KDM3A knockdown regulates COMP, LOX, COL8A1 and ACOT1 genes in myocardial fibrosis.

Cardiovascular disease (CVD) is one of the main causes of death in Saudi Arabia. Cardiac remodeling plays a critical role in the pathophysiology of heart failure. Major focus of our study was to identify crucial genes involved in the pathological remodeling of the heart caused by pressure overload. We utilized various in-silico tools to analyze and interpret microarray data obtained from the Gene Expression Omnibus (GEO) database (GSE120739), including GEO2R analysis, Metascape analysis, WebGestalt analysis, and IPA (Ingenuity pathway analysis). Our findings indicate that certain genes, including Cartilage Oligomeric Matrix Protein (COMP), collagen type VIII alpha 1 chain (COL8A1) and Lysyl Oxidase (LOX) under the influence caused by knockdown of KDM3A, were down regulated by the extracellular matrix pathway. Moreover, genes, such as Acyl-CoA Thioesterase 1 (ACOT1) were up regulated by the fatty acid metabolism pathway. Overexpression of lysine-specific demethylase 3A (KDM3A) leads to the up regulation of fibrosis-related genes COMP, COL8A1, and LOX and the down regulation of ACOT1, result in enhanced fibrosis and heart failure. Our results suggest that COMP, COL8A1, LOX, and ACOT1 warrant further investigation in the development of cardiac fibrosis and as potential biomarkers for causing heart failure.

MLKL regulates radiation-induced death in breast cancer cells: an interplay between apoptotic and necroptotic signals.

Resistance to caspase-dependent apoptosis is often responsible for treatments failure in cancer. Necroptosis is a type of programmed necrosis that occurs under caspase-deficient conditions that could overcome apoptosis resistance. Our purpose was to investigate the interrelationship between apoptotic and necroptotic death pathways and their influence on the response of breast cancer cells to radiotherapy in vitro. Human BC cell lines MCF-7 and MDA-MB-231 were treated with ionizing radiation, and then several markers of apoptosis, necroptosis, and survival were assessed in the presence and absence of necroptosis inhibition. MLKL knockdown was achieved by siRNA transfection. Our main findings emphasize the role of necroptosis in cellular response to radiation represented in the dose- and time-dependent elevated expression of necroptotic markers RIPK1, RIPK3, and MLKL. Knockdown of necroptotic marker MLKL by siRNA led to a significant elevation in MDA-MB-231 and MCF-7 survival with a dose modifying factor (DMF) of 1.23 and 1.61, respectively. Apoptotic markers Caspase 8 and TRADD showed transitory or delayed upregulation, indicating that apoptosis was not the main mechanism by which cells respond to radiation exposure. Apoptotic markers also showed a significant elevation following MLKL knockdown, suggesting its role either as a secondary or death alternative pathway. The result of our study emphasizes the critical role of the necroptotic pathway in regulating breast cancer cells responses to radiotherapy and suggests a promising utilization of its key modulator, MLKL, as a treatment strategy to improve the response to radiotherapy.

A 3D scaling law for supravalvular aortic stenosis suited for stethoscopic auscultations.

In this study a frequency scaling law for 3D anatomically representative supravalvular aortic stenosis (SVAS) cases is proposed. The law is uncovered for stethoscopy's preferred auscultation range (70-120 Hz). LES simulations are performed on the CFD solver Fluent, leveraging Simulia's Living Heart Human Model (LHHM), modified to feature hourglass stenoses that range between 30 to 80 percent (mild to severe) in addition to the descending aorta. For physiological hemodynamic boundary conditions the Windkessel model is implemented via a UDF subroutine. The flow-generated acoustic signal is then extracted using the FW-H model and analyzed using FFT. A preferred receiver location that matches clinical practice is confirmed (right intercostal space) and a correlation between the degree of stenosis and a corresponding acoustic frequency is obtained. Five clinical auscultation signals are tested against the scaling law, with the findings interpreted in relation to the NHS classification of stenosis and to the assessments of experienced cardiologists. The scaling law is thus shown to succeed as a potential quantitative decision-support tool for clinicians, enabling them to reliably interpret stethoscopic auscultations for all degrees of stenosis, which is especially useful for moderate degrees of SVAS. Computational investigation of more complex stenotic cases would enhance the clinical relevance of this proposed scaling law, and will be explored in future research.

Optimization of ultrasound- and enzymatic-assisted extractions of polyphenols from dried red onion peels and evaluation of their antioxidant activities.

There is a recognized need for exploring new natural antioxidants that have high antioxidant potential. Thus, the aim of this study was to optimize the extraction process of onion peels using ultrasound- and enzymatic-assisted extractions (UAE and EAE) methods to utilize the optimal extracts as natural antioxidants. Box-Behnken Design (BBD) was implemented to reach the optimal extracts with the highest simultaneous content of total phenolic content (TPC) and total flavonoid content (TFC). The optimal UAE and EAE extracts were subjected to High Performance Liquid Chromatography (HPLC) analysis to identify their chemical profile. The antioxidant activities of optimal extracts obtained by UAE and EAE were evaluated in vitro using DPPH and FRAP assays and their abilities to increase the oxidative stability of sunflower oil were studied using Rancimat test. The optimal conditions for UAE were 34.02 W, 26.87 mL/g solid, and 45.43 min, meanwhile they were 30.00 mL/g solid, 45.43 min at enzyme concentration of 0.52% for EAE method. DPPH and FRAP assays results revealed that EAE optimal extract show superior antioxidant activity over UAE optimal extract. The protection factor of optimal EAE extract against sunflower oil oxidation was close to that of butylated hydroxytoluene (BHT).

The effect of hepatic steatosis on 18F-FDG uptake in PET-CT examinations of cancer Egyptian patients.

BACKGROUND: Hepatic steatosis is the most common chronic hepatic disease. Imaging diagnosis of hepatic steatosis has been evaluated as an alternative to invasive histological diagnosis. STUDY AIMS: The study aimed to assess the effect of hepatic steatosis on Flourine-18 fluorodeoxyglucose (18F-FDG) uptakes in cancer patients. PATIENTS AND METHODS: Blood samples were collected from 50 cancer patients and analyzed to calculate fatty liver index and Hepatic steatosis index (HIS). Hepatic steatosis examined using high-resolution ultrasound and positron emission tomography-computed tomography (PET-CT). Linear attenuation coefficient, standardized-uptake value (SUV) mean (SUV mean), and SUV maximum (SUVmax) were measured. Accordingly, patients were divided equally into non-fatty liver, and fatty liver groups. RESULTS: A significant increase in SUVmax and SUV mean was observed in the fatty liver group more than in the non-fatty liver group. HSI significantly increased in the fatty liver group compared to the non-fatty liver group. Liver tissue uptake FDG was significantly correlated with HSI values. SUV max significantly correlated with body mass index (BMI) in the non-fatty group only. CONCLUSION: Hepatic changes in cancer patients affect the liver metabolic activity and thus the 18 F-FDG uptake. Therefore, further corrections should be considered when the liver is used as a comparator for PET-CT scans of cancer patients.

A CFD-FFT approach to hemoacoustics that enables degree of stenosis prediction from stethoscopic signals.

In this paper, we identify a new (acoustic) frequency-stenosis relation whose frequencies lie within the recommended auscultation threshold of stethoscopy (< 120 Hz). We show that this relation can be used to extend the application of phonoangiography (quantifying the degree of stenosis from bruits) to widely accessible stethoscopes. The relation is successfully identified from an analysis restricted to the acoustic signature of the von Karman vortex street, which we automatically single out by means of a metric we propose that is based on an area-weighted average of the Q-criterion for the post-stenotic region. Specifically, we perform CFD simulations on internal flow geometries that represent stenotic blood vessels of different severities. We then extract their emitted acoustic signals using the Ffowcs Williams-Hawkings equation, which we subtract from a clean signal (stenosis free) at the same heart rate. Next, we transform this differential signal to the frequency domain and carefully classify its acoustic signatures per six (stenosis-)invariant flow phases of a cardiac cycle that are newly identified in this paper. We then automatically restrict our acoustic analysis to the sounds emitted by the von Karman vortex street (phase 4) by means of our Q-criterion-based metric. Our analysis of its acoustic signature reveals a strong linear relationship between the degree of stenosis and its dominant frequency, which differs considerably from the break frequency and the heart rate (known dominant frequencies in the literature). Applying our new relation to available stethoscopic data, we find that its predictions are consistent with clinical assessment. Our finding of this linear correlation is also unlike prevalent scaling laws in the literature, which feature a small exponent (i.e., low stenosis percentage sensitivity over much of the clinical range). They hence can only distinguish mild, moderate, and severe cases. Conversely, our linear law can identify variations in the degree of stenosis sensitively and accurately for the full clinical range, thus significantly improving the utility of the relevant scaling laws... Future research will investigate incorporating the vibroacoustic role of adjacent organs to expand the clinical applicability of our findings. Extending our approach to more complex 3D stenotic morphologies and including the vibroacoustic role of surrounding organs will be explored in future research to advance the clinical reach of our findings.

Radioprotective Effect of Thymoquinone in X-irradiated Rats.

BACKGROUND: Thymoquinone, has anti-inflammatory, anti-oxidant, and cardio protection properties. This study aimed to evaluate the radioprotective effect of thymoquinone in whole body X-irradiated rats. METHODS: This study conducted on 40 male adult Wistar albino rats randomized into the following groups: Group I: Control rats did not receive thymoquinone or ionizing radiation. Group II: Whole-body irradiated rats with 6 Gy of X-ray. Group III: Rats orally intubated with thymoquinone (10 mg/kg/day) for 7 days then subjected to whole-body irradiation with 6 Gy then supplemented with thymoquinone for another 7 days. Group IV: Rats orally intubated with thymoquinone (20 mg/kg/day) for 7 days then subjected to whole-body irradiation with 6 Gy then supplemented with thymoquinone (20 mg/kg/day) for another 7 days. LDH, CK-MB, ALT, AST, MDA, TAC, Catalase activity, GPX, GSR and GSH were measured. RESULTS: Lipid peroxidation biomarker in the blood of X-irradiated rats significantly increased and accompanied by decrease in the levels of GSH, GSR, GPX, catalase as well as TAC. Moreover, exposure to IR significantly increases cardiac and liver enzymes. However, administration of TQ to X-irradiated rats with either 10 mg/kg or 20 mg/kg have the same reform effects and significantly protects rats against adverse effects of IR. CONCLUSION: Exposure to X-ray leads to significant changes in cellular biochemical and morphological conditions. Administration of TQ before radiation treatment significantly decreases the adverse effects of IR. TQ can improve cardiac function, decrease myocardial enzyme levels and inhibit oxidative stress.

Molecular identification of microbial contaminations in the fitness center in Makkah region

As the condition increases and seeks to remain healthy, the number of people who plan to join a fitness center or "gym" has increased markedly. From where this individual does understand, the study of the variety of bacteria showing the stolen has led him to care for people, with a popular fitness center located in the province of Makka, Saudi Arabia. Different bacteria must be eliminated from other gyms in Makkah, Saudi Arabia, in a total of three areas 46 two sports equipment. Both types and characteristics of bacteria, while some have been tested in hemolytic surgery for antibiotic resistance. Corynebacterium antibiotics in different forms did not react the same; however, isolates tested for M17 and N12 showed the greatest resistance to antibiotics. Furthermore, sixteen bacterial strains of human blood ß-agar displayed high hemolytic activity. In the gym isolates 2 (9 strains) followed in gym 1 (7 modes), B row hemolytic activity was highest. It is important to note that gram-positive bacteria were positive in all kinds of ways, and catalase was positive. Six strains belonging to the genus Bacillus, Brachybacterium, Geobacillus, Microbacterium, Micrococcus, and Staphylococcus and other pathogenic bacteria were known as possible individuals to use the morphological, biochemical, and rRNA gene of the 16S series. In general, this research illustrates the health and fitness centers in the individual being studied and the risks that are considered necessary to periodically study possible microbial contamination in the mixture in the gym to ensure people's protection.

Anterolateral ligament reconstruction improves the clinical and functional outcomes of anterior cruciate ligament reconstruction in athletes.

PURPOSE: To compare the outcomes of anterior cruciate ligament (ACL) reconstruction with those of combined ACL and anterolateral ligament (ALL) reconstruction in ACL-deficient knees. The objective of this study was to improve knowledge regarding the treatment of ACL-deficient knees with combined ACL and ALL reconstruction. Combined ACL and ALL reconstruction has been hypothesized to result in better clinical and functional outcomes than isolated ACL reconstruction (ACLR). METHODS: One-hundred and seven adult male athletes with ACL tears and high-grade pivot shifts were randomized into two groups. Those in group A (n = 54) underwent ACLR, while those in group B (n = 53) underwent combined ACL and ALL reconstruction. The median age was 26 (18-40) and 24 (18-33) years in groups A and B, respectively, and the median follow-up was 60 (55-65) months. Physical examination findings, instrumented knee laxity tested using a KT-1000 arthrometer, and International Knee Documentation Committee Scale (IKDC) scores were used to evaluate the outcomes. RESULTS: One-hundred and two patients were available for follow-up: 52 in group A and 50 in group B. Postoperatively, the pivot shift was normal in 43 (82.7%) and 48 (96%) patients in groups A and B, respectively (p < 0.001). The median instrumented knee laxity was 2.5 ± 0.7 (1.2-6.1) mm in patients in group A and 1.2 ± 0.7 (1.2-3.2) mm in patients in group B (p < 0.001). Additionally, 44 (84.6%) patients in group A had normal IKDC scores and 3 (5.8%) had nearly normal scores, while 48 (96.0%) patients in group B had normal IKDC scores and 2 (4%) had nearly normal scores (p < 0.001). CONCLUSION: Combined ACL and ALL reconstruction, compared with isolated ACLR resulted in favourable clinical and functional outcomes, as demonstrated by decreased rotational instability and instrumented knee laxity, a lower graft rupture rate and better postoperative IKDC scores. LEVEL OF EVIDENCE: 1.

Study the relationship of endothelial damage / dysfunction due to occupational exposure to low dose ionizing radiation versus high dose exposure during radiotherapy.

BACKGROUND: Vascular injuries caused by irradiation include acute vasculitis with neutrophil invasion, endothelial cell (EC) swelling, capillary loss, and activation of coagulator mechanisms, along with local ischemia and fibrosis. The circulating endothelial cells (CECs), increase dramatically in diseases with vascular damage. AIM: The aim of this study is to provide data on the endothelial dysfunction due to occupational exposure to low dose ionizing radiation versus high dose exposure during radiotherapy (RT). PATIENTS AND METHODS: This study included 100 subjects divided into three main groups: Group I: High dose exposure group: 50 breast cancer patients treated with post-operative radiotherapy. Group II: Low dose exposure group: 25 hospital radiation workers. Group III: 25 healthy volunteers' age and sex matched as control group who had never worked in radiation-related jobs. TM levels measured by enzyme linked immunosorbent assay (ELISA). Circulating endothelial cells (CEC) enumerated in peripheral blood by flow cytometric analysis of their signature receptor CD146. RESULTS: % CD146+ cells and plasma TM were significantly increased in radiation workers and after exposure to radiotherapy treatment in breast cancer patients. When comparing patients group with radiation workers group, we found significant elevation in plasma TM in radiation workers while insignificant difference was found in % CD146+ cells. CONCLUSION: CECs and plasma TM both are increased in radiation workers and patients treated with radiotherapy. They may constitute valuable markers of endothelial injury. Workers exposed to low doses of ionizing radiation may develop significant endothelial dysfunction predisposes them to cardiovascular complications namely thrombosis, mostly due to oxidative stress among other causes.

Available Technologies, Applications and Benefits of Teleorthodontics. A Literature Review and Possible Applications during the COVID-19 Pandemic.

BACKGROUND: COVID-2019 spread rapidly throughout the world from China. This infection is highly contagiousness, has a high morbidity, and is capable of evolving into a potentially lethal form of interstitial pneumonia. Numerous countries shut-down various activities that were considered "not essential." Dental treatment was in this category and, at the time of writing, only non-deferrable emergencies are still allowed in many countries. Therefore, follow-up visits of ongoing active therapies (e.g., orthodontic treatment) must be handled taking special precautions. This literature review aims at reducing in-office appointments by providing an overview of the technologies available and their reliability in the long-distance monitoring of patients, i.e., teledentistry. METHODS: A literature review was made according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. Randomized clinical trials, cross sectional, observational, and case-control studies were evaluated with the Mixed Methods Appraisal Tool for quality assessment and study limitations. RESULTS: A primary search found 80 articles, 69/80 were excluded as non-relevant on the basis of: the abstract, title, study design, bias, and/or lack of relevance. Twelve articles were included in the qualitative analysis. CONCLUSIONS: Teleorthodontics can manage most emergencies, reassuring and following patients remotely. The aim set by dental teleassistance was met as it reduced patients' office visits whilst maintaining regular monitoring, without compromising the results. Although our preliminary findings should be further investigated to objectively evaluate the efficacy, cost-effectiveness, and long-term results, we are confident that teleassistance in orthodontics will have a role to play in the near future.

Outcomes of hip arthroscopy for femoroacetabular impingement: The effect of morphological type and chondrolabral damage.

INTRODUCTION: Hip arthroscopy for treatment of femoroacetabular impingement (FAI) has shown significant pain and functional improvement. However, the differential outcome of each of the FAI morphological types in contrast to one another remains largely unknown. This study was conducted to detect a possible difference in outcome among different FAI types treated using hip arthroscopy. METHODS: In this prospective non randomized comparative study, after exclusion of non-FAI cases and cases with advanced arthritic changes, 90 hips in 85 patients that had hip arthroscopy for the treatment of FAI between 2011 and 2015 in our center were analyzed. The collected patient reported outcome measures (PROMs) included visual analog scale (VAS) of pain, the modified Harris hip score (mHHS), and the non arthritic hip score (NAHS) both preoperatively and at final follow-up. Patient satisfaction was collected at final follow-up. Postoperative PROMs were subjected to three main comparisons based on each of FAI type, labral procedure, and extent of cartilage damage. Repeat comparison based on FAI type after matching of exact chondrolabral condition was also attempted. RESULTS: Mean follow-up was 32.8 months (five patients lost from follow-up). There was a significant improvement in the overall PROMs. This improvement was significantly higher in the cam group in contrast to the mixed group. After matching for chondrolabral condition, this difference was consistent and more evident. DISCUSSION: The outcome of arthroscopic treatment of pure cam FAI is significantly better than that of mixed FAI. Matching of the same chondrolabral condition and repeating the comparison yields similar results.

Telomerase activity, cytokeratin 20 and cytokeratin 19 in urine cells of bladder cancer patients.

AIM OF THE STUDY: This work aims to search for markers suitable for the screening of bladder cancer, which should be specific, sensitive, reproducible, non-invasive and at acceptable cost. PATIENTS AND METHODS: The study included 50 patients diagnosed as bladder cancer (35 TCC, 15 SCC) of different stages and grades, 30 patients with various urothelial diseases, besides 20 apparently healthy subjects of matched age and sex to the malignant group. A random midstream urine sample was collected in a sterile container for the determination of telomerase by RT-PCR, keratin 19 by ELSA CYFRA 21-1 IRMA kit, keratin 20 by RT-PCR and immunohistochemical staining, and urine cytology. RESULTS: For all parameters (telomerase, K19, K20 and cytology) the malignant group was significantly different from both the benign and the control groups. None of the four studied parameters was correlated to the stage of the disease, and when it comes to grade, only K19 showed a significant positive correlation with grade both in TCC and SCC. When ROC curves for all parameters were compared, K19 had the largest area under the curve, and then comes K20. CONCLUSION: K 19 may be used as a biological marker for the diagnosis of bladder cancer. K19 could not be used for differential diagnosis of different types of bladder cancer, meanwhile it could be a marker for differentiation that decreases in less differentiated tumors. As a tumor marker, K20 reflects inability to differentiate tumor type or grade in TCC, while in SCC of the bladder it is correlated with the grade. As a method, RT-PCR is superior to immunostaining for the detection of bladder cancer, meanwhile K20 immunohistochemistry (IHC) results were much better than urine cytology as a bladder cancer screening test. Haematuria and inflammation reduced the specificity of telomerase assay, which reduced its validity as a tumor marker of bladder cancer. K19 and K20 are the best candidates as screening tests for the diagnosis of bladder cancer, representing the highest sensitivity and specificity, beside the radiological and histopathology. Meanwhile, telomerase, although it was a sensitive enough marker, it reflected a high false positive rate.