Case-control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study.

BACKGROUND: Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. METHODS: We designed a retrospective case-control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. RESULTS: 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. CONCLUSIONS: Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy.

Antiviral activity of myricetin glycosylated compounds isolated from Marcetia taxifolia against chikungunya virus.

The chikungunya virus (CHIKV) has produced epidemic outbreaks of significant public health impact. The clinical symptoms of this disease are fever, polyarthralgia, and skin rash, generally self-limiting, although patients may develop a chronic disabling condition or suffer lethal complications. Unfortunately, there is no specific treatment or vaccine available. Thus, the search for effective therapies to control CHIKV infection is an urgent need. This study evaluated the antiviral activity of flavonoids isolated from Marcetia taxifolia by in vitro and in silico analysis. Cytotoxicity of compounds was determined by MTT assay and viral load was assessed in cell substrates supernatants by plaque-forming and RT-qPCR assays. Selected molecules were analyzed by molecular docking assays. Myricetin 3-rhamnoside (MR) and myricetin 3-(6-rhamnosylgalactoside) (MRG) were tested for antiviral assays and analyzed by the TCID50 method and RT-qPCR. MR exhibited dose-dependent antiviral activity, reducing viral titer at concentrations of 150-18.8 µg/mL by at least 1-log. Similarly, MRG showed a significant decrease in viral titer at concentrations of 37.5, 9.4, and 2.3 µg/mL. RT-qPCR analysis also displayed a substantial reduction of CHIKV RNA for both flavonoids. Furthermore, molecular docking of the selected flavonoids proposed the nsP3 macrodomain as a possible target of action. Our study reveals that MR and MRG could be considered promising anti-CHIKV therapeutic agents. Molecular modeling studies showed MR and MRG ligands with a high affinity for the N-terminal region of the nsP3 macrodomain, postulating them as a potential target of action for the CHIKV control.

State of the art in subtotal cholecystectomy: An overview.

Introduction: Subtotal cholecystectomy is a type of surgical bail-out procedure indicated when facing difficult laparoscopic cholecystectomy due to not reaching the critical view of safety, inadequate identification of the anatomical structures involved and/or risk of injury. Materials and methods: A comprehensive search on PubMed were performed using the following Mesh terms: Subtotal cholecystectomy and Partial cholecystectomy. The PubMed databases were used to search for English-language reports related to Subtotal cholecystectomy between January 1, 1987, the date of the first published laparoscopic cholecystectomy, through January 2023. 41 studies were included. Results: Subtotal cholecystectomy's incidence oscillates between 4.00% and 9.38%. Strasberg et al., divided subtotal cholecystectomies in "fenestrating" and "reconstituting" types based on if the remaining portion of the gallbladder was left open or closed. Subtotal cholecystectomy can sometimes be a challenging procedure and is associated to a high rate of complications such as biliary fistula, retained gallstones, subhepatic or subphrenic collections, among others. Conslusion: Subtotal cholecystectomy is a safe alternative when facing difficult cholecystectomy in which the critical view of safety is not reached in order to avoid complications. A classification system should be implemented in surgical descriptions to compare the different surgical techniques employed. In order to avoid bile leakage and cholecystitis of the remnant gallbladder, the surgical technique must be performed skillfully. There is still a current lack of information on alternative techniques such as omental plugging or falciform patch in order to judge their utility. There needs to be further research on long-term complications such as malignancy of the remnant gallbladder.

Metastatic differentiated thyroid cancer: worst prognosis in patients with metachronous metastases.

PURPOSE: To describe the overall survival and progression-free survival in patients diagnosed with differentiated thyroid carcinoma with synchronous and metachronous metastatic involvement. MATERIALS AND METHODS: A retrospective cohort study was conducted with 101 patients with differentiated thyroid cancer (DTC) who had metastatic involvement at diagnosis or during follow-up, who were treated at the National Cancer Institute between January 1, 2010 and December 31 of 2015. RESULTS: 81 patients (80.2%) were women and the mean age at diagnosis was 49 years (12-80). Synchronous metastases were detected in 54.5% of patients and metachronous metastasis was diagnosed in 45.5% of patients, in whom the mean time between initial diagnosis and the finding of distant metastases was 5 years. Pulmonary involvement occurred in almost all patients, with 131I uptake in 58% of synchronous metastases and in 21% of metachronous. There were 10 events in the patients with 131I-avid metastases with a median time to progression that was not reached, and there were 23 events in patients with 131I-refractory metastases with a median time to progression of 96 months; The median time to progression was significantly longer in patients with synchronous metastases compared to those with metachronous metastases (Not reached vs 95 months, P = 0.017) The 5-year overall survival rate was 95% to the entire cohort. CONCLUSIONS: The present study contributes to the expansion of the knowledge about this clinical course of DTC with the finding of a worst prognosis in patients with metachronous metastases.

SDHB exon 1 deletion: A recurrent germline mutation in Colombian patients with pheochromocytomas and paragangliomas.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) (known as PPGL in combination) are rare neuroendocrine tumors of the adrenal medulla and extra-adrenal ganglia. About 40% of the patients with PPGL have a hereditary predisposition. Here we present a case-series of 19 unrelated Colombian patients with a clinical diagnosis of PPGL tumors that underwent germline genetic testing as part of the Hereditary Cancer Program developed at the Instituto Nacional de Cancerología, Colombia (INC-C), the largest reference cancer center in the country. Ten of 19 patients (52.63%) were identified as carriers of a pathogenic/likely pathogenic (P/LP) germline variant in a known susceptibility gene. The majority of the P/LP variants were in the SDHB gene (9/10): one corresponded to a nonsense variant c.268C>T (p.Arg90*) and eight cases were found to be carriers of a recurrent CNV consisting of a large deletion of one copy of exon 1, explaining 42% (8/19) of all the affected cases. Only one additional case was found to be a carrier of a missense mutation in the VHL gene: c.355T>C (p.Phe119Leu). Our study highlights the major role of SDHB in Colombian patients with a clinical diagnosis of PGL/PCC tumors and supports the recommendation of including the analysis of large deletions/duplications of the SDHB gene as part of the genetic counselling to improve the detection rate of hereditary cases and their clinical care.

Carcinoma adrenocortical: Presentación y desenlaces en una institución oncológica / Adrenocortical carcinoma: Presentation and outcomes at an oncological institute

Resumen Introducción: El carcinoma adrenocortical es una neoplasia endocrina infrecuente pero con un comportamiento altamente agresivo y pobre pronóstico. Dado su baja prevalencia, la experiencia de los centros de referencia es fundamental para aumentar el conocimiento de esta entidad. Métodos: Se elaboró una serie de casos de pacientes con carcinoma adrenocortical, tratados en una institución oncológica de referencia entre enero de 2007 y diciembre de 2017. Se describieron las características clínicas e histopatológicas de los pacientes. Se estimó el tiempo de supervivencia libre de progresión y el tiempo de supervivencia global (SG) de forma gráfica y con funciones de tiempo al evento mediante la función de Kaplan-Meier. Resultados: Se identificaron 19 pacientes, 14 de los cuales fueron mujeres con edad media al diagnóstico de 43.4 años (rango 20 - 65). El 58% de los pacientes tuvo secreción hormonal, siendo el síndrome de Cushing el predominante. 7 pacientes tuvieron compromiso metastásico al momento del diagnóstico. Todos los pacientes fueron llevados a adrenalectomía y el estado postquirúrgico en 10 pacientes fue R0. Al final del periodo de estudio, 11 pacientes estaban vivos. La mediana de supervivencia libre de progresión fue de 18 meses +/- 7.86 y la mediana de supervivencia global fue de 30 meses +/-19.80. Conclusión: En la población de pacientes analizada, se encontraron desenlaces de supervivencia libre de progresión y supervivencia global similares a lo reportado en centros de alta experiencia en patología adrenal.

Abstract Introduction: Adrenocortical carcinoma is a rare endocrine neoplasm, but with highly aggressive behavior and a poor prognosis. Given its low prevalence, the experience of reference centers is essential to characterize the factors associated with this disease. Methods: It is a case series of patients with adrenocortical carcinoma, treated at a reference oncology institute between January 2007 and December 2017. The clinical and histopathological characteristics of patients are described. Progression-free survival and overall survival (OS) were estimated graphically and with time-to-event data using the Kaplan-Meier function. Results: 19 patients were identified; 14 of them were women with a mean age at diagnosis of 43.4 years (range 20-65). 58% of the patients had hormone secretion, with Cushing's syndrome being the predominant one. 7 patients had metastatic compromise at the time of diagnosis. All patients underwent adrenalectomy, and R0 was the post-surgical status in 10 of them. At the end of the study period, 11 patients were alive. The median progression-free survival was 18 months +/- 7.86, and the median overall survival was 30 months +/- 19.8. Conclusion: In the analyzed patient population, outcomes of progression-free survival and overall survival were similar to that reported at centers with extensive experience in adrenal disease.

Safety and efficacy of sorafenib in patients with advanced thyroid carcinoma: a phase II study (NCT02084732)

ABSTRACT Objective: Sorafenib significantly prolonged progression-free survival in patients with iodine-refractory advanced thyroid cancer. The present study was initiated before sorafenib was approved in Colombia and therefore represents an effort by an oncology institution to evaluate its efficacy and safety in this population. Subjects and methods: This phase II clinical trial had a single treatment arm. We included adult patients with progressive metastatic iodine-refractory thyroid cancer who received treatment with sorafenib 800 mg/day (400 mg every 12 hours) up to a maximum of 24 months or until the occurrence of limiting related toxicity, the progression of the disease, or voluntary withdrawal. Results: Nineteen patients received the treatment and were included in the safety analysis. However, for the efficacy analysis, 6 patients were excluded because they received only one month of therapy. Thirteen (68%) patients were women, and the mean age at diagnosis was 61.8 years. No complete responses were observed; 5 patients had a partial response (35.7%), 6 patients had stable disease, and 3 showed progression. Mean progression-free survival was calculated at 18 months (95% CI 10.7-20.3). Overall survival was estimated at 21.3 months (95% CI 17.8-24.8). Conclusion: For the first time in Colombia, the efficacy of sorafenib was evaluated in patients with advanced and progressive thyroid carcinoma refractory to radioactive iodine, with an efficacy and a safety profile similar to those previously reported.

On the use of evolutionary mismatch theories in debating human prosociality.

According to some evolutionary theorists human prosocial dispositions emerged in a context of inter-group competition and violence that made our psychology parochially prosocial, ie. cooperative towards in-groups and competitive towards strangers. This evolutionary hypothesis is sometimes employed in bioethical debates to argue that human nature and contemporary environments, and especially large-scale societies, are mismatched. In this article we caution against the use of mismatch theories in moral philosophy in general and discuss empirical evidence that puts into question mismatch theories based on parochial prosociality. Evolutionary mismatch theories play at best a rhetorical role in these moral debates and may misrepresent the status of relevant evolutionary research. We finally recommend that moral philosophers interested in the evolutionary literature also engage with dispositions such as xenophilia and social tolerance to counterbalance the focus on psychological mismatches adopted so far.

Safety and efficacy of sorafenib in patients with advanced thyroid carcinoma: a phase II study (NCT02084732).

OBJECTIVE: Sorafenib significantly prolonged progression-free survival in patients with iodine-refractory advanced thyroid cancer. The present study was initiated before sorafenib was approved in Colombia and therefore represents an effort by an oncology institution to evaluate its efficacy and safety in this population. METHODS: This phase II clinical trial had a single treatment arm. We included adult patients with progressive metastatic iodine-refractory thyroid cancer who received treatment with sorafenib 800 mg/day (400 mg every 12 hours) up to a maximum of 24 months or until the occurrence of limiting related toxicity, the progression of the disease, or voluntary withdrawal. RESULTS: Nineteen patients received the treatment and were included in the safety analysis. However, for the efficacy analysis, 6 patients were excluded because they received only one month of therapy. Thirteen (68%) patients were women, and the mean age at diagnosis was 61.8 years. No complete responses were observed; 5 patients had a partial response (35.7%), 6 patients had stable disease, and 3 showed progression. Mean progression-free survival was calculated at 18 months (95% CI 10.7-20.3). Overall survival was estimated at 21.3 months (95% CI 17.8-24.8). CONCLUSION: For the first time in Colombia, the efficacy of sorafenib was evaluated in patients with advanced and progressive thyroid carcinoma refractory to radioactive iodine, with an efficacy and a safety profile similar to those previously reported.

Exposure to radiotherapy for first primary cancer as a risk factor for second primary thyroid cancer: A case-control study.

BACKGROUND: Second primary neoplasms are associated with high mortality and morbidity rates in cancer survivors successfully treated for the first malignancy. Studies suggested an association between the type of first neoplasm and risk of subsequent thyroid cancer, with part of this risk attributable to exposure to radiotherapy during treatment of the first primary tumor. This study aimed to determine whether radiotherapy is a risk factor for thyroid cancer in patients previously treated for another neoplasm. METHODS: This retrospective case-control study included patients diagnosed with their first cancer between 2007 and 2017. Patients who subsequently developed thyroid cancer as a second primary neoplasm were defined as "cases", and patients who did not develop a second cancer were defined as "controls". Exposure to radiotherapy was the primary risk factor of interest; other risk factors were the site to which radiotherapy was delivered and the first neoplasm type. RESULTS: Exposure to radiotherapy was associated with an increased risk of thyroid cancer (odds ratio [OR]=2.410, 95% confidence interval [CI]: 1.219-4.764), in particular, in women (OR=3.121, 95% CI: 1.232-7.907) and in patients receiving radiotherapy to the thorax (OR=6.298, 95% CI: 2.581-15.370). The median survival time from first cancer recovery to thyroid cancer occurrence was 63.80 months; there was no difference in survival between patients who did and did not receive radiotherapy (P=0.899). CONCLUSION: Radiation to the thorax can increase the risk of thyroid cancer as a second neoplasm among patients with cancer successfully treated for their first cancer.

Uveal Melanoma, Angiogenesis and Immunotherapy, Is There Any Hope?

Uveal melanoma is considered a rare disease but it is the most common intraocular malignancy in adults. Local treatments are effective, but the systemic recurrence rate is unacceptably high. Moreover, once metastasis have developed the prognosis is poor, with a 5-year survival rate of less than 5%, and systemic therapies, including immunotherapy, have rendered poor results. The tumour biology is complex, but angiogenesis is a highly important pathway in these tumours. Vasculogenic mimicry, the ability of melanomas to generate vascular channels independently of endothelial cells, could play an important role, but no effective therapy targeting this process has been developed so far. Angiogenesis modulates the tumour microenvironment of melanomas, and a close interplay is established between them. Therefore, combining immune strategies with drugs targeting angiogenesis offers a new therapeutic paradigm. In preclinical studies, these approaches effectively target these tumours, and a phase I clinical study has shown encouraging results in cutaneous melanomas. In this review, we will discuss the importance of angiogenesis in uveal melanoma, with a special focus on vasculogenic mimicry, and describe the interplay between angiogenesis and the tumour microenvironment. In addition, we will suggest future therapeutic approaches based on these observations and mention ways in which to potentially enhance current treatments.

Cognición corporizada y comprensión semántica / Embodied Cognition and Semantic Comprehension / Cognição corporizada e compreensão semântica

Resumen Esta reflexión está orientada a presentar los avances en el estudio de la naturaleza del lenguaje con énfasis en los procesos de comprensión semántica, desde las teorías corporizadas y motrices de la cognición. Se establecen los lineamientos principales que sostienen dichas teorías y su aporte al área de las ciencias del lenguaje y la psicolingüística. En un primer apartado se resumen las ideas fundacionales de la teoría corporizada y enactiva, y se definen las propuestas sobre el lenguaje desde esta postura, para presentar, de manera general, el movimiento de la semántica corporizada. Posteriormente, se retoman estos planteamientos para relacionarlos con los problemas en el procesamiento de lenguaje de los pacientes con enfermedad de Parkinson. Esta enfermedad neurológica, al estar asociada con déficits motores y del movimiento voluntario, resulta una plataforma ideal para la validación de teorías que sugieren una estrecha relación entre la actividad motriz en contexto, la neurofisiología de la acción y los procesos de comprensión lingüística.

Abstract This review and analysis of the literature aims to show in a brief manner the recent findings in the study of the nature of language and semantic comprehension from the embodied and motor theories of cognition. The guidelines that uphold the embodied and enactive theories of cognition and their role for the study of language in psycholinguistics are established, as it is becoming common to find increasing support for them. In a first part of the article the main principles of the theory are shared as well as the different ideas about language that have been proposed under the name of embodied semantics. Then, the case of Parkinson's disease and language processing impairments in Parkinson's patients is taken as a critical case. This neurological disease associated with voluntary movement and motor deficits, is ideal for validating theories that propose a close relationship between motor activity in context, as well as the neurophysiology of action and the processes of understanding language.

Resumo Esta reflexão sobre resultados de literatura tem como finalidade presentar os avances recentes no estudo da natureza da linguagem com ênfase nos processos de compreensão semântica desde as teorias corporizadas e motrizes da cognição. São estabelecidos os lineamentos principais que sustentam as teorias mencionadas e seu aporte à área das ciências da linguagem e a psicolinguística. Na primeira parte são resumidas as ideias fundacionais da teoria corporizada e enativa, são definidas as diferentes propostas sobre a linguagem e o significado que existem desde esta postura, para apresentar, de maneira geral, o movimento da semântica corporizada. Depois, são retomadas estas ideias em relação com os problemas no processamento da linguagem que padecem os pacientes com doença de Parkinson. Esta doença neurológica, ao estar associada com déficits motores e do movimento voluntário, supõe uma plataforma ideal para a validação de teorias que propõem uma relação estreita entre a atividade motriz em contexto, a neurofisiologia da ação e os processos de compreensão linguística.

Einstein@Home discovers a radio-quiet gamma-ray millisecond pulsar.

Millisecond pulsars (MSPs) are old neutron stars that spin hundreds of times per second and appear to pulsate as their emission beams cross our line of sight. To date, radio pulsations have been detected from all rotation-powered MSPs. In an attempt to discover radio-quiet gamma-ray MSPs, we used the aggregated power from the computers of tens of thousands of volunteers participating in the Einstein@Home distributed computing project to search for pulsations from unidentified gamma-ray sources in Fermi Large Area Telescope data. This survey discovered two isolated MSPs, one of which is the only known rotation-powered MSP to remain undetected in radio observations. These gamma-ray MSPs were discovered in completely blind searches without prior constraints from other observations, raising hopes for detecting MSPs from a predicted Galactic bulge population.

Embolización de metástasis hepáticas en insulinoma maligno: de la hipoglicemia a la hiperglicemia / Embolisation of liver metastasis in malignant insulinoma: from hyperglycaemia to hypoglycaemia

Resumen Se describe el caso de un paciente de 75 años sin antecedentes de relevancia, que fue diagnosticado con insulinoma maligno en estado avanzado, con metástasis hepáticas, con síntomas por hipoglucemia hiperinsulinémica refractaria al tratamiento, y con diazóxido y octreotide de acción corta. El paciente presentó una respuesta clínica poco esperada a la embolización transarterial de metástasis hepáticas, pues a pesar de que persisten las lesiones tumorales, desarrolló hiperglucemia persistente y requirió manejo con insulina. Adicionalmente, se hace una breve revisión de la literatura sobre las opciones terapéuticas disponibles para el tratamiento sintomático de la hipoglucemia hiperinsulinémica.

Abstract The case is presented of a 75 year-old man who was diagnosed with malignant insulinoma in an advanced stage with diffuse liver metastases and symptoms due to hyperinsulinaemic hypoglycaemia refractory to treatment with diazoxide and short-acting octreotide. The patient had an unexpected clinical response to trans-arterial embolisation of liver metastases, since, despite still having the tumour, he developed persistent hyperglycaemia that required insulin treatment. A brief review of the literature is also presented on the treatment options for hyperinsulinaemic hypoglycaemia.

Neurofenomenología. Proyecto para una ciencia de la experiencia vivida / Neurophenomenology: project for a science of past experiences

Introducción: La ciencia cognitiva, desde mediados del siglo XX, es reconocida ampliamente como el área de convergencia genuina de todos los avances científicos relacionados con el estudio de la mente humana y los mecanismos que posibilitan el conocimiento. Se ha constituido desde entonces como un espacio multidisciplinar, en el que los intereses investigativos de diferentes actores y disciplinas han adquirido carta de ciudadanía, y han permitido novedosas esperanzas respecto al estudio de las particularidades humanas desde Perspectivas científicas. Objetivos: Este trabajo propone evaluar críticamente la inclusión de discusiones que la biología teórica ha estado asumiendo en su discurso, respecto al estudio del fenómeno cognitivo; principal atención merece el proyecto enactivo, y de manera extensiva, la neurofenomenología de Francisco J. Varela. Desarrollo: A través de una corta y comprimida historia de la ciencia cognitiva estableceremos los puntos clave para entender el surgimiento de la postura enactiva y el giro corporizado influido por la fenomenología continental en la ciencia cognitiva, así como los lineamientos generales de la neurofenomenología. Conclusiones: El problema duro de la conciencia aún se enfrenta a varios reduccionismos, que relegan lo cognitivo a un tipo de mecanismo exclusivamente racional, individualizado, abstracto e incorpóreo, lo que ha permitido el fortalecimiento del paradigma funcionalista en la filosofía de la mente. Una solución a las dicotomías clásicas en las ciencias de la mente debe empezar, a nuestro parecer, con un rechazo a estas asunciones…

Introduction: Since the middle of 20th Century, cognitive science has been recognized as the genuine convergence field for all scientific advances in human mind studies with the mecha-nisms enabling knowledge. Since then, it has become a multidisciplinary area where several research disciplines and actors have acquired citizenship, allowing new expectations on the scientific study of human uniqueness. Objectives: Critical assessment of the discussion that the discourse of theoretical biology has been assuming regarding the study of the cognitive phenomenon with special attention to the enactive project and, extensively, to the neuro-phenomenology of Francisco J. Varela. Methods: Starting with a brief and synthesized history of cognitive science, we will establish the key principles for understanding the emergence of the enactive paradigm and the “embodied” turn influenced by continental phenomenology in the cognitive science, as well as the general guidelines of Neurophenomenology. Conclusions: The “hard problem” of consciousness still faces several types of reductionism relegating the cognitive issue to a kind of merely rational, individual, abstract and disembodied mechanism, thus strengthening the functionalist paradigm in mind philosophy. A solution to classic dichotomies in mind sciences must start rejecting such assumptions…

[Neurophenomenology: Project for a Science of Past Experiences]. / Neurofenomenología. Proyecto para una ciencia de la experiencia vivida.

INTRODUCTION: Since the middle of 20(th) Century, cognitive science has been recognized as the genuine convergence field for all scientific advances in human mind studies with the mechanisms enabling knowledge. Since then, it has become a multidisciplinary area where several research disciplines and actors have acquired citizenship, allowing new expectations on the scientific study of human uniqueness. OBJECTIVES: Critical assessment of the discussion that the discourse of theoretical biology has been assuming regarding the study of the cognitive phenomenon with special attention to the enactive project and, extensively, to the neuro-phenomenology of Francisco J. Varela. METHODS: Starting with a brief and synthesized history of cognitive science, we will establish the key principles for understanding the emergence of the enactive paradigm and the "embodied" turn influenced by continental phenomenology in the cognitive science, as well as the general guidelines of Neurophenomenology. CONCLUSIONS: The "hard problem" of consciousness still faces several types of reductionism relegating the cognitive issue to a kind of merely rational, individual, abstract and disembodied mechanism, thus strengthening the functionalist paradigm in mind philosophy. A solution to classic dichotomies in mind sciences must start rejecting such assumptions.

Aspectos clave del ciclo de la úrea con relacion al metabolismo energético y proteico en vacas lactantes / Key aspects of the urea cicle, related to energetic and proteic metabolism in lactating dairy cows

El uso de altas cantidades de fertilizantes nitrogenados en las lecherías especializadas, ha conducido a cambios importantes en las características nutricionales de los forrajes, incrementando el contenido de nitrogeno total (proteina cruda) y su fracción soluble (fracción) a expensas de la proteína verdadera. Este hecho ha generado un aumento exagerado del contenido de nitrogeno fermentable que aparece como amonio el cual no alcanza a ser utilizado por la flora ruminal y pasacon relativa facilidad al torrente circulatorio; posteriormente debe ser transformado en el higado a area y eliminado en la orina o en la leche. Las vacas lactantes utilizan sus reservas proteicas (ademas del propionato ruminal), a favor de la sintesis de glucosa. Los aminoacidos producto del catabolismo proteico, sufren un proceso de transaminación para confluir, la mayoria de ellos, en el glutamato a partir de Á-cetoglutarato como cetoacido receptor. En el interior de la mitocondria, en presencia dela glutamato deshidrogenasa es liberado el amonio y este, en presencia de la carbamoil C fosfato sintetasa, bicarbonato y dos moles de ATP, forma el carbamoil fosfato (CaP), el que más adelante liberarón área. El amonio libre procedente de la absorción ruminal puede formar también Carbamoil Fosfato (CbP), sin embargo, esta reacción tiene baja afinidad a diferencia de la formación del glutamato a partir del mismo amonio y Á- cetoglutarato. La unión del glutamato con otra molécula de amonio produce glutamina la cual es un vehículo muy empleado por el organismo para deshacerse del amonio a nivel renal. La retención del amonio como glutamato constituye un gasto del Á- cetoglutarato, el cual es un importante precursor de la glucosa con lo que la gluconeogenesis a partir de este metabolito se puede ver disminuida. Paralelamente, el aumento en la actividad ureogênica conlleva al incremento en las necesidades de ciertos aminoácidos, como la metionina, para la...