Co-targeting of cyclooxygenase-2 and foxM1 is a viable strategy in inducing anticancer effects in colorectal cancer cells

Background: Cross-talk between deregulated signaling pathways in cancer cells causes uncontrolled growth and proliferation. These cancers cells become more aggressive and quickly develop resistance to therapy. Therefore targeting of these deregulated pathways simultaneously can result in efficient cell death of cancer cells. In this study we investigated co-expression of Cox-2 and FoxM1 in a cohort of colorectal carcinoma (CRC) samples and also examined whether inhibition of Cox-2 and FoxM1 simultaneously can lead to inhibition of cell viability and induction of apoptosis in colorectal cancer cell lines and in vivo xenografMethods: Protein expression of Cox-2 and FoxM1 was determined in a large cohort of 770 clinical CRC samples in a tissue micro-array format by immunohistochemistry. Cell death was measured using live dead assay. Apoptosis was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Calcusyn software was utilized to estimate the synergistic doses using chou and Talalay method. Results: Co-expression of Cox-2 and FoxM1 was detected in 33.3 % (232/697) of CRC’s and associated with an aggressive phenotype characterized by younger age (p = 0.0191), high proliferative index marker; Ki-67 (p = 0.004) and MMP-9 (p = 0.0116) as well as activation of AKT (p = 0.0214). In vitro, inhibition of FoxM1 and Cox-2 with pharmacological inhibitors; Thiostrepton and NS398 resulted in efficient down-regulation of FoxM1 and Cox-2 expression along with in-activation of AKT and inhibition of colony formation, invasion and migratory capability of CRC cells. In addition, there was also inhibition of cell viability and induction of apoptosis via the mitochondrial apoptotic pathway in CRC cell lines. Finally, treatment of CRC xenograft tumors in nude mice with combination of Cox-2 and FoxM1 inhibitors inhibited tumor growth significantly via down-regulation of Cox-2 and FoxM1 expression. Conclusions: These findings demonstrate that co-expression of Cox-2 and FoxM1 might play a critical role in the pathogenesis of CRC. Therefore, targeting of these pathways simultaneously with sub toxic doses of pharmacological inhibitors can be a potential therapeutic approach for the treatment of this subset of CRC

Exploring the Knowledge, Attitude and Practice Regarding Hepatitis B Infection Among Dental Students in Saudi Arabia: A Cross-Sectional Study

BACKGROUND: Hepatitis B infection is a universal health problem. Worldwide, 5% of health-care-related injections continued unsafe. Dentist considers being at high-risk group for cross infection. Therefore, their knowledge and practice towards Hepatitis B virus (HBV) positive patients should be at an optimal level. AIM: The current study is aimed to evaluate and comparison of the knowledge, attitude and practice of Saudi dental students and interns towards HBV infection. METHODS: A self-explanatory questionnaire comprising of 16 questions was designed to assess and compare students’ knowledge, attitude and risk perception regarding hepatitis B infection among dental students across Saudi Arabia. RESULTS: The response rate was 91.6% the overall knowledge of the participants was poor. The attitude was fair, with the female show a significant difference in attitude and practice (P-value < 0.05). The overall practice was good, 78.1% was vaccinated against HBV, and 73.2% stated that they regularly use personal protection equipment. The higher levels show a good attitude and practice compared with the lower levels; the difference was significant (P value < 0.05). CONCLUSION: The overall knowledge was below average, continuous health education courses are mandatory

Metabolomics: a promising tool for deciphering metabolic impairment in heavy metal toxicities

Heavy metals are the metal compounds found in earth’s crust and have densities higher than that of water. Common heavy metals include the lead, arsenic, mercury, cadmium, copper, manganese, chromium, nickel, and aluminum. Their environmental levels are consistently rising above the permissible limits and they are highly toxic as enter living systems via inhalation, ingestion, or inoculation. Prolonged exposures cause the disruption of metabolism, altered gene and/or protein expression, and dysregulated metabolite profiles. Metabolomics is a state of the art analytical tool widely used for pathomolecular inv22estigations, biomarkers, drug discovery and validation of biotransformation pathways in the fields of biomedicine, nutrition, agriculture, and industry. Here, we overview studies using metabolomics as a dynamic tool to decipher the mechanisms of metabolic impairment related to heavy metal toxicities caused by the environmental or experimental exposures in different living systems. These investigations highlight the key role of metabolomics in identifying perturbations in pathways of lipid and amino acid metabolism, with a critical role of oxidative stress in metabolic impairment. We present the conclusions with future perspectives on metabolomics applications in meeting emerging needs

Accelerating biomedical image segmentation using equilibrium optimization with a deep learning approach

Biomedical image segmentation is a vital task in the analysis of medical imaging, including the detection and delineation of pathological regions or anatomical structures within medical images. It has played a pivotal role in a variety of medical applications, involving diagnoses, monitoring of diseases, and treatment planning. Conventionally, clinicians or expert radiologists have manually conducted biomedical image segmentation, which is prone to human error, subjective, and time-consuming. With the advancement in computer vision and deep learning (DL) algorithms, automated and semi-automated segmentation techniques have attracted much research interest. DL approaches, particularly convolutional neural networks (CNN), have revolutionized biomedical image segmentation. With this motivation, we developed a novel equilibrium optimization algorithm with a deep learning-based biomedical image segmentation (EOADL-BIS) technique. The purpose of the EOADL-BIS technique is to integrate EOA with the Faster RCNN model for an accurate and efficient biomedical image segmentation process. To accomplish this, the EOADL-BIS technique involves Faster R-CNN architecture with ResNeXt as a backbone network for image segmentation. The region proposal network (RPN) proficiently creates a collection of a set of region proposals, which are then fed into the ResNeXt for classification and precise localization. During the training process of the Faster RCNN algorithm, the EOA was utilized to optimize the hyperparameter of the ResNeXt model which increased the segmentation results and reduced the loss function. The experimental outcome of the EOADL-BIS algorithm was tested on distinct benchmark medical image databases. The experimental results stated the greater efficiency of the EOADL-BIS algorithm compared to other DL-based segmentation approaches

Population pharmacokinetics of vancomycin in very low birth weight neonates

IntroductionVancomycin dosing in very low birth weight (VLBW) neonates is challenging. Compared with the general neonatal population, VLBW neonates are less likely to achieve the vancomycin therapeutic targets. Current dosing recommendations are based on studies of the general neonatal population, as only a very limited number of studies have evaluated vancomycin pharmacokinetics in VLBW neonates. The main aim of this study was to develop a vancomycin population pharmacokinetic model to optimize vancomycin dosing in VLBW neonates.MethodsThis multicenter study was conducted at six major hospitals in Saudi Arabia. The study included VLBW neonates who received vancomycin and had at least one vancomycin serum trough concentration measurement at a steady state. We developed a pharmacokinetic model and performed Monte Carlo simulations to develop an optimized dosing regimen for VLBW infants. We evaluated two different targets: AUC0–24 of 400–600 or 400–800 µg. h/mL. We also estimated the probability of trough concentrations >15 and 20 µg/mL.ResultsIn total, we included 236 neonates, 162 in the training dataset, and 74 in the validation dataset. A one-compartment model was used, and the distribution volume was significantly associated only with weight, whereas clearance was significantly associated with weight, postmenstrual age (PMA), and serum creatinine (Scr).DiscussionWe developed dosing regimens for VLBW neonates, considering the probability of achieving vancomycin therapeutic targets, as well as different toxicity thresholds. The dosing regimens were classified according to PMA and Scr. These dosing regimens can be used to optimize the initial dose of vancomycin in VLBW neonates

Assessment of knowledge, attitude and practice of diabetic people in Najran, Kingdom of Saudi Arabia

Background: This cross-sectional hospital based study aimed at determining the level of knowledge, attitude and practice of diabetes among local people of Najran, Saudi Arabia.Methods: We aimed to investigate the levels of knowledge, attitude and practice among diabetic people in Najran area.Results: 10% of the participants scored >7, 28% scored >5 and 62% scored 5 and less in Knowledge questionnaire. None [0.00%] of the participants scored 7 or more out of the attitude questionnaire. 100% of the participants scored 5 and less out of 12. 100% of the participants scored >6 and 0% scored 12 or more in the practice questionnaire.Conclusions: Our study revealed that the level of knowledge, attitude and practice of diabetes in the area of Najran is very poor. We suggest that a structured educational program to be adopted by the health authorities in Saudi Arabia

Viral shedding and antibody response in 37 patients with MERS-coronavirus infection

Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 106 (6 × 1010) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 104 copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection

COVID-19 Delta Variant: Perceptions, Worries, and Vaccine-Booster Acceptability among Healthcare Workers

Background: As the COVID-19 Delta variant has spread across the globe, healthcare workers’ (HCWs) knowledge, worries, and vaccine booster acceptance should be assessed. Methods: Online questionnaires aimed at HCWs in Saudi Arabia were distributed between 9 and 12 August 2021, aiming to evaluate HCWs’ perceptions and worries about the Delta variant as well as their feelings about receiving a booster-vaccine. Results: A total of 1279 HCWs participated, with 51.1% being physicians and 41.7% nurses. 92.5% were aware of the emergence of the Delta variant. Still, only 28.7% were found to have sufficient knowledge of the variant, and their level of worry about it was higher than their level of worry about the Alpha variant (2.32/5 versus 1.79/5). The main information sources cited by the participants were social media (50.5%), while 30.5% used scientific journals. Overall, 55.3% were willing to receive a vaccine booster, while one third would have preferred to receive a new mRNA vaccine specifically developed for the Delta variant. Factors associated with vaccine booster acceptance were receiving both vaccination doses (p = 0.008), believing that the Pfizer-BioNTech BNT162b2 vaccine is effective against variants (p < 0.001), and agreement that mixing/matching vaccines is effective against variants (p < 0.001). Conclusions: A high percentage of HCWs were aware of the Delta variant, but only a small fraction had decent quality of knowledge about it. The participants exhibited high worry levels and showed a modest acceptance of receiving a vaccine booster dose. These results should encourage public health officials to scale up educational efforts to disseminate reliable information about the different variants and provide recommendations about receiving a vaccine booster. Further research on methods to alleviate HCWs’ worries about emerging variants is warranted