Impact of NMDA receptors block versus GABA-A receptors modulation on synaptic plasticity and brain electrical activity in metabolic syndrome.

PURPOSE: Metabolic syndrome (MetS) is a common disorder associated with disturbed neurotransmitter homeostasis. Memantine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, was first used in Alzheimer's disease. Allopregnanolone (Allo), a potent positive allosteric modulator of the Gamma-Amino-Butyric Acid (GABA)-A receptors, decreases in neurodegenerative diseases. The study investigated the impact of Memantine versus Allo administration on the animal model of MetS to clarify whether the mechanism of abnormalities is related more to excitatory or inhibitory neurotransmitter dysfunction. MATERIALS AND METHODS: Fifty-six male rats were allocated into 7 groups: 4 control groups, 1 MetS group, and 2 treated MetS groups. They underwent assessment of cognition-related behavior by open field and forced swimming tests, electroencephalogram (EEG) recording, serum markers confirming the establishment of MetS model and hippocampal Glial Fibrillary Acidic Protein (GFAP) and Brain-Derived Neurotrophic Factor (BDNF). RESULTS: Allo improved anxiety-like behavior and decreased grooming frequency compared to Memantine. Both drugs increased GFAP and BDNF expression, improving synaptic plasticity and cognition-related behaviors. The therapeutic effect of Allo was more beneficial regarding lipid profile and anxiety. We reported progressive slowing of EEG waves in the MetS group with Memantine and Allo treatment with increased relative theta and decreased relative delta rhythms. CONCLUSIONS: Both Allo and Memantine boosted the outcome parameters in the animal model of MetS. Allo markedly improved the anxiety-like behavior in the form of significantly decreased grooming frequency compared to the Memantine-treated groups. Both drugs were associated with increased hippocampal GFAP and BDNF expression, indicating an improvement in synaptic plasticity and so, cognition-related behaviors.

Clinical Characteristics and Prognostic Factors of Endometrial Cancer Patients With Liver Metastasis: A Surveillance, Epidemiology, and End Results Database (SEER)-Based Study of 1,034 Women.

Background There are several patterns of metastatic spread from endometrial cancer (EC). Although studies have been conducted to study the EC population with distant metastasis in the bone and lungs, there is still a lack of studies on liver metastasis. This study aims to evaluate and assess the clinical features and prognostic factors of EC patients with liver metastasis. Methodology We conducted a retrospective cohort study adhering to the guidelines for reporting observational research. We utilized the Surveillance, Epidemiology, and End Results database to gather data on female patients diagnosed with EC and reported liver metastasis. We estimated survival curves using the Kaplan-Meier method and evaluated differences in survival using the log-rank test. We also conducted univariable and multivariable Cox proportional hazards regression analyses to determine the hazard ratios with 95% confidence intervals for overall survival (OS) and identify factors that impact survival. Results We analyzed data from 1,034 EC patients with liver metastasis. Median OS after liver metastasis was six months, and cancer-specific survival was seven months. Univariate Cox regression analysis revealed several factors associated with decreased OS in EC patients. These included age (≥60 years), non-endometrioid and sarcoma histological subtypes, absence of surgery, no chemotherapy, and the presence of distant metastasis to the lung, brain, and bone. Conversely, married marital status and white race were linked to a better prognosis. Subsequent multivariate Cox regression analysis identified age (≥60 years), non-endometrioid histological subtype, absence of surgery, no chemotherapy, and the presence of distant metastasis to lung, brain, and bone remaining as independent risk factors for decreased OS. In contrast, the white race still emerged as an independent prognostic factor for better OS. Conclusions Various risk factors, such as age, race, lung, bone, or brain metastasis, as well as chemotherapy and surgery, may influence the prognosis of individuals with primary EC liver metastases.

Transcatheter aortic valve implantation versus surgical aortic valve replacement for pure aortic regurgitation: a systematic review and meta-analysis of 33,484 patients.

INTRODUCTION: The published studies comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in pure aortic regurgitation (AR) are conflicting. We conducted this systematic review and meta-analysis to compare TAVI with SAVR in pure AR. METHODS: We searched PubMed, Embase, Web of Science (WOS), Scopus, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) from inception until 23 June 2023. Review Manager was used for statistical analysis. The risk ratio (RR) with a 95% confidence interval (CI) was used to compare dichotomous outcomes. Continuous outcomes were compared using the mean difference (MD) and 95% CI. The inconsistency test (I2) assessed the heterogeneity. We used the Newcastle-Ottawa scale to assess the quality of included studies. We evaluated the strength of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. RESULTS: We included six studies with 5633 patients in the TAVI group and 27,851 in SAVR. In-hospital mortality was comparable between TAVI and SAVR (RR = 0.89, 95% CI [0.56, 1.42], P = 0.63) (I2 = 86%, P < 0.001). TAVI was favored over SAVR regarding in-hospital stroke (RR = 0.50; 95% CI [0.39, 0.66], P < 0.001) (I2 = 11%, P = 0.34), in-hospital acute kidney injury (RR = 0.56; 95% CI: [0.41, 0.76], P < 0.001) (I2 = 91%, P < 0.001), major bleeding (RR = 0.23; 95% CI: [0.17, 0.32], P < 0.001) (I2 = 78%, P < 0.001), and shorter hospital say (MD = - 4.76 days; 95% CI: [- 5.27, - 4.25], P < 0.001) (I2 = 88%, P < 0.001). In contrast, TAVI was associated with a higher rate of pacemaker implantation (RR = 1.68; 95% CI: [1.50, 1.88], P < 0.001) (I2 = 0% P = 0.83). CONCLUSION: TAVI reduces in-hospital stroke and is associated with better safety outcomes than SAVR in patients with pure AR.

Knowledge, attitude, and perception of Arab medical students towards artificial intelligence in medicine and radiology: A multi-national cross-sectional study.

OBJECTIVES: We aimed to assess undergraduate medical students' knowledge, attitude, and perception regarding artificial intelligence (AI) in medicine. METHODS: A multi-national, multi-center cross-sectional study was conducted from March to April 2022, targeting undergraduate medical students in nine Arab countries. The study utilized a web-based questionnaire, with data collection carried out with the help of national leaders and local collaborators. Logistic regression analysis was performed to identify predictors of knowledge, attitude, and perception among the participants. Additionally, cluster analysis was employed to identify shared patterns within their responses. RESULTS: Of the 4492 students surveyed, 92.4% had not received formal AI training. Regarding AI and deep learning (DL), 87.1% exhibited a low level of knowledge. Most students (84.9%) believed AI would revolutionize medicine and radiology, with 48.9% agreeing that it could reduce the need for radiologists. Students with high/moderate AI knowledge and training had higher odds of agreeing to endorse AI replacing radiologists, reducing their numbers, and being less likely to consider radiology as a career compared to those with low knowledge/no AI training. Additionally, the majority agreed that AI would aid in the automated detection and diagnosis of pathologies. CONCLUSIONS: Arab medical students exhibit a notable deficit in their knowledge and training pertaining to AI. Despite this, they hold a positive perception of AI implementation in medicine and radiology, demonstrating a clear understanding of its significance for the healthcare system and medical curriculum. CLINICAL RELEVANCE STATEMENT: This study highlights the need for widespread education and training in artificial intelligence for Arab medical students, indicating its significance for healthcare systems and medical curricula. KEY POINTS: • Arab medical students demonstrate a significant knowledge and training gap when it comes to using AI in the fields of medicine and radiology. • Arab medical students recognize the importance of integrating AI into the medical curriculum. Students with a deeper understanding of AI were more likely to agree that all medical students should receive AI education. However, those with previous AI training were less supportive of this idea. • Students with moderate/high AI knowledge and training displayed increased odds of agreeing that AI has the potential to replace radiologists, reduce the demand for their services, and were less inclined to pursue a career in radiology, when compared to students with low knowledge/no AI training.

Safety and efficacy of dinutuximab in the treatment of neuroblastoma: A review.

Dinutuximab, which is a monoclonal antibody targeting GD2 expressed in neuroblasts, improves survival when included in the therapy regimen. This article reviews the importance of dinutuximab in managing neuroblastoma (NB). Dinutuximab targets high levels of GD2 expression in NB cells, thus increasing event-free survival when used in the maintenance therapy of high-risk patients with NB. Although several collaborative studies have set the standard of care for maintenance therapy, the long-term follow-up and continuous evaluation of the use of antibodies and the co-administration of other pharmacological or immunomodulatory drugs remain to be studied. Trials have shown that the use of dinutuximab for maintenance therapy can prolong the time before the first relapse and improve overall survival. However, there is uncertainty in the function of cytokines co-administered with dinutuximab, which may lead to increased toxicity without additional benefits. Recent studies on relapsed and refractory NB have shown the potential efficacy of dinutuximab. Further research is required to properly incorporate Dinutuximab in current treatment modalities.

Medical and Surgical Management of Symptomatic and Asymptomatic Carotid Artery Stenosis: A Comprehensive Literature Review.

Carotid artery stenosis is a condition where the carotid artery is blocked by fatty cholesterol deposits called plaque, increasing the risk of stroke. Elderly individuals with high cardiovascular risk are more susceptible, along with smokers, those with high cholesterol, males, and older individuals. Young females may also be affected by fibromuscular dysplasia. Carotid stenosis significantly raises stroke risk, and the severity is closely linked to stroke incidence and other cardiovascular events. Early detection and treatment are essential to prevent complications. Treatment options include medical and surgical interventions, such as carotid endarterectomy (CEA) and carotid artery stenting (CAS). The choice between surgery and medical management varies depending on patient characteristics and risk factors. This review explores carotid artery stenosis pathophysiology, risk factors, the importance of early detection and treatment, and the surgical approaches of CEA and CAS, addressing their roles and controversies. Healthcare professionals must understand these aspects to provide optimal care to patients with this condition.

Budd-Chiari Syndrome following COVID-19 infection: a case report.

Introduction and importance: Budd-Chiari Syndrome (BCS) is a rare disorder that affects the liver and is caused by blockage of the hepatic veins. Coronavirus disease 2019 (COVID-19) has been linked to an increased risk of developing BCS due to its ability to cause inflammation in the body, which can lead to clotting disorders. Case presentation: A 43-year-old female presented to the emergency department complaining of severe epigastric and right upper quadrant pain and progressive abdominal distention. Upon examination, investigation, and triphasic liver computed tomography with contrast, the patient was diagnosed with BCS. Clinical discussion: The patient was started on anticoagulant therapy with low-molecular-weight heparin and supportive treatment. She was hospitalized for 3 weeks and discharged on oral warfarin 5 mg/day after showing clinical improvement. Conclusion: Hepatosplenomegaly and abdominal distention after COVID-19 infection raise suspicion for BCS. Therefore, early detection of these signs is essential for immediate management.

Efficacy and Safety of Extensive Intraperitoneal Lavage for Patients with Gastric Cancer - A Systematic Review and Meta-analysis.

PURPOSE: Extensive intraperitoneal lavage (EIPL) is a novel therapeutic intervention that aims to limit the chance of peritoneal metastasis during gastrectomy. Clinical trials on using EIPL after gastrectomy show controversial results. We aimed to summarize the evidence of efficacy and safety for using EIPL after gastrectomy to limit the possibility of peritoneal metastasis and improve survival. METHODS: A literature search on PubMed, Scopus, Embase, and Web of Sciences was conducted till June 2023 to identify eligible RCTs that assess the efficacy and safety of EIPL after gastrectomy. The hazard ratio with 95% CI was used to determine the survival probability, the risk ratio with 95% CI was used to assess the surgical outcomes, and ROB-2 and GRADE guidelines were used to assess the risk of bias and the certainty of evidence respectively. RESULTS: Six eligible studies with a total of 1993 patients were included in the meta-analysis. Regarding survival benefits, the survival of the EIPL group did not differ significantly from the non-EIPL group, and the pooled HR of overall survival was 0.86 (95% CI 0.58-1.26) P = 0.44, the disease-free survival was 0.81 (0.58-1.13) P = 0.21, and peritoneal recurrence-free survival was 0.97 (0.79-1.2) P = 0.25. There is no significant association between EIPL and short-term postoperative outcomes. The use of EIPL does not appear to affect postoperative mortality, infection, anastomotic leakage, bleeding, ileus, or hospital stay. CONCLUSION: Our study yielded insufficient evidence about the survival benefits and surgical outcomes of EIPL in patients with gastric cancer after gastrectomy. Therefore, it is not recommended for treating gastric cancer patients.

Comparing MitoQ10 and heat therapy: Evaluating mechanisms and therapeutic potential for polycystic ovary syndrome induced by circadian rhythm disruption.

Environmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed to evaluate the effects of circadian rhythm disruption on reproductive and metabolic functions and investigate the potential therapeutic benefits of MitoQ10 and hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, and three groups with PCOS induced by continuous light exposure(L/L). The reproductive, endocrine, and structural manifestations ofL/L-induced PCOS were confirmed by serum biochemical measurements, ultrasound evaluation of ovarian size, and vaginal smear examination at week 14. Subsequently, the rats were divided into the L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At the end of week 22, all rats were sacrificed. Treatmentwith MitoQ10 or HTT partially reversed the reproductive, endocrine, and structural features of PCOS, leading to a decreased amplitude of isolated uterine contractions, ovarian cystic changes and size, and endometrial thickness. Furthermore, both interventions improved the elevated serum levels of anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) and their transcription target genes, FKBP52 immunostaining in ovarian tissues, and uterine estrogen receptor alpha (ER-α) and PRimmunostaining. In conclusion, MitoQ10 supplementation and HTT demonstrated the potential for ameliorating metabolic, reproductive, and structural perturbations associated with PCOS induced by circadian rhythm disruption. These findings suggest a potential therapeutic role for these interventions in managing PCOS in women.

Characteristics of sudden hearing loss after different COVID-19 vaccinations: a systematic review and meta-analysis.

INTRODUCTION: COVID-19 vaccines are essential to prevent complications and reduce the burden of SARS-CoV-2. However, these vaccines showed side effects such as fatigue, pain, fever, and rarely hearing loss. In this review, we aim to summarize studies investigating hearing loss following COVID-19 vaccination and try to find the possible association and risk factors for this hazardous complication. METHODS: We performed a comprehensive search of five electronic databases (PubMed, Scopus, Web of Science, google scholar, Cochrane) from inception until 9 October 2022. We finally included 16 studies after the first and second scans. We used SPSS to analyze the extracted data. RESULTS: A total of 630 patients were identified, with a mean age of 57.3. Of the patients, 328 out of 609 vaccinated patients took the Pfizer-BioNTech BNT162b2 vaccine, while 242 (40%) took the Moderna COVID-19 vaccine. The mean time from vaccination to hearing impairment was 6.2, ranging from a few hours to one month after the last dose. The results found a significant difference between vaccine types in terms of incidence and prognosis of the condition, while they showed that the number of doses prior to the onset had no significance. CONCLUSION: SNHL has been reported in a small number of people who have received the COVID-19 vaccine, but it is unclear at this time whether the vaccine is directly causing this condition. However, the COVID-19 vaccine has been demonstrated to be safe and effective in preventing illness, and the benefits of vaccination are significant compared to any potential risks. PROTOCOL REGISTRATION: The protocol of this study was registered on Prospero CRD42022367180.

Infodemic and the fear of monkeypox: call for action.

Monkeypox (MPX) was declared a public health emergency of international concern by the World Health Organization (WHO), as of July 23rd, 2022. Fake news spread on social media has already surfaced and contributed to worsening of this concerning situation, making it difficult for the health care experts' voices to be heard. Therefore, we recommend some solutions to overcome this situation, including raising public awareness and preventing stigma through sharing engagement with civil society organizations, and better cooperation between policymakers, the medical community, and social media platforms regarding providing accurate official news about MPX. WHO-one health approach should be established and prioritized.

Humoral immune response to COVID-19 infection or vaccination among celiac disease patients.

Introduction: Celiac disease (CD) is the most common autoimmune disease (AD) of the small intestine, affecting 1-2% of the population globally. It is characterized by the serological presence of autoantibodies (Abs), tissue transglutaminase antibody (tTGA), immunoglobulin (Ig) A, and IgG. Production of antibodies against SARS-CoV-2 after infection with the virus or vaccination is not well understood, especially among CD patients. The goal of this study was to measure the IgG antibodies in Jordanian patients infected with or vaccinated against the SARS-CoV-2 virus with different types of vaccines (Pfizer- BioNTech BNT162b2, Sinopharm BBIBP-CorV or Oxford-AstraZeneca ChAdOx1-S) and compare them with the levels in non-celiac controls. IgG levels induced by different vaccines were also compared. Material and methods: The data for this cross-sectional study were obtained via a survey, whereby respondents were identified through convenience sampling. The healthy controls were given Questionnaire A while CD patients completed Questionnaire B. The blood samples from all participants were tested for the COVID-19 nucleocapsid protein (NP) IgG serum levels for participants previously infected with SARS-CoV-2, and spike (S) protein (S1/S2) IgG serum levels for vaccine recipients. Results: The study involved 116 individuals, 60 (51.7%) of whom were CD patients. The NP IgG serum levels in the infected and S1/S2 IgG levels in the vaccinated CD patients were significantly lower than the levels in controls (48.3 ±44.5 vs. 81.1 ±34.4 and 49 ±45.8 vs. 75.7 ±38.6, p = 0.002). Moreover, only the Pfizer vaccine induced significantly more IgG antibodies in controls compared to CD patients (88.8 ±29.1 vs. 58.3 ±45.4, p = 0.01). On the other hand, the IgG levels were significantly higher in CD patients who received the Pfizer relative to the AstraZeneca vaccine (58.3 ±45.5 vs. 13.0 ±23.6, p = 0.03). After adjusting for presence of CD, age, sex, body mass index (BMI), comorbidities, vaccine type, smoking, gluten adherence, and time since infection or vaccination, SARS-CoV-2 S1/S2 IgG Abs and/or NP IgG Abs positivity was significantly associated with CD absence and negatively with vaccine type (AstraZeneca) with the odds ratios (ORs) of 9.6 (95% CI = 1.5-59.2, p = 0.015) and 0.03 (95% CI = 0.004-0.244. p = 0.001), respectively. Conclusions: We concluded that patients with CD had lower SARS-CoV-2 S1/S2 IgG Abs and NP IgG Abs levels than controls, and CD patients who received the Pfizer vaccine had higher IgG levels than patients who received the AstraZeneca vaccine. We recommend that further research be conducted to address the dynamics of the antibody responses in CD patients regarding COVID-19 infection.

The safety and efficacy of CAR-T cells in the treatment of prostate cancer: review.

OBJECTIVE: A new breakthrough development in cancer treatment is chimeric antigen receptor (CAR)-T cell therapy. In this review, we focussed on its efficacy & safety in prostate cancer, obstacles impeding its clinical use, and some strategies trying to overcome them. METHODS: Searching for relevant articles was done using the PubMed and Cochrane Library databases. Studies had to be published in full-text in English in order to be considered. RESULTS: Many factors can limit optimal CAR-T cell outcomes, including the hostile Prostate microenvironment, age, comorbidities, and tumour grade. The adverse effects of the therapy, particularly the cytokine release syndrome, are a major source of worry after treatment administration. Attempts to alter gamma/delta T-cells and NK cells with CAR, on the other hand, have demonstrated higher effectiveness and safety than conventional CAR-T cells. CONCLUSION: To improve the use of immunotherapies, a greater understanding of the prostate cancer microenvironment is required. Concerning toxicity, more research is needed to find the most specific and highly expressed prostate antigens. Furthermore, discovering predictive biomarkers for toxicities, as well as choosing the correct patient for therapy, might decrease immune-related side effects and achieve a greater response.

Glypican-3 Differentiates Intraductal Carcinoma and Paget's Disease from Other Types of Breast Cancer.

Background and Objectives: breast cancer remains the most common health burden affecting females worldwide. Despite developments in breast cancer diagnostic approaches and treatment strategies, the clinical management of metastatic breast cancer remains challenging. Thus, there is a need to identify new biomarkers and novel drug targets for breast cancer diagnosis and therapy. Recently, aberrant glypican-3 (GPC3) expression in cancers has gained considerable interest in cancer research. The studies, however, have yielded contradictory results about GPC3 expression in breast cancer. Therefore, the current study aims to analyse GPC3 expression across a large panel of different breast cancer subtypes. Materials and Methods: GPC3 expression was immunohistochemically evaluated in 230 breast cancer patients along with eight normal tissues and its associations to clinical and demographic characteristics, as well as immunohistochemical biomarkers for breast cancer. Moreover, a public database consisting of breast cancer patients' survival data and GPC3 gene expression information was used to assess the prognostic value of GPC3 in the survival of breast cancer patients. Results: GPC3 expression was only characterised in 7.5% of different histological breast cancer subtypes. None of the normal breast tissues displayed GPC3 expression. Interestingly, all cases of Paget's disease, as well as 42.9% of intraductal and 16.7% of mucinous carcinomas were found to have GPC3 expression, where it was able to significantly discriminate Paget's disease and intraductal carcinoma from other breast cancer subtypes. Importantly, GPC3 expression was found more often in tumours that tested positive for the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), indicating more favourable histological subtypes of breast cancer. Consequently, longer relapse-free survival (RFS) was significantly correlated with higher GPC3 mRNA expression. Conclusions: Our study proposes that GPC3 is a promising breast cancer subtype-specific biomarker. Moreover, GPC3 may have the potential to be a molecular target for the development of new therapeutics for specific subtypes of breast cancer.