Cytokine release syndrome after chimeric antigen receptor T cell therapy in patients with diffuse large B-cell lymphoma: a systematic review.

INTRODUCTION: Chimeric antigen receptor T (CAR-T) cell therapy is an innovative technology that has shown promising results in clinical trials. Treatment is based on modifying the patient's own T cells to express artificial surface receptors to specifically recognize and attack the tumor cells. OBJECTIVE: To synthesize available evidence on the incidence and management strategies of cytokine release syndrome in patients with diffuse large B-cell lymphoma who received CAR-T cell therapy. METHODS: This is a systematic literature review. The search was conducted in the PubMed, Scopus, and Web of science databases. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42022359258. RESULTS: Nineteen studies were included with a total of 1193 patients who received CAR-T cell therapy. Of these patients, 804 (67%) developed some degree of cytokine release syndrome. The frequencies of Grade 3 and 4 cytokine release syndrome were 10% and 3%, respectively. The regimen most used in the management of the syndrome included tocilizumab and/or glucocorticoids. CONCLUSION: The results obtained in this review demonstrate high rates of cytokine release syndrome in patients with diffuse large B-cell lymphoma treated with CAR-T cell therapy, however these events are manageable, supporting the conclusion that this therapy is safe in these patients.

Crotamine derived from Crotalus durissus terrificus venom combined with drugs increases in vitro antibacterial and antifungal activities.

This study investigated crotamine (CTA), a peptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, known for its exceptional cell penetration potential. The objective was to explore the antibacterial and antifungal activity of CTA, its ability to inhibit efflux pumps and evaluate the effectiveness of its pharmacological combination with antibiotics and antifungals. In microbiological assays, CTA in combination with antibiotics was tested against strains of S. aureus and the inhibition of NorA, Tet(K) and MepA efflux pumps was also evaluated. CTA alone did not present clinically relevant direct antibacterial action, presenting MIC > 209.7 µM against strains S. aureus 1199B, IS-58, K2068. The standard efflux pump inhibitor CCCP showed significant effects in all negative relationships to assay reproducibility. Against the S. aureus 1199B strain, CTA (20.5 µM) associated with norfloxacin diluted 10 × (320.67 µM) showed a potentiating effect, in relation to the control. Against the S. aureus IS-58 strain, the CTA associated with tetracycline did not show a significant combinatorial effect, either with 2304 or 230.4 µM tetracycline. CTA at a concentration of 2.05 µM associated with ciprofloxacin at a concentration of 309.4 µM showed a significant potentiating effect. In association with EtBr, CTA at concentrations of 2.05 and 20.5 µM potentiated the effect in all strains tested, reducing the prevention of NorA, Tet(K) and MepA efflux pumps. In the C. albicans strain, a potentiating effect of fluconazole (334.3 µM) was observed when combined with CTA (2.05 µM). Against the C. tropicalis strain, a significant effect was also observed in the association of fluconazole 334.3 µM, where CTA 2.05 µM considerably reduced fungal growth and decreased the potentiation of fluconazole. Against the C. krusei strain, no significant potentiating effect of fluconazole was obtained by CTA. Our results indicate that CTA in pharmacological combination potentiates the effects of antibiotics and antifungal. This represents a new and promising antimicrobial strategy for treating a wide variety of infections.

Pharmacological potential of limonene against opportunistic fungi: Impact on Candida virulence.

The present article aims to evaluate the antifungal and antivirulence effect of the phytoconstituent Limonene against Candida spp. Antifungal assays were performed, where the concentration capable of inhibiting 50 % of fungal growth, the growth inhibition curve, the minimum fungicidal concentration, the evaluation of the modifying effect with fluconazole, the inhibitory effect of the substances on the morphological transition of Candida spp. and the statistical analysis of the results were determined. With this study, it was seen that limonene demonstrated growth inhibition for the strains tested and when associated the natural compound with Fluconazole, there was potentiation of the effect of the drug, since the inhibition of growth by the combination occurred at lower concentrations against all strains tested, when compared to the drug alone, which inhibited growth at the highest concentration. In the test to determine the Minimum Fungicidal Concentration of the products tested alone and in combination, it was found that in the case of Candida strains, growth inhibition by limonene occurred at a concentration of 1024 µg/mL. For Fluconazole, growth impairment ranged from > 1024 µg/mL to 256 µg/mL for the strains. And when combined, limonene potentiated the action of FCZ, making fungal colonization unfeasible at concentrations below 1024 µg/mL. Regarding the morphological transition from yeast to hyphae, limonene was used at concentrations of 1024 µg/mL and 512 µg/mL, and it was found that, for CA and CK, the filaments were reduced in number and size at the highest concentration and against CT, the morphological transition from yeast to hyphae/pseudohyphae was totally inhibited, and if compared to the growth control, limonene was able to reduce fungal growth at concentrations greater than 512 µg/mL. This compound has antimicrobial activity described, due to its ability to interfere in the gene expression of the fungus, the limited therapeutic options and the recent emergence of multidrug-resistant Candida species represent a significant challenge for human medicine and highlight the need for new therapeutic approaches, and in this study a great potential of limonene was revealed in relation to the perspective of increasing the efficiency of commercial drug. This work can bring an important contribution to the scientific database, while emphasizing that in-depth studies and tests on the subject, in order to better investigate its effectiveness and mechanisms by which they exert their effects, are still necessary.

Effect of experimental dentin etchants on dentin bond strength, metalloproteinase inhibition, and antibiofilm activity.

OBJECTIVE: this study evaluated dentin microtensile bond strength (µTBS) and failure modes (at 24 h and one year), bonding interface regarding hybridization, surface morphology regarding demineralization, in situ metalloproteinase (MMP) activity, and antibacterial effect of three dentin etchants compared to 35% phosphoric acid (PA). MATERIALS AND METHODS: The Adper Single Bond 2 adhesive (3 M Oral Care) was applied on moist dentin etched with PA (control) or on air-dried dentin etched with 3% aluminum nitrate + 2% oxalic acid (AN), 6.8% ferric oxalate + 10% citric acid (FO), or 10% citric acid (CA). The µTBS test used 40 human teeth (n = 10). Failure modes and surface morphology were analyzed by scanning electron microscopy (n = 3), while bonding interface morphology and MMP activity were evaluated by laser scanning confocal microscopy (n = 3). Antibacterial activity was evaluated against S. Mutans biofilm by means of viable cells count (CFU/mL). RESULTS: PA presented the highest bond strengths regardless of aging time. PA, AN, and CA showed stable bond strengths after one year of storage. Adhesive and mixed failures were predominant in all groups. Thin hybrid layers with short resin tags were observed for the experimental etchants. The AN-based etchant was able to inhibit MMP activity. All tested etchants presented antibacterial activity against S. Mutans biofilm. SIGNIFICANCE: This study suggests different dentin etchants capable of inhibiting MMP activity while also acting as cavity disinfectants.

Influence of resistance training on muscle architecture in older adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Resistance training (RT) consists of planned exercise programs to increase muscle strength capacity through neural and structural adaptations, such as changes in the geometric arrangement of muscle fibers. This study aimed to analyze the influence of RT on muscle architecture in older people. METHODS: This PROSPERO-registered systematic review and meta-analysis (identification number CRD42022340477) followed the PRISMA guidelines. Four electronic databases were searched for eligible randomized controlled trials (RCTs) that observed older individuals submitted to RT programs that reported muscle architecture outcomes. RESULTS: Seventeen RCTs met the eligibility criteria with a total of 488 participants. The main results of the meta-analysis showed that RT interventions had a significant effect on the thickness of the medial gastrocnemius (SMD = 0.12; 95% CI: - 0.07 to 0.17; p < 0.00001; I2 = 0%). CONCLUSION: Based on available evidence, studies included in this review showed improvement in maximum isometric force, pennation angle, fascicle length, thickness, and muscle activation after RT interventions. In turn, the meta-analysis suggested a potential for improving the thickness of the medial gastrocnemius after the intervention. However, any clinical implications drawn from the analyses should be interpreted with caution, as these findings are substantially limited due to a low number of included studies and a potential heterogeneity between studies.

Acute exercise reduces feeding by activating IL-6/Tubby axis in the mouse hypothalamus.

Background: Acute exercise contributes to decreased feeding through leptin and interleukin/Janus kinase 2/signal transducers and activators of transcription 3 (IL-6/JAK2/STAT3) signaling. Considering the pleiotropic use of substrates by JAK2 and that JAK2 can phosphorylate the Tubby protein (TUB) in CHO-IR cells, we speculated that acute exercise can activate the IL-6/JAK2/TUB pathway to decrease food intake. Aims: We investigated whether acute exercise induced tyrosine phosphorylation and the association of TUB and JAK2 in the hypothalamus and if IL-6 is involved in this response, whether acute exercise increases the IL-6/TUB axis to regulate feeding, and if leptin has an additive effect over this mechanism. Methods: We applied a combination of genetic, pharmacological, and molecular approaches. Key findings: The in vivo experiments showed that acute exercise increased the tyrosine phosphorylation and association of JAK2/TUB in the hypothalamus, which reduced feeding. This response was dependent on IL-6. Leptin had no additive effect on this mechanism. Significance: The results of this study suggest a novel hypothalamic pathway by which IL-6 released by exercise regulates feeding and reinforces the beneficial effects of exercise.

Análise comparativa da percepção corporal sobre o treinamento entre indivíduos onívoros e vegetarianos / Análisis comparativo de la percepción corporal sobre el entrenamiento entre individuos omnívoros y vegetarianos / Comparative analysis of body perception on training between omnivorous and vegetarian individuals

Dietas vegetarianas vêm sendo cada vez mais adotadas no mundo. Com isso, há uma preocupação com a adequação nutricional e desempenho esportivo crescente entre profissionais de saúde e treinadores. O objetivo do presente estudo foi analisar a percepção corporal sobre o treinamento físico entre indivíduos onívoros e vegetarianos e, de forma secundária, comparar a percepção entre as diferentes dietas vegetarianas no desempenho esportivo. A amostra teve um total de 189 participantes (47 do sexo masculino e 142 do sexo feminino), sendo 91 onívoros (31 do sexo masculino e 60 do sexo feminino) e 98 vegetarianos (17 do sexo masculino e 81 do sexo feminino). Foi utilizado o questionário de Percepção do Corpo na Performance Esportiva (Pecopes), constituído por duas dimensões: dimensão 1 = percepção do corpo no desempenho esportivo; dimensão 2 = percepção do corpo no treinamento técnico e tático. Os resultados mostraram uma diferença significativa na dimensão 1 favorável aos vegetarianos quando comparados aos onívoros. O subgrupo ovolactovegetariano também obteve resultado significativamente superior aos onívoros na dimensão 1. Assim, foi possível concluir que os participantes vegetarianos do presente estudo apresentaram uma melhor percepção do corpo no desempenho esportivo comparado com os onívoros, porém não foram encontradas diferenças na percepção do corpo quanto ao treinamento técnico e tático.

Las dietas vegetarianas se adoptan cada vez más en el mundo. Por lo tanto, existe una preocupación por la adecuación nutricional y el aumento del rendimiento deportivo entre los profesionales de la salud y los entrenadores. El objetivo del presente estudio fue analizar la percepción corporal del entrenamiento físico entre individuos omnívoros y vegetarianos y, en segundo lugar, comparar la percepción de diferentes dietas vegetarianas sobre el rendimiento deportivo. La muestra tuvo un total de 189 participantes (47 hombres y 142 mujeres), siendo 91 omnívoros (31 hombres y 60 mujeres) y 98 vegetarianos (17 hombres y 81 mujeres). Se utilizó el cuestionario de Percepción del Cuerpo en el Rendimiento Deportivo (Pecopes), que consta de dos dimensiones: dimensión 1 = percepción del cuerpo en el rendimiento deportivo; dimensión 2 = percepción corporal en el entrenamiento técnico y táctico. Los resultados mostraron una diferencia significativa en la dimensión 1 favorable a los vegetarianos en comparación con los omnívoros. El subgrupo ovolactovegetariano también tuvo un resultado significativamente mayor que los omnívoros en la dimensión 1. Así, fue posible concluir que los participantes vegetarianos en el presente estudio tenían una mejor percepción del cuerpo en el rendimiento deportivo en comparación con los omnívoros, pero no hubo diferencias. que se encuentran en la percepción del cuerpo con respecto al entrenamiento técnico y táctico.

Vegetarian diets are increasingly being adopted around the world. Thus, there is a concern about nutritional adequacy and growing sports performance among health professionals and coaches. This study aimed to analyze the body perception of physical training between omnivorous and vegetarian individuals and, secondarily, to compare the perception of different vegetarian diets on sports performance. The sample had a total of 189 participants (47 males and 142 females), being 91 omnivores (31 males and 60 females) and 98 vegetarians (17 males and 81 females). We used the Body Perception on Sports Performance (Pecopes) questionnaire, which consists of two dimensions: dimension 1 = perception of the body in sports performance; dimension 2 = body perception in technical and tactical training. The results showed a significant difference in dimension 1, favorable to vegetarians when compared to omnivores. The ovolactovegetarian subgroup also obtained a significantly higher result than omnivores in dimension 1. Thus, it was possible to conclude that vegetarian participants in the present study had a better body perception during sports performance compared to omnivores, but there were no differences in body perception regarding technical and tactical training.

Clima de seguridad del paciente en Unidades de Cuidados Intensivos en un hospital privado / Patient Safety Climate in Intensive Care Units at a Private Hospital

Introducción: El clima de seguridad del paciente se refleja en las actitudes y percepciones individuales de los profesionales con respecto a los puntos clave de la seguridad del paciente en la institución. Objetivo: Analizar el clima de seguridad del paciente desde la percepción del equipo de enfermería de las Unidades de Cuidados Intensivos de un hospital privado en Brasil. Métodos: Investigación cuantitativa de diseño descriptivo de corte transversal desarrollada en septiembre de 2020 en tres unidades de un hospital privado de la ciudad de Curitiba, Paraná, Brasil. Los participantes fueron 60 profesionales, 14 enfermeras y 46 técnicos de enfermería, que constituye una muestra no probabilística e intencional. La recopilación de datos se produjo mediante la aplicación de la Safety Attitudes Questionnaire. Los datos recolectados fueron analizados por estadística descriptiva, prueba t de Student y Mann-Whitney. Las puntuaciones ≥ 75 por ciento indican una percepción positiva del clima de seguridad. Resultados: El clima medio general de seguridad del paciente fue de 67,63 por ciento. La satisfacción en el trabajo obtuvo la mayor puntuación (76,29 por ciento), mientras que la percepción de la gestión hospitalaria fue la más baja (58,53 por ciento). Las enfermeras presentaron puntuaciones más positivas y con diferencia significativa para "Percepción del manejo en el hospital" (p = 0,022), en comparación con los técnicos de enfermería. Conclusión: El equipo de enfermería percibe debilidades con relación a la gestión, y las acciones estimulantes para reducir las diferencias entre los trabajadores son relevantes para mejorar el clima institucional(AU)

Introduction: The patient safety climate is reflected in individual attitudes and perceptions of professionals regarding the key points of patient safety at the institutional level. Objective: To analyze the patient safety climate as perceived by the nursing staff of the intensive care units of a private hospital in Brazil. Methods: A quantitative research with a cross-sectional and descriptive design was developed in September 2020 in three units of a private hospital in Curitiba City, Paraná State, Brazil. The participants were sixty professionals, fourteen nurses and 46 nursing technicians, which made up a nonprobabilistic and intentional sample. Data collection was done through the application of the Safety Attitudes Questionnaire. The collected data were analyzed using descriptive statistics, Student's t-test and Mann-Whitney test. The scores greater than or equal to 75 percent are indicative of a positive perception about safety climate. Results: The overall mean patient safety climate was 67.63 percent. Job satisfaction scored the highest (76.29 percent), while perception of hospital management was the lowest (58.53 percent). Nurses presented more positive scores and with significant difference for the category "perception of hospital management" (p=0.002), compared to nursing technicians. Conclusion: The nursing staff perceives weaknesses with respect to management, while stimulating actions for reducing differences among workers are relevant to improve the institutional climate(AU)

Correlation between pain, anthropometric measurements, stress and biochemical markers in women with low back pain.

Aim: To analyze the associations between pain duration, pain levels, anthropometric measures, perceived stress and biochemical markers in women with low back pain. Materials & methods: Forty-two participants were submitted to body mass, height, abdominal circumference, cortisol and creatine kinase (CK) collections. Pain duration, pain levels and stress were analyzed through specific questionnaires. Results: There were positive correlations between abdominal circumference and body mass, duration of pain and age, abdominal circumference, CK and age, CK and BMI, CK and abdominal circumference, and CK and duration of pain (p < 0.05). Conclusion: The higher the level of tissue damage over the years, the greater the tendency for higher levels of low back pain perception. Central fat was related to greater load on the spine.

Lay abstract Low back pain (LBP) is one of the factors that hinders the routine and productivity of women. LBP can cause functional disability and negatively interfere with work activities. The increase in pain can be caused by mechanical postural factors (such as behavioral habits), traumatic (such as accidents), and psychosocial factors (such as physical inactivity). Chronic LBP can influence behavioral aspects due to adaptations of pain feedback, such as postures to avoid pain and sedentary lifestyle. In this study, we observed that duration of LBP was related to higher levels of creatine kinase, which is an enzyme of our body that can be related to tissue damage. Moreover, the abdominal circumference, due to the accumulation of fat in this region, presented correlation with higher levels of tissue damage by creatine kinase and longer exposure time with LBP.