One-pot derivatization spectrofluorimetric method for detection of aspartame in sweetener commercial tablets and soft drinks: Greenness assessments of the methodology.

Aspartame is an artificial sweetener used in drinks and many foods. International Agency for Research on Cancer classified aspartame as possibly carcinogenic to humans (IARC Group 2B). In this study, a sensitive and selective spectrofluorimetric method was developed to detect aspartame. The method is based on switching on the fluorescence activity of aspartame upon its condensation with O-phthalaldehyde (Roth's reaction) in the presence of 2-mercaptoethanol. The reaction product was detected fluorometrically at λem of 438 nm after λex of 340 nm. All reaction conditions required to yield the optimal fluorescence intensity were observed and investigated. Furthermore, the approach was validated according to ICH guidelines. Upon plotting the concentrations of aspartame against their associated fluorescence intensity values, the relationship between the two variables was linear within the range of 0.5-3.0 µg/mL. Furthermore, the method was employed to analyze the quantity of aspartame in commercial packages and soft drinks with an acceptable level of recovery. In addition, the Green Solvents Selecting Tool, Complementary Green Analytical Procedure Index, and the Analytical Greenness Metric tool were used to evaluate the sustainability and the greenness of the developed methodology.

NRASQ61R mutation drives elevated angiopoietin-2 expression in human endothelial cells and a genetic mouse model.

BACKGROUND: Angiopoietin-2 (Ang-2) is increased in the blood of patients with kaposiform lymphangiomatosis (KLA) and kaposiform hemangioendothelioma (KHE). While the genetic causes of KHE are not clear, a somatic activating NRASQ61R mutation has been found in the lesions of KLA patients. PROCEDURE: Our study tested the hypothesis that the NRASQ61R mutation drives elevated Ang-2 expression in endothelial cells. Ang-2 was measured in human endothelial progenitor cells (EPC) expressing NRASQ61R and a genetic mouse model with endothelial targeted NRASQ61R. To determine the signaling pathways driving Ang-2, NRASQ61R EPC were treated with signaling pathway inhibitors. RESULTS: Ang-2 levels were increased in EPC expressing NRASQ61R compared to NRASWT by Western blot analysis of cell lysates and ELISA of the cell culture media. Ang-2 levels were elevated in the blood of NRASQ61R mutant mice. NRASQ61R mutant mice also had reduced platelet counts and splenomegaly with hypervascular lesions, like some KLA patients. mTOR inhibitor rapamycin attenuated Ang-2 expression by NRASQ61R EPC. However, MEK1/2 inhibitor trametinib was more effective blocking increases in Ang-2. CONCLUSIONS: Our studies show that the NRASQ61R mutation in endothelial cells induces Ang-2 expression in vitro and in vivo. In cultured human endothelial cells, NRASQ61R drives elevated Ang-2 through MAP kinase and mTOR-dependent signaling pathways.

The Expression of Serglycin Is Required for Active Transforming Growth Factor ß Receptor I Tumorigenic Signaling in Glioblastoma Cells and Paracrine Activation of Stromal Fibroblasts via CXCR-2.

Serglycin (SRGN) is a pro-tumorigenic proteoglycan expressed and secreted by various aggressive tumors including glioblastoma (GBM). In our study, we investigated the interplay and biological outcomes of SRGN with TGFßRI, CXCR-2 and inflammatory mediators in GBM cells and fibroblasts. SRGN overexpression is associated with poor survival in GBM patients. High SRGN levels also exhibit a positive correlation with increased levels of various inflammatory mediators including members of TGFß signaling pathway, cytokines and receptors including CXCR-2 and proteolytic enzymes in GBM patients. SRGN-suppressed GBM cells show decreased expressions of TGFßRI associated with lower responsiveness to the manipulation of TGFß/TGFßRI pathway and the regulation of pro-tumorigenic properties. Active TGFßRI signaling in control GBM cells promotes their proliferation, invasion, proteolytic and inflammatory potential. Fibroblasts cultured with culture media derived by control SRGN-expressing GBM cells exhibit increased proliferation, migration and overexpression of cytokines and proteolytic enzymes including CXCL-1, IL-8, IL-6, IL-1ß, CCL-20, CCL-2, and MMP-9. Culture media derived by SRGN-suppressed GBM cells fail to induce the above properties to fibroblasts. Importantly, the activation of fibroblasts by GBM cells not only relies on the expression of SRGN in GBM cells but also on active CXCR-2 signaling both in GBM cells and fibroblasts.

The Incidence of Hematological Toxicities in Colorectal Cancer Patients Treated With Fluoropyrimidine-Based Regimens at Princess Noorah Oncology Center.

Background Fluoropyrimidine-based regimens are used for the management of colorectal cancer, which is the second most common cancer in Saudi Arabia. We aimed to study the incidence of hematological toxicities in colorectal cancer patients treated with fluoropyrimidine and fluoropyrimidine-based regimens at Princess Noorah Oncology Center, King Abdulaziz Medical City- Jeddah, Saudi Arabia.  Methods A retrospective cohort study that included adult colorectal cancer patients who were treated with fluoropyrimidine-based regimens from January 1, 2018 to December 31, 2018 at Princess Noorah Oncology Center, Jeddah, Saudi Arabia was performed. Our primary objective was to determine the incidence of anemia, neutropenia, and thrombocytopenia in colorectal cancer patients treated with fluoropyrimidines and fluoropyrimidine-based regimens. Secondary objectives were to assess the grade of hematological toxicities associated with 5-fluorouracil (5-FU) use and to determine the frequency of unplanned hospital admissions or emergency department (ED) visits after receiving fluoropyrimidine-based regimens. The collected data contained patients' characteristics (weight, height, age, gender, and diagnosis), chemotherapy agents, and hematological toxicity-related findings such as absolute neutrophil count, hemoglobin, platelet count, and number of ED visits or hospital admissions during fluoropyrimidine-based chemotherapy regimens. Results Of the 570 cycles of the fluoropyrimidine-based regimen received by 68 patients, hematological toxicities were observed in 508 (89.1%) cycles, and grade ≥ 3 grade toxicities were found in 46 (8.1%) cycles. The results demonstrated a statistically significant difference in the incidence of grade 3-4 neutropenia between patients who received bolus administration of 5-FU and those who did not (8.5% vs. 2.3% respectively, p=0.025). The incidence of grade 3-4 anemia was higher in the bolus group (11.3%) compared to the group where bolus was omitted (4.6%); however, the difference was not statistically significant (p=0.059). Furthermore, there was no significant difference among the two groups for grade 3 and grade 4 thrombocytopenia (0.0% with bolus given and 0.7% with bolus omission p=1.00). Conclusion Our retrospective study showed that there have been significantly higher grade 3-4 hematological toxicities observed with bolus administration of 5-FU, which confirms the previous reports.

Cryotherapy for Eccrine Poroma: A Case Report.

Eccrine poroma (EP) is a benign adnexal tumor that is derived from acrosyringium, the intraepidermal eccrine duct of sweat glands. The standard treatment for eccrine poroma is complete excision. However, this case report highlights cryotherapy as one of the modalities in treating eccrine poroma. We present a case of a 33-year-old male patient who was a known case of generalized vitiligo since he was nine years old. During our skin checkup before starting him on phototherapy, we found a mass over the palmar aspect of the middle finger of the right hand that started to appear five years ago. The mass gradually increased in size, was painless, has no discharge, and was not associated with a history of trauma or infection. The review of systems was unremarkable. Skin examination revealed an asymptomatic, 2.0 × 1.5 cm-sized, solitary, collarette-encircled, dome-shaped, flesh-colored, non-pigmented, deep-red nodule protrusion from the palmar aspect of the middle finger of the right hand. Poroma was considered as the diagnosis, and a punch skin biopsy was performed to confirm the diagnosis and to roll out pyogenic granuloma, amelanotic melanoma, and porocarcinoma as differential diagnoses. A 3 mm punch skin biopsy was performed under local anesthesia and was found to be histologically consistent with eccrine poroma. Hence, cryosurgery was chosen based on histological favorable features. We used cryospray in a single session of 15 seconds in three applications, with five-second intervals in between (skin frosting recovery). Furthermore, the lesion was completely curative with a single session of cryotherapy. The patient followed up for one year without evidence of recurrence.

Prosthetic vascular grafts engineered to combat calcification: Progress and future directions.

Calcification in prosthetic vascular conduits is a major challenge in cardiac and vascular surgery that compromises the long-term performance of these devices. Significant research efforts have been made to understand the etiology of calcification in the cardiovascular system and to combat calcification in various cardiovascular devices. Novel biomaterial design and tissue engineering strategies have shown promise in preventing or delaying calcification in prosthetic vascular grafts. In this review, we highlight recent advancements in the development of acellular prosthetic vascular grafts with preclinical success in attenuating calcification through advanced biomaterial design. We also discuss the mechanisms of action involved in the designs that will contribute to the further understanding of cardiovascular calcification. Lastly, recent insights into the etiology of vascular calcification will guide the design of future prosthetic vascular grafts with greater potential for translational success.

The Impact of Leukemia on the Detection of Short Tandem Repeat (STR) Markers.

INTRODUCTION: Short tandem repeats (STRs) have been used for various identity typing methods worldwide. They have high discrimination power in human identification in forensics, paternity testing, missed personal identification, genetic diseases, and gene regulatory functions. They have also been used to detect and monitor the stability of diseases, including various types of cancer. This study aimed to investigate the impact of leukemia on the detection and stability of STR markers. METHODS: DNA was isolated from 30 participants (15 with chronic myeloid leukemia( CML) and 15 healthy controls) and used to amplify STR markers using specific primers. RESULTS: We found that the blood of those with leukemia had more 9.3 and 9 alleles at the tyrosine hydroxylase 1 (TH01) marker than the blood of the healthy control samples. The results of this study will help researchers understand leukemia's effect on the detection and stability of STR markers in leukemic patients compared to healthy individuals. CONCLUSION: Our results demonstrate that STR markers could become useful in genetic studies of leukemia cases.

A case of papillary hyperplasia of thyroid misdiagnosed as papillary thyroid carcinoma: Case report and review of literature.

Overdiagnosis of papillary thyroid hyperplasia which may mimic papillary thyroid carcinoma in fine-needle aspiration and frozen section has a serious impact on the patient. Therefore, it is important to know the difference between them to avoid over or undertreatment.

Neuroimaging manifestations and genetic heterogeneity of Walker-Warburg syndrome in Saudi patients.

BACKGROUND: Walker-Warburg syndrome (WWS), an autosomal recessive disease, is the most severe phenotype of congenital muscular dystrophies. Its diagnosis remains primarily clinical and radiological. Identification of its causative variants will assist genetic counseling. We aim to describe genetic and neuroimaging findings of WWS and investigate the correlation between them. METHODS: We retrospectively reviewed the clinical, genetic and neuroimaging findings of eleven Saudi neonates diagnosed with WWS between April 2012 and December 2018 in a single tertiary care center. Correlation between neuroimaging and genetic findings was investigated. RESULTS: All patients had macrocephaly except one who had intrauterine growth restriction. Dysmorphic features were identified in nearly half of the patients. Creatine kinase levels were available in nine patients and were always elevated. Homozygous pathogenic variants were identified in all patients spanning POMT1 (n = 5), TMEM5 (n = 3), ISPD (n = 2) and POMT2 (n = 1) including one patient who had a dual molecular diagnosis of ISPD and PGAP2. On neuroimaging, all patients showed cobblestone cortex, classical infratentorial findings, and hydrocephalus. Other cerebral cortical malformations included subependymal heterotopia, polymicrogyria and open-lip schizencephaly in four, two and one patients, respectively. Buphthalmos and microphthalmia were the most prevalent orbital findings and found in all patients either unilaterally or bilaterally. CONCLUSION: WWS is a genetically heterogeneous disorder among Saudis. The case with an additional PGAP2-related phenotype exemplifies the increased risk of dual autosomal recessive disorders in consanguineous populations. MRI is excellent in demonstrating spectrum of WWS brain and orbital malformations; however, no definite correlation could be found between the MRI findings and the genetic variant.

Diagnostic imaging and surgical management of a congenital cervical teratoma.

Congenital cervical teratomas are rare tumours arising from the neck and consist of three major tissue layers of an embryo: the ectoderm, endoderm, and mesoderm. A great majority of cervical teratomas are benign tumours. However, the clinical significance of these tumours arises from the complications they can cause during pregnancy due to the postnatal mass effect on the airway and oesophagus of the neonate. Diagnosis of a congenital cervical teratoma is possible during an early prenatal ultrasound evaluation. The appearance depends on the size of the tumour, but it is typically a large neck mass with solid and cystic components that causes hyperextension of the neck and is frequently associated with polyhydramnios. In the postnatal period, ultrasound helps in differentiating cervical teratoma from other common congenital cervical masses. MRI is the modality of choice to evaluate the consistency of the tumour, surrounding soft tissue extent of the tumour, and any mass effect on other cervical structures. In our case report, we present a case of a full-term baby that was delivered with a large cervical mass. MRI was helpful in demonstrating the complex content of the mass, surrounding soft tissue extension, and mass effect on other major cervical structures. The clear demarcation of the mass facilitated complete surgical removal without complications.