A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes.

A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.

Validation of a qualitative real-time PCR assay for the detection of Candida auris in hospital inpatient screening.

Candida auris is a multidrug-resistant opportunistic fungal pathogen capable of causing serious infections and healthcare-associated outbreaks. Screening for colonization with C. auris has become routine and is recommended in many hospitals and healthcare facilities as an infection control and prevention strategy. Subsequently, and since there are currently no FDA-approved tests for this purpose, clinical microbiology laboratories have become responsible for developing protocols to detect C. auris using axial and inguinal screening swabs. In a College of American Pathologists-accredited large academic healthcare center setting, we implemented a laboratory-developed nucleic-acid amplification test for the detection of C. auris DNA. Our test validation evaluated the performance of the DiaSorin C. auris primer set used in a real-time qualitative PCR assay on the LIAISON MDX thermocycler with the Simplexa Universal Disc. The assay was highly sensitive and specific, with a limit of detection of 1-2 CFU/reaction, with no observed cross-reactivity with other Candida spp., bacterial skin commensal organisms or commonly encountered viruses. When run in parallel with a culture-based detection method, the PCR assay was 100% sensitive and specific. The assay was precise, with low variability between replicates within and between runs. Lastly, pre-analytical factors, including swab storage time, temperature, and transport media, were assessed and found to have no significant effect on the detection of C. auris at variable concentrations. Taken together, this study expands the available options for nucleic acid detection of C. auris and characterizes pre-analytical factors for implementation in both high- and low-volume laboratory settings. IMPORTANCE: This study overviews the validation and implementation of a molecular screening tool for the detection of Candida auris in a College of American Pathologist-accredited clinical laboratory. This molecular laboratory-developed test is both highly sensitive and specific and has significant health-system cost-savings associated with significantly reduced turn-around-time compared to traditional standard-of-care culture-based work up. This method and workflow is of interest to support clinical microbiology diagnostics and to help aid in hospital inpatient, and infection prevention control screening.

Impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on Bisoprolol peak concentration and clinical response in acute coronary syndrome patients.

AIMS: Acute coronary syndrome (ACS) represents a major cause of death. Bisoprolol is commonly used in the management of ACS. This study aims to investigate the impact of CYP2D6*2A, CYP2D6*4 and CYP3A5*3 genetic polymorphisms on pharmacokinetics and clinical response of bisoprolol in ACS patients. METHODS: This is an open-label cohort study that included 127 ACS patients and studied the effect of CYP3A5*3, CYP2D6*2A and CYP2D6*4 genotyping using real-time polymerase chain reaction on steady state bisoprolol plasma peak concentration analysed by high performance liquid chromatography-fluorescence detector. RESULTS: Regarding CYP3A5*3, the mean peak bisoprolol concentration for CC, CT and TT genotypes were 4.25 ± 1.20, 3.93 ± 1.10 and 1.79 ± 0.69 ng/mL, respectively (P < .001). Higher systolic (126 ± 5.47 mmHg), diastolic blood pressure (82 ± 2.73 mmHg) and heart rate (97.80 ± 3.03 beats/min) were also observed in CYP3A5*3 TT carriers (P < .05). In CYP2D6*2A, the peak concentration of bisoprolol was lower in CC carriers (3.54 ± 1 ng/mL) compared to GG (4.38 ± 1.25 ng/mL) and GC carriers (4.07 ± 1.29 ng/mL, P = .019). In CYP2D6*4, the mean bisoprolol peak concentration in CC carriers was 3.98 ± 1.31 ng/mL, which was lower than T allele carriers (4.5 ± 0.8, P = .02). No differences in heart rate, systolic, diastolic blood pressure or bisoprolol dose were observed among CYP2D6*2A or CYP2D6*4 variants. Smokers exhibited lower bisoprolol peak concentration (3.96 ± 1.2 ng/mL) compared to nonsmokers (4.55 ± 1.34 ng/mL, P = .037). CONCLUSION: There is an association between CYP3A5*3, CYP2D6*4, CYP2D6*2A variants and bisoprolol peak concentration, which may serve as a guide in the future in choosing the optimum dose of bisoprolol in ACS patients.

Production of Disinfective Coating Layer to Facial Masks Supplemented with Camellia sinensis Extract.

Although usefulness of masks for protection against respiratory pathogens, accumulation of pathogens on their surface represents a source of infection spread. Here we prepared a plant extract-based disinfecting layer to be used in coating masks thus inhibiting their capacity to transmit airborne pathogens. To reach this, a polypropylene membrane base was coated with a layer of polyvinyledine difluoride polymer containing 500 µg/ml of Camellia sinensis (Black tea) methanolic extract. Direct inhibitory effects of C. sinensis were initially demonstrated against Staphylococcus aureus (respiratory bacteria), influenza A virus (enveloped virus) and adenovirus 1 (non-enveloped virus) which were directly proportional to both extract concentration and incubation time with the pathogen. This was later confirmed by the capacity of the supplemented membrane with the plant extract to block infectivity of the above mentioned pathogens, recorded % inhibition values were 61, 72 and 50 for S. aureus, influenza and adenovirus, respectively. In addition to the disinfecting capacity of the membrane its hydrophobic nature and pore size (154 nm) prevented penetration of dust particles or water droplets carrying respiratory pathogens. In summary, introducing this layer could protect users from infection and decrease infection risk upon handling contaminated masks surfaces.

Validation of the arabic version of the EuroQol-5-dimension 5-level (EQ-5D-5 L) in patients with spinal degenerative diseases.

OBJECTIVE: This study aims to test the reliability and validity of the translated Arabic version of EQ-5D-5 L. METHODS: The study was conducted on 100 patients operated upon for degenerative spine diseases coming for follow up in the outpatient clinic of a Tertiary care hospital. Test-retest reliability was assessed by completing the self-administered tool in two follow up visits, one week apart, by 50 patients. Internal consistency was evaluated by Cronbach's alpha. Intra-class correlation coefficients and kappa statistics were performed to test for the agreement between the two ratings. Criterion validity was assessed by comparing the responses of 100 patients to the EQ-5D-5 L with scores of two validated questionnaires; the Arabic version of the Oswestry disability index and the Arabic version of short-form health survey-36. The construct validity was assessed using known-groups comparison to test for hypothesized differences concerning demographic and clinical variables. RESULTS: The Arabic version of EQ-5D-5 L questionnaire had a high reliability with high observed internal consistency (Cronbach's alpha = 0.816, CI: 0.719-0.886). It showed strong temporal stability, with ICCs of the EQ-5D-5 L score, index and EQ-visual analog scale (EQ-VAS) of 0.852, 0.801, and 0.839 respectively. Agreement by kappa was moderate; above 0.4, for all domains, except for the "Usual activities" domain. EQ-5D-5 L domains, VAS and index had moderate to strong significant correlations with SF-36 and ODI subscales and total scores in the correct direction indicating a good criterion validity of the instrument. CONCLUSION: The Arabic version of EQ-5D-5 L is reliable and valid for assessment of HRQoL of Arabic speaking patients.

Work-related musculoskeletal complaints and ergonomic risk factors among Egyptian anesthesiologists: a cross-sectional study.

BACKGROUND: Anesthesiologists are vulnerable to work-related musculoskeletal disorders (WMSDs) due to sustained repetitive movements and awkward postures. This study aimed to assess the prevalence of WMSDs among anesthesiologists and to evaluate its association with ergonomic risk factors. METHODS: A convenience sample of 380 Egyptian anesthesiologists were invited to participate in this cross-sectional study through an electronic questionnaire. Data were collected from May to August 2022 and involved questions about participants' demographic, health, and work-related characteristics; the ergonomic risks and perceived hazards; and the musculoskeletal complaints during the past 12 months and 7 days - using Nordic Musculoskeletal Questionnaire (NMQ). Descriptive, bivariate, and multivariate statistical analyses were used to estimate the prevalence of MSD and identify its determinants in the studied sample. RESULTS: A total of 215 anesthesiologists were included in this study, with a 56.8% response rate, 66% males with an average age of 38 (± 0.7) years. 21% were resident physicians, 47% were specialists, and 32% were consultants. The 12-month prevalence of MSD among anesthesiologists was 71.6% (95% CI: 65.6- 77.7%). Multivariate analysis showed that the main determinants of MSD among the studied sample were age of 45-years and older (OR: 3.22, 95% CI: 1.21-8.52, p = 0.018), regular physical exercise (OR: 0.25, 95% CI: 0.10-0.65, p = 0.005), insufficient rest time between procedures (OR: 2.25, 95% CI: 1.15-4.41, p = 0.018), and three or more awkward postures of the trunk (OR: 3.55, 95% CI: 1.43-8.82, p = 0.006). CONCLUSIONS: The study highlights a high prevalence of WMSDs among Egyptian anesthesiologists, linked to advancing age, lack of regular exercise, insufficient rest between procedures, and frequent awkward postures. Addressing these ergonomic risk factors through targeted workplace interventions is crucial for promoting the overall well-being of anesthesiologists and ensuring the provision of safe anesthesia services.

The effects of dexmedetomidine on intraoperative neurophysiologic monitoring modalities during corrective scoliosis surgery in pediatric patients: A systematic review.

BACKGROUND: During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha-2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients. OBJECTIVES: This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562). METHODS: We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case-control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded. RESULTS: We found substantial heterogeneity in the risk of bias (per Cochrane-preferred tools) of the included articles (n = 5); results are summarized without meta-analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power. CONCLUSION: Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients.

Identification of tetracycline combinations as EphB1 tyrosine kinase inhibitors for treatment of neuropathic pain.

Previous studies have demonstrated that the synaptic EphB1 receptor tyrosine kinase is a major mediator of neuropathic pain, suggesting that targeting the activity of this receptor might be a viable therapeutic option. Therefore, we set out to determine if any FDA-approved drugs can act as inhibitors of the EphB1 intracellular catalytic domain. An in silico screen was first used to identify a number of tetracycline antibiotics which demonstrated potential docking to the ATP-binding catalytic domain of EphB1. Kinase assays showed that demeclocycline, chlortetracycline, and minocycline inhibit EphB1 kinase activity at low micromolar concentrations. In addition, we cocrystallized chlortetracycline and EphB1 receptor, which confirmed its binding to the ATP-binding domain. Finally, in vivo administration of the three-tetracycline combination inhibited the phosphorylation of EphB1 in the brain, spinal cord, and dorsal root ganglion (DRG) and effectively blocked neuropathic pain in mice. These results indicate that demeclocycline, chlortetracycline, and minocycline can be repurposed for treatment of neuropathic pain and potentially for other indications that would benefit from inhibition of EphB1 receptor kinase activity.

Evaluating the understanding of the ethical and moral challenges of Big Data and AI among Jordanian medical students, physicians in training, and senior practitioners: a cross-sectional study.

AIMS: To examine the understanding of the ethical dilemmas associated with Big Data and artificial intelligence (AI) among Jordanian medical students, physicians in training, and senior practitioners. METHODS: We implemented a literature-validated questionnaire to examine the knowledge, attitudes, and practices of the target population during the period between April and August 2023. Themes of ethical debate included privacy breaches, consent, ownership, augmented biases, epistemology, and accountability. Participants' responses were showcased using descriptive statistics and compared between groups using t-test or ANOVA. RESULTS: We included 466 participants. The greater majority of respondents were interns and residents (50.2%), followed by medical students (38.0%). Most participants were affiliated with university institutions (62.4%). In terms of privacy, participants acknowledged that Big Data and AI were susceptible to privacy breaches (39.3%); however, 59.0% found such breaches justifiable under certain conditions. For ethical debacles involving informed consent, 41.6% and 44.6% were aware that obtaining informed consent posed an ethical limitation in Big Data and AI applications and denounced the concept of "broad consent", respectively. In terms of ownership, 49.6% acknowledged that data cannot be owned yet accepted that institutions could hold a quasi-control of such data (59.0%). Less than 50% of participants were aware of Big Data and AI's abilities to augment or create new biases in healthcare. Furthermore, participants agreed that researchers, institutions, and legislative bodies were responsible for ensuring the ethical implementation of Big Data and AI. Finally, while demonstrating limited experience with using such technology, participants generally had positive views of the role of Big Data and AI in complementing healthcare. CONCLUSION: Jordanian medical students, physicians in training and senior practitioners have limited awareness of the ethical risks associated with Big Data and AI. Institutions are responsible for raising awareness, especially with the upsurge of such technology.

Comparison of endoscope-assisted and microscope-assisted type I tympanoplasty; a systematic review and meta-analysis.

OBJECTIVES: To analyze and compare the available data about the outcomes of endoscopic and microscopic type I tympanoplasty. DATA SOURCES: PubMed, Cochrane library Ovid, Scopus, Google scholar, and ClinicalTrials. METHODS: We conducted a meta-analysis in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We included comparative studies describing type I tympanoplasty, and comparing surgical outcomes of the endoscope with the microscope in terms of efficacy and safety. RESULTS: Our systematic search yielded 22 studies meeting the inclusion criteria and eligible for analysis. The pooled graft uptake rates and audiological results of endoscopic and microscopic tympanoplasty demonstrated non-significant differences. In contrast, endoscopic type I tympanoplasty outperforms microscopic tympanoplasty regarding a highly significant decrease not only in pooled mean operative time but also in the pooled complications rate. CONCLUSIONS: Based on our meta-analysis, the surgical outcomes of endoscope-assisted and microscope-assisted type I tympanoplasty in terms of postoperative hearing outcomes and the graft uptake rate were comparable. On the contrary, operative time and complications rate proved to be significantly reduced with endoscopy compared to microscopy. Hence, the endoscope is as efficient as the microscope in type I tympanoplasty but less invasive, fewer in complications and shorter in operative time.

Detecting Psychological Interventions Using Bilateral Electromyographic Wearable Sensors.

This study investigated the impact of auditory stimuli on muscular activation patterns using wearable surface electromyography (EMG) sensors. Employing four key muscles (Sternocleidomastoid Muscle (SCM), Cervical Erector Muscle (CEM), Quadricep Muscles (QMs), and Tibialis Muscle (TM)) and time domain features, we differentiated the effects of four interventions: silence, music, positive reinforcement, and negative reinforcement. The results demonstrated distinct muscle responses to the interventions, with the SCM and CEM being the most sensitive to changes and the TM being the most active and stimulus dependent. Post hoc analyses revealed significant intervention-specific activations in the CEM and TM for specific time points and intervention pairs, suggesting dynamic modulation and time-dependent integration. Multi-feature analysis identified both statistical and Hjorth features as potent discriminators, reflecting diverse adaptations in muscle recruitment, activation intensity, control, and signal dynamics. These features hold promise as potential biomarkers for monitoring muscle function in various clinical and research applications. Finally, muscle-specific Random Forest classification achieved the highest accuracy and Area Under the ROC Curve for the TM, indicating its potential for differentiating interventions with high precision. This study paves the way for personalized neuroadaptive interventions in rehabilitation, sports science, ergonomics, and healthcare by exploiting the diverse and dynamic landscape of muscle responses to auditory stimuli.

Arthroscopic biceps tenodesis using press-fit bony plug: a case series study.

PURPOSE: To assess the feasibility, operative time, clinical outcomes, possible complications, and failure rates of all-through arthroscopic biceps tenodesis using press-fit bony plug technique. METHODS: This prospective case series study involved 30 skeletally mature patients with long head of biceps pathology (tendinitis after failure of conservative treatment, subluxation, dislocation, or tendon tears). All patients were followed up for 24 months at least. RESULTS: Twenty-nine patients regained full shoulder and elbow range of motion; one case suffered from reflex sympathetic dystrophy. There was a significant improvement in the constant, ASES, and VAS scores when comparing the pre-operative and post-operative values. The average biceps strength was 96% compared to the opposite healthy side. No cases were complicated by neuro-vascular deficits or failure of the tenodesis. CONCLUSION: Press-fit biceps tenodesis is safe and accessible with low economic demands. We recommend this technique to be used more often when addressing patients with long head of biceps pathologies. REGISTRATION DATA: Registration number: N-1562023. Registration date: June 2022 "Retrospectively registered".

Regulation of Cell Cycle Progression through RB Phosphorylation by Nilotinib and AT-9283 in Human Melanoma A375P Cells.

BCR-ABL tyrosine kinase inhibitors are commonly employed for the treatment of chronic myeloid leukemia, yet their impact on human malignant melanoma remains uncertain. In this study, we delved into the underlying mechanisms of specific BCR-ABL tyrosine kinase inhibitors (imatinib, nilotinib, ZM-306416, and AT-9283) in human melanoma A375P cells. We first evaluated the influence of these inhibitors on cell growth using cell proliferation and wound-healing assays. Subsequently, we scrutinized cell cycle regulation in drug-treated A375P cells using flow cytometry and Western blot assays. Notably, imatinib, nilotinib, ZM-306416, and AT-9283 significantly reduced cell proliferation and migration in A375P cells. In particular, nilotinib and AT-9283 impeded the G1/S transition of the cell cycle by down-regulating cell cycle-associated proteins, including cyclin E, cyclin A, and CDK2. Moreover, these inhibitors reduced RB phosphorylation, subsequently inhibiting E2F transcriptional activity. Consequently, the expression of the E2F target genes (CCNA2, CCNE1, POLA1, and TK-1) was markedly suppressed in nilotinib and AT9283-treated A375P cells. In summary, our findings suggest that BCR-ABL tyrosine kinase inhibitors may regulate the G1-to-S transition in human melanoma A375P cells by modulating the RB-E2F complex.

Effect of glazing and thermocycling on the fracture toughness and hardness of a New fully crystallized aluminosilicate CAD/CAM ceramic material.

BACKGROUND: The mechanical properties of fully crystallized lithium aluminosilicate ceramics may be influenced by intraoral temperature variations and postmilling surface treatment. The purpose of this study is to explore the interplay among glazing, thermocycling, and the mechanical characteristics (namely, fracture toughness and hardness) of fully crystallized lithium aluminosilicate ceramics. METHODS: Bending bars (n = 40) cut from LisiCAD blocks (GC, Japan) were randomly assigned to glazed or unglazed groups (n = 20) and subjected to the single edge v-notch beam method to create notches. A glazing firing cycle was applied to the glazed group, while the unglazed group was not subjected to glazing. Half of the specimens (n = 10) from both groups underwent thermocycling before fracture toughness testing. The fracture toughness (KIC) was evaluated at 23 ± 1 °C using a universal testing machine configured for three-point bending, and the crack length was measured via light microscopy. Seven specimens per group were selected for the hardness test. Hardness was assessed using a Vickers microhardness tester with a 1 kg load for 20 s, and each specimen underwent five indentations following ISO 14705:2016. The Shapiro-Wilk and Kolmogorov-Smirnov tests were used to evaluate the normality of the data and a two-way ANOVA was utilized for statistical analysis. The significance level was set at (α = 0.05). RESULTS: Regardless of the thermocycling conditions, the glazed specimens exhibited significantly greater fracture toughness than did their unglazed counterparts (P < 0.001). Thermocycling had no significant impact on the fracture toughness of either the glazed or unglazed specimens. Furthermore, statistical analysis revealed no significant effects on hardness with thermocycling in either group, and glazing alone did not substantially affect hardness. CONCLUSIONS: The impact of glazing on the fracture toughness of LiSiCAD restorations is noteworthy, but it has no significant influence on their hardness. Furthermore, within the parameters of this study, thermocycling was found to exert negligible effects on both fracture toughness and hardness.

Could Osteopontin be a useful biomarker in the diagnosis and severity assessment of osteoarthritis? A systematic review and meta-analysis of recent evidence.

PURPOSE: Osteoarthritis (OA) patients demonstrated higher Osteopontin (OPN) plasma, serum, and synovial fluid concentrations than healthy individuals. In the present study, we aimed to investigate whether OPN could be used as a diagnostic or prognostic marker for OA symptom/disease severity. METHODS: Using Web of Science, PubMed, Scopus, and Embase, we conducted a systematic review and meta-analysis of studies that measured OPN levels in OA patients' plasma, serum, or synovial fluid. After setting the eligibility criteria, data extraction, and quality assessment of the identified studies, we performed statistical analysis using Revman 5.4 and Open Meta analyst. RESULTS: OPN has been found to be associated with advanced knee joint damage in OA patients. In addition, higher expression of OPN is thought to be associated with disease progression. Nevertheless, further studies should examine the role of other markers of chronic bone damage, such as leptin and sclerostin. This systematic review and meta-analysis included 14 studies with a total of 776 cases and 530 controls. OPN was significantly elevated in osteoarthritis patients' plasma, serum, and synovial fluid samples, with significant heterogeneity between studies. CONCLUSION: We recommend that OPN plasma and synovial fluid levels be measured as a diagnostic and prognostic marker to determine the severity of OA symptoms.

Efficient Ternary Mn-Based Spinel Oxide with Multiple Active Sites for Oxygen Evolution Reaction Discovered via High-Throughput Screening Methods.

The discovery of more efficient and stable catalysts for oxygen evolution reaction (OER) is vital in improving the efficiency of renewable energy generation devices. Given the large numbers of possible binary and ternary metal oxide OER catalysts, high-throughput methods are necessary to accelerate the rate of discovery. Herein, Mn-based spinel oxide, Fe10 Co40 Mn50 O, is identified for the first time using high-throughput methods demonstrating remarkable catalytic activity (overpotential of 310 mV on fluorine-doped tin oxide (FTO) substrate and 237 mV on Ni foam at 10 mA cm-2 ). Using a combination of soft X-ray absorption spectroscopy and electrochemical measurements, the high catalytic activity is attributed to 1) the formation of multiple active sites in different geometric sites, tetrahedral and octahedral sites; and 2) the formation of active oxyhydroxide phase due to the strong interaction of Co2+ and Fe3+ . Structural and surface characterizations after OER show preservation of Fe10 Co40 Mn50 O surface structure highlighting its durability against irreversible redox damage on the catalytic surface. This work demonstrates the use of a high-throughput approach for the rapid identification of a new catalyst, provides a deeper understanding of catalyst design, and addresses the urgent need for a better and stable catalyst to target greener fuel.

Exosomal miRNA-mediated intercellular communications and immunomodulatory effects in tumor microenvironments.

Extracellular communication, in other words, crosstalk between cells, has a pivotal role in the survival of an organism. This communication occurs by different methods, one of which is extracellular vesicles. Exosomes, which are small lipid extracellular vesicles, have recently been discovered to have a role in signal transduction between cells inside the body. These vesicles contain important bioactive molecules including lipids, proteins, DNA, mRNA, and noncoding RNAs such as microRNAs (miRNAs). Exosomes are secreted by all cells including immune cells (macrophages, lymphocytes, granulocytes, dendritic cells, mast cells) and tumor cells. The tumor microenvironment (TME) represents a complex network that supports the growth of tumor cells. This microenvironment encompasses tumor cells themselves, the extracellular matrix, fibroblasts, endothelial cells, blood vessels, immune cells, and non-cellular components such as exosomes and cytokines. This review aims to provide insights into the latest discoveries concerning how the immune system communicates internally and with other cell types, with a specific focus on research involving exosomal miRNAs in macrophages, dendritic cells, B lymphocytes, and T lymphocytes. Additionally, we will explore the role of exosomal miRNA in the TME and the immunomodulatory effect.

The modulation and mechanism of probiotic-derived polysaccharide capsules on the immune response in allergic diseases.

Allergic diseases, derived from the dysregulation of immune tolerance mechanisms, have been rising in the last two decades. Recently, increasing evidence has shown that probiotic-derived polysaccharide capsules exhibit a protective effect against allergic diseases, involving regulation of Th1/Th2 balance, induction of differentiation of T regulatory cells and activation of dendritic cells (DCs). DCs have a central role in controlling the immune response through their interaction with gut microbiota via their pattern recognition receptors, including Toll-like receptors and C-type-lectin receptors. This review discusses the effects and critical mechanism of probiotic-derived polysaccharide capsules in regulating the immune system to alleviate allergic diseases. We first describe the development of immune response in allergic diseases and recent relevant findings. Particular emphasis is placed on the effects of probiotic-derived polysaccharide capsules on allergic immune response. Then, we discuss the underlying mechanism of the impact of probiotic-derived polysaccharide capsules on DCs-mediated immune tolerance induction.

Hydroxy levamisole and its phase II conjugates as potential indicators of levamisole doping in thoroughbred horses.

RATIONALE: According to previous research, aminorex is the major metabolite of levamisole; however, in the screening of levamisole-positive racehorse urine and plasma samples, aminorex could only be detected in trace amounts or not at all. In forensic laboratories, hydroxy levamisole and its phase II conjugates make it easier to confirm levamisole misuse and to differentiate between the abuse of levamisole and aminorex. This study aimed to identify the major levamisole metabolites that can be detected along with the parent drug. METHODS: The study describes levamisole and its metabolites in thoroughbred horses following oral administration and in vitro with equine liver microsomes. The plausible structures of the detected metabolites were postulated using liquid chromatography combined with high-resolution mass spectrometry. RESULTS: Under the experimental conditions 26 metabolites (17 phase I, 2 phase II, and 7 conjugates of phase I metabolites) were detected (M1-M26). The major phase I metabolites identified were formed by hydroxylation. In phase II, the glucuronic acid conjugates of levamisole and hydroxy levamisole were detected as the major metabolites. In plasma, the parent drug and major metabolites are detectable for up to eight days, while in urine, they are detectable for up to twenty days. Levamisole levels rapidly increased at 45 min following administration, then declined gradually until detectable levels were reached approximately 8 days after administration, according to a pharmacokinetics study. CONCLUSIONS: A prolonged elimination profile and relatively high concentration of hydroxy metabolites suggest that the detection of hydroxy metabolites is imperative for investigating levamisole doping in horses.

Oxytocin versus a combination of tranexamic acid and ethamsylate in reducing intraoperative bleeding during abdominal myomectomy: a randomized clinical trial.

OBJECTIVE: Myomectomy is the preferred surgical approach to manage uterine fibroids. However, uterine fibroids are highly vascular tumors and, consequently, extremely susceptible to problems from myomectomy-related hemorrhage. Hence, we aim to compare oxytocin efficacy and safety profile versus tranexamic acid (TA) with ethamsylate for reducing bleeding during myomectomy. METHODS: This randomized, double-blinded multicenter study was performed between 20th August 2020 and 20th October 2020 at El-Galaa Teaching Hospital, El Hussein University Hospital, Al-Azhar University Hospitals of Assiut, and Al-Azhar University Hospitals of Damietta. One hundred and eighty patients were enrolled and divided into three groups: group (1) received an injection of 30 IU of oxytocin in 500 ml of normal saline; group (2) received injections of 1 g of TA, 250 mg of Ethamsylate, and 110 ml of normal saline IV; and group (3) received an injection of 110 ml of normal saline IV just before surgical incision. RESULTS: In 180 premenopausal women, oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy (666.25 ± 183.03, 630.72 ± 145.83, and 646.67 ± 168.92, respectively (P = 0.506)). Non-significant trends were observed for a reduction in operation time (P = 0.760), intra/postoperative blood transfusion (P = 0.624), hospital stay (P = 0.986), postoperative fever (P = 0.659), and wound infection (P = 1). CONCLUSION: Oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy which opens a new question about the role of the use of the hemostatic drug during myomectomy especially in centers with limited resources and had higher rates. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202008739887429 and was approved on 24/08/2020.