The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model.

Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.

Physicomechanical characterizations and in vitro release studies of electrospun ethyl cellulose fibers, solvent cast carboxymethyl cellulose films, and their composites.

Frequent change of wound dressings introduces wound inflammation and infections. In this study, we electrospun phenytoin (PHT) loaded ethyl cellulose (EC) microfibers and solvent cast tetracycline hydrochloride (TCH) loaded carboxymethyl cellulose (CMC) films with the aim to demonstrate tailorable in vitro drug release behaviors suitable for long-term use of wound dressings. Results from tensile testing showed a significant decrease in average elastic moduli from 8.8 ± 0.6 to 3.3 ± 0.3 MPa after incorporating PHT into EC fibers. PHT-loaded EC fibers displayed a slow and zero-ordered release up to 80 % of the total drug at 48 h, while TCH-loaded CMC films demonstrated a rapid and complete release within 30 min. Furthermore, drug-loaded EC/CMC composites were fabricated into fiber-in-film and fiber-on-film composites. Fiber-in-film composites showed stage release of TCH and PHT at 8 h, while fiber-on-film composites demonstrated simultaneous release of PHT and TCH with a prolonged release of TCH from CMC films. In general, electrospun PHT-loaded EC microfibers, solvent cast TCH-loaded CMC films, and their composites were studied to provide a fundamental scientific understanding on the novelty of the ability to modulate drug release characteristics based on the composite designs.

Effects of 5-fluorouracil, thymoquinone, and mammary stem cells' exosomes on in vitro cultured breast cancer cells.

Background: 5-fluorouracil (5-FU) is an antimetabolic agent used for treating slowly growing solid tumors like breast and ovarian carcinoma. Thymoquinone (TQ) is the main biologically active constituent of Nigella sativa, it has been found to demonstrate anticancerous effects in several preclinical studies, and this is because TQ possesses multitarget nature. Stem cells-derived exosomes are in the spotlight of research and are promising tissue regenerative and anticancer cell-derived nanovesicles. Aim: Herein, we studied the antineoplastic effects of Exosomes derived from mammary stem cells (MaSCs-Exo) on breast cancer cells, alone or combined with TQ when compared to a breast cancer chemotherapeutic agent; 5-FU. Methods: Our approach included performing viability test and measuring the expression of pro-apoptotic gene (Bax), anti-apoptotic gene (BCL-2) and angiogenic gene (VEGF) on Human MCF-7 cells (breast adenocarcinoma cells), the MCF-7 cells were cultured and incubated with medium containing 5-FU (25 µg/ml), TQ (200 µg/ml), MaSCs-Exo (100 µg protein equivalent), a combination of TQ (200 µg/ml) and MaSCs-Exo (100 µg). Results: Our obtained results show that TQ and MaSCs-Exo each can effectively inhibit breast cancer cell line (MCF-7) proliferation and growth. Also, the results show that the combination of TQ and MaSCs-Exo had higher cytotoxic effects on MCF-7 breast cancer cells than TQ or 5-FU, alone. Conclusion: The present study shows a promising anticancer potential of exosomes isolated from mammary stem cells; this effect was potentiated by adding TQ with MaSCs-derived exosomes.

Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post-COVID-19 pulmonary fibrosis.

BACKGROUND: Rho kinase (ROCK) pathway plays a critical role in post-COVID-19 pulmonary fibrosis (PCPF) and its intervention with angiotensin-converting enzyme 2 (ACE2) and vascular endothelial growth factor (VEGF) will be a potential therapeutic target. OBJECTIVES: The present study was conducted to investigate the efficacy of zoledronate (ZA) on carbon tetrachloride (CCl4) induced pulmonary fibrosis (PF) in rats through targeting ACE2, ROCK, and VEGF signaling pathways. METHODS: Fifty male Wistar rats were divided into five groups: control, vehicle-treated, PF, PF-ZA 50, and PF-ZA 100 groups. ZA was given in two different doses 100 and 50 µg/kg/week intraperitoneally. After anesthesia, mean arterial blood pressure (MBP) was measured. After scarification, lung coefficient was calculated. Lung levels of ACE 2, interleukin-1ß (IL-1ß), transforming growth factor-ß (TGF-ß), VEGF, glutathione (GSH), and superoxide dismutase (SOD) were measured. Expression of ROCK, phosphorylated myosin phosphatase target subunit 1 (P-MYPT1), and matrix metalloproteinase (MMP-1), along with histopathological changes and immune-histochemical staining for lung α-smooth muscle actin (α-SMA), tumor necrosis factor-alpha (TNFα), and caspase-3, were evaluated. RESULTS: ZA significantly prevented the decrease in MBP. ZA significantly increased ACE2, GSH, and SOD and significantly decreased IL-1ß, TGF-ß, and VEGF in lung in comparison to PF group. ZA prevented the histopathological changes induced by CCl4. ZA inhibited lung expression of ROCK, P-MYPT1, MMP-1, α-SMA, TNFα, and caspase-3 with significant differences favoring the high dose intervention. CONCLUSION: ZA in a dose-dependent manner prevented the pathological effect of CCl4 in the lung by targeting mevalonate pathway. It could be promising therapy against PCPF.

Biosynthesis and characterization of silver nanoparticles from Punica granatum (pomegranate) peel waste and its application to inhibit foodborne pathogens.

Polyphenolics have been predicted to effectively develop antimicrobial agents for the food industry as food additives and promote human health. This study aims to synthesize pomegranate peel extract (PPE) with silver nanoparticles (AgNPs) against eight foodborne pathogens. Multispectroscopic analysis of UV-vis spectroscopy, Zeta potential, Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) analysis were used to characterize the interaction between PPE and AgNPs. Eight foodborne pathogenic strains (six bacterial and two fungal strains) Bacillus subtilis ATCC 6633, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 8379, Klebsiella pneumoniae ATCC 00607, Salmonella typhi DSM 17058, Shigella sonnei DSM 5570, Aspergillus flavus ATCC 9643, and Rhizopus oryzae ATCC 96382 were used to test the inhibitory potential of PPW-AgNPs. The reaction colour of PPE-AgNPs from yellow to brown indicated that the nanoparticles were successfully formed. The UV absorption of PPE-AgNPs was detected at 440 nm of 0.9 SPR. SEM image of PPE-AgNPs exhibited spherical shapes with a zeta potential of - 20.1 mV. PPE-AgNPs showed high antimicrobial activity against all tested strains. The highest inhibition activity of PPE-AgNPs was recorded for the B. subtilis strain followed by K. pneumonia, while the highest resistance was noticed for R. oryzae. The components of pomegranate peel were analyzed using gas chromatography-mass spectrometry (GC-MS). The major constituents of pomegranate peel is phenol (51.1%), followed by Isocitronellol (19.41%) and 1-Propanol, 2-(2-hydroxypropyl)- (16.05%). PPE is key in the simple, eco-friendly green synthesis of extracellular stable AgNPs as an alternative source for harmful chemical disinfectants.

Mycobacterium tuberculosis epidemiology in Oman: whole-genome sequencing uncovers transmission pathways.

Tuberculosis (TB) originating from expatriates that hail from high TB-burden countries is hypothesized to play a role in continued TB transmission in Oman. Here, we used whole-genome sequencing (WGS) to assess national TB transmission dynamics. The annual incidence per 100,000 population per year was calculated for nationals and expatriates. A convenience sample of Mycobacterium tuberculosis (MTB) isolates from 2018 to 2019 was sequenced and analyzed with publicly available TB sequences from Bangladesh, Tanzania, the Philippines, India, and Pakistan. Relatedness was assessed by generating core-genome single nucleotide polymorphism (SNP) distances. The incidence of TB was five cases per 100,000 persons in 2018 and seven cases per 100,000 persons in 2020 (R2 = 0.34, P = 0.60). Incidence among nationals was 3.9 per 100,000 persons in 2018 and 3.5 per 100,000 persons in 2020 (R2 = 0.20, P = 0.70), and incidence among expatriates was 7.2 per 100,000 persons in 2018 and 12.7 per 100,000 persons in 2020 (R2 = 0.74, P = 0.34). Sixty-eight local MTB isolates were sequenced and analyzed with 393 global isolates. Isolates belonged to nine distinct spoligotypes. Two isolates, originating from an expatriate and an Omani national, were grouped into a WGS-based cluster (SNP distance < 12), which was corroborated by an epidemiological investigation. Relatedness of local and global isolates (SNP distance < 100) was also seen. The relatedness between MTB strains in Oman and those in expatriate countries of origin can aid inform TB control policy. Our results provide evidence that WGS can complement epidemiological analysis to achieve the End TB strategy goal in Oman. IMPORTANCE Tuberculosis (TB) incidence in Oman remains above national program control targets. TB transmission originating from expatriates from high TB-burden countries has been hypothesized to play a role. We used whole-genome sequencing (WGS) to assess TB transmission dynamics between expatriates and Omani nationals to inform TB control efforts. Available Mycobacterium tuberculosis isolates from 2018 to 2019 underwent WGS and analysis with publicly available TB sequences from Bangladesh, the Philippines, India, and Pakistan to assess for genetic relatedness. Our analysis revealed evidence of previously unrecognized transmission between an expatriate and an Omani national, which was corroborated by epidemiological investigation. Analysis of local and global isolates revealed evidence of distant relatedness between local and global isolates. Our results provide evidence that WGS can complement classic public health surveillance to inform targeted interventions to achieve the End TB strategy goal in Oman.

A comparative study between angiotensin receptor neprilysin inhibitor (thiorphan/irbesartan) with each of nitrate and carvedilol in a rat model of myocardial ischemic reperfusion injury.

The combined angiotensin receptor neprilysin inhibitor is a promising cardioprotective pharmacological agent. This study investigated the beneficial effects of thiorphan (TH)/irbesartan (IRB), in myocardial ischemia-reperfusion (IR) injury, compared to each of nitroglycerin and carvedilol. Male Wistar rats were divided into five groups (10 rats/group): Sham, untreated I/R, TH/IRB + IR (0.1/10 mg/kg), nitroglycerin + IR (0.2 mg/kg), and carvedilol + IR (10 mg/kg). Mean arterial blood pressure, cardiac functions and arrhythmia incidence, duration and score were assessed. Cardiac levels of creatine kinase-MB (CK-MB), oxidative stress, endothelin-1, ATP, Na+ /K+ ATPase pump activity and mitochondria complexes activities were measured. Histopathological examination, Bcl/Bax immunohistochemistry studies and electron microscopy examination of left ventricle were performed. TH/IRB preserved the cardiac functions and mitochondrial complexes activities, mitigated cardiac damage, reduced oxidative stress and arrhythmia severity, improved the histopathological changes and decreased cardiac apoptosis. TH/IRB showed a comparable effect to each of nitroglycerin and carvedilol in alleviating the IR injury consequences. TH/IRB showed significant preservation of mitochondrial complexes activity I and II compared to nitroglycerin. TH/IRB significantly increased LVdP/dtmax and decreased oxidative stress, cardiac damage and endothelin-1 along with increasing the ATP content, Na+ /K+ ATPase pump activity and mitochondrial complexes activity when compared to carvedilol. TH/IRB showed a cardioprotective effect in reducing IR injury that is comparable to each of nitroglycerin and carvedilol that could be explained in part by its ability to preserve mitochondrial function, increase ATP, decrease oxidative stress as well as endothelin 1.

Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model.

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis. METHODS: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding. RESULTS: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals. CONCLUSION: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.

Cyclosporine Ameliorates Silica-Induced Autoimmune Hepatitis in Rat Model by Altering the Expression of Toll-Like Receptor-4, Interleukin-2, and Tumor Necrosis Factor-α.

BACKGROUND: Autoimmune hepatitis (AIH) is an inflammatory liver disease that is characterized histologically by interface hepatitis, biochemically by elevated transaminase levels, and serologically by the presence of autoantibodies. Toll-like receptor (TLR)-4 is a TLR family member that, upon activation in hepatocytes, initiates a cascade of events. Interleukin-2 (IL-2) and tumour necrosis factor α (TNF-α) are potent inflammatory cytokines secreted in AIH, playing an important role in the early development of inflammation and hepatocyte damage. OBJECTIVES: This study examined the role of cyclosporine in AIH and illustrated its actions on altered hepatic function in the silica-induced AIH model. METHODS: AIH was induced in Wistar rats using sodium silicate. The rats were divided into four groups: the control group, silica-AIH group, cyclosporine-treated group, and prevention group. TLR-4 and IL-2 mRNA expressions in liver tissues were tested by RTPCR. RESULTS: AIH was associated with up-regulation of liver enzymes, IL-2 and TLR-4 gene expression, while cyclosporine significantly down-regulated the expression of both. The relative quantity of TLR-4 mRNA was 1±0, 13.57±1.91, 4±0.38, and 2±0 in control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Also, the relative quantity of IL-2 mRNA was 1±0, 14.79±1.42, 7.07±0.96, and 3.4±0.55 in control, AIH, cyclosporine, and prevention groups, respectively (p<0.001). Additionally, immunohistochemical staining for TNF-α in liver sections was increased in the silica-AIH group but was found to decrease in the cyclosporine-treated and prevention groups. CONCLUSION: This study advocates the therapeutic role of cyclosporine in treating immune-mediated hepatic diseases. Cyclosporine improves histological alterations in the liver and inhibits the production of proinflammatory cytokines.

Angiotensin receptor-neprilysin inhibitor (thiorphan/irbesartan) improved cardiac function in a rat model of myocardial ischemic reperfusion injury.

Mitochondria-mediated apoptosis plays a critical role in myocardial ischemia reperfusion (IR) injury and causes a negative impact on cardiac efficiency and function. The combined angiotensin receptor-neprilysin inhibitor (ARNI) is a promising cardioprotective pharmacological agent that could rescue the heart from IR injury. This study investigated the cardioprotective effect of thiorphan (TH) in combination with three different doses of irbesartan (IRB) on myocardial IR injury and detected the most effective dose combination. Male Wistar rats were used and divided into five groups (10 rats/group): (I) Sham, (II) ischemia-reperfusion I/R, (III) TH/IRB + IR (0.1/5 mg/kg), (IV) TH/IRB + IR (0.1/10 mg/kg), and (V) TH/IRB + IR (0.1/15 mg/kg) groups. Thiorphan and irbesartan were injected intraperitoneally 15 min before IR induction. Mean arterial blood pressure, left ventricular end diastolic pressure (LVEDP), left ventricular maximum rate of pressure (LVdp/dtmax ), and cardiac levels of creatine kinase-MB, malondialdehyde, superoxide dismutase, and endothelin-1 were measured. Cardiac mitochondria complexes activities, histopathological examination of myocardial tissues, immunohistochemistry studies for myocardial apoptosis (Bax and Bcl-2), and electron microscopy examination of left ventricle were performed. TH/IRB combination preserved cardiac functions and mitochondria complex activities and mitigated cardiac damage, oxidative stress, and apoptosis following IR. Also, there was an evident improvement in histopathological changes and electron microscopy examination of left ventricle compared with I/R group. TH/IRB in a dose of 0.1/10 mg/kg showed significant improvement compared with the other treated groups. Thiorphan/irbesartan improved cardiac functions following IR injury. This could be explained by the reported improvement of mitochondria complex activities and reduction of oxidative stress, endothelin-1, and apoptosis.

Prospective insight into the role of benzyl propylene glycoside as a modulator of the cGAS-STING signaling pathway in the management of nonalcoholic fatty pancreas animal model

BACKGROUND: Nonalcoholic fatty pancreatitis (NAFP) is one of the metabolic syndrome manifestations that need further studies to determine its molecular determinants and find effective medications. We aimed to investigate the potential effect of benzyl propylene glycoside on NAFP management via targeting the pancreatic cGAS-STING pathway-related genes (DDX58, NFκB1 & CHUK) and their upstream regulator miRNA (miR-1976) that were retrieved from bioinformatics analysis. METHODS: The rats were fed either normal chow or a high-fat high-sucrose diet (HFHS), as a nutritional model for NAFP. After 8 weeks, the HFHS-fed rats were subdivided randomly into 4 groups; untreated HFHS group (NAFP model group) and three treated groups which received 3 doses of benzyl propylene glycoside (10, 20, and 30 mg/kg) daily for 4 weeks, parallel with HFHS feeding. RESULTS: The molecular analysis revealed that benzyl propylene glycoside could modulate the expression of the pancreatic cGAS-STING pathway-related through the downregulation of the expression of DDX58, NFκB1, and CHUK mRNAs and upregulation of miR-1976 expression. Moreover, the applied treatment reversed insulin resistance, inflammation, and fibrosis observed in the untreated NAFP group, as evidenced by improved lipid panel, decreased body weight and the serum level of lipase and amylase, reduced protein levels of NFκB1 and caspase-3 with a significant reduction in area % of collagen fibers in the pancreatic sections of treated animals. CONCLUSION: benzyl propylene glycoside showed a potential ability to attenuate NAFP development, inhibit pancreatic inflammation and fibrosis and reduce the pathological and metabolic disturbances monitored in the applied NAFP animal model. The detected effect was correlated with modulation of the expression of pancreatic (DDX58, NFκB1, and CHUK mRNAs and miR-1976) panel.

Fifteen years' experience of radiation therapy for resected advanced heterotopic ossification following motor vehicle accidents: outcome and side effects.

BACKGROUND: Surgical resection is the primary treatment for advanced-stage heterotopic ossification (HO), with a high incidence of local recurrence reaching up to 50%. Postoperative radiotherapy (PORT) and indomethacin are commonly used prophylactic strategies following surgery. The study aims to assess the safety and effectiveness of PORT in advanced-stage HO patients having motor vehicle accidents (MVA). METHODS: Medical records of patients having HO following MVA between 2006 and 2021 were retrospectively reviewed. Thirty-nine patients with advanced disease (35 had hip HO and 4 had elbow HO) were included in the study. RESULTS: Excision of HO with joint preservation was performed for 82% of patients, while 18% had a joint replacement. Seven to 8 Gy radiation was given to all patients within 3 days postoperatively. A ninty seven percent of patients regained partially the movement range. The mean follow-up time was 74 months. Six patients had treatment failure, with only one having a recurrence of HO. The 8-year treatment failure-free rate (8-y TFFR) was 79.3±9%, and the 5-year HO failure-free rate (5y-HOFFR) was 97.2±3%. Acute side effects were experienced in 13% of patients but resolved without any consequences. Despite the relatively long follow-up time, we did not report any absolute infertility or secondary malignancies related to the radiation. The testicular mean calculated dose was 33±44 cGy, and the mean measured dose was 58±40 cGy. Of the 35 patients who received radiation to the pelvis, 26 were married, and all did not experience infertility post-treatment. CONCLUSION: PORT proved an effective and safe treatment for advanced-stage HO disease. The treatment failure is mainly related to surgical difficulties due to advanced disease. Treatment using a 3-dimensional or intensity-modulated radiation therapy is not associated with serious side effects like second malignancy or absolute infertility.

Factors Affecting Isocenter Displacement and Planning Target Volume Margin for Patients With Rectal Cancer Receiving Radiation Therapy.

Purpose: Setup errors are inherent in the process of daily radiation therapy (RT) delivery. Pelvic RT for rectal cancer is one of the body sites associated with the largest shift among other body sites. This study aimed to evaluate interfraction random and systematic errors and hence propose the optimum planning target volume (PTV) in patients with rectal cancer. Methods and Materials: Translational and angular isocenter displacements were retrospectively collected for 189 patients. Random and systematic errors were determined, and then the PTV margin was computed. Effect of positioning, body mass index (BMI), and type of immobilization were studied. Portal images before and after online correction were used to define PTV for no-daily image-guided radiotherapy (IGRT) and daily IGRT respectively. Results: Before the online correction, the systematic errors were 2.5, 2.8, and 3.0 mm for superior-inferior (SI), right-left (RL), and anterior-posterior (AP) directions, respectively, compared with 2.1, 1.7, and 1.8 mm after online correction. The random errors were 6.2, 7.4, and 8.2 mm in SI, RL, and AP, respectively, before online correction, compared with 4, 4.2, and 4.5 mm after online correction. The recommended PTV margin was 0.7 and 1.0 cm for daily IGRT and no-daily IGRT, respectively. The prone position and BMI >30 kg/m2 warrant higher margins in no-daily IGRT cases, 1.2 and 1.4 cm, respectively. Conclusions: The prone position, BMI >30 kg/m2, and belly board device are associated with larger daily setup errors warranting higher PTV margins for no-daily IGRT; however, that can be avoided by using daily IGRT.

Dosimetric effects of embolization material artefacts in arteriovenous malformations stereotactic radiosurgery on treatment planning calculation.

Background and Purpose: Stereotactic Radiosurgery (SRS) is a specialized radiotherapy treatment technique for Arteriovenous Malformations (AVM) in which Computed Tomography (CT) images are used for dose calculations. The purpose of this study was to investigate CT image distortions caused by embolic agents and quantify the influence of these distortions on dose calculations. Methods: Eight AVM patients administered embolic agents prior to SRS were included. Original plans were compared to new recalculated plans using two sets of images. The first set was created by masking the embolic material and artefacts, the second was the diagnostic CT images. In addition, treatment plans were created for an anthropomorphic phantom with water inserts, then with known volumes of embolic materials to study the dosimetric effect of each material. Results: Relative to patients' original plans, maximum Monitor Unit (MU) difference was -4.4% with whole brain masking, -1.3% with artefact masking, -4.1% with embolic masking, and -4.5% with artefact-free diagnostic images. Calculated dose differences were within ± 3.5% for all plans. In phantom, Gamma pass rate was 96% for both embolic agents with conformal fields and 99.9% with dynamic arcs. Dose and MU differences in phantom plans were negligible. Conclusion: Relative dose differences between the original plans and the corrected ones were not clinically remarkable. We recommend evaluating the effect of embolic materials on individual patients' plans. The whole brain corrected planning CT images or diagnostic CT images could be utilized to calculate the magnitude of dose reduction caused by embolic materials and correct it if necessary.

Treatment-seeking behaviour, awareness and preventive practice toward malaria in Abu Ushar, Gezira state, Sudan: a household survey experience from a rural area.

BACKGROUND: Usage of mosquito bed nets and the practice of other prevention methods are essential for the prevention of malaria in endemic areas. Proper community knowledge about malaria and prompt treatment-seeking behaviour for early diagnosis and treatment are crucial for eliminating the disease. This study aimed to assess the awareness, treatment-seeking behaviour, and prevention practices towards malaria in Abu Ushar, Gezira State, Sudan. METHODS: A community-based, cross-sectional study was conducted in March 2021, including 310 households in Abu Ushar, Aljazeera, Sudan. Data were collected through face-to-face interviews with head of the household using an interviewer-administered questionnaire. Data were entered and analysed using R software. RESULTS: A total of 310 households were enrolled in this study. Sixty per cent had children under the age of 5 years. The majority of these households (94.8%) had a history of malaria in the past 12 months. Overall, awareness of malaria was good; 197 (63.5%) households had bed nets in their houses; 75.8% of total households identified fever with shivering as a symptom of malaria. Regarding treatment-seeking behaviour, 77.9% seek treatment from the nearby primary health centre, and 60% seek treatment within the first day. Only 45.3% stated that everyone in the household sleeps under bed nets. CONCLUSION: High awareness about malaria and preventive measures was found among participants in households. Most households had previous infections with malaria. Therefore, an interventional programme should be established in this area to reduce this high rate of malaria.

Anti-inflammatory effect of trans-anethol in a rat model of myocardial ischemia-reperfusion injury.

Myocardial ischemia­reperfusion injury (MI/R) is considered a main risk factor for global cardiac mortality and morbidity, for which no effective treatment exists. Both inflammation and epigenetic regulation play a pivotal role in the early stage of MI/R. The present study aimed at investigating the prospective anti-inflammatory role of trans-anethole (TNA) in targeting MI/R and its related mechanism in upregulating the expression of the inflammatory and cardiac-related gene (VAV3), and its epigenetic regulators (lncRNA-JRKL-AS1 and miR-1298) that were retrieved from in-silico data analysis in an ischemia/reperfusion (I/R) rat model. MATERIALS & METHODS: TNA was administered in 3 doses (50, 100, and 200 mg/kg), 15 min prior to coronary ligation in male Wistar rats. The left ventricular end-diastolic pressure and dP/dtmax were assessed. Histopathological, biochemical, and molecular analyses were performed to assess the effects of TNA pre-treatment on the I/R rats model. RESULTS: TNA alleviated the I/R-induced cardiac injury pathologically and improved the cardiac function tests and enzymes. At the molecular level, TNA upregulated the expression level of the retrieved RNA-based panel (VAV3 mRNA/miR-1298/lncRNA JRKL-AS1). At the protein level, TNA decreased the cardiac content of the pro-inflammatory cytokine TNF-α. CONCLUSION: TNA has demonstrated a potential ability to alleviate the cardiac injury and attenuate the inflammatory response following ischemia-reperfusion in the rat model through modulation of the expression of RNA panel (VAV3 mRNA/miR-1298/lncRNA JRKL-AS1) and TNF- α protein.

Experimental and Molecular Modeling Studies on the Complexation of Chromium(III) with the Angiotensin-Converting Enzyme Inhibitor Captopril.

Captopril (CPT) is an inhibitor of angiotensin I converting enzyme, used as a medication for the treatment of people with high blood pressure, renal insufficiency, and cardiovascular diseases. It inhibits the angiogenesis process, vasoconstriction, and tumor metastasis. Some metal-captopril complexes exhibit antimicrobial activities. In the current work, the formation of the CrIII-CPT complex was studied spectrophotometrically and potentiometrically in aqueous solution. Kinetics of CrIII-CPT complex formation was spectrophotometrically studied over the pH range 3.20-4.20, at an ionic strength of 0.3 M at 30-50 °C. CrIII-CPT complex formation was potentiometrically studied at 25 °C, where ligand protonation constants and complexes' overall stability constants were calculated. UV-vis absorption spectra were executed to confirm the complex formation. Density functional theory and molecular dynamics simulation were performed to search the geometries of the CrIII-CPT complex. Atoms in molecules and interaction region indicator calculations are used to investigate intermolecular interactions for the formation of CrIII-CPT complex. The antimicrobial activity of the CPT ligand and CrIII-CPT complex on the prevention and control of environmental pathogenic bacteria, as tested on both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli) via agar disc diffusion method, assess the ability to use as an antimicrobial agent. CPT had shown good antimicrobial activity against both types of bacteria, which had increased slightly the zone of inhibition in Cr-CPT that indicates the increased efficacy due to Cr(III) antimicrobial activity via its oxidative damage to the bacterial cell wall. No previous study tested the CPT antimicrobial activity against Gram-positive ones such as S. aureus.

The outcome of postoperative radiation therapy following plastic surgical resection of recurrent ear keloid: a single institution experience.

BACKGROUND: Ear keloids are abnormal continuously growing healing process following cutaneous injury. Surgical excision is the standard treatment strategy; however, 50-80% of cases develop recurrence. Adjuvant radiotherapy (RT) is commonly offered with a marked decrease in the recurrence rate. The variation in RT protocols used in different studies leads to a bias of results analysis. The aim is to present our experience of using surgical excision with postoperative radiotherapy for recurrent ear keloids. Also, studying different variables especially dose and keloid size that affects recurrence rate. Radiotherapy complications were reported and assessed. PATIENTS AND METHODS: Keloids between 2006 and 2021 were retrospectively reviewed. Fifty-five ear keloids out of 83 cases who received RT after surgical excision were included in the study. Different dose regimens including 13 Gy/1fx, 8 Gy/1fx, 10 Gy/2fx, 15 Gy/3fx, and other fractionated regimens were used. The Median follow-up period was 35 months. Recurrence-free rate (RFR), side effects, and prognostic factors were assessed. RESULTS: The overall 2-year RFR was 88 ± 5%. The 2-year RFR was 83 ± 8% for dose regimens with biological effective dose (BED) ≤ 40 and 92 ± 5% for regimens with BED > 40 Gy with an insignificant p value. The 2-year RFR was 74 ± 10% compared to 97 ± 3% for keloids > 2 cm and keloids ≤ 2 cm respectively (p value 0.02). The higher dose used for keloids with > 2 cm size significantly improved RFR. The orthovoltage therapy showed marginally better 2-year RFR compared to electron beam therapy; however, statistically insignificant (p value 0.09). The side effects were minimal with no reported second malignancy or serious G3-4 complications. CONCLUSION: Excision followed by RT is a safe and effective treatment for recurrent ear keloids. Low and modest radiation doses are effective; however, a higher dose is recommended for keloids > 2 cm. We recommend a prospective larger-scale study to test the effect of dose and keloid size on the treatment results.

Machine Learning Model for Predicting Postoperative Survival of Patients with Colorectal Cancer.

PURPOSE: Machine learning (ML) is a strong candidate for making accurate predictions, as we can use large amount of data with powerful computational algorithms. We developed a ML based model to predict survival of patients with colorectal cancer (CRC) using data from two independent datasets. MATERIALS AND METHODS: A total of 364,316 and 1,572 CRC patients were included from the Surveillance, Epidemiology, and End Results (SEER) and a Korean dataset, respectively. As SEER combines data from 18 cancer registries, internal validation was done using 18-Fold-Cross-Validation then external validation was performed by testing the trained model on the Korean dataset. Performance was evaluated using area under the receiver operating characteristic curve (AUROC), sensitivity and positive predictive values. RESULTS: Clinicopathological characteristics were significantly different between the two datasets and the SEER showed a significant lower 5-year survival rate compared to the Korean dataset (60.1% vs. 75.3%, p < 0.001). The ML-based model using the Light gradient boosting algorithm achieved a better performance in predicting 5-year-survival compared to American Joint Committee on Cancer stage (AUROC, 0.804 vs. 0.736; p < 0.001). The most important features which influenced model performance were age, number of examined lymph nodes, and tumor size. Sensitivity and positive predictive values of predicting 5-year-survival for classes including dead or alive were reported as 68.14%, 77.51% and 49.88%, 88.1% respectively in the validation set. Survival probability can be checked using the web-based survival predictor (http://colorectalcancer.pythonanywhere.com). CONCLUSION: ML-based model achieved a much better performance compared to staging in individualized estimation of survival of patients with CRC.