Browse Articles

Bioinspired enamel repair via inorganic ionic polymerization using calcium phosphate ionic clusters and nano-hydroxyapatite

Abstract Traditional restorative materials often fail to integrate seamlessly with natural tooth structures due to differences in chemical composition, leading to microleakage and related clinical problems. This study aims to create a material entirely composed of calcium phosphates, the main component of dental enamel, to repair minor enamel cavities. Inspired by the biomineralization process and employing the inorganic ionic polymerization strategy, a cohesive calcium phosphate mass was developed to repair minor enamel cavities. Calcium phosphate ionic clusters (CPICs) and three types of calcium phosphate powder were utilized; (bone-derived and synthetic hydroxyapatite; (BHA and SHA), and dried CPICs. Two different techniques, namely layer by layer (LbL) and premixing (PM), were employed to mix CPICs with one type of calcium phosphate powder to form a cohesive mass. Different analysis techniques were used including FTIR, XRD, SEM and TEM. Among the tested approaches, the mass formed by mixing BHA with CPICs using the PM technique demonstrated superior integration with enamel walls and infiltration of calcium phosphate particles into enamel. To the best of our knowledge, repairing cavitated enamel defects using a bioinspired approach with a material composed entirely of calcium phosphate has not yet been achieved.

DFT and dynamic simulations of OleuoPectin structures as a potential anticoagulant agent

Abstract Oleuropein, a biologically active compound with variable pharmacological properties, is poorly absorbed in the gut, causing gastrointestinal upset in sensitive individuals. Model molecules of Oleuropein, pectin, and some proposed interactions were built up and geometrically optimized via both semiempirical and DFT high theoretical levels. QSAR descriptors were calculated to ascertain the ability of pectin to improve the Oleuropein structure’s hydrophilicity with Log p (-1.171). DFT calculations reveal that the proposed Oleu-Pec structures have stable characteristics and high reactivity with dipole moments up to 7.86 Debye. They also proposed that Pec is most likely to interact with Oleu through physical interaction between its OH group and that of Oleu. MESP maps indicated the active sites revealing their tendency to go through either nucleophilic or electrophilic pathways. Furthermore, global reactivity descriptors were calculated to reveal the improved electronic features of Oleu-Pec structures upon adding Pec to Oleu, proposing it for further promising biomedical applications. The integrated approach of docking and molecular dynamics (MD) simulations applied to the P2Y12 receptor in conjunction with the ligands 2-Oleu(OH)-Pec(OH), Oleuropein, Pectin, compared with native inhibitor (AZJ) provides valuable insights into their binding characteristics. Among these ligands, the 2-Oleu(OH)-Pec(OH) emerges as a highly promising candidate, demonstrating exceptional stability with a docking RMSD of 0.68 Å, a robust binding affinity of -6.80 kcal/mol, and an extensive interaction network comprising 18 total bonds, including 12 hydrogen bonds. MD simulations further validate its stability, showcasing a consistent RMSD (~ 0.41 nm), 2–4 intermolecular hydrogen bonds, and the lowest MM/PBSA ΔG value of -54.64 kcal/mol. Principal Component Analysis (PCA) reinforces these findings by revealing the tightest clustering, indicating minimal conformational variability. The synergy observed between Oleuropein and Pectin in the dual-ligand configuration enhances the overall binding strength, surpassing that of the individual components. These outcomes underscore the potential of 2-Oleu(OH)-Pec(OH) as a promising P2Y12 inhibitor for applications in anti-thrombotic therapy.

Development and evaluation of gluten free pasta from brown rice, quinoa, and chickpeas for celiac disease patients

Abstract The demand for gluten-free products for people suffering from a gluten allergy is increasing. Therefore, the aim of this study was to produce high-quality gluten-free pasta from brown rice flour (BRF), quinoa flour (QF) and chickpea flour (CPF), semolina flour (S) was used as control sample. The chemical composition of the raw materials showed the higher protein, carbohydrate and fat content of CPF, S and QF, respectively. In addition, the content of Ca, K, and Fe was higher in CPF. The total concentration of essential amino acids in CPF, BRF and QF was between 38.9 and 34.04%. Pasta was prepared with different levels of CPF, BRF, and QF. The quality of the pasta was evaluated chemically and physically. The chemical analysis showed that the formula (BRQ5) had the highest protein, fat, ash and fiber content. The color analysis showed that the darkness of the pasta increased with increasing QF. The overall acceptability of the different pasta showed that the control (S) had the highest acceptability, followed by BR and BRQ1. The analysis of the texture profile showed that the hardness of the uncooked control pasta was the highest. In summary, it can be recommended to produce gluten-free pasta with the BRQ1 formula.

Exploring virulence factors, virulome, and multidrug resistance of Klebsiella pneumoniae strains isolated from patients with central Line-associated bloodstream infections

Abstract This study aimed to analyze the antibiotic resistance patterns and virulence profiles of Klebsiella pneumoniae, a prevalent gram-negative pathogen linked to CLABSI patients globally. Of a total of 185 microbial isolates, 51 (27.5%) were K. pneumoniae isolates. The results of antimicrobial susceptibility testing using the disk diffusion method were compared to those of the VITEK-2. Phenotypic analysis revealed that 88.3% were biofilm producers and 50.9% were extended-spectrum beta-lactamase (ESBL) producers. Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) revealed a discriminatory power of 0.7111 between ten selected isolates. The PCR detection of the virulence genes, including FimH, rmpA, iutA, and fyuA, revealed that the ten selected isolates harbored all these genes, except one without the fyuA gene. The presence of the rmpA and the iutA genes confirmed them as hypervirulent (hv) K. pneumoniae. The genes (EAST-1, CNF-1) were present in 20% and 60% of the isolates, respectively. All isolates had the bla TEM and bla SHV resistance genes, while 50% had the bla NDM carbapenemase resistance gene. In conclusion, all selected K. pneumoniae isolates were proven to be ESBL producers and carbapenem-resistant, highlighting significant multidrug resistance. We found a strong correlation between biofilm formation and multidrug resistance, as well as between phenotypic and genotypic detection of various virulence factors. Infections from hyKp strains represent a growing public threat. Our findings aim to enhance therapeutic options for patients and help reduce complications and mortality.

70 Years of observational weather data show increasing fire danger for boreal Europe and reveal bias of ERA5 reanalysed data

Abstract Retrospective analyses of fire danger typically use reanalysed data, but its relation to observed fire danger is not well researched. Here we use daily weather observations to calculate fire danger for nine weather stations in Sweden, spanning 1100 km N–S, for the period 1951–2020, making it among the longest series of observed fire danger to date. All sites except the northernmost one exhibited increasing seasonal FWI-metrics over the period and linear trends were statistically significant for three sites. On average, annual peak 7-day moving-average FWI increased by 18% over 70 years. Increasing trends were mostly driven by higher noon-temperature and not by altered precipitation patterns. Further, observed fire danger differed substantially from that based on ERA5 reanalysis data. For FWI > 5, reanalysis FWI-values were on average 25% lower than corresponding observational values. The strength of reanalysis data is to form gridded data using single assimilation schemes against homogeneous model fits and it is not designed to fully represent actual point scale weather. While reanalysis data enables comprehensive geographical analyses, this study shows how it also underestimates peak fire weather in northern Europe. We recommend checking extreme-value bias against point observations in future studies.

Induction of chronic prostatitis does not alter the innate contractile properties of the prostate or urethra in rats

Abstract The current study aimed to examine how smooth muscle contractile properties and expression of functional proteins in the urethra and prostate are affected in an animal model of chronic prostatitis/chronic pelvic pain syndrome (CPPS). Thirty-two male Sprague-Dawley rats received an intraprostatic injection with saline or zymosan, serving as control and a model for CPPS, respectively. Two weeks later, the urethra and dorsal prostate were excised and studied functionally in organ baths. Following this, protein expression and urethral inflammation was examined immunohistochemically. Neither prostate nor urethra showed any significant changes in contractility compared to the control group, despite a tendency for increased cholinergic contractile responses in the CPPS urethra. Induction of CPPS led to an increased expression of muscarinic M3 receptors in the urethra. In the prostate, there were no significant differences in protein expression. HE staining showed no signs of inflammation in the urethra in either group. Previous studies have shown that CPPS can alter bladder contractility. Currently, CPPS did not affect contractile responses in neither prostate nor urethra. These findings are consistent with the theory of prostate-to-bladder cross-organ sensitization. Future studies exploring this may be of great relevance in the development of new treatment options for CPPS.

The ability of captive spider monkeys, Ateles geoffroyi, to visually discriminate between different sizes of food and of non-edible objects

Abstract Field studies suggest that the size of potential food items plays an important role in the food selection behavior of nonhuman primates. However, there is only limited knowledge about how good primates are at visually discriminating between the size of three-dimensional objects of the same kind and shape. We therefore conducted two experiments on ten adult spider monkeys: a two-choice test based on spontaneous preferences with differently-sized pieces of food of the same kind and shape, and a two-choice test based on an operant conditioning procedure in which the animals were trained to choose the larger one of two cube-shaped wooden blocks. We found that the spider monkeys displayed a robust and spontaneous preference for the larger one of two simultaneously presented pieces of food of the same kind when the size difference was 11% or larger. This was true with cube-shaped food pieces as well as with ball-shaped and hemisphere-shaped food pieces. Considering that the normal size variation among fully ripe fruits of a given plant species is at least 10% this suggests that spider monkeys are as picky as necessary to make size-based food choices in line with optimal foraging theory. We also found that the spider monkeys successfully discriminated between two simultaneously presented wooden cubes when their edge length differed by only 2 mm which was the smallest size difference tested. Thus, they displayed a well-developed ability to visually discriminate between three-dimensional non-edible objects of the same kind and shape which is at least as good as that of other nonhuman primate species tested previously on similar tasks. Our findings support the notion that frugivory may have favored the evolution of cognitive abilities in the physical domain which may, possibly, include the ability to perform fine visual size discriminations.

Thymoquinone controlled obesity and invigorated cognitive and memory performance in rats consuming a high-fat diet via modulating oxidative stress, inflammation and apoptosis

Abstract The current study investigated the mitigating effects of thymoquinone (TQ) against high-fat diet (HFD)-mediated brain injury, cognitive and memory impairment, and the underlying mechanisms. Twenty-four adult male Wistar rats were divided into four groups of six rats each. Rats were fed HFD for 12 weeks to induce obesity. On the 9th week, TQ was administered orally to obese rats for four weeks. The effects of TQ were estimated by neurobehavioral testing, biochemical analysis, DNA damage, molecular docking, and histopathological examination of brains and visceral fat. TQ reduced body weight, body weight gain and adipocyte size, improved hyperlipidemia, and normalized the levels of leptin and adiponectin. TQ significantly attenuated the increase in HbA1c percent and insulin resistance. TQ decreased the accumulation of amyloid-β and tau proteins and improved the levels of neurotransmitters in the brains of obese rats. TQ-treated obese rats showed improved thickening of the pyramidal cell layer in the hippocampus and improved cognitive function and memory impairments. Molecular docking analysis indicated that TQ exhibited a marked affinity for inhibiting binding sites of tau and amyloid-β proteins. Furthermore, TQ controlled oxidative stress and enhanced the Nrf2 expression in the pyramidal cell layer and the activity of HO-1, SOD, and CAT in the brain. The restoration of redox balance by TQ was associated with normalization of inflammatory indicators and alleviation of DNA damage in the brains of HFD-treated animals. These changes contributed to the normalization of mitochondrial apoptotic pathway mediators (p53, Bcl-2, Bax, and caspase-3) and maintained the histological structure of the hippocampus. In conclusion, TQ attenuated brain injury, cognitive impairment, and memory deficit with improvement of body weight gain and metabolic status in obese rats through interrelated biological processes, including regulation of redox balance, inflammatory response, neurotransmitter equilibrium, and regression of DNA injury and apoptosis.

A genetically tractable branch of environmental Pedobacter from the phylum Bacteroidota represents a hotspot for natural product discovery

Abstract Emerging global challenges, such as antimicrobial resistance, have shifted the focus of natural product discovery from well-characterized microbial producers to underexplored taxonomic groups. Here, we computationally and experimentally characterize the biosynthetic potential of the genus Pedobacter , a Bacteroidota taxon known for antibiotic production that harbors numerous uncharacterized secondary metabolite (SM)-encoding biosynthetic gene clusters (BGCs). Through phylogenomic analysis of the genus Pedobacter , we identify a distinct clade enriched in lipopeptide-associated BGCs, most of which lack known chemical products. By developing de novo genetic tools and integrating metabolomics, we linked specific secondary metabolites to their corresponding BGCs. Using synthetic and analytical chemistry as proof of concept, we isolated and structurally characterized twelve linear lipopeptides (cryopeptins A–N), containing rare dehydrovalines from Pedobacter cryoconitis PAMC 27485. We demonstrate that all cryopeptins, despite their structural heterogeneity, are biosynthesized by a single multi-domain non-ribosomal peptide synthetase (NRPS) gene cluster. Mechanistically, we propose that this BGC drives chemical diversity through combinatorial fatty acid incorporation and iterative amino acid assembly, resulting in variable peptide chain lengths. This work highlights the biosynthetic versatility of Pedobacter and outlines methods for genetic manipulation in this genus to systematically access its cryptic natural product repertoire.

Optimizing RetinaNet anchors using differential evolution for improved object detection

Abstract Object detection is a fundamental task in computer vision. It has two primary types: one-stage detectors known for their high speed and efficiency, and two-stage detectors, which offer higher accuracy but are often slower due to their complex architecture. Balancing these two aspects has been a significant challenge in the field. RetinaNet, a premier single-stage object detector, is renowned for its remarkable balance between speed and accuracy. Its success is largely due to the groundbreaking focal loss function, which adeptly addresses the issue of class imbalance prevalent in object detection tasks. This innovative approach significantly enhances detection accuracy while maintaining high speed, making RetinaNet an ideal choice for a wide range of real-world applications. However, its performance decreases when applied to datasets containing objects with unique characteristics, such as objects with elongated or squat shapes. In such cases, the default anchor parameters may not fully meet the requirements of these specialized objects. To overcome this limitation, we present an enhancement to the RetinaNet model to improve its ability to handle variations in objects across different domains. Specifically, we propose an optimization algorithm based on Differential Evolution (DE) that adjusts anchor scales and ratios while determining the most appropriate number of these parameters for each dataset based on the annotated data. Through extensive experiments on datasets spanning diverse domains such as the Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI), the Unconstrained Face Detection Dataset (UFDD), the TomatoPlantFactoryDataset, and the widely used Common Objects in Context (COCO) 2017 benchmark, we demonstrate that our proposed method significantly outperforms both the original RetinaNet and anchor-free methods by a considerable margin.

Neuroprotective and probiotic potential of Lactiplantibacillus plantarum AM2 in cognitive impairment

Abstract This study aimed to isolate and characterize an acetylcholine-producing probiotic strain and to evaluate its potential anti-Alzheimer properties in D-galactose rat model. Nine Lactobacillus isolates were isolated and purified on MRS agar, with six demonstrating acetylcholine (ACh) production capability. Among these, Lactiplantibacillus sp. AM2 showed the highest ACh production (78.4 pg/mL) and was identified as Lactiplantibacillus plantarum through morphological, biochemical, 16S rRNA sequencing and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). The in-vitro probiotic characterization of Lactiplantibacillus plantarum AM2 included tolerance testing for acidic conditions and bile salts, viability under simulated digestive conditions, antimicrobial activity assessment, and sensitivity testing to antibiotics. Behavioral and biochemical tests were conducted in a D-galactose-induced cognitive impairment rat model to evaluate cognitive performance, serum glucose levels, oxidative stress markers, and antioxidant capacity. Histopathological evaluations of the hippocampus were also performed. Lactiplantibacillus plantarum AM2 demonstrated strong tolerance to acidic conditions and bile salts, maintaining over 80% viability after exposure to simulated gastric and pancreatic juices. The strain showed hydrophobicity toward hexadecane, octane, and xylene. It also exhibited significant antimicrobial activity against pathogenic bacteria and was sensitive to multiple antibiotics. In cognitive impairment tests, rats administered with Lactiplantibacillus plantarum AM2 showed reduced time latency in the Morris Water Maze, suggesting cognitive enhancement. Biochemical analyses revealed improvements in serum glucose levels, reduced oxidative stress markers, and increased glutathione and total antioxidant capacity. Histopathological analyses showed mitigation of hippocampal damage, promoting recovery of normal cellular architecture. These findings highlight Lactiplantibacillus plantarum AM2 as a promising probiotic candidate with neuroprotective potential and notable ACh production. Further research is warranted to explore its application in therapeutic contexts.

Suprachoroidal implantation of corticosteroid slow release implants for the treatment of cystoid macular edema

Abstract In cases of an unstable iris-lens diaphragm, intravitreal corticosteroid slow-release implants (CSRI) may accidentally migrate into the anterior chamber, leading to damage to the corneal endothelium. The purpose of this study was to evaluate the efficacy and safety of a suprachoroidal application of these primarily intravitreal implants to address this issue. In this single-center, retrospective proof of principle study, we observed consecutive cases of patients receiving dexamethasone and fluocinolon acetonide implants that were administered into the suprachoroidal space in patients with CME and instability of the iris-lens diaphragm. Treatment responses of the CME on OCT, incidence of secondary intraocular pressure increases, visual acuity and surgery related complications were evaluated. In total, 16 patients were treated and mean follow up was 1.8 ± 0.97 months. The procedure was well tolerated with no severe intraoperative or postoperative side effects. Mean central retinal thickness (CRT) decreased significantly from 563.13 to 382.12 (p = 0.002). There was no incidence of steroid induced glaucoma. Mean best corrected visual acuity (BCVA) significantly improved from 1.07 logMAR to 0.65 logMAR (p = 0.01). Suprachoroidal implantation of corticosteroid slow-release implants proves to be a safe and feasible alternative for complex eyes with CME and a disruption of the anterior-posterior segment border.

Multistage pig identification using a sequential ear tag detection pipeline

Abstract Reliable animal identification in livestock husbandry is essential for various applications, including behavioral monitoring, welfare assessment, and the analysis of social structures. Although recent advancements in deep learning models have improved animal identification using biometric markers, their applicability remains limited for species without distinctive traits like pigs. Consequently, synthetic features such as ear tags have become widely adopted. However, challenges such as poor lighting conditions and the complexity of ear tag coding continue to restrict the effectiveness of Computer Vision and Deep Learning techniques. In this study, we introduce a robust, lighting-invariant method for individual pig identification that leverages commercially available ear tags within a sequential detection pipeline. Our approach employs four object detection models in succession to detect pigs, localize ear tags, perform rotation correction via pin detection, and recognize digits, ultimately generating a reliable ID proposal. In a first evaluation stage, we assessed the performance of each model independently, achieving a mAP0.95 value of 0.970, 0.979, 0.974 and 0.979 for the pig detection, ear tag detection, pin detection and ID classification model, respectively. In addition, our method was further evaluated in two different camera environments to assess its performance in both familiar and unfamiliar conditions. The results demonstrate that the proposed approach achieves a very high precision of 0.996 in a familiar top-down camera scenario and maintained a strong generalization performance in an unfamiliar, close-up setup with a precision of 0.913 and a recall of 0.903. Furthermore, by publicly proposing three custom datasets for ear tag, pin, and digit detection, we aim to support reproducibility and further research in automated animal identification for precision livestock farming. The findings of this study demonstrate the effectiveness of ID-based animal identification and the proposed method could be integrated within advanced multi-object tracking systems to enable continuous animal observation and for monitoring specific target areas, thereby significantly enhancing overall livestock management systems.

Prevalence of and risk factors for postoperative delirium among children after cardiac surgery in a Single-Centre retrospective study

Abstract Due to the increasing focus on neurodevelopment in children with congenital heart disease (CHD), early predictive markers are crucial for implementing interventions and improving neurodevelopmental outcomes. As postoperative delirium (PD) is known to have a long-term impact on neurocognitive function in adults, studies on the prevalence of and modifiable risk factors for PD offer new perspectives. We conducted a retrospective, single-centre study screening for PD using the Cornell Assessment of Pediatric Delirium (CAPD). We distinguished PD from iatrogenic withdrawal syndrome (IWS) by using the Withdrawal Assessment Tool 1 (WAT-1). A confirmatory, multivariate regression analysis was performed and included various pre-, intra-, and postoperative variables. The screening compliance rate was 95% among the 311 patients. The prevalence of PD was 40.2%, and 46.4% of the patients developed IWS. Infants were at the highest risk for PD (OR 2.9, p  = 0.05). Prolonged mechanical ventilation > 100 h (OR 7.4, p  = 0.003), infusion therapy with ketamine (OR 3.3, p  = 0.009), IWS (mild: OR 7.7, p = < 0.001, severe: OR 17.0, p = < 0.001) and low cardiac output syndrome (LCOS) (OR 3.9, p  = 0.02) were significant predictive risk factors for PD. Overall, PD and IWS are highly prevalent in paediatric cardiac intensive care units (pCICUs), especially in infants and children with prolonged ventilation durations who require multiple sedatives. This is one of the most extensive single-centre studies in the pCICU population, and the results revealed that IWS and lactatemia in the context of LCOS are novel predictors of PD.

One step synthesis of Ag nanoparticles incorporated PVA nanocomposite via plasma reduction route

Abstract PVA/Ag nanocomposite films were synthesized via a one-step plasma-solution reduction method with varying processing times. Following synthesis, the PVA/Ag NP solutions were cast to form films, which were subsequently characterized by TEM, XRD, FTIR, XPS, UV–Vis, and Raman spectroscopy. Antimicrobial activity was evaluated using an agar diffusion test. TEM analysis confirmed the presence of Ag NPs with diverse sizes and shapes, averaging around 16.1 nm. XRD analysis showed a distinct peak at 2θ = 38°, corresponding to the Ag (111) plane in films synthesized at 10, 15, and 20 min, indicating the formation of crystalline Ag NPs. XPS results demonstrated an increased O/C ratio in plasma-synthesized PVA/Ag nanocomposite films, along with a new peak at 369.15 eV attributed to the Ag 3d orbital, confirming the presence of Ag NPs within the PVA matrix. FTIR spectra further suggested the formation of coordinate bonds between Ag NPs and PVA polymer chains. UV–Vis analysis revealed a localized surface plasmon resonance (LSPR) peak at approximately 425 nm, with a redshift to 445 nm at a longer processing time (20 min). This suggests alterations in NP size or interaction with the matrix. The optical bandgap of PVA/AgNP films decreased with longer plasma processing time, accompanied by increased film opacity. Raman analysis highlighted the potential use of PVA/Ag NP films (synthesized at 5 min) as substrates for surface-enhanced Raman spectroscopy (SERS). The PVA/Ag NP composite synthesized at a plasma processing time of 20 min exhibited considerable antibacterial activity against S. aureus and C. albicans. Also, the percentage of biofilm inhibition of S. aureus was 65%, compared to the control. Collectively, these findings suggest that plasma-synthesized PVA/Ag NP nanocomposite films are promising candidates for various applications, including optical devices, food packaging, SERS, and wound dressings.

Correction: Paired proteomic analysis reveals protein alterations in sun-exposed skin of professional drivers

Children’s cortical speech tracking in face-to-face and online video communication

Abstract In today’s digital age, online video communication has become an important way for children to interact with their social partners, especially given the increased use of such tools during the pandemic. While previous studies suggest that children can learn and engage well in virtual settings, there is limited evidence examining the neural mechanisms supporting speech processing in face-to-face and video interactions. This study examines 5-year-old German speaking children’s cortical speech tracking (n = 29), a measure of how their brains process speech, in both scenarios. Our findings indicate comparable levels of cortical speech tracking in both conditions, albeit with subtle differences. This implies that children exhibit similar neural responses to speech in both situations and may adopt different strategies to overcome potential challenges in video communication. These neural results align with previous behavioural findings, supporting the notion that live online video interactions can serve as an effective communication medium for children.

A novel nanoparticle glutathione and Lepidium sativum treatment for gentamicin-induced acute renal failure in rats

Abstract Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

Experiences of stigma among caregivers of children with disabilities in Freetown

Abstract Stigma surrounding disability continues to shape the lives of affected individuals and their families across diverse contexts. Studies indicate that caregivers of children living with disabilities (CLWDs) face stigma through their close association with the CLWD and the internalization of these beliefs. In Sierra Leone, experiences of stigma among caregivers may be intensified by beliefs that link disability to spiritual or moral failings of the CLWD’s family and extend blame for the child’s condition to the caregiver. This study explores how caregivers experience and respond to these intersecting forms of stigma and the social support they encounter or desire. We conducted six focus group discussions with 37 caregivers of CLWDs in Freetown, Sierra Leone, recruited through hospitals and a non-governmental organization providing therapeutic services. Discussions were guided by a semi-structured interview protocol and analyzed using qualitative content analysis. Caregivers reported experiencing stigma through labeling, avoidance, societal blame, and coercion into traditional practices. Stigma was deeply rooted in cultural narratives that attribute disability to supernatural causes, often extending blame to caregivers. Participants employed three overarching strategies to navigate stigma: withdrawing, coping (e.g., spiritual reframing, focusing on positive interactions), and resisting (e.g., challenging superstitious beliefs, advocating for inclusion). Despite some positive experiences of empathy and social inclusion, caregivers expressed a strong need for more practical support, community awareness, and holistic interventions to reduce stigma and foster understanding. This study sheds light on how intersecting forms of stigma—stigma by association, attributions of blame, and internalized stigma—shape the experiences of caregivers in Sierra Leone. While participants demonstrated resilience and adaptive strategies, the dual stigma of association and societal blame underscores the urgent need for inclusive policies and community-based interventions. Amplifying the voices of caregivers and addressing their needs holistically are essential steps toward reducing stigma and creating supportive environments. This study contributes to the broader discourse on caregiving and stigma, offering insights for research and interventions in similar cultural contexts.

Evaluation of podoplanin expression in vulvar squamous cell carcinoma and stromal fibroblasts and its prognostic implications

Abstract Although the immunohistochemical expression of the transmembrane sialoglycoprotein podoplanin (D2-40) has been repeatedly reported as a factor of prognosis in various tumor entities—its potential prognostic relevance in squamous cell carcinomas of the vulva remains to be evaluated. In the present study, we evaluated 68 patients with primary vulvar carcinomas (VC) and analyzed the cytoplasmic/membranous immunohistochemical expression of podoplanin in viable tumor cells and cancer-associated fibroblasts (CAFs) within the adjacent peritumoral stroma. To determine potential associations between podoplanin expression and traditional clinicopathological parameters (e.g., tumor stage, infiltration depth, groin lymph node metastasis), as well as with local recurrences, metastases, and patient’s overall survival, subsequent data analysis was conducted using Spearman correlation analysis, Fisher’s exact test and the log-rank test (Mantel-Cox). Although our results did not substantiate a positive correlation of podoplanin expression in tumor cells or CAFs with traditional histomorphological parameters, we propose a prognostic potential of podoplanin as a tissue-based biomarker in HPV-associated VC. In our exploratory pilot study, we observed a significantly improved overall survival in this distinct subgroup (Log-rank (Mantel-Cox) test; p = 0.0399). The results of our retrospective study may support the expectations that podoplanin, a common and widely available antibody, could be used as a tool for prognostic purposes in the future. Further research and validation are necessary before these markers can be implemented in clinical practice.