Expert consensus: Profiling and management of advanced or metastatic epithelial ovarian cancer / Consenso de expertos basado en la evidencia: perfilamiento y manejo del carcinoma epitelial de ovario de alto grado avanzado.

Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie ­ AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.

Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la "Conferencia de consenso de procedimientos operativos estandarizados de ESMO". Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.

Subacute high-refined carbohydrate diet leads to abnormal reproductive control of the hypothalamic-pituitary axis in female rats.

We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHß+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHß+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.

High-refined carbohydrate diet alters different metabolic functions in female rats.

A diet containing refined carbohydrate (HCD) caused obesity and white adipose tissue (WAT) abnormalities, but it is unclear if HCD is linked with other metabolic dysfunctions in female models. Thus, we assessed whether HCD results in WAT, pancreas, liver, skeletal muscle (SM) and thyroid (TH) abnormalities in female rats. Female rats were fed with HCD for 15 days and metabolic morphophysiology, inflammation, oxidative stress (OS), and fibrosis markers were assessed. HCD rats presented large adipocytes, hyperleptinemia, and WAT OS. HCD caused irregular glucose metabolism, low insulin levels, and large pancreatic isle. Granulomas, reduced glycogen, and OS were observed in HCD livers. HCD caused hypertrophy and increased in glycogen in SM. HCD caused irregular TH morphophysiology, reduced colloid area and high T3 levels. In all selected tissues, inflammation and fibrosis were observed in HCD rats. Collectively, these data suggest that the HCD impairs metabolic function linked with irregularities in WAT, pancreas, liver, SM and TH in female rats.

Tributyltin and high-refined carbohydrate diet lead to metabolic and reproductive abnormalities, exacerbating premature ovary failure features in the female rats.

Exposure to the obesogen tributyltin (TBT) alone or high carbohydrate diet (HCD) alone leads to obesity and reproductive complications, such as premature ovary failure (POF) features. However, little is known about interactions between TBT and nutrition and their combined impact on reproduction. In this study, we assessed whether acute TBT and HCD exposure results in reproductive and metabolic irregularities. Female rats were treated with TBT (100 ng/kg/day) and fed with HCD for 15 days and metabolic and reproductive outcomes were assessed. TBT and HCD rats displayed metabolic impairments, such as increased adiposity, abnormal lipid profile and triglyceride and glucose (TYG) index, worsening adipocyte hypertrophy in HCD-TBT rats. These metabolic consequences were linked with reproductive disorders. Specifically, HCD-TBT rats displayed irregular estrous cyclicity, high follicle-stimulating hormone (FSH) levels, low anti-Müllerian hormone (AMH) levels, reduction in ovarian reserve, and corpora lutea (CL) number, with increases in atretic follicles, suggesting that HCD-TBT exposure exacerbated POF features. Further, strong negative correlations were observed between adipocyte hypertrophy and ovarian reserve, CL number and AMH levels. HCD-TBT exposure resulted in reproductive tract inflammation and fibrosis. Collectively, these data suggest that TBT plus HCD exposure leads to metabolic and reproductive abnormalities, exacerbating POF features in female rats.

Impact of Olive Oil Supplement Intake on Dendritic Cell Maturation after Strenuous Physical Exercise: A Preliminary Study.

Physical exercise is known to have a dose-dependent effect on the immune system and can result in an inflammatory process in athletes that is proportional to the intensity and duration of exertion. This inflammatory process can be measured by cell markers such as dendritic cells (DCs), which, in humans, consist of the myeloid DC (mDCs) and plasmacytoid DC (pDCs) subpopulations. The aim of this study was to measure DC differentiation to determine the possible anti-inflammatory effects, after intense aerobic effort, of the intake of a 25 mL extra-virgin olive oil supplement. Three healthy sports-trained subjects went through resistance exercise loads on two days separated by a week: on one day after active supplement intake and on the other day after placebo supplement intake. The results show that the highest increase (77%) in the percentage of mDCs as a proportion of pDCs was immediately after testing. Independently of the supplement taken, mature mDCs showed a decreasing trend between the test one hour after and 24 h after testing ended. Nevertheless, measured in terms of the coefficient of variation, only the decrease (46%) for extra-virgin olive oil supplementation was statistically significant (95% CI: 30-62%; p = 0.05). In conclusion, an extra-virgin olive oil supplement could reduce the inflammatory impact of intense aerobic effort and improve recovery at 24 h.

Características antropométricas y capacidad cardiorrespiratoria de corredores de montaña masculinos y femeninos / Anthropometric characteristics and cardiorespiratory capacity of male and female trail runners

INTRODUCCIÓN: Los objetivos de este estudio fueron comparar las características antropométricas y cardiorrespiratorias de corredores de montaña masculinos y femeninos, y examinar la asociación entre las variables antropométricas y cardiorrespiratorias. MATERIAL Y MÉTODOS: Un total de 48 corredores de montaña, 16 mujeres y 32 hombres participaron en el estudio. Se midieron los parámetros antropométricos y se realizó un test incremental máximo en tapiz rodante con rampa para la valoración cardiorrespiratoria. RESULTADOS: Los resultados arrojaron diferencias significativas en las características antropométricas correspondientes a masa, talla, índice de masa corporal (IMC), perímetros, diámetros, % masa muscular, % masa residual y componente mesomórfico entre hombres y mujeres, siendo significativamente superiores en el grupo masculino (p < 0,05). El grupo femenino obtuvo en pliegues tricipital, muslo, pierna eilecorestal, así como en la suma Σ 8 pliegues, % de grasa, en la masa grasa, masa ósea y en el componente endomórfico valores significativamente mayores (p < 0,05). Con respecto a la capacidad cardiorrespiratoria, el grupo masculino obtuvo valores significativamente mayores en el volumen sistólico inicial (p < 0,01, TE = -1,45, alto), consumo de oxígeno en el segundo umbral ventilatorio (VO2VT2) (p < 0,01, TE = -1,66, alto) y consumo de oxígeno máximo (VO2máx) (p < 0,05, TE = -1,78, alto). Se obtuvo una correlación alta entre la suma de 8 pliegues y el VO2máx (r = -0,79, p < 0,01), entre el % de grasa y el VO2máx (r = -0,81, p < 0,01) y entre el % de grasa y el VO2VT2 (r = -0,79, p < 0,01). CONCLUSIONES: Los resultados parecen evidenciar diferencias entre corredores de montaña hombres y mujeres en las características antropométricas y en la capacidad cardiorrespiratoria y que las características antropométricas pueden influir en el rendimiento cardiorrespiratorio de los corredores de montaña

INTRODUCTION: The objectives of this study were to compare the anthropometric characteristics and the cardiorespiratory capacity of male and female mountain runners, and to examine the association between anthropometric and cardiorespiratory variables. MATERIAL AND METHOD: A total of 48 mountain runners, 16 women and 32 men take part in the study. Anthropometric parameters were measured and a maximum incremental test was performed on treadmill with ramp for cardiorespiratory assessment. RESULTS: The results showed significant differences in the anthropometric characteristics corresponding to mass, height, body mass index (BMI), perimeters, diameters, % muscle mass, % residual mass and mesomorphic component between men and women, being significantly higher in the male group (p < 0.05). The female group obtained significantly higher values (p < 0.05) in tricipital, thigh, leg and ilecorestal skinfolds, as well as in 8 folds sum, % fat, fat mass, bone mass and in the endomorphic component. With respect to cardiorespiratory capacity, the male group obtained significantly higher values in the initial systolic volume (p < 0.01, TE = -1.45, large), oxygen consumption at the second ventilatory threshold (VO2VT2) (p < 0.01, TE = -1.66, large) and maximum oxygen consumption (VO2max) (p < 0.05, TE = -1.78, large). A large correlation was obtained between the sum of 8 skinfolds and the VO2max (r = -0.79, p < 0.01), between the % fat and the VO2max (r = -0.81, p < 0.01) and between % fat and VO2VT2 (r = -0.79, p < 0.01). CONCLUSIONS: The results seem to show differences between male and female mountain runners in anthropometric characteristics and cardiorespiratory capacity and that anthropometric characteristics can influence the cardiorespiratory performance of mountain runners

The impact of endocrine-disrupting chemical exposure in the mammalian hypothalamic-pituitary axis.

The hypothalamic-pituitary axis (HP axis) plays a critical and integrative role in the endocrine system control to maintain homeostasis. The HP axis is responsible for the hormonal events necessary to regulate the thyroid, adrenal glands, gonads, somatic growth, among other functions. Endocrine-disrupting chemicals (EDCs) are a worldwide public health concern. There is growing evidence that exposure to EDCs such as bisphenol A (BPA), some phthalates, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and biphenyls (PBBs), dichlorodiphenyltrichloroethane (DDT), tributyltin (TBT), and atrazine (ATR), is associated with HP axis abnormalities. EDCs act on hormone receptors and their downstream signaling pathways and can interfere with hormone synthesis, metabolism, and actions. Because the HP axis function is particularly sensitive to endogenous hormonal changes, disruptions by EDCs can alter HP axis proper function, leading to important endocrine irregularities. Here, we review the evidence that EDCs could directly affect the mammalian HP axis function.

High-refined carbohydrate diet leads to polycystic ovary syndrome-like features and reduced ovarian reserve in female rats.

Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.

Physical Test to Estimate Suitable Workloads for an Exercise Program in Breast Cancer Survivors.

Guillamó, E, Travier, N, Oviedo, GR, Fonseca-Nunes, A, Alamo, JM, Cos, F, Roca, A, Niño, O, Agudo, A, and Javierre, C. Physical test to estimate suitable workloads for an exercise program in breast cancer survivors. J Strength Cond Res 34(12): 3593-3599, 2020-Epidemiologic studies suggest that patients with breast cancer who gain weight after diagnosis have a higher risk of recurrence and death. Regular physical exercise can help minimize postdiagnosis weight gain. The objective of the study was to assess the effectiveness of a physical test for individualizing the workloads used during a fitness program. To continuously individualize the intensity of the training, a test was designed and integrated into the sessions. The test consisted in monitoring heart rate and workload during 2 bouts of cycling at moderate intensity. The workload parameters recorded during the tests were later used as reference values to plan the intensity of the next in-person training sessions. The 5 tests conducted during the 12 weeks of the intervention showed significant differences in intensity (F = 3.034, p = 0.047). Compared with the first evaluation, the intensities measured during the third, fourth, and fifth tests presented increases of 9.9% (p = 0.02), 13.2% (p = 0.019), and 17.5% (p = 0.002), respectively. A significant increase in workload with respect to body weight was observed in the physical assessment performed after the program (t = 13.2, p = 0.0001). The peak oxygen consumption with respect to body weight (peak V[Combining Dot Above]O2) achieved by the subjects during the assessment at the end of the program had also increased (t = 9.72, p = 0.0001). The intensity test, introduced in the training sessions along with the physical exercise program, was an easy-to-use, practical tool for monitoring intensity. It allows an adjustment of the workload over the program period that respects the individual progression of each patient.

Effects of Tributyltin (TBT) on Rat Bone and Mineral Metabolism.

BACKGROUND/AIMS: Tributyltin (TBT) is an organotin (OTs) and biohazard organometallic pollutant. Recently our group has shown that TBT, even in very low doses, has deleterious effects on several tissues most likely due to its role as an endocrine-disrupting molecule. Other studies have confirmed that OT exposure could be responsible for neural, endocrine, and reproductive dysfunctions via in vitro and in vivo models. However, TBT effects on bone lack concise data despite the fact that bone turnover is regulated by endocrine molecules, such as parathormone (PTH), estrogen (E2), etc. Our group has already shown that TBT disrupts adrenal and female gonadal functions. METHODS: We studied the effects of TBT on bone metabolism and structure using DXA, microCT scan, and SEM. We also determined the calcium (Ca²âº) and phosphate (Pi) metabolism in TBT-treated rats as well as some biomarkers for bone formation and resorption. RESULTS: Surprisingly, we found that TBT leads to higher bone mineral density (BMD) although lesions in spinal bone were observed by either microCT scan or SEM. Biomarkers for bone resorption, such as the urinary deoxipyridinolines (DPD) excretion ratio was increased in TBT-treated animals versus mock-treated controls. Osteocalcin (OC) and alkaline phosphatase (AP) are markers of bone formation and are also elevated suggesting that the bone matrix suffers from a higher turnover. Serum Ca²âº (total and ionized) do not changed by TBT treatment although hypercalciuria is observed. CONCLUSION: It is known that Sn atoms have three valence states (Sn²âº, Sn³âº, and Sn4⁺); hence, we hypothesized that Sn (more likely Sn²âº) could be competing with Ca²âº and/or Mg²âº in hydroxyapatite mineral matrix to disturb bone turnover. Further work is needed to confirm this hypothesis.

Organotin Exposure and Vertebrate Reproduction: A Review.

Organotin (OTs) compounds are organometallic compounds that are widely used in industry, such as in the manufacture of plastics, pesticides, paints, and others. OTs are released into the environment by anthropogenic actions, leading to contact with aquatic and terrestrial organisms that occur in animal feeding. Although OTs are degraded environmentally, reports have shown the effects of this contamination over the years because it can affect organisms of different trophic levels. OTs act as endocrine-disrupting chemicals (EDCs), which can lead to several abnormalities in organisms. In male animals, OTs decrease the weights of the testis and epididymis and reduce the spermatid count, among other dysfunctions. In female animals, OTs alter the weights of the ovaries and uteri and induce damage to the ovaries. In addition, OTs prevent fetal implantation and reduce mammalian pregnancy rates. OTs cross the placental barrier and accumulate in the placental and fetal tissues. Exposure to OTs in utero leads to the accumulation of lipid droplets in the Sertoli cells and gonocytes of male offspring in addition to inducing early puberty in females. In both genders, this damage is associated with the imbalance of sex hormones and the modulation of the hypothalamic-pituitary-gonadal axis. Here, we report that OTs act as reproductive disruptors in vertebrate studies; among the compounds are tetrabutyltin, tributyltin chloride, tributyltin acetate, triphenyltin chloride, triphenyltin hydroxide, dibutyltin chloride, dibutyltin dichloride, diphenyltin dichloride, monobutyltin, and azocyclotin.

High temperature CO2 capture of hydroxyapatite extracted from tilapia scales / Captura de CO2 a altas temperaturas, de hidroxiapatitas extraídas de escamas de tilapia / Captura de CO2 a altas temperaturas por hidroxiapatita extraída de escamas de tilápia

Abstract Hydroxyapatite (HAp) was obtained from tilapia scales by two extraction methods: direct calcination and acid-base treatment. The physicochemical characteristics of the obtained HAps were evaluated by thermogravimetric analysis, X-ray fluorescence, X-ray diffraction, scanning electron microscopy, surface area, infrared spectroscopy, and basicity measurement at 298 K by CO2 -pulse titration. Furthermore, the CO2 capture capacity of the solids at high temperature was also determined. Both methods showed the presence of a HAp phase although significant differences in the properties of the solids were found. The HAp obtained by direct calcination, exhibited a lower crystallinity and a greater surface area and basicity than the HAp obtained by the acid-base treatment. These features were correlated with the solid's CO2 capture capacity. In this work, CO2 capture capacity values for HAp yielded by calcination ranged from 2.5 to 3.2 mg CO2 /g captured at 973 K, and for the acid-base treatment-derived HAp, CO2 capture capacity values between 1.2 to 2.5 mg CO2 /g were recorded. These results reveal the potential of HAps extracted from tilapia scales as solids with high CO2 capture capacity, thermal stability, and capture/release cycles reversibility.

Resumen Se obtuvo hidroxiapatita (HAp) de escamas de tilapia por dos métodos de extracción: calcinación directa y tratamiento ácido-base. Las características fisicoquímicas de las HAps obtenidas fueron evaluadas por análisis termogravimétrico, fluorescencia de rayos X, difracción de rayos X, microscopía electrónica de barrido, área superficial, espectroscopia infrarroja y medición de basicidad a 298 K por titulación por pulso de CO2. Adicionalmente, se determinó la capacidad de captura de CO2 de los sólidos a alta temperatura. Ambos métodos mostraron la presencia de una fase de HAp, aunque se encontraron diferencias significativas en las propiedades de los sólidos. La HAp obtenida por calcinación directa exhibió una menor cristalinidad y una mayor área superficial y basicidad que la HAp obtenida con el tratamiento acido-base. Estas características se correlacionaron con la capacidad de captura de CO2 del sólido. En este trabajo, los valores de captura del CO2 con la HAp producidos por calcinación oscilaron entre 2.5 to 3.2 mg CO2/g capturado a 973 K, y con la HAp derivada del tratamiento ácido-base, se registraron valores de captura entre 1.2 to 2.5 mg CO2/g. Estos resultados revelan el potencial de HAps extraídos de escamas de tilapia como sólidos con una alta capacidad de captura de CO2, estabilidad térmica y reversibilidad de los ciclos de captura/liberación.

Resumo A hidroxiapatita (HAp) foi obtida a partir da escama de tilapia usando dois métodos de extração: calcinação direta e tratamento ácido-base. As características físico-químicas das hidroxiapatitas foram avaliadas por análise termogravimétrica, fluorescência de raios-X, difração de raios-X, microscopia eletrônica de varredura, área superficial, espectroscopia de infravermelho e medição de basicidade a 298 K por titulação de pulso de CO2. Além disso, determinou-se a capacidade de captura de CO2 dos sólidos a alta temperatura. Os dois métodos mostraram a presença da fase HAp, no entanto, diferenças significativas foram encontradas nas propriedades dos sólidos, sendo a HAp obtida por calcinação direta a que apresentou menor cristalinidade, maior área superficial e basicidade, características que foram correlacionadas com a capacidade de captura de CO2. Foram encontrados valores entre 2.5 a 3.2 mg CO2/g capturado a 973 K para a HAp obtida por calcinação e, entre 1.2 a 2.5 mg CO2/g para a HAp obtida por tratamento ácido-base. Isto revelou o potencial de HAp's extraídas da escama de tilapia como sólidos com alta capacidade de captura de CO2, estabilidade térmica e reversibilidade na liberação de CO2.

Different training programs decrease blood pressure during submaximal exercise.

OBJECTIVE: Our purpose was to study the effects of aerobic, resistance, and mixed (aerobic and resistance) training programs on blood pressure, both at rest and during submaximal exercise in healthy people. METHODS: We randomized 39 physically active, healthy participants into aerobic, resistance, and mixed (aerobic and resistance) exercise groups, and a control group. The exercise groups trained for 60 min three times/week for 6 weeks, and a submaximal cycle ergometer test was performed before and after training, and 3 weeks after detraining. Continuous blood pressure was determined before and during the test. RESULTS: At the submaximal test, both systolic and diastolic blood pressures decreased significantly (p < 0.05) after detraining in the exercise groups. However, between pre-training and detraining, we found significant reductions at rest only in the mixed exercise group (p < 0.05). CONCLUSION: Although all exercise had similar effects on blood pressure during submaximal exercise, the mixed aerobic and resistance exercise may be optimal for blood pressure reduction, by the addition of diverse physiological pathways.

Asimetría del ventrículo laríngeo: un estudio anatómico directo en material cadavérico / Asymmetry of laryngeal ventricle: a direct anatomical study in cadavers

Por su localización anatómica en el cuello, su papel funcional en la respiración en la fonación y su importancia en los procesos de intubación endotraqueal, la caracterización morfológica de la laringe reviste gran importancia en el campo de la morfología, fonoaudiología y de especialidades clínicas como la otorrinolaringología y anestesia. En una muestra de 16 laringes fijadas en formol del anfiteatro de la Universidad Autónoma de Bucaramanga, se registraron las longitudes de las estructuras cartilaginosas, comparando el lado derecho y el lado izquierdo. No se encontraron diferencias significativas en las estructuras cartilaginosas de la laringe de acuerdo al lado (asimetría), excepto en la amplitud del ventrículo laríngeo. Se midió la profundidad del ventrículo laríngeo en el punto medio; el ventrículo laríngeo derecho presentó una profundidad promedio de 2,50 mm. y el izquierdo de 2,31 mm, presentando diferencia significativa (p= 0,0102). Las diferencias encontradas se deben a la forma que tienen los pliegues vestibulares y vocales; en unas muestras los pliegues son aplanados, lo que hace que la amplitud sea uniforme, en otras los pliegues tienen forma de S itálica, lo que ocasiona variaciones en la profundidad del ventrículo. Teniendo en cuenta que la amplitud del ventrículo laríngeo varía dependiendo del estado funcional de la laringe, ya sea durante la respiración, o la fonación, este hallazgo, representa un aporte importante para motivar la realización de estudios, con un tamaño de muestra más grande, en otros grupos poblacionales y estudios funcionales que determinen si las variaciones del espacio tienen efecto en la fonación.

For its anatomical location in the neck, its functional role in breathing in phonation and its importance in the process of endotracheal intubation, the morphological characterization of the larynx is of great importance in the field of morphology, speech therapy and clinical specialties such as otolaryngology and anesthesia. In a sample of 16 larynges fixed in formalin at the amphitheater of the Universidad Autónoma de Bucaramanga., the lengths of the cartilaginous structures were recorded, comparing the right side and the left side. No significant differences in the cartilaginous structures of the larynx in reference to side (asymmetry) was found except amplitude of laryngeal ventricle. The depth of the laryngeal ventricle at the midpoint was measured; the right laryngeal ventricle showed an average depth of 2.50 mm. and left 2.31 mm, showing significant difference (p = 0.0102). The differences are due to the vestibular and vocal folds; samples in the folds are flattened, making the amplitude uniform, in other folds they are shaped italic S, causing variations in the depth of the ventricle. Given that the amplitude of the laryngeal ventricle varies depending on the functional state of the larynx, either during respiration or phonation, this finding represents an important contribution to motivate studies, with larger size sample, in other population groups and functional studies to determine whether variations in space have an effect on phonation.

Cardiorespiratory Coordination after Training and Detraining. A Principal Component Analysis Approach.

Our purpose was to study the effects of different training modalities and detraining on cardiorespiratory coordination (CRC). Thirty-two young males were randomly assigned to four training groups: aerobic (AT), resistance (RT), aerobic plus resistance (AT + RT), and control (C). They were assessed before training, after training (6 weeks) and after detraining (3 weeks) by means of a graded maximal test. A principal component (PC) analysis of selected cardiovascular and cardiorespiratory variables was performed to evaluate CRC. The first PC (PC1) coefficient of congruence in the three conditions (before training, after training and after detraining) was compared between groups. Two PCs were identified in 81% of participants before the training period. After this period the number of PCs and the projection of the selected variables onto them changed only in the groups subject to a training programme. The PC1 coefficient of congruence was significantly lower in the training groups compared with the C group [H (3, N=32) = 11.28; p = 0.01]. In conclusion, training produced changes in CRC, reflected by the change in the number of PCs and the congruence values of PC1. These changes may be more sensitive than the usually explored cardiorespiratory reserve, and they probably precede it.

Reliability and validity of the 6-min walk test in adults and seniors with intellectual disabilities.

INTRODUCTION: Adults with intellectual disabilities (ID) have significantly lower rates of physical activity and fitness than adults without ID. The 6-min walk test (6 MWT) is an inexpensive and simple way to test mobility and submaximal work capacity. PURPOSE: To evaluate the test-retest reliability and validity of the 6 MWT in adults and seniors with ID and explore factors contributing to the 6 MWT distance (6 MWD). METHODS: 46 participants with mild, moderate and severe ID levels (age=41 ± 11 years) performed the 6 MWT three times (T1; T2; T3) to determine test-retest reliability. To test validity, peak oxygen uptake (VO2 peak) was measured using a treadmill protocol. To analyze factors contributing to the 6 MWD, sex, height, fat mass % and fat free mass %, ID level, isometric leg strength and relative VO2 peak were also measured. RESULTS: The walking distances for T1, T2 and T3 were 460.3 ± 76.9; 489.4 ± 81.2 and 491.4 ± 77.9 m, respectively. The 6 MWDs between T1-T2 and T1-T3 were significantly different (p<0.001), but T2 and T3 were not different. The intraclass correlation coefficient between T2 and T3 was 0.96 indicating high reliability. Relative VO2 peak and isometric leg strength significantly contributed to the 6 MWD (R(2)=0.55). CONCLUSIONS: The 6 MWT is an easy, inexpensive, reliable and valid test in adults and seniors with ID. Familiarization is necessary to obtain reliable values. Relative VO2 peak and leg strength have significant impact on the distance walked.

Does prolonged systemic glucocorticoid use increase risk of tophus formation among gouty arthritis patients?

AIM: To determine the relationship of steroid use with tophus formation and other comorbid conditions among male gout patients. METHODS: Review of medical records of Filipino gout patients under the care of rheumatologists was conducted. Univariate analysis (chi-square, Student's t-test) and multiple logistic regression analysis were performed to establish the risk for tophus formation among glucocorticoid users. Bivariate analysis was separately done to determine the confounding effect of steroid use in the association of comorbidities and tophi formation. RESULTS: There were 295 Filipino men with a mean age of 56 years and a mean duration of 12 years of gouty arthritis who were included in the study. Multivariate analysis showed a five times higher likelihood (OR 4.81 95% CI 1.92-12.04, P < 0.001) for tophus formation among prolonged steroid users. Confounders identified were disease duration of gout (> or = 10 years), presence of chronic kidney disease (CKD) and elevated serum creatinine level (SCr). Bivariate analysis of comorbidities showed that steroid use introduced a considerable bias in the relationship of hypertension, elevated SCr, CKD and dyslipidemia. CONCLUSION: Patients with equivalent prednisone intake of at least 15 mg/week for > or = 3 months is associated with tophi formation. In the presence of hypertension, renal impairment, and elevated serum creatinine level, use of steroids confounds the individual risk that each factor carries.