Deciphering the enigma of Lassa virus transmission dynamics and strategies for effective epidemic control through awareness campaigns and rodenticides.

This study aims to formulate a mathematical framework to examine how the Lassa virus spreads in humans of opposite genders. The stability of the model is analyzed at an equilibrium point in the absence of the Lassa fever. The model's effectiveness is evaluated using real-life data, and all the parameters needed to determine the basic reproduction number are estimated. Sensitivity analysis is performed to pinpoint the crucial parameters significantly influencing the spread of the infection. The interaction between threshold parameters and the basic reproduction number is simulated. Control theory is employed to devise and evaluate strategies, such as awareness campaigns, advocating condom usage, and deploying rodenticides to reduce the possibility of virus transmission efficiently.

The therapeutic efficacy of neem (Azadirecta indica) leaf extract against coinfection with Chlamydophila psittaci and low pathogenic avian influenza virus H9N2 in broiler chickens.

Avian chlamydiosis is a serious avian infection that carries a significant zoonotic danger to the poultry industry. The respiratory co-infections caused by the low pathogenic avian influenza virus H9N2 (LPAIV H9N2) also cause significant financial losses in the poultry industry. The purpose of this study was to examine the pathogenicity of Chlamydophila psittaci, and LPAIV H9N2 individually and in combination in broiler chickens, as well as to determine whether or not aqueous neem (Azadirachta indica) leaf extract is effective against infections caused by these pathogens. Therefore, 120 broiler cobb chicks were equally divided into 4 groups (30 birds each) with triplicates with 10 birds. Broilers in group 1 (G1) were infected with only C. psittaci, broilers in group 2 (G2) were infected with only LPAIV H9N2, broilers in group 3 (G3) were infected with C. psittaci and LPAIV H9N2, and broilers in group 4 (G4) remained not challenged and non-treated with any therapeutic or preventive treatment (negative control). At 21 d postinfection (dpi), birds in G1, G2, and G3 were divided into 3 subgroups of 10 birds each: subgroup (A) remained infected and untreated (positive control), subgroup (B) infected and received oxytetracycline for 5 consecutive d, and subgroup (C) infected and received 8% aqueous neem leaf extract for 5 consecutive d. The multiplication of C. psittaci in birds in G1, in various tissues was evaluated using Giemsa staining and the data showed that multiplication was much higher in the lung, spleen, and liver from 6 h to 21 dpi, but low in the heart from 8 to 21 dpi. During simultaneous co-infection in G3, the birds developed significant clinical symptoms and postmortem lesions (PM). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect viral shedding from oropharyngeal and cloacal swabs between 2 dpi and 8 dpi, with cycle threshold (CT) values ranging from 22 to 24. In contrast, bacterial shedding began 6 h after infection and continued until 21 dpi, with CT values ranging from 23 to 26. Administration of an aqueous neem leaf extract at an 8% concentration (Group C) resulted in a numerical rise in average body weight across all treatment groups in the third and fourth week, as well as a reduction in LPAIV H9N2 and C. psittaci replication in the respiratory and gut of treated birds compared to those treated with oxytetracycline (Group B). Overall, respiratory co-infections pose a considerable risk to the poultry business, which is a big threat. To control C. psittaci and LPAIV H9N2 in broiler chickens, oral supplementation of 8% aqueous neem leaf extract is recommended. This treatment improves the birds' performance, as evidenced by an increase in their average body weight. In addition, the application of 8% aqueous neem leaf extract lowers C. psittaci replication within tissues and diminishes LPAIV H9N2 shedding.

Design, synthesis and biological evaluation of novel pyrazole-based compounds as potential chemotherapeutic agents.

Aim: Design and synthesis of pyrazole-based chemotherapeutic agents. Materials & methods: A series of novel diphenyl pyrazole-chalcone derivatives were synthesized and assessed for their cytotoxic activities against 14 cancer cell lines and their antimicrobial activities against MRSA and Escherichia coli along with their safety using HSF normal cell line. Results & conclusion: Majority of the compounds showed moderate-to-significant anticancer activity with selective high percentage inhibition (>80%) against HNO-97 while being nontoxic toward normal cells. Compounds 6b and 6d were the most potent congeners with IC50 of 10 and 10.56 µM respectively. The synthesized compounds exhibited moderate to potent antimicrobial activities. Interestingly, compound 6d exhibited a minimum inhibitory concentration of 15.7 µg/ml against MRSA; and a minimum inhibitory concentration of 7.8 µg/ml versus E. coli.

[Box: see text].

Maintaining periodontally compromised teeth seems more cost-effective than replacing them with dental implants.

DESIGN: A systematic appraisal without statistical aggregation. DATA SOURCES: The researchers utilized Ovid (Medline), Embase, Web of Science, and CINAHL databases. They performed a comprehensive literature search, which concluded in July 2023. References of selected studies and systematic reviews were examined for additional relevant articles. STUDY SELECTION: The review included studies (randomized controlled trials [RCTs], systematic reviews [SRs], narrative reviews, retrospective studies, cross-sectional studies, case series, case reports) discussing the cost-effectiveness of preserving teeth versus replacing them with implants in patients with severe periodontal disease. Non-English publications, letters, conference abstracts, and brief reports were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles and abstracts using a systematic review screening tool, resolving conflicts with a third reviewer. The extracted data included study design, patient demographics, treatment details, economic models, costs, and clinical implications. Quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools, with scores converted to percentages. RESULTS: A total of 633 studies were identified for periodontal treatment, with 9 included after screening, while 114 studies were identified for dental implants, of which 3 were included after screening. The included studies were published between 2008 and 2018, predominantly from Germany, and mainly comprised retrospective designs, along with some prospective and model-based analyses. Follow-up periods ranged from 36 months to 33 years. Treatment costs were found to increase with disease severity, with surgical treatments being more expensive than nonsurgical ones, and supportive periodontal treatment (SPT) representing the highest cost share in periodontal treatment. Maintaining implants proved more costly than maintaining teeth, especially in cases of peri-implantitis. For chronic periodontitis, total treatment costs per tooth were €222 ± €98 over 18.7 years, and for aggressive periodontitis, €267 ± €148 over 16.9 years. Regular SPT cost €806 per tooth per year over 28.7 years, with significant cost variations across studies. A 2013 study found that maintaining implants was five times costlier than maintaining teeth, particularly if peri-implantitis developed. A 2018 study indicated that implant-supported crowns (ISCs) were the most expensive therapy. Only one study directly compared costs within the same patient, finding periodontal treatment to be more cost-effective than implants. Costs also increased with irregular SPT, aggressive periodontitis, and specialist treatments compared to regular SPT, chronic periodontitis, and treatments by general dental practitioners. The quality of included studies scored between 45% and 84.6%, indicating moderate to high quality, with methodological issues including unclear strategies for handling confounding factors and incomplete follow-up. CONCLUSIONS: Implants are effective for replacing missing teeth but are associated with higher long-term costs and complications. Maintaining periodontally compromised teeth is generally more cost-effective, therefore, maintenance costs and potential complications should be carefully considered in treatment planning. There is a need for studies comparing the long-term cost-effectiveness of saving teeth compared to replacing them with implants, considering several variables for informed clinical decision-making.

Ultrasonographic Characterizations of Radial Artery for Transradial Approach in the Saudi Population: A Pilot Study.

Background The radial artery originates from the brachial artery at the level of the neck of the radius in the cubital fossa. It has multiple branches all over its course, and it is an important artery for multiple procedures across several fields. Objectives The objective of this article is to assess the size and characteristics of the radial artery in the Saudi population for the transradial approach. It aims to compare the diameters of the distal and proximal radial arteries using ultrasonography and determine the clinical significance of the findings in selecting an appropriate catheter size among different demographic groups. Additionally, the study aims to contrast the obtained results with international standards to provide a comprehensive analysis of the radial artery characteristics in the Saudi population. Methods A pilot study was conducted at a Medina region hospital in Madinah from December 2022 to July 2023. An ultrasonographic assessment of the right radial artery was performed on a sample of 45 volunteers. Results Our results showed a significantly larger mean diameter of the right ulnar artery in males compared to females. No other significant differences were observed in the characteristics of the right proximal radial artery (PRA), distal radial artery (DRA), or ulnar artery between genders. Significant differences in arterial characteristics were observed across different body mass index (BMI) categories for several parameters. Depth measurements in the right PRA displayed notable differences across age groups, and the ulnar artery showed significant variability among age categories. No statistically significant differences were found in arterial characteristics across smoking categories. Conclusion Our study on Saudi Arabian radial artery ultrasonography reveals potential clinical correlations, highlighting the influence of age and BMI on arterial characteristics. Further research is needed to confirm these findings and explore demographic determinants.

Phytochemical and biological investigation of Astragalus Caprinus L.

BACKGROUND: cultivated and wild plants are used to treat different ailments. The Astragalus genus is found in temperate and dry climates; thus, it is found in Egypt and the arab world. Astragalus caprinus has a good amount of bioactive chemicals, which may help explain its therapeutic effects in reducing the risk of consequences from disease. METHOD: The phytochemical investigation of the herb and roots of Astragalus caprinus L. included the analytical characterization for the petroleum ether components by GC/MS, unsaponifiable matter (unsap. fraction), and fatty acids (FAME) investigation by GLC analysis. Main flavonoids were chromatographically isolated from ethyl acetate and n-butanol extracts. In vitro antimicrobial activity has been tested against the Gram-positive bacteria Staphylococcus aureus and Streptococcus mutans for different plant extracts, the Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumonia, the fungus Candida albicans and Aspergillus niger, and the Escherichia coli bacterium. Metabolite cytotoxicity was examined using the MTT assay against HepG-2 (human liver carcinoma) and MCF-7 (breast carcinoma). RESULTS: Identifying the important components of the herb and root petroleum ether extracts was achieved. Using column chromatography, luteolin, cosmosiin (apigenin-7-O-glucoside), and cynaroside (luteolin-7-O-glucoside) were separated and identified using UV, NMR, and Mass Spectroscopy. Root extracts displayed potential antimicrobial activity against most of the tested pathogens. Both extracts (herb and roots) were active against the MCF-7 cell line and HepG-2 cell line with IC50 62.5 ± 0.64 and 72.4 ± 2.3 µg/ml, and 75.9 ± 2.5 and 96.8 ± 4.2 µg/ml, respectively. CONCLUSION: Astragalus caprinus seems to be a promising source of bioactive compounds that could potentially aid in preventing disease complications and address common health issues in developing countries. Moreover, the various parts of this plant could be utilized as natural raw materials for producing health-boosting products that could address common health issues in developing countries.

The influence of dietary supplementation with fermented agro-industrial residue of faba bean on Japanese quail performance, immunity, gut microbiota, blood chemistry, and antioxidant status.

Antibiotic overuse in poultry feeds has disastrous implications; consequently, long-term alternatives must be developed. As a result, the current study aims to assess the impact of Aspergillus niger filtrate (ANF) high in organic acids grown on agro-industrial residue of faba bean (AIRFB) on quail diet, as well as their influence on bird productivity, digestion, carcass yield, blood chemistry, and intestinal microbiota. A total of 240 Japanese quails (aged 7 d) were used in this study, divided equally among 5 experimental groups with 48 quails each. Group 1 (G1) received a basal diet without any ANF, group 2 (G2) received a basal diet supplemented with 0.5 mL ANF/kg diet, group 3 (G3) received a basal diet supplemented with 1.0 mL ANF/kg diet, group 4 (G4) received a basal diet supplemented with 1.5 mL ANF/kg diet, and group 5 (G5) received a basal diet supplemented with 2 mL ANF/kg diet. The performance parameters were monitored at 1 to 3, 3 to 5, and 1 to 5 wk. Adding ANF increased body weight at 3 and 5 wk, as well as body weight gain at 1 to 3, 3 to 5, and 1 to 5 wk, compared to the control diet. The ANF fed quails had the highest feed conversion ratio compared to the control group. The addition of ANF to the quail diet had no effect on the weight of the carcass, gizzard, heart, liver, giblets, or dressing; however, it did lower triglycerides, low-density lipoprotein, and very low-density lipoprotein while increasing high-density lipoprotein levels. The quail groups that received ANF had enhanced immunological indices such as IgG, IgM, IgA, and lysozymes. It also increased the levels of superoxide dismutase and total antioxidant contents, as well as catalase, and digestive enzymes such as protease, amylase, and lipase. However, it lowered the blood MDA levels compared to control. It has been demonstrated that the total gut microbiota, Escherichia coli, total coliforms, and the population of Salmonella are all reduced in ANF-fed quails. Histological examination of ANF quails' liver and intestinal sections revealed normal hepatic parenchyma, typical leaf-like intestinal villi, and comparatively short and frequently free lumina. In conclusion, Japanese quail showed improvements in performance, digestive enzymes, antioxidant indices, immunity, and capacity to reduce intestinal pathogenic bacteria after consuming diet supplemented with ANF.

Lung-MAP Next-Generation Sequencing Analysis of Advanced Squamous Cell Lung Cancers (SWOG S1400).

INTRODUCTION: Squamous cell cancer (SqCC) is a lung cancer subtype with few targeted therapy options. Molecular characterization, that is, by next-generation sequencing (NGS), is needed to identify potential targets. Lung Cancer Master Protocol Southwest Oncology Group S1400 enrolled patients with previously treated stage IV or recurrent SqCC to assess NGS biomarkers for therapeutic sub-studies. METHODS: Tumors underwent NGS using Foundation Medicine's FoundationOne research platform, which sequenced the exons and/or introns of 313 cancer-related genes. Mutually exclusive gene set analysis and Selected Events Linked by Evolutionary Conditions across Human Tumors were performed to identify mutually exclusive and co-occurring gene alterations. Comparisons were performed with data on 495 lung SqCC downloaded from The Cancer Genome Atlas. Cox proportional hazards models were used to assess associations between genetic variants and survival. RESULTS: NGS data are reported for 1672 patients enrolled on S1400 between 2014 and 2019. Mutually exclusive gene set analysis identified two non-overlapping sets of mutually exclusive alterations with a false discovery rate of less than 15%: NFE2L2, KEAP1, and PARP4; and CDKN2A and RB1. PARP4, a relatively uncharacterized gene, showed three frequent mutations suggesting functional significance: 3116T>C (I1039T), 3176A>G (Q1059R), and 3509C>T (T1170I). When taken together, NFE2L2 and KEAP1 alterations were associated with poorer survival. CONCLUSIONS: As the largest dataset to date of lung SqCC profiled on a clinical trial, the S1400 NGS dataset establishes a rich resource for biomarker discovery. Mutual exclusivity of PARP4 and NFE2L2 or KEAP1 alterations suggests that PARP4 may have an uncharacterized role in a key pathway known to impact oxidative stress response and treatment resistance.

Polyphenols: Chemistry, bioavailability, bioactivity, nutritional aspects and human health benefits: A review.

Polyphenols, including phenolics, alkaloids, and terpenes, are secondary metabolites that are commonly found in fruits, vegetables, and beverages, such as tea, coffee, wine, chocolate, and beer. These compounds have gained considerable attention and market demand because of their potential health benefits. However, their application is limited due to their low absorption rates and reduced tissue distribution efficiency. Engineering polyphenol-protein complexes or conjugates can enhance the antioxidant properties, bioavailability, and stability of polyphenols and improve digestive enzyme hydrolysis, target-specific delivery, and overall biological functions. Complex polyphenols, such as melanin, tannins, and ellagitannins, can promote gut microbiota balance, bolster antioxidant defense, and improve overall human health. Despite these benefits, the safety of polyphenol complexes must be thoroughly evaluated before their use as functional food additives or supplements. This review provides a detailed overview of the types of macromolecular polyphenols, their chemical composition, and their role in food enrichment. The mechanisms by which complex polyphenols act as antioxidative, anti-inflammatory, and anticancer agents have also been discussed.

Ecological impacts and management strategies of pesticide pollution on aquatic life and human beings.

Pesticide contamination has become a global concern. Pesticides can sorb onto suspended particles and deposit into the sedimentary layers of aquatic environments, resulting in ecosystem degradation, pollution, and diseases. Pesticides impact the behavior of aquatic environments by contaminating organic matter in water, which serves as the primary food source for aquatic food webs. Pesticide residues can increase ammonium, nitrite, nitrate, and sulfate in aquatic systems; thus, threatening ecological environment and human health. Several physical, chemical, and biological methodologies have been implemented to effectively remove pesticide traces from aquatic environments. The present review highlights the potential consequences of pesticide exposure on fish and humans, focusing on the (epi)genetic alterations affecting growth, behavior, and immune system. Mitigation strategies (e.g., bioremediation) to prevent/minimize the detrimental impacts of pesticides are also discussed. This review aims to shed light on the awareness in reducing the risk of water pollution for safe and sustainable pesticide management.

Synergistic effects (adsorption and biodegradation) of Streptomyces hydrogenans immobilization on nano-reed biochar for further application in upflow anaerobic sludge blanket.

Water pollution due to wastewater is a serious issue that needs to be studied as many organic compounds are released from wastewater, affecting the ecosystem. Therefore, appropriate treatment methods should be used to prevent these effects. Phragmites australis biochar immobilized with bacteria was prepared in this study for use as an adsorbent in a pilot-scale up-flow anaerobic sludge blanket (UASB) to remove organic matter from wastewater in a buffalo farm. Combining reed biochar and immobilized Streptomyces hydrogenans introduces a synergistic effect: reed biochar serves as a substrate for microbial colonization and provides a conducive environment for microbial growth while Streptomyces hydrogenans, immobilized on the biochar, enhances the degradation of organic matter through its metabolic activities. Suitable techniques were employed, including infrared spectroscopy (FTIR) to determine the functional groups before and after adsorption, scanning electron microscopy (SEM) to determine the morphology of the composite before and after adsorption, X-ray diffraction (XRD) to examine the mineralogical changes through reflectometry, high-resolution diffraction and Brunauer-Emmett-Teller (BET) analyses to determine the surface area that always carried out by nitrogen adsorption/desorption technique based on the BET isotherm. Two-level factorial design experiments optimized using biochar, immobilized with bacteria, were employed to enhance the UASB performance. Chemical oxygen demand (COD) removal and biogas production were studied as a function of four experimental parameters: biochar dose, buffalo sludge dose, pH, and bacteria type. The buffalo sludge (manure) dose negatively affected the model's performance. The results showed better COD removal with Streptomyces hydrogenans S11 inoculation. The optimum biochar dose, buffalo sludge dose, and pH were 20 g L-1, 0%, and 7.5, respectively. The COD removal efficiency under these experimental conditions reached 92.70% with a biogas production of 5.0 mL. The experimental results of a validated point from the model were 90.80% for COD removal ratio and 4.80 mL for biogas production at 2 g L-1 biochar dose, 0% buffalo sludge dose, and pH 7.5 using Streptomyces hydrogenans S11 bacteria. A buffalo wastewater (BWW) anaerobic digestion experimental model was best fitted to the data under optimal conditions. This study aligns with the United Nations Sustainable Development Goals (SDGs), specifically SDG 6 (clean water and sanitation) and SDG 12 (responsible consumption and production). The implications of our work extend to large-scale applications, promising a greener and more sustainable future for wastewater treatment.

Ecotoxicity and environmental safety assessment of two-dimensional niobium carbides (MXenes).

Two-dimensional (2D) MXenes have gained great interest in water treatment, biomedical, and environmental applications. The antimicrobial activity and cell toxicity of several MXenes including Nb4C3Tx and Nb2CTx have already been explored. However, potential side effects related to Nb-MXene toxicity, especially on aquatic pneuma, have rarely been studied. Using zebrafish embryos, we investigated and compared the potential acute toxicity between two forms of Nb-MXene: the multilayer (ML-Nb4C3Tx, ML-Nb2CTx) and the delaminated (DL-Nb2CTx, and DL-Nb4C3Tx) Nb-MXene. The LC50 of ML-Nb4C3Tx, ML-Nb2CTx, DL-Nb2CTx, and DL-Nb4C3Tx were estimated to be 220, 215, 225, and 128 mg/L, respectively. Although DL-Nb2CTx, and DL-Nb4C3Tx derivatives have similar sizes, DL-Nb4C3Tx not only shows the higher mortality (LC50 = 128 mg/L Vs 225 mg/L), but also the highest teratogenic effect (NOEC = 100 mg/L Vs 200 mg/L). LDH release assay suggested more cell membrane damage and a higher superoxide anion production in DL-Nb4C3Tx than DL-Nb2CTx,. Interestingly, both DL-Nb-MXene nanosheets showed insignificant cardiac, hepatic, or behavioral toxic effects compared to the negative control. Embryos treated with the NOEC of DL-Nb2CTx presented hyperlocomotion, while embryos treated with the NOEC of DL-Nb4C3Tx presented hyperlocomotion, suggesting developmental neurotoxic effect and muscle impairment induced by both DL-Nb-MXene. According to the Fish and Wildlife Service (FSW) Acute Toxicity Rating Scale, all tested Nb-MXene nanosheets were classified as "Practically not toxic". However, DL-Nb4C3Tx should be treated with caution as it might cause a neurotoxic effect on fauna when it ends up in wastewater in high concentrations.

Drug repurposing of pyrazolotriazine derivatives as potential anti-SARS-CoV-2 agents: in vitro and in silico studies.

The search for new molecules targeting SARS-CoV-2 has been a priority since 2020. The continuous evolution of new mutants increases the need for more research in the area. One way to find new leads is to repurpose existing drugs and molecules against the required target. Here, we present the in vitro and in silico screening of ten previously synthesized and reported compounds as anti-COVID 19 agents. The compounds were screened in vitro against VERO-E6 cells to find their Cytotoxic Concentration (CC50) and their Inhibitory Concentration (IC50). Compounds 1, 2, and 5 revealed a promising anti-SARS-CoV-2 of (IC50 = 2.4, 11.2 and 2.8 µM), respectively while compounds 3 and 7 showed moderate activity of (IC50 = 17.8 and 26.1 µM) compared to Chloroquine which showed an IC50 of 24.9 µM. Among tested compounds, 1 showed the highest selectivity (CC50/IC50) of 192.8. Docking, molecular dynamics and ADME studies were done to investigate potential interactions between compounds and SARS-CoV-2 targets as well as to study the possibility of using them as lead compounds.

An Assessment of the Knowledge, Attitude, and Practice of Probiotics and Prebiotics among the Population of the United Arab Emirates.

Probiotics and prebiotics offer a range of advantageous effects on human health. The knowledge, attitudes, and practices (KAP) of individuals can impact their inclination to consume probiotics and prebiotics. The main objective of this study was to examine the KAP of the people in the United Arab Emirates (UAE) about probiotics and prebiotics consumption. Additionally, the study aimed to assess the impact of KAP and sociodemographic factors on the use of probiotics and prebiotics. In order to accomplish this objective, a verified online questionnaire was used with a five-point Likert scale and distributed using an online platform (Google Forms). A cross-sectional research, non-probability sampling was implemented, and G*Power statistical power analysis was used to estimate a sample size of 385 participants. A total of 408 replies were gathered. The population under study consisted of residents in the UAE between the ages of 18 to 64 years old, excluding populations under the age of 18 and those living outside the UAE. A total of 392 participants met the criteria for inclusion in this study. The research ethics committees of UAE University granted the study approval (ERSC_2024_4359), and the validity of the findings was confirmed through face-to-face interviews with around 50 individuals and a Cronbach's alpha test with result of 0.84. The statistical software SPSS version 29.0 for Mac OS was utilized to examine the relationships between KAP variables, including Chi-square tests and Pearson's correlation coefficients. The tests were selected based on their capacity to handle categorical and continuous data, respectively. The female population was 85.2% of the total, while the male population accounts for 14.8%. The age distribution of participants shows that the largest proportion, 68.4%, falls within the 18-24 age range. Out of the participants, 61.5% held a bachelor's degree. Most of the participants, 56.4%, were students, while 29.1% were employees. The average results indicate a significant inclination towards probiotics and prebiotics, as demonstrated by the scores above the midpoint for the six knowledge questions (M = 2.70), six attitude questions (M = 3.10), and six practice questions (M = 3.04). Several studies have examined this phenomenon; however, additional research comparing individuals in the UAE is necessary to fully comprehend the influence of KAP on the consumption of probiotics and prebiotics in the UAE.

MEK inhibitors: a promising targeted therapy for cardiovascular disease.

Cardiovascular disease (CVD) represents the leading cause of mortality and disability all over the world. Identifying new targeted therapeutic approaches has become a priority of biomedical research to improve patient outcomes and quality of life. The RAS-RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathway is gaining growing interest as a potential signaling cascade implicated in the pathogenesis of CVD. This pathway is pivotal in regulating cellular processes like proliferation, growth, migration, differentiation, and survival, which are vital in maintaining cardiovascular homeostasis. In addition, ERK signaling is involved in controlling angiogenesis, vascular tone, myocardial contractility, and oxidative stress. Dysregulation of this signaling cascade has been linked to cell dysfunction and vascular and cardiac pathological remodeling, which contribute to the onset and progression of CVD. Recent and ongoing research has provided insights into potential therapeutic interventions targeting the RAS-RAF-MEK-ERK pathway to improve cardiovascular pathologies. Preclinical studies have demonstrated the efficacy of targeted therapy with MEK inhibitors (MEKI) in attenuating ERK activation and mitigating CVD progression in animal models. In this article, we first describe how ERK signaling contributes to preserving cardiovascular health. We then summarize current knowledge of the roles played by ERK in the development and progression of cardiac and vascular disorders, including atherosclerosis, myocardial infarction, cardiac hypertrophy, heart failure, and aortic aneurysm. We finally report novel therapeutic strategies for these CVDs encompassing MEKI and discuss advantages, challenges, and future developments for MEKI therapeutics.

Age-Specific Outcomes of Bioprosthetic vs. Mechanical Aortic Valve Replacement: Balancing Reoperation Risk with Anticoagulation Burden.

BACKGROUND: The choice of prosthesis for aortic valve replacement (AVR) remains challenging. The risk of anticoagulation complications vs. the risk of aortic valve reintervention should be weighed. This study compared the outcomes of bioprosthetic vs. mechanical AVR in patients older and younger than 50. METHODS: This retrospective study was conducted from 2009 to 2019 and involved 292 adult patients who underwent isolated AVR. The patients were divided according to their age (above 50 years or 50 years and younger) and the type of valves used in each age group. The outcomes of bioprosthetic valves (Groups 1a (>50 years) and 1b (≤50 years)) were compared with those of mechanical valves (Groups 2a (>50 years) and 2b (≤50 years)) in each age group. RESULTS: The groups had nearly equal rates of preexisting comorbidities except for Group 1b, in which the rate of hypertension was greater (32.6% vs. 14.7%; p = 0.025). This group also had higher rates of old stroke (8.7% vs. 0%, p = 0.011) and higher creatinine clearance (127.62 (108.82-150.23) vs. 110.02 (84.87-144.49) mL/min; p = 0.026) than Group 1b. Patients in Group 1a were significantly older than Group 2a (64 (58-71) vs. 58 (54-67) years; p = 0.002). There was no significant difference in the NYHA class between the groups. The preoperative ejection fraction and other echocardiographic parameters did not differ significantly between the groups. Re-exploration for bleeding was more common in patients older than 50 years who underwent mechanical valve replacement (p = 0.021). There was no difference in other postoperative complications between the groups. The groups had no differences in survival, stroke, or bleeding rates. Aortic valve reintervention was significantly greater in patients ≤ 50 years old with bioprosthetic valves. There were no differences between groups in the changes in left ventricular mass, ejection fraction, or peak aortic valve pressure during the 5-year follow-up. CONCLUSIONS: The outcomes of mechanical and bioprosthetic valve replacement were comparable in patients older than 50 years. Using bioprosthetic valves in patients younger than 50 years was associated with a greater rate of valve reintervention, with no beneficial effect on the risk of bleeding or stroke.

A high-quality genome assembly and annotation of Thielaviopsis punctulata DSM102798.

Black scorch disease (BSD), caused by the fungal pathogen Thielaviopsis punctulata (Tp) DSM102798, poses a significant threat to date palm cultivation in the United Arab Emirates (UAE). In this study, Chicago and Hi-C libraries were prepared as input for the Dovetail HiRise pipeline to scaffold the genome of Tp DSM102798. We generated an assembly with a total length of 28.23 Mb comprising 1,256 scaffolds, and the assembly had a contig N50 of 18.56 kb, L50 of three, and a BUSCO completeness score of 98.6% for 758 orthologous genes. Annotation of this assembly produced 7,169 genes and 3,501 Gene Ontology (GO) terms. Compared to five other Thielaviopsis genomes, Tp DSM102798 exhibited the highest continuity with a cumulative size of 27.598 Mb for the first seven scaffolds, surpassing the assemblies of all examined strains. These findings offer a foundation for targeted strategies that enhance date palm resistance against BSD, and foster more sustainable and resilient agricultural systems.