Investigation the role of CD24 in metastatic colorectal cancer

CD24 is a small (81 amino acids) GPI anchored protein which is involved in promoting cell motility and stemness and may be a part of the metastatic process. It is a heavily glycosylated molecule and contains numerous O-glycosylation sites together with two N-glycosylation sites. N-glycosylation is thought to be important in protein function, and therefore, the aim of this study is to (a) investigate the importance of N-glycosylation in the function of CD24, (b) identify other potentially functional sites in CD24 by deletion mapping, (c) define downstream targets of CD24, and (d) identify the extrinsic signals of which activate CD24. (a) Through site-directed mutagenesis, we changed the glycosylated residues N32 (ACC to CAA) and Q52 (AAT to CAG) in CD24. Mutating each of these sites individually, when compared to pCCD24WT (wild-type CD24), caused a partial reduction in ability to induce cell motility and cell invasion (cell motility p=0.0001 cell invasion p=0.0001) and, unexpectedly, resulted in significantly enhanced cell proliferation (p=0.0001). Mutation of both sites resulted in a near loss of motility induction and retained cell proliferation. (b) We mapped the functional sites of CD24 by deleting seven amino acid segments of the whole of the mature peptide. Apart from the N-glycosylation sites, no other functional domains were identified which altered cell motility or proliferation. (c) Previously, in our lab it has been shown that Cten is downstream motility-inducing target of CD24. We hypothesised that CD24 may signal through the Notch pathway since Notch1 has an important role in maintaining CSCs. Results showed that forced expression of CD24 upregulates Notch1 and Cten whilst knockdown of CD24 causes loss of Notch1 and Cten expression. However, forced expression of CD24 with simultaneous knockdown of Notch1 resulted in failure to induce Cten. (d) CD24 is reported to act as a ligand of P-selectin. We found that stimulating CD24 expressing cell lines induced with P-selectin induced cell motility (p=0.0011) and caused an increased in the protein expression of downstream targets of CD24. Stimulating cell lines expressing CD24 with mutant glycosylation sites resulted in a failure to induce motility or CD24 targets. We conclude, the removal of the N-glycosylation sites in CD24 resulted in a loss of cell migration and invasion, thereby suggesting the importance of these sites in mediating the migration and invasion functions of CD24. Unexpectedly, these mutations also appeared to stimulate cell proliferation, suggesting that wild type CD24 can functionally inhibit cell proliferation. Deletion mapping did not reveal any other functional sites on the mature CD24 suggesting that O-glycosylation is relatively affecting the glycosylation in the biology of CD24. Notch1 was to be an important downstream target of CD24 and a regulator of Cten. The binding of P-selectin with CD24 resulted in increased motility of CD24 which is also dependent on N-glycosylation

Towards the innovation of an integrated 'one-stop-shop' online services utility management: exploring customer' technology acceptance

The revolutions in internet online service delivery have transformed the way that people interact with technology, resulting in an exponential growth in the number of online users. The various consumer characteristics and ways of providing services online have had a dramatic change on user acceptance and perceived value of technological innovation. Therefore, user perception is a vital issue in investigating user intentions in adopting online services. The scope of this paper is to examine the perceptions of adopters and non-adopters of online utility management, in terms of their experience towards existing service delivery approaches and their expectations of future innovations as regards perceived characteristics. The user perceptions contribute to defining an initial roadmap for exploring the evolution of ‘utilities service management’ on the Internet and their approaches to online service delivery. It highlights the general need for a value-added and integrated utilities service management solution as well as the specific demand of internet users for the integrated online delivery of utilities services to serve their particular interests. This paper discusses several traditional approaches in related fields of electronic service delivery and shows how the current situation demands a shift towards an integrated utilities service management solution that considers the interests of all stakeholders

Use of novel oral anticoagulants for Treatment of cerebral venous sinus Thrombosis: a case series and follow up

Thrombosis of cerebral venous sinuses and/or cortical veins (CVST) is an infrequent type of stroke for which anticoagulation is considered standard of treatment. However, 40% of CVST patients have evidence of parenchymal changes like edema or haemorrhage on neuroimaging which complicates use of anticoagulation in such cases. Therefore, Novel Oral Anticoagulants (NOACs) are recently being used for treatment of CVST as they are associated with half the risk of intracerebral haemorrhage as caused by vitamin K antagonist. Case reports and case series have reported use of NOACs in CVST with good outcomes both clinically and radiologically. We report use of NOACs in five cases of CVST without any worsening or recurrence of symptoms or complication on follow up

Knowledge, attitudes and practice among high school teachers toward students with mental disorders in Riyadh, Saudi Arabia

Background: Mental disorders are highly prevalent among adolescents, and they correlate negatively with students’ achievement, performance, and leadless school engagement and participation. School Teachers can contribute significantly to the early detection and intervention strategies for mental disorders among adolescents. This study estimates high school teachers’ knowledge, attitude, and practice toward mental disorders and determines the association between selected demographic factors.Methods: The ethical committee of King Saud University, Riyadh, Saudi Arabia, approved this cross-sectional study. Multistage random sampling was done, which included 62 male and 48 female high schools in Riyadh between August and December 2021. An Anonymous self-administered questionnaire consisting of 39-item was used for data collection.Results: A total 487 responses were received from the high school teachers, on a scale of 10 maximum score, only (60.4%) showed adequate knowledge regarding mental disorders. Even though, Majority of teachers (76.2%) show a favorable attitude toward mental disorders on a scale of 24 maximum scores. Furthermore, approximately one-third of study participants (34.4%) on a scale of 4 points maximum show good practice toward mental disorders.     Conclusions: This study revealed teachers’ lack of knowledge about mental disorders with poor practice. Even though school teachers have shown favourable attitudes in most aspects toward mental disorders, implantation of the mental health literacy program is recommended to enhance the essential role of school staff in providing the needed support for promoting student mental health

Multiple sclerosis following bariatric surgery: A report of five cases

Multiple sclerosis (MS) is a debilitating chronic inflammatory demyelinating disease that affects the central nervous system. The underlying cause of multiple sclerosis is unknown, yet there are various predisposing factors. Currently, bariatric surgery is an increasingly common solution for obesity. It has been reported that bariatric procedures result in miscellaneous neurological complications. To the best of our knowledge, this is the first case series to report the occurrence of MS following bariatric surgery. Here we report the cases of five patients who were recruited for inclusion following neurological examination, complete cerebrospinal fluid (CSF) study, enhanced cranial as well as spinal cord magnetic resonance (MR) images. Diagnosis of multiple sclerosis was made based on McDonalds criteria (2010). All cases were diagnosed with relapsing-remitting form of multiple sclerosis (RRMS) after various types of bariatric surgeries

Relationship Between Glycated Haemoglobin and Carotid Atherosclerotic Disease Among Patients with Acute Ischaemic Stroke

Objectives: This study aimed to determine the relationship between glycaemic control and carotid atherosclerotic disease among patients with acute ischaemic stroke (AIS). Methods: This retrospective cross-sectional study took place in the Neurology Department of King Fahad Hospital of University, Khobar, Saudi Arabia, from April to October 2017. Data were collected from the medical records of 244 patients with a diagnosis of AIS confirmed by computed tomography. Doppler ultrasounds of the carotid artery were performed to determine the presence of increased carotid intima media thickness (CIMT) and plaques. Results: Significantly higher mean glycated haemoglobin (HbA1c) levels were noted in cases with high CIMT values (P = 0.002), but not in cases with carotid plaques (P = 0.360). In addition, there was a significant association between diabetes mellitus (DM) and high CIMT (P = 0.045), but not with carotid plaques (P = 0.075). Finally, while dyslipidaemia and age were independently correlated with high CIMT values (P = 0.034 and 0.050 each). Conclusion: High HbA1c levels were associated with high CIMT values, but not with carotid plaques. Therefore, HbA1c levels may be useful as an indirect marker of the initial stages of carotid artery atherosclerosis. Keywords: Glycated Hemoglobin A1c; Diabetes Mellitus; Carotid Intima-Media Thickness; Atherosclerotic Plaque; Stroke

Investigation the role of CD24 in metastatic colorectal cancer

CD24 is a small (81 amino acids) GPI anchored protein which is involved in promoting cell motility and stemness and may be a part of the metastatic process. It is a heavily glycosylated molecule and contains numerous O-glycosylation sites together with two N-glycosylation sites. N-glycosylation is thought to be important in protein function, and therefore, the aim of this study is to (a) investigate the importance of N-glycosylation in the function of CD24, (b) identify other potentially functional sites in CD24 by deletion mapping, (c) define downstream targets of CD24, and (d) identify the extrinsic signals of which activate CD24. (a) Through site-directed mutagenesis, we changed the glycosylated residues N32 (ACC to CAA) and Q52 (AAT to CAG) in CD24. Mutating each of these sites individually, when compared to pCCD24WT (wild-type CD24), caused a partial reduction in ability to induce cell motility and cell invasion (cell motility p=0.0001 cell invasion p=0.0001) and, unexpectedly, resulted in significantly enhanced cell proliferation (p=0.0001). Mutation of both sites resulted in a near loss of motility induction and retained cell proliferation. (b) We mapped the functional sites of CD24 by deleting seven amino acid segments of the whole of the mature peptide. Apart from the N-glycosylation sites, no other functional domains were identified which altered cell motility or proliferation. (c) Previously, in our lab it has been shown that Cten is downstream motility-inducing target of CD24. We hypothesised that CD24 may signal through the Notch pathway since Notch1 has an important role in maintaining CSCs. Results showed that forced expression of CD24 upregulates Notch1 and Cten whilst knockdown of CD24 causes loss of Notch1 and Cten expression. However, forced expression of CD24 with simultaneous knockdown of Notch1 resulted in failure to induce Cten. (d) CD24 is reported to act as a ligand of P-selectin. We found that stimulating CD24 expressing cell lines induced with P-selectin induced cell motility (p=0.0011) and caused an increased in the protein expression of downstream targets of CD24. Stimulating cell lines expressing CD24 with mutant glycosylation sites resulted in a failure to induce motility or CD24 targets. We conclude, the removal of the N-glycosylation sites in CD24 resulted in a loss of cell migration and invasion, thereby suggesting the importance of these sites in mediating the migration and invasion functions of CD24. Unexpectedly, these mutations also appeared to stimulate cell proliferation, suggesting that wild type CD24 can functionally inhibit cell proliferation. Deletion mapping did not reveal any other functional sites on the mature CD24 suggesting that O-glycosylation is relatively affecting the glycosylation in the biology of CD24. Notch1 was to be an important downstream target of CD24 and a regulator of Cten. The binding of P-selectin with CD24 resulted in increased motility of CD24 which is also dependent on N-glycosylation

Knowledge and Attitude of Physicians toward Prescribing Antibiotics and the Risk of Resistance in Two Reference Hospitals

Introduction Antibiotics are essential and abundantly prescribed in hospitals because of their effectiveness and lifesaving benefits. However, the unnecessary use of antibiotics has been observed in earlier studies, and it has persisted through recent years as a major issue since it is one of the leading causes of antibiotic resistance. The increase in antibiotic resistance nowadays is one of the most critical concerns in global public health around the world. The objective of this study was to evaluate the knowledge and perceptions related to antibiotic prescription among physicians at our medical centers. Method A cross-sectional survey of non-infectious diseases specialized physicians. The study was conducted during 2015 at two tertiary care centers in Riyadh, Saudi Arabia. Result Of the 107 returned questionnaires, 93 were complete and valuable. Most respondents (82%) perceived antibiotic resistance to be a critical problem globally, and 78% also think that it is a very important national problem. These attitudes did not differ across specialty or level of training. Widespread antibiotic use and inappropriate empirical choices were believed by 81% of the participants to be important general causes of resistance. Only half of respondents thought that antibiotic restriction is a useful intervention to decrease the antibiotic resistance. The physicians believed educational interventions are the most useful and effective way to improve prescription patterns and decrease antibiotic resistance. Complications due to infection with resistant organisms were acknowledged by almost all of the participants, with some differences in their estimations of how often it will occur. Conclusion Antimicrobial resistance, globally and nationally, is considered as a serious threat, and physicians in this survey acknowledged that. Among the most significant factors is antimicrobial misuse, either by overprescribing or providing inappropriate drugs with some ambivalence, as well as the importance of hand hygiene and antibiotic restrictions. By adhering to local guidelines, continuous education, and other practical interventions, the burden of resistance can be alleviated, as highlighted in this survey

The Effect of Socio-economic status on the Oral Hygiene of Elementary School Children in the City of Dammam, Saudi Arabia

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