Evidence for B cell exhaustion in chronic graft-versus-host disease

Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21− B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21− B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27−CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21− B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21− B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21− B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21−CD27−CD10− B cell frequencies as a biomarker of disease severity

Smoking Tobacco Prevalence Among College Students in the Kingdom of Saudi Arabia: Systematic Review and Meta-Analysis

INTRODUCTION: During the last two decades, several studies have been published regarding the prevalence of tobacco smoking among college students in the Kingdom of Saudi Arabia (KSA). This systematic review and meta-analysis is intended to determine and examine the smoking prevalence in Saudi college students from 2010-2018. METHODS: PubMed, Science Direct, APA PsycNET, Web of Science, and CINAHL were used to search for published articles reporting the smoking prevalence among Saudi college students. After eliminating irrelevant articles, investigators independently assessed the quality of each article, based on Russell & Gregory guidelines. MetaXL software was used to calculate the pooled prevalence among included studies, using the IVhert model. Heterogeneity among the included studies was evaluated, using I2 statistic. Sensitivity analyses were conducted between male and female genders. RESULTS: Of the 295 published articles, 29 articles used a cross-sectional design to determine smoking prevalence among Saudi college students. Most of the studies were conducted in Riyadh at health-science-related colleges; the rest were performed in different cities and colleges. The meta-analysis showed that the pooled estimate of smoking prevalence among college students in the KSA was 17% (95% CI: 11-23%). Saudi male students had a prevalence rate of 26% (95% CI: 24-29%), whereas for Saudi female students the prevalence was 5% (95% CI: 3-7%). CONCLUSIONS: Smoking among Saudi college students was higher than in the majority of regional countries (e.g. Iran). Saudi male students had a higher smoking prevalence than Saudi female college students. Additionally, studies that reported a high prevalence targeted students in specific disciplines. Public health authorities in the KSA should develop a surveillance system that monitors the prevalence of tobacco smoking on campuses. A surveillance system of monitoring tobacco use among Saudi college students could be beneficial in determining the degree of the tobacco problem and in improving current tobacco control programs

Role of human interleukin-17 producing T cells (Th17) and regulatory (Foxp3+) T cells in graft versus host disease (GvHD)

Allogeneic stem cell transplantation (AHSCT) remains the only curative option for a number of patients with haematological malignancies. The interplay between a number of T cell subsets including Th1, Th2, Th17 and regulatory-T cells (Treg) has been linked to the establishment of graft-versus-leukaemia (GvL) as well as its deleterious counterpart graft-versus-host-disease (GvHD). A recent study defined a subset of memory antigen-specific CD8+T cells, with the ability to efflux cytotoxic drugs through the (ABC)-superfamily multidrug efflux complex. I hypothesized that a subset of CD4+T cells, capable of drug efflux through the MDR pump also exists. I confirmed the existence of CD4+T cells with "stem-like" properties, capable of rapidly effluxing Rhodamine123 as well as cytotoxic drugs such as daunorubicin. I confirmed that the effluxing properties of these cells are through ABCB1 and ABCC1 transporters. Similar to their CD8 counterpart, the rhodamine-effluxing subset of CD4+T cells had a memory phenotype and was enriched within the CD161+T cell compartment. Lastly, using CMV and Flu as model antigens, I showed that viral-specific memory CD4+T cells are enriched within the rhodamine-effluxing CD4+CD161+T cell population. Once I characterized these cells, I hypothesized that, through effluxing corticosteroids and other immunosuppressant drugs,CD161+CD4+ T cells may also play a role in acute GvHD. CD161+CD4+ T cells are precursors of Th17 cells. I demonstrated that, whereas Tregs are prone to apoptosis when exposed to corticosteroids, CD4+CD161+Th17 cells rapidly efflux and survive exposure to corticosteroids and other immunosuppressive drugs in vitro. Inhibition of the ABCB1 and ABCC1 with inhibitors such as vinblastine induced apoptosis of this CD4+CD161+Th17 steroid-refractory T cell subset. I observed that patients with steroid-refractory GvHD had significantly higher frequencies of CD161+CD4+ T cells compared to patients with no or steroid-responsive GvHD. I also enumerated CD161+CD4+ T cells and Foxp3+T cells in the stem cell graft and donor lymphocytes and found an association between higher CD4+CD161+ and lower Foxp3+T cells frequencies and the risk of GvHD post-transplant. These data advance our understanding of potential mechanisms of steroid-refractory GvHD and have important implications for the development of novel therapeutic approaches for the treatment of this challenging group of patients

Body composition, blood pressure and dietary habits among young qatari male adults

Introduction: Due to a rapidly changing lifestyle in Qatar, determinants of non-communicable diseases and linked levels of risk factors have risen. These facts pose a national challenge (1). Information about Qatari adults` (19-30yr.) dietary habits is essential because of the increase in the incidence and prevalence of obesity in Qataris. In 2006, the percentage of Qatari boys who are overweight and obese is 28.6%, and 7.9%, respectively (3). Aim of this study was to determine body composition, blood pressure and dietary habits of the next cohort, those 18-29 yrs old. Methods: 80 Qatari male students, 18-29 yrs of age, from Qatar University (QU) participated. Blood pressure (BP) was measured by Omron HEM-780, body composition (body weight and percent of body fat (BF), were measured by OMRON BF-400. Dietary habits were evaluated using the NHANES Food Frequency Questionnaire. For data analysis, Chi-square test and univariate analyses of variance were conducted using SPSS version 20. Results: The mean systolic and diastolic BP was 128.6±1.42 mmHg, 73.32±1.1 mmHg, respectively. The mean arterial pressure (MAP) was 91.74±1.06 mmHg. The mean BF is 23.79±1.19%. 30.77% of the subjects were classified as overweight, 38.46% as obese. The crosstab statistical analyses yielded a difference between fast food (FF) vs. seafood (SF) consumptions (p=.007). No statistical difference between vegetables consumption vs. pasta intake occur. However, the subjects` soda consumption was greater than fruit juices (p=.05). The BF is expressed by an interaction between salad and SF consumption, p=.047, ηp2=.409, but these main effects are not qualified by a separate interaction on BF (p=.234, ηp2=.181 vs. p=.34, ηp2=.149, respectively). No interaction was found between FF, SF or sweets and blood pressure values. Conclusion: Obesity is uniformly considered to be the most important factor in developing non-communicable diseases in Qatar (2). Our study supports the results. In our sample, the prevalence of overweight and obesity was higher compared to previously published studies. No correlation between dietary habits and MAP occurred though, due to the wide range of nutrients consumed. High caloric diets are prevalent among QU students

Causes of delay in Saudi public construction projects

When executing construction projects, delays are among the challenges that must be faced. In Saudi Arabia, numerous public construction projects have been undertaken as part of the government’s national development plans over the last three decades. One of the critical problems concerning these projects is the frequent and lengthy delay that occurs. This paper investigates the causes of delays in Saudi public construction projects. The causes of delay were categorized based on the different stages of a construction project, namely (1) factors before the award of tenders, (2) factors during the award of tenders, (3) factors after the award of tenders, and (4) general factors. This study identified 50 delay factors by conducting a focus group. A questionnaire was administered and distributed to 211 participants from construction industry. The top 20 causes of delay were identified. A final simplified formula was developed to calculate the effect of each cause of delay on site. A case study was carried out to show the time delay percentage compared with its master schedule using the developed simplified formula. The findings of the study are intended to provide those involved in public construction projects with appropriate solutions for countering any delays. Keywords: Delay factors, Public projects, Construction delay, Saudi Arabi

Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia

The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-alpha and IFN-gamma production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-alpha production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-alpha and IFN-gamma production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival

The future self in future making projects

LAUREA MAGISTRALEIn un'era di incertezza senza precedenti, i modelli predittivi tradizionali spesso non raggiungono gli obiettivi desiderabili a lungo termine. Pertanto, stiamo assistendo a uno slancio di approcci orientati al futuro che, piuttosto che prevedere il futuro, mirano a progettarlo. Questa tesi indaga come la percezione del futuro individuale, la capacità di comprendere, anticipare e preparare per il futuro, influenzi e migliori progetti di creazione del futuro. La ricerca indica che gli individui che percepiscono una forte continuità tra il loro sé presente e quello futuro mostrano migliori capacità decisionali, maggiore adattabilità e maggiore resilienza. Questa maggiore autocontinuità futura favorisce una comprensione più profonda di come le azioni attuali influenzano i risultati a lungo termine, promuovendo così un comportamento proattivo e una gestione efficace del cambiamento. Lo studio impiega metodologie miste che combinano questionari, interviste e future auto-lettere, con gli studenti in un corso che si concentra sulla comprensione e la gestione del cambiamento nei progetti futuri. Questo studio rivela che le percezioni degli studenti del loro sé futuro influenzano in modo significativo i loro comportamenti attuali e processi decisionali con il contesto di progetti futuri. I risultati indicano che una solida autocontinuità futura consente agli individui di allineare meglio le azioni attuali con le intenzioni future a lungo termine, favorendo il cambiamento proattivo. Inoltre, queste intuizioni sottolineano le implicazioni più ampie per la resilienza della società; coltivando mentalità orientate al futuro, gli individui contribuiscono alla creazione di un futuro più desiderabile e adattabile.In an era of unprecedented uncertainty, traditional predictive models often fall short to pursue desirable long-term outcomes. Therefore, we are witnessing a spur of future-making approaches that, rather than predict futures, aim to design it. This thesis investigates how individual future-self perception, the ability to understand, anticipate, and prepare for the future, influences and enhances future-making projects. Research indicates that individuals who perceive a strong continuity between their present and future selves exhibit enhanced decision-making capabilities, increased adaptability, and greater resilience. This heightened future self-continuity fosters a deeper understanding of how current actions impact long-term outcomes, thereby promoting proactive behavior and effective change management. The study employs mixed methodologies combining questionnaires, interviews, and future self-letters, with students in a course that focuses on understanding and managing change in future making projects. This study reveals that students' perceptions of their future selves significantly influence their current behaviors and decision-making processes with the context of future making projects. The findings indicate that a robust future self-continuity enables individuals to better align present actions with long-term future intentions, fostering proactive change. Moreover, these insights underscore the broader implications for societal resilience; by cultivating future-oriented mindsets, individuals contribute to the creation of a more desirable and adaptive future