(-)-Carvone Inhibits Oxytocin-induced Writhing Via Uterine Relaxation in Rodents.

(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.

Clinical Correlation of Transcription Factor SOX3 in Cancer: Unveiling Its Role in Tumorigenesis.

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular modelsBy providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

DORSALIS PEDIS NEUROVASCULAR FLAP, OUR EXPERIENCE.

Objectives: Analyze the donor site morbidity of the dorsalis pedis neurovascular flap in traumatic injuries with hand tissue loss. Material and Methods: The study involved dorsalis pedis neurovascular flaps that were used to reconstruct the hands of eight male patients, between 1983 and 2003, aged between 21 and 53 years (mean 34.6, SD ± 10.5 years). The size of the lesions ranged from 35 to 78 cm2 (mean 53, SD ± 14.4 cm2). Surgical procedures were performed two to 21 days after the injuries had occurred. The patients were followed up for an average of 10.3 years (ranging 8-14, SD ± 2.1 years). Results: Regarding the donor site, in one case there was hematoma formation, which was drained; in another case, the skin graft needed to be reassessed. All patients experienced delayed healing, with complete healing from 2 to 12 months after the surgery (mean 4.3, SD ± 3.2 months). Conclusion: Despite the advantages of the dorsalis pedis neurovascular flap, we consider that the sequelae in the donor site is cosmetically unacceptable. Nowadays, this procedure is only indicated and justified when associated with the second toe transfer. Level of Evidence IV; Case series .

Objetivos: Analisar a morbidade da área doadora do retalho neurovascular do dorso do pé em lesões traumáticas com perda de tecido da mão. Material e métodos: O estudo envolveu retalhos neurovasculares do dorso do pé usados para reconstruir as mãos de oito pacientes do sexo masculino, entre 1983 e 2003, com idades entre 21 e53 anos (média de 34,6, DP ± 10,5 anos). O tamanho das lesões variou de 35 a 78 cm2 (média de 53, DP ± 14,4 cm2). Os procedimentos cirúrgicos foram realizados entre dois a 21 dias após a ocorrência das lesões. Os pacientes foram acompanhados por uma média de10,3 anos (variando de 8 a 14, DP ± 2,1 anos). Resultados: Quanto ao local doador, em um caso houve formação de hematoma, que foi drenado; em outro caso, o enxerto de pele precisou ser reavaliado. Todos os pacientes apresentaram retardo na cicatrização, com cicatrização completa de 2 a 12 meses após a cirurgia (média de 4,3, DP ± 3,2 meses). Conclusão: Apesar das vantagens do retalho neurovascular do dorso do pé, consideramos que as sequelas no local doador são cosmeticamente inaceitáveis. Atualmente, esse procedimento só é indicado e justificado quando associado à transferência do segundo dedo do pé. Nível de evidência IV; Série de casos .

Análise da assistência prestada na atenção primária e fatores associados na perspectiva de idosos diabéticos / Analysis of the assistance provided in primary care and associated factors from the perspective of elderly patients with diabetes / Análisis de la asistencia proporcionada en atención primaria y factores asociados desde la perspectiva del anciano con diabetes

A atenção primária à saúde é fundamental para validar a atenção à saúde de idosos diabéticos, sendo importante sua qualificação por meio de abordagens que evidenciem as perspectivas dos usuários. Neste trabalho, objetivou-se analisar os aspectos associados à satisfação com a assistência prestada no âmbito da atenção primária na perspectiva de idosos com diabetes. Trata-se de um estudo quantitativo, de corte transversal, realizado com 37 idosos diabéticos cadastrados na Estratégia Saúde da Família de um município do estado do Paraná. Aplicou-se um instrumento adaptado que continha questões sobre a caracterização sociodemográfica e clínica, a assistência prestada ao usuário e a satisfação com o atendimento recebido. Os dados foram submetidos à análise descritiva utilizando frequências absolutas e relativas. A avaliação positiva/intermediária da assistência prevaleceu em 70,3% dos entrevistados. Os fatores que apresentaram relação foram: aferição da pressão arterial (100%) e da glicemia capilar (80,77%); ausculta cardíaca (76,92%); oferecimento de antidiabéticos orais/insulina (84,62%) e de orientações sobre seu uso (69,23%), sobre a doença e formas de tratamento (69,23%), sobre complicações (65,38%), sobre a importância da prática de atividade física (61,54%) e de uma alimentação adequada (61,54%); questionamento sobre a saúde e o diabetes (76,92%); percepção do interesse profissional em perguntar sobre o tratamento medicamentoso (92,31%) e sua frequência (84,62%), em compreender, acolher e esclarecer preocupações, dúvidas ou problemas com o diabetes (84,62%) e em dar tempo suficiente para o paciente se expressar (84,62%). Os resultados reforçam a importância da promoção da saúde permeada pelo acolhimento e pelo diálogo sobre boas práticas em saúde, além de uma avaliação clínica de qualidade e oferta de subsídios necessários ao tratamento da doença.

The primary health care is fundamental to validate the health care of elderly diabetics, and it is important to qualify it with approaches that show the perspectives of users. In this work, the objective was to analyze aspects associated with satisfaction with the care provided in the context of primary care from the perspective of elderly people with diabetes. This is a quantitative, cross-sectional study conducted with 37 elderly diabetics registered in the Family Health Strategy in a municipality in the state of Paraná. An adapted instrument was applied, including questions about the sociodemographic and clinical characterization, the assistance provided to the user, and the satisfaction with the care received. Data were submitted to descriptive analysis using absolute and relative frequencies. The positive/intermediate assessment of care prevailed in 70.3% of respondents. The factors that were related were: blood pressure measurement (100%) and capillary blood glucose (80.77%), cardiac auscultation (76.92%); offer of oral antidiabetics/insulin (84.62%), and guidance on their use (69.23%), on the disease and forms of treatment (69.23%), complications (65.38%), importance of physical activity (61.54%), and proper nutrition (61.54%); questioning about health and diabetes (76.92%); perception of professional interest in questioning drug treatment (92.31%), and its frequency (84.62%), in understanding, welcoming, and clarifying concerns, doubts, or problems with diabetes (84.62%), and giving enough time for the patients to express themselves (84.62%). The results reinforce the importance of health promotion permeated by acceptance and dialogue about good health practices, in addition to a clinical quality assessment and the provision of subsidies relevant to the treatment of the disease.

La atención primaria de salud es fundamental para validar la atención a la salud de los ancianos diabéticos, y es importante calificarla mediante enfoques que muestren las perspectivas de los usuarios. El objetivo de este trabajo fue analizar los aspectos asociados a la satisfacción con la atención prestada en el contexto de la atención primaria en la perspectiva de los ancianos con diabetes. Se trata de un estudio cuantitativo, transversal, realizado con 37 ancianos diabéticos afiliados a la Estrategia de Salud Familiar, que actúa en un municipio del estado de Paraná (Brasil). Se aplicó un instrumento adaptado que contenía preguntas sobre la caracterización sociodemográfica y clínica, la asistencia prestada al usuario y la satisfacción con la atención recibida. Los datos se sometieron a análisis descriptivo utilizando frecuencias absolutas y relativas. La valoración positiva/intermedia del cuidado predominó en el 70,3% de los encuestados. Los factores que se relacionaron fueron: Medición de la presión arterial (100%) y glucemia capilar (80,77%); auscultación cardiaca (76,92%); recibir antidiabéticos orales/insulina (84,62%) y orientación sobre su uso (69,23%), sobre enfermedad y formas de tratamiento (69,23%), sobre complicaciones (65,38%), sobre la importancia de la actividad física (61,54%) y de nutrición adecuada (61,54%); cuestionamiento sobre salud y diabetes (76,92%); percepción del interés profesional en cuestionar el tratamiento farmacológico (92,31%) y su frecuencia (84,62%) en comprender, acoger y aclarar inquietudes, dudas o problemas con la diabetes (84,62%) y darse tiempo suficiente para expresarse (84,62%). Los resultados demuestran la importancia de la promoción de la salud permeada por la aceptación y el diálogo sobre buenas prácticas de salud, además de una evaluación de la calidad clínica y la provisión de subsidios pertinentes al tratamiento de la enfermedad.

Isolated Area Postrema Syndrome Preceding the Diagnosis of Giant Cell Arteritis: A Case Report.

OBJECTIVE: We report a case of biopsy-proven giant cell arteritis after an initial presentation of area postrema syndrome. METHODS: A 65-year-old man was evaluated using MRI, temporal artery biopsy, and ultrasound. RESULTS: The patient presented with refractory nausea, vomiting, and hiccups that caused weight loss without any other neurologic or clinical symptoms. His MRI scan 15 days later revealed a hyperintense sign on the area postrema with no abnormal diffusion or contrast enhancement, compatible with isolated area postrema syndrome. An extensive workup for inflammation and other etiologies including neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disorder, and multiple sclerosis (MS) showed negative results. The patient responded to treatment with methylprednisolone. Two months after the initial clinical manifestation, the patient developed fatigue, headache, and scalp tenderness. He was diagnosed with giant cell arteritis after ultrasonography and biopsy were performed. He responded well to oral glucocorticoids and had only 1 relapse during tapering. He has not had arteritic ischemic optic neuropathy or any new episodes of area postrema syndrome. DISCUSSION: This case demonstrates the importance of expanding the differential diagnosis in patients with area postrema syndrome and no other signs of NMOSD.

Antitumor effect of selenium-rich Brazil nuts and selenomethionine dietary supplementation on pre-existing 4T1 mammary tumor growth in mice.

Selenium (Se) is an essential micronutrient known to play an important role in the antioxidant system that can potentially influence tumor growth. We aimed to investigate the effects of dietary Se supplementation after detection of 4T1 mammary tumor growth in BALB/c mice. Thirty female mice received subcutaneous inoculation of 4T1 cells. After five days, all animals presenting palpable tumors were randomly assigned to three groups: a control group (Se-control) receiving a diet with adequate Se (0.15 mg/kg) and two other groups that received Se-supplemented diets (1.4 mg/kg of total Se) with either Brazilian nuts (Se-Nuts) or selenomethionine (SeMet). Data were assessed by either One or Two-way ANOVA followed by Tukey's HSD or Bonferroni's post hoc tests, respectively. Both Se-supplemented diets reduced tumor volume from the thirteenth day of feeding compared with the Se-adequate (control) diet (p < 0.05). The SeMet group presented a higher Se blood concentration (p < 0.05) than the Se-control group, with the Se-Nuts group presenting intermediate values. Selenoprotein P gene expression in the liver was higher in the Se-Nuts group than in the Se-control group (p < 0.05), while the SeMet group presented intermediate expression. Dietary Se supplementation, starting after detection of 4T1 palpable lesions, reduced tumor volume in mice.

Health risk assessment and differential distribution of Arsenic and metals in organs of Urophycis brasiliensis a commercial fish from Southwestern Atlantic coast.

The concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, and Zn were analyzed in muscle, gills, and liver of Urophycis brasiliensis from two Southwestern Atlantic catch areas (Brazil and Argentina). Additionally, the health risk of general and fishermen populations through fish consumption was estimated. The gills showed the highest concentrations of most of the elements, followed by the liver. With the exception of As, the muscle was the organ with the lowest concentrations of most elements. Levels of arsenic in muscle of U. brasiliensis were exceeded the maximum permissible levels for human consumption recommended by local and international guidelines. The target hazard quotients (THQs) and the carcinogenic risk (CR) showed no risk for individual and all elements. These results highlight the importance of arsenic speciation in U. brasiliensis muscle in order to generate more reliable risk estimates.

Dorsalis pedis neurovascular flap, our experience / Retalho neurovascular dorsal do pé, nossa experiência

ABSTRACT Objectives: Analyze the donor site morbidity of the dorsalis pedis neurovascular flap in traumatic injuries with hand tissue loss. Material and Methods: The study involved dorsalis pedis neurovascular flaps that were used to reconstruct the hands of eight male patients, between 1983 and 2003, aged between 21 and 53 years (mean 34.6, SD ± 10.5 years). The size of the lesions ranged from 35 to 78 cm2 (mean 53, SD ± 14.4 cm2). Surgical procedures were performed two to 21 days after the injuries had occurred. The patients were followed up for an average of 10.3 years (ranging 8-14, SD ± 2.1 years). Results: Regarding the donor site, in one case there was hematoma formation, which was drained; in another case, the skin graft needed to be reassessed. All patients experienced delayed healing, with complete healing from 2 to 12 months after the surgery (mean 4.3, SD ± 3.2 months). Conclusion: Despite the advantages of the dorsalis pedis neurovascular flap, we consider that the sequelae in the donor site is cosmetically unacceptable. Nowadays, this procedure is only indicated and justified when associated with the second toe transfer. Level of Evidence IV; Case series .

RESUMO Objetivos: Analisar a morbidade da área doadora do retalho neurovascular do dorso do pé em lesões traumáticas com perda de tecido da mão. Material e métodos: O estudo envolveu retalhos neurovasculares do dorso do pé usados para reconstruir as mãos de oito pacientes do sexo masculino, entre 1983 e 2003, com idades entre 21 e53 anos (média de 34,6, DP ± 10,5 anos). O tamanho das lesões variou de 35 a 78 cm2 (média de 53, DP ± 14,4 cm2). Os procedimentos cirúrgicos foram realizados entre dois a 21 dias após a ocorrência das lesões. Os pacientes foram acompanhados por uma média de10,3 anos (variando de 8 a 14, DP ± 2,1 anos). Resultados: Quanto ao local doador, em um caso houve formação de hematoma, que foi drenado; em outro caso, o enxerto de pele precisou ser reavaliado. Todos os pacientes apresentaram retardo na cicatrização, com cicatrização completa de 2 a 12 meses após a cirurgia (média de 4,3, DP ± 3,2 meses). Conclusão: Apesar das vantagens do retalho neurovascular do dorso do pé, consideramos que as sequelas no local doador são cosmeticamente inaceitáveis. Atualmente, esse procedimento só é indicado e justificado quando associado à transferência do segundo dedo do pé. Nível de evidência IV; Série de casos .

Epithelial-mesenchymal transition inhibition by metformin reduces melanoma lung metastasis in a murine model.

Melanoma is an aggressive cancer with fast metastatic spread and reduced survival time. One common event during the neoplastic progression is the epithelial-mesenchymal transition (EMT), which enhances invasiveness, cell migration, and metastasis. In this study, we investigated the effects of metformin at EMT in melanoma cell lines B16-F10 and A-375, in vitro, and the impact of EMT downregulation on melanoma progression in vivo. The metformin cells treatment reduces the migration potential in vitro and reduced the development of pulmonary metastases and the expressions of N-cadherin, vimentin, ZEB1, and ZEB2 at the metastases site, in vivo. These results indicate that metformin can promote EMT downregulation impairing the metastatic potential of melanoma cells.

Diffuse spinal cord metastasis after resection of SMARCB1 sinonasal carcinoma manifesting with a right foot drop-a case report.

INTRODUCTION: The sinonasal carcinoma are rare tumors of the head and neck. The undifferentiated sinonasal carcinoma subtypes are constantly being explored and new mutations, with different prognosis markers and biological behaviors are being described. The SMARCB1 negative sinonasal carcinoma subtypes have been recently described with few reports of leptomeningeal and spinal cord invasion. CASE PRESENTATION: This study presents the case of a 59-year-old woman, with no previous disease, presenting initially with epistaxis that evolved to cranial nerve deficits and a left eye complete oftalmoplegia. After diagnostic investigation, she had a diagnosis of a left ethmoid sinus sinonasal carcinoma. Following resection of the tumor, she evolved with a right foot drop that eventually has been linked to diffuse spinal cord impairment. The histopathological diagnosis confirmed a SMARCB1 negative sinonasal carcinoma. Due to the diffuse metastasis, she underwent palliative care and died eight months after the surgery. DISCUSSION: Spinal cord metastasis may manifest with different clinical signs. Our case shows a rare manifestation of SMARCB1-deficient sinonasal carcinoma, a new subtype of sinonasal carcinoma, summarizing the importance of a high grade of suspicion of spinal cord invasion on these patients. SMARCB1 sinonasal carcinomas are rare new tumors of the head and neck, whose biological behaviors are yet to be explored. To the best of our knowledge, this is one of the few case reports describing simultaneous spread of this tumor to the central nervous system and spinal cord.

Management of the positive sentinel lymph node following neoadjuvant chemotherapy: results of a survey conducted with breast surgeons.

Introduction: Despite the lack of randomised evidence, there is a current trend towards omitting axillary surgery in cases of positive sentinel lymph node (SLN) following neoadjuvant chemotherapy (NACT). This study evaluated practice patterns of Brazilian breast surgeons when managing positive SLN following NACT. Methods: This was a nationwide electronic survey of breast surgeons affiliated with the Brazilian Society of Mastology. Management approaches for positive SLN after NACT (axillary dissection (AD), regional nodal irradiation (RNI) or no additional treatment) were evaluated as a function of residual disease volume in the SLN (macro-metastasis, micro-metastasis or isolated tumour cells (ITC)). Results: Survey response rate was 49%, with 799/1,627 questionnaires returned. Most respondents were <50 years old (61%), lived in south-eastern Brazil (50%), in a major city (67%), worked in an academic institute (80%) and were board-certified (80%). AD recommendation rate decreased according to residual nodal disease volume: 91% of respondents recommended AD for cases of macro-metastasis, 64% for micro-metastasis and 38% for ITC (p < 0.00001). Furthermore, 35% would recommend no additional surgery for micro-metastasis, while 27% would recommend no treatment at all for ITC (p < 0.00001). Not working in an academic institute was associated with RNI for micro-metastasis (p = 0.02), but not for macro-metastasis or ITC. Being board-certified did not affect axillary management. Conclusion: Most respondents would recommend AD and/or RNI in residual nodal disease following NACT irrespective of disease volume. Nevertheless, a trend towards surgical de-escalation was found with low-volume disease (micro-metastasis and ITC). Ongoing randomised trials will clarify the impact of this trend.

Citizen science as a tool for understanding the silent dispersion of toadfish Opsanus beta (Goode and Bean, 1880).

Citizen science is an excellent tool in studies of the spatial distribution of non-native species. In Brazil, Opsanus beta has recently been introduced. Studies indicate the occurrence of this species in five estuaries off the Brazilian coast (Guanabara Bay, Sepetiba Bay, Santos Bay, Paranaguá Estuarine Complex and Guaratuba Bay). The present study aims to understand the dispersion of this species on the Brazilian coast through citizen science. Between January and May 2021, information about O. beta was weekly posted in 32 recreational fishing Facebook groups. Sixty-five fishers reported catches of O. beta in estuaries (Guanabara Bay, Sepetiba Bay, Santos Bay and Paranaguá Estuarine Complex). In addition, there were reports from other shallow areas outside adjacent estuaries (Bertioga and Peruíbe, in Sao Paulo State) and the first occurrence record for Laguna (Santa Catarina State), a southern estuarine zone (28° 29' 45″ S to 48° 45' 36″ W). In four estuaries along the Brazilian coast where O. beta was recorded, there are internal ports that trade with countries from the Gulf of Mexico and Caribbean Sea (species original range), indicating ballast water as a possible introduction route. In Laguna, the introduction may have occurred by maritime cabotage services. The reproductive capacity, the aquarists' interest, the absence of introduction policies aimed at this species and the cabotage fleet transportation may be factors that help further extend the dispersal of O. beta on the Brazilian coast.

Canine and feline uveal melanocytic tumours: Histologic and immunohistochemical characteristics of 32 cases.

OBJECTIVE: Gross, histopathological, and immunohistochemical characteristics of uveal melanocytic neoplasms in dogs and cats were investigated. SAMPLES: Thirty-two enucleated globes with uveal melanocytic neoplasms, 27 from dogs and 5 from cats, were examined. PROCEDURES: Morphological characteristics of uveal melanocytic neoplasms in dogs and cats were evaluated with anti-PNL2, anti-Melan-A, anti-Ki-67, anti-caspase-3, and anti-BAP1 immunomarkers. Statistical analysis was performed to compare canine melanocytomas and melanomas. RESULTS: The 32 uveal neoplasms were classified as melanocytomas (19/27 in dogs) or melanomas (8/27 in dogs, 5/5 in cats). Most tumours (84%) were located in the anterior uvea. Neoplastic cells were classified as epithelioid, spindle-shaped, mixed, or special type (balloon and signet ring cells). The percentage of cells with melanin, melanin concentration within cells, anisocytosis and anisokaryosis, mitotic count, lymphocytic inflammation, necrosis, vascular invasion, and glaucoma were also characterized. Anisocytosis, percentage of neoplastic cells with melanin, mitotic count, and indices (proliferation and apoptotic) varied significantly between canine uveal melanomas and melanocytomas; in general, melanomas had greater cell variability, were less pigmented, and had a higher mitotic count. The melanocytic origin of the neoplasms was confirmed by positive anti-PNL2 immunolabelling (29/32) and positive anti-Melan-A immunolabelling (3/32). In canine uveal melanomas, anisocytosis and anisokaryosis correlated with less pigmentation and minimal pigmentation correlated with a high percentage of immunolabelling for caspase-3. CONCLUSIONS: Uveal melanocytomas were more common in dogs, and uveal melanomas were more frequent in cats. Anisocytosis, percentage of neoplastic cells with melanin, and mitotic count are important histologic characteristics of malignancy to evaluate in uveal melanocytic neoplasms. The proliferation and apoptotic indices are relevant when comparing malignant tumours with benign tumours.

The Attitudes of Brazilian Breast Surgeons on Axillary Management in Early Breast Cancer-10 Years after the ACOSOG Z0011 Trial First Publication.

PURPOSE: To evaluate the impact of the ACOSOG Z0011 trial on axillary breast cancer surgery management in Brazil following publication of that study (2010) and again in 2020. PATIENTS AND METHODS: A survey of members of the Brazilian Society of Mastology. RESULTS: Of 1627 breast surgeons, 799 (49.1%) completed and returned the questionnaire. For patients with the Z11 inclusion criteria, following detection of a positive sentinel lymph node (SLN), axillary dissection (AD) was recommended by 99.2% of respondents before publication of the study, 47.5% in 2010 and 18.5% in 2020 (p < 0.001). In breast-conserving surgery, if there were micro-metastases, 2.6% would perform AD, 30.3% axillary radiotherapy, and 67.1% no additional axillary treatment, while with macro-metastases, these proportions were 21.3%, 52.2%, and 26.5%, respectively. In cases of mastectomy and of nodal extracapsular extension, 43.4% and 36% of surgeons, respectively, recommended AD. For clinically negative axilla and suspicious findings at ultrasonography, 69% of the surgeons would apply the Z11 approach. Most applied the Z11 criteria in cases of younger patients (83.6%) and triple-negative and/or HER2 positive tumors (74%). AD was significantly more likely to be recommended by surgeons who did not work in academic institutes, who worked in locations other than capital cities, who were not board-certified, and who were ≥ 50 years old. CONCLUSIONS: This survey revealed substantial changes in axillary surgery management in cN0/pathologically positive SLN, particularly following publication of the updated Z11 results and other similar studies. A better education environment and long-term follow-up were factors associated with the incorporation of Z11-related changes in practice.

Bifidobacterium longum subsp. longum 51A attenuates intestinal injury against irinotecan-induced mucositis in mice.

Intestinal mucositis (IM) is a critical side-effect associated with antineoplastic therapy. Treatment available is only palliative and often not effective. However, alternative therapeutic strategies, such as probiotics, have attracted significant attention due to their immune-modulatory action in several diseases. Thus, the present study aims to elucidate the therapeutic potential of the probiotic strain Bifidobacterium longum 51A in a murine model of mucositis induced by irinotecan. Due to the scarcity of studies on dose-response and viability (probiotic vs paraprobiotic), we first evaluated which dose and cell viability would be most effective in treating mucositis. In this study, the oral pretreatment with viable B. longum 51A at a concentration of 1 × 109 CFU/mL reduced the daily disease activity index (p < 0.01), protected the intestinal architecture, preserved the length of the intestine (p < 0.05), and reduced intestinal permeability (p < 0.01), inflammation, and oxidative damage (p < 0.01) induced by irinotecan. Also, treatment with B. longum 51A increased the production of secretory immunoglobulin A (p < 0.05) in the intestinal fluid of mice with mucositis. Furthermore, B. longum 51A reversed the mucositis-induced increase in Enterobacteriaceae bacterial group in the gut (p < 0.01). In conclusion, these results showed that oral administration of B. longum 51A protects mice against intestinal damage caused by irinotecan, suggesting its use as a potential probiotic in therapy during mucositis.

The impact of stressors and overload on informal caregivers of patients with cirrhosis: The first use of the Burden Scale for Family Caregivers in Brazil.

INTRODUCTION: Cirrhosis affects liver functions and compromises much of the body's organs. The significant increase in chronic diseases, including cirrhosis, has led to changes in medical practice and health systems, leading the informal caregiver to play a major role because of family ties or some level of proximity to the patient, assuming daily care function. However, the burden generated by informal caregivers for uninterrupted care is present at different levels (physical, mental, social, professional, and financial) and even in the prognosis of the patient. OBJECTIVE: The present study aims to evaluate the impact of stressors and overload on informal caregivers of cirrhosis patients. METHOD: Cross-sectional study, conducted with 54 informal caregivers of cirrhosis patients, followed up at the Liver Transplant Service Outpatient Clinic of the University of São Paulo School of Medicine Hospital das Clínicas, where they had access to a sociodemographic questionnaire, history of the patient's disease and the scale Burden Scale for Family Caregivers. RESULTS: It was observed that higher levels of education and income of the caregiver correlates with a lower degree of stress. In addition, there is a significant difference found in the caregiver's age variable, which indicates that the youngest are those who have the highest degree of stress. The variable Na mEg/l of the patient also presents a statistically significant difference. CONCLUSION: Our study was a precursor using the BSFC scale of worldwide coverage and that had not yet been applied in any study in Brazil, thus allowing a look at the various aspects that affect the quality of life of caregivers of patients with cirrhosis. Our results and the literature corroborate the importance not only of the patient, but also the informal caregiver's health.

Investigation of the relaxing effect of a camphor nanoemulsion on rat isolated trachea.

Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-[1,2,4]-oxadiazole-[4,3,-a]-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50. As conclusion, NEC may be involved with ß-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, ß-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC. In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.

Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice.

Doxorubicin (DOX), a chemotherapy drug successfully used in the therapy of various types of cancer, is currently associated with the mucositis development, an inflammation that can cause ulcerative lesions in the mucosa of the gastrointestinal tract, abdominal pain and secondary infections. To increase the safety of the chemotherapy, we loaded DOX into nanostructured lipid carriers (NLCs). The NLC-DOX was characterized by HPLC, DLS, NTA, Zeta potential, FTIR, DSC, TEM and cryogenic-TEM. The ability of NLC-DOX to control the DOX release was evaluated through in vitro release studies. Moreover, the effect of NLC-DOX on intestinal mucosa was compared to a free DOX solution in C57BL/6 mice. The NLC-DOX showed spherical shape, high drug encapsulation efficiency (84.8 ± 4.6%), high drug loading (55.2 ± 3.4 mg/g) and low average diameter (66.0-78.8 nm). The DSC and FTIR analyses showed high interaction between the NLC components, resulting in controlled drug release. Treatment with NLC-DOX attenuated DOX-induced mucositis in mice, improving shortening on villus height and crypt depth, decreased inflammatory parameters, preserved intestinal permeability and increased expression of tight junctions (ZO-1 and Ocludin). These results indicated that encapsulation of DOX in NLCs is viable and reduces the drug toxicity to mucosal structures.

Change in neoadjuvant chemotherapy could alter the prognosis of patients with pancreatic adenocarcinoma: A case report.

BACKGROUND: Neoadjuvant treatment has become a standard of care for borderline or locally advanced pancreatic cancer and is increasingly considered even for up-front resectable disease. The aim of this article is to present the case of a 62-year-old patient with locally advanced pancreatic adenocarcinoma who was successfully treated with gemcitabine plus nab-paclitaxel after the failure of the first line treatment. CASE SUMMARY: Computerized tomography scan and magnetic resonance imaging demonstrated a nodular lesion of ill-defined limits in the body of the pancreas, measuring approximately 4.2 cm × 2.7 cm, with an infiltrative aspect. The tumor had contact with the superior mesenteric vein, splenomesenteric junction and the proximal segment of the splenic artery, causing focal reduction of its lumens. Due to vascular involvement, neoadjuvant chemotherapy treatment with eight cycles of "folinic acid, 5-fluorouracil, irinotecan and oxaliplatine" (FOLFIRINOX) were performed. At the end of the cycles, surgery was performed, but the procedure was interrupted due to finding of lesions suspected of metastasis. Gemcitabine plus nab-paclitaxel was then successfully used for neoadjuvant treatment with subsequent R0 surgical resection. CONCLUSION: Gemcitabine plus nab-paclitaxel may be effective as an alternative regimen when FOLFIRINOX fails as the first line of treatment, suggesting the need for further studies to identify which patients would benefit from each type of therapeutic approach.