Immune checkpoints in circulating and tumor-Infiltrating CD4 + T Cell Subsets in Colorectal cancer patients

Blockade of inhibitory immune checkpoints (ICs) is a promising therapeutic approach; however, it has shown limited success in some cancers including colorectal cancer (CRC). The tumor microenvironment (TME) is largely responsible for response to therapy, and its constituents may provide robust biomarkers for successful immunotherapeutic approaches. In this study, we performed phenotypical characterization and critical analyses of key inhibitory ICs and T regulatory cell (Treg)-related markers on CD4+ T cell subsets in CRC patients, and compared with normal colon tissues and peripheral blood from the same patients. We also investigated correlations between the levels of different CD4+ T cell subsets and the clinicopathologic features including disease stage and tumor budding. We found a significant increase in the levels of CD4+FoxP3+Helios+ T cells, which represent potentially highly immunosuppressive Tregs, in the CRC TME. Additionally, tumor-infiltrating CD4+ T cells upregulated programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), T cell immunoglobulin and mucin domain-3 (TIM-3) and lymphocyte-activation gene 3 (LAG-3). We also characterized the expression of PD-1, CTLA-4, TIM-3, and LAG-3 on different CD4+FoxP3−/+Helios−/+ T cell subsets. Interestingly, we found that CTLA-4, TIM-3, and LAG-3 were mainly co-expressed on FoxP3+Helios+ Tregs in the TME. Additionally, FoxP3high Tregs expressed higher levels of Helios, CTLA-4 and TIM-3 than FoxP3low T cells. These results highlight the significance of Tregs in the CRC TME and suggest that Tregs may hamper response to IC blockade in CRC patients, but effects of different IC inhibition regimes on Treg levels or activity warrants further investigations. We also found that CD4+CTLA-4+ T cells in circulation are increased in patients with advanced disease stage. This study simultaneously provides important insights into the differential levels of CD4+ T cell subpopulations and IC expression in CRC TME, compared to periphery and associations with clinicopathologic features, which could be used as potential biomarkers for CRC progression and response to therapy

How to counter organisational inertia to enable knowledge management practices adoption in public sector organisations

Purpose: Knowledge management (KM) is associated with higher performance and innovative culture; KM can help public sector to be fiscally lean and meet diverse stakeholders’ needs. However, hierarchical structures, bureaucratic culture and rigid processes inhibit KM adoption and generate inertia. This study explores the nature and causes of this inertia within the context of UAE public sector. Methodology/approach: Using an in-depth case study of a UAE public sector organisation, this study explores how organisational inertia can be countered to enable knowledge management adoption. Semi-structured interviews are conducted with 17 top- and middle-level managers from operational, management and strategic levels. Interview data is triangulated with content analysis from multiple sources, including the UAE government and case organisation documents. Findings: The results show transformation leadership, external factors, and organisational culture mediate the negative effect of inertia on KM practices adoption. We find that information technology plays a key role in enabling knowledge creation, access, adoption and sharing. Furthermore, we uncover a virtuous cycle between organisational culture and KM practices adoption in public sector. In addition, we develop a new model (relationship between KM practices, organisational inertia, organisational culture, transformational leadership traits and 4 external factors), and four propositions for empirical testing by future researchers. We also present a cross-case comparison of our results with six private/quasi-private sector cases who have implemented KM practices. Originality/value: Inertia in public section is a result of bureaucracy and authority bounded by the rules and regulations. Adopting a qualitative methodology and case study method, the research explores the phenomena of how inertia impacts KM adoption in public sector environments. Our findings reveal the underlying mechanisms of how internal and external organisational factors impact inertia. Internally, supportive organisational culture and transformational leadership traits positively effect KM adoption, which in turn has a positive effect on organisational culture to counter organisational inertia. Externally, a progressive national culture, strategy, and policy can support a knowledge-based organisation that embraces change. This study develops a new model (interactions between internal and external factors impacting KM practices in public sector), four propositions and a new two-stage process model for KM adoption in public sector. We present a case-comparison of how the constructs interact in a public sector as compared to six private/quasi-private sector cases from literatur

Child maltreatment and neglect in the United Arab Emirates and relationship with low self-esteem and symptoms of depression

Objectives: To our knowledge, this study is the first in the United Arab Emirates (UAE) to investigate the prevalence of child maltreatment in relation to depressive symptoms and self-esteem.Study design: Exposure to physical maltreatment, emotional abuse and neglect was evaluated in 518 adolescents (86% response rate) randomly selected from schools in Al Ain in the Emirate of Abu Dhabi. The Rosenberg self-esteem scale and the Beck Depression Inventory were used to measure self-esteem and depressive symptoms by using multivariate logistic regression analyses.Results: The mean age of study participants was 14.3 years. Emotional abuse was the most frequent form of maltreatment (33.9%), physical abuse (12.6%) and neglect (12.1%) followed. Male sex was a positive predictor of physical abuse (OR = 2.12; 95% CI 1.18-3.77), whilst higher maternal level of education was protective (OR = 0.40; 95% CI 0.19-0.86). Daily screen time (OR = 2.77; 95% CI 1.17-6.56) and tobacco smoking (OR = 1.86; 95% CI 1.09-3.18) positively predicted emotional abuse. Emotionally maltreated and neglected participants were less likely to report high level of self-esteem and more likely to report symptoms of depression.Conclusions: Child maltreatment in the UAE is of a similar magnitude to what reported in other countries around the world and significantly associated with low self-esteem and depressive symptoms

“Crying and Chaos” – Starting School Experiences of Teachers in the United Arab Emirates (UAE)

The transition to full time schooling can be considered as the most important academic move that children make. Cross-cultural research demonstrates that a positive start to school leads to a more successful school career, academically and socially. Therefore, understanding the viewpoints of teachers about the first days in school is essential in understanding what contributes to a successful transition. This study focused on teacher experiences and perspectives of children starting school in the private school system in the United Arab Emirates (UAE). Ten teachers were interviewed using semi structured interviews. Thematic analysis revealed two themes: ‘A New Order’ and ‘Talking not Crying’, along with associated sub-themes. The findings indicated that the focus of the first few days at school was on establishing routines and order, which would indicate successful transition. Crying rather than talking is seen as a barrier to the establishment of the new order and, therefore, is seen as a hindrance to a successful transition. Consideration of cultural factors in how teachers view transition is given with suggestions for best practice in the context, specifically in relation to transition preparation and how to target hard to reach groups. Areas of focus and directions for future research are highlighted

Cigarette smoking and smokeless tobacco use among male south Asian migrants in the United Arab Emirates: A cross-sectional study

Background: Few data were available on smoking and smokeless tobacco use in South Asian migrants in the United Arab Emirates (UAE). This study aimed to identify the prevalence and correlates of cigarette smoking and smokeless tobacco use in male South Asian migrants in the UAE.Methods: We used a cross-sectional study to recruit a random representative sample of male South Asian migrants, including Indian (n = 433), Pakistani (n = 383) and Bangladeshi (n = 559) nationalities. We used multivariable logistic regression analysis to identify significant correlates of cigarettes smoking and smokeless tobacco use.Results: 1375 South Asian migrant adult males participated in the study (response rate 76%) with a mean age of 34 years (SD ± 10). The overall prevalence of cigarette smoking was 28% (95%CI 25-30%) and smokeless tobacco use was 11% (95%CI 10-13%). The prevalence of current cigarette smoking was 21, 23, and 37% among participants from India, Pakistan and Bangladesh, respectively. The prevalence of current smokeless tobacco use was 6, 12, and 16% for Indian, Pakistani, and Bangladeshi participants, respectively. Among study participants, Bangladeshi nationality, hypertension, and alcohol use were significant correlates of current cigarette smoking. Significant correlates of smokeless tobacco use included increased age, less than college level education, alcohol use, and Pakistani or Bangladeshi nationality.Conclusions: Current smoking and smokeless tobacco use in South Asian migrants represent a significant public health burden in the UAE. Effective public health measures are needed to reduce tobacco use in this migrant population

Effect of High Fiber Cereal Intake on Satiety and Gastrointestinal Symptoms during Ramadan.

(1) Background: Fasting during Ramadan involves large changes in daily eating patterns which strongly impacts the daily biorhythm and challenges the regular function of the digestive tract. The aim of this study was to assess satiety, bowel habits, body composition, blood glycaemia, and blood lipidemia after the consumption of high fiber cereal at dawn (Sohor) during the month of Ramadan; (2) Methods: A two-arm randomized, controlled, single-blinded, parallel-design study was conducted in Ramadan month. Participants were randomized to consume either 90 g of high fiber cereal (11 g fiber/90 g) at Sohor for 20 consecutive days (intervention group, n = 45) or to maintain their habitual diet intake (control group; n = 36); (3) Results: The intervention group reported higher satiety rating scores, improved bowel habits and reduced bloating frequency after the 20-day intervention. Significantly higher intake of carbohydrates and dietary fiber were observed in the intervention group. Total cholesterol and low density lipoprotein (LDL) cholesterol were significantly lower among the intervention group compared to the control group (p-value = 0.043, and p-value = 0.033, respectively) at the end of the intervention. No significant differences in body weight, body fat percentage, waist circumference, body mass index, blood glucose, high density lipoprotein (HDL) cholesterol, and triglycerides were observed between the two groups; (4) Conclusions: Consuming high fiber cereal had a positive effect on health and well-being during the month of Ramadan with better satiety, improved bowel functions, and improved blood lipids

RNA-seq analysis of colorectal tumor-infiltrating myeloid-derived suppressor cell subsets revealed gene signatures of poor prognosis

Elevated levels of myeloid-derived suppressor cells (MDSCs), including polymorphonuclear MDSCs (PMN-MDSCs) and immature MDSCs (I-MDSCs), are usually associated with disease progression in cancer patients, including colorectal cancer (CRC). However, biological mechanisms and molecular pathways regulated by MDSC subpopulations in the CRC tumor microenvironment (TME) have not been fully investigated. In this study, we performed transcriptomic analysis of tumor-infiltrating I-MDSCs and PMN-MDSCs isolated from tumor tissues of six CRC patients, compared to antigen-presenting cells (APCs). We also compared the transcriptomic profiles of tumor-infiltrating PMN-MDSCs to I-MDSCs. Our results showed different molecular pathways regulated by each MDSC subset, potentially reflecting their phenotypical/molecular/functional characteristics in the CRC TME. Moreover, we identified gene signatures in PMN-MDSC and I-MDSC of poor overall survival (OS) and disease-free survival (DFS) using the Cancer Genome Atlas (TCGA) dataset from patients with colon adenocarcinoma (COAD). However, functional studies are required to validate these findings

Troubled Waters: Threats and Extinction Risk of the Sharks, Rays and Chimaeras of the Arabian Sea and Adjacent Waters

The extinction risk of sharks, rays and chimaeras is higher than that for most other vertebrates due to low intrinsic population growth rates of many species and the fishing intensity they face. The Arabian Sea and adjacent waters border some of the most important chondrichthyan fishing and trading nations globally, yet there has been no previous attempt to assess the conservation status of species occurring here. Using IUCN Red List of Threatened Species Categories and Criteria and their guidelines for application at the regional level, we present the first assessment of extinction risk for 153 species of sharks, rays and chimaeras. Results indicate that this region, home to 15% of described chondrichthyans including 30 endemic species, has some of the most threatened chondrichthyan populations in the world. Seventy-eight species (50.9%) were assessed as threatened (Critically Endangered, Endangered or Vulnerable), and 27 species (17.6%) as Near Threatened. Twenty-nine species (19%) were Data Deficient with insufficient information to assess their status. Chondrichthyan populations have significantly declined due to largely uncontrolled and unregulated fisheries combined with habitat degradation. Further, there is limited political will and national and regional capacities to assess, manage, conserve or rebuild stocks. Outside the few deepsea locations that are lightly exploited, the prognosis for the recovery of most species is poor in the near-absence of management. Concerted national and regional management measures are urgently needed to ensure extinctions are avoided, the sustainability of more productive species is secured, and to avoid the continued thinning of the regional food security portfolio

The effect of Gum Arabic (Acacia Senegal) on cardiovascular risk factors and gastrointestinal symptoms in adults at risk of metabolic syndrome: A randomized clinical trial

Gum Arabic (GA) is a widely-used additive in food processing, but is also historically used in a number of traditional therapies. It has been shown to have a broad range of health benefits, particularly in improving important cardiovascular risk indicators. Metabolic syndrome and its associated cardiac outcomes are a significant burden on modern healthcare systems, and complementary interventions to aid in its management are required. We aimed to examine the effect of GA on those with, or at risk of, metabolic syndrome to identify an effect on improving important disease parameters related to cardiovascular outcomes. A single-blind, randomized, placebo-controlled trial was conducted to identify the effects of daily GA supplementation on metabolic and cardiovascular risk factors. A total of 80 participants were randomized to receive 20 g of GA daily (n = 40) or placebo (1 g pectin, n = 40) for 12 weeks. Key endpoints included body-anthropometric indices, diet and physical activity assessment, and blood chemistry (HbA1c, fasting glucose, and blood lipids). Of the 80 enrolled, 61 completed the study (intervention: 31, control: 30) with 19 dropping out due to poor treatment compliance. After 12 weeks, the participants receiving the GA showed significant decreases in systolic and diastolic blood pressure, fat-free body mass, energy and carbohydrate consumption, and fasting plasma glucose, as well as increased intake of dietary fiber. They also reported improvements in self-perceived bloating and quality of bowel movements, as well as a decreased appetite score following GA consumption. These results suggest that GA could be a safe and beneficial adjunct to other treatments for those with, or at risk of, metabolic syndrome

Associations between Birth Weight and Adult Sleep Characteristics: A Cross-Sectional Analysis from the UAEHFS

Abnormal birth weight, particularly low birth weight (LBW), is known to have long-term adverse health consequences in adulthood, with disrupted sleep being suggested as a mediator or modifier of this link. We thus aimed to assess the associations between birth weight and self-reported adult sleep characteristics: sleep duration, difficulty waking up in the morning, daily nap frequency, sleep problems at night, snoring, daytime tiredness or sleepiness, and ever-stop breathing during sleep. This cross-sectional analysis used the United Arab Emirates Healthy Future Study data collected from February 2016 to March 2023 involving 2124 Emiratis aged 18–61 years. We performed a Poisson regression under unadjusted and age-sex-and-BMI-adjusted models to obtain the risk ratio and its 95% confidence interval for our analysis of the association between birth weight and each adult sleep characteristics, compared to individuals with normal birth weight (≥2.5 kg). Those with LBW had significantly a 17% increased risk of difficulty waking up in the morning, compared to those with normal birth weight. In addition, females with LBW history were also at an increased risk of reporting difficulty waking up in the morning. Studies with objective sleep assessments that include measurements of more confounding factors are recommended to confirm these risks