Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans.

BACKGROUND: Candida albicans is a fungal pathogen causing human infections. Here we investigated differential gene expression patterns and functional enrichment in C. albicans strains grown under different conditions. METHODS: A systematic GEO database search identified 239 "Candida albicans" datasets, of which 14 were selected after rigorous criteria application. Retrieval of raw sequencing data from the ENA database was accompanied by essential metadata extraction from dataset descriptions and original articles. Pre-processing via the tailored nf-core pipeline for C. albicans involved alignment, gene/transcript quantification, and diverse quality control measures. Quality assessment via PCA and DESeq2 identified significant genes (FDR < = 0.05, log2-fold change > = 1 or <= -1), while topGO conducted GO term enrichment analysis. Exclusions were made based on data quality and strain relevance, resulting in the selection of seven datasets from the SC5314 strain background for in-depth investigation. RESULTS: The meta-analysis of seven selected studies unveiled a substantial number of genes exhibiting significant up-regulation (24,689) and down-regulation (18,074). These differentially expressed genes were further categorized into 2,497 significantly up-regulated and 2,573 significantly down-regulated Gene Ontology (GO) IDs. GO term enrichment analysis clustered these terms into distinct groups, providing insights into the functional implications. Three target gene lists were compiled based on previous studies, focusing on central metabolism, ion homeostasis, and pathogenicity. Frequency analysis revealed genes with higher occurrence within the identified GO clusters, suggesting their potential as antifungal targets. Notably, the genes TPS2, TPS1, RIM21, PRA1, SAP4, and SAP6 exhibited higher frequencies within the clusters. Through frequency analysis within the GO clusters, several key genes emerged as potential targets for antifungal therapies. These include RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101 which exhibited higher occurrence within the identified clusters. CONCLUSION: This comprehensive study significantly advances our understanding of the dynamic nature of gene expression in C. albicans. The identification of genes with enhanced potential as antifungal drug targets underpins their value for future interventions. The highlighted genes, including TPS2, TPS1, RIM21, PRA1, SAP4, SAP6, RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101, hold promise for the development of targeted antifungal therapies.

Ameliorating and Therapeutic Impact of Curcumin Nanoparticles Against Aluminum Oxide Nanoparticles Induced Kidney Toxicity, DNA Damage, Oxidative Stress, PCNA and TNFα Alteration in Male Rats.

Aluminum oxide nanoparticles (Al2O3 NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform (Cur NPs) against Al2O3 NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al2O3 NPs; G4, (Cur NPs + Al2O3 NPs) received Cur NPs and Al2O3 NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al2O3 NPs + Cur NPs) received Al2O3 NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al2O3 NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al2O3 NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al2O3 NPs + Cur NPs than Cur NPs + Al2O3 NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al2O3 NPs in male albino rats.

Effect of dual tasking on postural control in individuals with schizophrenia.

OBJECTIVE: To investigate the effect of dual tasking on postural control in individuals with schizophrenia. METHODS: Fifteen outpatients with schizophrenia and 15 healthy controls were included. Postural control was assessed with postural sway velocity (PSV) using Balance Master System during three different tasks: single task (standing on a force platform), cognitive task (categorical verbal fluency) and motor task (holding a cup of water) in four conditions: on firm surface with eyes open (1) and closed (2), on foam surface with eyes open (3) and closed (4). RESULTS: Individuals with schizophrenia presented higher PSV during single standing on foam surface with eyes open and closed. During the cognitive task, they showed higher PSV on foam surface with eyes closed. During the motor task PSV in schizophrenia group was higher on firm surface with eyes closed and on foam surface with eyes open and closed. Individuals with schizophrenia showed higher PSV during cognitive task on firm surface with eyes closed compared to the single task. CONCLUSIONS: Dual tasking results in a deterioration in postural control in individuals with schizophrenia. A cognitive task specifically alters postural control in the absence of visual information suggesting a possible sensorimotor dysfunction in this population.

Surf Redfish-Based ZnO-NPs and Their Biological Activity with Reference to Their Non-Target Toxicity.

The marine environment is a rich source of bioactive compounds. Therefore, the sea cucumber was isolated from the Red Sea at the Al-Ain Al-Sokhna coast and it was identified as surf redfish (Actinopyga mauritiana). The aqueous extract of the surf redfish was utilized as an ecofriendly, novel and sustainable approach to fabricate zinc oxide nanoparticles (ZnO-NPs). The biosynthesized ZnO-NPs were physico-chemically characterized and evaluated for their possible antibacterial and insecticidal activities. Additionally, their safety in the non-target organism model (Nile tilapia fish) was also investigated. ZnO-NPs were spherical with an average size of 24.69 ± 11.61 nm and had a peak at 350 nm as shown by TEM and UV-Vis, respectively. XRD analysis indicated a crystalline phase of ZnO-NPs with an average size of 21.7 nm. The FTIR pattern showed biological residues from the surf redfish extract, highlighting their potential role in the biosynthesis process. DLS indicated a negative zeta potential (-19.2 mV) of the ZnO-NPs which is a good preliminary indicator for their stability. ZnO-NPs showed larvicidal activity against mosquito Culex pipiens (LC50 = 15.412 ppm and LC90 = 52.745 ppm) and a potent adulticidal effect to the housefly Musca domestica (LD50 = 21.132 ppm and LD90 = 84.930 ppm). Tested concentrations of ZnO-NPs showed strong activity against the 3rd larval instar. Topical assays revealed dose-dependent adulticidal activity against M. domestica after 24 h of treatment with ZnO-NPs. ZnO-NPs presented a wide antibacterial activity against two fish-pathogen bacteria, Pseudomonas aeruginosa and Aeromonas hydrophila. Histopathological and hematological investigations of the non-target organism, Nile tilapia fish exposed to 75-600 ppm ZnO-NPs provide dose-dependent impacts. Overall, data highlighted the potential applications of surf redfish-mediated ZnO-NPs as an effective and safe way to control mosquitoes, houseflies and fish pathogenic bacteria.

Change management in sustainability transformation: A model for business organizations.

This study zooms in on sustainability transformation processes by deploying Stouten, Rousseau, and Cremer's (SRC) model of ten key evidence-based steps in managing planned organizational change as an anchor to develop a sequential sustainability transformation model (STM) for business organizations. The study highlights phases and steps in sustainability transformation with environmental, social, and governance (ESG) factors. Implementing planned organizational change models in sustainability transformation provides new evidence that the governance (G) factor plays the most significant role among ESG factors. Moreover, the study reveals the importance of developing more robust metrics to gauge governance factors. This study also connects change management with sustainability transformation and addresses future research in this nexus.

Neurosurgical Education Using Cadaver-Free Brain Models and Augmented Reality: First Experiences from a Hands-On Simulation Course for Medical Students.

Background and Objectives: Neurosurgery has been underrepresented in the medical school curriculum. Advances in augmented reality and 3D printing have opened the way for early practical training through simulations. We assessed the usability of the UpSurgeOn simulation-based training model and report first experiences from a hands-on neurosurgery course for medical students. Materials and Methods: We organized a two-day microneurosurgery simulation course tailored to medical students. On day one, three neurosurgeons demonstrated anatomical explorations with the help of life-like physical simulators (BrainBox, UpSurgeOn). The surgical field was projected onto large high-definition screens by a robotic-assisted exoscope (RoboticScope, BHS Technologies). On day two, the students were equipped with microsurgical instruments to explore the surgical anatomy of the pterional, temporal and endoscopic retrosigmoid approaches. With the help of the RoboticScope, they simulated five clipping procedures using the Aneurysm BrainBox. All medical students filled out a digital Likert-scale-based questionnaire to evaluate their experiences. Results: Sixteen medical students participated in the course. No medical students had previous experience with UpSurgeOn. All participants agreed that the app helped develop anatomical orientation. They unanimously agreed that this model should be part of residency training. Fourteen out of sixteen students felt that the course solidified their decision to pursue neurosurgery. The same fourteen students rated their learning experience as totally positive, and the remaining two rated it as rather positive. Conclusions: The UpSurgeOn educational app and cadaver-free models were perceived as usable and effective tools for the hands-on neuroanatomy and neurosurgery teaching of medical students. Comparative studies may help measure the long-term benefits of UpSurgeOn-assisted teaching over conventional resources.

Prognostic factors and scoring systems associated with outcome in pediatric acute liver failure.

BACKGROUND: Pediatric acute liver failure (PALF) is an uncommon, devastating illness with significant mortality. Liver transplantation remains the mainstay of treatment for irreversible PALF. The purpose of this study was to determine the etiology and prognostic factors associated with outcome of PALF in South Africa and to evaluate prognostic scoring systems used. METHODS: Records of 45 pediatric patients younger than 16 years of age who presented with PALF from 1 January 2015 till 31 October 2020 were analysed. Patients were divided into two groups with one group consisting of patients with spontaneous recovery of the liver with supportive treatment (6/45:13.3%) and the second group consisting of patients with poor outcomes who demised (19/45: 42%) or underwent liver transplantation (20/45: 44%). RESULTS: The median age of presentation was 3.3 years (IQR 1.8-6.9) with the 1-5 years age group constituting majority of patients (55.6%). Median time to follow up was 6.1 months (IQR 0.2-28.8). Higher liver injury unit scores were observed in patients who had poorer outcomes (P = 0.008) with a threshold of greater than 246 having a sensitivity of 84% and specificity of 83% (P < 0.001). Higher peak PELD/MELD (P = 0.006) and admission UKELD (P = 0.002) scores, were found in patients with poorer outcomes. Kings College Hospital criteria (KCHC) was useful in predicting which patients would die without liver transplantation (P = 0.002). Liver transplantation was performed in 20/45 (44%) patients with a post transplantation 1 year patient and graft survival of 80%. CONCLUSION: Although, survival of PALF patients was lower than high and other low-middle income countries, outcomes post transplantation were good. Our study demonstrates the utility of dynamic scoring systems in PALF patients, it underscores the need for early referral and clinical monitoring in a tertiary center once the criteria for PALF have been met.

Arthroscopic Wafer Procedure Versus Ulnar Shortening Osteotomy for Treatment of Idiopathic Ulnar Impaction Syndrome: A Randomized Controlled Trial.

PURPOSE: We compared the arthroscopic wafer procedure (AWP) and ulnar shortening osteotomy (USO) for treatment of idiopathic ulnar impaction syndrome in terms of clinical, functional improvement and time of return to work. METHODS: This single-center study was conducted at an academic level 1 referral center between 2014 and 2020. Sixty patients with idiopathic ulnar impaction syndrome were prospectively randomized to treatment with either AWP or USO. At the final follow-up, patients were evaluated by the Disabilities of the Arm, Shoulder, and Hand; the Modified Mayo Wrist Score; the visual analog scale for pain; wrist range of motion; and grip strength. Also, the time of return to work and complications were reported. RESULTS: The mean follow-up periods were 22 ± 5.7 months in the AWP group and 21.1 ± 5.3 months in the USO group. All patients in the USO group achieved union by 12 weeks. At the final follow-up, there were no statistically significant differences in the outcome measures (Disabilities of the Arm, Shoulder, and Hand score; Modified Mayo Wrist Score; visual analog scale score; range of motion; and grip strength) in either group. Fewer complications and an earlier return to work were observed in the AWP group. CONCLUSIONS: Both techniques yielded comparable outcomes, with earlier return to work, a lower incidence of complications, and fewer secondary procedures in the AWP group. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model.

Calpain activation has been implicated in various pathologies, including neurodegeneration. Thus, calpain inhibition could effectively prevent spinal cord injury (SCI) associated with neurodegeneration. In the current study, a dog SCI model was used to evaluate the therapeutic potential of a selective calpain inhibitor (PD150606) in combination with methylprednisolone sodium succinate (MPSS) as an anti-inflammatory drug. SCI was experimentally induced in sixteen mongrel dogs through an epidural balloon compression technique. The dogs were allocated randomly into four groups: control, MPSS, PD150606, and MPSS+PD150606. Clinical evaluation, serum biochemical, somatosensory evoked potentials, histopathological, and immunoblotting analyses were performed to assess treated dogs during the study. The current findings revealed that the combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score. The increased levels of inflammatory markers (GFAP and CD11) and calcium-binding proteins (Iba1 and S100) were significantly reduced in the combination group and to a lesser extent in MPSS or PD150606 treatment alone. Interestingly, the combined treatment effectively inhibited the calpain-induced cleavage of p35, limited cdk5 activation, and inhibited tau phosphorylation. These results suggest that early MPSS+PD150606 therapy after acute SCI may prevent subsequent neurodegeneration via calpain inhibition.

Evaluation of Antioxidant Activity and Biotransformation of Opuntia Ficus Fruit: The Effect of In Vitro and Ex Vivo Gut Microbiota Metabolism.

Opuntia ficus-indica biological effects are attributed to several bioactive metabolites. However, these actions could be altered in vivo by biotransformation reactions mainly via gut microbiota. This study assessed gut microbiota effect on the biotransformation of O. ficus-indica metabolites both in vitro and ex vivo. Two-time aliquots (0.5 and 24 h) from the in vitro assay were harvested post incubation of O. ficus-indica methanol extract with microbial consortium, while untreated and treated samples with fecal bacterial culture from the ex vivo assay were prepared. Metabolites were analyzed using UHPLC-QTOF-MS, with flavonoid glycosides completely hydrolyzed in vitro at 24 h being converted to two major metabolites, 3-(4-hydroxyphenyl)propanoic acid and phloroglucinol, concurrent with an increase in the gallic acid level. In case of the ex vivo assay, detected flavonoid glycosides in untreated sample were completely absent from treated counterpart with few flavonoid aglycones and 3-(4-hydroxyphenyl)propanoic acid in parallel to an increase in piscidic acid. In both assays, fatty and organic acids were completely hydrolyzed being used as energy units for bacterial growth. Chemometric tools were employed revealing malic and (iso)citric acids as the main discriminating metabolites in vitro showing an increased abundance at 0.5 h, whereas in ex vivo assay, (iso)citric, aconitic and mesaconic acids showed an increase at untreated sample. Piscidic acid was a significant marker for the ex vivo treated sample. DPPH, ORAC and FRAP assays were further employed to determine whether these changes could be associated with changes in antioxidant activity, and all assays showed a decline in antioxidant potential post biotransformation.