The incidence and clinical manifestations of human brucellosis in a referral hospital in Southern Saudi Arabia between 2015 and 2019.

We determined the incidence and clinical manifestations of human brucellosis from patients who attended a referral hospital in South of Saudi Arabia. A record-based retrospective study was conducted from January 2015 to December 2019 at King Abdulla Hospital, Bisha, Saudi Arabia. Information on patients' demographic characteristics, detailed records of signs and symptoms, and the laboratory findings were reviewed. Of 6,586 patients included, 15.8% (n = 1,041) were infected with brucellosis. The age of infected individuals ranged from five to 95 years, with an average of 35.1 ± 21.2 years. Most infected patients were male (72.3%). Young adults (26-44 years) were the most common age group with the disease (34.1%). The annual rate of infection significantly decreased (P < 0.0001) from 33.2% in 2015 to 12.5% in 2019. An escalating number of brucellosis cases was seen in the spring and peaked during the summer. Fever (35.3%), joint pain (25.5%), generalized body ache (10.7%), and neurological symptoms (10.0%) were the most frequent clinical manifestation associated with brucellosis. Joint pain was commonly found among children (44.4%). Neurological findings were more frequent among adult patients. The study concluded that brucellosis is endemic in Southern Saudi Arabia and needs local health authority to implement preventive and educational program measures. Infected patients may present with diverse, nonspecific clinical manifestations that require intuition from clinicians to detect the disease.

Gene Expression Analysis of Pediatric Acute Myeloid Leukemia Identified a Hyperactive ASXL1/BAP1 Axis Linked with Poor Prognosis and over Expressed Epigenetic Modifiers.

Genetic aberrations in the epigenome are rare in pediatric AML, hence expression data in epigenetic regulation and its downstream effect is lacking in childhood AML. Our pilot study screened epigenetic modifiers and its related oncogenic signal transduction pathways concerning clinical outcomes in a small cohort of pediatric AML in KSA. RNA from diagnostic BM biopsies (n = 35) was subjected to expression analysis employing the nCounter Pan-Cancer pathway panel. The patients were dichotomized into low ASXL1 (17/35; 49%) and high ASXL1 (18/35; 51%) groups based on ROC curve analysis. Age, gender, hematological data or molecular risk factors (FLT3 mutation/molecular fusion) exposed no significant differences across these two distinct ASXL1 expression groups (P > 0.05). High ASXL1 expression showed linkage with high expression of other epigenetic modifiers (TET2/EZH2/IDH1&2). Our data showed that high ASXL1 mRNA is interrelated with increased BRCA1 associated protein-1 (BAP1) and its target gene E2F Transcription Factor 1 (E2F1) expression. High ASXL1 expression was associated with high mortality {10/18 (56%) vs. 1/17; (6%) P < 0 .002}. Low ASXL1 expressers showed better OS {740 days vs. 579 days; log-rank P= < 0.023; HR 7.54 (0.98-54.1)}. The association between high ASXL1 expression and epigenetic modifiers is interesting but unexplained and require further investigation. High ASXL1 expression is associated with BAP1 and its target genes. Patients with high ASXL1 expression showed poor OS without any association with a conventional molecular prognostic marker.

Prevalence of Depressive Symptoms and Its Correlates among Male Medical Students at the University of Bisha, Saudi Arabia.

BACKGROUND: Identifying the potential factors of depression among medical students is the first step towards academic excellence and future safe medical practice. METHODS: A cross-sectional study was conducted from December 2019 to February 2020 at the University of Bisha, College of Medicine (UBCOM), Bisha Province, Saudi Arabia. Male medical students from year one to year six were involved. A self-administered questionnaire was used to collect data about students' socio-demographic and academic characteristics. The Arabic version of the PHQ-9 scale with a score of ≥10 was used to identify depression. Logistic regression analysis was used to assess the prevalence and correlates of depression. RESULTS: Of the 190 male students enrolled, 26.8% had depressive symptoms, of whom 45.1% were experiencing moderate to severe symptoms. The significantly highest depression rate was found among the second-year students, at 43.8% (OR = 2.544; 95% CI 1.178-5.714; p = 0.018), and the lowest rate was found among year one students, at 8.9% (OR = 0.203; 95% CI 0.075-0.560; p = 0.002). Univariate regression revealed a significant correlation between depression and dissatisfaction with family income, loss of family members, having psychological illness, difficulties in personal relationships, regretting studying medicine, failure in an academic year, a lower grade than expected, conflict with tutors, lack of college facilities and heavy academic load. In multivariate analysis, loss of family members (AOR = 3.69; 95% CI 1.86-7.413), difficulties in personal relationships (AOR = 2.371; 95% CI 1.009-5.575), regretting studying medicine (AOR = 3.764; 95% CI 1.657-8.550), and failing an academic year (AOR = 2.559; 95% CI 1.112-5.887) were independently correlated with depression. CONCLUSIONS: The study concluded that medical students at UBCOM experience depressive symptoms associated with various risk indicators. Optimizing the educational and social environment and infrastructure facilities at UBCOM might promote students' mental health and well-being.

Hypertension clinical pathway: Experience of Aseer region, Saudi Arabia.

BACKGROUND: Hypertension (HTN) is a common chronic health problem with many complications and high morbidity rates. This study aimed to describe the HTN pathway, to assess the performance of screening and registration programs, to explore the challenges and suggest solutions for those challenges. MATERIALS AND METHODS: This study was conducted in primary care centers in the Aseer region, Saudi Arabia, at the end of 2022. The study consisted of three parts namely: Screening for HTN, registration of known hypertensive patients and opinions of representatives of Primary Healthcare Centers (PHCs) on challenges to the implementation of HTN pathway and suggestions for overcoming these challenges. Three Google forms were developed by the investigators to achieve the objectives of this study. The first two forms were completed by doctors and nurses at each PHC and reviewed by the leader of HTN pathway, and the third form completed by a representative of each PHC. SPSS version 26 was used for data management and analysis. Chi-square test was used to determine association between categorical variables; binary logistic regression analysis was performed to determine the correlates of being hypertensive and having good control of HTN. RESULTS: A total of 159,243 individuals were screened for HTN, 55% of whom were females and 94% were Saudis. The prevalence of HTN was 13%; 70% were overweight or obese and 14% had diabetes. The total registered number of patients was 55,628; 50% had good HTN control. Major challenges were inadequate health coaches, care coordinators, laboratory and radiology facilities, lack of coordination with hospitals, and ineffective appointment system. CONCLUSION: This study revealed that the current HTN pathway was successful with regard to screening and registration of patients with HTN. Many challenges need an executive plan with SMART objectives to optimize the care for HTN patients in the region.

Differences in Clinical Nature and Outcome Among Young Patients Suffering from an Acute Coronary Syndrome.

PURPOSE: Acute coronary syndrome (ACS) is a life-threatening cardiac disease identified by acute, regional reductions in coronary blood flow, resulting in myocardial ischemia, or infarction, and manifesting as discomfort in the chest area, neck, or arms. Frequently, ACS is provoked by an atherosclerotic plaque; therefore, coronary atherosclerosis is converted into a chronic disease to an acute medical emergency. The purpose of this study was to explore the differences among these variables in patients less than 45 years of age suffering from this major health problem compared to older adults admitted with an ACS diagnosis, and to adopt an optimized temporary management. PATIENTS AND METHODS: A retrospective chart review study was conducted on a total of 652 ACS patients admitted at King Fahad Hospital of the University (KFHU) between 2015 and 2020. The patients' medical records were utilized for obtaining demographic data, presenting symptoms, risk factors, and clinical outcomes. RESULTS: Overall, 652 patients were enrolled. Of these, 109 patients (16.7%) were under 45, with a mean age of 38 ± 7. Younger patients showed a higher rate of palpitation (23.9% versus. 13.6%; P = 0.019). A positive smoking history and a family history of CAD were seen more often in younger patients (42.2% vs 27.3%, P < 0.001; 22.9% vs 9.4%, P < 0.001, respectively). Older patients had greater renal impairment with higher creatinine (median = 1.10 mg/dl (range, 0.3-13.0) vs 1.0 (0.3-19.0; p = 0. 001), BUN (median = 16.0 (mange, 0.9-141.0) vs 12.0 (0.9-49.0); P < 0.001)). Younger patients had higher levels of LDL and total cholesterol (median 138c. 115; p < 0.001) and cholesterol (median 209 vs 178.5; p < 0.001). Hospital mortality was 0.9% in younger patients versus 7.4% in older patients (P = 0.004). CONCLUSION: Palpitations, smoking, family history, higher LDL levels, and total cholesterol levels were more prevalent in adults younger than 45 years old with ACS. Impaired renal function, hypertension, and diabetes were more in older patients with ACS.

Smartphone addiction among medical students in Bisha, Saudi Arabia.

CONTEXT: Smartphones are quickly becoming the most pervasive technological device on the planet. AIMS: This study aims to assess smartphone addiction and the factors associated with it among medical students. SETTINGS AND DESIGN: This study was carried out in Bisha, Saudi Arabia, following a cross-sectional study design. METHODS AND MATERIAL: The data collection tool comprised a self-administered questionnaire. The validated Problematic Use of Mobile Phones (PUMP) scale was used. The PUMP score was calculated by summing up the scores for the individual questions such that higher scores indicate higher levels of addiction. STATISTICAL ANALYSIS USED: Pearson's correlation coefficient was applied to observe the linear relationship between the PUMP scale total score and the quantitative study variables. RESULTS: The mean total PUMP score was 61.55, with a standard deviation of 13.16. The correlation coefficient between daily hours of smartphone usage and total PUMP score was 0.39, with a statistically significant P value (P < 0.0001). The correlation coefficient between smartphone use for games and total PUMP score was 0.19, with a statistically significant P value (P = 0.009). The correlation coefficient between GPA scores and total PUMP scores was -0.21, with a statistically significant P value (P = 0.003). CONCLUSIONS: There is a high prevalence of smartphone addiction among medical students in Bisha city. There is a significant positive correlation between daily hours of smartphone usage and total PUMP score. Playing games on smartphones is significantly associated with smartphone addiction. There is a significant negative correlation relation between GPA score and total PUMP score.

Grewia mollis Leaf Extracts and Fractions Demonstrated Good Inhibitory Activity on Pro-Inflammatory Enzymes and with Lower Cytotoxicity in vitro.

INTRODUCTION: Plant extracts are used to treat illnesses, promote health, and maintain general well-being in traditional medicine. Grewia mollis Juss (Malvaceae) is one of the medicinal herbs that is used traditionally to treat chronic diseases and related pain because currently used anti-inflammatory drugs may cause severe side effects, and naturally occurring compounds with reduced cytotoxicity could be explored for therapeutic goals. MATERIALS AND METHODS: Dried leaf of G. mollis was extracted with aqueous and organic solvents and partitioned based on polarity using solvent-solvent methods. The extracts were tested in anti-inflammatory assays against cyclooxygenases and lipoxygenase, and the safety profile was determined in a cell-based in-vitro assay. RESULTS: The n-hexane fraction of G. mollis leaf extracts had significant activity against both COX-1 (IC50 =0.97±1.9 µg/mL) and COX-2 (IC50 =1.13±0.2 µg/mL) better than the indomethacin positive control (IC50 =1.3±0.6 and 1.52±0.2 µg/mL), respectively (p≤ 0.05). Also, all the extracts and fractions of G. mollis tested inhibited the activity of 15-LOX (IC50 =12.48±2.9 to 29.43±9.9 µg/mL) better than the quercetin reference control (IC50 =61.82±5.5 µg/mL), with the butanol fraction demonstrating the best anti-15 LOX action (IC50 =12.48±2.9 µg/mL). Furthermore, all the extracts and fractions of G. mollis had relatively lower cytotoxicity on vero monkey kidney cells (LD50 =30.56-479±0.07 µg/mL) compared to the doxorubicin positive control (LD50 =2.59 µg/mL), but the selectivity index (SI=1.04-1.89) determination suggested that some of the extracts may contain toxic constituents. CONCLUSION: Organic extracts of the leaves of Grewia mollis contained bioactive molecules with potent action on COX-2 and 15-LOX. Targeted high-resolution high-performance liquid chromatographic (HPLC) methods have streamlined and enhanced bioactive compound isolation and purification process. This allows for the separation of undesirable compounds that could cause metabolic cytotoxicity in the plant extract mixtures. The method could be used to develop an alternative therapeutic strategy to manage pain associated with chronic inflammation where the use of NSAID is problematic.

Assessment of health-related quality of life among obese patients in Abha, Saudi Arabia.

CONTEXT: Numerous studies have demonstrated that obese individuals experience significant impairments in quality of life as a result of their obesity, with greater impairments associated with greater degrees of obesity. AIMS: To assess the quality of life (QOL) and its clinical and sociodemographic determinants among adolescents and adult obese patients (>12 years old) attending obesity and/or nutritional clinics at Aseer Central Hospital, Abha, KSA. SETTING AND STUDY DESIGN: This cross-sectional study was conducted in Aseer central hospital. SUBJECTS AND METHODS: A cross-sectional study was carried out among a representative sample of all obese patients attending nutrition and obesity clinic at Aseer central hospital for a period of 2 months. A self-administered questionnaire was used to collect data. STATISTICAL ANALYSES: Statistical Package for the Social Sciences (SPSS) ver. 20 was used to do the statistical analyses. RESULTS: Overall, 198 obese patients completed the questionnaire and measurements gave a response rate of 84.3%. Their age ranged between 19 and 56 years with a mean age of 31.6 years and standard deviation of 6 years. In total, 56.1% were females. CONCLUSIONS: The study showed that the severe obese individuals (grade 3) suffer from poorer health-related QOL (HRQOL) compared to those of grades 1 and 2, as the increase in body mass index (BMI) lowers the HRQOL domains.

Steps toward the prevention of hemoglobinopathies in the kingdom of Saudi Arabia.

Saudi Arabia is known to have high prevalence of hereditary blood disorder similar to neighboring Mediterranean countries, in particular sickle-cell disease and thalassemia. With increasing number of affected individual (Saadallah AA, Rashed MS. J Inherit Metab Dis. 2007;30:482-489), the Ministry of Health (MOH) had implemented a mandatory premarital testing for hemoglobinopathies (sickle-cell disease and thalassemia). Since November 2003, all Saudi couples planning for marriage are required to perform the test (Alhamdan NA, Almazrou YY, Alswaidi FM, Coudhry AJ. Genet Med. 2007;9(6):372-377). Besides its preventive efforts, the MOH had also increased its efforts to improve the health care given to affected hereditary blood disease patients. To that effect, a plan to increase the number of specialized hereditary blood disease centers in different regions is existing. In addition, a Consultation Board, Hereditary Blood Disease Advisory Committee, was formed in January 2008. This committee, under the directorate of MOH, took the responsibility of laying down the foundation for internationally high standard of medical care given in treatment center dealing with patients with hereditary blood disorders. In this report, we will shed some light on such accomplishment.

Medical students' perception of their educational environment at Imam Abdulrahman Bin Faisal University, Kingdom of Saudi Arabia.

OBJECTIVE: The purpose of this study was to investigate students' perception of the educational climate in a medical school in Dammam, Kingdom of Saudi Arabia (KSA). The difference in the perception of preclinical year students and clinical year students was also evaluated. MATERIALS AND METHODS: This cross-sectional study was conducted among 2nd to 6th year students at the medical college of Imam Abdulrahman Bin Faisal University. "Dundee Ready Educational Environment Measure" (DREEM) was used to evaluate the educational environment. RESULTS: Out of 518, 238 students participated in the study; participation rate of 45.9%. The average DREEM score was 112.38 with a SD of 22.4. Students' perception of atmosphere got the highest score (27.1 ± 6.7) of the five DREEM subscales. The 3rd year had the highest DREEM score compared to students of other levels, while the DREEM score of preclinical students was significantly higher than that of the clinical year students. CONCLUSION: Perception of medical students about the educational climate was more positive than negative. Although the DREEM score and its subdomains showed a positive educational environment, students still mentioned some problematic areas that need to be addressed. Findings of this study could encourage other medical colleges in the KSA to focus on weak areas and address the issues raised by students, especially clinical year students.

Knowledge, attitude, and performance of primary healthcare physicians in Aseer Region, Saudi Arabia about attention deficit hyperactivity disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders. This study aimed to assess the knowledge, attitude, and practice of primary health-care (PHC) physicians on diagnosis and management of ADHD. MATERIALS AND METHODS: This was a cross-sectional study included 340 PHC physicians in Aseer Region, Saudi Arabia. A self-administered questionnaire was used to collect data on personal characteristics, knowledge, attitude, and practice of the diagnosis and management of ADHD. RESULTS: Nearly 47.6% of the PHC physicians were aged <30 years, 60.3% were male, 79.1% were Saudi nationals, and 84.1% had completed MBBS. Only 13.2% had attended continuing medical education courses on ADHD, 63.2% had read about ADHD; Internet was the main source of information (30.7%). Participants' attitude toward ADHD was mainly positive, while 32.1% had poor knowledge and 17.6% had diagnosed ADHD cases in the last year, but 73.3% had referred the diagnosed cases to specialists. Participants' knowledge differed significantly according to their age, gender, and nationality. CONCLUSIONS: PHC physicians' knowledge about ADHD was suboptimal, but they had a positive attitude toward their role with regard to ADHD. PHC physicians should focus on the clinical and diagnostic aspects of ADHD. Awareness and interest of undergraduate medical students and newly graduated physicians in ADHD should be raised. The Ministry of Health should encourage attendance at extracurricular courses and workshops.

Cytogenetic Profile and FLT3 Gene Mutations of Childhood Acute Lymphoblastic Leukemia.

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent genetic aberrations. The identification of those abnormalities is clinically important because they are considered significant risk-stratifying markers. AIMS: There are insufficient data of cytogenetic profiles in Saudi Arabian patients with childhood ALL leukemia. We have examined a cohort of 110 cases of ALL to determine the cytogenetic profiles and prevalence of FLT3 mutations and analysis of the more frequently observed abnormalities and its correlations to other biologic factors and patient outcomes and to compare our results with previously published results. MATERIALS AND METHODS: Patients-We reviewed all cases from 2007 to 2016 with an established diagnosis of childhood ALL. Of the 110 patients, 98 were B-lineage ALL and 12 T-cell ALL. All the patients were treated by UKALL 2003 protocol and risk stratified according previously published criteria. Cytogenetic analysis-Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Analysis of FLT3 mutations-Bone marrow or blood samples were screened for FLT3 mutations (internal tandem duplications, and point mutations, D835) using polymerase chain reaction methods. RESULT: Cytogenetic analysis showed chromosomal anomalies in 68 out of 102 cases with an overall incidence 66.7%. The most frequent chromosomal anomalies in ALL were hyperdiploidy, t(9;22), t(12;21), and MLL gene rearrangements. Our data are in accordance with those published previously and showed that FLT3 mutations are not common in patients with ALL (4.7%) and have no prognostic relevance in pediatric patients with ALL. On the contrary, t(9;22), MLL gene rearrangements and hypodiploidy were signs of a bad prognosis in childhood ALL with high rate of relapse and shorter overall survival compared with the standard-risk group (P = .031).The event-free survival was also found to be worse (P = .040). CONCLUSIONS: Our data are in accordance with those published previously, confirming the overall frequency of cytogenetic abnormalities and their prognostic relevance.

Snake venom causes apoptosis by increasing the reactive oxygen species in colorectal and breast cancer cell lines.

Snake venom possesses various kinds of proteins and neurotoxic polypeptides, which can negatively interfere with the neurotransmitter signaling cascade. This phenomenon occurs mainly due to the blocking of ion channels in the body system. Envenomation prevents or severely interrupts nerve impulses from being transmitted, inhibition of adenosine triphosphate synthesis, and proper functioning of the cardiac muscles. However, some beneficial properties of venoms have also been reported. The aim of this study was to examine the snake venom as an anticancer agent due to its inhibitory effects on cancer progression such as cell motility, cell invasion, and colony formation. In this study, the effect of venoms on phenotypic changes and the change on molecular level in colorectal and breast cancer cell lines were examined. A reduction of 60%-90% in cell motility, colony formation, and cell invasion was observed when these cell lines were treated with different concentrations of snake venom. In addition, the increase in oxidative stress that results in an increase in the number of apoptotic cancer cells was significantly higher in the venom-treated cell lines. Further analysis showed that there was a decrease in the expression of pro-inflammatory cytokines and signaling proteins, strongly suggesting a promising role for snake venom against breast and colorectal cancer cell progression. In conclusion, the snake venoms used in this study showed significant anticancer properties against colorectal and breast cancer cell lines.

Frequency and Prognostic Relevance of FLT3 Mutations in Saudi Acute Myeloid Leukemia Patients.

The Fms-like tyrosine kinase-3 (FLT3) is a receptor tyrosine kinase that plays a key role in cell survival, proliferation, and differentiation of hematopoietic stem cells. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia (AML). AML patients with FLT3 internal tandem duplication (ITD) mutations have poor cure rates the prognostic significance of point mutations; tyrosine kinase domain (TKD) is still unclear. We analyzed the frequency of FLT3 mutations (ITD and D835) in patients with AML at diagnosis; no sufficient data currently exist regarding FLT3 mutations in Saudi AML patients. This study was aimed at evaluating the frequency of FLT3 mutations in patients with AML and its significance for prognosis. The frequency of FLT3 mutations in our study (18.56%) was lower than many of the reported studies, FLT3-ITD mutations were observed in 14.4%, and FLT3-TKD in 4.1%, of 97 newly diagnosed AML patients (82 adult and 15 pediatric). Our data show significant increase of FLT3 mutations in male more than female (13 male, 5 female). Our results support the view that FLT3-ITD mutation has strong prognostic factor in AML patients and is associated with high rate of relapse, and high leucocytes and blast count at diagnosis and relapse.

FLT3 Internal Tandem Duplication and D835 Mutations in Patients with Acute Lymphoblastic Leukemia and its Clinical Significance.

The fms-like tyrosine kinase 3 (FLT3) gene is a member of the class III receptor tyrosine kinase family. Mutations of FLT3 were first described in 1997 and account for the most frequent molecular mutations in acute myeloid leukemia. Currently, there is no published data on FLT3 mutations in Saudi acute lymphoblastic leukemia (ALL) patients. In this retrospective study, we have examined a cohort of 77 ALL patients to determine the prevalence of FLT3 mutations and the possible prognostic relevance of these mutations in ALL patients. Correlations to other biologic factors such as karyotype, molecular mutations, and leukocyte count were also considered. FLT3 internal tandem duplication (ITD) mutations and point mutation in tyrosine kinase domain (D835) were analyzed in ALL patients, at diagnosis, by polymerase chain reaction (PCR). Two cases (2.6%, 2/77) were positive for FLT3 mutations; one was found to have FLT3/ITD and the other FLT3/D835. Our findings suggest that FLT3 mutations are not common in Saudi ALL and do not affect clinical outcome.