RESUMO
Background: Tension-Type Headache (TTH) is regarded as the third most prevalent disorder worldwide, prompting children to seek medical attention. Our objective is to investigate the prevalence of TTH among students aged 6 to 18 years in various geographical regions of Iran, while also assessing the impact of headaches on their quality of life. Methods: Employing a cross-sectional survey, we have carefully distributed self-completed structured questionnaires to students in 121 meticulously selected schools throughout the country, ensuring the representation of its diverse population. Results: Among the 2,958 potential participants, we have included a total of 2031 individuals in our study. This comprises 57.3% children and 42.7% adolescents, with 50.02% being males and 49.97% females. Specifically, we have examined 950 subjects with TTH and 1,081 individuals without any form of headache. TTH was diagnosed in 32.1% of the participants. Notably, we have observed a significant difference in the average age between the TTH subjects and those without headaches. Participants without headaches were more likely to be enrolled in primary schools, while those diagnosed with TTH predominantly attended high schools. We found no significant relationship between urban-rural areas or different geographic regions and the prevalence of TTH or its subtypes. Phonophobia was commonly associated with TTHs. Lastly, the mean quality-of-life score was highest for individuals without headaches, followed by those with low frequency episodic TTH, high frequency episodic TTH, and chronic TTHs. There was also a significant relation between headache severity and quality of life scores. Conclusion: The significant prevalence of TTH in children and adolescents and its adverse impact on the daily activities of individuals underscore the utmost importance of accurate diagnosis and efficient management.
RESUMO
Chimeric antigen receptor (CAR) T cells and natural killer (NK) cells are genetically engineered immune cells that can detect target antigens on the surface of target cells and eliminate them following adoptive transfer. Recent progress in CAR-based therapies has led to outstanding clinical success in certain patients with leukemias and lymphomas and offered therapeutic benefits to those resistant to conventional therapies. The universal approach to stable CAR transgene delivery into the T/NK cells is the use of viral particles. Such approaches mediate semi-random transgene insertions spanning the entire genome with a high preference for integration into sites surrounding highly-expressed genes and active loci. Regardless of the variable CAR expression level based on the integration site of the CAR transgene, foreign integrated DNA fragments may affect the neighboring endogenous genes and chromatin structure and potentially change a transduced T/NK cell behavior and function or even favor cellular transformation. In contrast, site-specific integration of CAR constructs using recent genome-editing technologies could overcome the limitations and disadvantages of universal random gene integration. Herein, we explain random and site-specific integration of CAR transgenes in CAR-T/NK cell therapies. Also, we tend to summarize the methods for site-specific integration as well as the clinical outcomes of certain gene disruptions or enhancements due to CAR transgene integration. Also, the advantages and limitations of using site-specific integration methods are discussed in this review. Ultimately, we will introduce the genomic safe harbor (GSH) standards and suggest some appropriate safety prospects for CAR integration in CAR-T/NK cell therapies.
RESUMO
Chimeric antigen receptor (CAR) therapy is a method directing T lymphocytes against antigens on the surface of tumors, increasing target cell elimination. Genetic engineering enhances the capability of immune cells to detect new antigens expressed on cell surfaces. CAR T cell therapy is a significant breakthrough for treating human malignancies; however, different side effects (e.g., cytokine release syndrome) restrict its application. Improving design and using various combined receptors enhance the performance of these cells. This review discusses limitations and risk factors associated with CAR T cell therapy. We also review some alternative approaches for developing the next generation of CAR T cells.
