Abstract Background While many risk models have been developed to predict prognosis in heart failure (HF), these models are rarely useful for the clinical practitioner as they include multiple variables that might be time-consuming to obtain, they are usually difficult to calculate, and they may suffer from statistical overfitting. Objectives To investigate whether a simpler model, namely the ACEF-MDRD score, could be used for predicting one-year mortality in HF patients. Methods 748 cases within the SELFIE-HF registry had complete data to calculate the ACEF-MDRD score. Patients were grouped into tertiles for analyses. For all tests, a p-value <0.05 was accepted as significant. Results Significantly more patients within the ACEF-MDRD high tertile (30.0%) died within one year, as compared to other tertiles (10.8% and 16.1%, respectively, for ACEF-MDRD low and ACEF-MDRD med , p<0.001 for both comparisons). There was a stepwise decrease in one-year survival as the ACEF-MDRD score increased (log-rank p<0.001). ACEF-MDRD was an independent predictor of survival after adjusting for other variables (OR: 1.14, 95%CI:1.04 – 1.24, p=0.006). ACEF-MDRD score offered similar accuracy to the GWTG-HF score for predicting one-year mortality (p=0.14). Conclusions ACEF-MDRD is a predictor of mortality in patients with HF, and its usefulness is comparable to similar yet more complicated models.

Resumo Fundamento Embora muitos modelos de risco tenham sido desenvolvidos para prever o prognóstico na insuficiência cardíaca (IC), esses modelos raramente são úteis para o clínico, pois incluem múltiplas variáveis que podem ser demoradas para serem obtidas, são geralmente difíceis de calcular e podem sofrer de overfitting estatístico. Objetivos Investigar se um modelo mais simples, nomeadamente o escore ACEF-MDRD, poderia ser usado para prever a mortalidade em um ano em pacientes com IC. Métodos 748 casos do registro SELFIE-HF tinham dados completos para calcular o escore ACEF-MDRD. Os pacientes foram agrupados em tercis para análise. Para todos os testes, um valor de p <0,05 foi aceito como significativo. Resultados Significativamente mais pacientes dentro do tercil ACEF-MDRD alto (30,0%) morreram dentro de um ano, em comparação com outros tercis (10,8% e 16,1%, respectivamente, para ACEF-MDRD baixo e ACEF-MDRD med , p<0,001 para ambas as comparações). Houve uma diminuição gradual na sobrevida em um ano à medida que o escore ACEF-MDRD aumentou (log-rank p<0,001). ACEF-MDRD foi preditor independente de sobrevida após ajuste para outras variáveis (OR: 1,14, IC95%:1,04 – 1,24, p=0,006). O escore ACEF-MDRD ofereceu precisão semelhante ao escore GWTG-HF para prever a mortalidade em um ano (p=0,14). Conclusões ACEF-MDRD é um preditor de mortalidade em pacientes com IC e sua utilidade é comparável a modelos semelhantes, porém mais complicados.

Abstract: This study aimed to examine the relationship between the burnout of physicians and nurses and their moral sensitivity during the pandemic. This was a descriptive and correlational study. This study was carried out with physicians and nurses who were continuing to work actively during the pandemic. Snowboard sampling method was utilized. The total mean score of the participants on the MSQ was 90.78±19.10. The total mean score of the COVID-19 Burnout Scale was 34.52±9.65. A statistically weak and significant correlation was found between the COVID-19 Burnout Scale and the MSQ total score, as well as the “benefit” and “conflict” sub-dimensions. It was determined that as MSQ total scores, “benefit” and “conflict” scores decreased in healthcare workers, COVID-19 burnout scores increased. In our study, the moral sensitivity of the participants was found to be moderate, and their burnout levels were found to be high. Although there was a weak relationship, it was observed that burnout levels increased as moral sensitivity levels increased. It is crucial that we learn from pandemic experiences and transfer this knowledge to future generations. In particular, we must assimilate these important lessons into training in order to develop and protect the moral sensitivity of healthcare professionals.

Resumen: Este estudio pretendía examinar la relación entre el burnout de médicos y enfermeras y su sensibilidad moral durante la pandemia. Se trató de un estudio descriptivo y correlacional, y se llevó a cabo con médicos y enfermeras que seguían trabajando activamente durante la pandemia. Se utilizó el método de muestreo de Snowboard. La puntuación media total de los participantes en el MSQ fue de 90,78±19,10. La puntuación media total de la Escala de Burnout COVID-19 fue de 34,52±9,65. Se encontró una correlación estadísticamente débil y significativa entre la Escala de Burnout COVID-19 y la puntuación total del MSQ, así como las subdimensiones “beneficio” y “conflicto”. Se determinó que, a medida que disminuían las puntuaciones totales del MSQ y las puntuaciones de “beneficio” y “conflicto” en los trabajadores sanitarios, aumentaban las puntuaciones de burnout de la COVID-19. En nuestro estudio, se observó que la sensibilidad moral de los participantes era moderada y que sus niveles de burnout eran elevados. Aunque existía una relación débil, se observó que los niveles de burnout aumentaban a medida que lo hacían los de sensibilidad moral. Es crucial que aprendamos de las experiencias pandémicas y transmitamos estos conocimientos a las generaciones futuras. En particular, debemos asimilar estas importantes lecciones en la formación para desarrollar y proteger la sensibilidad moral de los profesionales sanitarios.

Resumo: Esse estudo objetivou examinar a relação entre o burnout de médicos e enfermeiras e sua sensibilidade moral durante a pandemia. Esse era um estudo descritivo e correlacional. Esse estudo foi realizado com médicos e enfermeiras que continuaram trabalhando ativamente durante a pandemia. O método da amostragem em snowboard foi utilizado. A média total dos participantes no MSQ foi 90,78±19,10. A média total na Escala de Burnout pela COVID-19 foi 34,52±9,65. Uma correlação fraca e significante foi encontrada entre os escores totais na Escalas de Burnout pela COVID-19 e MSQ, assim como nas subdimensões “benefício” e “conflito”. Determinou-se que como os escores totais na MSQ e os escores “benefício” e “conflito” diminuiram em trabalhadores de cuidados à saúde, os escores de burnout pela COVID-19 aumentaram. Em nosso estudo, a sensibilidade moral dos participantes foi considerada ser moderada e seus níveis de burnout considerados serem altos. Embora tenha havido uma correlação fraca, foi observado que os níveis de burnout aumentaram quando os níveis de sensibilidade moral aumentaram. É essencial que aprendamos das experiências com a pandemia e passemos esse conhecimento para as futuras gerações. Em particular, nós devemos assimilar essas importantes lições em treinamentos, de forma a desenvolver e proteger a sensibilidade moral de profissionais de cuidados à saúde.

ABSTRACT Introduction: The relationship between mitral annular calcification (MAC) and the controlling nutritional status (CONUT) score has not been previously studied. In this study, we investigated the relationship between MAC and CONUT score to evaluate the nutritional status of patients with MAC. Methods: A total of 275 patients, including 150 patients with MAC and 125 patients without MAC, who presented to a cardiology outpatient clinic were enrolled in the study. Results: There was no difference in the CONUT score between the two groups. Correlation analysis indicated that CONUT score was positively correlated with left atrial (LA) diameter (r=0.190, P=0.020) and interventricular septum thickness (r=0.179, P=0.028) in the MAC+ group. In multivariate regression analysis, only LA diameter (odds ratio 95% confidence interval = 1,054-1,189, P=0.0001) was independently associated with MAC. Conclusion: The present study investigated the relationship between CONUT score and MAC for the first time in the literature. We demonstrated that CONUT score was not significantly higher in patients with MAC without chronic diseases. However, CONUT score was correlated with LA diameter in patients with MAC. We therefore conclude that, for patients admitted with MAC and high LA diameter, CONUT is a valuable nutritional and inflammatory status index.

Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. Methods: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. Results: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

RESUMEN Introducción: Nuestro objetivo fue investigar el efecto de diferentes regímenes inmunosupresores sobre los niveles de SUPAR y ox-LDL, que son marcadores tempranos de inflamación en receptores de trasplante renal. Material y métodos: Un total de 83 pacientes se inscribieron en nuestro estudio. Mientras que cuarenta y ocho de ellos recibieron mTORi, treinta y cinco pacientes recibieron CNI. De acuerdo con el régimen inmunosupresor, los pacientes se dividieron en grupos receptores de CNI y m-TORi y se midieron los niveles séricos de SUPAR y ox-LDL. Resultados: Los valores de Log-SUPAR fueron menores en el grupo que recibió m-TORi (3,40 ± 0,1 vs 3,48 ± 0,4, p = 0,010). Los niveles de OxLDL/LDL fueron mayores (0,0168± 005 vs 0,0132 ±004, p=0,009) en el grupo CNI. En el análisis de regresión lineal, se detectó una relación estadísticamente significativa entre el uso de m-TORi y log-SUPAR (β = -0,052, IC del 95% [-0,224, -0,012], p = 0,041). Se encontró una relación negativa e independiente entre HT y log-SUPAR (β = -0.60, 95% IC--0.112, -0.018], p = 0.0024) y ox-LDL (β = -0.169 [-0.330, -0.008], p = 0,040). Se detectó una correlación muy fuerte (r = 1,0, p <0,001) y una relación independiente (β = 0,321 [0,313, 0,330], p <0,001) entre ox-LDL y SUPAR. Conclusión: Como resultado, cuando se comparó la inmunosupresión entre m-TORi y CNI, la primera se asoció con niveles más bajos de SUPAR y oxLDL.

ABSTRACT Introduction: We aimed to investigate the effect of different immunosuppressive regimens on SUPAR and ox-LDL levels which are early markers of inflammation in renal transplant recipients. Methods: A total number of 83 patients were enrolled in our study. While fourty- eight of those were received mTORi, thirty five patients were been receiving CNI. According to the immunosuppressive regimen patients were divided into CNI and m-TORi receving groups and serum SUPAR and ox-LDL levels were measured. Results: Log-SUPAR values were lower in the group receiving m-TORi (3.40 ± 0.1 vs 3.48 ± 0.4, p=0.010). OxLDL / LDL levels were higher (0.0168± 005 vs 0.0132 ±004, p=0.009) in the CNI group. In linear regression analysis, a statistically significant relationship was detected between the use of m-TORi and log-SUPAR (β = -0.052, 95% CI [-0.224, -0.012], p = 0.041) . A negative and independent relationship was found between HT and log-SUPAR (β = -0.60, 95% CI--0.112, -0.018], p=0.0024) and ox-LDL (β = -0.169 [-0.330, -0.008], p=0.040). Very strong correlation (r=1.0, p=<0.001) and independent relationship (β=0.321 [0.313,0.330], p=<0.001) was detected between ox-LDL and SUPAR. Conclusion: As a result, when compared immunsuppression between m-TORi and CNI, the former was associated with lower SUPAR and oxLDL levels.

Resumo Introdução O papiloma invertido nasossinusal é conhecido por sua alta taxa de recorrência. Os sistemas de estadiamento ajudam a reduzir a recorrência e evitar cirurgias excessivas e orientam a seleção da abordagem cirúrgica ideal. Objetivo Avaliar a eficácia de diferentes abordagens endoscópicas no papiloma invertido, de acordo com o local de origem e o volume do tumor. Método Para o estadiamento, usou-se o sistema de classificação de Krouse, baseado no volume do tumor; além disso, os tumores foram agrupados de acordo com seus locais de origem: parede nasal lateral, parede medial e outras paredes do seio maxilar. O principal método de tratamento para todos os pacientes foi a cirurgia endoscópica nasossinusal. Foram feitos, em diferentes combinações, os seguintes tipos de cirurgia: antrostomia estendida do meato médio, Caldwell-Luc endoscópica e maxilectomia medial endoscópica. Resultados Foram incluídos 55 pacientes (42 homens) com média de 54,9 ± 14,4 anos. Trinta e sete pacientes foram diagnosticados com papiloma invertido avançado (67,2%). Foi observada recorrência em 12 pacientes (21,8%). No estágio inicial com origem na parede nasal lateral, não foi observada recorrência no grupo de ressecção simples de tumor (0/10). No estágio inicial com origem na parede medial, não foi observada recorrência no grupo de antrostomia estendida do meato médio (0/8). Com tumor em estágio avançado com origem na parede medial, as taxas de recorrência na antrostomia estendida do meato médio, antrostomia estendida do meato médio + Caldwell-Luc endoscópica e maxilectomia medial endoscópica foram de 100,0%, 53,8% e 13,6%, respectivamente (p = 0,002). No tumor em estágio avançado em outras paredes do seio maxilar, as taxas de recorrência na antrostomia estendida do meato médio + Caldwell-Luc endoscópica e maxilectomia medial endoscópica foram de 20% e 16,6%, respectivamente (p = 0,887). Conclusão O local de origem do tumor, o estágio do tumor e os tipos de cirurgia mostram impacto na recorrência. Apesar da consideração de que na maioria dos casos o local de origem do tumor pode, de forma isolada, orientar a seleção apropriada do tipo de cirurgia, o estágio do tumor tem importância substancial na seleção do tipo de cirurgia para papiloma invertido nasossinusal. Um planejamento cirúrgico considerando tanto o volume quanto o local de origem do tumor pode ajudar os cirurgiões a selecionar o tipo ideal de cirurgia endoscópica para evitar recorrências ou remoções excessivas.

Abstract Introduction Sinonasal inverted papilloma is noted for its high rate of recurrence. Staging systems aid to reduce recurrence and avoid excessive surgeries by guiding the selection of the optimal surgical approach. Objective To evaluate the effectiveness of different endoscopic approaches in inverted papilloma by assessing tumor origin site and tumor volume. Methods Krouse classification system that is based on tumor volume was used for staging; furthermore, tumor origin sites were grouped as lateral nasal wall, medial wall and other walls of maxillary sinus. The main treatment method for all patients was endoscopic sinus surgery. Endoscopic extended middle meatal antrostomy, endoscopic Caldwell-Luc and endoscopic medial maxillectomy were the additional surgery types performed in different combinations. Results Fifty-five patients (42 male) with a mean 54.9 ± 14.4 years of age were included. 37 patients were diagnosed with advanced stage inverted papilloma (67.2 %). Recurrence was observed in 12 patients (21.8 %). In early stage lateral nasal wall origination, no recurrence was observed in the simple tumor resection group (0/10). In early stage medial wall origination, no recurrence was observed in the extended middle meatal antrostomy group (0/8). In advanced stage medial wall origination, the recurrence rates of extended middle meatal antrostomy, extended middle meatal antrostomy + endoscopic Caldwell- Luc and endoscopic medial maxillectomy were 100.0 %, 53.8 % and 13.6 %, respectively (p = 0.002). In advanced stage other walls of maxillary sinus origination, recurrence rates of extended middle meatal antrostomy + endoscopic Caldwell-Luc and endoscopic medial maxillectomy were 20 % and 16.6 %, respectively (p = 0.887). Conclusion Tumor origin site, tumor stage and surgery types show an impact on recurrence. Despite the fact that tumor origin site singly could lead to appropriate selection of the surgery type in most cases, tumor stage carries substantial importance in selection of surgery type for sinonasal-inverted papilloma. An operation plan regarding both tumor volume and tumor origin site may aid surgeons in selecting optimal endoscopic surgical method to avoid recurrence or excessive surgeries.

RESUMO OBJETIVO: Ao trabalhar em áreas de radiação, trabalhadores descrevem muitos sintomas físicos e mentais. Este estudo teve como objetivo avaliar esses sintomas em trabalhadores expostos à radiação utilizando a Escala de Ansiedade de Beck (BAI - Beck Anxiety Inventory). MÉTODOS: Um total de 42 trabalhadores expostos à radiação (22 homens e 20 mulheres, com idade média de 34±7 anos) e 47 controles (22 do sexo masculino e 27 do sexo feminino, com idade média de 31±8 anos) que trabalham em áreas do hospital sem radiação foram incluídos no estudo. Todos os participantes responderam anonimamente ao questionário da BAI. RESULTADOS: Os dados demográficos dos trabalhadores dos dois grupos não apresentaram diferenças significativas. Na BAI, os itens de tonturas ou vertigens (p =0,01), medo (p= 0,01), instabilidade (p=0,02) e batimento cardíaco mais forte e acelerado (p=0,02) foram significativamente mais elevados no grupo exposto à radiação em comparação ao grupo de controle. A pontuação da BAI também foi significativamente maior no grupo exposto à radiação (11,1 ± 6,8 versus 8,7 ± 3,8, p = 0,04). CONCLUSÃO: Esses resultados sugerem a possibilidade de que a radiação pode desempenhar um papel importante nas propriedades psicométricas dos trabalhadores. Os efeitos da radiação na saúde dos funcionários precisam ser mais bem investigados e compreendidos.

SUMMARY OBJECTIVE: Workers describe many physical and mental symptoms when working in radiation areas. This study aimed to assess these symptoms in radiation workers using the Beck Anxiety Inventory (BAI). METHODS: A total of 42 radiation workers (22 males and 20 females, mean age 34±7 years) and 47 control subjects (22 males and 27 females, mean age 31± 8 years) who work in non-radiation areas in the hospital were included in the study. All participants anonymously filled out the Beck Anxiety Inventory (BAI) questionnaire. RESULTS: The demographic data of workers were not significantly different between groups. In the BAI, the dizzy or lightheaded (p =0.01), terrified (p= 0.01), unsteady (p=0.02), heart-pounding and racing (p=0.02) items were significantly higher in the radiation-exposed group compared to the control group. |The BAI score was also significantly higher in the radiation-exposed group (11.1±6.8 vs. 8.7±3.8, p =0.04) CONCLUSION: These results suggest the possibility that radiation may play a role in the psychometric properties of workers. The effects of radiation on the health of employees need to be further investigated and understood.

Abstract INTRODUCTION: Sepsis is an important cause of mortality and morbidity, and inflammatory response and oxidative stress play major roles underlying its pathophysiology. Here, we evaluated the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats. METHODS: Twenty-eight adult Sprague Dawley rats were classified into Control (Group 1), Sepsis (Group 2), Sepsis+Cefazolin (Group 3), and Sepsis+Cefazolin+Etanercept (Group 4) groups. Kidney tissue and serum samples were obtained for biochemical and histopathological investigations and examined for the C reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), triggering receptor expressed on myeloid cells (TREM), and malondialdehyde (MDA) levels. RESULTS: The levels of TNF-α, TREM, and MDA in serum and kidney samples were significantly higher in rats from sepsis group than in rats from control group (p < 0.05). Group 3 showed a significant reduction in serum levels of TNF-α, CRP, and TREM as compared with Group 2 (p < 0.05). Serum TNF-α, CRP, TREM, and MDA levels and kidney TNF-α and TREM levels were significantly lower in Group 4 than in Group 2 (p < 0.05). Serum TNF-α and TREM levels in Group 4 were significantly lower than those in Group 3, and histopathological scores were significantly lower in Group 3 and Group 4 than in Group 2 (p < 0.05). Histopathological scores of Group 4 were significantly lower than those of Group 3 (p < 0.05). CONCLUSIONS: Etanercept, a TNF-α inhibitor, may ameliorate sepsis-induced oxidative stress, inflammation, and histopathological damage.

SUMMARY: Mobile phone use has increased rapidly. The central nervous system has been shown to be adversely affected by its electromagnetic field (EMF) resulting in headache and sleep disturbances. How the cells make up the CNS and are affected by EMF is unclear. However, because of their central role in inflammation through diverse stimuli including radiation, this study aimed to investigate the effects of electromagnetic fields induced by mobile phones on mast cells in rat dura mater. A total of 18 adult, female, SpragueDawley rats were divided into two groups. The choice of female rats for his study was based on recent surveys demonstrating that mobile phone use is more frequent and prolonged among females. The study group was exposed to 900 MHz electromagnetic field (1 h/day for 45 days). In the end of the study, duramater tissue was extracted and stained using Toluidine blue. Mast cells were counted and results were analysed using Student t test. Mean mast cell number was 202.33±9.82 and 456.78±35.01 in the control and study groups, respectively (p<0.05). Analysis of serum electrolyte and immunoglobulin E levels showed no statistically significant difference between the two groups (p>0.05). The study showed that mobile phone exposure increased mast cell number and degranulation in rat dura mater. Further studies are required to evaluate the clinical implications of these findings.

RESUMEN: El uso del teléfono móvil ha aumentado rápidamente. Se ha demostrado que el sistema nervioso central (SNC) se ve afectado de manera adversa debido al campo electromagnético (CEM) que produce dolor de cabeza y trastornos del sueño. No está claro cómo se ve afectada la composición celular del SNC por el CEM. Sin embargo, debido a su función principal en la inflamación a través de diversos estímulos que incluyen la radiación, este estudio tuvo como objetivo investigar los efectos de los campos electromagnéticos inducidos por los teléfonos móviles en los mastocitos de la duramadre de ratas. Un total de 18 ratas Sprague-Dawley adultas, hembras, se dividieron en dos grupos. Se usaron ratas hembras para este estudio en base a investigaciones recientes que han demostrado que el uso de teléfonos móviles es más frecuente y prolongado en las mujeres. Los grupos de estudio fueron expuestos a un campo electromagnético de 900 MHz (1 h / día durante 45 días). Al término del estudio, fue extirpado el tejido de la duramadre y teñido con azul de toluidina. Se contaron los mastocitos y se analizaron los resultados utilizando la prueba t de Student. La cantidad media de células cebadas fue de 202,33 ± 9.82 y 456,78 ± 35,01 en los grupos control y estudio, respectivamente (p <0,05). El análisis del electrolito sérico y los niveles de inmunoglobulina E no mostraron diferencias estadísticamente significativas entre los dos grupos (p> 0,05). El estudio mostró que la exposición a teléfonos móviles aumentó el número de mastocitos y la desgranulación en la duramadre de las ratas. Se requieren estudios adicionales para evaluar las implicaciones clínicas de estos hallazgos.

Caper (Capparis ovata Desf. and Capparis spinosa L.) is naturally widespread in Turkey. Traditionally, buds, fruits, seeds and roots of this plant are used as tonic, diuretic, anti-rheumatic, expectorant, antidiabetic, and antifungal. The aim of this study is to evaluate potential hypoglycemic effect of C. ovata var. palaestina extracts in alloxan-induced diabetic mice. For this purpose; diabetic mice were administered with 100, 300, 500 mg/kg (i.p.) doses of methanol extract of bud and fruit. Blood glucose levels were screened 60, 120, 240 and 360 min. after treatment. Furthermore, high resolution mass spectrometry (HRMS) analysis, ABTS and DPPH free radical scavenging activity test, and phenolic and flavonoid compounds analysis of extracts were carried out. The data obtained from in vivo study revealed that fruit-methanol 500 mg/kg (FM3), bud-methanol 300 mg/kg (BM2), bud-methanol 500 mg/kg (BM3) extracts showed significant hypoglycemic activity. All extracts indicated significant antioxidant activity, however bud-methanol (BM) extract demonstrated the most potent antioxidant activity. Moreover high levels of phenolic substances and flavonoids were involved in all extracts, but the highest levels were found in FM extract. HRMS study showed that rutin, quercetin 3-O-glucoside (isoquercitrin) and stachydrine substances had seen in BM extract. The results of this study showed that the C. ovata var. palaestina extracts which, indicate hypoglycemic, antioxidant activities, might provide additional support in diabetes.

Abstract Purpose: To evaluate the efficacy of nivolumab and comparison with dacarbazine (DTIC) on peritoneal carcinomatosis of malignant melanoma in mouse model. Methods: Mouse skin melanoma cells was injected under the capsule of the peritoneal surface in the left side of the abdomen. On postoperative day ten, mouses randomised into three groups. Group 1: Control, Group 2: HIPEC (Hyperthermic intraperitoneal chemotherapy) with DTIC and Group 3: HIPEC with Nivolumab. After the sacrification on postoperative day fifteen, peritoneum evaluated macroscopically and histopathologically by using peritoneal regression grading score (PRGS). Results: In the 15th day exploration, all animals developed extensive intraperitoneal tumor growth in Group 1. In Group 2 and Group 3 median tumor size was 0.7±0.3cm and 0.3±0.2cm respectively (p: 0.023). Peritoneal carcinomatosis index (PCI) were significantly lower in Group 3 than other groups (p: 0.019). The lowest total tumor nodules in group 3 was 4 ± 2. The PGRS score was found significantly lower in Group 3 than other groups (p: 0.03). Lymphocytic response rate was found higher in the Group 3. Conclusions: It has been found that nivolumab significantly better than DTIC on peritoneal metastases of malign melanoma in mouse models. Nivolumab treatment gives promising results with pathological evidence in the treatment of metastatic disease of malignant melanoma.

Resumo Justificativa: O objetivo deste estudo foi investigar os efeitos do brometo de rocurônio administrado intracerebroventricularmente sobre o sistema nervoso central, determinar a dose do limiar convulsivo de rocurônio em ratos e investigar os efeitos de rocurônio no sistema nervoso central em diluições de 1/5, 1/10 e 1/100 da dose do limiar convulsivo determinada. Métodos: Uma cânula permanente foi colocada no ventrículo lateral do cérebro dos animais. O estudo foi projetado em duas fases. Na primeira, a dose do limiar convulsivo do brometo de rocurônio foi determinada. Na segunda, o Grupo R 1/5 (n = 6), o Grupo 1/10 (n = 6) e Grupo 1/100 (n = 6) foram formados com doses de 1/5, 1/10 e 1/100, respectivamente, da dose do limiar convulsivo de brometo de rocurônio obtida. Resultados: Descobrimos que o valor do limiar convulsivo de brometo de rocurônio é 0,056 ± 0,009 µmoL. O limiar convulsivo, como uma função do peso corporal dos ratos, foi calculado como 0,286 µmoL/kg-1. Uma dose de 1/5 da dose do limiar convulsivo causou principalmente abertura postural dos membros e tremores em todo o corpo, enquanto uma dose de 1/10 da dose do limiar convulsivo causou agitação e tremores. Uma dose de 1/100 da dose do limiar convulsivo foi associada à diminuição da atividade locomotora. Conclusões: Este estudo mostrou que o brometo de rocurônio tem efeitos deletérios relacionados com a dose sobre o sistema nervoso central e pode produzir efeitos excitatórios dependentes da dose e convulsões.

Abstract Background: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. Methods: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n = 6), Group 1/10 (n = 6), and Group 1/100 (n = 6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. Results: The rocuronium bromide seizure threshold value was found to be 0.056 ± 0.009 µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286 µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. Conclusions: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.