Carbon nanotube-coated recombinant human surfactant protein D reduces cell viability in an ovarian cancer cell line, SKOV3, and modulates mTOR pathway and pro-inflammatory cytokine response

Copyright © 2022 The Authors. Nanoparticles such as carbon nanotubes (CNTs) have various clinical and diagnostic applications as utilised for imaging and drug delivery. Therapeutic proteins/peptides can be loaded on CNT coronas to specifically hit immune cells in overdrive or uncontrolled malignant cells. Previously, it was reported that a recombinant version of human surfactant protein D (rfhSP-D) containing trimeric C-type lectin domains induced apoptosis in several tumour cells/cell lines, including SKOV3, which is an ovarian tumour cell line. Solid-phase rfhSP-D coated on a microtiter plate is considerably more potent in inducing apoptosis in breast tumour cells. We have immobilised highly purified, endotoxin-free rfhSP-D on CNTs and assessed its antiproliferative effect on SKOV3 cells. Biotinylated rfhSP-D-CNTs were phagocytosed by SKOV3 cells, followed by apoptosis in a time-dependent manner. Gene expression analysis revealed compromised mTOR complex as a mechanism of apoptosis. When rfhSP-D-CNTs were added to a culture system of SKOV3 cells, it produced a highly proinflammatory immune response that is likely anti-tumorigenic. Thus, rfhSP-D-CNT seems a worthwhile nanocarrier for testing in vivo using an animal model of orthotopic ovarian cancer.This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, Riyadh, KSA, through the Research Funding Program (Grant No# FRP-1440-27)

Full-length human Surfactant Protein A inhibits Influenza A Virus infection of A549 lung epithelial cells: a recombinant form containing neck and lectin domains promotes infectivity

Hydrophilic lung surfactant proteins have emerged as key immunomodulators aimed at recognition and clearance of pulmonary pathogens. Surfactant protein A (SP-A) is a surfactant-associated innate immune pattern recognition molecule, which is known to interact with a variety of pathogens, and display anti-microbial effects. SP-A, being carbohydrate pattern recognition molecule, has been suggested to have a wide range of innate immune functions against pathogens. In addition, SP-A can work against respiratory pathogens, including influenza A virus (IAV). Some pandemic pH1N1 strains resist neutralization by SP-A due to differences in the N-glycosylation of viral hemagglutinin (HA). Here, we provide evidence, for the first time, that a recombinant form of human SP-A (rfhSP-A) composed of α-helical neck and carbohydrate recognition domains can actually promote the IAV replication, as observed by an upregulation of M1 expression in lung epithelial cell line, A549, when challenged with pH1N1 and H3N2 IAV subtypes. rfhSP-A (10 μg/ml) bound neuraminidase (NA) (˜60 kDa), matrix protein 1 (M1) (˜25 kDa) and M2 (˜17 kDa) in a calcium dependent manner, as revealed by far western blotting, and direct binding ELISA. However, human full length native SP-A downregulated mRNA expression levels of M1 in A549 cells challenged with IAV subtypes. Furthermore, qPCR analysis showed that transcriptional levels of TNF-α, IL-12, IL-6, IFN-α and RANTES were enhanced following rfhSP-A treatment by both IAV subtypes at 6 h post-IAV infection of A549 lung epithelial cells. In the case of full length SP-A treatment, mRNA expression levels of TNF-α, and IL-6 were downregulated during the mid-to-late stage of IAV infection of A549 cells. Multiplex cytokine/chemokine array revealed enhanced levels of both IL-6 and TNF-α due to rfhSP-A treatment in the case of both IAV subtypes tested, while no significant effect was seen in the case of IL-12. Enhancement of IAV infection of pH1N1 and H3N2 subtypes by truncated rfhSP-A, concomitant with infection inhibition by full-length SP-A, appears to suggest that a complete SP-A molecule is required for protection against IAV. This is in contrast to a recombinant form of trimeric lectin domains of human SP-D (rfhSP-D) that acts as an entry inhibitor of IAV.KACST (14-MED258-20

The Alvarado score for predicting acute appendicitis: a systematic review

Background: The Alvarado score can be used to stratify patients with symptoms of suspected appendicitis; the validity of the score in certain patient groups and at different cut points is still unclear. The aim of this study was to assess the discrimination (diagnostic accuracy) and calibration performance of the Alvarado score. Methods: A systematic search of validation studies in Medline, Embase, DARE and The Cochrane library was performed up to April 2011. We assessed the diagnostic accuracy of the score at the two cut-off points: score of 5 (1 to 4 vs. 5 to 10) and score of 7 (1 to 6 vs. 7 to 10). Calibration was analysed across low (1 to 4), intermediate (5 to 6) and high (7 to 10) risk strata. The analysis focused on three sub-groups: men, women and children. Results: Forty-two studies were included in the review. In terms of diagnostic accuracy, the cut-point of 5 was good at 'ruling out' admission for appendicitis (sensitivity 99% overall, 96% men, 99% woman, 99% children). At the cut-point of 7, recommended for 'ruling in' appendicitis and progression to surgery, the score performed poorly in each subgroup (specificity overall 81%, men 57%, woman 73%, children 76%). The Alvarado score is well calibrated in men across all risk strata (low RR 1.06, 95% CI 0.87 to 1.28; intermediate 1.09, 0.86 to 1.37 and high 1.02, 0.97 to 1.08). The score over-predicts the probability of appendicitis in children in the intermediate and high risk groups and in women across all risk strata. Conclusions: The Alvarado score is a useful diagnostic 'rule out' score at a cut point of 5 for all patient groups. The score is well calibrated in men, inconsistent in children and over-predicts the probability of appendicitis in women across all strata of risk

Does weight loss improve semen quality and reproductive hormones? results from a cohort of severely obese men

<p>Abstract</p> <p>Background</p> <p>A high body mass index (BMI) has been associated with reduced semen quality and male subfecundity, but no studies following obese men losing weight have yet been published. We examined semen quality and reproductive hormones among morbidly obese men and studied if weight loss improved the reproductive indicators.</p> <p>Methods</p> <p>In this pilot cohort study, 43 men with BMI > 33 kg/m²were followed through a 14 week residential weight loss program. The participants provided semen samples and had blood samples drawn, filled in questionnaires, and had clinical examinations before and after the intervention. Conventional semen characteristics as well as sperm DNA integrity, analysed by the sperm chromatin structure assay (SCSA) were obtained. Serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and inhibin B (Inh-B) were measured.</p> <p>Results</p> <p>Participants were from 20 to 59 years of age (median = 32) with BMI ranging from 33 to 61 kg/m². At baseline, after adjustment for potential confounders, BMI was inversely associated with sperm concentration (p = 0.02), total sperm count (p = 0.02), sperm morphology (p = 0.04), and motile sperm (p = 0.005) as well as testosterone (p = 0.04) and Inh-B (p = 0.04) and positively associated to estradiol (p < 0.005). The median (range) percentage weight loss after the intervention was 15% (3.5 - 25.4). Weight loss was associated with an increase in total sperm count (p = 0.02), semen volume (p = 0.04), testosterone (p = 0.02), SHBG (p = 0.03) and AMH (p = 0.02). The group with the largest weight loss had a statistically significant increase in total sperm count [193 millions (95% CI: 45; 341)] and normal sperm morphology [4% (95% CI: 1; 7)].</p> <p>Conclusion</p> <p>This study found obesity to be associated with poor semen quality and altered reproductive hormonal profile. Weight loss may potentially lead to improvement in semen quality. Whether the improvement is a result of the reduction in body weight per se or improved lifestyles remains unknown.</p

The effect of explicit instruction of textual discourse markers on saudi EFL learners’ reading comprehension

\ua9 2015 Canadian Center of Science and Education, All right reserved. Discourse markers (DMs) instruction is currently receiving an increasing amount of attention in the literature on second language learning. As noted by Al-Yaari, Al Hammadi, Alyami, and Almaflehi (2013), and Algouzi (2014), the use of DMs is insufficient to support the development of the language skills, especially reading, of Saudi English as a Foreign Language (EFL) learners’. Recurrent reports (e.g., Al Abik, 2014; Al-Mansour &amp; Al-Shorman, 2011) have shown that Saudi EFL learners perform poorly on reading comprehension tasks. Since these studies were generally descriptive, the current study attempted to fill the gap by providing empirical data, particular to low-proficiency learners in the Saudi EFL context, based on an eight-session intervention programme to familiarise learners with DMs. This study hypothesised that explicit DM instruction could improve learners’ reading comprehension and that there would be a significant positive relationship between Saudi EFL learners’ knowledge of DMs and their reading performance. To test these hypotheses, two classes with a total of 70 Saudi male third-grade secondary students were assigned as control and experimental groups. The experimental group was introduced to the intervention programme, whereas the control group was only taught the prescribed reading lessons. Two forms of tests in both DMs and reading comprehension were administered to the two groups before and after the intervention. A correlation analysis was also run to determine the relationship between learners’ knowledge of DMs and their reading performance. Results confirmed, with a large effect size, that explicit instruction in DMs improved low-proficiency EFL learners’ reading comprehension. The finding also suggested that knowledge of DMs correlated highly with reading comprehension. In other words, learners who were good at recognising DMs performed better in reading comprehension tasks, whereas those who were poor at recognising DMs performed poorly. Practical suggestions for pedagogy and future research were also identified

Knowledge and attitudes of dentists toward shortened dental arch therapy in Saudi Arabia

Objective: The aim of this study was to assess and compare the knowledge and attitudes of dentists toward shortened dental arch (SDA) therapy in Saudi Arabia.Materials and Methods: In this cross‑sectional study, self‑designed‑structured questionnaires were distributed among specialists (SP), residents (RES), and general dental practitioners (GDP) in Saudi Arabia. The questionnaire enquired about dentists’ opinion regarding function, esthetic, and comfort in patients with SDA. It also enquired about the risks associated with SDA treatment (tooth wear, temporomandibular dysfunction (TMD), and tooth migration). Participants also graded SDA decision‑making factors for their significance. Frequency distribution and Chi‑square test were performed to compare the responses.Results: A total of 300 questionnaires were completed. 53.9% of SP applied SDA therapy in &lt;10% of patients. However, 54.8% of RES and 46.6% of GDP never used SDA therapy. SDA was considered by dentists to provide a satisfactory or acceptable function (76.4%), esthetics (76.1%), and comfort (76.8%). There was a significant difference in opinions of SP, GDP, and RES, in relation to the effect of SDA on esthetics (P = 0.039), tooth‑wear (P &lt; 0.001), TMD (P &lt; 0.001), and tooth migration (P = 0.002).Conclusion: The knowledge of SP and GDP with regards to SDA therapy was broadly in line with current standards. Less than 10% of patients had objections towards SDA therapy. SDA therapy was clinically applied in fewer than 10% of cases.Keywords: Attitude, dentist, knowledge, shortened dental arc

Prevalence of Burnout Syndrome and the Associated Factors Among Healthcare Professionals in Saudi Arabia: A National Cross-Sectional Study

Background: Burnout syndrome (BOS) is a syndrome characterised by high emotional exhaustion with depersonalisation and low professional accomplishment associated with the workplace. It is well known that working in the healthcare industry significantly increases stress and psychological fatigue rates. Objective: To explore the prevalence of BOS and its associated factors among healthcare professionals in Saudi Arabia. Methods: In this cross-sectional study, 385 healthcare professionals out of 809,533 were randomly surveyed. The questionnaire had three components: sociodemographic data, the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) tool to assess BOS, and questions about personal, work-related and health status information. Results: Most of the 450 participating professionals were males and were married (66.2% and 75.8%, respectively). Precisely, 42.4% of the participants had high emotional fatigue, 42.4% experienced high depersonalisation, and 33.8% showed low personal accomplishment. Females, younger age groups, nurses, those with fewer years of experience, those with on-call duties, those with increased daily working hours, those with sleep difficulties, those who are exercising, and those experiencing high discrimination and harassment were associated with the development of burnout syndrome. Conclusion: It is essential to establish multidimensional and diversified therapies to decrease the incidence of BOS syndrome and its effect on healthcare