Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.

BACKGROUND: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions. METHODS: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes. A regression model was built using colorectal cancer-specific fitness genes, which was validated in other three independent cohorts. 30 published gene expression signatures were also retrieved. FINDINGS: We defined a total of 1828 genes that were colorectal cancer-specific fitness genes and identified a 22 colorectal cancer-specific fitness gene (CFG22) score. A high CFG22 score represented unfavorable recurrence and mortality rates, which was validated in three independent cohorts. Combined with age, and TNM stage, the CFG22 model can provide guidance for the prognosis of colorectal cancer patients. Analysis of genomic abnormalities and infiltrating immune cells in the CFG22 risk stratification revealed molecular pathological difference between the subgroups. Besides, drug analysis found that CFG22 high patients were more sensitive to clofibrate. INTERPRETATION: The CFG22 model provided a powerful auxiliary prediction tool for identifying colorectal cancer patients with high recurrence risk and poor prognosis, optimizing precise treatment and improving clinical efficacy.

Polyphenolic profile, processing impact, and bioaccessibility of apple fermented products.

Health-promoting foods have become increasingly popular due to intensified consumer interest and awareness of illnesses. There is a global market for apple fruits, which are affordable, nutritious, tasty, and produced in large quantities for direct consumption as well as food processing to make derived products. The food matrix of apples is suitable for fermentation, besides containing a high amount of phenolics and polyphenols. Fermentation of apples is one of the most common methods of preserving apple fruit and its byproducts. With different fermentation techniques, apple fruit can be used to make a wide range of products, such as fermented apple juice, cider, liqueurs, apple cider, apple vinegar and fermented apple solids, because it is not only a low-cost and simple method of processing the fruit, but it can also sometimes increase the bioavailability of nutrients and the levels of components that can improve health and sensory quality. To understand the health benefits of food products and how the fermentation process impacts polyphenols, it is also crucial to observe the effects of digestion on polyphenol bioaccessibility. Polyphenolic profile changes can be observed via both in vitro and in vivo digestion methods; however, in vitro digestion methods have the advantage of observing every step of gastrointestinal track effects and have less cost as well. In this review, the polyphenolic profile, processing impact, and bioaccessibility of apple-fermented products is assessed, with most available studies showing polyphenol profiles and bioaccessibility in apple varieties and fermented apple products.

Photo-Physical Characteristics of Janus Green B in Different Solvents and its Interaction Mechanism with Silver Nanoparticles.

This work explores the effects of solvent polarity on Janus Green B (JGB) photophysical properties. The Lippert-Mataga, Billot, and Ravi equations were utilized to calculate the singlet-state excited dipole moments (µe) and ground state dipole moments (µg) using absorption and fluorescence spectra analyses. The results showed an increase in the former, which is suggestive of electronic structural alterations upon excitation. Analysis of fluorescence quantum yield values revealed that JGB's environment had an impact on its emission characteristics; it was particularly sensitive to silver nanoparticles, suggesting possible interactions. While simulations of electron density, electrostatic potential, and energy gap (Eg) helped to understand the electronic structure of JGB, theoretical absorption spectra produced by Time Dependent Density Function Theory (TD-DFT) calculations offered insights into electronic transitions during absorption. To sum up, the present study contributes to our comprehension of the molecular behavior of JGB in various solvents by elucidating the intricate relationship among solvent polarity, molecular environment, and interactions with silver nanoparticles. Additionally, theoretical computations support the interpretation of experimental results.

The utility of dynamic contrast-enhanced intranodal magnetic resonance lymphangiography (MRL) in the investigation of primary lymphatic anomalies.

AIM: The aim of this study was to describe the technique of DCMRL to identify central lymphatic abnormalities in patients with primary lymphatic anomalies and discuss utility of the findings. MATERIALS AND METHODS: Twenty-eight patients with primary lymphatic abnormalities underwent dynamic magnetic resonance imaging (MRI) following injection of gadolinium directly into inguinal lymph nodes at a tertiary lymphovascular referral center. RESULTS: Technical success was achieved in 23 patients (82.1%). Pathological imaging findings included obstructed, hypoplastic, or absent lymphatic channels with collateralization/rerouting or reflux of flow, lymphangiectasia, lymphatic pseudoaneurysms, and lymph leaks. Protocol modifications for improved imaging are highlighted including technical aspects of lymph node injection, image acquisition and MRI parameters. In two patients, imaging findings warranted embolization of the abnormal lymphatic channels with subsequent symptomatic improvement. CONCLUSION: DCMRL has been shown to be a safe, reproducible technique in patients with primary lymphatic anomalies enabling imaging of the central lymphatic system.

Prevalence and determinants of non-communicable diseases and risk factors among adults in Lebanon: a multicentric cross-sectional study.

OBJECTIVES: Evidence on non-communicable disease (NCD) prevalence and associated risk factors informs primary health care consolidation regarding prevention and treatment strategies. In Lebanon, the government and many international organisations are still working to decrease the burden of NCDs. The aim of this study was to assess the prevalence of selected NCDs and their risk factors among adults in Lebanon, and to investigate the relationship between these risk factors and NCDs. STUDY DESIGN: A multicentric cross-sectional study was conducted over one year, from 1 June 2022 to 31 June 2023, across five Lebanese governorates. METHODS: Participants aged ≥18 years were considered eligible for enrolment in the study. Data on the sociodemographic, behavioural and medical characteristics of participants were collected. RESULTS: From the total study population (n = 4540), 52.4% reported one or more NCDs. The prevalence of most prominent NCDs were hypertension (32.8%), diabetes (26.8%), cardiovascular disease (16.1%), asthma (7.1%) and cancer (3.7%). Results showed a significant association between gender and smoking, high-fibre diet and asthma (P-value <0.05). Findings showed a highly significant association between age categories and smoking, high-fibre diet, physical activity, diagnosis with NCDs, hypertension, diabetes and cardiovascular disease (P-value <0.0001). CONCLUSIONS: This study showed a high prevalence of NCDs among adults living in Lebanon. Prevention, treatment and control of NCDs and their risk factors are a public health priority in Lebanon, and resources are required to provide targeted interventions with a multisectoral approach.

Quality of life tools among patients on dialysis: A systematic review.

Introduction:  The universal increase in obesity and diabetes has increased the chronic kidney disease (CKD) rate. In 2017, almost 800 million individuals suffered from CKD worldwide. Kidney dialysis becomes necessary as the disease progresses. Dialysis negatively impacts CKD patients' quality of life (QoL). It causes several complications that affect patients' physical, social, psychological, and spiritual aspects of life. This systematic review aims to identify condition-specific tools used to assess CKD patients' quality of life on dialysis. Material and Methods: A systematic literature search was conducted to investigate studies using QoL tools among patients on dialysis from February 2000 to June 2023. The search was conducted in several databases and followed the PRISMA guidelines. The focus was to identify tools that capture intrinsic factors, such as spiritual subdomains, rather than extrinsic factors, such as environmental subdomains. Results: The review identified five studies and seven dialysis-specific tools for assessing the QoL of CKD patients on dialysis. The physical domain was the most assessed, followed by the psychological and social domains. Fatigue, muscle weakness, sleep disorders, and pain were identified as the most common concerns in the physical domain. Conclusion: Dialysis negatively impacts all aspects of QoL in CKD patients. This review can guide clinicians in understanding the disease and treatment burden by identifying the most appropriate tools for assessing the QoL of adult CKD patients undergoing dialysis. There is a need for further studies to explore the detrimental effects of CKD treatment and better understand its impact on patients' QoL.

"Losing the Brakes"-Suppressed Inhibitors Triggering Uncontrolled Wnt/ß-Catenin Signaling May Provide a Potential Therapeutic Target in Elderly Acute Myeloid Leukemia.

Dysregulated Wnt/ß-catenin signal transduction is implicated in initiation, propagation, and poor prognosis in AML. Epigenetic inactivation is central to Wnt/ß-catenin hyperactivity, and Wnt/ß-catenin inhibitors are being investigated as targeted therapy. Dysregulated Wnt/ß-catenin signaling has also been linked to accelerated aging. Since AML is a disease of old age (>60 yrs), we hypothesized age-related differential activity of Wnt/ß-catenin signaling in AML patients. We probed Wnt/ß-catenin expression in a series of AML in the elderly (>60 yrs) and compared it to a cohort of pediatric AML (<18 yrs). RNA from diagnostic bone marrow biopsies (n = 101) were evaluated for key Wnt/ß-catenin molecule expression utilizing the NanoString platform. Differential expression of significance was defined as >2.5-fold difference (p < 0.01). A total of 36 pediatric AML (<18 yrs) and 36 elderly AML (>60 yrs) were identified in this cohort. Normal bone marrows (n = 10) were employed as controls. Wnt/ß-catenin target genes (MYC, MYB, and RUNX1) showed upregulation, while Wnt/ß-catenin inhibitors (CXXR, DKK1-4, SFRP1-4, SOST, and WIFI) were suppressed in elderly AML compared to pediatric AML and controls. Our data denote that suppressed inhibitor expression (through mutation or hypermethylation) is an additional contributing factor in Wnt/ß-catenin hyperactivity in elderly AML, thus supporting Wnt/ß-catenin inhibitors as potential targeted therapy.

Delving into the death signaling pathway of hemp oil and gamma radiation in solid tumor bearing mice.

Many studies reported the diverse therapeutic potential of essential oils. They have a crucial role in cancer prevention and treatment. Antioxidant, antimutagenic, and antiproliferative are mechanisms involved. Also, essential oils may enhance immune function and surveillance, induce enzymes, enhance detoxification, and modulate multidrug resistance. Hemp oil, obtained from Cannabis sativaL. seeds, is known for its health-enhancing properties and bioactivity. Adult female Swiss albino mice were injected with viable Ehrlich ascites carcinoma cells (2.5 × 106 cells/mouse), and then administered with hemp oil (20 mg/kg) daily for 10 consecutive days pre-, and then 10 days post-exposure to 6 Gy whole-body gamma irradiation. Hemp oil significantly increased Beclin1, VMP1, LC3, cytochrome c, and Bax. More interestingly, Hemp oil showed a significant decrease in Bcl2 and P13k either alone or in combination with γ radiation. Finally, this study documented the possible role of hemp oil in inducing two cell death types, autophagy and apoptosis, as it may be applied as an adjuvant in cancer treatment.

Microstructure, morphology and physicochemical properties of nanocomposites containing hydroxyapatite/vivianite/graphene oxide for biomedical applications.

Designing a nanocomposite that accumulates biocompatibility and antimicrobial behaviour is an essential requirement for biomedical applications. Hydroxyapatite (HAP), graphene oxide, and vivianite in one ternary nanocomposite with three phases and shapes led to an increase in cell viability to 97.6% ± 4 for the osteoblast cells in vitro. The obtained nanocomposites were investigated for their structural features using X-ray diffraction, while the microstructure features were analyzed using a scanning electron microscope (SEM) and a transmission electron microscope. The analysis showed a decrease in the crystal size to 13 nm, while the HAP grains reached 30 nm. The elongated shape of vivianite reached 200 nm on SEM micrographs. The monoclinic and hexagonal crystal systems of HAP and vivianite were presented in the ternary nanocomposite. The maximum roughness peak height reached 236.1 nm for the ternary nanocomposite from 203.3 nm, while the maximum height of the roughness parameter reached 440.7 nm for the di-nanocomposite of HAP/graphene oxide from 419.7 nm. The corrosion current density reached 0.004 µA/cm2 . The ferrous (Fe2+ ) and calcium (Ca2+ ) ions released were measured and confirmed. Therefore, the morphology of the nanocomposites affected bacterial activity. This was estimated as an inhibition zone and reached 14.5 ± 0.9 and 13.4 ± 1.1 mm for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) after 24 h. The increase in viability and the antibacterial activity refer to the compatibility of the nanocomposite in different medical applications.

Degradation of methylene blue using co-dopants Mg and Se in an hydroxyapatite composite.

In this work, a comparative study was made of different magnesium ion content incorporated into hydroxyapatite (HAP) and modified with selenite ions, with the aim to develop the degradation performance of methylene blue. Although the dopant metal (Mg2+ ) was present at a relatively low ratio, it induced a change in the microstructure, morphology, surface area, external surface charge, particle size, and degradation performance. The effect of magnesium and selenium binary doping on microstructure and degradation of methylene blue was evaluated. The external surface charge measured by zeta potential clarified that the highest negativity was -11.8 mV and this was accomplished in 1.0 Mg/Se-HAP. Furthermore, the roughness average increased from 36.8 nm, reaching 59.2 nm upon the addition of Mg(II). Moreover, transmission electron microscope micrographs showed that compositions were formed as rod shapes. The process of degradation was optimized, showing effectiveness in methylene blue degradation of 62.4% after 150 min of exposure to visible light. Electrostatic attraction and H-bonding, and coordination played vital roles in the adsorption process. The recyclability of the as-prepared compositions demonstrated that the effectiveness had been reduced to ~54.2% after five times of re-use.

Prevalence of Polypharmacy and Factors Associated with it Among Saudi Older Adults - Results from the Saudi National Survey for Elderly Health (SNSEH).

Background and Objectives: The percentage of Saudi older adults (SOA) is increasing over time. With advanced age, the prevalence of chronic diseases and multiple disabilities are increasing. This leads to increase utilization of multiple medications. The objectives of this study were to describe medication utilization, determine the prevalence of polypharmacy (PP) and factors associated with it among SOA. Methods: This cross-sectional study was conducted among community-dwelling SOA aged ≥ 60 years old using the Saudi National Survey for Elderly Health (SNSEH). The survey was conducted between 2006 and 2007 by the Ministry of Health on a nationally representative sample of SOA. The data included demographics, socioeconomic and health information such as diseases and medications. Polypharmacy was defined as the concurrent use of medications from ≥ 5 therapeutic classes. A modified Poisson multivariable regression was used to study factors associated with PP controlling for confounders. All analyses were done using STATA 14. Results: The study included 2,946 SOA; 50.4% were males, 60.9% were 60-70 years old, and 69.6% were illiterate. The most common medications used among SOA were: Paracetamol (67%), joint pain medications and NSAIDs (50% each), anti-diabetic and multivitamins and minerals (47% each). PP was identified in (51.5%) of participants. The most medication associated with PP were: Paracetamol (79.9%), multivitamins and minerals (71.6%), steroid and DMARDs (70.1%), NSAIDs (66.4%), anti-diabetic and anti-hypertensive (61.3%). Higher risk of PP was associated with diabetes (RR: 1.863; 95% CI: 1.686-2.059), hypertension (RR: 1.829; 95% CI: 1.624-2.060), having pain (RR: 2.282; 95% CI: 1.918-2.713), urinary incontinence (RR: 1.389; 95% CI: 1.238-1.560; ref: no urinary incontinence) or suggestive depression (RR: 1.379; 95% CI: 1.259-1.512). Similarly, compared to low income (<2500 SAR), higher incomes were more likely to have PP. On the other hand, compared to the central region, southern and northern regions were less likely to have PP (RR = 0.741; 95% CI: 0.652-0.843 and RR: 0.736; 95% CI: 0.596-0.908, respectively). Severe cognitive impairment was associated with a lower risk of PP (RR: 0.708; 95% CI: 0.501-1.000). Conclusion: The prevalence of PP among a nationally representative SOA was very high, i.e., 51.5%. Higher risk of PP was associated with many factors such as region, income, diabetes, hypertension, musculoskeletal pain, urinary incontinence, and depression. PP leads to many negative implications such as drug interactions, combined side effects, hospitalization, and death. Therefore, raising the knowledge of health care providers on the consequences of PP and providing medication therapy management services may help decrease the negative consequences of PP and improve therapy outcomes.

A report on the impact of rapid prenatal exome sequencing on the clinical management of 52 ongoing pregnancies: a retrospective review.

OBJECTIVE: Studies have shown that prenatal exome sequencing (PES) improves diagnostic yield in cases of fetal structural malformation. We have retrospectively analysed PES cases from two of the largest fetal medicine centres in the UK to determine the impact of results on management of a pregnancy. DESIGN: A retrospective review of clinical case notes. SETTING: Two tertiary fetal medicine centres. POPULATION: Pregnancies with fetal structural abnormalities referred to clinical genetics via a multidisciplinary team. METHODS: We retrospectively reviewed the notes of all patients who had undergone PES. DNA samples were obtained via chorionic villus sampling or amniocentesis. Variants were filtered using patient-specific panels and interpreted using American College of Medical Genetics guidelines. RESULTS: A molecular diagnosis was made in 42% (18/43) ongoing pregnancies; of this group, there was a significant management implication in 44% (8/18). A positive result contributed to the decision to terminate a pregnancy in 16% (7/43) of cases. A negative result had a significant impact on management in two cases by affirming the decision to continue pregnancy. CONCLUSIONS: We demonstrate that the results of PES can inform pregnancy management. Challenges include variant interpretation with limited phenotype information. These results emphasise the importance of the MDT and collecting phenotype and variant data. As this testing is soon to be widely available, we should look to move beyond diagnostic yield as a measure of the value of PES. TWEETABLE ABSTRACT: Prenatal exome sequencing can aid decision-making in pregnancy management; review ahead of routine implementation in NHS.

The Characteristics of Clinical Studies Submitted to the Saudi Food and Drug Authority from 2009 until 2020.

BACKGROUND: Clinical trials are crucial in contemporary evidence-based medicine for discovering new treatments for diseases. Their registration in a registry increases the transparency in the dissemination of knowledge about clinical research. It is essential to understand the activity of clinical trials in a country, thus identifying research gaps. OBJECTIVE: This study, therefore, aims to describe the clinical trial activity since the inception of clinical trials' administration and national clinical trials' registry within the Kingdom of Saudi Arabia (KSA). METHOD: A descriptive study was conducted by reviewing all clinical studies that have been registered during 2009 and June 2020. The inclusion criterion was all phases of the clinical trials registered in the national registry during that period. Data analysis was done using descriptive statistics. RESULTS: Since 2009, 352 studies have been registered. However, a total of 333 studies with complete data was included in the analysis. A total of 80 sponsors funded the clinical studies in the KSA. The majority of the clinical studies are funded by multinational pharmaceutical companies. Oncology (13.81%) and diabetes (11.71%) were the most common therapeutic areas and constituted the largest proportion of the overall studies. 44% were phase 4 and 40% were phase 3 studies. CONCLUSION: With a population approaching 34 million, the number of clinical trials in the KSA is not sufficient. Since the inception of the clinical trial's administration and SCTR, the emphasis has been on phase 3 and phase 4 clinical studies. The most studied therapeutic areas were oncology and diabetes. Many clinical studies in the KSA were sponsored by multinational pharmaceutical companies.

New terpenic and phenolic compounds from Suaeda monoica reverse oxidative and apoptotic damages in human endothelial cells.

Elevation in hyperglycemia-associated methylglyoxal level can trigger vascular endothelial cells oxidative stress and apoptosis. The present work assesses the cell proliferative, anti-oxidative and anti-apoptotic potential of Suaeda monoica derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester and a labdane-type norditerpenic xyloside as well as two new phenols: an alkylated ß-naphthol and a ß-methoxy naphthalene in cultured human umbilical vein endothelial cells (HUVEC). Of these, suaedanortriterpenedione (53.7%), normonisesquaterpenol (51.4%) and norditerpenic xyloside (48%) showed the most promising cell proliferative activities compared to others. Moreover, normonisesquaterpenol, norditerpenic xyloside and suaedanortriterpenedione efficiently reversed the oxidative and apoptotic cell damage via downregulation of capase-3/7 by 44.3%, 42.2% and 39.4%, respectively against dichlorofluorescin, whereas by 46.2%, 43.5% and 42.5%, respectively against methylglyoxal. Aminoguanidine, the reference drug inhibited caspase-3/7 activity by 56.2% and 54.7% through attenuation of dichlorofluorescin and methylglyoxal, respectively. Further in silico molecular docking analysis revealed formation of stable complexes between the tested compounds and caspase-3/7. Conclusively, we for the first time demonstrate the growth stimulatory, anti-oxidative and anti-apoptotic salutations of S. monoica derived novel compounds in human endothelial cells. This warrants their further assessment as vascular cell protective and rejuvenating therapeutics, especially in hyperglycemic conditions.

Corrigendum to "New terpenic and phenolic compounds from Suaeda monoica reverse oxidative and apoptotic damages in human endothelial cells". [Saudi Pharm. J. 29(10) (2021) 1102-1111].

[This corrects the article DOI: 10.1016/j.jsps.2021.08.007.].

Non-immune fetal hydrops: etiology and outcome according to gestational age at diagnosis.

OBJECTIVE: Fetal hydrops is associated with increased perinatal morbidity and mortality. The etiology and outcome of fetal hydrops may differ according to the gestational age at diagnosis. The aim of this study was to evaluate the cause, evolution and outcome of non-immune fetal hydrops (NIFH), according to the gestational age at diagnosis. METHODS: This was a retrospective cohort study of all singleton pregnancies complicated by NIFH, at the Fetal Medicine Unit at St George's University Hospital, London, UK, between 2000 and 2018. All fetuses had detailed anomaly and cardiac ultrasound scans, karyotyping and infection screening. Prenatal diagnostic and therapeutic intervention, gestational age at diagnosis and delivery, as well as pregnancy outcome, were recorded. Regression analysis was used to test for potential association between possible risk factors and perinatal mortality. RESULTS: We included 273 fetuses with NIFH. The etiology of the condition varied significantly in the three trimesters. Excluding 30 women who declined invasive testing, the cause of NIFH was defined as unknown in 62 of the remaining 243 cases (25.5%). Chromosomal aneuploidy was the most common cause of NIFH in the first trimester. It continued to be a significant etiologic factor in the second trimester, along with congenital infection. In the third trimester, the most common etiology was cardiovascular abnormality. Among the 152 (55.7%) women continuing the pregnancy, 48 (31.6%) underwent fetal intervention, including the insertion of pleuroamniotic shunts, fetal blood transfusion and thoracentesis. Fetal intervention was associated significantly with lower perinatal mortality (odds ratio (OR), 0.30 (95% CI, 0.14-0.61); P < 0.001); this association remained significant after excluding cases with a diagnosis of anemia or infection (OR, 0.29 (95% CI, 0.13-0.66); P = 0.003). In 104 fetuses not undergoing active fetal intervention, the gestational age at diagnosis was the only parameter that was significantly associated with the risk of perinatal mortality (OR, 0.92 (95% CI, 0.85-0.99); P = 0.035), while the affected body cavity and polyhydramnios were not (P > 0.05). CONCLUSIONS: An earlier gestational age at diagnosis of NIFH was associated with an increased risk of aneuploidy and worse pregnancy outcome, including a higher risk of perinatal loss. Fetal therapy was associated significantly with lower perinatal mortality. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Hospital Prevalence of Colorectal Cancer among Colonoscopy Recipients Attending a Tertiary Hospital in Oman: A Cross-Sectional Study.

PURPOSE: Evidence from industrialized/developed countries showed that colorectal cancer (CRC) incidence rates have significantly dropped due to the widespread use of colonoscopy. In Arab countries, however, the CRC had been reported to have increased. Despite the concerted effort in the primary prevention and widespread use of colonoscopy, to our knowledge, there have been no reports of the prevalence rate of CRC among colonoscopy recipients from Oman. This study aims to explore the CRC prevalence estimates over selected sociodemographic characteristics among colonoscopy-recipients at a tertiary hospital in Oman over five years of follow-up. The regional variations in Oman were also examined in this study. METHODS: This hospital-based cross-sectional study reviewed reports of colonoscopies performed over 5-years of retrospective follow-up at a tertiary hospital in Oman. CRC prevalence estimates were calculated over age, gender, governorate, and time of follow-up. RESULTS: A total of 442 CRC cases were enumerated among 3701 colonoscopies, with an overall CRC prevalence estimate of 11.9 per 100 colonoscopies (95% CI: 10.9, 13.0). Gender-specific CRC prevalence was higher among males compared with females (13.3 vs. 10.5). Age-specific CRC prevalence increased with advancing age, from 2.8 among those less than 40 years of age to 26.5 among aged 70 years or more. Regional CRC prevalence was highest among residents in Batinah Governorate. Over the 5-years of follow-up, there was a slow rise in CRC prevalence with an annual increment of 0.59%. CONCLUSION: The study provides supportive evidence for a steady increase in CRC prevalence over age categories and years of follow-up and depicted the variations of gender-specific CRC prevalence estimates over increasing age categories. The study calls for timely formulation and adoption of national CRC screening programs centered on the colonoscopy use as primary prevention and maximizing its utilization and efficiency.

A Polyphenols-Rich Extract from Moricandia sinaica Boiss. Exhibits Analgesic, Anti-Inflammatory and Antipyretic Activities In Vivo.

In this study, the aerial parts of Moricandia sinaica were evaluated for their in vivo analgesic, anti-inflammatory and antipyretic activities. The analgesic activities were examined using acetic acid-induced writhing, the hot plate test and the tail flick method. The anti-inflammatory and the antipyretic activities were evaluated using carrageenan-induced paw edema in rats and brewer's yeast-induced pyrexia in mice, respectively. The aqueous fraction of the methanol extract (MS-3) showed to be the most bioactive among the other investigated fractions. At the dose of 500 mg/kg, the fraction (MS-3) showed a significant percentage inhibition of the carrageenan-induced edema by 52.4% (p < 0.05). In addition, MS-3 exhibited a significant inhibition of acetic acid-induced writhes by 44.4% and 61.5% (p < 0.001) at 250-mg/kg and 500-mg/kg doses, respectively. At 120 min post-treatment, the rat groups treated with MS-3 displayed statistically significant reduction in rectal temperature (p < 0.001) by 1.7 °C and 2.2 °C at 250- and 500-mg/kg doses, respectively. The phytochemical composition of the fraction (MS-3) was characterized by high-performance liquid chromatography-mass spectrometry (HPLC-PDA-MS/MS). Molecular docking studies demonstrated that the polyphenols identified in MS-3 revealed good binding energy upon docking to some target proteins involved in pain response and inflammation, such as the cannabinoid receptors CB1 and CB2, the fatty acid amide hydrolase (FAAH) and the cyclooxygenase COX-1 and COX-2 enzymes. Based on the findings from the present work, it could be concluded that the aerial parts extract of M. sinaica exerts potential analgesic, anti-inflammatory and antipyretic effects in rats.

Cell proliferation activity delineated by molecular docking of four new compounds isolated from the aerial parts of Suaeda monoica Forssk. ex. J.F. Gmel.

Using different chromatographic methods, four new compounds were isolated from the aerial parts of Suaeda monoica (Chenopodiaceae) along with 2-hydroxy-1-naphthoic acid (SCM-3). The structures of the new compounds were established as 6'-hydroxy-10'-geranilanyl naphtha-1-oate (SMC-1), 4,4,8ß,10ß-Tetramethyl-9ß-isobutanyl decalin-13-ol-13-O-ß-D-xylopyranoside (SCM-2), 6'-(2-hydroxynaphthalen-3-yl) hexanoic acid (SCM-4) and 1'-(2-Methoxy-3-naphthyl)-4'-(2''-methylbenzoyl)-n-butane (SMC-5) by IR, EIMS and NMR (1 & 2D) analyses. All compounds (50 µg/mL) were tested for cell proliferative potential on cultured human liver cell HepG2 cells by MTT assay. The results revealed a marked cell proliferative potential of all compounds (1.42-1.48 fold) as compared to untreated control. The results of molecular docking and binding with specific proteins such as PTEN (Phosphatase and Tensin homolog) and p53 also justify the cell proliferative potential of the isolated compounds. Glide program with Schrodinger suit 2018 was used to evaluate the binding between SMC compounds and proteins (PTEN and p53). The binding affinity of all compounds was in order of 104-105 M-1 towards both PTEN and p53. All the SMC compounds have been found to bind at the active site of PTEN, thereby may prevent the binding of phosphatidylinositiol 3,4,5-triphosphate (PI3P). In the locked position, PTEN would not be able to hydrolyze PI3P and hence the PI3P regulated signaling pathway remains active. Similarly, SMC molecules were found to interact with the amino acid residues (Ser99, Thr170, Gly199, and Asp224) which are critically involved in the formation of tetrameric p53. The blockage of p53 to attain its active conformation thus may prevent the recruitment of p53 on DNA and hence may promote cell proliferation.

The role of contrast-enhanced spectral mammography in the evaluation of the postoperative breast cancer.

AIM: To assess the utility of contrast-enhanced spectral mammography (CESM) to detect malignancy in the postoperative breast of cancer patients. MATERIALS AND METHODS: The study was a prospective analysis of 76 women following operations for breast cancer. CESM was performed with low (22-33 kVp) and high (44-49 kVp) energy exposures after intravenous injection of contrast agent. Breast abnormalities were evaluated regarding the presence, morphology, and pattern of contrast medium uptake. The reference standard was histopathology of the Tru-Cut biopsy or surgical biopsy in cases where malignancy was suspected and absence of abnormality at follow-up sessions in benign cases. RESULTS: Seventy cases were eligible for data analysis, and malignancy was detected in 48.6% (n=34/70). Enhancement at the operative bed was observed in 40 (57.14%) lesions. At traditional mammography, the diagnosis was false negative in 17/70 and false positive in 28/70 lesions, and presented a low sensitivity of 50%, a very low specificity of 22%, a positive predictive value of 37.7%, a negative predicative value of 32%, and an accuracy of 35.7%. CESM enhanced the performance of mammography and produced a sensitivity of 91.17%, a specificity of 75%, a positive predictive value of 77.5%, a negative predictive value of 90%, and an accuracy of 82.85%. CONCLUSION: CESM is a credible technique that could be used in conjunction with the traditional mammogram to screen for cancer in the postoperative breast.