A renewably sourced, circular photopolymer resin for additive manufacturing.

The additive manufacturing of photopolymer resins by means of vat photopolymerization enables the rapid fabrication of bespoke 3D-printed parts. Advances in methodology have continually improved resolution and manufacturing speed, yet both the process design and resin technology have remained largely consistent since its inception in the 1980s1. Liquid resin formulations, which are composed of reactive monomers and/or oligomers containing (meth)acrylates and epoxides, rapidly photopolymerize to create crosslinked polymer networks on exposure to a light stimulus in the presence of a photoinitiator2. These resin components are mostly obtained from petroleum feedstocks, although recent progress has been made through the derivatization of renewable biomass3-6 and the introduction of hydrolytically degradable bonds7-9. However, the resulting materials are still akin to conventional crosslinked rubbers and thermosets, thus limiting the recyclability of printed parts. At present, no existing photopolymer resin can be depolymerized and directly re-used in a circular, closed-loop pathway. Here we describe a photopolymer resin platform derived entirely from renewable lipoates that can be 3D-printed into high-resolution parts, efficiently deconstructed and subsequently reprinted in a circular manner. Previous inefficiencies with methods using internal dynamic covalent bonds10-17 to recycle and reprint 3D-printed photopolymers are resolved by exchanging conventional (meth)acrylates for dynamic cyclic disulfide species in lipoates. The lipoate resin platform is highly modular, whereby the composition and network architecture can be tuned to access printed materials with varied thermal and mechanical properties that are comparable to several commercial acrylic resins.

Effect of functional appliances on sleep-disordered breathing in Class II division 1 malocclusion children: Randomized controlled trial.

OBJECTIVES: A randomized controlled trial was undertaken to investigate the orthopaedic effect of functional appliances on the pharyngeal airway space and nocturnal breathing of children with skeletal class II due to mandibular retrusion. MATERIALS AND METHODS: Forty patients were randomized into a 1:1 ratio study (Twin block) group and a control (fixed appliance) group. Each group included equal numbers of boys and girls. Diagnosis with sleep-disordered breathing was not an inclusion criterion. The duration of the trial was 12 months (T0 - T12). Eligibility criteria included skeletal Class II division 1 malocclusion with mandibular retrognathism, SNA ≥82, SNB ≤78, ANB ≥4, overjet ≥6 mm, and patients in circumpubertal stage CVM2 and CVM3. The main outcomes were pharyngeal airway volume, oxygen desaturation index (ODI), and maximum expiratory pressure (MEP), while the secondary outcomes were skeletal and dental changes of the maxilla and mandible. Randomization was accomplished with random blocks of 20 patients with allocation concealed in sequentially numbered, opaque, and sealed envelopes. Blinding was only applicable for data analysis of radiographic measurements and data extracted from the pulse oximeter. RESULTS: The mean age of the patients was 10 ± 1.5 and 10 ± 1.2 at (T0) for the Twin Block and the control groups, respectively. The changes in the oropharyngeal (2.66 cc and 0.056; P = .03) and nasopharyngeal (1.3 cc and 0.84; P = .053) airway volumes for the Twin block and control groups, respectively, were significantly different for the oropharynx. There was a significant decrease in ODI by [median -3.55 (-5.05 to 0.50); P ≤ .001] and a significant increase [median 45 (0.0-110); P ≤ .001] in MEP for the Twin block group. A significant inverse correlation (r = -.589; P = .006) could be found between the total volume of the oropharynx and ODI. No serious harm was observed. CONCLUSIONS: The Twin block group showed significant change in oropharyngeal airway volume and improvement of nocturnal breathing. REGISTRATION: This trial was registered at https://www. CLINICALTRIALS: gov, registration number NCT04255511.

Gene Cloning, Heterologous Expression, and In Silico Analysis of Chitinase B from Serratia marcescens for Biocontrol of Spodoptera frugiperda Larvae Infesting Maize Crops.

Spodoptera frugiperda, the fall armyworm (FAW), is a highly invasive polyphagous insect pest that is considered a source of severe economic losses to agricultural production. Currently, the majority of chemical insecticides pose tremendous threats to humans and animals besides insect resistance. Thus, there is an urgent need to develop new pest management strategies with more specificity, efficiency, and sustainability. Chitin-degrading enzymes, including chitinases, are promising agents which may contribute to FAW control. Chitinase-producing microorganisms are reported normally in bacteria and fungi. In the present study, Serratia marcescens was successfully isolated and identified from the larvae of Spodoptera frugiperda. The bacterial strain NRC408 displayed the highest chitinase enzyme activity of 250 units per milligram of protein. Subsequently, the chitinase gene was cloned and heterologously expressed in E. coli BL21 (DE3). Recombinant chitinase B was overproduced to 2.5-fold, driven by the T7 expression system. Recombinant chitinase B was evaluated for its efficacy as an insecticidal bioagent against S. frugiperda larvae, which induced significant alteration in subsequent developmental stages and conspicuous malformations. Additionally, our study highlights that in silico analyses of the anticipated protein encoded by the chitinase gene (ChiB) offered improved predictions for enzyme binding and catalytic activity. The effectiveness of (ChiB) against S. frugiperda was evaluated in laboratory and controlled field conditions. The results indicated significant mortality, disturbed development, different induced malformations, and a reduction in larval populations. Thus, the current study consequently recommends chitinase B for the first time to control FAW.

The pre-conception maternal exposure to Sofosbuvir affects the mitochondrial biogenesis in prenatal fetal tissues: Experimental study on rats.

BACKGROUND: Hepatitis C virus (HCV) infection is a global public health problem and Egypt has the highest HCV prevalence worldwide. Hence, global efforts target to eliminate HCV by 2030. Sofosbuvir is a nucleotide analogue inhibitor of HCV polymerase essential for viral replication. Animal studies prove that Sofosbuvir metabolites cross the placenta and are excreted in the milk of nursing animals. We aimed to investigate the possible effects of preconception maternal exposure to Sofosbuvir on mitochondrial biogenesis in prenatal fetal liver, skeletal muscle, and placental tissues. METHODS: The study was conducted on 20 female albino rats divided into a control group receiving a placebo and an exposed group receiving 4 mg/kg orally/day for 3 months of Sofosbuvir. At the end of the treatment period, pregnancy was induced in both groups by mating with healthy male rats overnight. At gestational day 17, all pregnant female rats were sacrificed. Each fetus was dissected to obtain the fetal liver, skeletal muscle, and placental tissues. RESULTS: The results of our study indicated that the exposure of young female rats to Sofosbuvir affects pregnancy outcomes. Fetal liver and muscle showed lower mitochondrial DNA-copy number (mtDNA-CN) by about 24% and 29% respectively, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and its downstream targets; nuclear respiratory factor-1 and mitochondrial transcription factor A. While the placental tissues showed different patterns, particularly elevated in mtDNA-CN by about 43%. CONCLUSIONS: The study provides preliminary evidence of the detrimental effects of Sofosbuvir on the pregnancy outcomes of the exposed females and may impair the placental and fetal organs' development. These effects may be mediated through modulating mitochondrial homeostasis and functions.

QuantiFERON-CMV and monitor predict cytomegalovirus, mortality, and graft-versus-host disease in transplant recipients.

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON-CMV (QF-CMV) and QuantiFERON-Monitor (QFM) assays were used to test whether immune-competent adult allogeneic HSCT recipients with CMV-specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV-antigenemia test and QF-CMV results, graft versus host disease (GvHD), and mortality rates. The QF-CMV test revealed that CMV-specific T cells with higher interferon-γ (IFN-γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF-CMV results, GvHD, and mortality rates. Data showed that a one-unit rise in IFN-γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF-M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF-CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre-emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre-emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.

Prevalence of bruxism in down syndrome patients: A systematic review and meta-analysis.

BACKGROUND: Bruxism is a parafunctional activity characterised by grinding or clenching of teeth and is a common oral health concern in individuals with down syndrome (DS). Understanding the prevalence of bruxism in this population is crucial for developing effective management strategies. This systematic review and meta-analysis is aimed to investigate the prevalence of bruxism among individuals with DS and explore its association with other oral health issues. METHODS: A comprehensive search was conducted across multiple electronic databases to identify relevant studies. Cross-sectional and observational studies were included. Data on bruxism prevalence and associated factors were extracted, and a meta-analysis was performed using both fixed-effects (FE) and random-effects (RE) models of MedCalc software. Heterogeneity among studies was assessed using I2 statistics. New Castle-Ottawa Scale was used to evaluate methodological quality of the included studies. RESULTS: Eight studies met the pre-defined inclusion criteria and were included in the analysis. Seven studies used a questionnaire to assess bruxism. The pooled proportion estimate for occurrence of DS across the included studies was found to be 0.33 (95% CI: 0.22-0.45) as per the RE model and 0.35 (95% CI: 0.31-0.450) as per FE model in the quantitative analysis. All studies exhibited good methodological quality. CONCLUSION: This systematic review and meta-analysis provide evidence of a significant prevalence of bruxism among individuals with DS. The findings highlight the association of bruxism with other oral health issues and specific chromosomal abnormalities. Comprehensive oral health assessments, including diagnostic procedures like Polysomnography, are essential for addressing the unique oral health needs of individuals with DS. Further studies are recommended with a valid tool for the diagnosis. Early interventions and management strategies need to be tailored to this population, considering the multifaceted nature of oral health concerns in individuals with DS.

Direct-Acting Antiviral Drug Modulates the Mitochondrial Biogenesis in Different Tissues of Young Female Rats.

(1) Background: Hepatitis C virus (HCV) infection is endemic in Egypt, with the highest prevalence rate worldwide. Sofosbuvir (SOF) is a nucleos(t)ide analog that specifically inhibits HCV replication. This study aimed to explore the possible effects of the therapeutic dose of SOF on the mitochondrial biogenesis and functions of the liver, muscle, and ovarian tissues of young normal female rats. (2) Methods: This study was conducted on 20 female Wistar rats, classified into two groups, the control group and the exposed group; the latter was orally supplemented with 4 mg/kg/day of SOF for 3 months. (3) Results: The exposure to SOF impairs mitochondrial biogenesis via mitochondrial DNA copy number decline and suppressed mitochondrial biogenesis-regulated parameters at mRNA and protein levels. Also, SOF suppresses the DNA polymerase γ (POLG) expression, citrate synthase activity, and mitochondrial NADH dehydrogenase subunit-5 (ND5) content, which impairs mitochondrial functions. SOF increased lipid peroxidation and oxidative DNA damage markers and decreased tissue expression of nuclear factor erythroid 2-related factor 2 (Nfe2l2). (4) Conclusions: The present findings demonstrate the adverse effects of SOF on mitochondrial biogenesis and function in different tissues of young female rats, which mostly appeared in ovarian tissues.

The Intergeneration Long-Lasting Consequences of Pre-Conceptional Exposure to Sofosbuvir on the Ovarian Tissues of F1 Offspring: Experimental Study on Rats.

Sofosbuvir (SOF), a nucleos(t)ide polymerase inhibitor, has been used during the past decade for mass treatment of viral hepatitis C in endemic countries like Egypt, increasing the exposure of women at childbearing age to SOF. This study investigated the long-lasting consequences of the pre-conceptional exposure of young female rats to SOF on the ovarian tissues of F1 offspring and explored the possible molecular mechanisms of these intergenerational effects at various levels. The study was conducted on young female rats that were divided into control group and SOF-exposed group at a dose of 4 mg/kg/day for three months. After that, pregnancy was induced in both groups by mating with healthy male rats. After delivery, the female neonates were followed for 4 months, and the ovarian tissues were collected to assess the studied parameters. Pre-conceptional exposure to SOF affected the ovarian functions of F1 offspring through modulation of estrogen receptors, ovarian Kiss1 and its receptor, increased lipid peroxidation marker, DNA oxidation marker, and redox-sensitive nuclear factor kappa B, and decreased nuclear erythroid-2-related factor 2, mitochondrial function, and biogenesis. SOF affected the ovarian function of the F1 offspring by inducing oxidative stress and inflammation, leading to the modulation of mitochondrial functions and biogenesis.

The Anti-Obesity and Anti-Steatotic Effects of Chrysin in a Rat Model of Obesity Mediated through Modulating the Hepatic AMPK/mTOR/lipogenesis Pathways.

BACKGROUND: Obesity is a complex multifactorial disease characterized by excessive adiposity, and is linked to an increased risk of nonalcoholic fatty liver disease (NAFLD). Flavonoids are natural polyphenolic compounds that exert interesting pharmacological effects as antioxidant, anti-inflammatory, and lipid-lowering agents. In the present study, we investigated the possible therapeutic effects of the flavonoid chrysin on obesity and NAFLD in rats, and the role of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathways in mediating these effects. METHOD: Thirty-two Wistar male rats were divided into two groups: the control group and the obese group. Obesity was induced by feeding with an obesogenic diet for 3 months. The obese rats were subdivided into four subgroups, comprising an untreated group, and three groups treated orally with different doses of chrysin (25, 50, and 75 mg/kg/day for one month). Results revealed that chrysin treatment markedly ameliorated the histological changes and significantly and dose-dependently reduced the weight gain, hyperglycemia, and insulin resistance in the obese rats. Chrysin, besides its antioxidant boosting effects (increased GSH and decreased malondialdehyde), activated the AMPK pathway and suppressed the mTOR and lipogenic pathways, and stimulated expression of the genes controlling mitochondrial biogenesis in the hepatic tissues in a dose-dependent manner. In conclusion, chrysin could be a promising candidate for the treatment of obesity and associated NAFLD, aiding in attenuating weight gain and ameliorating glucose and lipid homeostasis and adipokines, boosting the hepatic mitochondrial biogenesis, and modulating AMPK/mTOR/SREBP-1c signaling pathways.

Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Silymarin inhibits the progression of Ehrlich solid tumor via targeting molecular pathways of cell death, proliferation, angiogenesis, and metastasis in female mice.

BACKGROUND: Plant-derived phytochemicals have been reported to exert anticancer activity. This study investigated the antitumor role of silymarin (Silybum marianum) (SMN) and its molecular targets in Ehrlich solid tumor xenografts in vivo. METHODS AND RESULTS: Female Swiss albino mice were divided into three groups (of five animals each) that were engrafted with Ehrlich tumor (ET) cells with or without SMN treatment. The 3rd groups treated with DMSO only vehicle control group. A significant reduction in animal body mass and tumor volume/weight were observed in xenografted mice treated with SMN. SMN modulated oxidative stress in tumors while enhancing the antioxidant levels in mouse serum. SMN activated both mitochondrial and death receptor-related apoptosis pathways and induced cell cycle arrest, marked by a significant downregulation of cyclin D1 in SMN-treated tumors. Significant decreases in RNA content and protein expression levels of Ki-67 and proliferating cell nuclear antigen were observed in ET cells. Additionally, SMN downregulated vascular endothelial growth factor and nuclear factor-kappa B levels indicating anti-angiogenesis activity of this agent. SMN upregulated the expression of E-cadherin in tumor tissue suggesting, that SMN has potential ability to inhibit metastasis. Tumor tissue from SMN-treated animals showed a remarkable degeneration and reduction in the neoplastic cell density. CONCLUSIONS: The anticancer effect was associated with apparent apoptosis in neoplastic cells with abundance of multifocal necrotic areas. SMN was found to inhibit ET growth via enhancing apoptosis, inhibition of cell division and reduction in angiogenesis in vivo. Hypothetical scheme of SMN antitumor effects (mechanism of signaling) in solid ET in vivo. SMN anticancer effect may be mediated by molecular mediators that affect proliferation, cell cycle activity, apoptotic pathways, angiogenesis, and metastasis.

Assessment of the protective effect of yeast cell wall ß-glucan encapsulating humic acid nanoparticles as an aflatoxin B1 adsorbent in vivo.

This study aimed to assess the protective effect of encapsulating humic acid-iron complexed nanoparticles (HA-Fe NPs) inside glucanmannan lipid particles (GMLPs) extracted from yeast cell wall against aflatoxin B (AFB1 ) toxicity in vivo. Four groups of male Sprague-Dawley rats were treated orally for 2 weeks included the control group, AFB1 treated group (80 µg/kg b.w); GMLP/HA-Fe NPs treated group (0.5 mg/kg b.w), and the group treated with AFB1 plus GMLP/HA-Fe NPs. GMLPs are empty 3-4 micron permeable microspheres that provide an efficient system for the synthesis and encapsulation of AFB1 -absorbing nanoparticles (NPs). Humic acid nanoparticles (HA-NPs) were incorporated inside the GMLP cavity by complexation with ferric chloride. In vivo study revealed that AFB1 significantly elevated serum alanine aminotransferase, aspartate aminotransferase, creatinine, uric acid, urea, cholesterol, triglycerides, LDL, malondialdehyde, and nitric oxide. It significantly decreased total protein, high-density lipoprotein, hepatic and renal CAT and glutathione peroxidase content and induced histological changes in the liver and kidney (p ≤ 0.05). The coadministration of the synthesized formulation GMLP/HA-Fe NPs with AFB1 has a protective effect against AFB1 -induced hepato-nephrotoxicity, oxidative stress and histological alterations in the liver and kidney.

Green Synthesis of Silymarin-Chitosan Nanoparticles as a New Nano Formulation with Enhanced Anti-Fibrotic Effects against Liver Fibrosis.

BACKGROUND: Silymarin (SIL) has long been utilized to treat a variety of liver illnesses, but due to its poor water solubility and low membrane permeability, it has a low oral bioavailability, limiting its therapeutic potential. AIM: Design and evaluate hepatic-targeted delivery of safe biocompatible formulated SIL-loaded chitosan nanoparticles (SCNPs) to enhance SIL's anti-fibrotic effectiveness in rats with CCl4-induced liver fibrosis. METHODS: The SCNPs and chitosan nanoparticles (CNPs) were prepared by ionotropic gelation technique and are characterized by physicochemical parameters such as particle size, morphology, zeta potential, and in vitro release studies. The therapeutic efficacy of successfully formulated SCNPs and CNPs were subjected to in vivo evaluation studies. Rats were daily administered SIL, SCNPs, and CNPs orally for 30 days. RESULTS: The in vivo study revealed that the synthesized SCNPs demonstrated a significant antifibrotic therapeutic action against CCl4-induced hepatic injury in rats when compared to treated groups of SIL and CNPs. SCNP-treated rats had a healthy body weight, with normal values for liver weight and liver index, as well as significant improvements in liver functions, inflammatory indicators, antioxidant pathway activation, and lipid peroxidation reduction. The antifibrotic activities of SCNPs were mediated by suppressing the expression of the main fibrosis mediators TGFßR1, COL3A1, and TGFßR2 by boosting the hepatic expression of protective miRNAs; miR-22, miR-29c, and miR-219a, respectively. The anti-fibrotic effects of SCNPs were supported by histopathology and immunohistochemistry (IHC) study. CONCLUSIONS: According to the above results, SCNPs might be the best suitable carrier to target liver cells in the treatment of liver fibrosis.

Ameliorative effects of astaxanthin on brain tissues of alzheimer's disease-like model: cross talk between neuronal-specific microRNA-124 and related pathways.

Alzheimer's disease (AD) is a chronic, progressive, multifactorial, and the most common neurodegenerative disease which causes dementia and mental deterioration in the elderly. The available treatments for AD are not disease-modifying drugs and only provide symptomatic relief. Astaxanthin (ATX), a second-generation antioxidant, is a dark red carotenoid and exhibits the highest antioxidant capacity, anti-inflammatory, neuroprotective, and antiapoptotic effects. In this study, we investigated the therapeutic effect of different doses of ATX on the cerebral cortex and hippocampus of AD-like rats. The AD-like model was induced in rats using hydrated aluminum chloride (AlCl3.6H2O) solution that was given orally at a dose of 75 mg/kg daily for 6 weeks. Morris water maze (MWM) behavioral test was performed to confirm the cognitive dysfunction then AD-like rats were orally treated with different doses of ATX (5, 10, and 15 mg/kg) dissolved in dimethyl sulfoxide (DMSO) for six weeks. The results indicated that ATX significantly and dose-dependently improved the performance of AD-like rats treated with ATX during MWM and suppress the accumulation of amyloid ß1-42 and malondialdehyde. Also, significantly inhibit acetylcholinesterase and monoamine oxidase activities and the expression of ß-site amyloid precursor protein cleaving enzyme 1 (BACE 1). ATX also significantly elevated the content of acetylcholine, serotonin, and nuclear factor erythroid-2-related factor 2 (Nrf2) and miRNA-124 expression. The effect of ATX treatment was confirmed by histopathological observations using H&E stain and morphometric tissue analysis. From this study, we concluded that ATX may be a promising therapeutic agent for AD through targeting different pathogenic pathways.

Changing trends in seroprevalence rates of transfusion-transmitted diseases among blood donors in Jordan.

BACKGROUND: Hepatitis B and C infections and transmission are a serious challenge to all healthcare systems. We studied seroprevalence rates of Transfusion Transmitted Diseases (TTD) among blood bank donors in Jordan from 2014 to 2019 as a follow-up study of our previously published work. In addition, we wanted to explore the efficacy of the mandatory vaccination of infants against hepatitis B virus (HBV) which was implemented by the Ministry of Health since 1995 for the eradication of HBV infection in Jordan. METHODS: We reviewed blood bank donors' records at King Hussein Cancer Center (KHCC) from January 1st, 2014, until December 31st, 2019. Results of seropositivity prevalence rates for HBsAg, anti-HBcore, and anti-HCV, using Enzyme-Linked ImmunoSorbent Assay (ELISA) were compared to seropositivity rates from our previously published data. In addition, our results were compared to data obtained from other blood banks in Jordan, as well as compared to published information from blood banks in neighboring countries. RESULTS: The prevalence rates (%) of seropositive blood donors for viral hepatitis for the years 2014, 2015, 2016, 2017, 2018, and 2019, were as follows: HBsAg rates were 0.3386, 0.2108, 0.1801, 0.1898, 0.2068, and 0.2741; anti-HBcore rates were 4.1112, 3.2271, 2.9748, 2.8405, 2.6879 and 3.0986; and anti-HCV rates were 0.1129, 0.0486, 0.0548, 0.0654, 0.0782, and 0.0839, respectively. There was a significant increase in the prevalence of HBsAg, Anti-HBcore and Anti-HCV antibodies in 2019 (one sample z-score test, p < 0.00001). CONCLUSIONS: Prevalence rates of hepatitis B and C infections among Jordanian blood bank donors showed a steady decline between 2009 and 2017, and these rates were much lower in Jordan than in neighboring countries. However, an increase in the prevalence rates of hepatitis B and C infections among blood bank donors was documented in 2019. While the reasons for this increase are not clear yet, these findings highlight the importance of renewed efforts to increase public health awareness of HBV and implement effective measures to prevent the transmission and infection with HBV, including national vaccination programs.

Eco-friendly sequential one-pot synthesis, molecular docking, and anticancer evaluation of arylidene-hydrazinyl-thiazole derivatives as CDK2 inhibitors.

One current approach in the treatment of cancer is the inhibition of cyclin dependent kinase (CDK) enzymes with small molecules. CDK are a class of enzymes, which catalyze the transfer of the terminal phosphate of a molecule of ATP to a protein that acts as a substrate. Among CDK enzymes, CDK2 has been implicated in a variety of cancers, supporting its potential as a novel target for cancer therapy across many tumor types. Here the discovery and development of arylidene-hydrazinyl-thiazole as a potentially CDK2 inhibitors is described, including details of the design and successful synthesis of the series analogs (27a-r) using one-pot approach under eco-friendly ultrasound and microwave conditions. Most of the newly synthesized compounds showed good growth inhibition when assayed for their in-vitro anti-proliferative activity against three cancer cell lines (HepG2, MCF-7 and HCT-116) compared to the reference drug roscovitine, with little toxicity on the normal fibroblast cell lines (WI-38). Furthermore, the compounds exhibiting the highest anti-proliferative activities were tested against a panel of kinase enzymes. These derivatives displayed an outstanding CDK2 inhibitory potential with varying degree of inhibition in the range of IC50 0.35-1.49 µM when compared with the standard inhibitor roscovitine having an IC50 value 0.71 µM. The most promising CDK2 inhibitor (27f) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in HepG2 cell line. The results indicated that this compound implied inhibition in the G2/M phase of the cell cycle, and it is a good apoptotic agent. Finally, Molecular docking study was performed to identify the structural elements which involved in the inhibitory activity with the prospective target, CDK2, and to rationalize the structure-activity relationship (SAR).

Design, synthesis, molecular docking and in silico ADMET profile of pyrano[2,3-d]pyrimidine derivatives as antimicrobial and anticancer agents.

Pyrano[2,3-d]pyrimidine derivatives were synthesized by treating cyclic compounds containing active methylene group with aldehyde and malononitrile in butanol. The behavior of pyrano[2,3-d]pyrimidine towards some electrophlies namely triethylorthoformate followed by nitrogen nucleophiles as isobutylamine, urea, phenylthiourea, p-toluidine, o-phenylenediamine, o-aminophenol, 2-amino-4-methyl-pyridine and acetic acid with the aim of obtaining some interesting non-mixed heterocyclic compounds. All synthesized compounds to some extent have shown good antimicrobial activity against different microbial strains that had been extracted by inhibiting cell wall synthesis. Compound 5b showed the highest antibacterial activities against B. subtilis, S. aureus and E. coli. On the other hand compound 5 g exhibited the highest antibacterial and antifungal activities against P. aeruginosa and A. niger respectively. In addition, they explore cytotoxic potentialities against different cell lines via DNA intercalation and Top-II inhibition. The cytotoxic activities clarify the strong inhibitory activity of derivative 5a against HepG2 cells with IC50 = 2.09 µM, while HCT-116 cells were highly susceptible to derivative 5c with IC50 = 2.61 µM, in the meantime, derivative 5f showed pronounced negative impact against MCF-7 (IC50 = 2.43 µM) when compared with other prepared compounds. All derivatives exhibited higher anticancer activities than doxorubicin against the three cell lines except compound 2 against both HepG2 and MCF-7 and compound 5e against HepG2 cell lines. Compounds 5a, 5c and 5f potently intercalate DNA at IC50 values of 26.96, 27.13 and 29.86 µM respectively, which were more potent than doxorubicin (IC50 value of 31.27 µM). Moreover, compounds 5a, 5c and 5f exhibited very good Topoisomerase II inhibitory activities with IC50 values of 0.752, 0.791 and 0.776 µM respectively, that were more potent than that of doxorubicin (IC50 = 0.94 µM). For a great extent, the molecular modeling studies were in agreement with that of in vitro cytotoxicity activity, DNA binding and Top-II inhibition results.

Effects of Computerised Clinical Decision Support on Adherence to VTE Prophylaxis Clinical Practice Guidelines among Hospitalised Patients.

OBJECTIVE: Venous thromboembolism (VTE) is an important patient safety concern. VTE leads to significant mortality and morbidity and a burden on healthcare resources. Despite the widespread availability of evidence-based clinical practice guidelines on VTE prophylaxis, we found that only 50.9% of our patients were receiving appropriate prophylaxis. The purpose of this study was to evaluate the impact of automation of an adapted VTE prophylaxis CPG using a clinical decision support system (the VTE-CDSS) on VTE prevention among hospitalised adult patients. DESIGN AND SETTING: A quasi-experimental study (pre- and post-implementation) was conducted at a large 900-bed tertiary teaching multi-specialty hospital in Riyadh, Saudi Arabia. PARTICIPANTS: The 1809 adult patients in the study included 871 enrolled during the pre-implementation stage and 938 enrolled during the post-implementation stage. INTERVENTION: Multi-faceted implementation interventions were utilised, including leadership engagement and support, quality and clinical champions, staff training and education and regular audit and feedback. MAIN OUTCOME MEASURE: Two rate-based process measures were calculated for each admission cohort (i.e. pre- and post-implementation): the percentage of inpatients who were assessed for VTE risk on admission and the percentage of inpatients who received appropriate VTE prophylaxis. Two outcome measures were calculated: the prevalence of hospital-acquired VTE (HA-VTE) events and the in-hospital all-cause mortality. RESULTS: The percentage of inpatients risk assessed for VTE on admission increased from 77.4% to 93.3% (P < 0.01). The percentage of patients who received appropriate VTE prophylaxis increased from 50.9% to 81.4% (P < 0.01). The HA-VTE events decreased by 50% from 0.33% to 0.15% (P < 0.01).All-cause in-hospital mortality did not significantly change after implementation of the VTE-CDSS compared with pre-implementation mortality (P > 0.05). CONCLUSION: The VTE-CDSS improved patient safety by enhancing adherence to the VTE prophylaxis best practice and adapted CPG. The multi-faceted implementation strategies approach improved the compliance rate of risk assessment and the adherence to prophylaxis recommendations and substantially reduced the HA-VTE prevalence. A successful CDSS requires a set of critical components to ensure better user compliance and positive patient outcomes.

Expression of PD-L1 using SP142 CDx in triple negative breast cancer.

Triple negative breast cancer (TNBC) represents a small subtype of breast cancer yet it has the worst outcome. Immunotherapy using immune checkpoint inhibitors combined with chemotherapy was recently approved by the FDA raising the hope for an improved outcome. The approval was based on demonstration of a positive PD-L1 expression using the SP142 CDx assay 1. We aimed to study a cohort of TNBC patients in terms of prevalence of the PD-L1 expression using the approved assay and to investigate its association with clinicopathological variables. This is a single center retrospective study consisting of 49 TNBC patients who had available archived paraffin-embedded tissue blocks from the primary tumors. All blocks were stained using the SP142 CDx assay as per the manufacture's instruction. Clinicopathological data were collected from medical records. Eighteen of the 49 (36.7%) patients were found to have a score of 1% or more by the immune cell-scoring algorithm. PDL-1 expression was significantly associated with the degree of tumor infiltrating lymphocytes (TILs). No additional significant relationship was found between PD-L1 expression and any of the other investigated clinicopathological variables. Although a trend of favorable prognostic association with PD-L1 expression was noted. The overall and event free survival were significantly related to pathological response to neoadjuvant therapy. Conclusion: Our PD-L1 rate of 36.7% is close to the results of the previously reported 40.9% in the IMpassion 130 trial. There were no significant association between positive PD-L1 expression and clinicopathological variables however a trend of a favorable outcome was observed.

Nanoformulated ellagic acid ameliorates pentylenetetrazol-induced experimental epileptic seizures by modulating oxidative stress, inflammatory cytokines and apoptosis in the brains of male mice.

The present study evaluated the neuroprotective and antiepileptic efficacy of ellagic acid (EA) encapsulated in calcium-alginate nanoparticles (Ca2+-ALG NPs) in pentylenetetrazol (PTZ)-induced seizures in male mice. EA was encapsulated in ALG NPs using a nanospray drying method followed by ionotropic crosslinking with Ca2+. Characterization of the developed Ca2+-crosslinked EA-ALG NPs showed spherical, high stability NPs; successful loading of EA within crosslinked ALG NPs; and sustained release of EA. Male Swiss albino mice were divided into ten groups as follows; Group I- (control), Group II (50 mg EA /kg) - (EA), Group III polyethylene glycol (PEG), Group IV EA NPs (50 mg/kg) - (EA NP), Group (50 mg/kg alginate) V void V NPs - (void NPs), Group VI: (37.5 PTZ mg/kg) -(PTZ), Group VII: PTZ and EA - (PTZ-EA). Group VIII: animals received PTZ and PEG concurrently (PTZ-PEG). Group IX; animals received PTZ and void NPs concurrently - (PTZ-void). Group X: animals received PTZ and EA NPs concurrently (PTZ-EA NPs). PTZ was used to induce experimental epilepsy. Ca2+-ALG NPs prevented seizures throughout the experimental period and had a more prominent effect than free EA did. Ca2+-ALG NPs prevented increased glutamate, decreased GABA concentrations and ameliorated increased amyloid-ß and homocysteine levels in the serum and brain. Ca2+-EA-ALG NPs were superior to free EA in improving increased IL-6 and TNF-α. Ca2+-ALG NPs ameliorated PTZ-induced oxidative stress, as evidenced by decreased 4HNE levels and enhanced GSH, GR and GPx levels in the brain. These changes were accompanied by amelioration of apoptosis and its regulating proteins, including Cytochrome C, P53, Bax, Bcl2 and caspase-3 and caspase-9, and protected against DNA damage. Histological examination of the hippocampus confirmed that the neuroprotective effect of Ca2+-EA-ALG NPs was superior and more effective than that of free EA.