Impact of preoperative intra-aortic balloon pump on outcomes in coronary artery bypass grafting for unprotected left-main coronary artery disease.

Background: Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes. Methods: This multicenter retrospective cohort study that included consecutive 914 patients who underwent CABG for unprotected LMCA disease from January 2015 to December 2019 in 14 tertiary referral centers. Patients were grouped according to the preoperative IABP insertion into patients with IABP (n=101) and without IABP (n=813). Propensity score matching adjusting for preoperative variables, with 1:1 match and a caliber of 0.03 identified 80 matched pairs. The primary outcomes used in propensity score matching were cardiac mortality and major adverse cardiac and cerebrovascular events (MACCE). Results: IABP was commonly inserted in patients with previous myocardial infarction (MI), chronic kidney disease, peripheral arterial disease, and congestive heart failure. IABP patients had higher EuroSCORE [ES >8%: 95 (11.86%) vs. 40 (39.60%), P<0.001] and SYNTAX {29 [interquartile range (IQR) 25-35] vs. 33 (IQR 26-36); P=0.02} scores. Preoperative cardiogenic shock and arrhythmia were more prevalent in patients with IABP, while acute coronary syndrome was more prevalent in patients without IABP. After matching, there was no difference in vasoactive inotropic score between groups [3.5 (IQR 1-7.5) vs. 6 (IQR 1-13.5), P=0.06], and lactate levels were nonsignificantly higher in patients with IABP [2.4 (IQR 1.4-4.5) vs. 3.1 (IQR 1.05-7.75), P=0.05]. There were no differences between groups in acute kidney injury [20 (25%) vs. 26 (32.5%), P=0.34], cerebrovascular accidents [3 (3.75%) vs. 4 (5%), P>0.99], heart failure [5 (6.25%) vs. 7 (8.75%), P=0.75], MI [7 (8.75%) vs. 8 (10%), P>0.99], major adverse cardiac and cerebrovascular events [10 (12.5%) vs. 17 (21.25%), P=0.21], and cardiac mortality [6 (7.50%) vs. 14 (17.50%), P=0.09]. Patients who received IABP had longer ventilation times [8.5 (IQR 6-23) vs. 15.5 (IQR 5-50.5) h, P=0.03] and intensive care unit (ICU) stays [3 (IQR 2-5) vs. 4 (IQR 2-7.5) days, P=0.01]. Conclusions: Preoperative IABP in patients with LMCA might not be associated with reduced cardiac mortality or hospital complications. IABP could increase the duration of mechanical ventilation and ICU stay, and its use should be individualized for each patient.

Advancing clinical understanding of surface electromyography biofeedback: bridging research, teaching, and commercial applications.

INTRODUCTION: Expanding the use of surface electromyography-biofeedback (EMG-BF) devices in different therapeutic settings highlights the gradually evolving role of visualizing muscle activity in the rehabilitation process. This review evaluates their concepts, uses, and trends, combining evidence-based research. AREAS COVERED: This review dissects the anatomy of EMG-BF systems, emphasizing their transformative integration with machine-learning (ML) and deep-learning (DL) paradigms. Advances such as the application of sophisticated DL architectures for high-density EMG data interpretation, optimization techniques for heightened DL model performance, and the fusion of EMG with electroencephalogram (EEG) signals have been spotlighted for enhancing biomechanical analyses in rehabilitation. The literature survey also categorizes EMG-BF devices based on functionality and clinical usage, supported by insights from commercial sectors. EXPERT OPINION: The current landscape of EMG-BF is rapidly evolving, chiefly propelled by innovations in artificial intelligence (AI). The incorporation of ML and DL into EMG-BF systems augments their accuracy, reliability, and scope, marking a leap in patient care. Despite challenges in model interpretability and signal noise, ongoing research promises to address these complexities, refining biofeedback modalities. The integration of AI not only predicts patient-specific recovery timelines but also tailors therapeutic interventions, heralding a new era of personalized medicine in rehabilitation and emotional detection.

Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke in Cancer Patients: A Single-Center Experience and Meta-Analysis.

Background and Objectives: The published data about mechanical thrombectomy (MT) in cancer patients is sparse. We present our institutional experience in this clinical scenario, and a meta-analysis. Methods: The baseline data, procedural data, clinical and radiological outcomes of MT were analyzed and compared among three groups of stroke patients: controls, patients with active malignancy (AM), and patients with history of malignancy (HOM). A meta-analysis of 12 studies was conducted to address the differences between controls and AM patients regarding selected outcomes. Results: The 3 groups (controls, AM, HOM) showed significant differences regarding previous history of stroke or TIA (7.8% vs 10.5% vs 38.5%, p = 0.006), alcohol consumption (0.9% vs 10.5% vs 0.0%, p = 0.04), thrombophilia (1.7% vs 15.8% vs 7.7%, p = 0.009), deep venous thrombosis (0.4 vs 26.3% vs 7.7%, p = 0.005). The AM group had significantly higher rates of sICH (3.5% [controls] vs 21.1% [AM] vs 0.0% [HOM], p = 0.007), and mortality at 3 months (27.5% [controls] vs 61.5% [AM] vs 40.0% [HOM] vs, p = 0.032). The control and HOM groups had significantly better functional independence at 3 months (52.1% [controls] vs 15.4% [AM] vs 60.0% [HOM], p = 0.032).In the meta-analysis, the AM arm showed significantly higher mortality during hospitalization (n = 6, OR 95% CI = 3.03 [1.62, 5.64]), and at 3 months (n = 10, OR 95% CI = 4.33 [2.80, 6.68]), and significantly lower rates of 3 months functional independence (mRS = 0-2) (n = 10, OR 95% CI = 0.47 [0.32, 0.70]). No significant difference was found in sICH rates (n = 6, pooled OR 95% CI = 2.03 [0.83, 4.95]). Discussion: Endovascular MT is technically successful and reasonably safe in treating AIS from LVO in active malignancy patients. However, the causes and implications of sICH require further investigation. Despite technical success, these patients experience poor clinical outcomes, and the long-term benefits of MT remain uncertain.

Two transcriptionally and functionally distinct waves of neutrophils during mouse acute liver injury.

BACKGROUND: Neutrophils are key mediators of inflammation during acute liver injury (ALI). Emerging evidence suggests that they also contribute to injury resolution and tissue repair. However, the different neutrophil subsets involved in these processes and their kinetics are undefined. Herein, we characterized neutrophil kinetics and heterogeneity during ALI. METHODS: We used the carbon tetrachloride model of ALI and employed flow cytometry, tissue imaging, and quantitative RT-PCR to characterize intrahepatic neutrophils during the necroinflammatory early and late repair phases of the wound healing response to ALI. We FACS sorted intrahepatic neutrophils at key time points and examined their transcriptional profiles using RNA-sequencing. Finally, we evaluated neutrophil protein translation, mitochondrial function and metabolism, reactive oxygen species content, and neutrophil extracellular traps generation. RESULTS: We detected 2 temporarily distinct waves of neutrophils during (1) necroinflammation (at 24 hours after injury) and (2) late repair (at 72 hours). Early neutrophils were proinflammatory, characterized by: (1) upregulation of inflammatory cytokines, (2) activation of the noncanonical NF-κB pathway, (3) reduction of protein translation, (4) decreased oxidative phosphorylation, and (5) higher propensity to generate reactive oxygen species and neutrophil extracellular traps. In contrast, late neutrophils were prorepair and enriched in genes and pathways associated with tissue repair and angiogenesis. Finally, early proinflammatory neutrophils were characterized by the expression of a short isoform of C-X-C chemokine receptor 5, while the late prorepair neutrophils were characterized by the expression of C-X-C chemokine receptor 4. CONCLUSIONS: This study underscores the phenotypic and functional heterogeneity of neutrophils and their dual role in inflammation and tissue repair during ALI.

Publisher Correction: Examining the prevalence of obesity in school children through an on-site obesity outpatient clinics survey based on student's lifestyles.

Eur Rev Med Pharmacol Sci 2023; 27 (6): 2494-2503-DOI: 10.26355/eurrev_202303_31783-PMID: 37013767-published online on March 30, 2023. This erratum corrects the references 8, 9, and 19, which have been mistakenly inserted in the text during the authors' drafting with the following: -       Reference 8 has been substituted with the following: 8. Sanders RH, Han A, Baker JS, Cobley S. Childhood obesity and its physical and psychological co-morbidities: a systematic review of Australian children and adolescents. Eur J Pediatr 2015; 174: 715-746. -       Reference 9 has been substituted with the following: 9. Nittari G, Scuri S, Petrelli F, Pirillo I, di Luca NM, Grappasonni I. Fighting obesity in children from European World Health Organization member states. Epidemiological data, medical-social aspects, and prevention programs. Clin Ter 2019; 170: e223-e230. -       Reference 19 has been substituted with the following: 19. Al-Hazzaa HM, Alrasheedi AA, Alsulaimani RA, Jabri L, Alhowikan AM, Alhussain MH, Bawaked RA, Alqahtani SA. Prevalence of overweight and obesity among saudi children: A comparison of two widely used international standards and the national growth references. Front Endocrinol (Lausanne) 2022; 13: 954755. Erratum in: Front Endocrinol (Lausanne) 2023; 14: 1305460. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31783.

Antimicrobial Resistance Profiles of Pseudomonas aeruginosa in the Arabian Gulf Region Over a 12-Year Period (2010-2021).

OBJECTIVES: To evaluate literature from a 12-year period (2010-2021) on the antimicrobial resistance profile of Pseudomonas aeruginosa from the Arabian Gulf countries (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). METHODS: An electronic literature search was conducted for articles on antimicrobial resistance in P. aeruginosa and associated phenotypes, covering the period of 1st January 2010 to 1st December 2021. RESULTS: Antimicrobial resistance in the Arabian Gulf was highest to meropenem (10.3-45.7%) and lowest to colistin (0.0-0.8%), among the agents tested. Annual data showed that ceftazidime resistance (Kuwait), piperacillin-tazobactam non-susceptibility (Qatar), and aztreonam, imipenem, and meropenem resistance (Saudi Arabia) increased by 12-17%. Multiple mechanisms of carbapenem resistance were identified and multiple clones were detected, including high-risk clones such as ST235. The most common carbapenemases detected were the VIM-type metallo-ß-lactamases. CONCLUSIONS: Among P. aeruginosa in the Arabian Gulf countries, resistance to meropenem was higher than to the other agents tested, and meropenem resistance increased in Saudi Arabia during the study period. Resistance to colistin, a classic antibiotic used to treat Pseudomonas spp. infections, remained low. The VIM-type ß-lactamase genes were dominant. We recommend local and regional antimicrobial resistance surveillance programs to detect the emergence of resistance genes and to monitor antimicrobial resistance trends in P. aeruginosa.

Lipoprotein(a) and Long-term In-stent Restenosis after Percutaneous Coronary Intervention.

AIM: Lipoprotein(a) [Lp(a)] has demonstrated its association with atherosclerosis and myocardial infarction. However, its role in the development of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is not clearly established. The aim of this study is to investigate the association between Lp(a) and ISR. METHODS: A retrospective study of adult patients who underwent successful PCI between January 2006 and December 2017 at the three Mayo Clinic sites and had a preprocedural Lp(a) measurement was conducted. Patients were divided into two groups according to the serum Lp(a) concentration (high Lp(a) ≥50 mg/dl and low Lp(a) <50 mg/dl). Univariable and multivariable analyses were performed to compare risk of ISR between patients with high Lp(a) versus those with low Lp(a). RESULTS: A total of 1209 patients were included, with mean age 65.9 ±11.7 years and 71.8% were male. Median follow-up after baseline PCI was 8.8 (IQR 7.4) years. Restenosis was observed in 162 (13.4%) patients. Median serum levels of Lp(a) were significantly higher in patients affected by ISR versus non-affected cases: 27 (IQR 73.8) vs. 20 (IQR 57.5) mg/dL, p=0.008. The rate of ISR was significantly higher among patients with high Lp(a) versus patients with low Lp(a) values (17.0% vs 11.6%, p=0.010). High Lp(a) values were independently associated with ISR events (HR 1.67, 95%CI 1.18 to 2.37, p=0.004), and this association was more prominent after the first year following the PCI. CONCLUSION: Lipoprotein(a) is an independent predictor for long-term in-stent restenosis and should be considered in the evaluation of patients undergoing PCI.

The role of Lp(a) in the development of in-stent restenosis is not clearly established. In this study including 1209 patients who underwent successful percutaneous coronary intervention and had a preprocedural Lp(a) measurement between 2006 and 2017, the rates of restenosis were significantly higher among patients with high Lp(a) versus patients with low Lp(a) values and high Lp(a) concentrations were independently associated with restenosis events. Lp(a) should be considered as a risk factor for long term in-stent restenosis in the evaluation of patients undergoing percutaneous coronary intervention and assessed as a potential therapeutic target for reducing residual cardiovascular risk in this population.

New sulfonamide-based glycosides incorporated 1,2,3-triazole as cytotoxic agents through VEGFR-2 and carbonic anhydrase inhibitory activity.

New sulfonamide-triazole-glycoside hybrids derivatives were designed, synthesised, and investigated for anticancer efficacy. The target glycosides' cytotoxic activity was studied with a panel of human cancer cell lines. Sulfonamide-based derivatives, 4, 7 and 9 exhibited promising activity against HepG-2 and MCF-7 (IC50 = 8.39-16.90 µM against HepG-2 and 19.57-21.15 µM against MCF-7) comparing with doxorubicin (IC50 = 13.76 ± 0.45, 17.44 ± 0.46 µM against HepG-2 and MCF-7, rescpectively). To detect the probable action mechanism, the inhibitory activity of these targets was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Compoumds 7 and 9 gave favorable potency (IC50 = 1.33, 0.38 µM against VEGFR-2, 66, 40 nM against hCA IX and 7.6, 3.2 nM against hCA XII, respectively), comparing with sorafenib and SLC-0111 (IC50 = 0.43 µM, 53 and 4.8 nM, respectively). Moreover, the docking simulation was assessed to supply better rationalization and gain insight into the binding affinity between the promising derivatives and their targeted enzymes that was used for further modification in the anticancer field.

Exploring novel microbial metabolites and drugs for inhibiting Clostridioides difficile.

Clostridioides difficile is an enteric pathogen that can cause a range of illnesses from mild diarrhea to pseudomembranous colitis and even death. This pathogen often takes advantage of microbial dysbiosis provoked by antibiotic use. With the increasing incidence and severity of infections, coupled with high recurrence rates, there is an urgent need to identify innovative therapies that can preserve the healthy state of the gut microbiota. In this study, we screened a microbial metabolite library against C. difficile. From a collection of 527 metabolites, we identified 18 compounds with no previously identified antimicrobial activity and metabolites that exhibited potent activity against C. difficile growth. Of these 18 hits, five drugs and three metabolites displayed the most potent anti-C. difficile activity and were subsequently assessed against 20 clinical isolates of C. difficile. These potent agents included ecteinascidin 770 (minimum inhibitory concentration against 50% of isolates [MIC50] ≤0.06 µg/mL); 8-hydroxyquinoline derivatives, such as broxyquinoline and choloroquinaldol (MIC50 = 0.125 µg/mL); ionomycin calcium salt, carbadox, and robenidine hydrochloride (MIC50 = 1 µg/mL); and dronedarone and milbemycin oxime (MIC50 = 4 µg/mL). Unlike vancomycin and fidaxomicin, which are the standard-of-care anti-C. difficile antibiotics, most of these metabolites showed robust bactericidal activity within 2-8 h with minimal impact on the growth of representative members of the normal gut microbiota. These results suggest that the drugs and microbial metabolite scaffolds may offer alternative avenues to address unmet needs in C. difficile disease prevention and treatment. IMPORTANCE: The most frequent infection associated with hospital settings is Clostridioides difficile, which can cause fatal diarrhea and severe colitis, toxic megacolon, sepsis, and leaky gut. Those who have taken antibiotics for other illnesses that affect the gut's healthy microbiota are more susceptible to C. difficile infection (CDI). Recently, some reports showed higher recurrence rates and resistance to anti-C. difficile, which may compromise the efficacy of CDI treatment. Our study is significant because it is anticipated to discover novel microbial metabolites and drugs with microbial origins that are safe for the intestinal flora, effective against C. difficile, and reduce the risk of recurrence associated with CDI.

Design, synthesis and anti-inflammatory assessment of certain substituted 1,2,4-triazoles bearing tetrahydroisoquinoline scaffold as COX 1/2-inhibitors.

Aiming to discover effective and safe non-steroidal anti-inflammatory agents, a new set of 1,2,4-triazole tetrahydroisoquinoline hybrids 9a-g, 11a-g and 12a-g was synthesized and evaluated as inhibitors of COX-1 and COX-2. In order to overcome the adverse effects of highly selective COX-2 and non-selective COX-2 inhibitors, the compounds of this study were designed with the goal of obtaining moderately selective COX-2 inhibitors. In this study compounds 9e, 9g and 11f are the most effective derivatives against COX-2 with IC50 values 0.87, 1.27 and 0.58 µM, respectively which are better than or comparable to the standard drug celecoxib (IC50 = 0.82 µM) but with lower selectivity indices as required by our goal design. The results of the in vivo anti-inflammatory inhibition test revealed that compounds 9e, 9g and 11f displayed a higher significant anti-inflammatory activity than celecoxib at all-time intervals. In addition, these compounds significantly decreased the production of inflammatory mediators PGE-2, TNF-ɑ and IL-6. Compounds 9e, 9g and 11f had a safe gastric profile compared to indomethacin, also compound 11f (ulcerogenic index = 1.33) was less ulcerous than the safe celecoxib (ulcerogenic index = 3). Moreover, histopathological investigations revealed a normal architecture of both paw skin and gastric mucosa after oral treatment of rats with compound 11f. Furthermore, molecular docking studies were performed on COX-1 and COX-2 to study the binding pattern of compounds 9e, 9g and 11f on both isoenzymes.

Assessment of Saudi Public Perceptions and Opinions towards Artificial Intelligence in Health Care.

Background and Objectives: The healthcare system in Saudi Arabia is growing rapidly with the utilization of advanced technologies. Therefore, this study aimed to assess the Saudi public perceptions and opinions towards artificial intelligence (AI) in health care. Materials and Methods: This cross-sectional web-based questionnaire study was conducted between January and April 2024. Data were analyzed from 830 participants. The perceptions of the public towards AI were assessed using 21-item questionnaires. Results: Among the respondents, 69.4% were males and 46% of them were aged above 41 years old. A total of 84.1% of the participants knew about AI, while 61.1% of them believed that AI is a tool that helps healthcare professionals, and 12.5% of them thought that AI may replace the physician, pharmacist, or nurse in the healthcare system. With regard to opinion on the widespread use of AI, 45.8% of the study population believed that healthcare professionals will be improved with the widespread use of artificial intelligence. The mean perception score of AI among males was 38.4 (SD = 6.1) and this was found to be higher than for females at 37.7 (SD = 5.3); however, no significant difference was observed (p = 0.072). Similarly, the mean perception score was higher among young adults aged between 20 and 25 years at 38.9 (SD = 6.1) compared to other age groups, but indicating no significant association between them (p = 0.198). Conclusions: The results showed that the Saudi public had a favorable opinion and perceptions of AI in health care. This suggests that health management recommendations should be made regarding how to successfully integrate and use medical AI while maintaining patient safety.

Deciphering the functional and structural complexity of the Solar Lake flat mat microbial benthic communities.

The Solar Lake in Taba, Egypt, encompasses one of the few modern-day microbial mats' systems metabolically analogous to Precambrian stromatolites. Solar Lake benthic communities and their adaptation to the Lake's unique limnological cycle have not been described for over two decades. In this study, we revisit the flat mat and describe the summer's shallow water versus exposed microbial community; the latter occurs in response to the seasonal partial receding of water. We employed metagenomic NovaSeq-6000 shotgun sequencing and 16S rRNA, mcrA, and dsrB quantitative PCR. A total of 292 medium-to-high-quality metagenome-assembled genomes (MAGs) were reconstructed. At the structural level, Candidatus Aenigmatarchaeota, Micrarchaeota, and Omnitrophota MAGs were exclusively detected in the shallow-water mats, whereas Halobacteria and Myxococcota MAGs were specific to the exposed microbial mat. Functionally, genes involved in reactive oxygen species (ROS) detoxification and osmotic pressure were more abundant in the exposed than in the shallow-water microbial mats, whereas genes involved in sulfate reduction/oxidation and nitrogen fixation were ubiquitously detected. Genes involved in the utilization of methylated amines for methane production were predominant when compared with genes associated with alternative methanogenesis pathways. Solar Lake methanogen MAGs belonged to Methanosarcinia, Bathyarchaeia, Candidatus Methanofastidiosales, and Archaeoglobales. The latter had the genetic capacity for anaerobic methane oxidation. Moreover, Coleofasciculus chthonoplastes, previously reported to dominate the winter shallow-water flat mat, had a substantial presence in the summer. These findings reveal the taxonomic and biochemical microbial zonation of the exposed and shallow-water Solar Lake flat mat benthic community and their capacity to ecologically adapt to the summer water recession. IMPORTANCE: Fifty-five years ago, the extremophilic "Solar Lake" was discovered on the Red Sea shores, garnering microbiologists' interest worldwide from the 1970s to 1990s. Nevertheless, research on the lake paused at the turn of the millennium. In our study, we revisited the Solar Lake benthic community using a genome-centric approach and described the distinct microbial communities in the exposed versus shallow-water mat unveiling microbial zonation in the benthic communities surrounding the Solar Lake. Our findings highlighted the unique structural and functional adaptations employed by these microbial mat communities. Moreover, we report new methanogens and phototrophs, including an intriguing methanogen from the Archaeoglobales family. We describe how the Solar Lake's flat mat microbial community adapts to stressors like oxygen intrusion and drought due to summer water level changes, which provides insights into the genomic strategies of microbial communities to cope with altered and extreme environmental conditions.

Emergence of the novel infectious bursal disease virus variant in vaccinated poultry flocks in Egypt.

RESEARCH HIGHLIGHTS: New variant IBDV which emerged in Egypt clustered with Chinese nVarIBDV.nVarIBDV spread subclinically across a wide geographic area.Mutation at 321 represents capsid's most exposed part, a defining feature.Antigenically modified vvIBDV still circulating in Egypt with typical lesions.

Triggering Breast Cancer Apoptosis via Cyclin-Dependent Kinase Inhibition and DNA Damage by Novel Pyrimidinone and 1,2,4-Triazolo[4,3-a]pyrimidinone Derivatives.

Combinations of apoptotic inducers are common clinical practice in breast cancer. However, their efficacy is limited by the heterogeneous pharmacokinetic profiles. An advantageous alternative is merging their molecular entities in hybrid multitargeted scaffolds exhibiting synergistic activities and uniform distribution. Herein, we report apoptotic inducers simultaneously targeting DNA and CDK-2 (cyclin-dependent kinase-2) inspired by studies revealing that CDK-2 inhibition sensitizes breast cancer to DNA-damaging agents. Accordingly, rationally substituted pyrimidines and triazolopyrimidines were synthesized and assayed by MTT against MCF-7, MDA-MB231, and Wi-38 cells compared to doxorubicin. The N-(4-amino-2-((2-hydrazinyl-2-oxoethyl)thio)-6-oxo-1,6-dihydropyrimidin-5-yl)acetamide 5 and its p-nitrophenylhydrazone 8 were the study hits against MCF-7 (IC50 = 0.050 and 0.146 µM) and MDA-MB231 (IC50 = 0.826 and 0.583 µM), induced DNA damage at 10.64 and 30.03 nM, and inhibited CDK-2 (IC50 = 0.172 and 0.189 µM). 5 induced MCF-7 apoptosis by 46.75% and disrupted cell cycle during S phase. Docking and MD simulations postulated their stable key interactions.

Shearing brittle intermetallics enhances cryogenic strength and ductility of steels.

Precipitates are crucial for crafting mechanically strong metallic materials. In this work, we report the dislocation cutting of B2 (ordered body-centered cubic) nanoprecipitates, typically considered nonshearable intermetallics, in a lightweight compositionally complex steel during cryogenic tensile loading. Shearing is enabled by the high strength level for dislocation glide within the austenitic matrix, attributed to the substantial strengthening from subnanoscale local chemical ordering zones and the pronounced solid solution strengthening from the multiprincipal elements in the matrix. This mechanism not only harnesses the intense strengthening and strain hardening provided by otherwise impenetrable brittle nanoprecipitates but also introduces ductility through their sequential shearing with ongoing deformation. Our steel thus showcases ultrahigh cryogenic tensile strength up to 2 gigapascal at a remarkable tensile elongation of 34%. This study reveals a new strategy for designing high-performance structural materials.

Passivation Layers in Mg-Metal Batteries: Robust Interphases for Li-Metal Batteries.

In advanced batteries, interphases serve as the key component in stabilizing the electrolyte with reactive electrode materials far beyond thermodynamic equilibria. While an active interphase facilitates the transport of working ions, an inactive interphase obstructs ion flow, constituting the primary barrier to the realization of battery chemistries. Here, a successful transformation of a traditionally inactive passivating layer on Mg-metal anode, characteristic of Mg-metal batteries with typical carbonate electrolytes, into an active and robust interphase in the Li-metal scenario is presented. By further strategically designing magnesiated Li+ electrolytes, the in situ development of this resilient interphase on Li-metal anodes, imparting enduring stability to Li-metal batteries with nickel-rich cathodes is induced. It is identified that the strong affinity between Mg2+ and anions in magnesiated Li+ electrolytes assembles ionic clusters with a bias for reducibility, thereby catalyzing the creation of anion-derived interphases rich in inorganic constituents. The prevalence of ionic clusters induced by magnesiation of electrolytes has brought properties only available in high-concentration electrolytes, suggesting a fresh paradigm of tailing electrolytes for highly reversible LMBs.

Development of Penicillin-Based Carbonic Anhydrase Inhibitors Targeting Multidrug-Resistant Neisseria gonorrhoeae.

The development of antibacterial drugs with new mechanisms of action is crucial in combating the rise of antibiotic-resistant infections. Bacterial carbonic anhydrases (CAs, EC 4.2.1.1) have been validated as promising antibacterial targets against pathogens such as Helicobacter pylori, Neisseria gonorrhoeae, and vancomycin-resistant enterococci. A multitarget strategy is proposed to design penicillin-based CA inhibitor hybrids for tackling resistance by targeting multiple bacterial pathways, thereby resensitizing drug-resistant strains to clinical antibiotics. The sulfonamide derivatives potently inhibited the CAs from N. gonorrhoeae and Escherichia coli with KI values in the range of 7.1-617.2 nM. Computational simulations with the main penicillin-binding protein (PBP) of N. gonorrhoeae indicated that these hybrid derivatives maintained the mechanism of action of the lead ß-lactams. A subset of derivatives showed potent PBP-related antigonococcal effects against multidrug-resistant N. gonorrhoeae strains, with several compounds significantly outperforming both the lead ß-lactam and CA inhibitor drugs (MIC values in the range 0.25 to 0.5 µg/mL).

The use of complementary and alternative medicine for functional gastrointestinal disorders among the saudi population.

Background and objective: Complementary and alternative medicine (CAM) is a common practice among patients, who experience functional gastrointestinal disorders (FGID). Among the Saudi population, less is known about CAM use for FGID. Therefore, this study aimed to determine the prevalence of CAM utilization for FGID amongst the Saudi population and determine the types of CAM used for treatment. Method: A cross-sectional study was carried out in Riyadh, Saudi Arabia during February 2023 through social media platforms using questionnaires adopted from the literature. There were three sections in the questionnaire including demographic information, questions to determine the prevalence of CAM use for FGID, the types of FGID, and the types of CAM utilization, and questions on the sources of information about CAM. Multivariable logistic regression was applied to find factors associated with CAM use. All statistical analyses were performed using SPSS version 26. Results: A total of 828 people participated in this study. The overall prevalence of CAM use for FGID problems was 87.2 %. There were no significant differences in CAM use for FGID problems between men (87.5 %) and women (86.3 %) (P = 0.727). The most commonly used types of CAM for FGID were ginger (73.4 %), chamomile (66.6 %), mint (61.6 %), turmeric (59.0 %), anise (55.5 %), fennel (43.1 %), and Activia yogurt©ï¸ (42.7 %). The most common FGID disorders for utilizing CAM were IBS (29.9 %), followed by constipation (29.8 %), dyspepsia (22.7 %), and bloating (17.0 %). In the multivariable regression, age, gender and employment status did not have an impact on the odds of using CAM. The subjects who had high school, university, and postgraduate education had significant odds ratios of CAM use (OR = 2.73; 95 % CI: 1.22-6.13), (OR = 4.18; 95 % CI: 2.03-8.58), and (OR = 20.85; 95 % CI: 5.51-78.80), respectively, compared to subjects who did not complete high school. Participants who had private insurance had a significant odds ratio (OR = 0.27; 95 % CI: 0.14-0.55) compared to governmental insurance. Conclusion: The use of CAM among the Saudi population is alarmingly high; however, the lack of standardized medical recommendations and treatment options may be the cause. Although there were no significant gender differences, participants with higher educational levels and private insurance coverage were more likely to use CAM for FGID. Patients suffering from FGID and limited access to medical advice and treatment options are vulnerable to being exposed to dubious and incredible information sources. Expanding access to preventative medical services, funding governmental medical websites to provide credible information, educating healthcare professionals about FGID, and conducting more research in safe and effective treatments for FGID is recommended.

Quenching of quorum sensing in multi-drug resistant Pseudomonas aeruginosa: insights on halo-bacterial metabolites and gamma irradiation as channels inhibitors.

BACKGROUND: Anti-virulence therapy is a promising strategy to treat multi-drug resistant (MDR) pathogens. Pseudomonas aeruginosa is a potent opportunistic pathogen because of an array of virulence factors that are regulated by quorum sensing systems. METHODS: The virulence features of four multi-drug resistant P. aeruginosa strains were investigated upon exposure to the sub-lethal dose of gamma rays (1 kGy), and sub-inhibitory concentrations of bioactive metabolites recovered from local halophilic strains in comparison to control. Then, the gene expression of AHL-mediated quorum sensing systems (las/rhl) was quantitatively determined in treated and untreated groups by real-time PCR. RESULTS: The bioactive metabolites recovered from halophilic strains previously isolated from saline ecosystems were identified as Halomonas cupida (Halo-Rt1), H. elongate (Halo-Rt2), Vigibacillus natechei (Halo-Rt3), Sediminibacillus terrae (Halo-Rt4) and H. almeriensis (Halo-Rt5). Results revealed that both gamma irradiation and bioactive metabolites significantly reduced the virulence factors of the tested MDR strains. The bioactive metabolites showed a maximum efficiency for inhibiting biofilm formation and rhamnolipids production whereas the gamma irradiation succeeded in decreasing other virulence factors to lower levels in comparison to control. Quantitative-PCR results showed that AHL-mediated quorum sensing systems (las/rhl) in P. aeruginosa strains were downregulated either by halo-bacterial metabolites or gamma irradiation in all treatments except the upregulation of both lasI internal gene and rhlR intact gene in P. aeruginosa NCR-RT3 and both rhlI internal gene and rhlR intact gene in P. aeruginosa U3 by nearly two folds or more upon exposure to gamma irradiation. The most potent result was observed in the expression of lasI internal gene that was downregulated by more than ninety folds in P. aeruginosa NCR-RT2 after treatment with metabolites of S. terrae (Halo-Rt4). Analyzing metabolites recovered from H. cupida (Halo-Rt1) and H. elongate (Halo-Rt2) using LC-ESI-MS/MS revealed many chemical compounds that have quorum quenching properties including glabrol, 5,8-dimethoxyquinoline-2-carbaldehyde, linoleoyl ethanolamide, agelasine, penigequinolones derivatives, berberine, tetracosanoic acid, and liquidambaric lactone in the former halophile and phloretin, lycoctonine, fucoxanthin, and crassicauline A in the latter one. CONCLUSION: QS inhibitors can significantly reduce the pathogenicity of MDR P. aeruginosa strains; and thus can be an effective and successful strategy for treating antibiotic resistant traits.

Multi-Modality Imaging in Vasculitis.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.