ-terpinene, p-cymene, and carvacrol) in the L1 stage with a substantial decrease in the L3 stage of leaf development. This considerable decrease in the content of monoterpenes was attributed to the decrease in the trichome density from L1 to L3. Further, we developed a de novo transcriptome assembly by carrying out RNA sequencing of different plant parts of M. citriodora. The transcriptome data revealed several putative unigenes involved in the biosynthesis of specialized terpenoid compounds, as well as regulatory genes involved in glandular trichome development. The data generated in the present study build a strong foundation for further improvement of M. citriodora, in terms of quantity and quality of its essential oil, through genetic engineering.

Ru(II)-Catalyzed Synthesis of Fused Imidazo[1,2-a]pyridine-chromenones and Methylene-Tethered Bis-imidazo[1,2-a]pyridines and Regioselective O-Acetoxylation of Imidazo[1,2-a]pyridines.

Herein, we disclose an unprecedented protocol via ruthenium-catalyzed annulation for the synthesis of 6H-chromeno[4',3':4,5]imidazo[1,2-a]pyridin-6-one, and functionalized 2-(3-formylimidazo[1,2-a]pyridin-2-yl)phenyl acetate has been revealed by intramolecular chelation-assisted C-H activation. Additionally, a one-pot approach for creating bis(2-phenylimidazo[1,2-a]pyridin-3-yl)methane (BIP) has been realized through ruthenium catalysis with the use of formic acid. This method was used in gram-scale synthesis of BIP and step-economical late-stage functionalization of a marketed drug, zolimidine, in good yield.

miWords: transformer-based composite deep learning for highly accurate discovery of pre-miRNA regions across plant genomes.

Discovering pre-microRNAs (miRNAs) is the core of miRNA discovery. Using traditional sequence/structural features, many tools have been published to discover miRNAs. However, in practical applications like genomic annotations, their actual performance has been very low. This becomes more grave in plants where unlike animals pre-miRNAs are much more complex and difficult to identify. A huge gap exists between animals and plants for the available software for miRNA discovery and species-specific miRNA information. Here, we present miWords, a composite deep learning system of transformers and convolutional neural networks which sees genome as a pool of sentences made of words with specific occurrence preferences and contexts, to accurately identify pre-miRNA regions across plant genomes. A comprehensive benchmarking was done involving >10 software representing different genre and many experimentally validated datasets. miWords emerged as the best one while breaching accuracy of 98% and performance lead of ~10%. miWords was also evaluated across Arabidopsis genome where also it outperformed the compared tools. As a demonstration, miWords was run across the tea genome, reporting 803 pre-miRNA regions, all validated by small RNA-seq reads from multiple samples, and most of them were functionally supported by the degradome sequencing data. miWords is freely available as stand-alone source codes at https://scbb.ihbt.res.in/miWords/index.php.

Simultaneous Sustained Drug Delivery, Tracking, and On-Demand Photoactivation of DNA-Hydrogel Formulated from a Biomass-Derived DNA Nanoparticle.

Conversion of biomass into nanoparticles for meaningful biomedical applications is a formidable proposition with excellent prospects but fewer patrons. A lack of general methodology for upscaled production and limited versatility of those nanoparticles are the main drawbacks. Herein, we report the creation of a DNA nanoparticle (DNA Dots) from onion genomic DNA (gDNA), a plant biomass source, through controlled hydrothermal pyrolysis in water without any chemicals. The DNA Dots are further formulated into a stimuli-responsive hydrogel through hybridization-mediated self-assembly with untransformed precursor gDNA. The versatility of the DNA Dots is recognized through its crosslinking ability with gDNA through its dangling DNA strands on the surface resulting from incomplete carbonization during annealing without the need for any external organic, inorganic, or polymeric crosslinkers. The gDNA-DNA Dots hybrid hydrogel is shown to be an excellent drug delivery vehicle for sustained release trackable through the inherent fluorescence of the DNA Dots. Interestingly, the DNA Dots are photoexcited with normal visible light to generate on-demand reactive oxygen species, making them exciting candidates for combination therapeutics. Most importantly, the ease with which the hydrogel is internalized in fibroblast cells with minimal cytotoxicity should encourage the nanotization of biomass as a tool for interesting sustainable biomedical applications.