Interaction between Experiment, Modeling and Simulation of Spatial Aspects in the JAK2/STAT5 Signaling Pathway

Fundamental progress in systems biology can only be achieved if experimentalists and theoreticians closely collaborate. Mathematical models cannot be formulated precisely without deep knowledge of the experiments while complex biological systems can often not be understood fully without mathematical interpretation of the dynamic processes involved. In this article, we describe how these two approaches can be combined to gain new insights on one of the most extensively studied signal transduction pathways, the Janus kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway. We focus on the parameters of a model describing how STAT proteins are transported from the membrane to the nucleus where STATs regulate gene expression. We discuss which parameters can be measured experimentally in different cell types and how the unknown parameters are estimated, what the limits of these techniques and how accurate the determinations are

Percutaneous posterolateral approach for the simulation of a far-lateral disc herniation in an ovine model

This work describes a minimally invasive damage model for ovine lumbar discs via partial nucleotomy using a posterolateral approach. Two cadavers were dissected to analyze the percutaneous corridor. Subsequently, 28 ovine had their annulus fibrosus punctured via awl penetration under fluoroscopic control and nucleus pulposus tissue removed via rongeur. Efficacy was assessed by animal morbidity, ease of access to T12-S1 disc spaces, and production of a mechanical injury as verified by discography, radiography, and histology. T12-S1 were accessible with minimal nerve damage morbidity. Scar tissue sealed the disc puncture site in all animals within 6 weeks, withstanding 1 MP of intradiscal pressure. Partial nucleotomy led to a significant reduction in intervertebral disk height and an increased histological degeneration score. Inducing a reproducible injury pattern of disc degeneration required minimal time, effort, and equipment. The posterolateral approach allows operation on several discs within a single surgery and multiple animal surgeries within a single day.Peer reviewe

Intervertebral Disc Regeneration Injection of a Cell-Loaded Collagen Hydrogel in a Sheep Model

Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant's therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant's influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by mu-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.Peer reviewe

Micro-computed tomography, scanning electron microscopy and energy X-ray spectroscopy studies of facet joint degeneration : A comparison to clinical imaging

Segmental degeneration in the human lumbar spine affects both the intervertebral discs and facet joints. Facet joint degeneration not only affects the cartilage surface, but also alters the cellular properties of the cartilage tissue and the structure of the subchondral bone. The primary focus of this study is the investigation of these microstructural changes that are caused by facet joint degeneration. Microstructural analyses of degenerated facet joint samples, obtained from patients following operative lumbar interbody fusion, have not previously been extensively investigated. This study analyzes human facet joint samples from the inferior articular process using scanning electron microscopy, micro-computed tomography, and energy dispersive X-ray spectroscopy to evaluate parameters of interest in facet joint degeneration such as elemental composition, cartilage layer thickness and cell density, calcification zone thickness, subchondral bone portion, and trabecular bone porosity. These microstructural analyses demonstrate fragmentation, cracking, and destruction of the cartilage layer, a thickened calcification zone, localized calcification areas, and cell cluster formation as pathological manifestations of facet joint degeneration. The detailed description of these microstructural changes is critical for a comprehensive understanding of the pathology of facet joint degeneration, as well as the subsequent development and efficacy analysis of regenerative treatment strategies.Peer reviewe

Microstructure analysis method for evaluating degenerated intervertebral disc tissue

Degeneration of intervertebral disc (IVD) tissue is characterized by several structural changes that result in variations in disc physiology and loss of biomechanical function. The complex process of degeneration exhibits highly intercorrelated biomechanical, biochemical, and cellular interactions. There is currently some understanding of the cellular changes in degenerated intervertebral disc tissue, but microstructural changes and deterioration of the tissue matrix has previously been rarely explored. In this work, sequestered IVD tissue was successfully characterized using histology, light microscopy, and scanning electron microscopy (SEM) to quantitatively evaluate parameters of interest for intervertebral disc degeneration (IDD) such as delamination of the collagenous matrix, cell density, cell size, and extra cellular matrix (ECM) thickness. Additional qualitative parameters investigated included matrix fibration and irregularity, neovascularization of the IVD, granular inclusions in the matrix, and cell cluster formation. The results of this study corroborated several previously published findings, including those positively correlating female gender and IVD cell density, age and cell size, and female gender and ECM thickness. Additionally, an array of quantitative and qualitative investigations of IVD degeneration could be successfully evaluated using the given methodology, resin-embedded SEM in particular. SEM is especially practical for studying micromorphological changes in tissue, as other microscopy methods can cause artificial tissue damage due to the preparation method. Investigation of the microstructural changes occurring in degenerated tissue provides a greater understanding of the complex process of disc degeneration as a whole. Developing a more complete picture of the degenerative changes taking place in the intervertebral disc is crucial for the advancement and application of regenerative therapies based on the pathology of intervertebral disc degeneration. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Incidencia de cáncer cervicouterino en usuarias gestantes y no gestantes estudiadas en el hospital regional de Pilar de enero a diciembre de 2021

Cervical cancer is a major public health problem that occurs in women of reproductive age, and is the cause of up to 50% of all neoplasia deaths in women. Every year about 233,000 women die from this cause in developing countries, it affects all populations in the world and is the second cause of death in underdeveloped countries. Among the risk factors for this type of cancer we find a linear correlation with sexual activity, women who start it before the age of 17, multiparity, smoking, the use of oral contraceptives for long periods, among others. The objective of the study was to determine the incidence of pregnant and non-pregnant users studied at the Pilar Regional Hospital from January to December 2021. A retrospective, descriptive cross-sectional study was carried out, in which the population consisted of all the patients who attended said hospital in the gynecology, family planning, prenatal and general file services. Of 350 records analyzed, 157 cases of women who presented cervical cancer were recorded, in terms of sociodemographic data the average age was 21 years and menarche an average of 13 years. According to cytology, 93% of the users gave a negative result. Regarding parity, 15% of them were primiparous. Of the contraceptive methods used, 76% did not use any method, only 8% used condoms.El cáncer cervicouterino es un importante problema de salud pública que se presenta en mujeres en edad reproductiva, y es la causa de hasta un 50% de todas las defunciones por neoplasia en la mujer. Cada año fallecen cerca de 233000 mujeres por esta causa en países en desarrollo, afecta a todas las poblaciones del mundo y ocupa la segunda causa de muerte en países subdesarrollados. Entre los factores de riesgo para este tipo de cáncer encontramos una correlación lineal con la actividad sexual, mujeres que inician la misma antes de los 17 años, la multiparidad, el hábito tabáquico, el uso de anticonceptivos orales por largos periodos, entre otros. El objetivo del estudio fue determinar la incidencia de las usuarias gestantes y no gestantes estudiadas en el Hospital Regional de Pilar de Enero a Diciembre de 2021. Se realizó un estudio retrospectivo, descriptivo de corte transversal, en la que la población estuvo constituida por todas las pacientes que acudieron a dicho nosocomio en los servicios de ginecología, planificación familiar, prenatal y archivo general. De 350 fichas analizadas se registraron 157 casos de mujeres que presentaron cáncer cervicouterino, en cuanto a los datos sociodemográficos la edad promedio fue de 21 años y la menarca un promedio de 13 años. De acuerdo a la citología el 93% de las usuarias dieron un resultado negativo. En cuanto a la paridad 15% de ellas eran primíparas. De los métodos anticonceptivos utilizados el 76% no utilizaban ningún método solo el 8% utilizaban el preservativo

Frecuencia de carcinoma ductal in situ en pacientes del servicio de mastología del hospital nacional de Itauguá-Paraguay en un periodo de enero 2012 a diciembre 2019

Breast cancer represents a public health problem due to its frequency and mainly because the diagnosis and treatment alter the quality of the women affected in all dimensions, it represents the leading cause of death from any type of cancer in the female population and its Prognosis depends fundamentally on the extent or stage of the disease in which it is diagnosed and the tumor subtype. Detection of ductal carcinoma in situ is evidence that public health programs are effective; Since this stage is curable, this is why it is important to carry out this study, in order to determine the number of patients arriving in early stages, who could benefit from less invasive but curative treatments. A descriptive, retrospective, cross-sectional study was carried out to determine the frequency of ductal carcinoma in situ in patients with a diagnosis of breast cancer from the HNI Mastology Service from 2012 to 2019. A total of 24 patients with said disease were found. diagnosis, which corresponded to 3.1% of all diagnosed cancers. Most of them came from the Central Department, approximately 50 years old, with no valuable family or personal pathological history, with a high-grade histological pattern with comedoconecrosis and positive hormone receptors; half received conservative treatment, and the rest, mastectomy; 20.83% of the patients received immediate reconstructive treatment. The low percentage of detection in early stages of breast cancer in our environment is noteworthy.El cáncer de mama representa un problema de salud pública debido a su frecuencia y principalmente porque el diagnóstico y tratamiento alteran la calidad de las mujeres afectadas en todas las dimensiones, representa la primera causa de muerte por cualquier tipo de cáncer en la población femenina y su pronóstico depende fundamentalmente de la extensión o de la etapa de la enfermedad en la que se diagnostique y del subtipo tumoral. La detección del carcinoma ductal in situ es la evidencia de que los programas de salud pública son efectivos; ya que este estadio es curable, he aquí la importancia de realizar este estudio, a fin de determinar la cantidad de pacientes que llegan en estadios precoces, que podrían ser beneficiadas de tratamientos menos cruentos pero curativos. Se realizó un estudio descriptivo, retrospectivo, de corte trasversal a fin de determinar la frecuencia de carcinoma ductal in situ en pacientes con diagnóstico de cáncer de mama del Servicio de Mastología del HNI del 2012 al 2019. Se encontró un total de 24 pacientes con dicho diagnóstico, que correspondió al 3,1% del total de cánceres diagnosticados. En su mayoría provenientes del Departamento Central, de aproximadamente 50 años, sin antecedentes patológicos familiares ni personales de valor, con patrón histológico de alto grado con comedoconecrosis y receptores hormonales positivos; la mitad recibió tratamiento conservado, y la restante, mastectomía; el 20,83% de las pacientes recibió tratamiento reconstructivo inmediato. Es destacable el bajo porcentaje de detección en estadios precoces del cáncer de mama en nuestro medio

Shattered Dreams of Anti-Fascist Unity: German Speaking Exiles in Mexico, Argentina and Bolivia, 1937-1945

Between the late 1930s and early 1940s Mexico City and Buenos Aires became the centres of activity for the two most relevant anti-fascist organisations of German-speaking exiles in Latin America: the communist-inspired Free German Movement (Bewegung Freies Deutschland;BFD) and the social-democratic oriented The Other Germany (Das Andere Deutschland;DAD). Both organisations envisaged the creation of an anti-fascist front within Latin America, one which would allow for greater unity of action, and thus carried out extensive congresses at Mexico City and Montevideo in 1943. Due to crucial ideological and tactical differences, this dream of anti-fascist unity led to a power struggle between BFD and DAD, well illustrated in the impact it had on Bolivia. This article seeks a new perspective on how, thanks to the establishment of transnational networks, a continental debate on the meaning and methods of anti-fascism then took place, while also shedding light on the influence the Latin American context had in shaping the exiles' plans for a new Germany

Prevalencia de la enfermedad de chagas en gestantes del hospital regional de Pilar en el periodo 2020- 2021

Chagas disease, also called American trypanosomiasis, is a life-threatening disease caused by the protozoan parasite Trypanosoma cruzi. The main vectors are insects of the triatomine species, the main vector in South America being Triatoma infestans. According to PAHO/WHO, this disease constitutes one of the main public health problems in several countries, mainly in Latin America. Clinically, 3 stages of the disease are recognized; the initial or acute stage, which is short-lived and is separated by an indeterminate asymptomatic stage, to then gradually enter the chronic stage, which generally appears late. Lesions occur mainly in the myocardium and viscera, with chronic patients presenting up to 30% cardiac alterations and 10% digestive, neurological or combined alterations. The objective of the study Determine the prevalence of Chagas disease in pregnant women studied in the HRP period 2020 to 2021. A descriptive, retrospective, cross-sectional study was carried out. The population made up of 7,160 pregnant women who attended the Pilar Regional Hospital in the Gynecology-Obstetrics service in the years 2020-2021. The sample consisted of 45 pregnant women studied in a public hospital in the Ñeembucu department of Paraguay, 14 (31%) represent the prevalence of Chagas disease in pregnant women. Among the sociodemographic data, we observe that the average age of the pregnant women who consulted is 29 years, 38 (84%) from the Rural area. Risk Factor 31 (68%) do not have a risk factor and 7 (16%) have Arterial Hypertension, 35 (78%) underwent the study in the third trimestreLa enfermedad de Chagas, también llamada tripanosomiasis americana,  enfermedad potencialmente mortal causada por el parásito protozoo Trypanosoma cruzi. Los principales vectores son insectos de la especie triatominos, siendo el principal vector en América del Sur el Triatoma infestans. Según la OPS/OMS, esta enfermedad constituye uno de los principales problemas de salud pública en diversos países, principalmente en América Latina. Clínicamente se reconocen 3 etapas de la enfermedad; la inicial o aguda que es de corta duración y está separada por una etapa asintomática indeterminada para luego entrar poco a poco en la etapa crónica la que generalmente aparece tardíamente. Las lesiones se producen principalmente en el miocardio y vísceras presentando los enfermos crónicos hasta un 30 % alteraciones cardiacas y un 10 % alteraciones digestivas, neurológicas o combinadas. El objetivo del estudio Determinar la prevalencia de enfermedad de Chagas en gestantes estudiadas en el HRP periodo 2020 al 2021. Se realizó un estudio descriptivo, retrospectivo transversal. La población  constituida por 7.160 embarazadas que acudieron al Hospital Regional de Pilar en el servicio de  Gineco-Obstetricia en los años 2020-2021. La muestra estuvo conformada por 45 embarazadas estudiadas en un hospital público del departamento Ñeembucu de Paraguay, 14 (31%) representa la prevalencia de Chagas en embarazadas. Entre los datos sociodemográficos observamos que la edad promedio de las gestantes que consultaron es de 29 años, 38(84%) del área Rural. Factor de Riesgo 31(68%) no presenta factor de riesgo y 7(16%) presenta Hipertensión Arterial, 35(78%) se realizó el estudio en el tercer trimestr

Antifascismo: un espacio de encuentro entre el exilio y la política nacional. El caso de Vicente Lombardo Toledano en México (1936-1945)

This article puts forward an original interpretation of antifascism, understood as a transatlantic political culture, focusing upon the case of the union leader Vicente Lombardo Toledano. Between the Spanish Civil War and the Second World War, antifascism in Mexico acquired several meanings, centred on the reinvention of the Mexican Revolution’s legacy, while benefiting from the collaboration between European antifascist exiles and local left-wing circles. Making use of novel sources, this article vindicates the key role that Mexico was then able to enjoy internationally due to its ideological commitments.Este artículo propone una lectura original del antifascismo, entendido como una cultura política trasatlántica, a partir del caso del líder sindicalista Vicente Lombardo Toledano. Se discute la evolución del significado del antifascismo en México, centrado en la recreación del legado de la Revolución Mexicana, en el período comprendido entre la Guerra Civil española y la Segunda Guerra Mundial, enfatizando la colaboración entre el exilio antifascista europeo y los círculos izquierdistas locales. A partir de varios documentos inéditos, se reivindica el protagonismo que México ejerció entonces en virtud de su compromiso ideológico