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Objective: To assess the effect of memantine combined with liraglutide on aluminum chloride (AlCl3) and D-galactose (D-GAL)- induced neurotoxicity in rats. Methods: Male Wistar rats were divided into 5 groups of 5 animals each: the positive control, the negative control, the memantine-treated group, the liraglutide-treated group, and the combination group treated with memantine and liraglutide. AlCl3 and D-GAL were used to induce neurotoxicity. Behavioral tests, brain beta-amyloid protein, and oxidative stress biomarkers were evaluated. Results: The Morris water maze test indicated an enhanced memory in the combination group. Moreover, the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain tissue. Neuronal inflammation and oxidative stress biomarkers were significantly reduced, and the levels of antioxidant parameters were enhanced. Conclusions: The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with Alzheimer’s disease.

Abstract Introduction Post-stereotactic radiation-induced neoplasms, although relatively rare, have raised the question of benefit regarding CyberKnife® treatments versus the risk of a secondary malignancy. The incidence of such neoplasms arising in the nervous system is thought to be low, given the paucity of case reports regarding such secondary lesions. Case presentation Here we describe a case of a 43-year-old Middle Eastern woman with primary clear cell renal cell carcinoma and a metastatic focus to the left brain parenchyma who presented with focal neurologic deficits. Following post-surgical stereotactic radiation in the region of the brain metastasis, the patient developed a secondary high-grade astrocytoma nearly 5 years after the initial treatment. Conclusion Although the benefit of CyberKnife® radiotherapy treatments continues to outweigh the relatively low risk of a radiation-induced secondary malignancy, knowledge of such risks and a review of the literature are warranted.

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P 10 cm and/or showing ≥3 mitoses/5 mm2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

Abstract Background A pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (COVID 19) incidence data are largely available online. Until August 17, COVID 19 has hit more than 22 million individuals all over the globe. So, it is urged to get clear information about the prevalence of the virus. Therefore, one can manipulate easily a suitable mathematical model to fit these published data. Methods We propose a mathematical model that considers the total population, in 25 countries, either infected by COVID 19 or confined (safe) during the period from November 17, 2019, to August 17, 2020. The model considers the total population as a complex number; the imaginary part is the number of infected individuals and the real part is the number of confined individuals. This classification combined with mathematical treatments leads to a transmission dynamics of the virus to be as wave-like motion. The virus can hit any country either by one wave or by successive waves (up to 11 waves). Findings We find net discrimination between the 25 countries investigated in this report. The immediate response to the first attack is a substantial parameter to determine whether the epidemic attack will be in one wave or it can be in successive waves. For example, the best case was such as individuals in China hit by one wave while the individuals in the USA were attacked by nine waves; it is the worst case all over the globe. In addition, the model differentiates between the daily reproduction numbers (R d0) and the median reproduction number (R 0). We have found that R d0 decreases exponentially with time from high values down to zero at the wave maximum point; and R 0 varies from a country to another. For example, the virus hit individuals in Germany in R 0 = 1.39 (96% CI 1.01–3.87) and in the USA R 0 = 3.81 (91% CI 1.71–5.15). We have found that twice the virus has hit both the USA and Iran. The great protestation of black matter lives in the USA and the great assemblage of the new Iranian year, on March 21, 2020, have been the cause of the second epidemic attack in both countries. Interpretation Our results show that COVID 19 transmission depends on the prompt reaction against the first viral-wave. The reaction depends on both the social behaviour of individuals and on the swift system-decision by the governmental decision-maker(s). The Chinese strictly follow the decision-maker and therefore the virus hit by only one wave; while in the USA, the system-decision was different and the American-responses were different, therefore ten waves followed the first wave.

Musim Alotaibi,1,2 Ahmed Ali,1,3 Duaa Bakhshwin,4 Yasser Alatawi,5 Sultan Alotaibi,6 Abdullah Alhifany,7 Badr Alharthi,2 Nasser Alharthi,2 Awatef Alyazidi,2 Yasmeen Alharthi,2 Aziza Alrafiah8 1Department of Pharmacology, King Abdulaziz University, Jeddah City, Kingdom of Saudi Arabia; 2Department of Pharmacy, King Faisal Medical Complex, Taif City, Kingdom of Saudi Arabia; 3Department of Pharmaceutics, Assiut University, Assiut City, Egypt; 4Department of Pharmacotherapy and Outcomes Science, King Abdulaziz University, Jeddah City, Kingdom of Saudi Arabia; 5Department of Pharmacy Practice, University of Tabuk, Tabuk City, Kingdom of Saudi Arabia; 6Department of Pharmacy, King Abdul-Aziz Medical, Jeddah City, Kingdom of Saudi Arabia; 7Department of Clinical Pharmacy College of Pharmacy, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia; 8Department of Medical Laboratory Technology, King Abdulaziz University, Jeddah City, Kingdom of Saudi ArabiaCorrespondence: Aziza Alrafiah P.O Box 80200, Jeddah, 21589, Kingdom of Saudi ArabiaTel +966 126401000 Ext. 23495Fax +966 126401000 Ext. 21686Email aalrafiah@kau.edu.saBackground: Coronavirus disease (COVID-19) is an infectious disease due to SARS-COV-2. Patients with risk factors are vulnerable to severe morbidity and mortality. Favipiravir (FPV) and hydroxychloroquine (HCQ) are considered possible COVID-19 treatments.Objective: To investigate the effectiveness and safety of FPV compared to HCQ in patients with COVID-19 as the standard of care approved by the national protocol there.Methods: This is a retrospective cohort study on patients with COVID-19 who were administered either FPV or HCQ at King Faisal Medical Complex, Taif, Saudi Arabia, from June 2020 to August 2020.Results: In total, 508 patients were included in the analysis. Patients were categorized into three groups by medication. Patients enrolled in this study were 244 (55.8%) on FPV, 193 (44.2%) on HCQ and 71 (13.81%) on neither medication. Patients who received FPV had higher age and greater comorbidity. Most of the patients were discharged on day 14 (n = 303, 59.6%), 26 (36.6%) in neither med, 154 (63.1%) in FPV and 123 (63.7%) in HCQ groups with significant difference between groups (P < 0.0001). Mortality rate was 8.2% (n = 20) in FPV and 7.3% (n = 14) in HCQ groups with significant difference between groups (P = 0.048). Regarding drug safety, 19.7% of patients treated with FPV vs 7.8% HCQ have adverse effects with significant difference between groups (P < 0.0001). Most of the side effects were increase ALT and AST. Meanwhile, prolonged Q-T interval was reported only in the HCQ group (2.6%). From Cox regression modeling, only mechanical ventilation due to Covid 19 was predictive for mortality (HR: 16.598, 95% CI: 7.095– 38.828, P < 0.0001). Meanwhile, there was no significant difference in the prediction of discharge of FPV (vs HCQ) (HR: 0.933, 95% CI: 0.729– 1.195, P = 0.5843), predictors of mortality were HCQ (vs FPV) (HR: 2.3, 95% CI: 0.994– 5.487, P = 0.0518). Kaplan–Meier survival curves showed improved survival time and discharged time among patients in the HCQ versus FPV group with an insignificant difference between them (P = 0.85, P = 0.06, respectively).Conclusion: The present study concluded that FPV and HCQ showed comparable efficacy in decrease mortality and oxygen requirements. FPV likely has a more favorable safety profile regarding cardiac toxicity. A randomized clinical trial with large patient numbers is recommended to confirm the effectiveness of these drugs in COVID-19 patients.Keywords: coronavirus disease, COVID-19, favipiravir, hydroxychloroquine, mortality, risk factors

This article, published in the International Journal of Surgical Pathology, presents a case study of a 53-year-old woman with a rapidly enlarging breast mass. The mass was initially diagnosed as a fibroadenoma but was later found to be a malignant phyllodes tumor (MPT) with heterologous telangiectatic osteosarcoma. MPTs are rare and aggressive tumors with a high risk of recurrence and metastasis. The presence of heterologous elements, such as osteosarcoma, classifies the tumor as MPT. This case is unusual because telangiectatic osteosarcoma arising in MPT is rare, with few reported cases in the literature. The article provides detailed histologic descriptions and diagnostic criteria for this type of tumor. The patient underwent resection and adjuvant radiation therapy and has remained disease-free for 19 months. [Extracted from the article]

Background: The antioxidant, hypoglycemic, and insulin-enhancing effects of ginger and cinnamon were previously confirmed in experimental and human studies, while the combined effect of ginger and cinnamon was not thoroughly investigated until now.Objectives: This study was designed to assess the antidiabetic effect of combined administration of ginger (Zingiber officinale Roscoe) and cinnamon (Cinnamomum cassia L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect.Materials and methods: STZ was utilized to induce diabetes mellitus in male Sprague–Dawley rats. Assessments of fasting blood glucose level (BGL), the total antioxidant capacity (TAC), serum insulin, HOMA-IR, and HOMA–β cells were performed. Pancreatic gene expression of β-catenin and p53 was assessed using RT-PCR. Assessment of histopathological alterations of pancreatic islet cells was performed using routine and immunohistochemical techniques.Results: BGL significantly decreased (p = 0.01), while serum insulin and TAC significantly increased (p < 0.001) in both metformin- and ginger plus cinnamon–treated groups compared to the untreated diabetic group. HOMA–β cell index significantly increased (p = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated (p < 0.001), while β-catenin was insignificantly downregulated (p = 0.32) in ginger plus cinnamon–treated groups. Insulin immunoexpression in β cells significantly increased (p = 0.001, p = 0.004) in metformin- and ginger plus cinnamon–treated groups, respectively.Conclusions: The combined administration of ginger and cinnamon has a significant hypoglycemic and antioxidant effect in STZ-induced diabetes mostly through enhancing repair of islet cells mediated via upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended.

Myxofibrosarcomas (MFS) present as slowly enlarging superficial masses in elderly patients. Even though these tumors fail to exhibit a distinct immunophenotype, diagnosis is straightforward when they present in subcutaneous tissue. Intramuscular MFS, however, are more challenging to diagnose as the differential also includes dedifferentiated liposarcoma with myxoid features. The vast majority of dedifferentiated liposarcomas show MDM2 amplification, whereas limited data exists as to the MDM2 status of MFS. We sought to explore the rate of MDM2 amplification in cases of classic MFS. Our archives were searched for MFS; only subcutaneous well-sampled resections were included. FISH for MDM2 amplification was performed on each tumor. A cohort of myxoid dedifferentiated liposarcoma resections was studied for comparison. Twenty-two MFS arose in patients aged 44 to 85 years. All tumors contained an infiltrative population of atypical cells embedded in a myxoid stroma with curvilinear blood vessels. MDM2 amplification by FISH was identified in 3 (of 22; 14%) tumors. Available follow up on 17 patients (range 1-96 months; median 13 months) revealed 6 patients with local recurrence and 1 with distant metastasis. Of 3 patients with MDM2- amplified MFS, 1 experienced recurrence and died of unrelated causes, while the second was alive without disease 12 months after diagnosis. Even though the rate of MDM2 amplification by FISH in MFS appears to be low, a subset of cases may show this genetic alteration, which pathologists should be aware of to avoid misclassification as myxoid dedifferentiated liposarcomas. Further studies are necessary to determine if amplification status adds prognostic value. [ABSTRACT FROM AUTHOR]

Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease. [ABSTRACT FROM AUTHOR]

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Background: Desmoplastic fibroblastoma (collagenous fibroma) is a rare soft tissue tumor that usually arises in the subcutis or skeletal muscle. Cases superficial to fascia are unusual and can cause diagnostic difficulty. We present 11 cases of superficial desmoplastic fibroblastoma involving a wide anatomic distribution. Methods: Archives were searched using the term "desmoplastic fibroblastoma" over a 10‐year period (2012–2022). Cases superficial to fascia were retrieved, and available clinicopathologic features were recorded. Only cases involving the dermis were included. Results: Eleven cases were identified, all of which were received in consultation. Tumors involved the head and neck (2), lower extremity (2), back (2), foot (1), shoulder (1), axilla (1), hand (1), and breast (1). Each consisted of a hypocellular proliferation of bland stellate to spindled fibroblasts set in a collagenous to focally myxoid stroma. The immunohistochemical stains available for review demonstrated SMA positivity (4/7) and negative immunoreactivity for CD34 (0/6), EMA (0/3), desmin (0/3), and S100 (0/7). Conclusions: Desmoplastic fibroblastoma may present superficially in the dermis to subcutis, posing a potential source of diagnostic difficulty. Recognition of the characteristic histopathologic features of desmoplastic fibroblastoma with judicial use of immunohistochemical stains should allow for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma is the second most common primary liver malignant neoplasm. It usually affects older individuals in their seventh decade of life with no gender predilection. Recently, a distinct subtype of cholangiocarcinoma has emerged with 2 proposed names: "cholangioblastic" and "solid tubulocystic." This variant predominantly occurs in younger women who lack the common risk factors for patients diagnosed with cholangiocarcinomas, such as older age and chronic liver disease or cirrhosis. We describe 3 new patients with a cholangioblastic variant of intrahepatic cholangiocarcinoma. At the time of diagnosis, the patients were aged 19-, 46-, and 28-year-old; 2 females and 1 male (the 46-year-old). None of our patients had a history of chronic liver disease or known predisposing factors for liver tumors. Tumor size ranged from 2.3 to 23 cm in greatest dimension. Histological examination of these tumors demonstrated reproducible morphology characterized by trabecular, nested, and multicystic patterns with micro and macro follicles filled with eosinophilic material. The immunohistochemical profile showed that the tumor cells were positive for keratin 7, inhibin, synaptophysin, and albumin in situ hybridization, while negative for HepPar1, arginase, and INSM1. All tumors lacked conventional intrahepatic cholangiocarcinoma/adenocarcinoma morphology. We also review the literature and emphasize that neuroendocrine tumors should be recognized as a major diagnostic pitfall of this variant. [ABSTRACT FROM AUTHOR]