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The development of synthetic hydrogels as a dermal patch offers unique advantage of providing moist environment around the wound site. The incorporation of curcumin in hydrogel plays a significant role in the healing process of chronic wounds. The present investigation aims to develop nano-formulated curcumin-fused lipogel to impart the dual advantages of sustained drug release and enhanced wound healing ability. The wound healing behaviour of the prepared lipogel has been assessed through series of techniques namely DPPH assay and bacterial inhibitory efficacy through the Kirby Bauer assay against E. coli and S. aureus. Further, the promotion of angiogenesis has been determined through an in-ovo CAM assay. The results obtained from the investigation revealed the enhanced solubility of curcumin in liposome formulation. Moreover, the encapsulation of curcumin in liposomes facilitated prolonged drug release and better antibacterial efficacy against the tested bacterial stains. The developed hydrogel also displayed good adhesion and water retention ability, which is an important prerequisite for better wound healing ability., 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 © 2024 Elsevier B.V. All rights reserved.)

We present structural properties at different temperatures and high-pressure (HP) of La 3 Rh 4 Sn 13 which is one of the interesting systems in the Remika phase RE 3 Rh 4 Sn 13 (RE=Sr, Ca, La, Pr, Ce) quasi-skutterudite series using synchrotron diffraction. Data at ambient conditions revealed the presence of several weak reflections, which could be accounted only with a superlattice I* structure (I4 1 32) with lattice parameter a~19.457 Å. However, above 350 K, a complete suppression of the weak superlattice reflections of the I* structure is observed. Data at higher temperatures is found to be well described by the I structure (Pm-3n) having half the lattice parameter compared to the I* structure. HP-XRPD at ambient temperature showed that pressures greater than 7.5 GPa result in similar suppression of the weak I* superlattice reflections. Data at higher pressures is found to be well described by the I structure (Pm-3n), similar to the high-temperature phase. HP Raman measurements demonstrated changes that seem to be consistent with a locally more ordered structure as in the case of the I*→I transition. Our findings on La 3 Rh 4 Sn 13 open up new avenues to study unexplored HP phenomena, especially the superconductivity in these Remika phase quasi-skutterudites., (© 2024 Wiley-VCH GmbH.)

Severe thermal skin burns are complicated by inflammation and apoptosis, which delays wound healing and contributes to significant morbidity. Diverse treatments demonstrate limited success in mitigating these processes to accelerate healing. Agents that alter cell behavior to improve healing would alter treatment paradigms. We repurposed 4-aminopyridine (4-AP), a drug approved by the US FDA for multiple sclerosis, to treat severe burns in mice (10-week-old C57BL/6 J male mice weighing 25 ± 3 g). We found that 4-AP, in the early stages of burn healing, significantly reduced the expression of pro-inflammatory cytokines IL1β and TNFα while increasing the expression of anti-inflammatory markers CD206, ARG-1, and IL10. We demonstrated increased intracellular calcium effects of 4-AP through Orai1-pSTAT6 signaling, where 4-AP significantly mitigated inflammatory effects by promoting M2 macrophage differentiation in in-vitro macrophages and post-skin burn tissues. 4-AP attenuated apoptosis, with decreases in apoptotic markers BAX, caspase-9, and caspase-3 and increases in anti-apoptotic markers BCL2 and BCL-XL. Furthermore, 4-AP promoted angiogenesis through increases in the expression of CD31, VEGF, and eNOS. Together, these likely contributed to accelerated burn wound closure, as demonstrated in increased keratinocyte proliferation (K14) and differentiation (K10) markers. In the later stages of burn healing, 4-AP increased TGFβ and FGF levels, which are known to mark the transformation of fibroblasts to myofibroblasts. This was further demonstrated by an increased expression of α-SMA and vimentin, as well as higher levels of collagen I and III, MMP 3, and 9 in mice treated with 4-AP. Our findings support the idea that 4-AP may have a novel, clinically relevant therapeutic use in promoting burn wound healing., (© 2024. The Author(s).)

Aim: Undernurition stands as a significant contributor to childhood mortality, particularly in developing nations such as India. At the grass root level, anthropometric monitoring indicators such as stunting, underweight and wasting take place within Anganwadi centres (village courtyard). The scrutiny of growth records, utilising these markers, not only quantifies the burden but also informs corrective measures. This study aimed to assess the prevailing growth monitoring records within the rural vicinity of Puducherry., Methods: A community-based cross-sectional study design was implemented to examine the health condition of children below 3 years of age, who were enrolled and utilising services in Anganwadi centres. The anthropometric data, such as weight and height, were collected from growth monitoring records maintained in Anganwadi. The proportions of undernutrition indicators such as stunting, underweight and wasting were presented with a 95% confidence interval (CI)., Results: Within our rural service area encompassing 13 Anganwadis, a total of 572 children aged 3 or less were registered. Notably, approximately 14.2% (95% CI: 11.5-17.3) of these children experienced underweight, 16.4% (95% CI: 13.6-19.7) were stunted and 13.3% (95% CI: 10.8-16.3) were wasted. In terms of gender disparities, the prevalence of undernurition was notably higher among boy children, with 15.4% being underweight, 16.9% stunted and 14.7% wasted., Conclusions: The prevalence of childhood undernurition is a public health concern, demanding the enhancement of existing nutritional initiatives to ameliorate the healthy well-being of these children. The timely identification of malnourished children holds paramount importance, as intensified interventions can be promptly employed to uplift the health status of these vulnerable individuals., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Severe thermal skin burns are complicated by inflammation and apoptosis, which delays wound healing and contributes to significant morbidity. Diverse treatments demonstrate limited success with mitigating these processes to accelerate healing. Agents that alter cell behavior to improve healing would alter treatment paradigms. We repurposed 4-aminopyridine (4-AP), a drug approved by the US FDA for multiple sclerosis, to treat severe burns. We found that 4-AP, in the early stages of burn healing, significantly reduced the expression of pro-inflammatory cytokines IL1β and TNFα while increasing the expression of anti-inflammatory markers CD206, ARG-1, and IL10. 4-AP attenuated apoptosis, with decreases in apoptotic markers BAX, caspase-9, and caspase-3 and increases in anti-apoptotic markers BCL2 and BCL-XL. Furthermore, 4-AP promoted angiogenesis through increases in the expression of CD31, VEGF, and eNOS. Together, these likely contributed to accelerated burn wound closure, as demonstrated in increased keratinocyte proliferation (K14) and differentiation (K10) markers. In the later stages of burn healing, 4-AP increased TGFβ and FGF levels, which are known to mark the transformation of fibroblasts to myofibroblasts. This was further demonstrated by an increased expression of α-SMA and vimentin, as well as higher levels of collagen I and III, MMP 3, and 9 in animals treated with 4-AP. Our findings support the idea that 4-AP may have a novel, clinically relevant therapeutic use in promoting burn wound healing., Competing Interests: COMPETING INTERESTS PKG and JCE are inventors on patents 1). Methods and materials for treating burns (US18/139,123); (2). Methods and materials for treating hair loss (US18/270,914); 3). Methods and materials for treating nerve injury and/or promoting wound healing (US17/759,224) submitted by the Penn State Research Foundation. All other authors declare that they have no competing financial interests.

A 48-year-old man with a history of mitral valve replacement (MVR) in March 2019 for rheumatic heart disease (RHD) and ischemic stroke in August 2019 presented with a history of sudden onset angina of 6 hours duration. He admits to defaulting oral anticoagulant (OAC) intake for the last 50 days. On arrival, he had atrial fibrillation with hemodynamic instability [blood pressure (BP) 70/40 mm Hg, saturation of peripheral oxygen (SpO2) 80% at room air and heart rate approx 140/minute], which was managed with intravenous diltiazem and hemodynamic stability achieved (BP 116/72 mm Hg, heart rate 86/minute). Urgent transthoracic echocardiogram (TTE) and fluoroscopy confirmed obstructive prosthetic mitral valve thrombosis. Though available recommendations suggest surgical intervention for the left-sided valve involvement in a stable patient, in view of the nonavailability of a surgical facility, the patient was thrombolyzed with Alteplase, a recombinant tissue plasminogen activator (rtPA). Since the patient was stable, a "long fibrinolytic protocol" of Alteplase 10 mg bolus, 50 mg during the 1st hour, and 20 mg each during the 2nd and 3rd hour (total of 100 mg) was given. Subsequent TTE revealed a mean gradient of 5 mm Hg, and cine fluoroscopy showed improved mitral valve motion, thereby indicating successful thrombolysis. The patient felt symptomatically relieved within 6 hours and is presently on OAC therapy with strict drug compliance., (© Journal of the Association of Physicians of India 2024.)

In order to maintain the polio eradication status, it has become evident that the surveillance of cases with acute flaccid paralysis and of environmental samples must be urgently supplemented with the surveillance of poliovirus excretions among individuals with inborn errors of immunity (IEI). All children with IEI were screened for the excretion of poliovirus during a collaborative study conducted by the ICMR-National Institute of Virology, Mumbai Unit, ICMR-National Institute of Immunohaematology, and World Health Organization, India. A seven-month -old male baby who presented with persistent pneumonia and lymphopenia was found to have severe combined immune deficiency (SCID) due to a missense variant in the RAG1 gene. He had received OPV at birth and at 20 weeks. Four stool samples collected at 4 weekly intervals yielded iVDPV type 1. The child's father, an asymptomatic 32-year-old male, was also found to be excreting iVDPV. A haploidentical hematopoietic stem cell transplant was performed, but the child succumbed due to severe myocarditis and pneumonia three weeks later. We report a rare case of transmission of iVDPV from an individual with IEI to a healthy household contact, demonstrating the threat of the spread of iVDPV from persons with IEI and the necessity to develop effective antivirals.

The increasing prevalence of bone replacements and complications associated with bone replacement procedures underscores the need for innovative tissue restoration approaches. Existing synthetic grafts cannot fully replicate bone vascularization and mechanical characteristics. This study introduces a novel strategy utilizing pectin, chitosan, and polyvinyl alcohol to create interpenetrating polymeric network (IPN) scaffolds incorporated with extracellular vesicles (EVs) isolated from human mesenchymal stem cells (hMSCs). We assess the osteointegration and osteoconduction abilities of these models in vitro using hMSCs and MG-63 osteosarcoma cells. Additionally, we confirm exosome properties through Transmission Electron Microscopy (TEM), immunoblotting, and Dynamic Light Scattering (DLS). In vivo , chick allantoic membrane assay investigates vascularization characteristics. The study did not include in vivo animal experiments. Our results demonstrate that the IPN scaffold is highly porous and interconnected, potentially suitable for bone implants. EVs, approximately 100 nm in size, enhance cell survival, proliferation, alkaline phosphatase activity, and the expression of osteogenic genes. EVs-mediated IPN scaffolds demonstrate promise as precise drug carriers, enabling customized treatments for bone-related conditions and regeneration efforts. Therefore, the EVs-mediated IPN scaffolds demonstrate promise as precise carriers for the transport of drugs, allowing for customized treatments for conditions connected to bone and efforts in regeneration., (© 2024 IOP Publishing Ltd.)

The clinical effectiveness of the available anticancer drugs has been reduced due to the development of drug resistance and serious adverse effects, which have restricted chemotherapy for cancer. Therefore, there is a persistent need for new anticancer medications with reduced side effects. Medical researchers are pursuing various methods to find new, potent, specifically targeted molecules for cancer treatment. Through various techniques, numerous molecules are discovered. However, among them, acridine stands out as a promising heterocycle that has captured the interest of medicinal chemists and acquired significant pharmacological value. The synthetic adaptability of acridine has enabled the creation of numerous derivatives with a wide range of architectural properties, further accelerating this broad spectrum of pharmacological activities. Recent studies have looked at the mechanisms by which acridine and its analogs inhibit tyrosine kinases, topoisomerases, telomerase, and DNA repair interaction. We have compiled our knowledge of acridine compounds for their anticancer activities, mechanisms of action, structure-activity relationship (SAR), and selective, specific activity against different cancer drug targets, as well as in vitro and in vivo anticancer activities of acridine and its analogs from the perspective of cancer drug discovery, in this review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

N-Nitrosamine impurities, including nitrosamine drug substance-related impurities (NDSRIs), have challenged pharmaceutical industry and regulators alike and affected the global drug supply over the past 5 years. Nitrosamines are a class of known carcinogens, but NDSRIs have posed additional challenges as many lack empirical data to establish acceptable intake (AI) limits. Read-across analysis from surrogates has been used to identify AI limits in some cases; however, this approach is limited by the availability of robustly-tested surrogates matching the structural features of NDSRIs, which usually contain a diverse array of functional groups. Furthermore, the absence of a surrogate has resulted in conservative AI limits in some cases, posing practical challenges for impurity control. Therefore, a new framework for determining recommended AI limits was urgently needed. Here, the Carcinogenic Potency Categorization Approach (CPCA) and its supporting scientific rationale are presented. The CPCA is a rapidly-applied structure-activity relationship-based method that assigns a nitrosamine to 1 of 5 categories, each with a corresponding AI limit, reflecting predicted carcinogenic potency. The CPCA considers the number and distribution of α-hydrogens at the N-nitroso center and other activating and deactivating structural features of a nitrosamine that affect the α-hydroxylation metabolic activation pathway of carcinogenesis. The CPCA has been adopted internationally by several drug regulatory authorities as a simplified approach and a starting point to determine recommended AI limits for nitrosamines without the need for compound-specific empirical data., 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., (Published by Elsevier Inc.)

Choosing suitable wound dressings is crucial for effective wound healing. Spun scaffolds with bioactive molecule functionalization are gaining attention as a promising approach to expedite tissue repair and regeneration. Here, we present the synthesis of novel multifunctional quercetin with morpholine and pyridine functional motifs (QFM) embedded in silk fibroin (SF)-spun fibers (SF-QFM) for preclinical skin repair therapies. The verification of the novel QFM structural arrangement was characterized using ATR-FTIR, NMR, and ESI-MS spectroscopy analysis. Extensive characterization of the spun SF-QFM fibrous mats revealed their excellent antibacterial and antioxidant properties, biocompatibility, biodegradability, and remarkable mechanical and controlled drug release capabilities. SF-QFM mats were studied for drug release in pH 7.4 PBS over 72 h. The QFM-controlled release is mainly driven by diffusion and follows Fickian's law. Significant QFM release (40%) occurred within the first 6 h, with a total release of 79% at the end of 72 h, which is considered beneficial in effectively reducing bacterial load and helping expedite the healing process. Interestingly, the SF-QFM-spun mat demonstrated significantly improved NIH 3T3 cell proliferation and migration compared to the pure SF mat, as evidenced by the complete migration of NIH 3T3 cells within 24 h in the scratch assay. Furthermore, the in vivo outcome of SF-QFM was demonstrated by the regeneration of fresh fibroblasts and the realignment of collagen fibers deposition at 9 days post-operation in a preclinical rat full-thickness skin defect model. Our findings collectively indicate that the SF-QFM electrospun nanofiber scaffolds hold significant capability as a cost-effective and efficient bioactive spun architecture for use in wound healing applications.

Peste des petits ruminants (PPR) presents economic challenges in enzootic countries impacting small ruminant productivity. The state of Karnataka, India, implemented a mass vaccination campaign in alignment with the PPR-Global Eradication Programme (GEP) and the National Strategic Plan for PPR eradication. This study was conducted from January to March 2023 to assess seroconversion in post-vaccinated goats and sheep at the epidemiological unit (epi-unit) level, aligning with the World Organisation for Animal Health (WOAH) and the Food and Agriculture Organization (FAO) guidelines in the PPR Global Control and Eradication Strategy (GCES). Before vaccination, 3466 random serum samples were collected from small ruminants of three age groups (6-12 months, 1-2 years, and >2 years) across 116 epi-units, spanning 82 taluks in 28 districts. Post-vaccination sero-monitoring included 1102 serum samples collected from small ruminants of the 6-12-month age group only, across 111 epi-units covering 64 taluks in 23 districts. The PPRV antibody status was determined using an indigenous hemagglutinin (H) protein monoclonal antibody-based competitive ELISA kit. Pre-vaccination, the PPR seropositivity rates were 55%, 62%, and 66% in the age groups of 6-12 months, 1-2 years, and >2 years, respectively, with a 61% PPRV antibody prevalence across all the age groups. Notably, 41% of the epi-units exhibited antibody prevalence rates of ≥70%, indicating a substantial population immunity, possibly attributed to the previous vaccination program in the state since 2011. In contrast, only 17% of the epi-units had below 30% seroprevalence rates, emphasizing the need for intensified vaccination. Statistical analysis of the data revealed significant correlations ( p < 0.05) between the presence of PPRV antibodies and host factors such as species, breed, and sex. Post-vaccination seroprevalence in the 6-12 months age group was found to be 73.4%, indicating the use of an efficacious vaccine. On the evaluation of vaccination immunity in the 6-12 months age group, it was revealed that over 69% of the epi-units achieved a response surpassing ≥70%, indicating a significant improvement from 42% of the epi-units in pre-vaccination. For active PPR eradication, a mass vaccination campaign (>95% coverage) targeting small ruminant populations aged >4 months is advocated, aiming to achieve the desired herd immunity of >80%. This study offers crucial insights into PPR baseline seroprevalence/immunity status and vaccine efficacy, guiding national strategies towards a PPR-free India and further supporting the global eradication initiative.

Dynamic interactions within the tumor micro-environment drive patient response to immune checkpoint inhibitors. Existing preclinical models lack true representation of this complexity. Using a Head and Neck cancer patient derived TruTumor histoculture platform, the response spectrum of 70 patients to anti-PD1 treatment is investigated in this study. With a subset of 55 patient samples, multiple assays to characterize T-cell reinvigoration and tumor cytotoxicity are performed. Based on levels of these two response parameters, patients are stratified into five sub-cohorts, with the best responder and non-responder sub-cohorts falling at extreme ends of the spectrum. The responder sub-cohort exhibits high T-cell reinvigoration, high tumor cytotoxicity with T-cells homing into the tumor upon treatment whereas immune suppression and tumor progression pathways are pre-dominant in the non-responders. Some moderate responders benefit from combination of anti-CTLA4 with anti-PD1, which is evident from better cytotoxic T-cell: T-regulatory cell ratio and enhancement of tumor cytotoxicity. Baseline and on-treatment gene expression signatures from this study stratify responders and non-responders in unrelated clinical datasets., (© 2024. The Author(s).)