Straightforward Synthesis of Novel Acene-Based Aryne Precursors

Large polycyclic o-(trimethylsilyl)aryl triflates are easily obtained by reaction of commercially available bisaryne precursors with cyclopentadienones. The transformation involves controlled generation of one of the aryne functionalities, trapping by Diels–Alder reaction with a dienone, and chelotropic extrusion of CO. The newly synthesized triflates are precursors of acene-based arynes, including a didehydropentaceneFinancial support from the Spanish Ministry of Science and Competitiveness (MINECO, CTQ2013-44142-P and MAT2013-46593-C6-6-P), the European Union (Project PAMS, contract no. 610446), Xunta de Galicia (GPC2014/25), and FEDER is gratefully acknowledged. D.R.-L. thanks the Spanish Ministry of Education for the award of an FPU fellowshipS

1,7-Naphthodiyne: a new platform for the synthesis of novel, sterically congested PAHs

The synthesis of an efficient precursor of the novel 1,7-naphthodiyne synthon is reported. Preliminary experiments demonstrate the usefulness of this platform for the synthesis of sterically congested polyarenes, such as helicenes and angularly fused acene derivatives. Furthermore, a novel intramolecular aryne trapping reaction is describedFinancial support from the Spanish Ministry of Economy and Competitiveness (MINECO, CTQ2013-44142-P and MAT2013-46593-C6-6-P), the European Union (Project PAMS, contract no. 610446), Xunta de Galicia (GPC2014/25) and FEDER is gratefully acknowledgedS

Microwave-induced covalent functionalization of few-layer graphene with arynes under solvent-free conditions

A non-conventional modification of exfoliated few-layer graphene (FLG) with different arynes under microwave (MW) irradiation and solvent-free conditions is reported. The described approach allows reaching fast, efficient and mild covalent functionalization of FLG.M. P. is the recipient of the AXA Chair (2016-2023). This work was supported by the EU H2020-Adhoc-2014-20 Graphene Core1 (no. 696656)S

Survival of spin state in magnetic porphyrins contacted by graphene nanoribbons

We report on the construction and magnetic characterization of a fully functional hybrid molecular system composed of a single magnetic porphyrin molecule bonded to graphene nanoribbons with atomically precise contacts. We use on-surface synthesis to direct the hybrid creation by combining two molecular precursors on a gold surface. High-resolution imaging with a scanning tunneling microscope finds that the porphyrin core fuses into the graphene nanoribbons through the formation of new carbon rings at chemically predefined positions. These ensure the stability of the hybrid and the extension of the conjugated character of the ribbon into the molecule. By means of inelastic tunneling spectroscopy, we prove the survival of the magnetic functionality of the contacted porphyrin. The molecular spin appears unaffected by the graphenoid electrodes, and we simply observe that the magnetic anisotropy appears modified depending on the precise structure of the contacts.We acknowledge the financial support from Spanish Agencia Estatal de Investigación (AEI) (project nos. MAT2016-78293-C6 and FIS2015-62538-ERC, and the Maria de Maeztu Units of Excellence Programme MDM-2016-0618), the Basque Government (Department Industry, grant no. PI-2015-1-42), the European project PAMS (610446), the Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2016 to 2019, ED431G/09), the European Research Council (grant agreement no. 635919), and the European Regional Development FundS

Diplomado de profundización supply chain management y logística

Las Pymes son las pequeñas y medianas empresas que hacen parte de la economía de un país; en nuestro caso de estudio, las Pymes de confecciones, cobijan gran parte del mercado Colombiano. Es por esta razón que se deben mejorar las condiciones internas de nuestras Pymes y así poder enfrentar la globalización y los grandes retos que trae consigo la competitividad. Los estándares de calidad, son el objetivo principal de las Pymes de confecciones en nuestro país, ya que de ahí depende su presencia y permanencia en el mercado. Para afrontar el mercado internacional, los estándares de calidad deben ser muy altos; de ello depende el éxito de las Pymes de confecciones de Colombia y de su permanencia en el mercado. Las Pymes de confecciones de nuestro país, deben montar estrategias de mercado para afrontar la competencia de los demás países textileros. Analizando el tema clave, como son los cuellos de botella en el proceso logístico de las Pymes de confecciones en Colombia, se eliminarían, si existiera rapidez, eficiencia y seguridad; con su erradicación, las empresas lograrían mayores ganancias, eficiencia y eficacia en las operaciones logísticas y por ende entregas justo a tiempo y la entera satisfacción del cliente.SMEs are small and medium enterprises that are part of the economy of a country; In our case study, SMEs of clothing, cover much of the Colombian market. It is for this reason that the internal conditions of our SMEs must be improved and thus be able to face globalization and the great challenges that competitiveness entails. The quality standards are the main objective of the SMEs of clothing in our country, since that depends on their presence and permanence in the market. To face the international market, quality standards must be very high; On this depends the success of the SMEs of garments of Colombia and their permanence in the market. The SMEs of clothing of our country, must set up market strategies to face the competition of the other textile countries. Analyzing the key issue, such as bottlenecks in the logistics process of SMEs in Colombia, would be eliminated, if there were speed, efficiency and safety; With its eradication, companies would achieve greater profits, efficiency and effectiveness in logistics operations and therefore deliveries just in time and the entire customer satisfaction

Dietary supplements in cognitive impairment and Alzheimer’s disease : a literature review

Objetivos: evaluar los efectos del consumo de ácidos grasos omega 3 en forma de suplementos, complementos o alimentos sobre la función cognitiva de los adultos. Métodos: se realizó una revisión de la literatura en las bases de datos Medline y Embase, buscando ensayos clínicos, estudios observacionales, revisiones sistemáticas y estudios experimentales que relacionaran los ácidos grasos omega 3 con función cognitiva y Alzheimer. Resultados: la mayoría de los estudios relacionó la suplementación de cápsulas con omega 3, el consumo de pescado u otros alimentos con contenido de omega 3, con resultados en pruebas de función cognitiva, desenlace de enfermedad o imágenes diagnósticas, encontrando en general efectos benéficos, que parecen ser mayores en personas sanas y con mejor función cognitiva de base. Hubo diferencias en los resultados encontrados en los ensayos clínicos y revisiones sistemáticas, que podrían atribuirse a la variabilidad en las dosis de la suplementación, el tiempo de seguimiento y la manera en que se midió la función y el deterioro cognitivo. Conclusión: el consumo de ácidos grasos omega 3 en forma de suplementos, complementos o alimentos ricos en estos como el pescado parece tener efectos benéficos en la función cognitiva de las personas adultas.Revisión de tema37-45Objectives: To evaluate the effects of omega 3 fatty acids consumption in the form of dietary supplement, complement or food-products presentation on adult cognitive function. Methods: A literature review in two databases (Medline and Embase) was undertaken, searching for clinical trials, observational studies, systematic reviews and experimental studies concerning omega-3 fatty acids and their relation with cognitive function and Alzheimer’s disease. Results: most studies linked supplementation with omega-3 capsules and consumption of fish and other omega-3 containing foods with results in cognitive function testing, outcomes in diseases or diagnostic imaging and found beneficial effects, which seem to be stronger in healthier persons with better cognitive function at baseline. There were differences in the results found in clinical trials and systematic reviews, which could be attributable to the variability in the supplementation dose, the length of follow-up and the methods used to assess cognitive function and decline. Conclusion: the use of omega-3 fatty acids in supplement, complement or food-products presentation seems to have beneficial effects in the cognitive function of healthy adults

Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction-modification with exercise-based cardiac rehabilitation and prognostic value.

BACKGROUND Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. OBJECTIVES To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). METHODS In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. RESULTS In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. CONCLUSIONS Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters

Familial hypercholesterolaemia: A study of 36 cases with a phenotype of homozygous familiar hypercholesterolaemia

La hipercolesterolemia familiar homocigótica (HFHo) se caracteriza por niveles muy elevados de cLDL y por enfermedad aterosclerótica temprana. Aunque la frecuencia es baja (1/300.000), las complicaciones son muy severas y pueden ser evitadas. Encontrar y tratar esta población de manera temprana podría reducir la mortalidad. Se describen 36 casos en Colombia, en donde se calcula que haya entre 160 y 200 casos. Resultados Un total de 36 pacientes con fenotipo sugestivo de HFHo fueron identificados y tratados en un período de observación de cuatro años. La media de edad fue 27 años (24 mujeres). 34 pacientes tuvieron un puntaje según la Red de Clínicas de Lípidos de Holanda (RCLH) mayor de 8 (diagnóstico definitivo) y los restantes 2 tenían puntaje equivalente a diagnóstico probable. Un cuarto de los casos procedían de la costa norte colombiana. En las pruebas genéticas, 14 fueron homocigóticos verdaderos para mutación del gen que codifica para el receptor de LDL (LDLR), 12 heterocigóticos compuestos, 2 heterocigóticos dobles y uno autosómico recesivo (LDLRAP1); 5 pacientes fueron heterocigóticos simples (LDLR) y 2 pacientes no autorizaron la prueba. En los homocigóticos verdaderos, la variante más frecuente encontrada fue la c.11G>A. 14 pacientes cursaron con enfermedad coronaria, 9 con estenosis carotídea, 8 con estenosis aórtica y 2 tuvieron ataques cerebrovasculares (ACV). 34 pacientes recibían estatinas (24 rosuvastatina), 30 recibían ezetimibe, 2 recibían evolocumab y 20 recibían lomitapide (dosis promedio 12,7mg). Ninguno recibió aféresis de cLDL. Los medicamentos, en general, fueron bien tolerados y la reducción promedio de cLDL con la terapia fue de 533,7mg/dl a 245,1mg/dl (54%). Conclusiones Todos los pacientes recibieron tratamiento hipolipemiante y se encontraron alteraciones genéticas diagnósticas en todos aquellos que autorizaron el examen. Los niveles elevados de cLDL conllevan tanto riesgo que el tratamiento debe establecerse aún sin conocer el diagnóstico genético.Homozygous familial hypercholesterolemia (HoFH) is characterized for very high levels of cLDL and early cardiovascular disease. Although incidence is low (1/300 000), complications are very severe and can be avoided. Finding and treating this population promptly could reduce mortality. We describe 36 cases in Colombia, where 160 to 200 cases are expected. Results 36 patients with phenotype of HoHF were identified and treated in a follow-up of 4 years. The mean age was 27 years (24 women). 34 of them had at least 8 points in the FH Dutch Lipid Clinic Criteria (definitive diagnosis) and two had probable diagnosis. A quarter of the cases came from the Colombian North Coast. In molecular tests, 14 were true homozygous for LDLR, 12 were compound heterozygous for LDLR, 2 double heterozygous and one was autosomal recessive; 5 were heterozygous and 2 patients did not authorized genetic test. In true homozygous subjects, the most frequent variant was c.11G>A. 14 patients had coronary disease, 9 carotid stenosis, 8 aortic stenosis and 2 had stroke. 34 patients were on statins (25 rosuvastatin), 30 were receiving ezetimibe, 2 were receiving a PSCK9 inhibitor (evolocumab) and 20 were on lomitapide with mean doses of 12.7mg. None received lipoprotein apheresis. Medications were very well tolerated. Changes in cLDL after therapy was from 533.7 mg/dL to 245 mg/dL, (54%). Conclusions Treatment was started in all patients. We found genetic mutations in all patients with genetic tests. The high levels of cLDL mean such a high risk that treatment must be started promptly, even without a genetic test

Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy

Objective: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM. Methods: TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls. Results: Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%). Conclusion: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction

Aportes de la clínica forense para conceptuar en materia probatoria sobre el riesgo para la vida en el delito de tentativa de homicidio en Colombia

The establishment of attempted murder requires the judicial inquiry to provide different evidences. Forensic technical report of nonfatal injuries at the request of the authorities can provide valuable medical concepts on the magnitude, location and severity of the injuries. So far, there has been no objective evidence built from medical science for the assessment of the likelihood of a fatal injury. In this article, we review the forensic and medical-legal concepts, which allow providing percentages of probability of fatal injury from world-renowned medical scales.El establecimiento del tipo penal de tentativa de homicidio exige a la investigación judicial aportar diferentes elementos probatorios. En este sentido, el informe técnico médico-legal de lesiones no fatales, realizado a solicitud de las autoridades, puede aportar valiosos conceptos médicos sobre la gravedad de las mismas, su localización y severidad. Sin embargo, hasta el momento no se han incorporado elementos determinantemente objetivos a partir de la ciencia médica forense para la valoración de la probabilidad que tenga una lesión para causar la muerte. En este artículo se revisan conceptos médico-legales y médicos en el contexto jurídico, que permitirían aportar una ponderación más estructurada de la probabilidad de causar la muerte de una lesión, fundamentalmente a partir de escalas médicas mundialmente reconocidas