In vitro and in silico evaluation of bioactivities and chemical composition of the aerial parts of Anchusa officinalis L. methanol extract.

The main objective of the study is to evaluate the antioxidant, anticancer, and antimicrobial activities of Anchusa officinalis L. in vitro and in silico. The dried aerial parts of A. officinalis L. were extracted with methanol. Total phenolic and flavonoid content was analyzed. Antioxidant and antimicrobial effects were tested against both gram-positive and gram-negative bacteria. Gas chromatography-mass spectrometry analysis revealed the presence of 10 phytochemical compounds, and cyclobutane (26.07%) was identified as the major photochemical compound. The methanol extract exhibited the maximum amount of total phenolic content (118.24 ± 4.42 mg QE/g dry weight of the dry extract) (R2 = 0.994) and the total flavonoid content was 94 ± 2.34 mg QE/g dry weight of the dry extract (R2 = 0.999). The IC50 value for 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid was 107.12 ± 3.42 µg/mL, and it was high for 1,1-diphenyl-2-picryl hydrazyl (123.94 ± 2.31 µg/mL). The IC50 value was 72.49 ± 3.14 against HepG2 cell lines, and a decreased value was obtained (102.54 ± 4.17 g/mL) against MCF-7 cell lines. The methanol extract increased the expression of caspase mRNA and Bax mRNA levels when compared to the control experiment (p < .05). The conclusions, A. officinalis L. aerial parts extract exhibited antibacterial, antifungal, and antioxidant activities.

Metabolism of FAD, FMN and riboflavin (vitamin B2) in the human parasitic blood fluke Schistosoma mansoni.

BACKGROUND: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. METHODS: Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm). RESULTS: We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M- 1.S- 1. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2. Since schistosomes are damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M- 1.S- 1. CONCLUSIONS: The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes.

Effect of Shearing and Annealing on the Pasting Properties of Different Starches.

The functional characteristics of starch can be altered by shear force, which makes the impact on its microstructure of great importance to the food industry. This study investigated the effects of freeze-drying on the gel texture, pasting capabilities, and swelling power of starches made from sweet potatoes (SP), chickpeas (CP), and wheat (WS) combined with Cordia (CG) and Ziziphus gum (ZG). The samples were annealed in water without shearing and in a rapid visco-analyzer (RVA) for 30 min at 60 °C while being spun at 690 rpm. Both native and freeze-dried samples were mixed with 1% or 3% ZG and CG. After annealing, the starches were examined using a texture analyzer and RVA. The results showed that freeze-drying had a substantial (p > 0.05) impact on the starch granule, in addition to the effect of annealing. The peak viscosity of freeze-dried native CP and SP starches increased, but the peak viscosity of freeze-dried wheat starch decreased. The setbacks for CP and WS increased, whereas the setbacks for SP varied slightly. Furthermore, it was demonstrated that annealing in an RVA exhibited a substantially lower peak viscosity than annealing in a water bath; the RVA's shearing effect may have been the cause of this difference. Cordia gum fared better than ZG in terms of peak viscosity, although ZG significantly reduced setback in comparison to CG. Among the various blends, the native WB sample had the lowest hardness (100 ± 4.9 g), while the freeze-dried WB SP sample had the greatest (175.5 ± 4.8 g). Shearing of starches broke up the granules into smaller pieces, which made them gel at lower temperatures. This could be a good thing when they are needed for food uses that require little cooking.

The impact of APOE ε4 in Alzheimer's disease: a meta-analysis of voxel-based morphometry studies.

Background: Alzheimer's disease (AD) is the most prevalent form of dementia, exerting substantial personal and societal impacts. The apolipoprotein E (APOE) ε4 allele is a known genetic factor that increases the risk of AD, contributing to more severe brain atrophy and exacerbated symptoms. Purpose: We aim to provide a comprehensive review of the impacts of the APOE ε4 allele on brain atrophy in AD and mild cognitive impairment (MCI) as a transitional stage of AD. Methods: We performed a coordinate-based meta-analysis of voxel-based morphometry (VBM) studies to identify the patterns of grey matter atrophy in APOE ε4 carriers vs. non-carriers. We obtained coordinate-based structural magnetic resonance imaging (MRI) data for 1135 individuals from 12 studies on PubMed and Google Scholar that met our inclusion criteria. Results: We found significant atrophy in the hippocampus and parahippocampus of APOE ε4 carriers compared to non-carriers, especially within the AD and MCI groups, while healthy controls showed no significant atrophy in these regions. Conclusion: Our meta-analysis sheds light on the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, emphasizing the allele's critical influence on neurodegeneration, especially in the hippocampus. Our findings contribute to the understanding of the disease's pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals with the APOE ε4 allele who are at risk for Alzheimer's Disease.

Memory impairment in Amyloidß-status Alzheimer's disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T.

INTRODUCTION: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI). METHODS: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidß-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study. RESULTS: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory. DISCUSSION: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy. CLINICALTRIALS: GOV: ID NCT04992975 (Clinicaltrial.gov 2023).

Metabolism of FAD, FMN and riboflavin (vitamin B2) in the human parasitic blood fluke Schistosoma mansoni.

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. In this work we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni. We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while the levels of FMN increase. We show that live schistosomes can cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2 in the extracellular environment. Since schistosomes can be damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case, suggesting that covalently bound FAD on IL-4I1 is inaccessible to SmNPP5. We also report here that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM. Thus, the sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by, we hypothesize, the recently described schistosome riboflavin transporter SmaRT. In this work we also identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes.

The riboflavin (vitamin B2) transporter protein (SmaRT) of the human intravascular parasitic trematode Schistosoma mansoni.

Schistosomes are intravascular parasitic worms infecting >200 million people globally. Here we examine how the worms acquire an essential nutrient - vitamin B2 (riboflavin). We demonstrate that all intravascular life stages (schistosomula, adult males and females) take up radiolabeled riboflavin. This process is impeded in the presence of excess unlabeled riboflavin and at 4 °C. We have identified a transporter homolog in worms designated SmaRT (Schistosoma mansoni riboflavin transporter) that localizes to the tegument and internal tissues of adults. CHO-S cells transfected with plasmid encoding SmaRT import significantly more radiolabeled riboflavin compared to controls. Uptake of radiolabel is impeded when SmaRT-expressing cells are incubated in an excess of unlabeled riboflavin but not by an excess of an irrelevant metabolite. Uptake is mediated in a sodium-independent manner and over a wide range of pH values (pH 5.5-9). This is the first identification of a bone fide riboflavin transporter in any platyhelminth.

Socioeconomic Disparities in Online Patient Portal Utilization Among Total Knee Arthroplasty Recipients.

BACKGROUND: Since 2021, the Centers for Medicare and Medicaid Services have mandated that patients have open access to their medical records. Many institutions use online portals, which allow patients to access their health information and communicate with care teams. Our research aimed to evaluate demographic patterns for online patient portal utilization in patients undergoing total knee arthroplasty (TKA). Further, we assessed if and how portal engagement contributes to perioperative outcomes. METHODS: This study retrospectively reviewed primary and elective TKA from 2017 to 2022 at a single academic institution. Patients were stratified into 2 groups based on their online portal status: activated (A) or not-activated (NA). Baseline characteristics and postoperative outcomes were collected from the electronic medical record and compared. RESULTS: In total, 10,995 patients were included: 8,330 (75.8%) were A and 2,625 (24.2%) were NA. The NA group was significantly older (P < .001); more likely to be Black (P < .001), women (P < .001), single/divorced/widowed (P < .001), non-English speaking (P < .001), and Medicare or Medicaid insured (P < .001); from zip codes with median incomes below $50,000 (P < .001), and more likely to be American Society of Anesthesiologists class III or IV (P < .001). Patient-reported outcome measure completion rates were significantly lower in the NA group (15.3 versus 47.7%, P < .001). Lengths of stay (LOS) were significantly higher in the NA group (2.7 versus 2.1 days, P < .001). The NA group was significantly more likely to be discharged to skilled nursing facilities (P < .001). Comparable rates of 90-day emergency department visits, readmissions, as well as 90-day and 2-year revisions, were observed across groups. CONCLUSIONS: There are significant disparities in online portal activation status based on patient demographics. Patients who have A portals had significantly higher Patient-reported outcome measure completion rates, shorter LOS, and higher rates of home discharge. Further research should determine which other factors may affect patient portal utilization and inform interventions to improve portal utilization among minority populations.

GLYCOLYTIC ENZYMES AS VACCINES AGAINST SCHISTOSOMIASIS: TESTING SCHISTOSOMA MANSONI PHOSPHOGLYCERATE MUTASE IN MICE.

Schistosomiasis is a globally burdensome parasitic disease caused by flatworms (blood flukes) in the genus Schistosoma. The current standard treatment for schistosomiasis is the drug praziquantel, but there is an urgent need to advance novel interventions such as vaccines. Several glycolytic enzymes have been evaluated as vaccine targets for schistosomiasis, and data from these studies are reviewed here. Although these parasites are canonically considered to be intracellular, proteomic analysis has revealed that many schistosome glycolytic enzymes are additionally found at the host-interactive surface. We have recently found that the intravascular stage of Schistosoma mansoni (Sm) expresses the glycolytic enzyme phosphoglycerate mutase (PGM) on the tegumental surface. Live parasites display PGM activity, and suppression of PGM gene expression by RNA interference diminishes surface enzyme activity. Recombinant SmPGM (rSmPGM) can cleave its glycolytic substrate, 3-phosphoglycerate and can both bind to plasminogen and promote its conversion to an active form (plasmin) in vitro, suggesting a moonlighting role for this enzyme in regulating thrombosis in vivo. We found that antibodies in sera from chronically infected mice recognize rSmPGM. We also tested the protective efficacy of rSmPGM as a vaccine in the murine model. Although immunization generates high titers of anti-SmPGM antibodies (against both recombinant and native SmPGM), no significant differences in worm numbers were found between vaccinated and control animals.

Endophytic Aspergillus hiratsukae mediated biosynthesis of silver nanoparticles and their antimicrobial and photocatalytic activities.

In the current study, endophytic Aspergillus hiratsukae was used for the biosynthesis of silver nanoparticles (Ag-NPs) for the first time. The characterizations were performed using X ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectroscopy. The obtained results demonstrated the successful formation of crystalline, spherical Ag-NPs with particle diameters ranging from 16 to 31 nm. The FT-IR studied and displayed the various functional groups involved, which played a role in capping and reducing agents for Ag-NPs production. The SEM-EDX revealed that the main constituent of the AS-formed sample was primarily Ag, with a weight percentage of 64.2%. The mycosynthesized Ag-NPs were assessed for antimicrobial as well as photocatalytic activities. The antimicrobial results indicated that the synthesized Ag-NPs possess notable antibacterial efficacy against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, with minimum inhibitory concentrations (MICs) of Ag-NPs ranging from 62.5 to 250 µg/mL. Moreover, the biosynthesized Ag-NPs demonstrated weak antifungal activity against Aspergillus brasiliensis and Candida albicans, with MICs of 500 and 1,000 µg/mL, respectively. In addition, the mycosynthesized Ag-NPs exhibited photocatalytic activity toward acid black 2 (nigrosine) dye under both light and dark stimulation. Notably, After 300 min exposure to light, the nigrosine dye was degraded by 93%. In contrast, 51% degradation was observed after 300 min in darkness. In conclusion, Ag-NPs were successfully biosynthesized using endophytic A. hiratsukae and also exhibited antimicrobial and photocatalytic activities that can be used in environmental applications.

Mid-term outcomes of a kinematically designed cruciate retaining total knee arthroplasty.

BACKGROUND: Advances in implant material and design have allowed for improvements in total knee arthroplasty (TKA) outcomes. A cruciate retaining (CR) TKA provides the least constraint of TKA designs by preserving the native posterior cruciate ligament. Limited research exists that has examined clinical outcomes or patient reported outcome measures (PROMs) of a large cohort of patients undergoing a CR TKA utilizing a kinematically designed implant. It was hypothesized that the studied CR Knee System would demonstrate favorable outcomes and a clinically significant improvement in pain and functional scores. AIM: To assess both short-term and mid-term clinical outcomes and PROMs of a novel CR TKA design. METHODS: A retrospective, multi-surgeon study identified 255 knees undergoing a TKA utilizing a kinematically designed CR Knee System (JOURNEY™ II CR; Smith and Nephew, Inc., Memphis, TN) at an urban, academic medical institution between March 2015 and July 2021 with a minimum of two-years of clinical follow-up with an orthopedic surgeon. Patient demographics, surgical information, clinical outcomes, and PROMs data were collected via query of electronic medical records. The PROMs collected in the present study included the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) and Patient-Reported Outcomes Measurement Information System (PROMIS®) scores. The significance of improvements in mean PROM scores from preoperative scores to scores collected at six months and two-years postoperatively was analyzed using Independent Samples t-tests. RESULTS: Of the 255 patients, 65.5% were female, 43.8% were White, and patients had an average age of 60.6 years. Primary osteoarthritis (96.9%) was the most common primary diagnosis. The mean surgical time was 105.3 minutes and mean length of stay was 2.1 d with most patients discharged home (92.5%). There were 18 emergency department (ED) visits within 90 d of surgery resulting in a 90 d ED visit rate of 7.1%, including a 2.4% orthopedic-related ED visit rate and a 4.7% non-orthopedic-related ED visit rate. There were three (1.2%) hospital readmissions within 90 d postoperatively. With a mean time to latest follow-up of 3.3 years, four patients (1.6%) required revision, two for arthrofibrosis, one for aseptic femoral loosening, and one for peri-prosthetic joint infection. There were significant improvements in KOOS JR, PROMIS Pain Intensity, PROMIS Pain Interference, PROMIS Mobility, and PROMIS Physical Health from preoperative scores to six month and two-year postoperative scores. CONCLUSION: The evaluated implant is an effective, novel design offering excellent outcomes and low complication rates. At a mean follow up of 3.3 years, four patients required revisions, three aseptic and one septic, resulting in an overall implant survival rate of 98.4% and an aseptic survival rate of 98.8%. The results of our study demonstrate the utility of this kinematically designed implant in the setting of primary TKA.

Innovations in the Isolation and Treatment of Biofilms in Periprosthetic Joint Infection: A Comprehensive Review of Current and Emerging Therapies in Bone and Joint Infection Management.

Periprosthetic joint infections (PJIs) are a devastating complication of joint arthroplasty surgeries that are often complicated by biofilm formation. The development of biofilms makes PJI treatment challenging as they create a barrier against antibiotics and host immune responses. This review article provides an overview of the current understanding of biofilm formation, factors that contribute to their production, and the most common organisms involved in this process. This article focuses on the identification of biofilms, as well as current methodologies and emerging therapies in the management of biofilms in PJI.

Shock wave lithotripsy in the era of COVID-19.

Objective: The objective of the study y was to evaluate factors which can improve shock wave lithotripsy (SWL) results to keep up with COVID-19 pandemic. Methods: Between June 2020 and June 2021, patients with radio-opaque or faint radio-opaque upper urinary tract stones, stone attenuation value ≤1200 HU, and stones size <2.5 cm were treated by electrohydraulic SWL. Patients with respiratory tract symptoms elevated temperature, contact with COVID-19 patients, or positive COVID-19 swab 2 weeks preoperatively, skin-to-stone distance >11 cm, and body mass index >30 kg/m2 were excluded from the study. Patients were prospectively enrolled in SWL done at a rate of 40-50 SWs/min under combined ultrasound and fluoroscopy-guided, ramped into high power in the 1st 300 shocks. Success rate and complications were recorded. Results: Five hundred and ninety patients completed the study. The success rate after 1st session was 408/590 patients (69.15%) which was augmented by 2nd session to reach 527/590 patients 89.3%. The success rate was 96.2% at 3 months postoperatively. Most complications were mild (Grade 1 or 2). Conclusions: SWL results improved using slow rate high power from the start of the session under combined fluoroscopy and ultrasound guidance. SWL may be a preferred option during a pandemic.

Polyphenolic characterization and biological assessment of Acacia nilotica (L.) wild. Ex delilie: An In vitro and In vivo appraisal of wound healing potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Acacia nilotica (L.) Wild. Ex Delilie is a shrub with significant ethnomedicinal stature. Therefore, in the undertaken study, its wound healing attributes are determined. AIM OF THE STUDY: The current study provided evidence of the traditional use of A. nilotica species and conferred A. nilotica bark extract as a potent candidate for wound healing agents. MATERIALS & METHODS: A. nilotica leaves extract (ANL-E); A. nilotica bark extract (ANB-E), and A. nilotica stem extract (ANS-E) were prepared using methanol-chloroform (1:1). Phytochemical analysis was performed using gallic acid equivalent (GAE) total phenolic content (TPC), quercetin equivalent (QE) total flavonoid content (TFC) assays and High-performance liquid chromatography (HPLC). In vitro antioxidant potential (free radical scavenging activity (FRSA), total antioxidant capacity (TAC), and ferric reducing antioxidant power (FRAP) assay), antibacterial activity (broth microdilution method) and hemolytic analysis was carried out. Wound healing proficiency of ANB-E was determined by wound excision model followed by estimating hydroxyproline content and endogenous antioxidant markers. RESULTS: Maximum phenolic and flavonoid content were depicted by ANB-E i.e., 50.9 ± 0.34 µg gallic acid equivalent/mg extract and 28.7 ± 0.13 µg quercetin equivalent/mg extract, respectively. HPLC analysis unraveled the presence of a significant amount of catechin in ANL-E, ANB-E and ANS-E (54.66 ± 0.02, 44.9 ± 0.004 and 31.36 ± 0.02 µg/mg extract) respectively. Highest percent free radical scavenging activity, total antioxidant capacity, and ferric reducing action power (i.e., 93.3 ± 0.42 %, 222.10 ± 0.76, and 222.86 ± 0.54 µg ascorbic acid equivalent/mg extract) were exhibited by ANB-E. Maximum antibacterial potential against Staphylococcus aureus was exhibited by ANB-E (MIC 12.5 µg/ml). Two of the extracts i.e., ANL-E and ANB-E were found biocompatible with less than 5 % hemolytic potential. Based upon findings of in vitro analysis, ANB-E (10, 5, and 2.5 % w/w, C1, C2, and C3, respectively) was selected for evaluating its in vivo wound healing potential. Maximum contraction of wound area and fastest epithelization i.e., 98 ± 0.05 % and 11.2 ± 1.00 (day) was exhibited by C1. Maximum hydroxyproline content, glutathione, catalase, and peroxidase were demonstrated by C1 i.e., 15.9 ± 0.52 µg/mg, 9.3 ± 0.17 mmol/mg, 7.2 ± 0.17 and 6.2 ± 0.14 U/mg, respectively. Maximal curbed lipid peroxidation i.e., 0.7 ± 0.15 mmol/mg was also depicted by C1. CONCLUSIONS: In a nutshell, the current investigation endorsed the wound healing potential of ANB-E suggesting it to be an excellent candidate for future studies.

Unlocking the diagnostic, prognostic roles, and immune implications of BAX gene expression in pan-cancer analysis.

OBJECTIVES: Cancer, a formidable disease, continues to challenge our understanding and therapeutic approaches. This study delves into the pan-cancer analysis of BCL2 Associated X (BAX) gene expression, seeking to unravel its significance in cancer development, prognosis, and potential therapeutic strategies. METHODS: A combination of bioinformatics and molecular experiments. RESULTS: Our pan-cancer investigation into BAX expression encompassed 33 distinct cancer types, revealing a remarkable and uniform increase in BAX expression. This groundbreaking finding emphasizes the potential universality of BAX's role in cancer development and progression. Further, our study explored the prognostic implications of BAX expression, highlighting a consistent association between up-regulated BAX and poor overall survival (OS) in Liver Hepatocellular Carcinoma (LIHC) and Skin Cutaneous Melanoma (SKCM). These results suggest that BAX may serve as an adverse prognostic indicator in these malignancies, emphasizing the importance of personalized treatment strategies. Epigenetic and genetic analyses of BAX provided valuable insights. Hypomethylation of the BAX promoter region was evident in LIHC and SKCM, which likely contributes to the up-regulation of BAX, while genetic mutations in the BAX gene itself were infrequent in these cancers. Our exploration of BAX-associated signaling pathways and the correlation between BAX expression and CD8+ T cell infiltration shed light on the intricate molecular landscape of cancer. BAX's interaction with key apoptotic and immune-related pathways reinforces its role as a central player in tumor development and the immune microenvironment. Moreover, our drug prediction analysis identified potential therapeutic agents for modulating BAX expression in the context of LIHC and SKCM, bridging the gap between research and clinical application. CONCLUSION: In sum, our comprehensive BAX study not only enhances our understanding of its significance as a biomarker gene but also offers novel avenues for therapeutic interventions, contributing to the ongoing quest for more effective cancer treatments and improved patient care.

Environmental pollutants PM2.5, PM10, carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) impair human cognitive functions.

OBJECTIVE: Environmental pollution is an emerging global public health problem across the world and causes serious threats to ecosystems, human health, and the planet. This study is designed to explore the impact of environmental pollution particulate matter PM2.5, PM10, carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) on cognitive functions in students from schools located in or away from air-polluted areas. SUBJECTS AND METHODS: In this study, two schools were selected: one was located near a traffic-polluted area (school #1), and the second was in an area away from the traffic-polluted area (school #2). In this study, a total of 300 students were recruited: 150 (75 male and 75 female) students from school #1 located in a traffic-polluted area, and 150 students (75 male and 75 female) from school #2 located away from a traffic polluted area. The overall average age of students was 13.53±1.20 years. The students were selected based on age, gender, health status, height, weight, BMI, ethnicity, and homogenous socio-economic and educational status. The pollutants PM2.5, PM10, CO, NO2, O3, and SO2 were recorded in the surrounding environment. The overall mean concentration of environmental pollutants in school #1 was 35.00±0.65 and in school #2 was 29.95±0.32. The levels of airborne particles were measured, and the cognitive functions were recorded using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The students performed the cognitive functions tasks, including the attention switching task (AST), choice reaction time (CRT), and motor screening task (MOT). RESULTS: The results revealed that the AST-Mean 928.34±182.23 vs. 483.79±146.73 (p=0.001), AST-mean congruent 889.12±197.12 vs. 473.30±120.11 (p=0.001), AST-mean in-congruent 988.98±201.27  vs. 483.87±144.57 (p=0.001), CRT-Mean 721.36±251.72  vs. 418.17±89.71 (p=0.001), and MOT-Mean 995.07±394.37 vs. 526.03±57.83 (p=0.001) were significantly delayed among the students who studied in school located in the traffic polluted area compared to students who studied in school which was located away from the traffic-polluted area. CONCLUSIONS: Environmental pollution was significantly higher in motor vehicle-congested areas. Cognitive functions were impaired among the students who were studying in a school located in a polluted area. The results further revealed that the students studying in schools located in environmentally polluted areas have attention, thinking, and decision-making abilities related to cognitive function impairment.

Human versus artificial intelligence-generated arthroplasty literature: A single-blinded analysis of perceived communication, quality, and authorship source.

BACKGROUND: Large language models (LLM) have unknown implications for medical research. This study assessed whether LLM-generated abstracts are distinguishable from human-written abstracts and to compare their perceived quality. METHODS: The LLM ChatGPT was used to generate 20 arthroplasty abstracts (AI-generated) based on full-text manuscripts, which were compared to originally published abstracts (human-written). Six blinded orthopaedic surgeons rated abstracts on overall quality, communication, and confidence in the authorship source. Authorship-confidence scores were compared to a test value representing complete inability to discern authorship. RESULTS: Modestly increased confidence in human authorship was observed for human-written abstracts compared with AI-generated abstracts (p = 0.028), though AI-generated abstract authorship-confidence scores were statistically consistent with inability to discern authorship (p = 0.999). Overall abstract quality was higher for human-written abstracts (p = 0.019). CONCLUSIONS: AI-generated abstracts' absolute authorship-confidence ratings demonstrated difficulty in discerning authorship but did not achieve the perceived quality of human-written abstracts. Caution is warranted in implementing LLMs into scientific writing.

Aspirin prophylaxis is not associated with increased risk of venous thromboembolism in arthroplasty for femoral neck fractures: a non-inferiority study.

PURPOSE: Venous thromboembolism (VTE) is a known complication of hip arthroplasty for femoral neck fractures (FNF) with various prophylactic anticoagulants utilized to decrease risk. The purpose of this study was to assess the efficacy and perioperative outcomes associated with aspirin for VTE prophylaxis following arthroplasty for FNF. METHODS: Medical records of 1,220 patients who underwent hip hemiarthroplasty (HHA) or total hip arthroplasty (THA) at an urban academic center from 2011 to 2022 were retrospectively reviewed. Patient characteristics and perioperative outcomes, including length of stay (LOS), VTE, 90-day hospital encounters, and discharge disposition, were collected. Outcomes for patients prescribed aspirin (n = 214) were compared to those prescribed non-aspirin VTE prophylaxis (n = 1006) using propensity score matching. RESULTS: Patients who received aspirin had higher rates of THA (36.0 vs 26.7%; p = 0.008). There were no significant risk-adjusted differences in the incidence of VTE (0.5 vs 0.5%, p = 1.000) and 90-day readmissions (10.4 vs 12.3%, p = 0.646) between patients prescribed aspirin and non-aspirin VTE prophylaxis, respectively. Patients prescribed non-aspirin agents had higher rates of non-home discharge (73.9 vs 58.5%; p < 0.001) and longer LOS (143.5 vs 124.9 h; p = 0.005). Sub-analysis of patients prescribed aspirin and non-aspirin prophylaxis based on comorbidity scores demonstrated no difference in VTE incidence for low (0.0 vs 1.6%, p = 1.000) and high scores (0.0 vs 0.0%, p = 1.000), respectively. CONCLUSION: Aspirin is not associated with increased incidence of VTE after HHA or THA for FNF. Aspirin prophylaxis should be considered in hip fracture patients to mitigate bleeding risk, particularly those with low to intermediate VTE risk. LEVEL OF EVIDENCE: Level III, Retrospective study.

Two-Year Outcomes of Novel Dual-Mobility Implant in Primary Total Hip Arthroplasty.

Introduction: Dual-mobility (DM) implants for total hip arthroplasty (THA) have gained popularity due to their potential to reduce hip instability and dislocation events that may lead to revision surgery. These implants consist of a femoral head articulated within a polyethylene liner, which articulates within an outer acetabular shell, creating a dual-bearing surface. Our study aimed to report our observations on the survivorship of a novel DM implant for primary total hip arthroplasty at two years. Methods: We conducted a retrospective, multicenter study to assess the clinical outcomes of patients undergoing a THA with a novel DM implant (OR3O acetabular system™, Smith & Nephew, Inc., Memphis, TN) from January 2020 to September 2021. Patient demographics, surgical information, and survivorship data were collected from medical records for patients with a minimum of two years of follow-up. Primary outcomes included overall implant survivorship at two years as well as aseptic survivorship, revision rates of the DM acetabular shell, and average time to revision. Patient-reported outcomes were collected in the form of HOOS JR. Results: A total of 250 hips in 245 patients had a minimum two-year follow-up. Primary osteoarthritis (80%) was the most common indication for index THA. The average aseptic survivorship of the DM acetabular components at two years for the cohort was 98.4% and survivorship of the acetabular implants overall was 97.6%. There were a total of four (1.6%) aseptic revisions of the DM acetabular component. Reasons for aseptic acetabular revision included one case of instability, one intraprosthetic dislocation, one periprosthetic acetabular fracture, and one malpositioned acetabular cup resulting in impingement. The mean time of follow-up was 893.9 days. Eighty-seven patients had preoperative and two-year HOOS JR available. HOOS JR improved by an average of 38.5 points. Conclusion: This novel DM acetabular implant demonstrates excellent survivorship at two years follow-up with low rates of instability and intraprosthetic dislocation and no episodes of metal-on-metal corrosion. Use of the DM implant demonstrated clinically relevant improvements in patient-reported outcomes at two years.

Aseptic Acetabular Revisions ≤90 Days, 91 Days to 2 Years, and >2 Years After Total Hip Arthroplasty: Comparing Etiologies, Complications, and Postoperative Outcomes.

BACKGROUND: Isolated acetabular component revision is an effective treatment for revision total hip arthroplasty patients who have well-fixed femoral implants. We aimed to evaluate the modes of acetabular failure following primary total hip arthroplasty and to identify factors associated with increased morbidities and postoperative outcomes. METHODS: We conducted a retrospective analysis and identified 318 isolated aseptic acetabular revisions. We separated patients by ≤90 days, 91 days to 2 years, and >2 years for acetabular revisions and compared demographics, reasons for revision, 90-day readmissions, rerevisions, and postrevision infections. Revisions ≤90 days, 91 days to 2 years, and >2 years accounted for 10.7, 19.2, and 70.1% of revisions, respectively. Revisions ≤90 days, 91 days to 2 years, and >2 years had their primary total hip arthroplasty at a mean age of 66, 63, and 55 years (P < .001), respectively. RESULTS: Revisions within 90 days were mainly indicated for dislocation/instability (58.8%) or periprosthetic fracture (23.5%) while revisions over 2 years were indicated for polyethylene wear/osteolysis (37.2%). Patients with revisions past 90 days were more likely to require rerevision compared to patients with revisions within 90 days (P < .001). There were no differences in readmissions (P = .28) or infection rates (P = .37). CONCLUSIONS: Acetabular revisions within 90 days were more commonly indicated for instability and periprosthetic fracture, while those over 2 years were indicated for polyethylene wear. Revisions past 90 days were more likely to require subsequent rerevisions without increased 90-day readmissions or infections. LEVEL III EVIDENCE: Retrospective cohort study.