Endothelial cells (ECs) normally form an anticoagulant surface under physiological conditions, but switch to support coagulation following pathogenic stimuli. This switch promotes thrombotic cardiovascular disease. To generate thrombin at physiologic rates, coagulation proteins assemble on a membrane containing anionic phospholipid, most notably phosphatidylserine (PS). PS can be rapidly externalized to the outer cell membrane leaflet by phospholipid “scramblases,” such as TMEM16F. TMEM16F-dependent PS externalization is well characterized in platelets. In contrast, how ECs externalize phospholipids to support coagulation is not understood. We employed a focused genetic screen to evaluate the contribution of transmembrane phospholipid transport on EC procoagulant activity. We identified 2 TMEM16 family members, TMEM16F and its closest paralog, TMEM16E, which were both required to support coagulation on ECs via PS externalization. Applying an intravital laser-injury model of thrombosis, we observed, unexpectedly, that PS externalization was concentrated at the vessel wall, not on platelets. TMEM16E-null mice demonstrated reduced vessel-wall–dependent fibrin formation. The TMEM16 inhibitor benzbromarone prevented PS externalization and EC procoagulant activity and protected mice from thrombosis without increasing bleeding following tail transection. These findings indicate the activated endothelial surface is a source of procoagulant phospholipid contributing to thrombus formation. TMEM16 phospholipid scramblases may be a therapeutic target for thrombotic cardiovascular disease.

BACKGROUND: In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism. Although activated platelets release Angpt1 from α-granules into circulation, the contributions of platelet Angpt1 to tumor growth, angiogenesis, and metastasis have not been investigated. METHODS: Using cytokine arrays and ELISAs, we first compared platelet Angpt1 levels in breast and melanoma mouse tumor models to tumor-free controls. We then assessed tumor growth and metastasis in mice lacking megakaryocyte and platelet Angpt1 (Angpt1 ^{Plt KO} ). The spontaneous metastasis of mammary-injected tumor cells to the lungs was quantified using RT-PCR (reverse transcription-polymerase chain reaction). The lung colonization of intravenously injected tumor cells and tumor cell extravasation were determined using fluorescent microscopy and flow cytometry. RESULTS: Platelet Angpt1 is selectively upregulated in the PyMT (polyoma middle tumor antigen) breast cancer mouse model, and platelets are the principal source of Angpt1 in blood circulation. While primary tumor growth and angiogenesis were unaffected, Angpt1 ^{Plt KO} mice had both increased spontaneous lung metastasis and tumor cell lung colonization following mammary or intravenous injection, respectively. Although platelet Angpt1 did not affect initial tumor cell entrapment in the lungs, Angpt1 ^{Plt KO} mice had increased tumor cell retention and extravasation. Serum from Angpt1 ^{Plt KO} mice increased endothelial permeability and reduced VE (vascular endothelial)-cadherin expression at endothelial junctions compared with serum from control mice (Angpt1 ^WT ). CONCLUSIONS: Platelets provide an intravascular source of Angpt1 that restrains tumor metastasis by preserving the lung microvasculature to limit tumor cell extravasation.

The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS), which activates and joins lysine with its corresponding transfer RNA (tRNA) through the ATP-dependent aminoacylation of the amino acid. KARS gene mutations have been linked to diverse neurologic phenotypes, such as neurosensorial hearing loss, leukodystrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, the impairment of the mitochondrial respiratory chain, and hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene and, in addition to the case report, the paper reviews the literature for other cases of KARS1-associated leukodystrophy.

Background. Nowadays the importance of lifestyles in the prevention of type 2 diabetes and the metabolic syndrome has been largely accertained.Objective. The purpose of our work is to implement programs that promote a nutritional culture in adolescents and young adults of the La Sabana University.Methods. The methodology entailed, after the corresponding informed consent, taking measures of the triceps and supraescapular skinfolds, waist circumference, body mass index (BMI), lean mass, and fat mass. Fasting blood samples were also taken to quantify cholesterol, triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL).Results. The results obtained show that of the 165 students, 10.3% were underweight, 13.93% were overweight and 0.6% were obese. With regards to gender, 4.8% of the men and 9% of the women were overweight, 3% of the men and 7.2% of the women were underweight, and 0.6% of the women were obese. The blood chemistry showed that 30% had hypercholesterolemia, 18% hypertriglyceridemia, 17% reported low HDL levels and 67% reported high LDL levels. Of all the cases studied, 40% are at risk of a metabolic syndrome. 60% claimed not to practice any physical activity - especially women who reported 44.70%.Conclusions. These findings have allowed us at the institution to implement a culture of healthy habits. The have also allowed us to identify students with risk factors for type 2 diabetes and metabolic syndrome. This is why the cardiometabolic monitoring and control based on healthy eating and physical activity are important.

The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS) which activates and joins the lysin with its corresponding transfer RNA (tRNA), through the ATP-dependent aminoacylation of the amino acid. The KARS gene mutations have been linked to diverse neurologic phenotypes such as: neurosensorial hearing loss, leukodistrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, impairment of the mitochondrial respiratory chain, hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene.

In the context of the COVID-19 pandemic, the adequate selection and appropriate use of previously acquired knowledge from similar historical situations and the one acquired lately amid the pandemic is vital to guarantee correct decision-making regarding the prevention, management and treatment of this disease in the pediatric population. Since the beginning of 2020, attention has shifted to controlling the pandemic and managing patients with this disease, the majority being those in the adult population. However, more severe courses of the disease have recently been observed in pediatric patients, and what was initially considered to be a harmless pathology in this population has generated greater alerts due to the presence of severe complications. Therefore, this review seeks to determine the latest prevention, diagnosis and treatment strategies endorsed and supported by scientific evidence, in order to provide the necessary tools to guarantee proper management and to reduce, as far as possible, the fatal outcomes in the pediatric population. En el contexto de la pandemia por COVID-19, es importante la selección y el uso adecuado de los conocimientos nuevos y de aquellos adquiridos en situaciones históricas similares, para garantizar una correcta toma de decisiones en cuanto a la prevención, manejo y tratamiento de esta enfermedad en la población pediátrica. Desde inicios del 2020, la atención se ha focalizado en el control de la pandemia y en el manejo de los pacientes con esta enfermedad, cuya mayoría se encuentra en la población adulta. Sin embargo, recientemente se han observado cursos más severos de la enfermedad en pacientes pediátricos y lo que inicialmente se consideraba como una patología inofensiva ha generado mayores alertas en esta población por la presencia de complicaciones severas. Por lo anterior, la presente revisión busca determinar las últimas estrategias de prevención, diagnóstico y tratamiento avaladas y soportadas por la evidencia científica, de manera que se aporten las herramientas necesaria para garantizar un manejo adecuado y disminuir, en la medida de lo posible, los desenlaces fatales en la población pediátrica.