Mitochondrial bioenergetics as a cell fate rheostat for responsive to Bcl-2 drugs: New cues for cancer chemotherapy.

Pro-survival BCL-2 proteins prevent the initiation of intrinsic apoptosis (mitochondria-dependent pathway) by inhibiting the pro-apoptotic proteins BAX and BAK, while BH3-only proteins promote apoptosis by blocking pro-survival BCL-2 proteins. Disruptions in this delicate balance contribute to cancer cell survival and chemoresistance. Recent advances in cancer therapeutics involve a new generation of drugs known as BH3-mimetics, which are small molecules designed to mimic the action of BH3-only proteins. Promising effects have been observed in patients with hematological and solid tumors undergoing treatment with these agents. However, the rapid emergence of mitochondria-dependent resistance to BH3-mimetics has been reported. This resistance involves increased mitochondrial respiration, altered mitophagy, and mitochondria with higher and tighter cristae. Conversely, mutations in isocitrate dehydrogenase 1 and 2, catalyzing R-2-hydroxyglutarate production, promote sensitivity to venetoclax. This evidence underscores the urgency for comprehensive studies on bioenergetics-based adaptive responses in both BH3 mimetics-sensitive and -resistant cancer cells. Ongoing clinical trials are evaluating BH3-mimetics in combination with standard chemotherapeutics. In this article, we discuss the role of mitochondrial bioenergetics in response to BH3-mimetics and explore potential therapeutic opportunities through metabolism-targeting strategies.

Olivary body exposure through far lateral and lower retrosigmoid approaches. Comparative analysis of the exposed surface and angle of attack.

OBJECTIVES: Throughout neurosurgical history, the treatment of intrinsic lesions located in the brainstem has been subject of much controversy. The brainstem is the anatomical structure of the central nervous system (CNS) that presents the highest concentration of nuclei and fibers, and its simple manipulation can lead to significant morbidity and mortality. Once one of the safe entry points at the medulla oblongata has been established, we wanted to evaluate the safest approach to the olivary body (the most used safe entry zone on the anterolateral surface of the medulla oblongata). The proposed objective was to evaluate the working channel from the surface of each of the far lateral and retrosigmoid approaches to the olivary body: distances, angles of attack and channel content. MATERIAL AND METHODS: To complete this work, a total of 10 heads injected with red/blue silicone were used. A total of 40 approaches were made in the 10 heads used (20 retrosigmoid and 20 far lateral). After completing the anatomical study and obtaining the data referring to all the approaches performed, it was decided to expand the sample of this research study by using 30 high-definition magnetic resonance imaging of anonymous patients without cranial or cerebral pathology. The reference points used were the same ones defined in the anatomical study. After defining the working channels in each of the approaches, the working distances, angle of attack, exposed surface, and the number of neurovascular structures present in the central trajectory were analyzed. RESULTS: The distances to the cranial and medial region of the olivary body were 52.71 mm (SD 3.59) from the retrosigmoid approach and 27.94 mm (SD 3.99) from the far lateral; to the most basal region of the olivary body, the distances were 49.93 (SD 3.72) from the retrosigmoid approach and 18.1 mm (SD 2.5) from the far lateral. The angle of attack to the caudal region was 19.44° (SD 1.3) for the retrosigmoid approach and 50.97° (SD 8.01) for the far lateral approach; the angle of attack to the cranial region was 20.3° (SD 1.22) for the retrosigmoid and 39.9° (SD 5.12) for the far lateral. Regarding neurovascular structures, the probability of finding an arterial structure is higher for the lateral far, whereas a neural structure will be more likely from a retrosigmoid approach. CONCLUSIONS: As conclusions of this work, we can say that far lateral approach presents more favorable conditions for the microsurgical treatment of intrinsic bulbar and bulbomedullary lesions approached through the caudal half of the olivary body. In those cases of bulbar and pontine-bulbar lesions approached through the cranial half of the olivary body, the retrosigmoid approach can be considered for selected cases.

Absolute quantification of cholesterol from thin tissue sections by silver-assisted laser desorption ionization mass spectrometry imaging.

Cholesterol is essential to all animal life, and its dysregulation is observed in many diseases. For some of these, the precise determination of cholesterol's histological location and absolute abundance at cellular length scales within tissue samples would open the door to a more fundamental understanding of the role of cholesterol in disease onset and progression. We have developed a fast and simple method for absolute quantification of cholesterol within brain samples based on the sensitive detection and mapping of cholesterol by silver-assisted laser desorption ionization mass spectrometry imaging (AgLDI MSI) from thin tissue sections. Reproducible calibration curves were generated by depositing a range of cholesterol-D7 concentrations on brain homogenate tissue sections combined with the homogeneous spray deposition of a non-animal steroid reference standard detectable by AgLDI MSI to minimize experimental variability. Results obtained from serial brain sections gave consistent cholesterol quantitative values in very good agreement with those obtained with other mass spectrometry-based methods.

Tumor mediastinal de células germinales en un paciente con melanoptisis / Mediastinal germ cell tumor in a patient with melanoptysis / Tumor de células germinativas mediastinais em paciente com melanoptise

Figuras A Y B: Radiografía de Tórax Anteroposterior (AP) y Lateral. Presencia de gran lesión al parecer del mediastino medio (Flechas blancas), con diámetros de 11 x 15 x 12 cm, de densidad homogénea, con efecto de masa y desviación de todas las estructuras (Flechas negras) y compresión sobre el lóbulo superior derecho (*), sin calcificaciones en su interior. Figura C. Tomografía computarizada de tórax con contraste corte coronal. En la región central del mediastino anterior, se identifica una masa hipodensa, heterogénea, con densidad de predominio de tejido blando, con algunas imágenes de densidad cálcica en su interior, de 14.3 x 10.2 x 12.6 (Línea amarilla) cm, que se encuentra desplazando la aorta ascendente, con trayecto tortuoso (Flecha azul), la flecha roja señala el tronco braquiocefálico. Figura D. Tomografía computarizada de tórax corte axial en ventana mediastinal. Masa hipodensa, heterogénea, con densidad de predominio de tejido blando, con algunas imágenes de densidad cálcica en su interior, la cual se encuentra desplazando y ocupando gran parte de la porción anterior del hemitórax derecho. Así mismo se encuentra desplazando estructuras mediastinales como el tronco de la pulmonar (Flecha azul), esta masa se encuentra generando atelectasia pasiva del lóbulo medio derecho (Flecha roja). Cómo citar. López-Salazar JP, Delgado-Serrano J. Tumor mediastinal de células germinales en un paciente con melanoptisis. MedUNAB. 2020;23(2): 191-194. doi:10.29375/01237047.3748

Figures A and B: Anteroposterior (AP) and Lateral Chest X-ray. Presence of a large mass, apparently from the middle mediastinum (white arrows), diameters of 11 x 15 x 12 cm, homogeneous density, with the mass effect on other mediastinal structures (black arrows) and compression on the right upper lobe (*), without inner calcifications. Figure C. Chest Computed Tomography, coronal section. In the anterior mediastinum it shows a hypodense, heterogeneous mass, with predominance of soft tissue density, with some calcifications inside, diameters of 14.3 x 10.2 x 12.6 (yellow line) cm, displacing the ascending aorta (blue arrow), the red arrow indicates the brachiocephalic trunk. Figure D. Computed tomography of the chest, axial section. Hypodense, heterogeneous mass, with predominance of soft tissue density, with some calcifications inside, which occupying a large parto f the anterior right hemithorax. It is also displacing mediastinal structures such as the trunk of the pulmonary artery (blue arrow), this mass is generating passive atelectasis of the right middle lobe (red arrow). Cómo citar. López-Salazar JP, Delgado-Serrano J. Tumor mediastinal de células germinales en un paciente con melanoptisis. MedUNAB. 2020;23(2): 191-194. doi:10.29375/01237047.3748

Figuras A e B: Radiografia de tórax (anteroposterior (AP) e lateral). Presença de grande massa, aparentemente do mediastino médio (Setas brancas), diâmetros de 11 x 15 x 12 cm, densidade homogênea, com efeito de massa em outras estruturas mediastinais (setas pretas) e compressão no lobo superior direito (*), sem calcificações internas. Figura C. Tomografia computadorizada de tórax, corte coronal. No mediastino anterior, mostra uma massa hipodensa e heterogênea, com predominância da densidade de partes moles, com algumas calcificações internas, diâmetros de 14,3 x 10,2 x 12,6 (Linha amarela) cm, deslocando a aorta ascendente (seta azul), a seta vermelha indica o tronco braquiocefálico. Figura D. Tomografia computadorizada de tórax, corte axial. Massa hipodensa, heterogênea, com predominância da densidade de partes moles, com algunas calcificações internas, que ocupam grande parte do hemitórax anterior direito. Também está deslocando estruturas mediastinais, como o tronco da artéria pulmonar (Seta azul), essa massa está gerando atelectasia passiva do lobo médio direito (Sseta vermelha). Cómo citar. López-Salazar JP, Delgado-Serrano J. Tumor mediastinal de células germinales en un paciente con melanoptisis. MedUNAB. 2020;23(2): 191-194. doi:10.29375/01237047.3748

Learning curves in intraoperative ultrasound guided surgery in breast cancer based on complete breast cancer excision and no need for second surgeries.

BACKGROUND: Intraoperative ultrasound guided surgery (IOUS) is an effective surgical technique for breast cancer with advantages over wire localization guided surgery (WL), enabling smaller lumpectomies without compromising margins. Nevertheless, it has had a slow implementation, maybe due to lacking a learning curve. Also differences in costs are not clearly reported. The aim of the study is to assess differences in volume of healthy breast tissue excised, to establish a learning curve and to prove it is cost saving. PATIENTS AND METHODS: From February 2009 to April 2013, women diagnosed with invasive breast cancer eligible for IOUS or WL breast conserving surgery were recorded into a prospectively maintained database. Both groups were compared for differences in margin status, second surgeries and excess of healthy tissue resected, defined by the calculated resection ratio (CRR). A raw cost study was assessed. IOUS learning curve was analyzed using Cumulative sum control chart (CUSUM). RESULTS: The study included 214 patients, 148 (69.16%) in the IOUS group and 66 (30.84%) in the WL group. IOUS showed significantly smaller surgical volumes (p = 0.02), smaller CRR (p = 0.006), higher rate of negative margins (p = 0.017) and less surgical time (p = 0.006) than WL. Learning curves based on complete tumor excision and no need for second surgeries showed that 11 cases were enough to master the technique. Around 900€ per surgery was saved using IOUS vs. WL. CONCLUSION: IOUS decreases excision of healthy breast tissue while increasing negative margin rates compared to WL. IOUS can be easily implemented; 11 cases are enough to acquire skills for performing the technique. Savings can be up to 900€ per surgery.

Percutaneous ultrasound-guided vacuum-assisted excision of benign breast lesions: A learning curve to assess outcomes.

OBJECTIVE:: To evaluate the efficacy and learning curve of ultrasoundguided vacuum-assisted excision (US-VAE) of benign breast lesions, and to assess characteristics associated with residual lesion. METHODS:: This was a retrospective study with institutional review board-approval. Sonographic and clinical follow-up were performed 6 months after intervention. Effectiveness and safety of the technique were analyzed. The cumulative summation (CUSUM) graphs were used to evaluate learning curves concerning complete excision and hematoma. RESULTS:: 152 ultrasound-VAEs in 143 patients were included. Initial complete resection was achieved in 90.8 % (138 of 152). 6-month follow-up was completed for 143 (94%) of cases and complete resection was observed in 72 % (100 of 143). Mean maximum size without residual tumor was 16.9 mm, while with residual lesion it was 21.9 mm (p = < 0.001), with a volume of 1.53 and 3.39 cm3, respectively (p = < 0.001). Increase in lesion size and volume was associated with less effectiveness (p = 0.05), clinical control (p = 0.05), and higher risk of clinically significant hematoma (p = 0.05). Receiver operating characteristic analysis demonstrate a volume threshold of 2.6 cm3 (r = 0.71, specificity 84.5%) for leaving no residual lesion. Cumulative summation graphs demonstrate that, on average, 11 excisions were required to acquire skills to perform complete excision in more than 80% at the end of the ultrasound-VAE and 18 excisions at 6 months. CONCLUSION:: Ultrasound-VAE is an effective treatment for benign breast lesions. Breast lesion volume should be considered when assessing for percutaneous treatment. ADVANCES IN KNOWLEDGE:: A follow-up of the learning process of ultrasound-VAE will be a valuable tool to assess the efectiveness and safety of the technique i.

Intraoperative Ultrasound-Guided Lumpectomy Versus Mammographic Wire Localization for Breast Cancer Patients After Neoadjuvant Treatment.

BACKGROUND: Intraoperative ultrasound (IOUS)-guided lumpectomy in early breast cancer has shown advantages over other techniques. However, the use of IOUS has been less explored after neoadjuvant treatment (NAT). This study aimed to compare IOUS- and wire localization (WL)-guided surgery in breast cancer patients after NAT. METHODS: The study enrolled patients treated with NAT who underwent breast-conserving surgery (BCS) between July 2008 and December 2012. For the patients with a hydrogel marker or residual tumor visible on ultrasound, an IOUS-guided surgery was performed (IOUS group). The patients with a standard marker or hydrogel marker not visible on ultrasound underwent a WL-guided surgery (WL group). RESULTS: The study investigated 214 patients: 145 (67.8 %) in the IOUS group and 69 (32.2 %) in the WL group. The patient and tumor characteristics were comparable between the two groups. For the patients who had a pathologic complete response (pCR) or microscopic disease, the volume excised was lower in the IOUS group (p = 0.03). The rate of reexcision for positive or close margins was similar in the two groups (p = 0.80). After a median follow-up period of 43 months, the local recurrence rates did not differ significantly between the two groups. CONCLUSIONS: Compared with WL surgery, IOUS seems to lower the volume of resection in patients with pCR or minimal microscopic disease after NAT without compromising margins and local recurrences. BCS can easily be achieved with IOUS for patients with a good response after NAT.

Estandarización de un protocolo para Northern blot no radioactivo usado en la detección de pequeños RNA en células Vero / Standardization of Northern blot non-radioactive protocol used in the detection of small RNAs in Vero line cells

El interés en la detección, identificación, y caracterización funcional de los pequeños RNAs no codificantes (sRNAs), ha generado la necesidad de optimizar las metodologías comúnmente usadas en su detección, la reacción en cadena de la polimerasa cuantitativa (RT-qPCR) y Northern blot, con el fin de que sean más sensibles y específicas. A pesar de la baja sensibilidad del Northern blot, esta metodología continúa siendo de uso común en la detección de sRNAs porque permite detectar el RNA pequeño así como a sus precursores, razón por la cual se usa como una metodología complementaria en este tipo de investigaciones. En este trabajo se describe la implementación de un nuevo protocolo para Northern blot no radioactivo, con modificaciones dirigidas a mejorar su sensibilidad y especificidad. El diseños de la sonda con la tecnología LNA, el marcaje de esta con Digoxigenina y por último la fijación del RNA a la membrana mediante 1-Ethyl-3-(-3-dimethylaminopropyl) carboniimide (EDC) y finalmente se discuten los fundamentos teóricos de estos cambios.

The interest in detection, identification and functional characterization of small non-coding RNAs (snRNAs), has generated the need to optimize the methodologies commonly used in its detection in specificity and sensitivity, The Quantitative reverse transcription PCR (RT-qPCR) and Northern blot. Even though the low sensitivity of Northern blot, this method continues to be commonly used in the sRNAs, because its capacity to detect the sRNA and its precursor, which is the reason why Northern blot is used as complementary method in this sort of Research. This work describes the implementation of an innovative non-radioactive Northern blot protocol, with modifications that improving the sensibility and specificity, with the discussion of the theoretical foundations of such modifications.

Diferencia de iones fuertes (DIF): un acercamiento a la teoría de Stewart / Strong ion difference (SID): an approach to Stewart’s theory

El ión hidrógeno tiene la propiedad de interactuar de manera rápida con diferentes moléculas en el organismo, así como enzimas, receptores y la participación en reacciones bioquímicas y es el mismo organismo el encargado de regular su concentración en los diferentes compartimentos del cuerpo. Y es donde los trabajos desarrollados por Stewart han demostrado que la homeostasis del ión hidrógeno en los trastornos acido base no depende de si mismo y/o del intercambio con bicarbonato para tamponar el déficit o el exceso, sino que lo convierte en una variable dependiente de otros factores para su regulación en cada uno de los compartimentos, dándole importante validez a la presencia de acidos débiles, manteniendo la influencia del CO2 y resaltando la capacidad de los iones fuertes como principales determinantes en la concentración de H+ y de esta manera explica la causa en las variaciones del pH en el ser humano.

Línea de base competencias ciudadanas: resultados de la encuesta cc01 / Citizenshi compeetencies baseline: results of the cc01 survey

El presente artículo entrega los resultados finales obtenidos a partir del levantamiento de una línea de base en el tema de ciudadanía durante el año 2006, resultado de la incorporación de la investigación social al proyecto de Competencias Ciudadanas: "Ciudadanos con todo y con todos", desarrollado desde el año 2004 y hasta al fecha por la Caja de compensación familiar de Caldas, CONFAMILIARES. Los resultados aquí expuestos y las generalizaciones posibles en el análisis, aplican al contexto educativo de la básica secundaria y la media del Departamento de Caldas, ya que los grupos a encuestar, resultado del muestreo, se distribuyeron en instituciones públicas de la mayoría de sus Municipios. Estos resultados son aplicables además al contexto de trabajadores vinculados a la Caja de Compensación, sin excluir que las generalizaciones contenidas, pueden guardar relaciones cercanas con mediciones que en este mismo tema y para el mismo grupo (colaboradores de empresas y ciudadanos), han elaborado el PNUD y otras entidades de investigación del Departamento. Para realizar el estudio diagnóstico mencionado se ejecutaron aproximadamente 230 encuestas divididas, en los dos grupos. Como modelo metodológico se utilizó la experiencia vivida en la cuidad de Bogotá, concordante con el periodo de gobierno del Alcalde Antanas Mocus, además de las mediciones ejecutadas en las ciudades de Cali y Medellín.

This article delivers the final results obtained from the baseline on the issue of citizenship in 2006, resulting from the incorporation of social research to project entitled Citizenship Competences: "Citizens with everything and everybody", developed since 2004 and up to the present by the Family Compensation Fund of Caldas, CONFAMILIARES. The results presented here and the generalizations possible in the analysis, applied to the educative context of basic secondary and middle education of the Department of Caldas, since the groups surveyed, resulting from sampling, were distributed in public institutions of the majority of its Municipalities. These findings are also applicable to the context of workers linked to the Compensation Fund, without excluding that contained generalizations can be closely related to measurements on the same subject and for the same group (business partners and citizens), developed by the UNDP and other research entities of the Caldas. In order to carry out abovementioned diagnosis study approximately 230 surveys were executed divided into two groups. The experience in the city of Bogota was used as a methodological model, consistent with the governing period of the Mayor Antanas Mocus, as well as measurements performed in the cities of Cali and Medellin.