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Background: Toxoplasma gondii (T. gondii) infects one third of the world's population with significant illness, mainly among immunocompromised individuals and pregnant women. Treatment options for toxoplasmosis are limited which signifies the need for novel, potent, and safe therapeutic options. The goal of this study was to assess the effectiveness of the ethanolic extract of Zingiber officinale (Z. officinale) in treating mice infected with the RH T. gondii strain., Materials and Methods: Gas Chromatography/Mass Spectrometry (GC/MS) was used to identify components of ethanolic extract of Z. officinale. A total of 80 mice were randomly allocated into four experimental groups that contained 20 mice each. The first group was left uninfected (uninfected control), while three groups were infected with T. gondii RH virulent strain tachyzoites at 2500 tachyzoites/mouse. One infected group was left untreated (infected, untreated), whereas the other two groups were treated orally with either spiramycin (positive control) or Z. officinale ethanolic extract at doses of 200 mg/kg and 500 mg/kg, respectively for 5 days, starting the day of infection. Ten mice from each group were used to assess mice survival in different groups, whereas the other ten mice in each group were sacrificed on the 5th day post-infectin (dpi) to estimate the treatment efficacy by quantifying liver parasite load, liver function, nitric oxide (NO) production, and levels of antioxidant enzymes. Additionally, histopathological studies were performed to evaluate the therapeutic effect of Z. officinale treatment on toxoplasmosis-induced pathological alterations in liver, brain, and spleen., Results: Treatment with Z. officinale ethanolic extract extended the survival of mice till 9th dpi compared to 7th dpi in infected untreated mice. Higher percentage of mice survived in Z. officinale-treated group compared to spiramycin-treatment group at different time points. Liver parasite loads were significantly lower in Z. officinale extract-treated mice and spiramycin-treated mice compared to infected untreated mice which correlated with significantly lower levels of serum liver enzymes (ALT, AST) and nitric oxide (NO), as well as significantly higher catalase (CAT) antioxidant enzyme activity. Scanning electron microscopy (SEM) examination of tachyzoites from the peritoneal fluid revealed marked damage in tachyzoites from Z. officinale-treated group compared to that from infected untreated mice. Moreover, treatment with Z. officinale ethanolic extract alleviated infection-induced pathological alterations and restored normal tissue morphology of liver, brain, and spleen., Conclusion: Our results demonstrated that Z. officinale treatment reduced parasite burden and reversed histopathological and biochemical alterations in acute murine toxoplasmosis. These findings support the potential utility of Z. officinale as a future effective natural therapeutic for toxoplasmosis. Further studies are needed to determine the effective active ingredient in Z. officinale extract that can be further optimized for treatment of toxoplasmosis., Competing Interests: Declarations. Statement of Novelty: Toxoplasmosis is a serious opportunistic disease with limited treatment options. The current study’s goal was to assess the effectiveness of the ethanolic extract of Z. officinale in treating mice that had been infected with the RH T. gondii strain experimentally. Findings in the present study - as demonstrated by prolonged survival rate, reduced parasite burden, improved T.gondii associated liver injury and histopathological alterations - supported the strong therapeutic potential of ginger in the treatment of toxoplasmosis. We hypothesize that the antioxidant capacity of ginger is the underlying mechanism of its anti-Toxoplasma effect in the current study. Thus, our results suggested ginger can be considered a safe chemotherapeutic agent in the treatment of toxoplasmosis. Further studies are needed to determine the effective component in ginger which can be used as a pharmaceutical target in treatment of toxoplasmosis. Institutional Review Board Statement: This study was conducted after approval from the Ethics Committee of the Faculty of Medicine, Alexandria University, Egypt (code: 0306090). All animal experiments were conducted in accordance with the Declaration of Helsinki guidelines. Conflict of Interest: The authors have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Schistosomiasis affects approximately 250 million people worldwide, with 200,000 deaths annually. It has been documented that the granulomatous response to Schistosoma mansoni ( S. mansoni ) oviposition is the root cause of progressive liver fibrosis in chronic infection, in 20% of the patients, and can lead to liver cirrhosis and/or liver cancer. The influence of helminths coinfection on schistosomiasis-induced liver pathological alterations remains poorly understood. Therefore, in this study, we investigated the effect of Trichinella spiralis ( T. spiralis ) infection on S. mansoni -induced hepatic fibrosis., Materials and Methods: Thirty adult male Balb-c mice were divided into three groups. Group 1 was left uninfected; group 2 was infected with S. mansoni cercariae and group 3 was orally infected with T. spiralis larvae, then 28 days later, this group was infected with S. mansoni cercariae. All groups were sacrificed at the end of the 8 th week post infection with S. mansoni to evaluate the effect of pre-infection with T. spiralis on S. mansoni induced liver fibrosis was evaluated parasitologically (worm burden and egg count in tissues), biochemically (levels of alanine aminotransferase and aspartate aminotransferase), histopathologically (H&E and MT staining, and immunohistochemical staining for the expression of α-SMA, IL-6, IL-1β, IL-17, IL-23, TNF-α, and TGF-β)., Results: The results in the present study demonstrated marked protective effect of T. spiralis against S. mansoni induced liver pathology. We demonstrated that pre-infection with T. spirais caused marked reduction in the number of S. mansoni adult worms (3.17 ± 0.98 vs. 18 ± 2.16, P = 0.114) and egg count in both the intestine (207.2 ± 64.3 vs. 8,619.43 ± 727.52, P = 0.009) and liver tissues (279 ± 87.2 vs. 7,916.86 ± 771.34; P = 0.014). Consistently, we found significant reductions in both number (3.4 ± 1.1 vs. 11.8.3 ± 1.22; P = 0.007) and size (84 ± 11 vs. 294.3 ± 16.22; P = 0.001) of the hepatic granulomas in mice pre-infected with T. spiralis larvae compared to those infected with only S. mansoni . Furthermore, pre- infection with T. spiralis markedly reduced S. mansoni - induced hepatic fibrosis, as evidenced by decreased collagen deposition, low expression of α-SMA, and significantly reduced levels of IL-17, IL-1B, IL-6, TGF-B, IL-23, and TNF-α compared to mice infected with S. mansoni only., Conclusions: Our data show that pre-infection with T. spiralis effectively protected mice from severe schistosomiasis and liver fibrosis. We believe that our findings support the potential utility of helminths for the preventing and ameliorating severe pathological alterations induced by schistosomiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 El-kady, Altwaim, Wakid, Banjar, Mohammed, Alfaifi, Elshazly, Al-Megrin, Alshehri, Sayed and Elshabrawy.)

Hepatocellular carcinoma is currently the most common malignancy of the liver. It typically occurs due to a series of oncogenic mutations that lead to aberrant cell replication. Most commonly, hepatocellular carcinoma (HCC) occurs as a result of pre-occurring liver diseases, such as hepatitis and cirrhosis. Given its aggressive nature and poor prognosis, the early screening and diagnosis of HCC are crucial. However, due to its plethora of underlying risk factors and pathophysiologies, patient presentation often varies in the early stages, with many patients presenting with few, if any, specific symptoms in the early stages. Conventionally, screening and diagnosis are performed through radiological examination, with diagnosis confirmed by biopsy. Imaging modalities tend to be limited by their requirement of large, expensive equipment; time-consuming operation; and a lack of accurate diagnosis, whereas a biopsy's invasive nature makes it unappealing for repetitive use. Recently, biosensors have gained attention for their potential to detect numerous conditions rapidly, cheaply, accurately, and without complex equipment and training. Through their sensing platforms, they aim to detect various biomarkers, such as nucleic acids, proteins, and even whole cells extracted by a liquid biopsy. Numerous biosensors have been developed that may detect HCC in its early stages. We discuss the recent updates in biosensing technology, highlighting its competitive potential compared to conventional methodology and its prospects as a tool for screening and diagnosis.

Exosomal microRNAs (miRNAs) have great potential in the fight against hepatocellular carcinoma (HCC), the fourth most common cause of cancer-related death worldwide. In this study, we explored the various applications of these small molecules while analyzing their complex roles in tumor development, metastasis, and changes in the tumor microenvironment. We also discussed the complex interactions that exist between exosomal miRNAs and other non-coding RNAs such as circular RNAs, and show how these interactions coordinate important biochemical pathways that propel the development of HCC. The possibility of targeting exosomal miRNAs for therapeutic intervention is paramount, even beyond their mechanistic significance. We also highlighted their growing potential as cutting-edge biomarkers that could lead to tailored treatment plans by enabling early identification, precise prognosis, and real-time treatment response monitoring. This thorough analysis revealed an intricate network of exosomal miRNAs lead to HCC progression. Finally, strategies for purification and isolation of exosomes and advanced biosensing techniques for detection of exosomal miRNAs are also discussed. Overall, this comprehensive review sheds light on the complex web of exosomal miRNAs in HCC, offering valuable insights for future advancements in diagnosis, prognosis, and ultimately, improved outcomes for patients battling this deadly disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 El Hayek, Alnaser-Almusa, Alsalameh, Alhalabi, Sabbah, Alshehri, Mir, Mani, Al-Kattan, Chinnappan and Yaqinuddin.)

Background: Cryptosporidiosis is an opportunistic parasitic disease widely distributed worldwide. Although Cryptosporidium sp. causes asymptomatic infection in healthy people, it may lead to severe illness in immunocompromised individuals. Limited effective therapeutic alternatives are available against cryptosporidiosis in this category of patients. So, there is an urgent need for therapeutic alternatives for cryptosporidiosis. Recently, the potential uses of Eugenol (EUG) have been considered a promising novel treatment for bacterial and parasitic infections. Consequently, it is suggested to investigate the effect of EUG as an option for the treatment of cryptosporidiosis., Materials and Methods: The in silico bioinformatics analysis was used to predict and determine the binding affinities and intermolecular interactions of EUG and Nitazoxanide (NTZ) toward several Cryptosporidium parvum ( C. parvum ) lowa II target proteins. For animal study, five groups of immunosuppressed Swiss albino mice (10 mice each) were used. Group I was left uninfected (control), and four groups were infected with 1,000 oocysts of Cryptosporidium sp. The first infected group was left untreated. The remaining three infected groups received NTZ, EUG, and EUG + NTZ, respectively, on the 6th day post-infection (dpi). All mice were sacrificed 30 dpi. The efficacy of the used formulas was assessed by counting the number of C. parvum oocysts excreted in stool of infected mice, histopathological examination of the ileum and liver tissues and determination of the expression of iNOS in the ileum of mice in different animal groups., Results: treatment with EUG resulted in a significant reduction in the number of oocysts secreted in stool when compared to infected untreated mice. In addition, oocyst excretion was significantly reduced in mice received a combination therapy of EUG and NTZ when compared with those received NTZ alone. EUG succeeded in reverting the histopathological alterations induced by Cryptosporidium infection either alone or in combination with NTZ. Moreover, mice received EUG showed marked reduction of the expression of iNOS in ileal tissues., Conclusion: Based on the results, the present study signified a basis for utilizing EUG as an affordable, safe, and alternative therapy combined with NTZ in the management of cryptosporidiosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gattan, Wakid, Qahwaji, Altwaim, Mahjoub, Alfaifi, Elshazly, Al-Megrin, Alshehri, Elshabrawy and El-kady.)

Background and Methodology: We aimed to investigate the clinical characteristics, outcomes, and mortality predictors in patients with acute pulmonary embolism (PE). Adult patients who were admitted to the Armed Forces Hospital Southern Region, Khamis Mushait, a large tertiary hospital in Southern Saudi Arabia, with the diagnosis of acute PE were retrospectively examined for the predictors of one-year mortality., Results: The overall in-hospital mortality was 15.6% among 212 patients. In univariate analysis, only age was significantly associated with increased early mortality, whereas age, obesity, presence of active malignancy, hypertension, use of thrombolytics, and Simplified Pulmonary Embolism Severity Index (sPESI) were significantly associated with increased late mortality. By use of binary logistic regression, the presence of obesity (HR 6.010, 95%CI 0.048-16.853, p=0.030), active malignancy (HR 3.040, 95%CI 1.147-8.059, p=0.025), and the use of thrombolytics (HR 8.074, 95%CI 2.719-23.977, p<0.001), were independently significant factors for late (overall) mortality, respectively., Conclusions: Among Saudi Arabian patients in the Southern Region, our data show that age is an independent factor for increased early and late mortality. The presence of obesity, active malignancy, and the use of thrombolytics, were independently significant factors for increased late (one-year) mortality. These factors should be taken into account for risk stratification and decisions on tailored management of patients with PE. Further prospective multicenter studies are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Abuelhassan et al.)

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p -values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) ( p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes.

Background: Previous studies have reported involvement of Toxoplasma gondii ( T. gondii) infections in the pathogenesis of some autoimmune diseases, such as polymyositis, rheumatoid arthritis, autoimmune thyroiditis, and Crohn's disease. However, data on the association between T. gondii infections and Type 1 diabetes mellitus (T1DM) are still controversial. Therefore, in the present study, we aimed to investigate the pancreatic pathological changes in mouse models with acute and chronic toxoplasmosis and their association with T1DM., Materials and Methods: Three groups (10 mice each) of male Swiss Albino mice were used. One group of mice was left uninfected, whereas the second and third groups were infected with the acute virulent T. gondii RH strain and the chronic less virulent Me49 T. gondii strain, respectively. T. gondii -induced pancreatic pathological changes were evaluated by histopathological examination of pancreatic tissues. Moreover, the expression of insulin, levels of caspase-3, and the pancreatic infiltration of CD8 + T cells were evaluated using immunohistochemical staining., Results: Pancreatic tissues of T. gondii -infected animals showed significant pathological alterations and variable degrees of insulitis. Mice with acute toxoplasmosis exhibited marked enlargement and reduced numbers of islets of Langerhans. However, mice with chronic toxoplasmosis showed considerable reduction in size and number of islets of Langerhans. Moreover, insulin staining revealed significant reduction in β cell numbers, whereas caspase-3 staining showed induced apoptosis in islets of Langerhans of acute toxoplasmosis and chronic toxoplasmosis mice compared to uninfected mice. We detected infiltration of CD8 + T cells only in islets of Langerhans of mice with chronic toxoplasmosis., Conclusions: Acute and chronic toxoplasmosis mice displayed marked pancreatic pathological changes with reduced numbers of islets of Langerhans and insulin-producing-β cells. Since damage of β cells of islets of Langerhans is associated with the development of T1DM, our findings may support a link between T. gondii infections and the development of T1DM.

The growing incidence of human monkeypox cases emphasizes the significance of prevention, early detection, and prompt responses for healthcare providers. The aim of this study was to assess the knowledge and attitudes toward monkeypox infection among physicians, a frontline healthcare worker group, in Saudi Arabia. A cross-sectional survey assessing knowledge and attitudes towards monkeypox infection on multiple-item scales was sent to physicians in Saudi Arabia. The associations between independent factors and either knowledge or attitude were assessed. The final analysis included 398 participants. Approximately 55% of the surveyed participants had a "good knowledge" score about human monkeypox. The adjusted logistic regression analysis showed that being a female physician, working in the private sector, and having information on human monkeypox during medical school or residency years were the only factors associated with a good level of knowledge about human monkeypox. However, physicians' knowledge and attitudes regarding monkeypox infection are inadequate and influenced by various factors. There is a significant knowledge gap between the therapeutic management of monkeypox and its vaccination. Training and knowledge assessments are important, especially when studies show significant improvement in related and specific knowledge.

Background: Trichinellosis is a helminthic disease caused by Trichinella spiralis via the ingestion of raw or undercooked meat of infected animals. Current estimates indicate that 11 million humans have trichinellosis, worldwide. The effective use of anti-trichinella medications is limited by side effects and resistance which highlight the critical need for safe and effective drugs, particularly those derived from medicinal plants. Therefore, in the present study, we aimed to evaluate the efficacy of the ethanolic extract of Artemisia annua ( A. annua ) in treatment of experimentally induced trichinellosis., Materials and Methods: Trichinellosis was induced experimentally in male 6-8 weeks BALB/c mice. BALB/c mice were divided into four groups, 10 mice each. One group was left uninfected and untreated, whereas three groups were infected with T. spiralis. One infected group of mice was left untreated (negative control) while the remaining two infected groups received either 300 mg/kg of the ethanolic extract of A. annua or 50 mg/kg of albendazole (positive control). All treatments started from the third day post-infection (dpi) for 3 successive days. All animals were sacrificed on the 7th dpi for evaluation of treatment efficacy., Results: Our findings showed that A. annua treatment reduced the T. spiralis adult-worm count in the intestine of infected animals. Moreover, treatment with A. annua restored the normal intestinal architecture, reduced edema, alleviated inflammation as demonstrated by reduced inflammatory infiltrate and expression of TGF-β in intestinal tissues of A. annua -treated animals compared to infected untreated animals., Conclusions: Our findings show that A. annua extract is effective in treating experimentally induced trichinellosis which highlight the therapeutic potential of A. annua for intestinal trichinellosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 El-kady, Abdel-Rahman, Sayed, Wakid, Alobaid, Mohamed, Alshehri, Elshazly, Al-Megrin, Iqbal, Elshabrawy and Timsah.)

Background: Toxoplasma gondii ( T. gondii ) is an opportunistic parasite that causes serious diseases in humans, particularly immunocompromised individuals and pregnant women. To date, there are limited numbers of therapeutics for chronic toxoplasmosis which necessitate the discovery of effective and safe therapeutics. In the present study, we aimed to evaluate the antitoxoplasmosis potential of ginger extract in mice with experimentally induced chronic toxoplasmosis. Results: Treatment with ginger extract significantly reduced cysts count in the brains of T. gondii -infected mice with a marked alleviation of edema and inflammation, and a reversal of neuronal injury. Moreover, ginger extract treatment reduced inflammation in liver and lungs and protected hepatocytes from infection-induced degeneration. Consistently, apoptosis was significantly mitigated in the brains of ginger extract-treated mice compared to infected untreated animals or spiramycin-treated animals. Methods: Four groups of Swiss albino mice (10 mice each) were used. The first group was not infected, whereas 3 groups were infected with Me49 T. gondii strains. One infected group remained untreated (infected untreated), whereas the other two infected groups were treated with either ginger extract (250 mg/kg) or spiramycin (positive control; 100 mg/kg), respectively. The therapeutic potential of ginger extract was evaluated by calculation of the parasite burden in infected animals, and examination of the infected tissues for reduced pathologic changes. Conclusions: Our results showed for the first time that ginger extract exhibited marked therapeutic effects in mice with chronic T. gondii infection which indicates that it can be used as a safe and effective treatment for chronic toxoplasmosis.

Objective: Following the recently conducted local studies on the growing misuse of pregabalin, Pregabalin misuse has received national attention. These studies have led to the authorities restricting the availability of pregabalin to hospital pharmacies alone. While the recent epidemiological studies and case reports found gabapentin to be misused worldwide, it was previously presumed to be free of any abuse potential. This study assesses the likelihood of there being a diversion to Gabapentin abuse following the Pregabalin restriction in Jeddah, KSA., Methods: A cross sectional observational study was conducted between November 2017 and December 2017 using a self-constructed online survey via Twitter and WhatsApp. The survey items included participants' demographics, additional history, Gabapentin for non-medical use (frequency, concurrent use with other drugs, and motivators), and how the participants knew about the Gabapentin misuse. The data was subjected to a descriptive analysis via the utilization of frequencies and percentages. The analysis was carried out by using SPSS V21., Results: Data of the 370 respondents who took the surveys were collected. Most of the respondents were women (n = 289; 78.1%) and below the age of 30 years (n = 300; 81.1%). A total of 72 respondents (19.5%) had a history of psychoactive drug abuse. Ten of the respondents reported Gabapentin misuse (2.7%). Half of the participants reported prior Pregabalin misuse, and were un-employed. Most of the misusers (n = 8; 80%) came to know about the psychotropic effects of Gabapentin from friends. The most common motives for using it were to 'have fun' and 'peer pressure' (n = 6; 60%). Half of the misusers used Gabapentin on a weekly basis., Conclusion: The findings of our study suggest a potential diversion from Pregabalin to Gabapentin misuse. Regulations and periodic reviews of the psychoactive prescription medications available in the community pharmacies are essential., (© 2021 The Authors.)

Coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on public mental health. Our objective was to assess prevalence of depression, anxiety, and stress among the general population in Saudi Arabia during this pandemic. A descriptive cross-sectional approach was used targeting all accessible populations in Saudi Arabia. Data were collected from participants using an electronic pre-structured questionnaire. Psychological impact was assessed using the Arabic version of Depression, Anxiety, and Stress Scale (DASS-21). A total of 1597 participants completed the survey. In total, 17.1% reported moderate to severe depressive symptoms; 10% reported moderate to severe anxiety symptoms; and 12% reported moderate to severe stress levels. Depression, anxiety, and stress were significantly higher among females, younger respondents, and health care providers. Depression was higher among smokers, singles, and non-working respondents. Anxiety was higher among those reporting contacts with COVID-19 positive cases, previously quarantined and those with chronic health problems. Our findings reaffirm the importance of providing appropriate knowledge and specialized interventions to promote the mental well-being of the Saudi population, paying particular attention to high-risk groups.

Objectives: Coronary artery bypass grafting (CABG) is among the most frequently performed cardiac surgical procedures. However, it is associated with high readmission rates for a plethora of causes, which can substantially increase healthcare costs. This study aimed to assess the rates and associated risk factors of 30-day readmissions for CABG patients., Methods: We conducted this retrospective cohort study at King Abdulaziz Medical City. The study targeted adult patients who underwent CABG between January 1, 2016, and January 31, 2019. Data were extracted from the BEST Care system. Frequencies and percentages were generated for categorical variables. Mean and standard deviation were calculated for quantitative variables. Bivariable and multivariable logistic regressions were used to detect readmission risk factors., Results: Among 534 adult patients, the overall 30-day readmission rate was 16.1% (n = 86). The multivariable logistic regression analysis showed that diabetes mellitus ( P  = .002), amiodarone use ( P  = .04), statin use ( P  = .04), amlodipine use ( P  = .006), asthma ( P  < .001), and hyperlipidemia ( P  = .04) were significantly correlated with 30-day readmission., Conclusions: Our study showed an estimated 16.1% 30-day readmission rate after CABG. Diabetes mellitus, asthma, hyperlipidemia, and use of medications such as amiodarone, statins, and amlodipine were associated with readmission. Further studies are needed to develop tailored and practical strategies to reduce CABG readmissions and mitigate patient and health care facility burdens., (© 2020 The Authors.)