Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies

ABSTRACT Introduction: Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19 + B-cell malignancies in numerous clinical trials. The CAR molecule, which recognizes cell-surface tumor-associated antigen independently of human leukocyte antigen (HLA), is composed by one or more signaling molecules to activate genetically modified T cells for killing, proliferation, and cytokine production. Objectives: In order to make this treatment available for a larger number of patients, we developed a simple and efficient platform to generate and expand CAR-T cells. Methods: Our approach is based on a lentiviral vector composed by a second-generation CAR that signals through a 41BB and CD3-ζ endodomain. Conclusions: In this work, we show a high-level production of the lentiviral vector, which was successfully used to generate CAR-T cells. The CAR-T cells produced were highly cytotoxic and specific against CD19+ cells in vitro and in vivo, being able to fully control disease progression in a xenograft B-cell lymphoma mouse model. Our work demonstrates the feasibility of producing CAR-T cells in an academic context and can serve as a paradigm for similar institutions. Nevertheless, the results presented may contribute favoring the translation of the research to the clinical practice.

High-frequency profile in adolescents and its relationship with the use of personal stereo devices / Perfil de alta frequência em adolescentes e sua relação com o uso de MP3 players

Abstract Objective: To analyze and correlate the audiometric findings of high frequencies (9–16 kHz) in adolescents with their hearing habits and attitudes, in order to prevent noise-induced hearing loss. Method: This was a descriptive cross-sectional study, which included 125 adolescents in a sample of normal-hearing students, at a state school. The subjects performed high-frequency audiometry testing and answered a self-administered questionnaire addressing information on sound habits concerning the use of personal stereo devices. The sample was divided according to the exposure characteristics (time, duration, intensity, etc.) and the results were compared with the observed thresholds, through the difference in proportions test, chi-squared, Student's t-test, and ANOVA, all at a significance level of 0.05. Results: Average high-frequency thresholds were registered below 15 dB HL and no significant correlation was found between high frequency audiometric findings and the degree of exposure. Conclusion: The prevalence of harmful sound habits due to the use of personal stereo devices is high in the adolescent population, but there was no correlation between exposure to high sound pressure levels through personal stereos and the high-frequency thresholds in this population.

Resumo Objetivo: Analisar e correlacionar os achados audiométricos de altas frequências (9-16 kHz) em adolescentes com seus hábitos e atitudes de audição para prevenir perda auditiva induzida por ruído. Método: Este é um estudo transversal descritivo que incluiu 125 adolescentes em uma amostra de alunos ouvintes em uma escola estadual. Os indivíduos foram submetidos a testes de audiometria de altas frequências e responderam a um questionário autoadministrado que abordava informações sobre hábitos sonoros com relação ao uso de MP3 players. A amostra foi dividida de acordo com as características de exposição (tempo, duração, intensidade etc.) e os resultados foram comparados com os limites observados, por meio dos testes de diferença de proporções, qui-quadrado, t de Student e análise de variância (Anova), todos em um nível de significância de 0,05. Resultados: Foi registrada média de limiares de altas frequências abaixo de 15 dB HL e não foi encontrada correção significativa entre os achados audiométricos de altas frequências e o grau de exposição. Conclusão: A prevalência de hábitos sonoros prejudiciais devido ao uso de MP3 players é alta na população adolescente, porém não houve correlação entre a exposição a altos níveis de pressão sonora por meio de MP3 players e os limiares de altas frequências nessa população.

Relationship between otolaryngologic complaints and systemic comorbidities observed in a group of hearing aid users

Introduction Optimization of the selection, adaptation, and benefit of hearing aids is necessary to characterize and manage hearing loss, user expectations, otolaryngologic symptoms, and systemic comorbidities. Objective To compare the occurrence of otologic complaints, systemic diseases, and effective use of hearing aids in men and women with deafness. Methods Patients from a Unified Health System-accredited hearing health service, who reported problems in adapting to their hearing aids, were evaluated by a physician and audiologist. An anamnesis, ENT evaluation, and audiological evaluation were performed. Results During the data collection period, 278 subjects came in for follow-up visits; of these, 61 (21%) reported otologic or operational problems with their equipment. The most prevalent type of hearing loss was basocochlear, a characteristic of presbycusis, in both men and women; the most frequently reported comorbidities were hypercholesterolemia (more significant in women) and hypertension (more significant in men). Fourteen subjects reported using their device discontinuously, with no significant difference between genders; the reasons for discontinuation of use were itching and ringing, with more complaints from women. Conclusion The incidence of systemic and audiological complaints is high in this population. These patients should be evaluated thoroughly, as resolutions of these complaints can contribute to improving the quality of life and assist in the process of hearing aid fitting.

Dichotic Hearing in Elderly Hearing Aid Users Who Choose to Use a Single-Ear Device

Introduction Elderly individuals with bilateral hearing loss often do not use hearing aids in both ears. Because of this, dichotic tests to assess hearing in this group may help identify peculiar degenerative processes of aging and hearing aid selection. Objective To evaluate dichotic hearing for a group of elderly hearing aid users who did not adapt to using binaural devices and to verify the correlation between ear dominance and the side chosen to use the device. Methods A cross-sectional descriptive study involving 30 subjects from 60 to 81 years old, of both genders, with an indication for bilateral hearing aids for over 6 months, but using only a single device. Medical history, pure tone audiometry, and dichotic listening tests were all completed. Results All subjects (100%) of the sample failed the dichotic digit test; 94% of the sample preferred to use the device in one ear because bilateral use bothered them and affected speech understanding. In 6%, the concern was aesthetics. In the dichotic digit test, there was significant predominance of the right ear over the left, and there was a significant correlation between the dominant side with the ear chosen by the participant for use of the hearing aid. Conclusion In elderly subjects with bilateral hearing loss who have chosen to use only one hearing aid, there is dominance of the right ear over the left in dichotic listening tasks. There is a correlation between the dominant ear and the ear chosen for hearing aid fitting...

Qualidade de vida: comparando resultados em idosos com e sem presbiacusia / Quality of life: comparing results in elderly with and without presbyacusis

OBJETIVO: Avaliar a qualidade de vida de um grupo de idosos presbiacúsicos após a protetização e comparar os resultados com um grupo de idosos normouvintes. MÉTODO: Estudo clínico descritivo transversal, do qual participaram 51 indivíduos, de ambos os gêneros, divididos em dois grupos: grupo estudo, formado por 36 presbiacúsicos, com idade média de 73 anos, e usuários de prótese auditiva (mínimo de seis meses de uso); grupo controle, formado por 15 idosos normouvintes, com idade média de 69 anos. Foi aplicado o questionário WHOQOL-bref, e os dados relativos aos quatro domínios abrangidos (físico, psicológico, meio ambiente e relações sociais) foram analisados e comparados entre os grupos. RESULTADOS: Qualitativamente, todos os sujeitos presbiacúsicos declararam que sua vida melhorou depois da adaptação da prótese, porém os escores do WHOQOL-breaf revelaram: em relação ao domínio físico, não houve diferença significativa entre as respostas dos dois grupos, certamente porque o avanço da idade traz no seu bojo uma série de limitações; nos demais domínios, houve diferença estatisticamente significante entre os grupos, sendo que no grupo de presbiacúsicos a qualidade de vida foi pior. Tal fato permite inferir que, no grupo de presbiacúsicos, apesar do uso da prótese, as limitações impostas pela idade continuam comprometendo a autoestima, as relações interpessoais e o convívio social. CONCLUSÃO: Nos dois grupos, a idade representa limitações no que se refere à qualidade de vida. No grupo com presbiacusia, foi possível verificar melhoria da percepção auditiva, porém a melhora da qualidade de vida geral desses indivíduos depende de outros fatores que podem não ter ...

OBJECTIVE: To evaluate the quality of life of a group of presbycusic elderly after using the device and comparing the results with a group of normal hearing elderly subjects. METHOD: This was a cross-sectional clinical study with 51 subjects participants who were divided in two groups: the study group was made up of 36 presbycusic subjects, with an average age of 73 years, of both genders, and hearing aid users (minimum of 6 months of use); the control group comprised 15 normal hearing elderly, with average age of 69. We used the WHOQOL-bref, and the data on four areas covered (physical, psychological, environmental and social relations) were analyzed and compared between groups. RESULTS: Qualitatively, all presbycusic subjects stated that their life improved after the use of the prosthesis; however, WHOQOL-bref scores reveal: in relation to the physical domain, there was no significant difference between the responses of the two groups, probably because aging brings with it a number of limitations; in other areas, there was a statistically significant difference between the groups, with the presbycusic group's quality of life being worse. This fact allows us to infer that, in the group of presbycusic subjects, despite the use of the prosthesis, the limitations imposed by age continue to affect self-esteem, interpersonal relationships, and social interaction. CONCLUSION: In both groups surveyed, age represents limitations regarding quality of life. In the group with presbycusis, it was possible to verify the improvement of auditory perception, but the improvement of overall quality of life of these individuals depends on other factors that may not be related to hearing loss when compared to the normal hearing group. .