Assessment of attitudes and practices towards COVID-19 pandemic: a survey on a cohort of educated Syrian population.

BACKGROUND: Coronavirus disease (COVID-19) caused the death of millions of people and affected the lives of hundreds of millions worldwide. The WHO recommendations aimed mainly to reduce transmission, minimize infection, and get people vaccinated. Nevertheless, opinions and attitudes about the disease varied. In this study, we evaluated personal attitudes and practices of a cohort of an educated Syrian population, after several waves of infection with COVID-19 and the release of different types of vaccines. METHODS: A cross-sectional internet-based survey was launched in January 2022.The survey queried the participants' personal experience, attitudes, practices towards COVID-19, and vaccination. RESULTS: The study included 408 individuals. The respondents were mainly females (72.6%), 20-29 years old (39.2%), and college graduates (59.3%). A large proportion (89.7%) reported having been infected at least once during the pandemic; a significant association was found with age (p = 0.001). Nearly half of the respondents got vaccinated; the majority were > 40 years old. Opinions differed regarding the effectiveness and safety of the vaccines; only a small percentage of the participants (17.4%) thought all vaccines were effective and safe. Remarkably, the level of education did not significantly dominate the participants' attitudes or practices towards the COVID-19 pandemic. Approximately half of the respondents (44.9%) stated their lives were affected by the pandemic and over the third were worried (38%). A significant association was detected with gender in favour of females. Most of the participants have taken at least one precautionary measure to limit the infection. CONCLUSION: The level of education did not significantly dominate the participants' attitudes or practices towards the COVID-19 pandemic. Female respondents were more cautious, concerned and committed to taking precautionary measures regardless of their education level. However, their unwillingness to receive the vaccine raises significant concerns. Efforts should be made to emphasize the importance of immunization, the safety and effectiveness of vaccines, and encourage vaccination among individuals.

Cholera in Syria, a crisis following crises: Assessment of knowledge, attitude, and practice in a cohort of syrian population.

Cholera is an acute bacterial disease caused by intestinal infection with Vibrio cholerae. It is one of the major re-emerging communicable diseases in Syria following the Syrian crisis and the Covid-19 pandemic. The current study was undertaken to explore the level of awareness in a cohort of the Syrian population by testing their knowledge and investigating their attitudes and practices. An internet-based survey that queried knowledge of cholera transmission, prevention, risk factors, and treatment was designed. Of particular interest was revealing sources of information associated with higher knowledge. Furthermore, individual attitudes and practices towards the disease were collected and analyzed. Participants were 1521, mostly females (68.3%), 18-25 years old (56.4%), single (72.7%), and college degree holders (75.9%). The main sources of information on cholera were school/college (31.7%), social media (28.7%), family and friends (13.2%), and online search engines (11.3%). The average total knowledge of the cohort was 40.39%. The participants >40 years old, highly educated, living in urban areas, and females demonstrated higher knowledge of cholera. Schools/colleges and online search engines were associated with better knowledge. Most of the cohort showed serious attitudes and considered cholera a very dangerous disease. They were very concerned about cholera resurfacing in the country and were worried about getting infected. The majority of the cohort were leading their lives favorably by eating out/takeaway <5 times a month; however, their practices regarding handling raw produce were suboptimal. Succeeding cholera re-emergence, females, highly educated, and >40 years old participants were more committed to changing practices and taking stricter safety measures. As cholera imposes a health threat not only to Syrians but to the people of the whole Middle East, preventive strategies were suggested, mainly raising awareness with more focused media means and vaccination of people at high risk in the affected areas of the governorates.

Artificial Intelligence (AI) for Detection and Localization of Unobturated Second Mesial Buccal (MB2) Canals in Cone-Beam Computed Tomography (CBCT).

The aim of this study was to develop a deep learning model to automatically detect and segment unobturated mesial buccal 2 (MB2) canals on endodontically obturated maxillary molars depicted in CBCT studies. Fifty-seven deidentified CBCT studies of maxillary molars with clinically confirmed unobturated MB2 canals were retrieved from a dental institution radiology database. One-hundred and two maxillary molar roots with and without unobturated MB2 canals were segmented using ITK-SNAP. The data were split into training and testing samples designated to train and evaluate the performance, respectively, of a convolutional neural network (CNN), U-Net. The detection performance revealed a sensitivity of 0.8, a specificity of 1, a high PPV of 1, and a NPV of 0.83 for the testing set, along with an accuracy of 0.9. The segmentation performance of unobturated MB2 canals, assessed using the custom metric, rendered a mean value of 0.3018 for the testing set. The current AI algorithm has the potential to identify obturated and unobturated canals in endodontically treated teeth. However, the AI algorithm is still somewhat affected by metallic artifacts, variations in canal calcifications, and the applied configuration. Thus, further development is needed to improve the algorithm and validate the accuracy using external validation data sets.

Evaluation of diagnostic parameters in detecting prediabetes in a cohort of Syrian healthcare providers and staff: correlations with risk factors.

Diabetes is spreading more rapidly in lower-middle-income countries like Syria. Early prevention programs are crucial and achievable through identification, treatment, and revision of prediabetes. Evaluation of hyperglycemia diagnostic parameters (FPG, OGTT, HbA1c) in detecting prediabetes was executed through three phases of screening asymptomatic adults and applying the parameters sequentially. Relationships with risk factors from the American Diabetes Association (ADA) were assessed. Correlations amongst lipid profile (total cholesterol, LDL, HDL, and TG) and hyperglycemic parameters were additionally explored. Participants (212) were mainly males (60.4%), married (61.5%), healthcare providers (28.8%), and had first-degree relatives with diabetes (32%). 10.6% had hypertension, 6.8% had dyslipidemia, and 10.7% of the female participants had PCO. Following the ADA criteria, 18% and 1.9% of the participants were diagnosed with prediabetes and diabetes, respectively. The cohort of participants with prediabetes and diabetes had higher percentage of first-degree relative with diabetes (70%), obesity (55%), hypertension (25%), dyslipidemia (15%), and PCO in females (20%). They were mainly professors (40%) and healthcare providers (25%). Interrelations amongst the hyperglycemic parameters were revealed, also with lipids and risk factors mainly age, BMI, familial diabetes, dyslipidemia, and hypertension. Reports on prediabetes are scarce in Syria. This study, one of a few on the topic, investigated the hyperglycemic parameters in detecting prediabetes and revealed the prevalence and the correlation with risk factors and lipids. It adds substantial information to our understanding of the intertwined associations of the studied variables.

Pharmacogenetics: Knowledge assessment amongst Syrian pharmacists and physicians.

BACKGROUND: Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries including Syria. Therefore we aimed at evaluating the depth of knowledge in pharmacogenetics and the attitude towards it amongst Syrian pharmacists and physicians. METHODS: We carried out an internet-based questionnaire consisted of 26 questions, sent through specialized websites and private groups with a large number of pharmacists and physicians members. The survey was available online for a period of 1 month. RESULTS: The total number of respondents was 154, mostly female pharmacists. Our statistical analysis showed a strong positive association between profession (in favour of pharmacists) and pharmacogenetics knowledge p = 0.049; however, no correlation with experience p = 0.811 was found. A significant difference was reported between the knowledge of pharmacists and physicians p = 0.001 concerning drugs that need pharmacogenetics testing before being prescribed. The majority of respondents had no information about applying genetic tests in Syria before prescribing medications nor did they possess the knowledge regarding drugs that show differential responses in patients according to their unique genotypes. In our study, the percentage knowledge assessment score was low in general (mean ± Standard deviation, SD) (46% ± 13.9%). The majority of the respondents agreed that pharmacists should provide counselling to patients on the subject of pharmacogenetics. Respondents' opinions varied concerning making pharmacogenetics learning a priority. CONCLUSION: Lack of pharmacogenetics knowledge was found amongst respondents in general. Our findings raise concerns about the lack of awareness amongst physicians, which may hinder the implementation of this crucial field in Syria. We suggest an emphasis on the role of education, training, and conducting genotyping research on the Syrian population.

Rare isolated primary peritoneal hydatid cysts: A case report from Syria.

Hydatid disease caused by Echinococcus granulosus is endemic in many regions of the world. The major primary site for the disease in adults is the liver and the secondary site are the lungs. Secondary peritoneal cysts are relatively common and expected to occur after rupture of the primary hepatic hydatid cyst. Primary peritoneal hydatid cyst disease without any other organ involvement has been previously reported, and yet it is still considered rare even in endemic areas. A case of a large primary peritoneal hydatid multicystic lesion without other organ involvement in a 25-year-old girl seen at the gastrointestinal outpatient clinic in the University of Kalamoon Medical City is presented and discussed. The disease was very extensive but surgical intervention was refused due to the patient being a young unmarried female. The patient was treated and observed over a period of ten months. She responded very well to medical treatment with albendazole. The case emphasizes the importance of hydatid disease being included in the differential diagnosis of any cyst in the abdominal cavity for patients living or coming from an area of endemic hydatid disease even without liver or lung involvement. This also goes to show that it can respond to medical treatment, which becomes even more valuable in conditions where surgical intervention might not be an option.

Induction of mitotic cell death by overriding G2/M checkpoint in endometrial cancer cells with non-functional p53.

OBJECTIVE: Endometrial tumors with non-functional p53, such as serous uterine endometrial carcinomas, are aggressive malignancies with a poor outcome, yet they have an Achilles' heel: due to loss of p53 function, these tumors may be sensitive to treatments which abrogate the G2/M checkpoint. Our objective was to exploit this weakness to induce mitotic cell death using two strategies: (1) EGFR inhibitor gefitinib combined with paclitaxel to arrest cells at mitosis, or (2) BI2536, an inhibitor of polo-like kinase 1 (PLK1), to block PLK1 activity. METHODS: We examined the impact of combining gefitinib and paclitaxel or PLK1 inhibitor on expression of G2/M checkpoint controllers, cell viability, and cell cycle progression in endometrial cancer cells with mutant p53. RESULTS: In cells lacking normal p53 activity, each treatment activated CDC25C and inactivated Wee1, which in turn activated cdc2 and sent cells rapidly through the G2/M checkpoint and into mitosis. Live cell imaging demonstrated irreversible mitotic arrest and eventual cell death. Combinatorial therapy with paclitaxel and gefitinib was highly synergistic and resulted in a 10-fold reduction in the IC50 for paclitaxel, from 14nM as a single agent to 1.3nM in the presence of gefitinib. However, BI2536 alone at low concentrations (5nM) was the most effective treatment and resulted in massive mitotic cell death. In a xenograft mouse model with p53-deficient cells, low dose BI2536 significantly inhibited tumor growth. CONCLUSIONS: These findings reveal induction of mitotic cell death as a therapeutic strategy for endometrial tumors lacking functional p53.

Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.

OBJECTIVE: The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. METHODS: Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n=111) and CD31 (n=56) was done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. RESULTS: Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression-free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. CONCLUSIONS: VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression-free survival and platinum resistance.

EGFR isoforms and gene regulation in human endometrial cancer cells.

BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) constitute a principal growth-promoting pathway in endometrial cancer cells. Pre-clinical studies were undertaken to compare the expression of EGFR isoforms and the downstream effects of activating or blocking EGFR function in Ishikawa H cells, derived from a moderately differentiated type I endometrioid adenocarcinoma, or in Hec50co cells, derived from a poorly differentiated type II adenocarcinoma with papillary serous sub-differentiation. RESULTS: We investigated whether EGFR mutations are present in the tyrosine kinase domain (exons 18-22) of EGFR and also whether EGFR isoforms are expressed in the Ishikawa H or Hec50co cell lines. Sequence of the EGFR tyrosine kinase domain proved to be wild type in both cell lines. While both cell lines expressed full-length EGFR (isoform A), EGFR and sEGFR (isoform D) were expressed at significantly lower levels in Hec50co cells compared to Ishikawa H cells. Analysis of gene expression following EGF vs. gefitinib treatment (a small molecule EGFR tyrosine kinase inhibitor) was performed. Early growth response 1, sphingosine kinase 2, dual specificity phosphatase 6, and glucocorticoid receptor DNA binding factor 1 are members of a cluster of genes downstream of EGFR that are differentially regulated by treatment with EGF compared to gefitinib in Ishikawa H cells, but not in Hec50co cells. CONCLUSIONS: Type I Ishikawa H and type II Hec50co endometrial carcinoma cells both express EGFR and sEGFR, but differ markedly in their responsiveness to the EGFR inhibitor gefitinib. This difference is paralleled by differences in the expression of sEGFR and EGFR, as well as in their transcriptional response following treatment with either EGF or gefitinib. The small cluster of differently regulated genes reported here in these type I vs. type II endometrial cancer-derived cell lines may identify candidate biomarkers useful for predicting sensitivity to EGFR blockade.

Activation of platelet-activating factor receptor and pleiotropic effects on tyrosine phospho-EGFR/Src/FAK/paxillin in ovarian cancer.

Among the proinflammatory mediators, platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a major primary and secondary messenger involved in intracellular and extracellular communication. Evidence suggests that PAF plays a significant role in oncogenic transformation, tumor growth, angiogenesis, and metastasis. However, PAF, with its receptor (PAFR) and their downstream signaling targets, has not been thoroughly studied in cancer. Here, we characterized the PAFR expression pattern in 4 normal human ovarian surface epithelial (HOSE) cell lines, 13 ovarian cancer cell lines, paraffin blocks (n = 84), and tissue microarrays (n = 230) from patients with ovarian cancer. Overexpression of PAFR was found in most nonmucinous types of ovarian cancer but not in HOSE and mucinous cancer cells. Correspondingly, PAF significantly induced cell proliferation and invasion only in PAFR-positive cells (i.e., OVCA429 and OVCA432), but not in PAFR-negative ovarian cells (HOSE and mucinous RMUG-L). The dependency of cell proliferation and invasion on PAFR was further confirmed using PAFR-specific small interfering RNA gene silencing probes, antibodies against PAFR and PAFR antagonist, ginkgolide B. Using quantitative multiplex phospho-antibody array technology, we found that tyrosine phosphorylation of EGFR/Src/FAK/paxillin was coordinately activated by PAF treatment, which was correlated with the activation of phosphatidylinositol 3-kinase and cyclin D1 as markers for cell proliferation, as well as matrix metalloproteinase 2 and 9 for invasion. Specific tyrosine Src inhibitor (PP2) reversibly blocked PAF-activated cancer cell proliferation and invasion. We suggest that PAFR is an essential upstream target of Src and other signal pathways to control the PAF-mediated cancer progression.

Models representing type I and type II human endometrial cancers: Ishikawa H and Hec50co cells.

OBJECTIVE: Endometrial cancer models are critical to the advancement of investigation, and Ishikawa H and Hec50co cells have been used as research tools. The purpose of these studies is to verify the degree to which these commonly used cell models share the molecular characteristics of the two major in vivo endometrial cancer subtypes, I and II. METHODS: The studies reported include an analysis of pathologic features, tumor suppressor mutations, detailed karyotyping, and cell cycle regulation. RESULTS: Ishikawa H cells are hormone responsive and have lost PTEN expression. In addition they have lost RB1 expression due to a deletion in exon 9. Hec50co cells have lost p53 expression due to a deletion at the junction of exon 6 and intron 6-7. Compared to Ishikawa H cells, Hec50co cells harbor many more chromosomal rearrangements (29 versus seven), and the doubling time is more rapid. The percent of cells in each phase of the cell cycle is reported and linked to cell cycle regulators. CONCLUSION: We present extensive data indicating that Ishikawa H cells are excellent models for type I endometrial cancers, and Hec50co cells faithfully replicate the molecular characteristics of type II endometrial cancers. These studies allow testing of new therapeutic regimens using appropriate cell models.

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer.

OBJECTIVE: These studies demonstrate how loss of function mutations or downregulation of key tumor suppressors missing from type I and type II endometrial cancer cells contributes to carcinogenesis and to resistance to the EGFR inhibitor gefitinib (ZD1839). METHODS: Cell models devoid of tumor suppressors PTEN and RB1 or PTEN were studied. PTEN, RB1 and p53 expression was reinstated, and the effects on cell cycle, apoptosis, and cell cycle regulators were evaluated. RESULTS: In Ishikawa H cells that model type I endometrial cancer in the loss of PTEN and RB1, re-expressing PTEN and RB1 increased the apoptotic and G1 phases and decreased the S and G2-M phases, which further sensitize the cells to gefitinib. Expressing p53 in Hec50co that model type II tumors by loss of this tumor suppressor arrested cells at the G1-S checkpoint, and apoptosis was also induced. Yet this did not improve sensitivity to gefitinib. Modulation of the cell cycle regulators responsible for these changes is explored, and a potential new therapeutic target, MDM2, is identified. CONCLUSION: The downregulation of p53 expression in type II Hec50co cells is linked to gefitinib resistance. In addition, the overexpression of MDM2, the principal factor that inhibits p53 function also occurs in these resistant cells. MDM2 phosphorylation is only partially blocked by gefitinib, and high MDM2 expression may relate to drug resistance.

Regulation of signaling phosphoproteins by epidermal growth factor and Iressa (ZD1839) in human endometrial cancer cells that model type I and II tumors.

To understand how type I and II endometrial tumors uniquely respond to tyrosine kinase inhibitor treatments, we evaluated the signaling pathways of epidermal growth factor (EGF) receptor (EGFR) under the effects of EGF and Iressa (ZD1839, gefitinib) using Ishikawa H and Hec50co cells that model type I and II endometrial carcinomas, respectively. The cells were assayed for the expression of EGFR and both cell lines express an average of 100,000 EGFR per cell; however, Ishikawa H cells express higher levels of HER-2/neu compared with Hec50co cells (1.38 x 10(5) compared with 2.04 x 10(4), respectively). Using the Kinetworks multi-immunoblotting approach, which profiles 31 signaling phosphoproteins, the most striking result was that Hec50co cells show a higher number of basal phosphorylated sites compared with Ishikawa H cells. Furthermore, we identified targets of Iressa treatment in both cell lines. Iressa, at a dose of 1 micromol/L, blocked the autophosphorylation of EGFR in Ishikawa H and Hec50co cells with some distinctive effects on downstream effectors. Nevertheless, in both cell lines, EGF stimulated and Iressa blocked the major EGFR target mitogen-activated protein kinases extracellular signal-regulated kinase 1 and 2 equally. The high basal phosphorylation of numerous signaling molecules in Hec50co cells that were not inhibited by Iressa indicates that other growth factor pathways are active in addition to EGFR. We conclude that endometrial cancer cells that model type I and II carcinomas have the capacity to respond to EGFR inhibition as a therapeutic strategy; however, the response of the more aggressive type II tumors may be limited by the constitutive activation of other signaling pathways.

A therapeutic model for advanced endometrial cancer: systemic progestin in combination with local adenoviral-mediated progesterone receptor expression.

Cancer of the uterine endometrium is a frequent gynecologic malignant disease for which few therapeutic options are available for advanced disease. Progesterone is the normal female hormone that limits growth and proliferation of endometrial cancers; however, progesterone receptors are frequently down-regulated, leading to treatment failures. The current studies explored the effectiveness of adenoviral-mediated progesterone receptor gene transduction in combination with progestin therapy in mouse xenograft models. Pretreatment of cells with progesterone receptor-encoding adenovirus and progestin inhibited the development of s.c. tumors in athymic mice. In the i.p. xenograft model, replacement of both isoforms of progesterone receptor, PRA and PRB, in combination with progestin treatment resulted in a significant 2.6-fold increase in overall survival time compared with control animals. These studies indicate that when progesterone receptor levels are maintained, progestin therapy is effective in limiting tumor growth. Future therapeutic regimens targeted at enhancing progesterone receptor expression have the potential to improve outcomes in women with endometrial cancer.