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In Saudi Arabia, breast cancer is the second-most frequently identified common malignant cause of death for women. The present investigation was carried out to assess the impact of different Soxhlet solvent extracts of Annona muricata on apoptosis induction in breast cancer cells. Cell survival was estimated by post-incubation of cells with the extract for 24 h using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Acridine orange (AO)/propidium iodide (PI) and 4′,6-diamidino-2-phenylindole (DAPI) staining were employed to study cell apoptosis. qRT-PCR was also employed to assess apoptotic genes’ expression, such as BAX and P53 genes. The results of the MTT assay showed that the chloroform extract inhibited the proliferation of MDA-MB-231 and MCF-7 cells dose-dependently. AO/PI and DAPI staining showed chromatin condensation and fragmentation. In treated cells, P53 expression significantly increased, correlated with the increase in BAX activity. The findings suggest that apoptosis may have been triggered post-chloroform extract treatment. Combining chloroform extract of A. muricata and doxorubicin at a 1:1 ratio increased the IC50 value (292.3 µg/mL). The chloroform extract of A. muricata contained a variety of substances, including diethyl carbonate (7.38%), 4-acetoxy-2,11-dodecadiene (58.13%), and hexadecanoic acid (34.48%), according to the results of the gas chromatography-mass spectrometry analysis. As a result, future research on the A. muricata chloroform extract as a potential anticancer drug could be suggested.

BackgroundCoronavirus disease 2019 (COVID-19) is an evolving infectious disease that dramatically spread all over the world in the early part of 2020. No studies have yet summarized the potential severity and mortality risks caused by COVID-19 in patients with chronic obstructive pulmonary disease (COPD), and we update information in smokers.MethodsWe systematically searched electronic databases from inception to March 24, 2020. Data were extracted by two independent authors in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using a modified version of the Newcastle-Ottawa Scale. We synthesized a narrative from eligible studies and conducted a meta-analysis using a random-effects model to calculate pooled prevalence rates and 95% confidence intervals (95%CI).ResultsIn total, 123 abstracts were screened and 61 full-text manuscripts were reviewed. A total of 15 studies met the inclusion criteria, which included a total of 2473 confirmed COVID-19 patients. All studies were included in the meta-analysis. The crude case fatality rate of COVID-19 was 7.4%. The pooled prevalence rates of COPD patients and smokers in COVID-19 cases were 2% (95% CI, 1%-3%) and 9% (95% CI, 4%-14%) respectively. COPD patients were at a higher risk of more severe disease (risk of severity = 63%, (22/35) compared to patients without COPD 33.4% (409/1224) [calculated RR, 1.88 (95% CI, 1.4-2.4)]. This was associated with higher mortality (60%). Our results showed that 22% (31/139) of current smokers and 46% (13/28) of ex-smokers had severe complications. The calculated RR showed that current smokers were 1.45 times more likely [95% CI: 1.03-2.04] to have severe complications compared to former and never smokers. Current smokers also had a higher mortality rate of 38.5%.ConclusionAlthough COPD prevalence in COVID-19 cases was low in current reports, COVID-19 infection was associated with substantial severity and mortality rates in COPD. Compared to former and never smokers, current smokers were at greater risk of severe complications and higher mortality rate. Effective preventive measures are required to reduce COVID-19 risk in COPD patients and current smokers.

ABSTRACT To optimize the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children, specimen collection and testing method are crucial considerations. Ideally, specimen collection is easy and causes minimal discomfort, and the laboratory approach is simple, accurate, and rapid. In this prospective cohort study we evaluated the accuracy of a point-of care nucleic acid device using caregiver/patient self-collected buccal swabs. Participants were recruited in 14 Canadian tertiary care pediatric emergency departments. Children

This study introduces a sustainable method for producing silver nanoparticles (AgNPs), focusing on sustainability and environmental protection. The technique includes the use of Salvia elegans aqueous leaf extract as a reducing agent. In addition, the research investigates the dose-dependent degradation of pUC19 DNA by silver nanoparticles, which is facilitated by the generation of singlet oxygen. The presence of S. elegans extract results in significant color changes, going from a colorless state to a dark brown hue, serving as an indication of the synthesis of AgNPs. A range of experimental methods were employed to analyze the biogenic AgNPs, such as UV–visible absorption spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The meticulously produced AgNPs demonstrate a high level of uniformity, featuring a spherical shape and a particle size of 60 nm. DNA photo-cleavage studies show that singlet oxygen plays a crucial role in triggering DNA damage caused by AgNPs, indicating their potential as powerful cytotoxic agents specifically aimed at cancer cells. Additional studies are required to clarify the effectiveness and specificity of AgNPs against various cancer cell types to assess their therapeutic potential. The cytotoxic effects of AgNPs, particularly in relation to DNA photocleavage, are of considerable interest in cancer research. This research holds promise for developing novel and sustainable cancer therapies based on the unique properties of biogenic silver nanoparticles.

Novel series of nitric oxide-releasing thiazolidine-2,4-diones (NO-TZD-3a-d,5,6) and 3,4,5-trimethoxychalcone-based multifunctional 1,4-dihydropyrimidines (CDHPM-10a-g) have been designed and synthesised as potent broad-spectrum anticancer agents with potential VEGFR-2 inhibition. The designed analogs were evaluated for their anticancer activities towards a full panel of NCI-60 tumour cell lines and CDHPM-10a-g emerged mean %inhibitions ranging from 76.40 to 147.69%. Among them, CDHPM-10e and CDHPM-10f demonstrated the highest MGI% of 147.69 and 140.24%, respectively. Compounds CDHPM-10a,b,d-f showed higher mean %inhibitory activity than the reference drug sorafenib (MGI% = 105.46%). Superiorly, the hybrid CDHPM-10e displayed the highest potencies towards all the herein tested subpanels of nine types of cancer with MGI50 of 1.83 µM. Also, it revealed potent cytostatic single-digit micromolar activity towards the herein examined cancer cell lines. The designed compounds CDHPM-10a-g were exposed as potent non-selective broad-spectrum anticancer agents over all NCI subpanels with an SI range of 0.66–1.97. In addition, the target analog CDHPM-10e revealed potency towards VEGFR-2 kinase comparable to that of sorafenib with a sub-micromolar IC50 value of 0.11 µM. Also, CDHPM-10e could effectively induce Sub-G1-phase arrest and prompt apoptosis via caspase and p53-dependent mechanisms. Furthermore, CDHPM-10e revealed significant anti-metastatic activity as detected by wound healing assay. The modelling study implies that CDHPM-10e overlaid well with sorafenib and formed a strong H-bond in the DFG binding domain. The ADMET studies hinted out that CDHPM-10e met Pfizer’s drug-likeness criteria. The presented novel potent anticancer agent merits further devotion as a new lead product in developing more chalcone-based VEGFR-2 inhibitors.

PurposeThis study examined the physiological effects of 12 weeks of detraining and retraining in a highly trained master triathlete (age 53.8 years).MethodsVariables associated with swimming, cycling, and running performance, including V˙O2max, peak power output (PPO), gross cycling efficiency (CE), running maximal aerobic velocity (MAV), running economy (RE), muscle strength, and body composition were assessed before the last race of the season (baseline), after 12 weeks of detraining, and after 12 weeks of retraining.ResultsDetraining resulted in a 9.1% and 10.9% decrease in relative V˙O2max for cycling and running, respectively. PPO and MAV declined by 12.7% and 8.6%, respectively. After detraining, CE decreased by 6.2%, and RE was 22% higher than the baseline. The maximal strength capacity of the knee extensor muscles decreased by an average of 8.2%. Body fat percentage increased from 10.5% to 13.8%, while lean mass decreased by 2.2 kg. After retraining, almost all variables returned to baseline or even slightly increased, except RE and lean mass, which did not return to baseline.ConclusionAfter 12 weeks of detraining, a lifelong master triathlete can regain his cardiorespiratory fitness (i.e., V˙O2max) with 12 weeks of progressive and structured retraining, but his running economy and lean mass remain slightly depressed.

This study focuses on the synthesis, characterization, and use of zinc oxide nanoparticles (ZnONPs) derived from W. bifurcata fruit peel extract. ZnONPs are frequently synthesized utilizing a green technique that is both cost-effective and ecologically friendly. ZnONPs were characterized utilizing analytical techniques. Ultra Violet visible (UV-Vis) spectra showed peaks at 364 nm, confirming the production of ZnONPs. Scanning Electron Microscope analysis indicated that the nanoparticles generated were spherical/agglomerated, with diameters ranging from 11 to 25 nm. FTIR spectroscopy was used to identify the particular functional groups responsible for the nanoparticles’ reduction, stabilization, and capping. Phytochemical analysis of the extract revealed that flavonoids, saponins, steroids, triterpenoids, and resins were present. The antibacterial activity of W. bifurcata synthesised nanoparticles was evaluated against pathogenic bacteria. The ZnONPs antioxidant activity was assessed using DPPH assay. The in vitro cytotoxicity was assessed against prostate cancer PC3 cells. The wound healing potential was assessed by employing in vitro scratch assay and in vivo excision model in Wistar rats. Because of its environmentally benign production, low toxicity, and biocompatibility, ZnONPs exhibited potential antibacterial, antioxidant, anticancer, and wound healing activities, indicating that they could be used in cancer treatment and wound management. Further study is required to examine the fundamental mechanisms and evaluate the safety and effectiveness of the test sample in clinical situations.

L-glutaminase is a unique enzyme with catalytic activity and the ability to modulate glutamine levels, making it a valuable enzyme with numerous potential applications. L-glutaminase triggers a distinctive reaction by converting L-glutamine into glutamic acid while releasing ammonia concurrently. This enzymatic process holds potential applications across diverse industries, notably in food and pharmaceuticals. The primary objective of the present research was to identify and isolate a fungal strain proficient in L-glutaminase production from soil found in maritime environments. The physical and nutritional conditions were optimized for maximum synthesis of L-glutaminase under solid state fermentation (SSF) and submerged fermentation conditions (SmF). The isolated organism was identified as Fusarium solani-melongenae strain CRI 24 by morphological and 18S rRNA analysis. The optimum carbon source under SmF and SSF was found to be starch (0.2% w/v). Wheat bran as solid substrate among others showed optimum enzyme activity. On the seventh day of incubation, at pH 8.0 and 0.7% L-glutamine concentration under SSF and SmF, the highest enzyme activity was detected. The greatest enzyme activity in SSF was seen at a moisture content of 10%. Fusarium solani-melongenae species produced the enzyme under optimal conditions and 4.20 and 4.73-fold increase (from 0.8 U/mL to 3.61 U/mL and from 0.781 U/mL to 3.69 U/mL) was achieved after optimization in submerged and in solid state fermentation, respectively. The selective isolation and optimization processes described in this work are a promising technique for the industrial production of L-glutaminase and can be applied in the pharmaceutical and food industries.

Background/Objectives: Palbociclib, an oral CDK 4/6 inhibitor, was evaluated in a Pediatric Brain Tumor Consortium (PBTC) phase 1 (NCT02255461; PBTC-042) study to treat children and young adults with recurrent, progressive, or refractory brain tumors. The objectives of this study were to characterize the palbociclib population pharmacokinetics in children enrolled on PBTC-042, to conduct a population pharmacodynamic analysis in this patient population, and to perform a simulation study to assess the role of palbociclib exposure on neutropenia and thrombocytopenia. Methods: The palbociclib population pharmacokinetics and pharmacodynamics were characterized in this patient population (n = 34 patients; 4.9–21.6 years old). Population pharmacokinetics were modeled using a one-compartment model with first-order absorption and elimination. Covariate analysis was performed, evaluating demographics, laboratory values, and concomitant medications. A pharmacodynamic model was used to describe the relation between palbociclib plasma exposure and changes in the ANC and platelet counts. Results: The population estimates for the apparent oral volume, apparent oral clearance, and absorption rate constant were 664.5 L/m2, 36.8 L/h/m2, and 0.48 h−1, respectively. The palbociclib apparent oral clearance was decreased in patients with higher AST values (p = 0.0066). The ANC and platelet pharmacodynamic models estimated that the median (5th–95th percentile) time individuals had grade 3 or greater neutropenia was 4 (0, 21) days. Simulations showed that given 75 mg/m2 palbociclib, 49% of the individuals were expected to have grade 3 or greater neutropenia. Conclusions: Palbociclib pharmacokinetics and pharmacodynamics were adequately characterized in this patient population, no unexpected adverse reactions were noted, and the drug was well tolerated.

Introduction: Over half of disabled children (53%) suffer from oral and dental health problems (Alwadi et al., 2022) due to poor attention from healthcare providers. Aims: Determine the level of family awareness of oral and dental healthcare methods for 5-16-year-old disabled children in Saudi Arabia. Methods: To achieve the study objective, the descriptive method by the social survey method was used. The required ethical approvals of centers and associations caring for people with disabilities in the region were obtained. These centers cooperated in publishing the study tool through social media applications; the questionnaire link was distributed to a sample of (312) parents of children aged 5-16 years with disabilities in Najran region, south of the Kingdom of Saudi Arabia, in October and November of 2022. Results: There was a weak level of family awareness of the methods of oral and dental healthcare for children aged 5-16 years with disabilities. Also, statistically significant differences at α = 0.05 were found in the level of family awareness of the methods of oral and dental healthcare for children aged 5-16 years with nature of the relationship with the child disability in favor of mothers and the academic qualification in favor of the university academic qualification. Nevertheless, the respondents’ answers did not differ by their child’s type of disability. Conclusion: The study recommended developing a comprehensive national strategic plan supervised by the Ministry of Health and the Ministry of Social Development to reduce the risk of oral and dental diseases.

BACKGROUND: Infection is the second-leading cause of death among cancer patients, but there have been few studies on the effectiveness of novel antimicrobial agents to treat carbapenem-resistant Enterobacterales in cancer patients. OBJECTIVE: Evaluate the mortality and clinical outcomes of ceftazi-dime-avibactam for OXA-48- and/or New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales infection in cancer patients. DESIGN: Retrospective observational cohort study SETTING: Tertiary academic medical center in Riyadh, Saudi Arabia SUBJECTS AND METHODS: This study included patients who had cancer and received ceftazidime-avibactam for at least 72 hours for infections caused by OXA-48- and/or NDM-producing Enterobacterales. We excluded patients who died within 72 hours of treatment, patients with polymicrobial infections, and patients who did not receive appropriate antimicrobial therapy. MAIN OUTCOMES AND MEASURES: Primary outcomes were 30-day mortality and hospital mortality. Secondary outcomes included clinical cure, relapse, and reinfection. SAMPLE SIZE: 32 cancer patients RESULTS: The 30-day mortality among all patients was 15/32 (47%), clinical cure was achieved in 19/32 (59%) of the patients, and the relapse and reinfection rates were 2/19 (10.5%) and 4/17 (23.5%), respectively. CONCLUSION: This is the largest study to evaluate clinical outcomes associated with infections caused by OXA-48- and/or NDM-producing Enterobacterales in cancer patients. The mortality rate remains high; however, ceftazidime-avibactam is an encouraging alternative for treating severe infections in cancer patients. LIMITATIONS: Small sample size and single center.

Abstract Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9–12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush–Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: −6.68; 95% CI: −8.23, −5.14), CGI-S (MD: −1.27; 95% CI: −1.73, −0.81), and NPITS scores (MD: −6.50; 95% CI: −7.53, −5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ 2 = 11.82, P = 0.001), abnormal MRI (χ 2 = 7.78, P = 0.005), and abnormal LP (χ 2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P