Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1.

Given the abundance of heme proteins (cytochromes) in the mitochondrion, it is evident that a meticulously orchestrated iron metabolism is essential for cardiac health. Here, we examined the functional significance of myocardial ferritin heavy chain (FtH) in a model of acute myocardial infarction. We report that FtH deletion did not alter either the mitochondrial regulatory and surveillance pathways (fission and fusion) or mitochondrial bioenergetics in response to injury. Furthermore, deletion of myocardial FtH did not affect cardiac function, assessed by measurement of left ventricular ejection fraction, on days 1, 7, and 21 post injury. To identify the modulated pathways providing cardiomyocyte protection coincident with FtH deletion, we performed unbiased transcriptomic analysis. We found that following injury, FtH deletion was associated with upregulation of several genes with anti-ferroptotic properties, including heme oxygenase-1 (HO-1) and the cystine/glutamate anti-porter (Slc7a11). These results suggested that HO-1 overexpression mitigates ferroptosis via upregulation of Slc7a11. Indeed, using transgenic mice with HO-1 overexpression, we demonstrate that overexpressed HO-1 is coupled with increased Slc7a11 expression. In conclusion, we demonstrate that following injury, myocardial FtH deletion leads to a compensatory upregulation in a number of anti-ferroptotic genes, including HO-1. Such HO-1 induction leads to overexpression of Slc7a11 and protects the heart against ischemia-reperfusion-mediated ferroptosis, preserves mitochondrial function, and overall function of the myocardium.

A Reproducible Mouse Model of Moderate CKD With Early Manifestations of Osteoblastic Transition of Cardiovascular System.

Chronic kidney disease (CKD) is a significant public health challenge with a substantial associated risk of mortality, morbidity, and health care expenditure. Culprits that lead to development and progression of CKD are multifaceted and heterogenous in nature. This notion underscores the need for diversification of animal models to investigate its pathophysiology, related complications, and to subsequently enable discovery of novel therapeutics. Importantly, animal models that could recapitulate complications of CKD in both genders are desperately needed. Cardiovascular disease is the most common cause of death in CKD patients that may be due in part to high prevalence of vascular calcification (VC). Using DBA/2 mice that are susceptible to development of VC, we sought to investigate the feasibility and reproducibility of a unilateral ischemia-reperfusion model followed by contralateral nephrectomy (UIRI/Nx) to induce CKD and its related complications in female and male mice. Our results demonstrate that irrespective of gender, mice faithfully displayed complications of moderate CKD following UIRI/Nx as evidenced by significant rise in serum creatinine, albuminuria, higher degree of collagen deposition, elevated expression of classic fibrotic markers, higher circulating levels of FGF-23, PTH and hepcidin. Moreover, we corroborate the osteoblastic transition of aortic smooth muscle cells and cardiomyocytes based on higher levels of osteoblastic markers namely, Cbfa-1, osteopontin, osteocalcin, and osterix. Our data confirms a viable, and consistent model of moderate CKD and its associated complications in both male and female mice. Furthermore, early evidence of osteoblastic transition of cardiovascular system in this model confirms its suitability for studying and implementing potential preventive and/or therapeutic approaches that are urgently needed in this field.

Assessment of residual stumps 12 months after saphenectomy without high ligation of the saphenofemoral junction.

BACKGROUND: Currently, the first-choice option recommended for varicose vein surgery is thermal ablation of the saphenous vein, but this procedure is not available on the Brazilian National Health Service (SUS - Sistema Único de Saúde). In an effort to improve results, surgical techniques have been developed to mimic the new technologies, without their high costs. The most prominent such method involves conventional saphenectomy, without ligation of tributaries. OBJECTIVES: To assess progression of the residual stump after saphenectomy without high ligation of the saphenofemoral junction but with stump invagination and to assess the behavior of anterior/posterior accessory veins. METHODS: Prospective intervention study. A total of 52 limbs were treated with saphenectomy without high ligation of the saphenofemoral junction followed by invagination of the residual stump. Patients were assessed preoperatively and at 7 days, and 3, 6, and 12 months postoperatively using vascular ultrasonography with Doppler to analyze the length of the residual stump, the diameters of the residual stump and the anterior/posterior accessory vein, reflux in the accessory vein, and presence of neovascularization. Statistical analysis involved calculation of means, standard deviations, medians, minimum and maximum values, frequencies, and percentages, and Fisher's test and the binomial test. RESULTS: There was evidence of a significant time effect on residual stump diameter (p < 0.001) and length (p = 0.002), but the same was not observed with relation to diameter (p = 0.355) or reflux of the anterior accessory vein. Neovascularization was found in 7 (14.3%) limbs. CONCLUSIONS: After use of the technique described, the residual stump retracted, its diameter reduced over the 1 year postoperative period, and it did not transfer reflux to the accessory vein. Neovascularization rates were in line with the literature.

Avaliação do coto residual após 12 meses de safenectomia sem ligadura alta da junção safeno-femoral / Assessment of residual stumps 12 months after saphenectomy without high ligation of the saphenofemoral junction

Resumo Contexto Atualmente, recomenda-se como primeira opção cirúrgica de varizes a termoablação da veia safena; porém, esse procedimento não é realizado pelo Sistema Único de Saúde do Brasil. Como forma de incluir melhores resultados, técnicas cirúrgicas esforçam-se para mimetizar as novas tecnologias sem seus custos, sendo a principal delas a realização da safenectomia convencional sem ligadura das suas tributárias. Objetivos Avaliar a evolução do coto residual após safenectomia sem ligadura alta da junção safeno-femoral associada à invaginação do mesmo, assim como avaliar o comportamento das veias acessórias anterior/posterior. Métodos Estudo prospectivo e intervencionista. Foram operados 52 membros pela técnica de safenectomia sem ligadura alta da junção safeno-femoral seguida da invaginação do coto residual. Os pacientes foram avaliados no pré e pós-operatório (7 dias, 3, 6 e 12 meses) através de ultrassonografia vascular com Doppler para análise de diâmetro e extensão do coto residual, diâmetro e refluxo na veia acessória anterior/posterior e presença de neovascularização. A análise estatística foi realizada por média, desvio padrão, mediana, valor mínimo e máximo, frequências e percentuais, teste de Fisher e bimodal. Resultados Evidenciou-se um efeito significativo do tempo sobre a medida de diâmetro (p < 0,001) e da extensão (p = 0,002) do coto residual, porém o mesmo não foi observado quanto ao diâmetro (p = 0,355) ou refluxo na veia acessória anterior. Foi identificada neovascularização em 7 (14,3%) membros. Conclusões Após a utilização da técnica descrita, o coto residual apresentou retração e diminuição do seu diâmetro no período de 1 ano e não transmitiu refluxo para veia acessória. As taxas de neovascularização foram condizentes com a literatura.

Abstract Background Currently, the first-choice option recommended for varicose vein surgery is thermal ablation of the saphenous vein, but this procedure is not available on the Brazilian National Health Service (SUS - Sistema Único de Saúde). In an effort to improve results, surgical techniques have been developed to mimic the new technologies, without their high costs. The most prominent such method involves conventional saphenectomy, without ligation of tributaries. Objectives To assess progression of the residual stump after saphenectomy without high ligation of the saphenofemoral junction but with stump invagination and to assess the behavior of anterior/posterior accessory veins. Methods Prospective intervention study. A total of 52 limbs were treated with saphenectomy without high ligation of the saphenofemoral junction followed by invagination of the residual stump. Patients were assessed preoperatively and at 7 days, and 3, 6, and 12 months postoperatively using vascular ultrasonography with Doppler to analyze the length of the residual stump, the diameters of the residual stump and the anterior/posterior accessory vein, reflux in the accessory vein, and presence of neovascularization. Statistical analysis involved calculation of means, standard deviations, medians, minimum and maximum values, frequencies, and percentages, and Fisher's test and the binomial test. Results There was evidence of a significant time effect on residual stump diameter (p < 0.001) and length (p = 0.002), but the same was not observed with relation to diameter (p = 0.355) or reflux of the anterior accessory vein. Neovascularization was found in 7 (14.3%) limbs. Conclusions After use of the technique described, the residual stump retracted, its diameter reduced over the 1 year postoperative period, and it did not transfer reflux to the accessory vein. Neovascularization rates were in line with the literature.

Absence of right common carotid artery in a patient with common origin of the innominate artery and left common carotid artery.

A 50-year-old woman was referred to the noninvasive vascular laboratory for carotid artery evaluation because of a bruit in the neck. Color Doppler ultrasound examination demonstrated absence of the right common carotid artery and parallel internal and external carotid arteries originating at the brachiocephalic trunk. Computed tomography angiography further described anomalous anatomy, demonstrating a common origin of the innominate artery and left common carotid artery. Knowledge of such unusual anatomy may become valuable in future evaluation or treatment of this patient.

Bilateral anterior tibial artery entrapment by the ankle extensor retinaculum: case report.

Vascular entrapment is rare. In the lower limbs it is generally asymptomatic, but may cause atypical intermittent claudication in young people without risk factors for atherosclerosis and inflammatory diseases. The most common type of compression involves the popliteal artery, causing symptoms in the region of the infra-patellar muscles. When discomfort is more distal, other entrapment points should be considered, such as the anterior tibial artery. This article reports the case of a patient with intermittent claudication in both feet due to extrinsic compression of the anterior tibial artery bilaterally by the extensor retinaculum of the ankle, diagnosed by vascular ultrasonography and angiotomography during plantar flexion maneuvers. The patient was treated surgically, resulting in improvement of clinical symptoms.

Síndrome do aprisionamento da artéria tibial anterior bilateral pelo retináculo extensor do tornozelo: relato de caso / Bilateral anterior tibial artery entrapment by the ankle extensor retinaculum: case report

Resumo Os aprisionamentos vasculares são raros. Nos membros inferiores, geralmente são assintomáticos, mas podem causar claudicação intermitente atípica em indivíduos jovens sem fatores de risco para aterosclerose ou doenças inflamatórias. O vaso mais frequentemente acometido é a artéria poplítea, causando a síndrome do aprisionamento da artéria poplítea (SAAP), com sintomas na região dos músculos infrapatelares. Quando o desconforto ao esforço é mais distal, deve-se pensar em outros locais de aprisionamento arterial, como a artéria tibial anterior. Neste trabalho, é relatado o caso de um paciente com claudicação intermitente nos pés devido ao aprisionamento da artéria tibial anterior (AATA) bilateral, causado pelo retináculo dos músculos extensores e diagnosticado pela ultrassonografia vascular e angiotomografia durante flexão plantar. O paciente foi tratado cirurgicamente, evoluindo com melhora dos sintomas clínicos.

Abstract Vascular entrapment is rare. In the lower limbs it is generally asymptomatic, but may cause atypical intermittent claudication in young people without risk factors for atherosclerosis and inflammatory diseases. The most common type of compression involves the popliteal artery, causing symptoms in the region of the infra-patellar muscles. When discomfort is more distal, other entrapment points should be considered, such as the anterior tibial artery. This article reports the case of a patient with intermittent claudication in both feet due to extrinsic compression of the anterior tibial artery bilaterally by the extensor retinaculum of the ankle, diagnosed by vascular ultrasonography and angiotomography during plantar flexion maneuvers. The patient was treated surgically, resulting in improvement of clinical symptoms.

LimeSeg: a coarse-grained lipid membrane simulation for 3D image segmentation.

BACKGROUND: 3D segmentation is often a prerequisite for 3D object display and quantitative measurements. Yet existing voxel-based methods do not directly give information on the object surface or topology. As for spatially continuous approaches such as level-set, active contours and meshes, although providing surfaces and concise shape description, they are generally not suitable for multiple object segmentation and/or for objects with an irregular shape, which can hamper their adoption by bioimage analysts. RESULTS: We developed LimeSeg, a computationally efficient and spatially continuous 3D segmentation method. LimeSeg is easy-to-use and can process many and/or highly convoluted objects. Based on the concept of SURFace ELements ("Surfels"), LimeSeg resembles a highly coarse-grained simulation of a lipid membrane in which a set of particles, analogous to lipid molecules, are attracted to local image maxima. The particles are self-generating and self-destructing thus providing the ability for the membrane to evolve towards the contour of the objects of interest. The capabilities of LimeSeg: simultaneous segmentation of numerous non overlapping objects, segmentation of highly convoluted objects and robustness for big datasets are demonstrated on experimental use cases (epithelial cells, brain MRI and FIB-SEM dataset of cellular membrane system respectively). CONCLUSION: In conclusion, we implemented a new and efficient 3D surface reconstruction plugin adapted for various sources of images, which is deployed in the user-friendly and well-known ImageJ environment.

"Praticamos SM, repudiamos agressão": classificações, redes e organização comunitária em torno do BDSM no contexto brasileiro / "Practicamos SM, repudiamos la agresión": clasificaciones, redes y organización comunitaria en torno al BDSM en el contexto brasileño / "We practice SM, we repudiate aggression": classifications, networks and communitary organization around BDSM in the Brazilian context

A apropriação com sentido erótico da categoria sadomasoquismo e/ou a adesão ao acrônimo BDSM têm se feito presentes no Brasil desde pelo menos a década de 1980, com a organização de uma comunidade que imagina a si mesma a partir da adesão a um conjunto diverso de práticas eróticas e a noções relacionadas à consensualidade e à segurança, marca-das pela (des)identificação com perspectivas patologizantes. A partir de perspectiva etnográfica, este artigo focaliza conexões, diálogos e o trânsito de categorias e classificações entre diferentes atores sociais envolvidos na disputa de sentidos acerca desse conjunto diverso de práticas e convenções. A produção de subjetividades e de agenciamentos coletivos é analisada tomando por base a relação com outros atores sociais, especialmente com as classificações oriundas dos saberes médico-científicos. O BDSM como lugar social é situado num espaço intersticial entre diagnósticos médicos, nichos de mercado erótico e comunidades políticas.

La apropiación con sentido erótico de la categoría sadomasoquismo y/o la adhesión al acrónimo BDSM se han hecho presentes en Brasil, desde por lo menos la década de 1980, con la organización de una comunidad que se imagina a sí misma a partir de la adhesión a un conjunto diverso de prácticas eróticas, y a nociones relacionadas con la consensualidad y la seguridad, marcadas por la (des)identificación con perspectivas patologizantes. Desde un abordaje etnográfico, este artículo pone el foco en conexiones, diálogos y tránsitos de categorías y clasificaciones entre diferentes actores sociales involucrados en la disputa de sentidos acerca de ese conjunto diverso de prácticas y convenciones. Se analiza la producción de subjetividades y agenciamientos colectivos basándose en la relación con otros actores sociales, especialmente con las clasificaciones provenientes de los saberes médico-científicos. El BDSM como lugar social es situado en el espacio intersticial entre diagnósticos médicos, nichos del mercado erótico y comunidades políticas.

The erotic appropriation of the category sadomasochism, as well as the adoption of the acronym BDSM have been present in Brazil since at least the 1980s. Communities that imagine themselves by joining a diverse set of erotic practices and notions related to consensuality and safety have organized, marked by their (dis)identification towards pathological perspectives. Working from an ethnographic perspective, this article focuses on links, dialogues and the transit of categories and classifications among different social actors involved in the dispute over the meanings of this diverse set of practices and conventions. The production of subjectivities and collective assemblages is analyzed based on the relationship with other social actors, especially with the classifications that come from the medical-scientific field of knowledge. BDSM is located as a social site in the interstitial space between medical diagnostics, erotic market niches, and political communities.

Discriminating biomolecules with coherent control strategies.

The activity of the GAP-Biophotonics research group at the University of Geneva in the field of coherent control for discriminating similar biomolecules, such as flavins, proteins and DNA bases, is presented and future developments are discussed.