Search

The most common main headache disease in children and adolescents is migraine. Migraine in children and teenagers is still diagnosed clinically. The doctor requires a thorough headache history that focuses on the kind, location, intensity, and duration of the pain. Most children's migraines are frontal rather than temporal/occipital and bilateral rather than unilateral, which makes them slightly different from adult migraines. Pediatric migraine can be successfully treated with a personalized regimen combining nonpharmacologic and pharmaceutical treatments. Pediatric patients have succeeded with pharmacological treatments for migraine prevention, including beta-blockers, calcium channel antagonists, serotonin antagonists, antidepressants, and antiepileptics. The study summarises current evidence regarding the Prevalence and Risk Factors of Migraine in Children. For article selection, the PubMed database and EBSCO Information Services were used. All relevant articles relevant to our topic and other articles were used in our review. Other articles that were not related to this field were excluded. The data was extracted in a specific format that the group members reviewed. The frequency of family fights and the amount of free time are two important contributors to the emergence of chronic headaches. The way the parents react to their daughter's headaches appears significant for females. Anaemia, obesity, disorders of the abdomen, and early menarche are a few more health issues connected to childhood headaches. Children frequently experience recurrent headaches, which is a serious medical comorbidity. The findings indicated that chronic migraine significantly contributes to headaches in children and adolescents, with various age groups being more concentrated in terms of headache features and risk factors.

Background: Nurses have been the frontline fighters during the COVID-19 pandemic. This challenge has placed nurses under huge workload pressure, which has in turn affected many aspects of their lives. During the COVID-19 pandemic in Saudi Arabia, many hospitals and healthcare systems have been adversely affected. However, few studies have examined the impact of workload during the COVID-19 pandemic on nurses’ social lives. Objective: This study aimed to examine the relationship between the workload during the COVID-19 pandemic and its impact on the social life of nurses. Methods: A quantitative cross-sectional study was conducted using an online questionnaire. Results: A total of 204 nurses participated in the study. There were 73.53% female and 26.47% male respondents with a mean age of 27.64 ± 10.62 years. The majority of the participants were Saudi (87.25%) and single (52.45%). The mean score of the impact of the COVID-19 pandemic and work pressure on nurses’ social lives was (7.31 ± 1.84) out of 10. There was found to be a significant relationship between workload during the COVID-19 pandemic and the social life of nurses. Conclusion: The study revealed how the workload in hospital during the pandemic period affected the healthcare workers’ social lives, especially nurses. Therefore, it is necessary to provide support to nurses and to know their needs during the pandemic period, which may motivate them and reduce their workload to improve their work/life balance and their performance.

Cardiovascular disease (CVD) represents the leading cause of mortality worldwide. In order to diagnose CVDs, there are a range of detection methods, among them, the impedance cardiography technique (ICG). It is a non-invasive and low-cost method. In this paper, we highlight recent advances and developments of the CDVs diagnosis mainly by the ICG method. We considered papers published during the last five years (from 2017 until 2022). Based on this study, we expressed the need for an ICG database for the different CDVs.

A novel encapsulated deep eutectic solvent (DES) was introduced for biodiesel production via a two-step process. The DES was encapsulated in medical capsules and were used to reduce the free fatty acid (FFA) content of acidic crude palm oil (ACPO) to the minimum acceptable level (

Introduction Stroke has become one of the most severe causes of long-term neurological impairment and disability and is considered one of the leading causes of mortality worldwide. This study aimed to determine time delays in stroke patients from symptoms onset to treatment with tissue plasminogen activator (tPA) initiation in King Abdullah Medical City Specialist Hospital, Makkah, Saudi Arabia. Patients and methods We reviewed 81 patients who suffered from acute stroke. The data were collected from patients' electronic and paper files. Patients were divided into two main categories based on interval time from recognition of symptoms to tPA treatment. Patients were divided into early treatment, if the duration was less than or equal to 120 minutes, and delayed treatment, if the interval time was more than 120 minutes. Results Nearly two-thirds (64.2%) were males, and more than half (5.6%) were in the older age group (65 years). Patients who underwent thrombectomy were 7.4%. The mean value of the National Institutes of Health Stroke Scale (NIHSS) score was 10.7 (SD: 7.14). The mean time from symptoms onset to arrival at the hospital was 82.4 (SD: 44.1) minutes, while the total time from recognition of symptoms to tPA treatment was 154 (SD: 50.8) minutes. The prevalence of patients with delayed treatment was 72.8%, and the rest were assumed to have early treatment (27.2%). None of the socio-demographic variables were predicted to influence delayed treatment. Conclusion A significant number of patients were delayed in treatment. Patients' socio-demographic data and NIHSS scores seem to have no significant effect on delayed treatment. Further research is needed to establish the delay in time for pre-hospital and in-hospital treatment of stroke patients.

Based on data from numerous languages, such as English, Frisian, and Danish, Merchant (2001) proposes the preposition stranding generalization (PSG), which states that only languages that allow preposition stranding under wh-movement also allow preposition stranding under sluicing. The availability of this generalization has been the subject of a number of studies. Two contrasting views have been identified in the literature. The first view confirms the availability of the PSG in a number of different languages. The other view claims that this generalization is untenable as there exist non-preposition stranding languages that allow preposition stranding under sluicing. Our aim in this paper is to examine the availability of the PSG in the dialect of Hijazi Arabic (HA). Based on empirical data from HA on the syntactic behavior of preposition stranding under wh-movement and under sluicing, we argue that this PSG does not hold in HA. It has been observed that HA is like Emirati Arabic, Brazilian Portuguese, and Indonesian in that it disallows preposition stranding under wh-movement but allows it under sluicing. Therefore, the results of this research may contribute to the ongoing discussions on the phenomenon of sluicing in linguistic theory to help obtain a more universal analysis of this interesting ellipsis construction.

In this work, we developed a prototype that adopted sound-based systems for localization of visually impaired individuals. The system was implemented based on a wireless ultrasound network, which helped the blind and visually impaired to navigate and maneuver autonomously. Ultrasonic-based systems use high-frequency sound waves to detect obstacles in the environment and provide location information to the user. Voice recognition and long short-term memory (LSTM) techniques were used to design the algorithms. The Dijkstra algorithm was also used to determine the shortest distance between two places. Assistive hardware tools, which included an ultrasonic sensor network, a global positioning system (GPS), and a digital compass, were utilized to implement this method. For indoor evaluation, three nodes were localized on the doors of different rooms inside the house, including the kitchen, bathroom, and bedroom. The coordinates (interactive latitude and longitude points) of four outdoor areas (mosque, laundry, supermarket, and home) were identified and stored in a microcomputer’s memory to evaluate the outdoor settings. The results showed that the root mean square error for indoor settings after 45 trials is about 0.192. In addition, the Dijkstra algorithm determined that the shortest distance between two places was within an accuracy of 97%.

In this study, we present a varying-radius cable equation for nerve fibres taking into account the varying diameter along the neuronal segments. Finite element neuronal models utilising the classical (fixed-radius) and varying-radius cable formulations were compared using simple and realistic morphologies under intra- and extracellular electrical stimulation protocols. We found that the use of the classical cable equation to model intracellular neural electrical stimulation exhibited an error of 17% in a passive resistive cable model with abrupt change in radius from 1 to 2 μm, when compared to the known analytical solution and varying-radius cable formulation. This error was observed to increase substantially using more realistic neuron morphologies and branching structures. In the case of extracellular stimulation however, the difference between the classical and varying-radius formulations was less pronounced, but we expect this difference will increase under more complex stimulation paradigms such as high-frequency stimulation. We conclude that for computational neuroscience applications, it is essential to use the varying-radius cable equation for accurate prediction of neuronal responses under electrical stimulation.

The use of various Internet networks and applications, which provides cost-effective, easy-to-access, and several free and pay service have been the focus of cloud storage systems over the last few years. Throughout technology management and education, the idea of cloud storage has received considerable attention, but we are interested in investigating the purpose of using cloud storage facilities at Malaysian universities. Thus, we identified that perceived usefulness, perceived ease of use social influence, facilitating conditions, and personal innovativeness have an effect on the intention of cloud storage usage. We also developed the hypotheses that these five factors can influence the intention of cloud storage usage. Through an online survey questionnaire, 366 undergraduates with convenience sampling and analyzed using the Social Sciences Application Statistical Suite (SPSS) answer data collection. Our research has shown that social influence does not show a vital role in influencing the intention of scholars to utilise cloud storage, while other influences have been recognized as they influence the intention. The results have consequences for researchers, manufacturers, and educational institutions both theoretically and practically.

Background: Skin diseases are common, especially in the developing countries. Mental health disorders are prevalent among those with skin diseases and affect their life and their treatment. Anxiety is one of the psychiatric disorders, and its symptoms were found among the patients with skin diseases. This survey analysis aimed to explore the prevalence and factors associated with anxiety among patients with skin diseases. Methodology: A self-administered structured questionnaire was distributed in outpatient clinics among adult patients, who were suffering from anxiety with common skin disease. The questionnaire included questions regarding socio-demographics, perceived stigma, social support, and anxiety. Data analysis was done through Statistical Package for the Social Science program version 22. Results: Patients with facial skin diseases were significantly the highest sufferers of anxiety among all patients with skin diseases (p-value < 0.001). Also, Eczema patients were significantly the most anxious and worried about their disease (p-value < 0.001). While Acne constituted a significant majority of those who were unable to stop or control their worries, to worry about different issues, to have problems in relaxing more than half days, and to be easily annoyed every day compared to other patients (p-value < 0.001). Conclusion: Patients with dermatological diseases have a high level of anxiety and worry, especially with acne and skin disease affecting visible areas like the face. Further studies are required in Saudi Arabia to explore the true estimates of this problem.

This paper proposes a modular inverter based on Cuk converters for solar photovoltaic (PV) systems to mitigate the voltage and current mismatch issue at the PV module level. The proposed modular Cuk inverter (MCI) is formed by connecting several low-voltage (LV) microinverters (MIs) in series and linking their output sides to the distribution network. This architecture does not require a central inverter, and hence, it eliminates the need for large dc-link intermediate capacitors. The proposed MCI provides more controllability over the PV system by having a decentralized structure. The MCI will improve the PV system efficiency by reducing the voltage and current stresses in the MIs and will enable better voltage regulation due to the provided controllability. Since the proposed MI topology is based on the Cuk converter, it offers continuous input and output currents that will reduce the required filtering capacitance and will provide a wide range of voltage regulation for either supplying the loads or charging the storage batteries. The paper presents the associated control scheme for the proposed MCI that employs two controlling loops. The input loop at the PV side is designed and tuned to eliminate the ripples from the input current, while the outer loop at the grid side will control the output ac current and hence the MCI power. Computer simulations are presented using MATLAB/SIMULINK software to examine the validity of the suggested inverter for distributed generation PV residential applications. A scaled-down experimental prototype controlled by TMS320F28335 DSP was built and used to validate the mathematical analyses and simulation results.

In today’s times, elderly individuals are keeping their natural teeth for longer owing to the rising popularity of fixed dental restorations and dental implants. It is seen that access to oral health care reduces and dental demands rise as people get older and more dependent on medical attention. For a high quality of life in terms of dental health, it is critical to have a functional dentition. A skilled oral health care provider is required for the geriatric population due to complex connections between dental health, some systemic illnesses, and medication side effects. For more than a century, there have been mobile dentistry services available as a way to help the underserved in society. Initially geared towards children, these services are now frequently used by adults and the elderly, particularly those in nursing homes, people with special needs, and those who have disabilities. When treating dependent elderly patients, it has been shown that home dental treatment is more economical than traditional dental care. Four distinct mobile dental service models by which a dental healthcare professional contacts a patient include the mobile dental vehicle model, portable equipment model, fixed equipment model, and the hybrid model. The services provided by the public sector in most countries employ a range of models, including the hybrid model, portable equipment, and fixed equipment, but the private sectors mostly use portable equipment to provide a mobile dental service. Dental care provided by university-based services ranges from routine to complicated procedures, whereas basic, routine care is mostly offered by the commercial sector. Mobile and portable dental models offer a practical substitute for typical dental clinic visits or when the fixed setup is not present. Mobile dental services also have shown utility for data gathering, strategy creation, and investigations on the potential effects of preventative and oral treatment provided by these services.

In this study, we present a sensorless, robust, and physiological tracking control method to drive the operational speed of implantable rotary blood pumps (IRBPs) for patients with heart failure (HF). The method used sensorless measurements of the pump flow to track the desired reference flow (Qr). A dynamical estimator model was used to estimate the average pump flow (Q^est) based on pulse-width modulation (PWM) signals. A proportional-integral (PI) controller integrated with a fuzzy logic control (FLC) system was developed to automatically adapt the pump flow. The Qr was modeled as a constant and trigonometric function using an elastance function (E(t)) to achieve a variation in the metabolic demand. The proposed method was evaluated in silico using a lumped parameter model of the cardiovascular system (CVS) under rest and exercise scenarios. The findings demonstrated that the proposed control system efficiently updated the pump speed of the IRBP to avoid suction or overperfusion. In all scenarios, the numerical results for the left atrium pressure (Pla), aortic pressure (Pao), and left ventricle pressure (Plv) were clinically accepted. The Q^est accurately tracked the Qr within an error of 0.25 L/min.

A modified monopole patch antenna for microwave-based hemorrhagic or ischemic stroke recognition is presented in this article. The designed antenna is fabricated on a cost-effective FR-4 lossy material with a 0.02 loss tangent and 4.4 dielectric constant. Its overall dimensions are 0.32 λ × 0.28 λ × 0.007 λ, where λ is the lower bandwidth 1.3 GHz frequency wavelength. An inset feeding approach is utilized to feed the antenna to reduce the input impedance (z = voltage/current). A total bandwidth (below −10 dB) of 2.4 GHz (1.3–3.7 GHz) is achieved with an effective peak gain of over 6 dBi and an efficiency of over 90%. A time-domain analysis confirms that the antenna produces minimal signal distortion. Simulated and experimental findings share a lot of similarities. Brain tissue is penetrated by the antenna to a satisfactory degree, while still exhibiting a safe specific absorption rate (SAR). The maximum SAR value measured for the head model is constrained to be equal to or below 0.1409 W/kg over the entire usable frequency band. Evaluation of theoretical and experimental evidence indicates the intended antenna is appropriate for Microwave Imaging (MWI) applications.

Fluid structure interaction simulations h hold promise in studying normal and abnormal cardiac function, including the effect of fluid dynamics on mitral valve (MV) leaflet motion. The goal of this study was to develop a 3D fluid structure interaction computational model to simulate bileaflet MV when interacting with blood motion in left ventricle (LV).The model consists of ideal geometric-shaped MV leaflets and the LV, with MV dimensions based on human anatomical measurements. An experimentally-based hyperelastic isotropic material was used to model the mechanical behaviour of the MV leaflets, with chordae tendineae and papillary muscle tips also incorporated. LV myocardial tissue was prescribed using a transverse isotropic hyperelastic formulation. Incompressible Navier-Stokes fluid formulations were used to govern the blood motion, and the Arbitrary Lagrangian Eulerian (ALE) method was employed to determine the mesh deformation of the fluid and solid domains due to trans-valvular pressure on MV boundaries and the resulting leaflet movement.The LV-MV generic model was able to reproduce physiological MV leaflet opening and closing profiles resulting from the time-varying atrial and ventricular pressures, as well as simulating normal and prolapsed MV states. Additionally, the model was able to simulate blood flow patterns after insertion of a prosthetic MV with and without left ventricular outflow tract flow obstruction. In the MV-LV normal model, the regurgitant blood flow fraction was 10.1 %, with no abnormality in cardiac function according to the mitral regurgitation severity grades reported by the American Society of Echocardiography.Our simulation approach provides insights into intraventricular fluid dynamics in a contracting LV with normal and prolapsed MV function, as well as aiding in the understanding of possible complications after transcatheter MV implantation prior to clinical trials.

Monitoring tissue composition could be persistent for many medical applications. Bioimpedance may be useful for monitoring several cardiovascular parameters such as cardiac output, stroke volume, blood pressure and heart rate. In addition, it could be useful for diagnosing the mitral insufficiency, stenosis, and other valvular heart diseases. The purpose of this study is to use the bioimpedance signal to determine the heart rate. This study involved 51 volunteers (28 male, 23 female) ranging from 20 to76 years. A current of 1 mA at 30 kHz was injected through two outer electrodes placed on the subject’s left arm and then the impedance was collected using two inner electrodes placed between the former outer electrodes. The acquired bioimpedance signal was pre-processed and used to identify the peaks and calculated the average interval. Thus, heart rates of each subject were calculated and then compared with actual measurement from FUZZY model MP3 digital blood pressure monitor. The results showed high correlation, 95.44 %, between the calculated heart rates and measurements. The various clinical applications of bioimpedance will help further promote the technique and several parameters can be determined using the electrical bioimpedance approach.

Electrical impedance tomography (EIT) is a low-cost noninvasive imaging method. The main purpose of this paper is to highlight the main aspects of the EIT method and to review the recent advances and developments. The advances in instrumentation and in the different image reconstruction methods and systems are demonstrated in this review. The main applications of the EIT are presented and a special attention made to the papers published during the last years (from 2015 until 2020). The advantages and limitations of EIT are also presented. In conclusion, EIT is a promising imaging approach with a strong potential that has a large margin of progression before reaching the maturity phase.

Very few studies have been concerned with assessing the prevalence of burnout and depressive symptoms, especially during an infectious outbreak on non-frontline health care workers, such as a psychiatrist. In such instances, the role of psychiatrists and other mental health providers as a source of psychological support to the public and frontline workers is indispensable and valuable. This study aims to assess the prevalence of burnout and depressive symptoms, and their correlation, during the COVID-19 pandemic among psychiatry residents in Saudi Arabia. A total of 121 out of 150 psychiatry residents in Saudi Arabia completed the Maslach Burnout Inventory and Patient’s Health Questionnaire for the assessment of burnout and depressive symptoms. Burnout symptoms were found in 27.3%, and another 27.3% reported having depression symptoms. In addition, 16.5% reported having both burnout and depressive symptoms, with a significant relationship between them. Participants in the first 2 years of training and having a history of receiving mental health treatment in the past 2 years were at higher risk. The need is urgent to increase investment in mental health services and to construct a plan to reduce this risk of burnout and depression among psychiatrists by developing preventative strategies to prevent burnout and promote wellness is more important than ever.

Currently, antiviral drugs and/or vaccines are not yet available to treat or prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we narrated the available data, from credible publishers, regarding the possible role of polyphenols and natural extracts-containing polyphenols in the prevention of coronavirus disease 2019 (COVID-19), and their immune-boosting properties. It was revealed that polyphenols could be considered as promising biologically active substances for the prevention of COVID-19. The underlying potential mechanism behind this action is mostly due to the antiviral activities and the immune-regulation functions of polyphenols against COVID-19-infections. Antivirus polyphenolic-based medications can mitigate SARS-CoV-2-enzymes, which are vital for virus duplication and infection. It was also found that triterpenoid, anthraquinone, flavonoids, and tannins are possible keys to scheming antiviral therapies for inhibiting SARS-CoV-2-proteases. The identified pharmacophore structures of polyphenols could be utilized in the explanation of novel anti-COVID-19 designs. The advantage of using mixtures containing polyphenols is related to the high-safety profile without having major side-effects, but further randomized controlled trials are required in the upcoming studies., Highlights • Polyphenols possess many potential health benefits, including antiviral effects. • Polyphenols consider promising bioactive substances for COVID-19 prevention. • Polyphenol-rich foods will be helpful during the COVID-19's treatment. • Polyphenols assist as blocking agent for protease's enzymatic activity of COVID-19.

Many wheelchair people depend on others to control the movement of their wheelchairs, which significantly influences their independence and quality of life. Smart wheelchairs offer a degree of self-dependence and freedom to drive their own vehicles. In this work, we designed and implemented a low-cost software and hardware method to steer a robotic wheelchair. Moreover, from our method, we developed our own Android mobile app based on Flutter software. A convolutional neural network (CNN)-based network-in-network (NIN) structure approach integrated with a voice recognition model was also developed and configured to build the mobile app. The technique was also implemented and configured using an offline Wi-Fi network hotspot between software and hardware components. Five voice commands (yes, no, left, right, and stop) guided and controlled the wheelchair through the Raspberry Pi and DC motor drives. The overall system was evaluated based on a trained and validated English speech corpus by Arabic native speakers for isolated words to assess the performance of the Android OS application. The maneuverability performance of indoor and outdoor navigation was also evaluated in terms of accuracy. The results indicated a degree of accuracy of approximately 87.2% of the accurate prediction of some of the five voice commands. Additionally, in the real-time performance test, the root-mean-square deviation (RMSD) values between the planned and actual nodes for indoor/outdoor maneuvering were 1.721 × 10−5 and 1.743 × 10−5, respectively.

Background: The objective was to evaluate the level of awareness regarding systemic lupus erythematosus (SLE) among the general population in the Al-Qassim region, Kingdom of Saudi Arabia (KSA).Methods: This was a cross-sectional study carried out between March and April 2021 and conducted among the general population at Al-Qassim region, KSA. A valid pre-tested electronic questionnaire was distributed through social media among the targeted population that included socio-demographic characteristics and questionnaires measuring awareness, attitude and their belief about SLE. All statistical analyses were performed using SPSS version 26.Results: A total of 377 participants were enrolled. The most common age group was more than 40 years old (39%), with slightly females (52.5%) than males. The prevalence of participants who had heard about SLE was 52.5%. Of those who have heard about SLE, a poor level of awareness was detected among 69.2% of participants, while 30.8% were at a good level. Factors associated with an increased level of awareness were having diagnosed been with SLE and those who indicated their doctor as their sources of SLE information.Conclusions: The awareness of the general population in the Al-Qassim region regarding SLE was insufficient. Obtaining SLE information from their doctor and having been diagnosed with SLE are associated with better awareness. We propose that awareness campaigns should be promoted.

Background Th appropriate placement and size selection of mitral prostheses in transcatheter mitral valve implantation (TMVI) is critical, as encroachment on the left ventricular outflow tract (LVOT) may lead to flow obstruction. Recent advances in computed tomography (CT) can be employed for pre-procedural planning of mitral prosthetic valve placement. This study aims to develop patient-specific computational fluid dynamics models of the left ventricle (LV) in the presence of a mitral valve prosthesis to investigate blood flow and LVOT pressure gradient during systole. Methods Patient-specific computational fluid dynamics simulations of TMVI with varied cardiac anatomy and insertion angles were performed (n = 30). Wide-volume full cycle cardiovascular CT images prior to TMVI were used as source anatomical data (n = 6 patients). Blood movement was governed by Navier-Stokes equations and the LV endocardial wall deformation was derived from each patient's CT images. Results The computed pressure gradients in the presence of the mitral prosthesis compared well with clinically measured gradients. Analysis of the effects of prosthetic valve angulation, aorto-mitral annular angle, ejection fraction, LV size and new LVOT area (neo-LVOT) after TMVI in silico revealed that the neo-LVOT area (p < 0.001) was the most significant factor affecting LVOT pressure gradient. Angulation of the mitral valve can substantially mitigate LVOT gradient. Conclusions Computational fluid dynamics simulation is a promising method to aid in pre-TMVI planning and understanding the factors underlying LVOT obstruction.

The Na+/K+-ATPase (NKA) complex is the master regulator of membrane potential and a target for anti-cancer therapies. Here, we investigate the effect of drug-induced oxidative stress on NKA activity. The natural product, plumbagin increases oxygen radicals through inhibition of oxidative phosphorylation. As a result, plumbagin treatment results in decreased production of ATP and a rapid increase in intracellular oxygen radicals. We show that plumbagin induces apoptosis in canine cancer cells via oxidative stress. We use this model to test the effect of oxidative stress on NKA activity. Using whole-cell patch-clamp electrophysiology we demonstrate that short-term exposure (4 min) to plumbagin results in 48% decrease in outward current at +50 mV. Even when exogenous ATP was supplied to the cells, plumbagin treatment resulted in 46% inhibition of outward current through NKA at +50 mV. In contrast, when the canine cancer cells were pre-treated with the oxygen radical scavenger, N-acetylcysteine, the NKA inhibitory activity of plumbagin was abrogated. These experiments demonstrate that the oxidative stress-causing agents such as plumbagin and its analogues, are a novel avenue to regulate NKA activity in tumors.

The first case of COVID-19 originated in Wuhan, China, after which it spread across more than 200 countries. By 21 July 2020, the rapid global spread of this disease had led to more than 15 million cases of infection, with a mortality rate of more than 4.0% of the total number of confirmed cases. This study aimed to predict the prevalence of COVID-19 and to investigate the effect of awareness and the impact of treatment in Saudi Arabia. In this paper, COVID-19 data were sourced from the Saudi Ministry of Health, covering the period from 31 March 2020 to 21 July 2020. The spread of COVID-19 was predicted using four different epidemiological models, namely the susceptible&ndash, infectious&ndash, recovered (SIR), generalized logistic, Richards, and Gompertz models. The assessment of models&rsquo, fit was performed and compared using four statistical indices (root-mean-square error (RMSE), R squared (R2), adjusted R2 (&nbsp, Radj2), and Akaike&rsquo, s information criterion (AIC)) in order to select the most appropriate model. Modified versions of the SIR model were utilized to assess the influence of awareness and treatment on the prevalence of COVID-19. Based on the statistical indices, the SIR model showed a good fit to reported data compared with the other models (RMSE = 2790.69, R2 = 99.88%, Radj2 = 99.98%, and AIC = 1796.05). The SIR model predicted that the cumulative number of infected cases would reach 359,794 and that the pandemic would end by early September 2020. Additionally, the modified version of the SIR model with social distancing revealed that there would be a reduction in the final cumulative epidemic size by 9.1% and 168.2% if social distancing were applied over the short and long term, respectively. Furthermore, different treatment scenarios were simulated, starting on 8 July 2020, using another modified version of the SIR model. Epidemiological modeling can help to predict the cumulative number of cases of infection and to understand the impact of social distancing and pharmaceutical intervention on the prevalence of COVID-19. The findings from this study can provide valuable information for governmental policymakers trying to control the spread of this pandemic.

Atovaquone is a FDA-approved antimalarial agent that has also shown potent anticancer properties. In the current study, we demonstrate that atovaquone is a prime candidate for treatment of high-grade serous ovarian cancer. We have tested atovaquone against a panel of ovarian cancer cells lines and shown that this drug inhibits proliferation and induces apoptosis at IC50 concentrations between 10-20 microM. Exposure to atovaquone results in increased apoptosis as indicated by an increase in cleaved caspase 3 and other relevant apoptotic markers. Additionally, our data also suggest that atovaquone is able to reactivate p53. Inhibition of p53 attenuates the cytotoxicity of atovaquone. However, the primary event that occurs in atovaquone-treated cells is the rapid surge in intracellular oxygen radicals. Imaging cytometry experiments conclusively demonstrate that the oxygen radical surge originates in the mitochondria. The oxidative stress caused by atovaquone is responsible for DNA damage and p53 activation. The atovaquone-induced oxygen radical surge also leads to damage to the Na+/K+-ATPase, perturbing the ability of the cancer cells to maintain an optimal membrane potential. This increase in oxygen radicals occurs because atovaquone targets the oxidative phosphorylation pathway in the mitochondria and blocks electron transport. Measurements conducted on the Seahorse analyzer show decreased consumption of oxygen and lower levels of ATP in the atovaquone-treated cells. In the malarial parasite, atovaquone targets mitochondrial complex III. In ovarian cancer cells, supplying succinate did not reverse atovaquone-induced inhibition of oxidative phosphorylation. On the other hand, when cells were supplemented with the substrate for complex IV, the oxygen consumption rate normalized in atovaquone-exposed cells. These experiments suggest that atovaquone is likely inhibiting complex I-III of mitochondria. Atovaquone is a naphthoquinone with significant structural similarity with the electron transporter ubiquinone. In silico modeling experiments indicate that atovaquone can bind to the ubiquinone binding pocket on complexes I-III. Based on these experiments, we propose that atovaquone is competing with ubiquinone to inhibit efficient electron transport and thereby increasing the intracellular oxygen radicals. Ovarian tumor-bearing mice tolerated prolonged treatment with Mepron®, the clinical formulation of atovaquone. Daily treatment of ID8 tumor-bearing C57BL/6 mice with atovaquone for 3-4 weeks resulted in a significant decrease in tumor growth. Additionally, we also show decreased proliferation of human ovarian tumors treated ex vivo with atovaquone. These experiments indicate that atovaquone can be used as a safe and effective drug for chemoprevention and chemotherapy of ovarian tumors. Citation Format: Arvinder Kapur, Mildred Felder, Yousef Alharbi, Allegra Cappuccini, Bikash Pattnaik, Lisa Barroilhet, Manish Patankar. Antimalarial agent, atovaquone, inhibits cancer cell proliferation by targeting oxidative phosphorylation and is a candidate for chemoprevention and chemotherapy of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B36.

With their role in connecting disease-associated antigens to the cellular immune response, antibodies hold considerable promise as therapeutic agents. This chapter discusses three classes of therapeutic antibodies that have been developed for use in ovarian cancer therapy. The first includes antibodies selected against tumor-associated antigens such as MUC16/CA125, mesothelin, epithelial cell adhesion molecule, and folate receptor α‎. Antibodies in the second class target proteins such as CTLA-4 and PD1 that act as immune response checkpoint receptors. The third class of antibodies target secreted factors that promote tumor growth: targets in this class include vascular endothelial growth factor, cytokines, and chemokines. The development of each of these is described. The chapter also discusses the complications presented by soluble antigens, which serve to limit the applicability of antigens (such as MUC16/CA125) that are both cell-surface associated and circulating and the prospects for the combination of antibody-based immunotherapy and chemotherapy.

Aerobic glycolysis is an important metabolic adaptation in tumors. However, there is mounting evidence that oxidative phosphorylation (OXPHOS) also contributes to metabolism in cancer cells. Therefore, agents targeting OXPHOS can serve as novel anticancer agents. We will present data on small molecule agents that inhibit the proliferation of ovarian and other cancer cells by inhibiting mitochondrial electron transport. We have focused our attention on citral, plumbagin, curcumin, cinnamaldehyde, piperlongumine, perillaldehyde, nonenal and other naturally occurring agents. All of these molecules share a common molecular epitope, the unsaturated carbonyl that participates in redox reactions. Cancer cells treated with these agents show a marked decrease in oxygen consumption rate and an increase in extracellular acidification. The redox ratio (NADH/FAD) and cellular ATP levels also decrease in response to these small molecule agents. In our search for additional and more potent OXPHOS inhibitors we have discovered that the FDA-approved anti-malarial drug atovaquone is an efficient inhibitor of electron transport in ovarian cancer cells. Chronic administration of atovaquone decreases the growth of ID8 tumors in C57BL/6 mice. Investigation in to the mechanism of action of the unsaturated carbonyl compounds indicates that their initial effect in cancer cells is the immediate and substantial rise in oxygen radicals as a result of OXPHOS inhibition. This increase in reactive oxygen causes extensive oxidative damage leading to DNA strand breaks. Subsequently, we have observed activation of p53-mediated apoptosis. These experiments are suggesting that inhibition of OXPHOS and the subsequent increase in intracellular oxygen radicals can result in the reactivation of the tumor suppressive responses of at least a subset of the p53 mutants. Additionally, our studies also indicate that the oxidative stress occurring as a result of OXPHOS inhibition directly leads to inhibition of ion transport through the Na+/K+-ATPase. As a result of this inhibition, cancer cells are unable to maintain a normal membrane potential. Studies are currently underway to determine if the inability to maintain membrane potential also contributes to apoptotic cancer cell death induced by these unsaturated carbonyl-containing compounds. Oxidative stress caused by these compounds leads to an increase in superoxide dismutase, catalase and glutathione synthesis via the activation of Nrf-2. Inhibition of Nrf-2 results in an increase in the potency of the unsaturated carbonyl compounds. We are therefore examining Nrf-2 increase as a form of chemoresistance mechanism that likely impinges on the anti-cancer activity of the unsaturated carbonyl compounds. These studies are allowing us to develop medicinal chemistry-based approaches to develop novel molecules with increased potency and targetability as OXPHOS inhibitors for the treatment of ovarian cancer. Citation Format: Arvinder Kapur, Amruta Nayak, Mildred Felder, Allegra Cappucini, Spencer Ericksen, Yousef Alharbi, Bikash Pattnaik, Lisa Barroilhet, and Manish S. Patankar. TARGETING OVARIAN TUMORS WITH OXPHOS INHIBITORS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-103.

Plumbagin and atovaquone are chemotoxic to ovarian, breast and other tumors. Both molecules inhibit oxidative phosphorylation causing a rapid increase in intracellular oxygen radicals and apoptosis. Oxidative stress is also known to inhibit the activity of Na+/K+-ATPase (NKA), the ion channel that maintains the membrane potential. Here, we investigate if the oxidative stress mediated by plumbagin and atovaquone also leads to inhibition of NKA activity. We confirm that plumbagin and atovaquone inhibit proliferation of three human (OVCAR-3, SKOV-3 and TYKNu) and one mouse (ID8) ovarian cancer cell lines. Using SKOV-3 and OVCAR-3 as models for ovarian cancer, we demonstrate that oxygen radical scavenger, N-acetylcysteine (NAC) attenuated the cytotoxicity of plumbagin and atovaquone. Using whole cell patch clamping we demonstrate that plumbagin and atovaquone inhibit outward and inward current flowing through NKA in SKOV-3 and OVCAR-3. Both drugs decrease cellular ATP. Providing exogenous ATP (5 mM) in the pipet solution used during patch clamping did not recover NKA activity in the plumbagin or atovaquone treated SKOV-3 and OVCAR-3 cells. However, pretreatment of the cells with NAC completely abrogated the NKA inhibitory activity of plumbagin and atovaquone. Exposure of the SKOV-3 cells to either of the drugs for 1-2 h resulted in a significant decrease in the expression of NKA. We conclude that oxidative stress caused by plumbagin and atovaquone degrades NKA and hence the membrane potential cannot be optimally maintained. Evaluation of compounds that induce oxidative stress should therefore consider contribution of NKA inhibition to the cytotoxic activity of such agents. Citation Format: Yousef Alharbi, Arvinder Kapur, Mildred Felder, Lisa Barroilhet, Bikash Pattnaik, Manish S. Patankar. Plumbagin and atovaquone inhibit Na+/K+-ATPase through the generation of oxidative stress [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 891.

Background: Delay in seeking medical care has many negative effects on the patient’s condition and medical cost, and it reduces the potential benefits of early interventions. Delay in seeking medical care, which is affected by many factors, is a common global problem. This study aimed to study the prevalence and causes of delay in seeking medical care in Al-Madina, Saudi Arabia. Method: This research was a cross-sectional study conducted among Al-Madina population using a self-administrated questionnaire which was only administered when the inclusion and exclusion criteria for the study have been met by the participants. The questionnaire collected the demographic characteristics and information about the prevalence and the reasons of delaying in seeking medical care in Al-Madina, Saudi Arabia. Results: The study included 441 subjects out of which 61.9% were females while 38.1% were males. Seventy-eight and point two percent had university education level. Only 27.4% of participants always seek medical care as soon as they feel they need it. Delayed seeking medical care due to a financial impediment was stated by 26.1% of the subjects. Merely 25.2% had health insurance. The language was the most important criteria when choosing health service providers for 42% of patients. Severe pain forces 40.1% of participants to seek medical care, while moderate pain drives only 4.3% to seek medical care while 58.9% seek medical care when the pain or discomfort increases with time. Conclusion: There was a high prevalence of delay in seeking medical care among Al-Medina population, Saudi Arabia. Economic factors and lack of health insurance are among the main obstacles in seeking medical care. Acute pain serves as the principal reason in seeking medical care among Al- Madina population.

The correct placement of mitral prostheses in transcatheter mitral valve replacement (TMVR) is crucial, since any obstruction of the left ventricular outflow tract (LVOT) by the mitral device may decrease the LVOT area, leading to flow obstruction. Recent advances in patient-specific modelling based

Cardiac glycosides (CG) are potent inhibitors of Na+/K+-ATPase (NKA), inducing apoptosis through the inhibition of ion current. We developed a synthetic CG, CEN09-106, with enhanced cytotoxic potential over conventional CGs such as oubain and others. For specific delivery to the tumor, CEN09-106 was conjugated through a stable chemical linker to antibodies targeted against cell surface proteins that form complexes with NKA. Due to this molecular design CEN09-106 is locally presented to the tumor and inhibits NKA activity. Internalization of CEN09-106 is not required for its cytotoxicity, and hence we refer to this family of antibody-CG complexes as extracellular drug conjugates (EDC). Ovarian tumors overexpress FXYD5, a modulator of NKA activity. We have developed EDC1 to target FXYD5. Here, we demonstrate the ability of EDC1 to target ovarian tumors and confirm its mechanism of action. First, we compared the activity of oubain, CEN09-106, and EDC1 in cell viability assays. While the potency of oubain was approximately 1-10 mM, CEN09-106 and EDC1 both had IC50 between 1-2.5 nM when tested against OVCAR-5, OV2008, and SKOV3 cells. Expression of FXYD5 in these cell lines was confirmed by flow cytometry. The inhibition of cell viability was attributed to apoptosis induced by CEN09-106 and EDC1 as measured by increase in cleaved caspase3 and annexin V binding and decrease in Bcl-2 expression. CEN09-106 and EDC1 also inhibited viability of the cisplatin-resistant C13 (IC50 ~2.5 nM) cells. Whole-cell patch-clamp recording of cancer cells revealed NKA ionic current in SKOV-3 and OV2008 cells after inhibition of majority of the cell surface ion transporters and channels. Outward ion current detected in SKOV3 and OV2008 prior to treatment with CEN09-106 and EDC1 was in the range of 500-1000 pA. Upon treatment with CEN09-106 and EDC1 (2.5 nM, each), the current in these two cell lines decreased to only 200-400 pA, a 60-75% decrease. In vivo administration of EDC1 in nonhuman primates established its low general toxicity profile. In vivo studies in xenograft mouse models are currently under way and are showing promising results with significant inhibition of SKOV3 and OV2008 tumors when CEN09-106 and EDC1 were administered intraperitoneally. In ongoing work, we are screening additional platinum-sensitive and -resistant ovarian cancer lines for their responses to EDC1. These basic and translational studies will serve as the foundation to demonstrate the clinical value of EDC1 in the treatment of patients with ovarian tumors. Citation Format: Yousef Alharbi, Arvinder Kapur, Jim Prudent, David Marshall, Mildred felder, Bikash Pattnaik, Manish Patankar. Antibody-conjugated cardiac glycosides: Potent agents for treatment of ovarian cancer. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B11.