Regulating the regulatory T cells as cell therapies in autoimmunity and cancer.

Regulatory T cells (Tregs), possess a pivotal function in the maintenance of immune homeostasis. The dysregulated activity of Tregs has been associated with the onset of autoimmune diseases and cancer. Hence, Tregs are promising targets for interventions aimed at steering the immune response toward the desired path, either by augmenting the immune system to eliminate infected and cancerous cells or by dampening it to curtail the damage to self-tissues in autoimmune disorders. The activation of Tregs has been observed to have a potent immunosuppressive effect against T cells that respond to self-antigens, thus safeguarding our body against autoimmunity. Therefore, promoting Treg cell stability presents a promising strategy for preventing or managing chronic inflammation that results from various autoimmune diseases. On the other hand, Tregs have been found to be overactivated in several forms of cancer, and their role as immune response regulators with immunosuppressive properties poses a significant impediment to the successful implementation of cancer immunotherapy. However, the targeting of Tregs in a systemic manner may lead to the onset of severe inflammation and autoimmune toxicity. It is imperative to develop more selective methods for targeting the function of Tregs in tumors. In this review, our objective is to elucidate the function of Tregs in tumors and autoimmunity while also delving into numerous therapeutic strategies for reprogramming their function. Our focus is on reprogramming Tregs in a highly activated phenotype driven by the activation of key surface receptors and metabolic reprogramming. Furthermore, we examine Treg-based therapies in autoimmunity, with a specific emphasis on Chimeric Antigen Receptor (CAR)-Treg therapy and T-cell receptor (TCR)-Treg therapy. Finally, we discuss key challenges and the future steps in reprogramming Tregs that could lead to the development of novel and effective cancer immunotherapies.

Nivolumab plus ipilimumab combination therapy in cancer: Current evidence to date.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy, yielding significant antitumor responses across multiple cancer types. Combination ICI therapy with anti-CTLA-4 and anti-PD-1 antibodies outperforms either antibody alone in terms of clinical efficacy. As a consequence, the U.S. Food and Drug Administration (FDA) approved ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) as the first-ever approved therapies for combined ICI in patients with metastatic melanoma. Despite the success of ICIs, treatment with checkpoint inhibitor combinations poses significant clinical challenges, such as increased rates of immune-related adverse events (irAEs) and drug resistance. Thus, identifying optimal prognostic biomarkers could help to monitor the safety and efficacy of ICIs and identify patients who may benefit the most from these treatments. In this review, we will first go over the fundamentals of the CTLA-4 and PD-1 pathways, as well as the mechanisms of ICI resistance. The results of clinical findings that evaluated the combination of ipilimumab and nivolumab are then summarized to support future research in the field of combination therapy. Finally, the irAEs associated with combined ICI therapy, as well as the underlying biomarkers involved in their management, are discussed.

Diagnostic performance of waist-to-height ratio in identifying cardiovascular risk factors and metabolic syndrome among adult Saudis. A cross-sectional study.

OBJECTIVES: To evaluate the diagnostic performance of waist to height ratio (WHtR) to screen for cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) among Saudis. METHODS: Between June 2013 and August 2014, a cross-sectional study of 3,063 adult Saudis of both genders from King Khalid Hospital, Riyadh, Saudi Arabia was conducted. Using the "WHO STEPwise Surveillance-Instrument V2.1", which uses sequential  steps including questionnaires and anthropometric and biochemical measurements of MetS and CVRF.  Waist to height ratio validity in defining central obesity, MetS, and CVRF were tested using receiver operating characteristic curve (ROC), sensitivity, specificity, positive and negative predictive values, and accuracy. Using multivariate regression analyses for adjustment of confounders as age and gender were applied to compute adjusted odds ratios (aOR).  Results: The diagnostic potential of WHtR was excellent for central obesity (area under the curve [AUC] = 0.98), and MetS (AUCs = 0.86); it was good for CVRF ≥2 (AUCs = 0.79) and was satisfactory for dyslipidemia (AUCs = 0.66). The sensitivities and negative predictive values exceeded 85% for diagnosing central obesity, diabetes, and hypertension. Adjusted odds ratios  for age and gender showed that WHtR ≥0.50 significantly increased the risk of diabetes, hypertension, and ≥2 CVRF by almost 4-fold, and increased the risk of dyslipidemia by 2-fold. Conclusion: Waist height ratio showed a good diagnostic performance for CVRF and MetS among Saudis. Furthermore, WHtR ≥0.5 increased the risk of dyslipidemia, diabetes mellitus and  hypertension.

Changes in dietary habits, physical activity and status of metabolic syndrome among expatriates in Saudi Arabia.

The aim of this paper is to assess the impact of living in Saudi Arabia on expatriate employees and their families' behavioural cardiovascular risk factors (BCVRFs), and to examine the association between changes in BCVRFs and metabolic syndrome (MetS). A cross-sectional study was conducted on 1437 individuals, aged ≥ 18 years, from King Saud University in Riyadh, Saudi Arabia. We used the World Health Organization STEPS questionnaire to ask every participant questions about BCVRFs twice: (1) to reflect their period of living in Saudi Arabia and (2) to shed light upon life in their country of origin. Their mean age was 40.9 (11.7) years. The prevalence of BCVRFs was as follows: tobacco use in 156 (11%), physical inactivity in 1049 (73%) low intake of fruit and vegetables in 1264 (88%) and MetS in 378 (26%). Residing in Saudi Arabia had reduced physical activity and intake of fruit and vegetables. There was also a significant increase in the fast food consumption. In conclusion, living in Saudi Arabia had a significant negative effect on BCVRFs. However, there was no statistically significant association between changes in fruit and vegetable intake and physical activity and MetS status, except that intake of fast food was lower among participants with MetS.

Non-Communicable Disease Risk Factors among Employees and Their Families of a Saudi University: An Epidemiological Study.

OBJECTIVES: To assess the prevalence of noncommunicable disease (NCD) risk factors among Saudi university employees and their families; to estimate the cardiovascular risk (CVR) amongst the study population in the following 10years. METHODS: The NCD risk factors prevalence was estimated using a cross-sectional approach for a sample of employees and their families aged ≥ 18 years old, in a Saudi university (Riyadh in Kingdom of Saudi Arabia; KSA). WHO STEPwise standardized tools were used to estimate NCD risk factors and the Framingham Coronary Heart Risk Score calculator was used to calculate the CVR. RESULTS: Five thousand and two hundred subjects were invited, of whom 4,500 participated in the study, providing a response rate of 87%. The mean age of participants was 39.3±13.4 years. The majority of participants reported low fruit/vegetables consumption (88%), and physically inactive (77%). More than two thirds of the cohort was found to be either overweight or obese (72%), where 36% were obese, and 59% had abdominal obesity. Of the total cohort, 22-37% were found to suffer from dyslipidaemia, 22% either diabetes or hypertension, with rather low reported current tobacco use (12%). One quarter of participants was estimated to have >10% risk to develop cardiovascular disease within the following 10-years. CONCLUSION: The prevalence of NCD risk factors was found to be substantially high among the university employees and their families in this study.

The Effect of Neurofeedback Therapy on Reducing Symptoms Associated with Attention Deficit Hyperactivity Disorder: A Case Series Study.

INTRODUCTION: This study aimed to evaluate the effectiveness of neurofeedback on attention deficit hyperactivity disorder. METHODS: This is a quasi-experimental study without a control group. The study population included all children aged 5 to 12 years old affected with attention deficit hyperactivity disorders in Tehran, Iran who were referred to psychiatric clinics and given the diagnosis. The sample included 12 children with attention deficit hyperactivity disorder who were selected based on their availability (non-random sampling). They received 30 sessions of neurofeedback treatment, 2 times per week. Before and after neurofeedback training, the children were evaluated and compared with the use of cognitive assessment system test. Data were analyzed using dependent T-test. RESULTS: The total mean score for pretest was 88.81 while the total mean score for the post test was 82.23. The mean in pretest for attention hyperactivity disorder was higher than the mean in the post test. Moreover, The difference of pretest and post test scores of children affected with learning disorder associated with ADHD was calculated that showed significant (P=0.003). CONCLUSION: Neurofeedback is effective in the improvement of attention deficit hyperactivity disorder.

Experiences of using a memory aid to structure and support daily activities in a small-scale group accommodation for people with dementia.

BACKGROUND: Use of technology to structure and support the daily activities of the residents in a small-scale group accommodation (SSGA) for dementia is a new innovation in the Netherlands. This paper presents the process of development of this new way of structuring activities and the findings of a pilot study looking at the experiences of using this device in people with dementia. METHOD: A qualitative method was chosen, data were collected using individual interviews with the residents (n = 6), focus groups interviews with informal carers (n = 5) and members of staff (n = 6). Data were analysed using Ritchie & Spencer's framework (1994). FINDINGS: Three main themes emerged: issues regarding the implementation, needs for further development and the learning experiences acquired during the development. The majority of the residents were happy with the use and function of the memory aid. However, the occurrence of installation errors, limited ease of use and a lack of knowledge regarding the function and use of the memory aid were issues that prevented a successful implementation. Findings highlighted shared views about ways of improving through adaptation of the software program and additional technological applications; internet connectivity, improving its accessibility by using a remote control and adding videos and photos. CONCLUSION: Lessons are learned about the use and transferability of this innovation in people with dementia and other vulnerable target groups including those with learning disabilities as well as its limitation and the needs for further development.

Health promotion and young prisoners: a European perspective.

PURPOSE: The purpose of this paper is to assess the health promotion needs of vulnerable young prisoners and the existing health promotion activities in custodial settings in seven European Union (EU) Member States. DESIGN/METHODOLOGY/APPROACH: The research comprised two components: the first involved identifying existing health promotion practices. The second involved mapping out young offenders' health promotion needs by carrying out a needs assessment. Both quantitative and qualitative methods were adopted. The quantitative element comprised surveys among young prisoners and prison staff and focused on the availability and perceived importance of health promotion activities in prison. The qualitative element comprised focus groups with young offenders and individual interviews with prison staff, field experts and NGO members. FINDINGS: The findings from the research have identified a number of similar, but also some diverse areas of unmet need for health promotion activities in prison settings across these diverse seven EU countries. There is no consistency of approach within and between countries regarding health promotion policy, guidance, resources and programmes for young prisoners. In order to improve the health of young prisoners and to establish and increase sustainability of existing health promotion programmes, there is a need for the establishment of National and EU standards. ORIGINALITY/VALUE: Providing health promotion activities for young prisoners while in custodial settings is key to addressing their unmet health and well-being needs and to facilitate their reintegration back into the community. Despite the barriers identified by this research, health promotion is to some extent being delivered in the partner countries and provides a foundation upon which further implementation of health promotion activities can be built especially when the benefits of health promotion activities, like dealing with the common problems of alcohol and drug addiction, mental health and communicable diseases are linked to successful reintegration.

Sustainability in local public health nutrition programmes: beyond nutrition education, towards community collaboration.

The present paper presents the approach, results and outcome of an innovative piece of action research amongst professionals (health and non-health) and the public (women and young people from low-income families in one of the deprived areas of Birmingham, UK). A cooperative inquiry approach was used and data were collected on concerns about health of professionals (n 15) and the public (n 19), as well as dietary practices, smoking pattern and access to healthy foods amongst the public (n 49). The methods of data collection were: desk research; observation; semi-structured individual and focus-group interviews; structured individual interviews. The findings highlight diverse views and expectations about health amongst the public and the professionals, and suggest the existence of tensions between the partnership and the ownership of inter-agency collaboration. It argues the importance of having a shared vision amongst health and non-health professionals regarding health strategy and the way forward for working together to promote the public's health. It recommends that by using the tenet of action research, and adapting a cooperative inquiry approach, members of a partnership project could learn through reflection on action and achieve personal development and social action.

Focus-group interview and data analysis.

In recent years focus-group interviews, as a means of qualitative data collection, have gained popularity amongst professionals within the health and social care arena. Despite this popularity, analysing qualitative data, particularly focus-group interviews, poses a challenge to most practitioner researchers. The present paper responds to the needs expressed by public health nutritionists, community dietitians and health development specialists following two training sessions organised collaboratively by the Health Development Agency, the Nutrition Society and the British Dietetic Association in 2003. The focus of the present paper is on the concepts and application of framework analysis, especially the use of Krueger's framework. It provides some practical steps for the analysis of individual data, as well as focus-group data using examples from the author's own research, in such a way as to assist the newcomer to qualitative research to engage with the methodology. Thus, it complements the papers by Draper (2004) and Fade (2004) that discuss in detail the complementary role of qualitative data in researching human behaviours, feelings and attitudes. Draper (2004) has provided theoretical and philosophical bases for qualitative data analysis. Fade (2004) has described interpretative phenomenology analysis as a method of analysing individual interview data. The present paper, using framework analysis concentrating on focus-group interviews, provides another approach to qualitative data analysis.