Pulsatillic acid as a potential inhibitor of protein kinase C-alpha in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a global health concern with a significant impact on morbidity and mortality. Small molecule inhibitors targeting genetic mutations like EGFR and ALK have shown promise in NSCLC treatment. This study focuses on Protein Kinase C-alpha (PKCα), implicated in NSCLC pathogenesis. Overexpression of PKCα correlates with advanced disease stages. Preclinical studies suggest its inhibition can suppress NSCLC cell growth. The research employs molecular docking to identify Pulsatillic acid (PA) as a potential PKCα inhibitor. ADMET predictions support PA's candidacy and PASS analysis and Swiss Target Prediction reveal its biological properties. Fluorescence-based binding assays demonstrate PA's inhibitory potency on PKCα, aligning with molecular docking findings. Cytotoxicity assays show PA's minimal impact on HEK-293 cell viability, with an IC50 of 21.03 µM in A549 cells. mRNA expression analysis in A549 cells indicates PA's potential inhibitory effect on PKCα. In conclusion, this study highlights that PA may emerge as a promising therapeutic candidate for NSCLC, emphasizing the need for further research, validation, and exploration of its translational potential. The study contributes valuable insights into NSCLC treatment strategies, emphasizing the significance of targeting PKCα.

In-silico and in-vitro studies revealed alpha-amyrin as a potent pnhibitor of TLR2 for the therapeutics of bacterial infection and sepsis.

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

Coronavirus disease 2019 pandemic stress and its effects on irritable bowel syndrome patients in Saudi Arabia.

ABSTRACT: Coronavirus disease 2019 (COVID-19 pandemic has affected the psychological health of people, causing a higher level of stress. Stress can exaggerate the symptoms of irritable bowel syndrome (IBS).To assess the effect of the COVID-19 pandemic stress on patients with IBS in Saudi Arabia.A descriptive cross-sectional approach was used, which targeted accessible subjects with IBS from different regions of Saudi Arabia. Data were collected from participants using a structured electronic questionnaire, which captured the participants' socio-demographic data, medical history, IBS clinical data, self-reported stress due to COVID-19, and its effect on IBS symptoms.A total of 1255 IBS patients completed the questionnaire. About 63.4% of them reported stress due to the pandemic. The most frequently reported causes of stress were fear of infection occurring in the family, followed by fear of self-infection (43.5%), and death due to COVID-19 infection (17.2%). Most of the stressed participants (56.6%) reported that stress usually exaggerated IBS symptoms. Almost 22% of them consulted a physician for stress aggravation of the symptoms, 18.1% used sedatives due to stress, 9.2% modified IBS medications due to the stress, and 75.5% of the participants reported impaired daily activities due to symptoms exacerbation. Coexisting chronic morbidities and inability to differentiate between COVID-19 gastrointestinal symptoms and IBS symptoms were significantly associated with COVID-19 related stress (P = .039 and .001, respectively).Two-thirds of IBS patients were stressed during the first few months of COVID-19 pandemic. Patients unable to differentiate between COVID-19 gastrointestinal tract symptoms and IBS symptoms, and patients suffering from chronic morbidities were more vulnerable. Pandemic stress exacerbated patients' symptoms and impacted their activities of daily life.

Current Practices and Existing Gaps of Continuing Medical Education among Resident Physicians in Abha City, Saudi Arabia.

BACKGROUND: Continuing medical education (CME) is an everlasting process throughout the physician's working life. It helps to deliver better services for the patients. OBJECTIVES: To explore CME among resident physicians in Abha City; their current practices, their opinions, and barriers faced. METHODS: A cross-sectional study was conducted among resident physicians at the Ministry of Health hospitals in Abha City using a validated self-administered questionnaire. It included personal characteristics, current CME practices, satisfaction with CME, and barriers to attendance. RESULTS: The present study included 300 residents from 15 training specialties. Their reported CME activities during the previous year were lectures and seminars (79.7%) followed by conferences (43.7%), case presentations (39.7%), workshops (34.0%), group discussion (29/7%), and journal clubs (27.3%). Astonishingly enough, very few (8%) attended online electronic CME activities. There were significant differences in CME satisfaction scores by different training specialties. Regarding residents' perceptions of the effectiveness of different CME activities (conferences/symposia, workshops/courses, and interdepartmental activities) the results showed that workshops and courses were significantly the most effective method compared to the other two methods in retention of knowledge, improving attitudes, improving clinical skills, improving managerial skills, and in improving practice behaviors. Barriers reported were being busy, lack of interest, high cost, and lack of suitable providers. CONCLUSION: Based on the findings of this study, it is recommended that online learning be promoted as a CME format for trainees. There should be support of residents and clinicians through the provision of protected time for their CME activities outside their daily clinical commitments.

Risk factors of colorectal cancer among Saudi Population: Case-control study.

BACKGROUND: Colorectal cancer (CRC) incidence and related mortalities have been steadily increasing in KSA over the past 20 years. CRC in the Kingdom of Saudi Arabia (KSA) population presents in younger ages and in more advanced disease states as compared to other countries. This study was aimed to determine factors (demographic, habitual, environmental, nutritional, and genetic) associated with CRC in Riyadh, KSA. MATERIALS AND METHODS: A matched case-control study conducted in the major hospitals in Riyadh (King Khalid university Hospital, King Faisal Specialist Hospital, Riyadh Military Hospital, Security Force Hospital, King Fahd Medical City). Here most of CRC cases are managed. The cases (n = 121) group included all recently diagnosed and pathologically confirmed Saudi cases of CRC identified during the period 1st of January 2017 till 31st of December 2018 who agreed to participate and fulfilled the inclusion criteria. A similar number of controls attending the study settings were selected consecutively from the clinics where cases were managed and matched on a 1:1 basis with cases based on age (+/-3 years) and gender. Data were collected using a structured questionnaire. Conditional logistic regression models were fitted to determine factors associated with risk of CRC. RESULT: This study included similar number of males and females in both groups: males 69 (57%) and females 52 (43%) in each group (Chi-square test P = 1.0). The mean (S.D) age in the cases group was 53.6 (S.D = 12.9) and 53.3 (S.D = 12.9) in the controls group (Student test P = 0.86). In the final multivariate conditional logistic regression model, variables independently associated with risk of colorectal cancer were body mass index (OR = 0.93; 95% CI 0.87-0.98; P = 0.011) employment status (inverse relation: OR = 0.33; 95% CI 0.14-0.77; P = 0.010), colon polyps (OR = 4.09; 95% CI 1.06-15.82; P = 0.041), and constipation (OR = 4.98; 95% CI 1.91-15.99; P = 0.001). CONCLUSION: Factors associated with CRC in the major referral hospitals in KSA were colon polyps, chronic constipation, and unemployment. These factors should be considered when screening for patients at risk for CRC.

Sleep hygiene, sleep-related problems, and their relations with quality of life in a primary-care population in southwest Saudi Arabia.

BACKGROUND: Little is recognized about factors affecting poor sleep hygiene and relations of sleep problems with the quality of life among adults. AIMS: To evaluate sleep hygiene, explore its associated factors, assess the prevalence of excessive daytime sleepiness (EDS) and insomnia, and their relations with sleep hygiene. Besides, correlate sleep problems with life quality. METHODS: A representative sample of primary healthcare population was surveyed using questionnaires comprising sociodemographic characters, personal lifestyles, validated Arabic versions of Epworth sleepiness scales, Athens insomnia scale, short-form health survey questionnaire (SF-12), and developed Arabic sleep hygiene index (SHI). RESULTS: A total of 401 adults participated in the study. The average SHI score was 17.25 ± 7.33. Poorer sleep hygiene was significantly detected in younger age, unmarried, unemployed, smokers, and energy drinks consumers (P < 0.05). Positive significant correlations were correlated with cellphone and video-gaming duration. About 56.61% and 39.90% of participants suffered insomnia symptoms and EDS, respectively. Significant poorer SHI was detected among insomnia and EDS sufferers. Negative significant correlations were observed between scores of both components of SF-12 and EDS, insomnia, and SHI. CONCLUSION: Significant negative associations were detected between SHI, EDS, insomnia, and both components of life quality. The role of sleep hygiene education programs in the promotion of sleep and quality of life need to be considered.

Molecular Mechanisms Contributing Bacterial Infections to the Incidence of Various Types of Cancer.

Cancer causes a major health concern worldwide due to high incidence and mortality rates. To accomplish this purpose, the Scopus, PubMed, and Web of Science databases were searched using the keywords bacteria and cancer. Most of published research addressed several different factors that induced cancer, such as toxins, medications, smoking, and obesity. Nonetheless, few studies are dealing with cancer induction via bacterial infection. In addition, mechanisms of cancer induction via bacterial infections are not well understood. Therefore, in this review, we will shed light on different bacteria that induced cancer via different molecular mechanisms. Among the bacterial infection that induced cancer, Helicobacter pylori was the first recognized bacteria which caused gastric cancer and might be also linked to extragastric cancer in humans. H. pylori has been associated with adenocarcinoma in the distal stomach by its ability to cause severe inflammations. It has been found that inflammations induced cancer via different mechanisms including induction of cell proliferation and production of high levels of free radicals. Recently, free radicals were found to induce and cause various types of cancer. Salmonella typhi has been found to be associated with gallbladder carcinoma (GBC). Also, intercellular infection of lungs with Chlamydia pneumoniae was found to contribute as one of the ethological factors of lung cancer. Moreover, infection of the urinary tract with Staphylococcus aureus, Klebsiella spp., and Proteus mirabilis has been found to cause bladder cancer. These microorganisms produce a high level of N-nitrosamines which are metabolically activated leading to the generation of alkylating agents that damage DNA and other macromolecules. It is concluded that a certain bacterium is linked with induction of a specific type of cancer via different molecular and biochemical mechanisms as discussed in the text in details. This infection could potentially affect human health in different ways. In addition, it is important to know the possible factors involved in cancer induction for better treatment of cancer patients.

Effect of Hypovitaminosis D on Lipid Profile in Hypothyroid Patients in Saudi Arabia.

BACKGROUND: Hypothyroidism is believed to be associated with dyslipidemia and is considered a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD). Vitamin D, due to its steroid hormone action, retains cell function and controls the metabolism of lipids. Therefore, the present study was carried out to show the association of the risk factors of ASCVD and deficiency of thyroid hormones and vitamin D levels since no previous studies have been performed on Saudi patients before. Methodology. A retrospective cohort study was carried out on 400 hypothyroid patients. Medical records of those patients were followed up and were classified as normal and hypothyroid patients according to their thyroid-stimulating hormone levels. TSH, vitamin D, and lipid profiles were determined using the ELISA technique. RESULT: Total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were significantly higher in hypothyroid patients than those in the normal group. We have found a significant correlation between TSH levels and the risk factors of ASCVD (total cholesterol, triglycerides, and LDL-C). Moreover, a significant correlation between vitamin D levels and the risk factors of ASCVD (total cholesterol, triglycerides, and LDL-C) has been found. In addition, there is a correlation between deficiency of Vit D and low-TSH levels (95% CI 1.092-4.05) indicating a higher risk for the development of ASCVD among those patients. CONCLUSION: Hypothyroid and vitamin D-deficient patients must be screened regularly at an early stage to predict and also to prevent cardiovascular diseases. Moreover, an adequate supply of vitamin D and TH should be given to those patients to prevent cardiovascular diseases at an early stage.

Knowledge and attitude regarding child abuse among primary health care physician in Abha, Saudi Arabia, 2018.

BACKGROUNDS: Child abuse or child maltreatment is physical, sexual, or psychological maltreatment or neglect of a child or children, especially by a parent or other caregiver. Child abuse may include any act or failure to act by a parent or other caregiver that results in actual or potential harm to a child, and can occur in a child's home or in the organizations, schools, or communities the child interacts with. This study was conducted to assess the primary health care (PHC) centers' physicians' knowledge and attitude toward child abuse including its types, and child neglect with their behavior regarding reporting of abuse cases. METHODS: A cross-sectional study was conducted in Abha which is the capital of Aseer Province, including all PHC physicians (about 475) working in PHC centers. Data regarding physicians' demographic characteristics, perception, and awareness regarding child abuse and neglect were collected by self-administrative questionnaire in the PHC center during their time between patients' consultation. RESULTS: The study included 300 PHC physicians whose ages ranged from 25 to 50 years old with mean age of 28 years. About 65% of the physicians were males and 69% of them were married with about 73% having at least one child. Overall, 96.3% of the physicians recorded good awareness level regarding types of child abuse and 97.3% recorded good awareness level regarding child neglect patterns. Underreporting of child abuse cases was recorded by about 64% of physicians. CONCLUSION: Regarding child abuse and neglect, PHC physicians have good knowledge, optimal attitude, and positive perception. There was also the problem of underreporting of suspected child abuse cases among PHC physicians in Saudi Arabia, with many barriers to report, such as community traditions; unclear reporting strategy was identified.

Burnout Syndrome among Emergency Physicians and Nurses in Abha and Khamis Mushait Cities, Aseer Region, Southwestern Saudi Arabia.

OBJECTIVES: To explore the magnitude and determinants of burnout among emergency physicians and nurses working at emergency departments of hospitals in Abha and Khamis Mushait cities. SUBJECTS AND METHODS: A cross-sectional hospital-based study was conducted in emergency departments of hospitals in Abha and Khamis Mushait cities belonging to Ministry of Health. All physicians (n=95) and nurses (n=187) currently working at these sites were invited to participate in the study by filling a validated self-administered questionnaire including two main sections: personal and professional characteristics of physicians and nurses as well as Maslach burnout inventory (MBI) to assess the three components of the burnout syndrome: emotional exhaustion, depersonalization, and reduced personal accomplishment. RESULTS: The study included 282 physicians and nurses. The age of more than half of them (54.3%) ranged between 31 and 35 years. Most of them (70.9%) were females. About two-thirds of the respondents (66.3%) were nurses while the remaining 33.7% were physicians. Majority of the emergency healthcare professionals (88.7%) had high emotional exhaustion. The prevalence of high depersonalization (cynicism) was 20.6% whereas that of low personal accomplishment was 41.1% among emergency healthcare professionals. The overall prevalence of burnout among healthcare professionals was 16.3%. Multivariate logistic regression analysis revealed that male healthcare professionals were at almost higher three-folded risk for developing burnout compared to females (aOR=2.76; 95% confidence interval (CI): 1.21-6.28, p=0.017)). Smokers were at higher significant risk for burnout compared to nonsmokers (aOR=15.37; 95% CI: 7.06-33.45, p<0.001). Healthcare professionals who reported a history of taking medications for sleep disorders expressed higher risk for burnout opposed to those with no history of sleep disorder medication (aOR=6.59; 95% CI: 2.08-20.81, p=0.001). CONCLUSION: A considerable proportion of physicians and nurses working at emergency departments of hospitals in Abha and Khamis Mushait cities had burnout syndrome, particularly high emotional exhaustion and low personal accomplishment.