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Background: Molecular identification of a wide range of organisms capable of carrying out biological nitrogen fixation (BNF) are diverse in nature and significantly improves plant growth. Biological N2 fixation reflects the activity of a phylogenetically diverse list of microorganisms. Molecular characterization provides efficient means to identify organisms with the potential of N2 fixation. Applying these techniques in an array of environments has considerably broadened our understanding of the suite of organisms that can carry out BNF. Methods: Thirty-four strains of free living N2 fixing bacterial strains were isolated from diverse plants cultivated in North Gujarat, including wheat, cotton, castor and pearl millet, using a nitrogen-free selective medium. Acetylene reduction assay was used to check the ability of all bacteria to fix nitrogen. Hybridization with nifH probe derived from Azotobacter vinelandii with isolated freeliving nitrogen-fixing bacteria showed a positive result. The selected strains were characterized by molecular analysis like; ARDRA and 16S rDNA sequencing. Result: Based on molecular characterization 17 strains to known groups of nitrogen-fixing bacteria, including organisms from the genus Azotobacter, Pseudomonas, Enterobacter, Arthrobacter, Bacillus, Variovorax, Nocardiodies, Rhodococcus, Mycobacterium, Planococcus, Microbacterium have been identified. One of the strains was identified as unknown bacteria. The potential strains were identified by 16 srDNA analysis and also corroborated by morphological and biochemical characterization. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) disorders are becoming increasingly common in young people in India and globally (1). Diet (eating habits, nutrient intake, and dietary diversity) and mental health (stress and anxiety levels) factors can independently and synergistically regulate gut health through dietary modulation of gut microbiota composition and gut-brain axis-related mechanistic pathways (2 - 3). However, few studies have investigated the associations between diet, mental health, and GI-related disturbances. Hence, this observational study was conducted to explore the possible effects of eating behaviors and stress and anxiety symptoms on self-reported measures of gastrointestinal health among 18-45-year-old adults in India. A purposive cluster sampling method guided the recruitment of participants (n=407). Two non- consecutive day 24-hour diet recalls were conducted to estimate nutrient intakes and calculate Individual Diet Diversity (IDD) and Food Variety Scores (FVS). Gastrointestinal health was assessed using a validated instrument comprising 35 items related to gastric, small intestine, and colon function, and GI inflammation. Perceived Stress Scale (PSS-10 scores 0 to 40 with higher scores representing higher levels of stress), and Generalized Anxiety Disorder Scale (GAD-7 scores >5 (mild), >10 (moderate), and >15 (severe)) were used to evaluate perceived stress and anxiety (4 - 5). Socioeconomic status and eating habits were self-reported and the anthropometry measurements were recorded. Multivariable logistic regression analysis was performed using sociodemographic characteristics, anthropometry measurements, eating habits, and stress and anxiety levels as independent (predictor) variables, and composite gastrointestinal health risk scores as the dependent variables. Participants reported mild anxiety (mean (M) = 7.09, standard deviation (SD)= 3.25) and moderate stress (M=18.44; SD= 9.89) with preponderance among females, higher age groups (> 35 years), and lower socioeconomic status. Overall, 38.8% and 45.3% were at high-risk score categories for gastric function and GI inflammation respectively. Higher energy and fat consumption, frequent breakfast skipping, and lower IDDS and FVS scores were associated with higher scores for stress and anxiety. Moreover, participants having moderate to severe anxiety reported a higher frequency of GI symptoms such as indigestion (M= 3.23 SD= 2.1-4.6, p= 0.023), excessive belching (M= 2.36 SD =1.21, p=0.043), and post-meal lower abdominal discomfort and cramps (M= 3.07, SD = 2.22, p < 0.001) as compared to those having nominal/mild anxiety. Age-adjusted regression models showed higher waist circumference (OR= 4.69, 95% CI =1.33- 7.28, p= 0.034), and stress scores (OR= 1.66, 95% CI= 1.32-1.90, p = 0.042), lower IDDS (OR= 2.34, 95% CI=1.80- 2.91, p <0.001) and presence of > 2 co-morbid conditions (OR= 8.12, 95% CI = 5.34- 11.21, p < 0.001) as predictors of higher GI disorder risk scores. The preliminary findings of the study highlight associations between diet, stress, and GI health, presenting opportunities to modulate diet and optimize mental health to prevent and reduce the severity of GI disorders. [ABSTRACT FROM AUTHOR]

Goat is mainly reared for the milk and meat purpose. The quality and quantity of milk and meat are dependent on digestive system. The Goat is ruminant animal and the Reticulum has special role in the digestive system. For the present study, fresh ruminant stomach of six healthy adult Surti goats were procured from the local abattoirs of Anand. After separating the reticulum, different gross, biometrical as well as histological examination had performed. The mean±SE value of weight of reticulum was 121.50±5.29gm. The mean±SE values of longitudinal circumference and transverse circumference were 29.08±1.27 cm and 25.95±1.86 cm, respectively. The mean±SE values of length and width of reticular cells were 19.17±0.67 mm and 13.97±0.48 mm, respectively. The mean±SE value of length of oesophageal groove was 8.80±0.28 cm. Histology of reticular mucosa showed characteristic reticular crests which were wide with stratified squamous epithelium having lamina propria protrusions of the mucosa. Muscularis mucosa was present only inside the reticular crest and absent at its base. Histology of oesophageal groove revealed stratified squamous epithelium, lamina propria, submucosa and musculosa. A group of smooth muscles was also present between lamina propria and submucosa. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the histological and histochemical changes in naturally occurring canine demodicosis. Results show that the canine demodicosis affected skin showed reduced distribution of elastic fibers and the distribution of mucopolysaccharides in the affected skin was also slightly reduced. It was also found that there was mild and sparse activity of succinic dehydrogenase (SDH) enzyme in the cells of epidermis and adnexa of the affected skin.

Three young calves with a history of lameness were subjected to detailed orthopaedic and radiographic examination to confirm fracture. Intramedullary pin was advocated for fixation after proper alignment of the fracture fragments with additional circlage wires in one calf. This technique helped to immobilize the fractured fragments from transverse movements and in case of oblique fractures proper holding of bone fragments was made possible with circlage wires. The bamboo splints of proper length were used for external support up to 60 days. All the animals showed partial weight bearing by 1sl post-operative day whereas complete weight bearing on 26 to 32 post-operative days. Post-operative radiography revealed no disturbances in reduction and displacement of fractured fragments in all three calves except in one calf, where proximal migration of Steinmann pin was observed at 15th post-operative day. Radiographs showed more radio-dense callus bridging the fractured fragments at 30lh day and more discrete and compact callus at 45th post-operative day. Radiographs showed reduction in callus size and disappearance of fracture gap in all calves at 60th post-operative day. Intramedullary pinning fixation gave satisfactory results in calves with tibial fractures but final decision was depend on patient condition and fracture type. [ABSTRACT FROM AUTHOR]

Novel unsaturated polyester amide resins (UPEAs) were prepared by the addition reaction of commercially available epoxy resin, namely diglycidyl ether synthesized from bisphenol-A and epichlorohydrin and having the molecular weight 340 with aromatic unsaturated bisamic acids. These UPEAs were characterized by elemental analysis and number average molecular weight determination by nonaqueous conductometric titrations. The curing study of these UPEAs was carried out by using benzoyl peroxide (BPO) as a catalyst and was monitored by using a differential scanning calorimeter (DSC). According to the curing temperature obtained from the DSC thermograms, the glass fiber reinforced composites (i.e., laminates) of these UPEA–BPO systems have been fabricated. The chemical, mechanical, and electrical properties of these glass fiber composites have also been evaluated. The unreinforced cured samples of the UPEA resins were also analyzed by using thermogravimetric analyzer (TGA). [ABSTRACT FROM AUTHOR]

There is great interest in fabricating devices that can detect and remove water pollutants, especially heavy metal ions and dyes from wastewater, to promote sustainable water use. In this study, an extract of Borassus flabellifer leaves (BoF-LE) was used to synthesize silver nanoparticles (BoF-AgNPs), with the BoF-LE serving as a reducing and capping agent. The sensitivity and selectivity of BoF-AgNPs for Mn(II) ions were tested by comparing with the control sample and other competent metal ions. Our results showed that BoF-AgNPs are extremely sensitive and selective in detecting Mn(II) ions, with a detection limit of 0.3 ppb. HR-TEM, UV-Vis spectroscopy, and DLS investigations were used to confirm that BoF-AgNPs detect Mn(II) ions by an aggregation-based mechanism. Additionally, it was found that BoF-AgNPs are effective in rapidly decolorizing MB dye, as demonstrated by their ability to decolorize MB by 92.66% within 7 min. This study is the first to report successful synthesis of BoF-AgNPs and their two applications, which are enabled with an Inhibit-AND logic gate. Using BoF-AgNPs to detect and degrade water pollutants may promote sustainable water use., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Kritika S. Sharma reports financial support was provided by Department of Science and Technology (DST), Ministry of Science & Technology, India. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Liposomes being a promising colloidal system facilitates delivery of drugs with limited pharmacokinetic properties to achieve desirable clinical applications. However, development of a stable liposomal system is always challenging due to multiple complexities involved. Aqueous instability of liposomes and impact of various process and formulation parameters can lead to serious alteration of its therapeutic performance. In the proposed work, the authors aim to develop stable Ibrutinib-loaded liposomes using lyophilization and Quality-by-Design and assess their long-term stability. Ibrutinib-loaded liposomes were developed and optimized using Quality-by-Design technique and were further PEGylated and characterized for the same. Effect of cryoprotectants during lyophilization and other parameters are evaluated to obtain a robust formulation. The stability studies were conducted upto 6 months at various storage conditions to evaluate the effect of lyophilization. The impact of formulation, processing and lyophilization parameters on physicochemical properties of developed liposomal systems were evaluated and are critically discussed. Liquid dispersion exhibited a %degradation of 16-36% at 25 °C/60% RH which was reduced for less than 1% in lyophilized formulation for 6 months. Critical analysis and assessment of various parameters lead to identification of optimum conditions to manufacture this drug product and also opens way forward for further evaluation and translational possibilities., (© 2024. Controlled Release Society.)

Objective: Black girls disproportionately face adverse sexual and reproductive health outcomes in their lifetime. In healthcare, Black girls experience racism and misogyny, which manifest as a combination of discriminatory practices and biases that result in their symptoms being dismissed or neglected, their voices silenced, inadequate treatment, and higher mortality rates. Pediatric providers are in an ideal position to influence, advocate, and strengthen Black girls' sexual and reproductive health. The purpose of this topical review is to discuss current guidelines and provide recommendations to improve pediatric sexual and reproductive care for Black girls., Methods: We examine current pediatric guidelines and recommendations for adolescent sexual and reproductive health., Results: Current guidelines recommended by organizations and professional societies such as the Centers for Disease Control and Prevention, World Health Organization, Society of Adolescent Health Medicine, and American Academy of Pediatrics are inconsistent and insufficient for the unique needs of Black girls., Conclusions: We offer three recommendations for pediatric providers to ensure the optimal sexual and reproductive health care for Black girls. These provider recommendations will aid in the protection of Black girls' sexual and reproductive health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The incidence of Central Nervous System (CNS) disorders, including Parkinson's disease, Alzheimer's disease, stroke, and malignancies, has risen significantly in recent decades, contributing to millions of deaths annually. Efficacious treatment of these disorders requires medicines targeting the brain. The Blood-Brain Barrier (BBB) poses a formidable challenge to effective drug delivery to the brain, hindering progress in CNS therapeutics. This review explores the latest developments in nanoparticulate carriers, highlighting their potential to overcome BBB limitations., Objective: This study aimed to evaluate and summarise the critical factors and pathways in the nanoparticle- based central nervous system's targeted drug delivery., Methods: An extensive literature search was conducted, comprising the initial development of nanoparticle- based central nervous system-targeted drug delivery approaches to the latest advancements using various online search tools., Results: The properties of nanoparticles, such as type of nanoparticles, size, shape, surface charge, hydrophobicity, and surface functionalisation, along with properties of the blood-brain barrier during normal and pathological conditions and their impact on the delivery of nanoparticles across the BBB, are identified and discussed here., Conclusion: Important properties and pathways that determine the penetration of nanoparticles across the central nervous system are reviewed in this article, along with recent advances in the field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Black girls in the USA face disproportionate rates of sexually transmitted infections (STIs), HIV, and sexual violence, prompting research into the sociocultural factors such as adultification, race and gender discrimination, and stereotyped messaging, impacting Black girls' sexual development. While existing literature finds that Black female caregivers utilise protective strategies to mitigate potential harm to Black girls, little is known about the role of Black male caregivers. This qualitative study employed the Becoming a Sexual Black Woman framework and one-on-one interviews to examine how 30 Black male caregivers of girls conceptualised parental protection and elated strategies. The thematic analysis revealed key themes of: Being a Provider, Being a Present Role Model, Protecting Black Girls' Bodies, Limiting Exposure to Stereotyped Messages, and Providing Emotional Protection. Black male caregivers navigated traditional gendered expectations and limited resources while utilising parental strategies that reflected patriarchal, sometimes misogynistic, and non-patriarchal ideals and norms. The study highlights the attitudes and beliefs of Black male caregivers regarding protecting Black girls from sexual violence and other related adverse outcomes. The findings offer insights for family-based interventions and programmes that empower Black girls to support their sexual development and health in the USA.

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal types of cancer with high mortality/incidence. Considering the crucial role of vascular endothelial growth factor (VEGF) in PDAC progression, its inhibition can be a viable strategy for the treatment. Pazopanib, a second-generation VEGF inhibitor, is approved for the treatment of various oncological conditions. However, due to associated limitations like low oral bioavailability (14-39%), high inter/intra-subject variability, stability issues, etc., high doses (800 mg) are required, which further lead to non-specific toxicities and also contribute toward cancer resistance. Thus, to overcome these challenges, pazopanib-loaded PEGylated nanoliposomes were developed and evaluated against pancreatic cancer cell lines. The nanoliposomes were prepared by thin-film hydration method, followed by characterization and stability studies. This QbD-enabled process design successfully led to the development of a suitable pazopanib liposomal formulation with desirable properties. The % entrapment of PZP-loaded non-PEGylated and PEGylated nanoliposomes was found to be 75.2% and 84.9%, respectively, whereas their particle size was found to be 129.7 nm and 182.0 nm, respectively. The developed liposomal formulations exhibited a prolonged release and showed desirable physicochemical properties. Furthermore, these liposomal formulations were also assessed for in vitro cell lines, such as cell cytotoxicity assay and cell uptake. These studies confirm the effectiveness of developed liposomal formulations against pancreatic cancer cell lines. The outcomes of this work provide encouraging results and a way forward to thoroughly investigate its potential for PDAC treatment., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background & objectives Trauma is one of the leading causes of disability and death, worldwide. Ninety per cent of trauma related mortality occurs in low- and middle-income countries (LMICs). Despite this, there is paucity of literature emanating from LMICs with studies that present and/or evaluate feasible interventions that can have a measurable impact on outcomes after injury, primarily mortality. The current article aims at developing such interventions key elements of implementation and measures of compliance and impact. Methods A literature review was conducted to evaluate the status of injury care among LMICs worldwide. Based on this review, interventions were identified/developed, that (i) were feasible to implement within the constraints of available resources; (ii) could be implemented within a two year timespan; and (iii) would improve outcomes primarily, mortality. These interventions were then discussed at a symposium of experts and stakeholders from around the world. Results The literature review identified gaps across the entire spectrum of injury care at all levels - primary, secondary and tertiary prevention. Additionally, lack of data systems capable of ensuring quality of care and driving performance improvement was identified. Utilizing the review as the basis and focusing on hospital level interventions, one policy intervention, five in-hospital interventions and one major research question were identified/developed that met the defined criteria. Interpretation & conclusions Gaps in trauma care in LMICs at every level and in data systems were identified. Feasible interventions that can be implemented within the resource constraints of LMICs in a reasonable timeframe and that can have a measurable impact on injury related mortality were developed and are presented.

Background: Bitter melon has been used to stop the growth of breast cancer (BRCA) cells. However, the underlying mechanism is still unclear., Aim: To predict the therapeutic effect of bitter melon against BRCA using network pharmacology and to explore the underlying pharmacological mechanisms., Methods: The active ingredients of bitter melon and the related protein targets were taken from the Indian Medicinal Plants, Phytochemistry and Therapeutics and SuperPred databases, respectively. The GeneCards database has been searched for BRCA-related targets. Through an intersection of the drug's targets and the disease's objectives, prospective bitter melon anti-BRCA targets were discovered. Gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses were carried out to comprehend the biological roles of the target proteins. The binding relationship between bitter melon's active ingredients and the suggested target proteins was verified using molecular docking techniques., Results: Three key substances, momordicoside K, kaempferol, and quercetin, were identified as being important in mediating the putative anti-BRCA effects of bitter melon through the active ingredient-anti-BRCA target network study. Heat shock protein 90 AA, proto-oncogene tyrosine-protein kinase, and signal transducer and activator of transcription 3 were found to be the top three proteins in the protein-protein interaction network study. The several pathways implicated in the anti-BRCA strategy for an active component include phosphatidylinositol 3-kinase/protein kinase B signaling, transcriptional dysregulation, axon guidance, calcium signaling, focal adhesion, janus kinase-signal transducer and activator of transcription signaling, cyclic adenosine monophosphate signaling, mammalian target of rapamycin signaling, and phospholipase D signaling., Conclusion: Overall, the integration of network pharmacology, molecular docking, and functional enrichment analyses shed light on potential mechanisms underlying bitter melon's ability to fight BRCA, implicating active ingredients and protein targets, as well as highlighting the major signaling pathways that may be altered by this natural product for therapeutic benefit., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest in this paper., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: People with diabetes have an increased risk of heart failure (HF), compared to those without diabetes. However, no comprehensive systematic review and meta-analysis has explored whether these associations could differ in relation to prevalent cardiovascular disease (CVD)., Aims: To estimate the association between diabetes and incident heart failure (HF), compared to without diabetes, in individuals with and without CVD., Methods: PubMed, Scopus, and Web of Science were searched for observational cohort studies from the earliest dates to 22 nd March 2023. A random-effects model calculated the pooled relative risk (RR)., Results: Of 11,609 articles, 31 and 6 studies reported data in people with type 2 diabetes (T2D) and type 1 diabetes (T1D) respectively. Individuals with T2D had an increased risk of HF irrespective of CVD prevalence: 1.61 (95% CI: 1.35-1.92) in those with CVD; 1.78 (1.60-1.99) without CVD; and 2.02 (1.75-2.33) with unspecified CVD prevalence. Meta-regression did not identify a significant difference comparing HF risk in T2D individuals with vs. without CVD (p=0.232)., Conclusion: Peoplewith T2D, compared to those without diabetes, have similar increased risk of HF, regardless of CVD prevalence. Strategiesproven to lower HF risk in T2D individuals should be prioritized for those with and without CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The medical profession has experienced a significant increase in the number of women practitioners in recent decades, leading to a reduction in the gender gap. According to the United States Medical Association, approximately 25% of physicians in the United States are now women. Although this progress is evident in the clinical setting, women's representation in academic medicine remains disproportionately low. The underrepresentation of women in academia has various consequences, including limited access to academic resources and hindered career growth. Previous studies have attempted to analyze these disparities, but results have been inconsistent, and the issue's complexity has not been fully understood. This study aims to examine the disparity in the gender of first authors in academic publications related to " Artificial intelligence (AI) and Attention Deficit Hyperkinetic Disorder (ADHD)" between 2010 and 2023. Analysis was conducted on June 21st, 2023, using the database PubMed. The search term "AI" AND "ADHD" was used to derive all articles over a period of 13 years, from January 1st, 2010, to December 31st, 2022, excluding the year 2023 due to limited available publications. The relevant articles were downloaded in Microsoft Excel sheets. The gender of the first authors was determined using the NamSor app V.2, an application programming interface (API) with a large dataset of names and countries of origin. A total of 204 articles were considered for this study. There were 78 female first authors and 126 male first authors. The highest number of publications with a male first author occurred in 2022, with 32 publications. The Netherlands, Singapore, Turkey, and China have the highest gender ratios, indicating a more favourable representation of both genders. The p-value of 0.2664 suggests that there is no significant association between gender and country. The findings revealed a gender disparity, with a higher number of male first authors. By addressing and rectifying these disparities, we can enhance the overall quality, diversity, and inclusivity of research in the field of ADHD and Artificial Intelligence., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abraham et al.)

Most cancer patients rarely benefit from monodrug therapy because of both cancer complexity and tumor environment. One of the main reasons for this failure is insufficient accumulation of the optimal dose at the tumorous site. Our investigation implies a promising strategy to engineer prodrug nanoparticles (NPs) of bortezomib (BTZ) and selenium (Se) using sialic acid (SAL) as a ligand to improve breast cancer therapy. BTZ was conjugated with SAL and HPMA ( N -2-hydroxypropyl methacrylamide) to prepare a prodrug conjugate; BTZ-SAL-HPMA (BSAL-HP) and then fabricated into prodrug NPs with Se (Se&#95;BSAL-HP prodrug NPs). The self-assembly of prodrug NPs functionalized with Se showed size (204.13 ± 0.02 nm) and zeta potential (-31.0 ± 0.11 mV) in dynamic light scattering (DLS) experiments and spherical shape in TEM and SEM analysis. Good stability and low pH drug release profile were characterized by Se&#95;BSAL-HP prodrug NPs. The tumor-selective boronate-ester-based prodrug NPs of BTZ in combination with Se endowed a synergistic effect against cancer cells. Compared to prodrug conjugate, Se&#95;BSAL-HP prodrug NPs exhibited higher cell cytotoxicity and enhanced cellular internalization with significant changes in mitochondria membrane potential (MMP). Elevated apoptosis was observed in the (G2/M) phase of the cell cycle for Se&#95;BSAL-HP prodrug NPs (2.7-fold) higher than BTZ. In vivo studies were performed on Sprague-Dawley rats and resulted in positive trends. The increased therapeutic activity of Se&#95;BSAL-HP prodrug NPs inhibited primary tumor growth and showed 43.05 fold decrease in tumor volume than the control in 4T1 tumor bearing mice. The surprising and remarkable outcomes for Se&#95;BSAL-HP prodrug NPs were probably due to the ROS triggering effect of boronate ester and selenium given together.

Over the decades, water contamination has increased substantially and has become a severe global issue. Degradation of natural resources is taking place at an alarming rate as a result of the use of chemicals like dyes, heavy metals, fertilizers, pesticides, and many more, necessitating the development of long-term pollution remediation methods/technologies. As a new development in the field of environmental engineering, electrodeionization incorporates both traditional ion exchange and electrodialysis. This communication provides an overview of hazardous contaminants such as dyes, heavy metals, fertilizers, and pesticides, as well as their converted forms, which are present in water. It highlights the risks of water pollutants to public health and the environment. Various electrochemical methods with a focus on electrodeionization for the treatment of wastewater and removal of hazardous contaminants are outlined in this review. Additionally, this review discusses the challenges and the future outlook for the development in this field of research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" products. However, the underlying challenges involved in the development, scalability, and characterization of these injectable products are critical. Moreover, the guidelines available do not provide a clear understanding of these complex products, making it difficult to anticipate the regulatory requirements. Thus, it becomes imperative to comprehend the criticalities and develop an understanding of these products. This review discusses various complexities involved in the parenteral products such as complex drug substances, excipients, dosage forms, drug administration devices like pre-filled syringes and injector pens, and its different characterization tools and techniques. The review also provides a brief discussion on the regulatory aspects and associated hurdles with other parenteral products., (© 2022. Controlled Release Society.)

Upadacitinib, an oral  Janus kinase  ( JAK )  inhibitor , is used to manage rheumatoid arthritis. The objective was to generate statistical evidence from the existing data for upadacitinib  efficacy and safety in various treatment regimens with different dosages in active rheumatoid arthritis patients. We searched PubMed, Cochrane, and ClinicalTrials.gov using PRISMA guidelines, providing data on the efficacy and safety of u padacitinib  versus placebo in rheumatoid arthritis. 20% improvement in the American College of Rheumatology (ACR20) score response at 12 weeks was the primary outcome measure. Safety in adverse events, infections, or hepatic dysfunction was considered. The Mantel-Haenszel formula with random effect was used for the pooled odds ratio (OR) at a 95% confidence interval (CI) for dichotomous data. Meta-analysis was performed using RevMan version 5.4. Statistical heterogeneity was reported using I2 statistics; I2 > 75% was considered significant heterogeneity. A P value of less than 0.05 was considered significant. Data from 3233 patients were included in the analysis. The use of upadacitinib was associated with increased rates of achieving an ACR20 response compared with placebo (pooled OR 3.71; 95% CI 3.26-4.23; p-value <0.00001). Compared to a placebo, a 12 mg twice daily dose had the greatest effect, followed by a 15 mg once daily dose. Compared to the placebo, the incidence of any adverse event (pooled OR 1.66; 95% CI 1.36-2.02; p-value 0.0001) and infection (pooled OR 1.46; 95% CI 1.23-1.74; p-value 0.001) was found to be significantly higher in upadacitinib. Other adverse events, such as hepatic disorders and herpes zoster infections, were not statistically significant (p-value> 0.05). Maximum adverse events were seen at 12 mg twice daily. Upadacitinib, 15 mg once daily in combination with Methotrexate, was the most efficacious treatment regimen and was not associated with a significant risk for treatment-related adverse events in rheumatoid arthritis patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Panchal et al.)

Cancer is one of the major causes of mortality, globally. Cancerous cells invade normal cells and metastasize to distant sites with the help of the lymphatic system. There are several mechanisms involved in the development and progression of cancer. Several treatment strategies including the use of phytoconstituents have evolved and been practiced for better therapeutic outcomes against cancer. Fisetin is one such naturally derived flavone that offers numerous pharmacological benefits, i.e., antioxidant, anti-inflammatory, antiangiogenic, and anticancer properties. It inhibits the rapid growth, invasiveness, and metastasis of tumors by hindering the multiplication of cancer cells, and prompts apoptosis by avoiding cell division related to actuation of caspase-9 and caspase-8. However, its poor bioavailability associated with its extreme hydrophobicity hampers its clinical utility. The issues related to fisetin delivery can be addressed by adapting to the developmental aspects of nanomedicines, such as formulating it into lipid or polymer-based systems, including nanocochleates and liposomes. This review aims to provide in-depth information regarding fisetin as a potential candidate for anticancer therapy, its properties and various formulation strategies.

Objective: Glioblastoma Multiforme (GBM), a devastating the most common primary malignant intracranial brain tumors. In India, the incidence of this malignancy is escalating, however, there are very few studies on this tumor entity from Indian population. The present study sought to investigate the prevalence and prognostic significance of Signal Transducer and Activator of Transcription 3 (STAT3) gene expression in GBM patients from Western India., Method: STAT3 gene expression using real-time PCR was detected in total 55 GBM patients. The impact of STAT3 aberrant expression on progression-free survival (PFS) and overall (OS) was analysed using univariate and multivariate survival analysis. The data were analysed using SPSS statistical software and p value ≤0.05 was considered as significant., Results: The aberrant STAT3 expression was found in 85% (47/55) of patients with -1.12 fold change down-regulation in 49% (23/47) and 3.36 fold change up-regulation was noted in 51% (24/47) of patients. In wild type IDH tumors (n=30), down regulation and up regulation of STAT3 was noted in 63% and 27% of patients, respectively, whereas, for IDH mutant GBM tumors (n=25), the incidence of low expression and high expression of STAT3 was noted in 16% and 68% of patients, respectively. Thus, we found that incidence of STAT3 down regulation was significantly high in patients with IDH wild type tumors, whereas, in IDH mutant GBM tumors, the incidence of up-regulated STAT3 was significantly high (P=0.021, χ2=12.81, r=+0.310). In Kaplan-Meier univariate survival analysis, a part from age (P=0.006), tumor location (P=0.025), and KPS score (P=0.002), co-detection of STAT3 up regulation and presence of IDH mutation (P=0.030) remained significant prognostic factors for PFS and OS. In multivariate survival analysis also, co-detection of STAT3 high expression and presence of IDH mutation remained independent prognosticators for PFS (HR=6.45, 95% CI=1.32-31.40, P=0.021) and OS (HR=8.69, 95% CI=1.66-45.51, P=0.010)., Conclusion: For GBM tumors, STAT3 up-regulation and presence of IDH mutations together predicts better survival. This reflects unique molecular etiology for GBM patients. Therefore, they would be useful in the future for targeted therapy and for clinicians they would be useful for better patient management. However, study on a larger sample size is required for validation., (© 2022. The Author(s).)

Protein kinases, a class of enzymes that govern various biological phenomena at a cellular level, are responsible for signal transduction in cells that regulate cellular proliferation, differentiation, and growth. Protein kinase enzyme mutation results in abnormal cell division leading to a pathological condition like cancer. Tyrosine kinase (TK) inhibitors, which helps as a potential drug candidate for the treatment of cancer, are continuously being developed. Majority of these drug candidates are being administered as conventional oral dosage form, which provides limited safety and efficacy due to non-specific delivery and uncontrolled biodistribution resulting into the adverse effects. A controlled drug delivery approach for the delivery of TK inhibitors may be a potential strategy with significant safety and efficacy profile. Novel drug delivery strategies provide target-specific drug delivery, improved pharmacokinetic behaviour, and sustained release leading to lower doses and dosing frequency with significantly reduced side effects. Along with basic aspects of tyrosine kinase, this review discusses various aspects related to the application of tyrosine kinase inhibitors in clinical oncological setting. Furthermore, the limitations/challenges and formulation advancements related to this class of candidates particularly for cancer management have been reviewed. It is expected that innovations in drug delivery approaches for TK inhibitors using novel techniques will surely provide a new insights for improved cancer treatment and patients' life quality., (Copyright © 2021 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Multivesicular liposomes (MVLs) are non-concentric, lipid-based micron-sized spherical particles. The usage of MVL for sustained drug delivery has seen progression over the last decade due to successful clinical and commercial applications. It provides attractive characteristics, such as high encapsulation efficiency, variety of sizes, structural stability, and different choices for the route of administration. Drug molecules are encapsulated in internal aqueous compartments of MVL, separated by lipid bilayer septa to form polyhedral structures. The integrity of these entrapped small molecules, peptides, or proteins is maintained throughout the therapy, thus providing sustained drug release on non-vascular administration. Despite the frequent use of unilamellar liposomes, characterization of MVLs is critical due to different puzzling problems, such as real-time size evaluation, initial burst, and in vivo performance. Moreover, available regulatory guidelines on liposomal drug product development are insufficient to assure ample in vitro-in vivo behavior of MVL. This review hereby highlights the innovations pertaining to development and manufacturing procedures, drug release mechanisms, and characterization techniques. The review also summarizes the applications, challenges, and future perspectives for successfully translating the research concept to a clinically accepted delivery system. Despite the intricacies involved in the development of MVL, establishing steadfast characterization techniques and regulatory paths could pave the way to its extensive clinical use., (© 2021. Controlled Release Society.)

Growing evidence suggests that community-based interventions in low- and middle-income countries (LMICs) can effectively address harmful social norms that promote or sustain gender inequality and drive violence against women (VAW). However, understanding what actions communities are already taking to address harmful social norms and prevent VAW is an essential first step for intervention development. Towards this goal, drawing on collective action theory, we conducted a realist analysis of secondary qualitative data collected with communities in India, Afghanistan, Peru and Rwanda. We coded interview and focus-group data from 232 participants to identify the contexts, mechanisms and outcomes (CMO) relevant for community action. We synthesized CMO configurations from each dataset into a conceptual framework composed of three middle-range theories of mechanisms driving community action to prevent VAW in LMICs. Our results highlight the importance of dedicated spaces for discussing VAW, VAW leaders as positive role models, and community perceptions of VAW as a problem worthy of intervention. In Rwanda and Peru, there was strong evidence to support the operation of these mechanisms. Contextual factors, including national and local policy and programmes targeting VAW, activated mechanisms that led to community action. In India and Afghanistan, evidence for the presence of these mechanisms was weaker, with social norms about women's position and violence being a private family matter preventing communities from addressing violence. Despite contextual differences, our data demonstrated communities in all four settings were somewhere along a pathway of change towards VAW prevention. This supports the need to build future prevention interventions on pre-existing mechanisms that trigger community action, rather than implementing existing interventions without local adaptation. Our conceptual framework serves as a tool for assessing these mechanisms of community action as part of intervention development research, centring community knowledge and fostering local ownership for more relevant and sustainable VAW prevention interventions., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

ICU readmission is associated with increased mortality, resource utilisation and hospital expenditure. In the general population, respiratory-related event is one of the most common causes of unexpected ICU readmission. Patients with neurological deficits faced an increased risks of ICU readmissions due to impaired mentation, protective reflexes and other factors. A retrospective review revealed that the leading cause of unexpected ICU readmissions in adult neurovascular patients admitted to our hospital was respiratory related. A respiratory therapists-driven assessment-and-treat protocol was developed for proactively assessing and treating adult neurovascular patients. On-duty respiratory therapists assessed all neurovascular patients on admission, assigned a respiratory severity score to each patient and then recommended interventions based on a standardised algorithm.Our quality improvement initiative had no effect on the rate of unexpected ICU readmissions in adult neurovascular patients. When compared with the baseline population, patients enrolled in the intervention group were significantly older ((79, 68-85 years) vs (71, 56-81 years)), but they spent comparable amount of time in the ICU (4.5 vs 4 days, p=0.42). When the respiratory severity score was trended in the intervention group, patients demonstrated significant improvement in their respiratory function, with a greater proportion of patients scoring in the minimal and mild categories and smaller proportion in the moderate category (p<0.01)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The current study sought to explore the significance of copy number variations (CNVs) of MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived [avian]) and ALK (anaplastic lymphoma kinase) genes individually as well as their combined impact on clinical outcome and overall survival of patients with neuroblastoma (NB)., Methods: A total 71 individuals including healthy controls (n = 11), circulating DNA (n = 11), and primary tumors (n = 49) were evaluated to detect CNVs of MYCN and ALK genes using droplet digital polymerase chain reaction. Data were correlated with univariate and multivariate survival analysis., Results: CNVs of MYCN and ALK were detected in 27% and 18.2% from circulating DNA samples. A statistically significant difference in CNVs was noted between healthy controls and circulating DNA samples for MYCN (P = 0.001) and ALK (P = 0.004) genes. Further, we noted >70% concordance in CNVs of MYCN (P = 0.030) and ALK (P = 0.040) from primary tumors and concordant plasma samples of patients with NB. Multivariate survival analysis for disease-free survival (P = 0.031) and overall survival (P = 0.011) showed that CNVs of both genes emerged at step 1 and thus remained as significant markers for predicting early recurrence and shorter survival, respectively, for patients with NB., Conclusions: Our study showed that the analysis of circulating DNA by droplet digital polymerase chain reaction is a helpful technique to identify high-risk patients for aggressive therapy at an early stage of disease. We also concluded that codetection of MYCN and ALK is a more powerful tool for identifying high-risk patients with NB. Thus, this study showed a novel coordinately significant prognostic role of MYCN and ALK CNVs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Energy storage plays an important role in the adoption of renewable energy to help solve climate change problems. Lithium-ion batteries (LIBs) are an excellent solution for energy storage due to their properties. In order to ensure the safety and efficient operation of LIB systems, battery management systems (BMSs) are required. The current design and functionality of BMSs suffer from a few critical drawbacks including low computational capability and limited data storage. Recently, there has been some effort in researching and developing smart BMSs utilizing the cloud platform. A cloud-based BMS would be able to solve the problems of computational capability and data storage in the current BMSs. It would also lead to more accurate and reliable battery algorithms and allow the development of other complex BMS functions. This study reviews the concept and design of cloud-based smart BMSs and provides some perspectives on their functionality and usability as well as their benefits for future battery applications. The potential division between the local and cloud functions of smart BMSs is also discussed. Cloud-based smart BMSs are expected to improve the reliability and overall performance of LIB systems, contributing to the mass adoption of renewable energy., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2022 by the authors.)