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The emergence and subsequent advancement of nanotechnology in recent years have greatly benefited the healthcare sector, particularly in the treatment of cancer. As per study, major fatalities are related to the lung cancer. For many years, oral tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor (EGFR) family of receptors have been used in the clinic to treat human malignancies, although they observed some very serious adverse effects in the treatment of lung cancer, especially in non-small cell lung cancer (NSCLC). Despite EGFR-TKIs’ exceptional qualities as small-molecule targeted medications, their applicability is nevertheless limited by their poor solubility, inconsistent oral bioavailability, high daily dose needs, high plasma albumin binding propensity, and initial/acquired drug resistance. Article’s purpose is to investigate EGFR-TKI’s effects on lung cancer and get around some of its drawbacks, nanotechnology will be an innovative strategy. An effective tool to increase the effectiveness of these pharmaceuticals is nanotechnology by methods other than oral. This article signifies that a range of nanomedicine delivery systems have been developed to effectively distribute EGFR-TKIs with improved drug release kinetics and tissue-targeting capacity. This review article intends to present information regarding lung cancer and EGFR relation, mechanism of recently approved EGFR-TKI’s targeted therapy, an updated landscape of EGFR-TKIs and their clinical status over lung cancer, advantages and disadvantages of nanotechnology, and new breakthroughs in nano-delivery which mentioned as a significantly better over traditional drug chemotherapy and delivery.

Erythema nodosum leprosum (ENL) is an immune-mediated inflammatory reaction (antigen-antibody reaction involving complement) of leprosy. Available standard treatment in the form of steroids or thalidomide does not work in all ENL patients. Apremilast is an oral phosphodiesterase-4 inhibitor with potent immunomodulatory action. At present, apremilast is approved for chronic plaque psoriasis and psoriatic arthritis, however, not in ENL. The aim of this study was to assess the effectiveness of apremilast in chronic recalcitrant ENL. It was a case series, in which apremilast was started in 10 consecutive patients with recalcitrant ENL with 10 mg morning dose with a daily increment of 10 mg until day 6, when the recommended dose of 30 mg twice daily for adults is reached. Follow-up was done every 1 month till 6 months. Three patients showed good responses. The drug was well tolerated with few side effects. The most common adverse effect reported was headache (n = 5), followed by nausea (n = 4) and diarrhea (n = 4). Apremilast has lower cost and better safety profile compared to thalidomide and may be an option with limited effectiveness for ENL.

Abstract Decision makers consistently face the challenge of simultaneously assessing numerous attributes, determining their respective importance, and selecting an appropriate method for calculating their weights. This article addresses the problem of automatic generation control (AGC) in a two area power system (2-APS) by proposing fuzzy analytic hierarchy process (FAHP), an multi-attribute decision-making (MADM) technique, to determine weights for sub-objective functions. The integral-time-absolute-errors (ITAE) of tie-line power fluctuation, frequency deviations and area control errors, are defined as the sub-objectives. Each of these is given a weight by the FAHP method, which then combines them into an single final objective function. This objective function is then used to design a PID controller. To improve the optimization of the objective function, the Jaya optimization algorithm (JOA) is used in conjunction with other optimization techniques such as sine cosine algorithm (SCA), Luus–Jaakola algorithm (LJA), Nelder–Mead simplex algorithm (NMSA), symbiotic organism search algorithm (SOSA) and elephant herding optimization algorithm (EHOA). Six distinct experimental cases are conducted to evaluate the controller’s performance under various load conditions, with data plotted to show responses corresponding to fluctuations in frequency and tie-line exchange. Furthermore, statistical analysis is performed to gain a better understanding of the effectiveness of the JOA-based PID controller. For non-parametric evaluation, Friedman rank test is also used to validate the performance of the proposed JOA-based controller.

Abstract Multi-criteria decision-making (MCDM) presents a significant challenge in decision-making processes, aiming to ascertain optimal choice by considering multiple criteria. This paper proposes rank order centroid (ROC) method, MCDM technique, to determine weights for sub-objective functions, specifically, addressing issue of automatic generation control (AGC) within two area interconnected power system (TAIPS). The sub-objective functions include integral time absolute errors (ITAE) for frequency deviations and control errors in both areas, along with ITAE of fluctuation in tie-line power. These are integrated into an overall objective function, with ROC method systematically assigning weights to each sub-objective. Subsequently, a PID controller is designed based on this objective function. To further optimize objective function, Jaya optimization algorithm (JOA) is implemented, alongside other optimization algorithms such as teacher–learner based optimization algorithm (TLBOA), Luus–Jaakola algorithm (LJA), Nelder–Mead simplex algorithm (NMSA), elephant herding optimization algorithm (EHOA), and differential evolution algorithm (DEA). Six distinct case analyses are conducted to evaluate controller’s performance under various load conditions, plotting data to illustrate responses to frequency and tie-line exchange fluctuations. Additionally, statistical analysis is performed to provide further insights into efficacy of JOA-based PID controller. Furthermore, to prove the efficacy of JOA-based proposed controller through non-parametric test, Friedman rank test is utilized.

Abstract Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses. Pathogen circulation dropped substantially after the initiation of COVID-19 stay-at-home orders in March 2020. During this period, mobility was a positive, leading indicator of transmission of all endemic viruses and lagging and negatively correlated with SARS-CoV-2 activity. Mobility was briefly predictive of SARS-CoV-2 transmission when restrictions relaxed but associations weakened in subsequent waves. The rebound of endemic viruses was heterogeneously timed but exhibited stronger, longer-lasting relationships with mobility than SARS-CoV-2. Overall, mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change and at the beginning of epidemic waves.

Abstract Disabled 2 (Dab2), an adaptor protein, is up regulated in the hair follicle stem cells (HFSCs); however, its role in any tissue stem cells has not been studied. In the present study, we have reported that Dab2 conditional knockout (Dab2-cKO) mice exhibited a delay in the HF cycle due to perturbed activation of HFSCs. Further, Dab2-cKO mice showed a reduction in the number of HFSCs and reduced colony forming ability of HFSCs. Dab2-cKO mice showed extended quiescence of HFSCs concomitant with an increased expression of Nfatc1. Dab2-cKO mice showed a decreased expression of anti-aging genes such as Col17a1, decorin, Sirt2 and Sirt7. Dab2-cKO mice did not show full hair coat recovery in aged mice thereby suggesting an accelerated aging process. Overall, we unveil for the first time, the role of Dab2 that regulate activation and self-renewal of HFSCs.

Tuberculosis being endemic in country like India can affect any organ though pulmonary tuberculosis is rampant and extrapulmonary is rare. Tuberculosis affecting parotid gland is a rare occurrence, usually unilateral. However, Mycobacterium tuberculosis causing cold abscess in bilateral parotid glands is even rarer. Here, we present a case of a young female presented with bilateral slow-growing swelling in the parotid region with evening raise of temperature for two months. On clinical examination, no signs of inflammation were seen. Ultrasonography showed thick-walled hypoechoic collection with septae and internal echoes within involving both superficial and deep lobes of the parotid gland. Fine-needle aspiration cytology (FNAC) suggested a caseating granuloma and acid fast bacilli were detected on ZN staining, thereby confirming the diagnosis of cold abscess. She was put on antitubercular drugs and there was a drastic reduction in the size of swelling.

Canine babesiosis is a tick-borne hemoprotozoan disease of canines. Two main infective agents of the disease are intra-erythrocytic i.e. Babesia vogeli and Babesia gibsoni. In the present study, a total of 145 numbers of dogs (90 male and 55 female) in and around Akola, Maharashtra were screened from January 2022 to September 2022 for Babesiosis and 18 animals (12.41%) were found clinically and cytologically positive. The incidence of babesiosis was higher in females (11/145, 7.58%) than in males (07/ 145, 4.83%). Out of 18 positive samples, 14 (9.65%) and 4 (2.75%) animals were found infected with small and large forms of Babesia spp., respectively. Further small form was confirmed as B. gibsoni and the large form was confirmed as B. vogeli by employing PCR assay. All the cases with babesiosis revealed moderate to severe regenerative anemia with occasional basophilic stippling and Howell jolly bodies with hemoglobin ranging from 7 to 11 g/dL. Characteristic clinical features were observed among 18 positive clinical cases. The present investigation reports the incidence of B. vogeli and B. gibsoni in canines in and around Akola of Maharashtra state of India.

Abstract Background The current investigation aimed to develop, optimise, and assess a mupirocin-loaded nanosponge-based topical delivery system for diabetic foot ulcer and to achieve prolonged drug release while improving drug deposition within the skin. The nanosponges carrying mupirocin were formulated using the emulsion solvent diffusion method. A 32 factorial design was utilised to investigate effect of two factors, specifically the concentration of ethyl cellulose and the stirring rate, on the physical attributes of the nanosponges. The optimised nanosponge formulation batch (F9) was subsequently incorporated into a Carbopol gel base, ensuring the desired physical attributes were achieved in the gel formulation containing nanosponges. The research included in vitro drug release evaluation, ex vivo drug deposition analysis, assessment of the antimicrobial action of the nanosponge formulation, and in vivo diabetic wound healing. Results Drug polymer compatibility analysis was conducted using FT-IR spectroscopy revealed no interactions among mupirocin and ethyl cellulose molecules. Further FT-IR spectroscopy, DSC spectroscopy, and XRD spectroscopy analysis of optimised formulation batch revealed that the drug was successfully entrapped in nanosponges. Scanning electron microscopy confirmed the spherical and porous nature of the prepared nanosponges. The drug release pattern across the cellulose dialysis membrane followed a diffusion-controlled release pattern, and the drug deposition analysis exhibited substantial retention of mupirocin in the skin from the nanosponges formulation for up to 24 h. Furthermore, the optimised nanosponges gel formulation demonstrated stability and non-irritant properties, as indicated by the HET-CAM test. In vivo evaluation of wound healing activity in a Streptozotocin-induced diabetes mellitus with excision wound model revealed significant actions pertaining to wound healing and closure after 16 days of treatment. Conclusion The mupirocin-loaded nanosponge gel contributed to remarkable and swift recovery and closure of wounds in diabetic rats. The nanosponges, acting as carriers for mupirocin, facilitated the effective delivery of the drug to the wound area, while the gel fostered an optimally humid environment conducive to wound care during the final stages of wound healing and sealing. Graphical abstract

Abstract Autonomic nervous system (ANS) activity causes acute variations in blood pressure (BP) and heart rate (HR). These systems are challenged during high intensity interval exercise (HIIE). However, BP variability (BPV) and HR variability (HRV) response to HIIE is unknown. We characterized BPV and HRV during an acute HIIE bout using spectral low frequency [LF] and high frequency [HF] domains. We hypothesized that BPV would increase and HRV would decrease during high‐intensity and active‐recovery of HIIE compared to baseline [BL] and BPV would reduce and HRV would increase during cool down, post‐HIIE, and 30 min post‐HIIE compared to BL. HIIE involved 10 min of alternating high‐intensity and active‐recovery (approximately 70% and 10% of Wattmax) on a recumbent stepper. We did a secondary analysis on 23 datasets. The participants were 25 ± 1.5 years, 48% females. Our results showed high‐intensity BPV LF was not significantly different from BL while HF increased. HRV LF and HF decreased compared to BL. During active‐recovery, LF and HF for BPV and HRV increased greater than high‐intensity. HRV LF and HF returned to BL after 30 min of recovery, whereas BPV HF was higher compared to BL. The rapid switching during HIIE uniquely modulates cardiovascular and ANS.

Background: Oral Submucous Fibrosis, OSF is an inflammatory mucosal disorder prevalent in areca nut chewing belts of the world. Although various treatments are available for its management, none provide complete resolution.Curcumin, an indigenous product, improves burning sensation, mouth opening along with other clinical signs of OSF and is potentially viable therapeutic option for its management. Objectives: To assess the available evidence for employing curcumin in improving symptoms in patients with OSF. Methods: Systematic search was carried out in e-databases from January 2010 until July 2023 to identify relevant clinical trials comparing curcumin to active and/or nonactive controls (placebo) for the management of OSF. Results: A total of 20 studies were used for qualitative analysis out of which 11 studies were considered for quantitative synthesis.Curcumin was found to be highly effective in alleviating pain/burning sensation, improving mouth opening (MO), cheek flexibility, tongue protrusion and induces positive histological changes in patients with OSF.The standardized mean difference in mouth opening between both the Curcumin and Multivitamin group showed a statistically significant difference favouring the Curcumin group (SMD, 0.37, 95% CI = 0.18–0.56, p - 0.0001, I2- 0%). Conclusion: Statistically curcumin was noted to be as effective as Aloe vera, lycopene and steroids in relieving symptoms of OSF in stages 1 and 2 and improving MO. It is seen to improve histopathological picture of lesions thereby suggesting its active role in preventing malignant transformation. Its found to be more effective than multivitamins in improving mouth opening of patients in OSF.

IntroductionPost-ovulatory aging is a time-dependent deterioration of ovulated oocytes and a major limiting factor reducing the fitness of offspring. This process may lead to the activation of cell death pathways like apoptosis in oocytes.MethodologyWe evaluated oocyte membrane integrity, egg developmental competency, and mRNA abundance of apoptosis-related genes by RT-qPCR. Oocytes from zebrafish Danio rerio were retained in vivo at 28.5°C for 24 h post-ovulation (HPO). Viability was assessed using trypan blue (TB) staining. The consequences of in vivo oocyte aging on the developmental competence of progeny were determined by the embryo survival at 24 h post fertilization, hatching, and larval malformation rates.ResultsThe fertilization, oocyte viability, and hatching rates were 91, 97, and 65% at 0 HPO and dropped to 62, 90, and 22% at 4 HPO, respectively. The fertilizing ability was reduced to 2% at 8 HPO, while 72% of oocytes had still intact plasma membranes. Among the apoptotic genes bcl-2 (b-cell lymphoma 2), bada (bcl2-associated agonist of cell death a), cathepsin D, cathepsin Z, caspase 6a, caspase 7, caspase 8, caspase 9, apaf1, tp53 (tumor protein p53), cdk1 (cyclin-dependent kinase 1) studied, mRNA abundance of anti-apoptotic bcl-2 decreased and pro-apoptotic cathepsin D increased at 24 HPO. Furthermore, tp53 and cdk1 mRNA transcripts decreased at 24 HPO compared to 0 HPO.DiscussionThus, TB staining did not detect the loss of oocyte competency if caused by aging. TB staining, however, could be used as a simple and rapid method to evaluate the quality of zebrafish oocytes before fertilization. Taken together, our results indicate the activation of cell death pathways in the advanced stages of oocyte aging in zebrafish.