Tumorigenic effect mediated by ROS/eicosanoids and their regulation on TP53 expression in a murine mammary gland adenocarcinoma.

The aim of this study was to investigate the in vivo and in vitro effects of dietary ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) and their derivatives on the expression of TP53 and their relationship with cellular proliferation and death in a murine mammary adenocarcinoma model. BALB/c mice were divided in three diet groups: chia oil (ChO) rich in ω-3, corn oil (CO) rich in ω-6/ω-3 and safflower oil (SO) rich in ω-6 and subcutaneously inoculated with LMM3 mammary tumor cell line. Results demonstrated that diets with higher concentration of omega-6 PUFAs induced an increment of linoleic and arachidonic acid on tumor cell membranes increasing ROS liberation, 12(S)-HHT generation, TP53, Ki67 expression and cell proliferation. However, diets enriched with high content in omega-3 PUFAs induced higher tumor cell apoptosis and tumor infiltration of CD3+ lymphocytes, lowest cell viability and proliferation. Dietary omega-3 PUFAs nutritional intervention can be used as a potential preventative strategy to inhibit the molecular signaling pathways involved in the mammary tumor growth process as the TP53.

Síndrome de Horner por migración paravertebral cefálica del anestésico local / Horner syndrome secondary to cephalic paravertebral migration of local anaesthetic

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Impact and safety of open lung biopsy in patients with acute respiratory distress syndrome (ARDS) / Impacto y seguridad de la biopsia abierta de pulmón en pacientes con síndrome de distrés respiratorio agudo

Introduction: Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder, and its pathological hallmark is diffuse alveolar damage (DAD). Given that open lung biopsy (OLB) can sometimes result in severe side effects, it is rarely performed in patients with ARDS. Aim: The aims of this study were to describe: (a) the rate of treatment change associated with the histological result; and (b) the incidence of side effects induced by OLB. Design and patients: A retrospective, single-center, descriptive observational study was carried out in Hospital Santa Clara (Bogotá, Colombia) from February 2007 to January 2014. Inclusion criteria: Critically ill patients over 18 years of age, undergoing invasive mechanical ventilation, diagnosed with ARDS of unknown etiology, and with OLB performed at the bedside. ARDS was diagnosed according to the Berlin definition. DAD was defined by the presence of a hyaline membrane plus at least one of the following: intra-alveolar edema, alveolar type I cell necrosis, alveolar type II cell (cuboidal cells) proliferation progressively covering the denuded alveolar-capillary membrane, interstitial proliferation of fibroblasts and myofibroblasts, or organizing interstitial fibrosis. The rate of treatment change (RTC) was established according to whether the OLB pathology report resulted in: a) the prescription or discontinuation of an antimicrobial; b) the indication of new procedures; c) medical interconsultation; or d) limitation of therapeutic effort. Patients were followed-up until death or hospital discharge. This study was approved by the Ethics Committee. Results: A total of 32 OLBs were performed during the study period; 17 were ruled out as they did not involve ARDS, and 15 were considered for further analysis. A histological diagnosis was reached in 14 of the 15 patients (12 DAD, one case of bronchiolitis obliterans organizing pneumonia and one case of Wegener's granulomatosis with alveolar hemorrhage). The RTC rate was 0.73. The most frequent intervention was discontinuation of antimicrobial or corticosteroid treatment. No deaths but four side effects (3 airway leaks and one hemothorax) were associated with the OLB procedure. All were resolved before ICU discharge. Conclusion: The information provided by OLB performed at the bedside in ARDS patients of unknown etiology could be relevant, as it may optimize treatment. The risk associated with OLB seems to be acceptable

Introducción: El síndrome de dificultad respiratoria aguda (ARDS, acute respiratory distress syndrome) es una enfermedad pulmonar inflamatoria y su característica distintiva patológica es el daño alveolar difuso (DAD, diffuse alveolar damage). Dado que la biopsia pulmonar abierta (OLB, open lung biopsy) a veces puede dar lugar a efectos secundarios graves, rara vez se realiza en pacientes con SDRA. Objetivos: Los objetivos de este estudio fueron describir: a) la tasa de cambio de tratamiento asociado con el resultado histológico y b) la tasa de efectos secundarios inducidos por la OLB. Diseño: Estudio observacional, descriptivo, unicéntrico y retrospectivo realizado en el Hospital Santa Clara, Bogotá (Colombia) desde febrero de 2007 a enero de 2014. Criterios de inclusión: Pacientes críticamente enfermos mayores de 18 años sometidos a ventilación mecánica invasiva, diagnosticados con SDRA de etiología desconocida en quienes se realizó la OLB al lado de la cama. El SDRA fue diagnosticado según la definición de Berlín. El DAD se definió por la presencia de membrana hialina y al menos uno de los siguientes criterios: edema intraalveolar, necrosis de células alveolares tipo I, proliferación de células alveolares tipo II (células cuboidales) con denudación progresiva de la membrana alveolar-capilar, proliferación intersticial de fibroblastos y miofibroblastos o fibrosis intersticial organizada. La tasa de cambio de tratamiento asociada con el resultado de la biopsia pulmonar abierta (RTC) se definió si, basándose en el análisis patológico de la biopsia de pulmón abierto: a) se prescribió o suspendió un antimicrobiano, b) se indicó un nuevo procedimiento, o c) interconsulta médica, o d) limitado el esfuerzo terapéutico. Los pacientes fueron seguidos hasta la muerte o el alta hospitalaria. Este estudio fue aprobado por el comité de ética. Resultados: Durante el período de estudio, se realizaron 32 OLB; 17 pacientes fueron descartados, ya que no tenían ARDS y 15 fueron considerados para análisis. Se llegó a diagnóstico histológico en 14 (12 casos con DAD, un caso con bronquiolitis obliterante con neumonía de organización y un caso con granulomatosis de Wegener asociada a hemorragia alveolar) de los 15 pacientes; RTC: 0,73. La intervención más frecuente fue la interrupción del tratamiento con antimicrobianos o esteroides. No hubo muertes, pero 4 acontecimientos adversos (3 neumotórax y un hemotórax) se asociaron con el procedimiento de OLB. Todos fueron resueltos antes del alta de la UCI. Conclusión: La OLB constituye un procedimiento de diagnóstico de alto rendimiento que determina un impacto relevante en el tratamiento de pacientes con SDRA. El riesgo asociado a este procedimiento es aceptable. La información proporcionada por la OLB, realizada junto a la cama en la UCI, en pacientes con SDRA de etiología desconocida es relevante, ya que puede optimizar el tratamiento. El riesgo asociado con la OLB parece ser aceptable

Impact and safety of open lung biopsy in patients with acute respiratory distress syndrome (ARDS).

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder, and its pathological hallmark is diffuse alveolar damage (DAD). Given that open lung biopsy (OLB) can sometimes result in severe side effects, it is rarely performed in patients with ARDS. AIM: The aims of this study were to describe: (a) the rate of treatment change associated with the histological result; and (b) the incidence of side effects induced by OLB. DESIGN AND PATIENTS: A retrospective, single-center, descriptive observational study was carried out in Hospital Santa Clara (Bogotá, Colombia) from February 2007 to January 2014. INCLUSION CRITERIA: Critically ill patients over 18 years of age, undergoing invasive mechanical ventilation, diagnosed with ARDS of unknown etiology, and with OLB performed at the bedside. ARDS was diagnosed according to the Berlin definition. DAD was defined by the presence of a hyaline membrane plus at least one of the following: intra-alveolar edema, alveolar type I cell necrosis, alveolar type II cell (cuboidal cells) proliferation progressively covering the denuded alveolar-capillary membrane, interstitial proliferation of fibroblasts and myofibroblasts, or organizing interstitial fibrosis. The rate of treatment change (RTC) was established according to whether the OLB pathology report resulted in: a) the prescription or discontinuation of an antimicrobial; b) the indication of new procedures; c) medical interconsultation; or d) limitation of therapeutic effort. Patients were followed-up until death or hospital discharge. This study was approved by the Ethics Committee. RESULTS: A total of 32 OLBs were performed during the study period; 17 were ruled out as they did not involve ARDS, and 15 were considered for further analysis. A histological diagnosis was reached in 14 of the 15 patients (12 DAD, one case of bronchiolitis obliterans organizing pneumonia and one case of Wegener's granulomatosis with alveolar hemorrhage). The RTC rate was 0.73. The most frequent intervention was discontinuation of antimicrobial or corticosteroid treatment. No deaths but four side effects (3 airway leaks and one hemothorax) were associated with the OLB procedure. All were resolved before ICU discharge. CONCLUSION: The information provided by OLB performed at the bedside in ARDS patients of unknown etiology could be relevant, as it may optimize treatment. The risk associated with OLB seems to be acceptable.

The effects of ω-6 and ω-3 fatty-acids on early stages of mice DMBA submandibular glands tumorigenesis.

The aim of this work was: to assess the impact of diets enriched in polyunsaturated fatty acids ω-3 and ω-6 families on the lipid profile of cell membrane and their effect on cycle regulation and apoptosis, evaluated by TP53 and Ki-67 expression in 9,10-dimethyl-1,2-benzanthracene (DMBA) induced tumor development in submandibular glands (SMG) in murine models. To generate tumorigenic changes, SMG mice in the experimental group were injected with 50µl of 0.5% of DMBA. Both control (no DMBA) and experimental groups of BALB/c mice were fed with: chia oil (ChO), rich in ω-3 fatty acid; corn oil (CO), rich in ω-6/ω-3 fatty acid; and safflower (SO) oil, rich in ω-6fatty acid. Results demonstrate novel differential effects of ω-3 and ω-6 PUFAs on the regulation of early tumorigenesis events in murine SMG injected with DMBA. This knowledge may help to develop chemoprotective treatments, therapeutic agents and health promotion and prevention activities in humans.

Biomechanisms of Comorbidity: Reviewing Integrative Analyses of Multi-omics Datasets and Electronic Health Records.

OBJECTIVES: Disease comorbidity is a pervasive phenomenon impacting patients' health outcomes, disease management, and clinical decisions. This review presents past, current and future research directions leveraging both phenotypic and molecular information to uncover disease similarity underpinning the biology and etiology of disease comorbidity. METHODS: We retrieved ~130 publications and retained 59, ranging from 2006 to 2015, that comprise a minimum number of five diseases and at least one type of biomolecule. We surveyed their methods, disease similarity metrics, and calculation of comorbidities in the electronic health records, if present. RESULTS: Among the surveyed studies, 44% generated or validated disease similarity metrics in context of comorbidity, with 60% being published in the last two years. As inputs, 87% of studies utilized intragenic loci and proteins while 13% employed RNA (mRNA, LncRNA or miRNA). Network modeling was predominantly used (35%) followed by statistics (28%) to impute similarity between these biomolecules and diseases. Studies with large numbers of biomolecules and diseases used network models or naïve overlap of disease-molecule associations, while machine learning, statistics, and information retrieval were utilized in smaller and moderate sized studies. Multiscale computations comprising shared function, network topology, and phenotypes were performed exclusively on proteins. CONCLUSION: This review highlighted the growing methods for identifying the molecular mechanisms underpinning comorbidities that leverage multiscale molecular information and patterns from electronic health records. The survey unveiled that intergenic polymorphisms have been overlooked for similarity imputation compared to their intragenic counterparts, offering new opportunities to bridge the mechanistic and similarity gaps of comorbidity.

Diagnostic reference levels and complexity indices in interventional radiology: a national programme.

OBJECTIVES: To propose national diagnostic reference levels (DRLs) for interventional radiology and to evaluate the impact of the procedural complexity on patient doses. METHODS: Eight interventional radiology units from Spanish hospitals were involved in this project. The participants agreed to undergo common quality control procedures for X-ray systems. Kerma area product (KAP) was collected from a sample of 1,649 procedures. A consensus document established the criteria to evaluate the complexity of seven types of procedures. DRLs were set as the 3rd quartile of KAP values. RESULTS: The KAP (3rd quartile) in Gy cm2 for the procedures included in the survey were: lower extremity arteriography (n = 784) 78; renal arteriography (n = 37) 107; transjugular hepatic biopsies (THB) (n = 30) 45; biliary drainage (BD) (n = 314) 30; uterine fibroid embolization (UFE) (n = 56) 214; colon endoprostheses (CE) (n = 31) 169; hepatic chemoembolization (HC) (n = 269) 303; femoropopliteal revascularization (FR) (n = 62) 119; and iliac stent (n = 66) 170. The complexity involved the increases in the following KAP factors from simple to complex procedures: THB x4; BD x13; UFE x3; CE x3; HC x5; FR x5 and IS x4. CONCLUSIONS: The evaluation of the procedure complexity in patient doses will allow the proper use of DRLs for the optimization of interventional radiology. KEY POINTS: • National DRLs for interventional procedures have been proposed given level of complexity • For clinical audits, the level of complexity should be taken into account. • An evaluation of the complexity levels of the procedure should be made.

A novel mutation in CELSR1 is associated with hereditary lymphedema.

BACKGROUND: Biological evidence reported in the literature supports the role of CELSR1 as being essential for valvular function in murine lymphatics. Yet thus far, there have been no variants in CELSR1 associated with lymphatic dysfunction in humans. CASE PRESENTATION: In this report, a rare early inactivating mutation in CELSR1 is found to be causal for non-syndromic, lower extremity lymphedema in a family across three generations. Near-infrared fluorescence lymphatic imaging shows that instead of being propelled within the lumen of well-defined lymphatic vessels, lymph moved in regions of both legs in an unusual fashion and within sheet-like structures. CONCLUSION: CELSRI may be responsible for primary, non-syndromic lymphedema in humans.

Herniación pulmonar como complicación tras reanimación cardiopulmonar / Lung herniation as a complication after cardiopulmonary resuscitation

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Diversity in the preimmune immunoglobulin repertoire of SHR lines susceptible and resistant to end-organ injury.

We used next-generation sequencing to identify immunoglobulin heavy chain (IGH) genetic variation in two closely related hypertensive rat lines that differ in susceptibility to end-organ disease (SHR-A3 and SHR-B2). The two SHR lines differ extensively at the IGH locus from the rat reference genome sequence and from each other, creating 306 sequence unique IGH genes. Compared with IGH genes mapped in the rat reference genome sequence, 98 are null gene alleles (31 are null in both SHR lines, 45 are null in SHR-A3 only and 23 are null in SHR-B2 only). Of the 306 divergent gene sequences, 126 result in amino acid substitution and, among these, SHR-A3 and SHR-B2 differ from one another at the amino acid level in 96 segments. Twelve pseudogenes in the rat reference genome sequence had changes displacing the stop codon and creating probable functional genes in either or both SHR-A3 and SHR-B2. A further five alleles that encoded functional rat reference genome sequence genes or open reading frames were converted to pseudogenes in either or both SHR-A3 and SHR-B2. These studies reveal that the preimmune immunoglobulin repertoire is highly divergent among SHR lines differing in end-organ injury susceptibility and this may modify immune mechanisms in hypertensive renal injury.

Bypass anillado ¿cuál es su real utilidad?: estudio comparativo a diez años / Banded gastric bypass: a ten years evaluation

Background: Placing a ring around the gastric reservoir could improve the weight lowering effects of gastric bypass. Previous studies have shown positive results of banded gastric bypass. Aim: To evaluate the long-term outcome of patients subjected to banded gastric bypass (GB) and non-banded GB procedures. Material and Methods: Ten years follow up of260 non randomized obese patients who underwent banded GB and 218 patients in whom the ring was not placed. Excess weight loss (EWL), quality of life (QOL), food tolerance (FT), and correction of comorbidities were assessed. Results: The percentage EWL at ten years of follow up was 82 and 63 percent among patients subjected to banded and non-banded gastric bypass, respectively (p < 0.01). In three patients with banded GB, there was a migration of the ring to the interior of the stomach. Stenosis of the gastro-jejuno anastomosis occurred in 4 and 0.4 percent of patients subjected to banded and non-banded GB Perception of quality of life was similar in both groups. The outcome in terms of comorbidities was not conclusive. Conclusions: There is a clear advantage in terms of EWL among patients subjected to banded GB. No differences in quality of life were found in both groups.

Introducción: Muchos cirujanos han procurado mejorar los resultados del bypass gástrico agregando algún mecanismo restrictivo, como es la instalación de un anillo alrededor del bolsillo. Estudios previos han mostrado resultados positivos con el bypass gástrico anillado (BPGA), sin embargo, no hay estudios comparativos con resultados en el largo plazo para establecer la real utilidad de agregar un anillo durante la cirugía del bypass gástrico. Objetivo: Este estudio está dirigido a comparar el resultado a largo plazo entre el bypass gástrico (BPG) y el bypass gástrico anillado (BPGA). Material y Método: Estudiamos 260 pacientes obesos operados con anillo y 218 sin anillo. Fueron seguidos por 10 años, y se investigaron la pérdida de exceso de peso (PEP), Ia calidad de vida (CDV), tolerancia a la alimentación, y resolución de comorbilidades. Resultados: Hay una clara diferencia en el por ciento PEP desde el tercer año de control; alcanza a un 19 por ciento de diferencia en favor del BPGA al término del estudio, cifra altamente significativa. El anillo disminuye en parte la facilidad de ingesta pero esto no es sentido por los pacientes como una disminución de la calidad de vida (CDV). Los resultados en cuanto a comorbilidades no son concluyentes. Conclusiones: Hay una clara diferencia en el resultado en cuanto a PEP La calidad de vida es similar en ambos grupos. Es importante seleccionar el material adecuado y el correcto tamaño del anillo para mejorar los resultados y evitar complicaciones.

Femtosecond spectral pulse shaping with holographic gratings recorded in photopolymerizable glasses.

The majority of the applications of ultrashort laser pulses require a control of its spectral bandwidth. In this paper we show the capability of volume phase holographic gratings recorded in photopolymerizable glasses for spectral pulse reshaping of ultrashort laser pulses originated in an Amplified Ti: Sapphire laser system and its second harmonic. Gratings with high laser induce damage threshold (LIDT) allowing wide spectral bandwidth operability satisfy these demands. We have performed LIDT testing in the photopolymerizable glass showing that the sample remains unaltered after more than 10 million pulses with 0,75 TW/cm2 at 1 KHz repetition rate. Furthermore, it has been developed a theoretical model, as an extension of the Kogelnik's theory, providing key gratings design for bandwidth operability. The main features of the diffracted beams are in agreement with the model, showing that non-linear effects are negligible in this material up to the fluence threshold for laser induced damage. The high versatility of the grating design along with the excellent LIDT indicates that this material is a promising candidate for ultrashort laser pulses manipulations.