FOXO1 and PAX5 Rearrangement in Alveolar Rhabdomyosarcoma in Saudi Pediatric Patients.

Objective: In this study, we investigate the molecular rearrangement of FOXO1 in alveolar rhabdomyosarcoma (ARHS) in Saudi pediatric patients. Method: We performed a molecular detection of molecular translocation in 30 pediatric cases of ARHS using FOXO1 dual color break-apart FISH probe (ZytoLight®, 13q14.11) and PAX5 dual color break-apart FISH probe (ZytoLight®, 9p13.2). Results: All analyzable cases of ARHS demonstrated FOXO1 translocation whereas PAX5 translocation was not detected in any case. Conclusion: Although the testing for PAX5 rearrangement was based on protein-protein network analysis, our study showed that PAX5 translocation is not conspicuous in ARHS. PAX7/3::FOXO1 fusion genes feature ARMS, rendering crossreactivity between PAX7 and PAX3 a possible explanation. Nevertheless, PAX5 immunoreactivity and molecular translocation could be an adjunctive pathway that is confined to aggressive ARMS.

Effect of Apremilast on LPS-induced immunomodulation and inflammation via activation of Nrf2/HO-1 pathways in rat lungs.

Lipopolysaccharides (LPS), the lipid component of gram-negative bacterial cell wall, is recognized as the key factor in acute lung inflammation and is found to exhibit severe immunologic reactions. Phosphodiesterase-4 (PDE-4) inhibitor: "apremilast (AP)" is an immune suppressant and anti-inflammatory drug which introduced to treat psoriatic arthritis. The contemporary experiment designed to study the protective influences of AP against LPS induced lung injury in rodents. Twenty-four (24) male experimental Wistar rats selected, acclimatized, and administered with normal saline, LPS, or AP + LPS respectively from 1 to 4 groups. The lung tissues were evaluated for biochemical parameters (MPO), Enzyme Linked Immunosorbent Assay (ELISA), flowcytometry assay, gene expressions, proteins expression and histopathological examination. AP ameliorates the lung injuries by attenuating immunomodulation and inflammation. LPS exposure upregulated IL-6, TNF-α, and MPO while downregulating IL-4 which were restored in AP pretreated rats. The changes in immunomodulation markers by LPS were reduced by AP treatment. Furthermore, results from the qPCR analysis represented an upregulation in IL-1ß, MPO, TNF-α, and p38 whereas downregulated in IL-10 and p53 gene expressions in disease control animals while AP pretreated rats exhibited significant reversal in these expressions. Western blot analysis suggested an upregulation of MCP-1, and NOS-2, whereas HO-1, and Nrf-2 expression were suppressed in LPS exposed animals, while pretreatment with AP showed down regulation in the expression MCP-1, NOS-2, and upregulation of HO-1, and Nrf-2 expression of the mentioned intracellular proteins. Histological studies further affirmed the toxic influences of LPS on the pulmonary tissues. It is concluded that, LPS exposure causes pulmonary toxicities via up regulation of oxidative stress, inflammatory cytokines and stimulation of IL-1ß, MPO, TNF-α, p38, MCP-1, and NOS-2 while downregulation of IL-4, IL-10, p53, HO-1, and Nrf-2 at different expression level. Pretreatment with AP controlled the toxic influences of LPS by modulating these signaling pathways.

EWSR1 rearrangement is not specific for hyalinizing clear cell carcinoma of salivary glands.

OBJECTIVE: In this study, we investigate the molecular rearrangement of EWSR1 in hyalinizing clear cell carcinoma (HCCC) (with and without eosinophilia) and clear cell variant of mucoepidermoid carcinoma (MEC) of salivary glands. METHOD: We performed a molecular detection of HCCC (Group 1) and clear cell variant of MEC (Group 2). Group 1 consisted of 5 cases of typical HCCC and 5 cases of HCCC with eosinophilia. Group 2 encompassed 5 cases of clear-cell MEC. For both groups, we conducted a FISH analysis using EWSR1 dual color break-apart FISH probe (ZytoLight®, 22q12.2) and MAML2 dual color break-apart FISH probe (ZytoLight®, 11q21). RESULTS: All analyzable cases of HCCC with or without eosinophilic components were negative for EWSR1 translocation. All cases of clear-cell MEC were positive for MAML2 translocation. No translocation was observed in HCCC. CONCLUSION: Our study showed that clear cells could cause diagnostic uncertainty and that EWSR1 can be detected in many primary neoplasms of salivary glands and metastatic tumors that were reported in salivary glands. We suggest that recommending EWSR1 as a diagnostic molecular marker for HCCC should be reconsidered.

Pathologist interobserver variability in diagnosing acute ascending intrauterine infection.

The histologic diagnosis of acute ascending intrauterine infection permits a higher-efficacy identification of both subclinical infection and clinical chorioamnionitis, but procedures for placental pathology need to adopt a unified approach and work toward reproducible grading and staging systems. We conducted a retrospective chart review of 696 placental records from single and multiple deliveries between January 2011 and February 2020. Then, we compared original diagnoses with diagnoses based on Redline criteria, which is an internationally recognized system of staging and grading. Of the 696 cases available for review, 255 had complete medical records. Findings showed a strong degree of agreement (90%-100%) between original investigators' histological diagnoses of acute ascending intrauterine infection and a review by researchers using Redline criteria. Although interobserver agreement was good, more education is needed on Redline criteria to avoid missed cases (primarily Stage 1), support protocols for pathologists and obstetricians/gynecologists in determining which cases need to be investigated, and the development of reporting standards for acute ascending intrauterine infection and feedback mechanisms during follow-up.

Protective effect of valsartan against doxorubicin-induced cardiotoxicity: Histopathology and metabolomics in vivo study.

Doxorubicin (DOX) treatment has been associated with cardiotoxicity. Therefore, it is crucial to search for a therapeutic that can effectively mitigate DOX-induced cardiotoxicity. This study was conducted to investigate the protective effects of valsartan (VAL) against DOX-induced cardiotoxicity. Sprague-Dawley rats were divided into four treatment groups: Group I: Control, Group II: VAL (30 mg/kg, ip), Group III: DOX (15 mg/kg, ip), and Group IV: VAL + DOX (30 + 15 mg/kg, ip). All groups were treated every other day for 14 days. Blood was isolated for biochemical and metabolomics studies, and sections of the heart were also analyzed for histopathological and immunohistochemical alterations to detect changes in P53, BAX, BCL-2, and P62 expression. The combination of VAL + DOX resulted in a marked decrease in cardiac biomarker enzymes (aminotransferase and creatine phosphokinase) compared to DOX monotherapy. In addition, the histopathological examination of the VAL + DOX combination revealed a low percentage of fibrosis and inflammation. Immunohistochemical expression of p53 and BAX was significantly reduced, whereas BCL-2 expression was significantly increased in the VAL + DOX treatment group compared to DOX monotherapy. Also, the combination of VAL + DOX reverses the negative effect of DOX on nuclear p62 expression. Analysis of serum metabolites showed that DOX monotherapy reduced the number of several amino acids, whereas the combination of VAL + DOX restored these metabolic pathways. This study revealed the potential cardioprotective effect of VAL, which may provide novel and promising approaches for managing cardiotoxicity induced by DOX.

Aggressive surgical management of recurrent intracranial juvenile xanthogranuloma: case report and review of the literature.

INTRODUCTION: Juvenile xanthogranuloma (JXG) with the central nervous system (CNS) involvement is a rare disease entity that remains poorly understood, especially when the condition develops following treatment for Langerhans cell histiocytosis (LCH). CASE REPORT: A 21-year-old man who was diagnosed with LCH at age 2, several years following which he developed signs and symptoms of CNS involvement. Magnetic resonance imaging (MRI) of the brain revealed JXG with bilateral choroid plexus involvement. As radiation therapy for the intraventricular masses proved unsuccessful, he underwent two surgical resections. In the following years, he developed another large JXG in the meninges, which was managed conservatively until he required surgery due to symptom progression. Twelve years after the first surgery, the patient is in stable condition with no evidence of recurrence. CONCLUSION: Due to the rarity of JXG in the CNS, optimal treatment strategies and the precise duration of therapy remain to be determined. Future studies should aim to develop an appropriate treatment algorithm for such rare cases.

Angiolipoma of the Orbit.

Angiolipoma is characteristically described as an encapsulated mass of mature adipose tissue containing clusters of small blood vessels. The authors have described an extremely rare case of angiolipoma of the orbit. This rare case is only the third reported in the orbit and should be readily recognized from other differential diagnoses. The patient had an excellent prognosis after full surgical excision.

Death certificate errors in one Saudi Arabian hospital.

Proper completion of death certificates is of vital importance. This study assessed the accuracy of death certification at one major hospital in Riyadh, Saudi Arabia. We collected all certificates from 1997 to 2016 and scored them on the degree of accuracy. We found no errors of incompleteness or missed contributors to death. However, in all certificates (100%), cause of death was either incorrect or absent; 75% provided no cause of death. Further large-scale studies should be conducted in other hospitals to determine the exact prevalence of these serious errors.

Apremilast reversed carfilzomib-induced cardiotoxicity through inhibition of oxidative stress, NF-κB and MAPK signaling in rats.

Carfilzomib (CFZ), is a potent, selective second generation proteasome inhibitor, used for the treatment of multiple myeloma. The aim of the present study was to investigate the possible protective effect of apremilast (AP) on the CFZ -induced cardiotoxicity. Rats were randomly divided into four groups: Group 1, served as the control group, received normal saline. Group 2, served as the toxic group, received CFZ (4 mg/kg, intraperitoneally [i.p.]). Groups 3 and 4, served as treatment groups, and received CFZ with concomitant oral administration of AP in doses of 10 and 20 mg/kg/day, respectively. In the present study, administration of CFZ resulted in a significant increase in serum aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB), which were reversed by treatment with AP. CFZ resulted in a significant increase in heart malondialdehyde (MDA) contents and decrease in cardiac glutathione (GSH) level and catalase (CAT) enzyme activity which were significantly reversed by treatment with AP. Induction of cardiotoxicity by CFZ significantly increased caspase-3 enzyme activity which were reversed by treatment with AP. RT-PCR analysis revealed an increased mRNA expression of NF-κB, ERK and JNK which were reversed by treatment with AP in cardiac tissues. Western blot analysis revealed an increased expression of caspase-3 and NF-κB p65 and a decrease expression of inhibitory kappa B-alpha (Iκbα) with CFZ, which were reversed by treatment with AP. In conclusion, apremilast showed protective effect against CFZ-induced cardiotoxicity.

Prevalence of Fetal Inflammatory Response Syndrome and Villitis of Unknown Etiology in the Placenta of Saudi Women and Their Association with Baby Sex.

Long-term health consequences are influenced by circumstances that occur during pregnancy. The convergence of the maternal and fetal circulations occurs in the placenta, which is the first organ to develop. Placental pathology provides an accurate diagnosis of amniotic sac inflammation, and pathological alterations in preterm placentas provide evidence for the causes of numerous perinatal pathologies, including spontaneous preterm births. This retrospective study aimed to re-examine placentas regarded as normal by the Obstetrics and Gynecology Department at our institution. Thirty-seven male and forty-seven female placentas were collected following full-term delivery, and the grading and staging of any evident inflammatory responses were evaluated and correlated with the babies' sex. Full-thickness placental samples that were considered normal and not sent to the histopathology department were obtained from the central and marginal regions of placental discs. Morphological examination of the fresh placenta was conducted, and fetal and maternal inflammatory response syndromes were assessed. In addition, placental villitis of unknown etiology (VUE) and chronic deciduitis were evaluated. Immunohistochemistry was performed to evaluate the patterns of inflammation in the placenta using anti-CD8 and anti-CD68 antibodies. The correlation between silent pathologies and clinical complications or the development of fetal inflammatory response syndrome was measured. In this study, 17 (20%) maternal and 10 (12%) fetal samples showed inflammatory responses. The frequencies of chronic deciduitis and VUE were higher among pregnant Saudi women than previously reported, probably because fetal inflammatory response syndrome goes unnoticed in Saudi Arabia. In addition, the prevalence of fetal and maternal inflammatory responses was higher in the placentas of the mothers of males than in those of females, suggesting that differences occur in the inflammatory response in the placenta depending on the sex of the newborn. Grading placental inflammation (in cases of VUE) typically predicts the degree of maternal anti-fetal cellular rejection; therefore, increasing the number of placental samples sent for microscopic inspection may be preferable because of their significance in identifying the causes of chronic disorders.

Expression of Glucose Transporters 1 and 3 in the Placenta of Pregnant Women with Gestational Diabetes Mellitus.

BACKGROUND: The annual prevalence of gestational diabetes mellitus-characterized by an increase in blood glucose in pregnant women-has been increasing worldwide. The goal of this study was to evaluate the expression of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in the placenta of women with gestational diabetes mellitus. METHODS: Sixty-five placentas from women admitted to the King Saud University Medical City, Riyadh, Saudi Arabia, were analyzed; 34 and 31 placentas were from healthy pregnant women and women with gestational diabetes, respectively. The expressions of GLUT1 and GLUT3 were assessed using RT-PCR, Western blotting, and immunohistochemical methods. The degree of apoptosis in the placental villi was estimated via a TUNEL assay. RESULTS: The results of the protein expression assays and immunohistochemical staining showed that the levels of GLUT1 and GLUT3 were significantly higher in the placentas of pregnant women with gestational diabetes than those in the placentas of healthy pregnant women. In addition, the findings showed an increase in apoptosis in the placenta of pregnant women with gestational diabetes compared to that in the placenta of healthy pregnant women. However, the results of gene expression assays showed no significant difference between the two groups. CONCLUSIONS: Based on these results, we conclude that gestational diabetes mellitus leads to an increased incidence of apoptosis in the placental villi and alters the level of GLUT1 and GLUT3 protein expressions in the placenta of women with gestational diabetes. Understanding the conditions in which the fetus develops in the womb of a pregnant woman with gestational diabetes may help researchers understand the underlying causes of the development of chronic diseases later in life.

Stereological and histopathological assessment of intrauterine growth restriction placenta from Saudi women.

Background: Placental insufficiency causes fetal adaptation, leading to fetal programming of chronic diseases. Placentas with intrauterine growth restriction (IUGR) are smaller than average and may contribute to low birth weight of the newborn. The number of patients with IUGR in the Saudi population is increasing; however, little is known about their placentas. The aim of this study was to assess morphometric and histopathological placental changes in Saudi patients with IUGR. Methods: Overall, 20 healthy pregnant Saudi women (control group) and 20 pregnant Saudi women with IUGR were enrolled. Maternal and fetal morphometric measurements were recorded. The placentas from both groups were processed for histopathological examination using stereological techniques. Results: The IUGR group had lower placental weight, volume, length, breadth, and surface area than the control group. The total volume of villi and surface area of the terminal villi were significantly reduced in the IUGR placentas. IUGR group had a reduction in birth weight; length; and circumference of the head, chest, abdomen, and thigh compared to control group. Conclusion: The reduction in placental mass, specifically the reduction in the volume and surface area of villi, the functional units, may have reduced the capacity for nutrient transport. This led to a significant reduction in neonatal measurements. The fetus rearranged nutrient distribution in favor of the brain and other essential organs; however, at the expense of thigh development and growth. This fetal trade-off strategy increases the risk of developing chronic diseases in adulthood. Therefore, IUGR infants may require more clinical attention.

Assessment of Risk Perception of COVID-19 Post Vaccination amongst the General Population of Riyadh Region.

COVID-19 is a highly contagious disease caused by SARS-CoV-2. Vaccination against the virus was first approved in Saudi Arabia in December 2020. Vaccinated individuals are still at risk of getting infected with the virus and can transmit the disease. Therefore, the perception of vaccinated individuals regarding the disease can help limit the spread of the virus. OBJECTIVES: To measure the risk perception of COVID-19 following vaccination and factors that have an effect on risk perception; to identify the health protective behaviours of the vaccinated individuals. METHODOLOGY: This is a quantitative analytical cross-sectional, questionnaire-based study. The target population includes individuals aged 18 and above who live in the Riyadh region and have been vaccinated, during the period of June 2021 to December 2021. RESULTS: The perception of 30.2% of participants did not change after vaccination, with many participants continuing to "always" take precautions even after vaccination. Numerous factors, such as age, gender, marital status, occupational status, employment status, and total household income, have shown significant effects towards risk perception. CONCLUSION: Many vaccinated individuals have continued to take precautionary steps and their risk perception has not changed.

Fatal Case of a Child Harboring Enterobius vermicularis.

Enterobius vermicularis is a threadlike parasite also known as "pinworms". It is the most common helminth infection, affecting the gastrointestinal tracts of children worldwide, although it seldom causes any fatalities. Enterobius vermicularis infections are usually asymptomatic and may only cause anal pruritis, with occasional reported cases of ectopic migration into the appendix or the female genital tract by adult pinworms. Here, we report a case of a 15-year-old girl who presented to the emergency department with high-grade fever, vomiting, and vague abdominal pain for three days. She was diagnosed with acute abdominal pain and underwent emergency ileocecectomy, but died the following day. Pathological examination of ileocecal junction showed intraluminal and intramural Enterobius vermicularis, which were attributed as the cause of her death in the absence of any other pathologies. Death due to Enterobius vermicularis is rare; this case calls for clinicians to be vigilant in exploring Enterobius vermicularis infections in patients with undiagnosed acute abdominal pain, since it could be a potential cause of death.

Assessing Knowledge, Acceptance, and Anticipated Impact of Telepathology in Saudi Arabia: Insights From Healthcare Workers and Patients.

INTRODUCTION: Telepathology, a rapidly evolving field in modern healthcare, has the potential to significantly impact the diagnosis and management of diseases. This study aimed to assess the prevalence of acceptance and knowledge, the likelihood of future use, and the perceived advantages and disadvantages of telepathology among healthcare workers (HCWs) and patients in Saudi Arabia. METHODS: A cross-sectional study was conducted with 388 participants, including 179 HCWs and 209 adult patients across Saudi Arabia. Data were collected using a bilingual, self-administered, and anonymous computer-based questionnaire. The Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY) was employed for data analysis. RESULTS: The participants had an average knowledge rate of 80.3% (n=312) concerning telepathology. A substantial 88.16% (n=342) were inclined towards its acceptance, and an optimistic 89.97% (n=349) foresaw its potential utility. Among the respondents, 70% (n=272) pinpointed "expedited results" as the principal merit of telepathology. However, 60% (n=233) flagged "the necessity for costly infrastructure" as its chief limitation. CONCLUSIONS: The insights derived underscore a prominent knowledge and endorsement of telepathology among the Saudi population and HCWs. Despite certain drawbacks, participants believe that telepathology is feasible and offers numerous benefits that could greatly enhance the healthcare system in Saudi Arabia. Future research should focus on evaluating its practical implementation and efficacy within healthcare facilities.

The Potential Protective Role of Naringenin against Dasatinib-Induced Hepatotoxicity.

Dasatinib (DASA) is a novel tyrosine kinase inhibitor, approved for leukemia treatment. However, the long-term use of DASA induces several complications, especially liver damage. On the other hand, Naringenin (NGN) is a potent antioxidant and anti-inflammatory agent which is known to exert protective effects in several liver disease animal models. Yet, the effect of NGN on DASA-induced hepatotoxicity has not been examined. This study investigated the hepatoprotective effects of NGN against DASA-induced acute liver injury, using a mouse model. The mice were given NGN (50, 100, and 200 mg/kg po) or saline for 7 days, followed by DASA on the eighth day (25 mg/kg p.o.). DASA treatment alone was found to cause overexpression of proinflammatory cytokines, such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and malonyl aldehyde (MDA), whereas attenuation of antioxidant genes including superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx). Interestingly, a pretreatment with NGN + DASA resulted in minimizing the proinflammatory mediators and restoring the levels of antioxidant genes. In addition, there was evidence of necro-inflammatory changes in histopathological findings in the liver samples after DASA administration which remarkably reduced with NGN + DASA. Thus, this study revealed that NGN could minimize the hepatotoxicity induced by DASA by providing anti-inflammatory and antioxidant protection.

Hydroxychloroquine ameliorates dasatinib-induced liver injury via decrease in hepatic lymphocytes infiltration.

Dasatinib is an effective treatment for chronic myeloid leukemia. However, cases of idiosyncratic hepatotoxicity were reported. This study was conducted to investigate the chemopreventive effects of hydroxychloroquine against dasatinib-induced hepatotoxicity. Balb/c mice were randomly assigned into four groups; vehicle control (5% DMSO, i.p., n = 6), dasatinib (50 mg/kg; i.p., n = 6), hydroxychloroquine (10 mg/kg, i.p., n = 6), and hydroxychloroquine + dasatinib (10 mg/kg + 50 mg/kg; i.p., n = 6). Treatments were given once every 2 days for 14 days. Serum and histopathological assessments of liver architecture and fibrosis were performed using H&E, Masson's trichrome, and reticulin staining. The infiltration of lymphocytes was assessed using immunohistochemistry. The gene expression of antioxidant enzymes (CAT, SOD-2, GPX-1) was assessed using real-time quantitative PCR. Dasatinib showed a significant increase in liver injury biomarkers (AST and ALT) with higher lymphocytes infiltration (as indicated by CD3+, CD4+, CD8+, and CD20+ immunohistochemistry). Hepatic tissue of Dasatinib group exhibited significant downregulation in the gene expression of antioxidant enzymes (CAT, SOD-2, and GPX-1) compared to the control group. However, the combination of hydroxychloroquine with dasatinib showed a slight increase in AST and ALT. Also, hydroxychloroquine + dasatinib treated mice showed a significant reduction in lymphocytes infiltration as compared to dasatinib. The results showed that dasatinib induces an immune response leading to an increase in lymphocytes infiltration which promotes hepatocyte destruction and persistent liver injury. The results also suggest that hydroxychloroquine ameliorates dasatinib-induced hepatotoxicity via reduction in hepatic infiltration of T and B immune cells.

Saudi physicians' perceptions of the validity of autopsy and its implications - Structural equation modeling.

INTRODUCTION: Although autopsy plays a vital role in forensic medicine, the rates have been recently declining around the world. We surveyed all interns and physicians at our hospital to determine how Saudi physicians viewed autopsies with regard to the challenges, priorities, and requirements, and also how they felt about autopsy-based research and postmortem examination techniques. The results shed light on how these constructs affected the physician's perception of the implications of autopsy. METHODS: We prepared a cross-sectional study using a self-administered multiple-choice questionnaire distributed to interns and physicians at our institution. From a population of 596 physicians, we sampled 234. Structural equation modeling was used to assess 6 constructs and their 40 indicators. RESULTS: The survey results demonstrated two main barriers for interns and physicians to perform autopsies: respect for the religious beliefs of the families of the deceased and respect for family mourning. CONCLUSION: Measures can be taken to improve autopsy rates, such as training of medical staff in communication and counselling, implementing a streamlined and stress-free process, and increasing public awareness of the benefits of autopsy through campaigns and educational programs. Among the many virtues of educating Saudi physicians and residents about the significance of increasing autopsy rates and familiarizing them with their procedures, developing professional competence among medico-legal experts cannot be overemphasized.

Factors Influencing Residents' Specialty Choices and Satisfaction: Impact of Gender, Career Motivation and Life Goals.

OBJECTIVE: Resident physicians working in medical specialties play an essential role in the makeup of the healthcare workforce. However, there is little theoretical understanding of how different medical specialties are perceived or how residents' choices are made. Many factors can influence resident physicians' choice of specialty. Previous studies have looked at personality differences within specialties, but were unable to describe the heterogeneity of viewpoints that existed within each specialty. Our objective, was to gather information about factors related to resident's life goals and career motivation as a means of improving residency program design and enhancing the college's advisory capacity. DESIGN: Our study used a self-report anonymous questionnaire to characterize the relationship between resident physicians' preferences and their choice of specialty. SETTING: King Saud University & King Saud University Medical City. PARTICIPANTS: 353 residents. RESULTS: The majority of respondents reported that their current specialty was one of their top three choices. Almost half were satisfied with their residency program, and 24.1% were very satisfied. Gender, specialty, and workload demonstrated significant associations with residency program satisfaction. CONCLUSIONS: Our findings highlight the effects of career motivation and life goals for resident physicians in enhancing their career satisfaction. Ensuring that residents are able to find time for personal needs has important consequences for their perceptions of wellbeing and may be an effective strategy for promoting career satisfaction.