Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia

PURPOSE OF REVIEW: To present up to date evidence on the pathogenicity of low-density lipoprotein receptor (LDLR) variants and to propose a strategy that is suitable for implementation in the clinical work-up of familial hypercholesterolaemia. RECENT FINDINGS: More than 1800 variants have been described in the LDLR gene of patients with a clinical diagnosis of familial hypercholesterolaemia; however, less than 15% have functional evidence of pathogenicity. SUMMARY: The spectrum of variants in the LDLR identified in patients with clinical familial hypercholesterolaemia is increasing as novel variants are still being reported. However, over 50% of all LDLR variants need further evidence before they can be confirmed as mutations causing disease. Even with applying the recent American College of Medical Genetics variant classification, a large number of variants are still considered variants of unknown significance. Before obtaining an undisputable confirmation of the effect on the expression and activity of the LDLR, reporting these variants as part of a clinical diagnosis to the patient holds the risk that it might need to be withdrawn in a later stage. An investment should be made to develop functional assays to characterize LDLR variants of unknown significance for a better patient diagnosis and to prevent confusion in the physician's office.The MB research has been supported by grants from the Portuguese Cardiology Society, Science and Technology Foundation and BioISI, centre grant UID/MULTI/ 04046/2013, from FCT/MCTES/PIDDAC, Portugal.info:eu-repo/semantics/publishedVersio

Food Value Of Mealworm Grown On Acrocomia Aculeata Pulp Flour

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Insects have played an important role as human food throughout history, especially in Africa, Asia and Latin America. A good example of edible insects is the mealworm, Tenebrio molitor Linnaeus, 1758 (Coleoptera, Tenebrionidae), which are eaten in Africa, Asia, the Americas and Australia. This species is easily bred in captivity, requiring simple management. The bocaiuva (Acrocomia aculeata (Jacq.) Lodd) is an abundant palm tree found in the Brazilian Cerrado, providing fruits with high nutritional value. The aim of this work was to determine the chemical composition of T. molitor grown in different artificial diets with bocaiuva pulp flour. The nutritional composition, fatty acid composition, antioxidant activity, trypsin activity and anti-nutritional factors of larvae were analyzed. The results showed that mealworms grown on artificial diet with bocaiuva are a good source of protein (44.83%) and lipid (40.45%), with significant levels of unsaturated fatty acids (65.99%), antioxidant activity (4.5 uM Trolox/g of oil extracted from larvae) and absence of anti-nutritional factors. This study indicates a new source of biomass for growing mealworms and shows that it is possible to breed mealworms in artificial diet with bocaiuva flour without compromising the nutritional quality of the larvae. © 2016 Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.113CAPES, Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Topografía Infraclavicular De Los Fascículos Del Plexo Braquial En Diferentes Posiciones Del Miembro Superior

Brachial plexus neuropathies are common complaints among patients seen at orthopedic clinics. The causes range from traumatic to occupational factors and symptoms include paresthesia, paresis, and functional disability of the upper limb. Treatment can be surgical or conservative, but detailed knowledge of the brachial plexus is required in both cases to avoid iatrogenic injuries and to facilitate anesthetic block, preventing possible vascular punctures. Therefore, the objective of this study was to evaluate the topography of the infraclavicular brachial plexus fascicles in different upper limb positions adopted during some clinical procedures. A formalin-preserved, adult, male cadaver was used. The infraclavicular and axillary regions were dissected and the distance of the brachial plexus fascicles from adjacent bone structures was measured. No anatomical variation in the formation of the brachial plexus was observed. The metric relationships between the brachial plexus and adjacent bone prominences differed depending on the degree of shoulder abduction. Detailed knowledge of the infraclavicular topography of neurovascular structures helps with the diagnosis and especially with the choice of conservative or surgical treatment of brachial plexus neuropathies. © 2016, Universidad de la Frontera. All rights reserved.3431063106

Estabilidad oxidativa de aceites de soja y maíz enriquecidos con extracto hidroalcohólico de Pluchea quitoc

Soybean and corn oils are among the most popular vegetable oils, and are ingredients which are widely used in cooking and in the food industry. These oils contain many unsaturated fatty acids such as oleic, linoleic and linolenic acids, which makes them easily oxidized by oxygen. Extensive efforts are being made to prevent or minimize vegetable oil oxidation through the development of antioxidants. Phenolic antioxidants which are present in some extracts can be used as food additives to prevent lipid oxidation. In this study chromatographic analyses (HPLC and GC) of the Pluchea quitoc hydroalcoholic extract were performed. The content of phenolic compounds by the Folin-Ciocalteau method and the antioxidant properties against radicals 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) were also evaluated. The effect of samples prepared with soybean and corn oils enriched with Pluchea quitoc hydroalcoholic extract was determined and compared with samples of these oils which were free of antioxidants and with samples containing the synthetic antioxidant BHT. The results showed potential for application of the extract. A high content of phenolic compounds (314 milligrams of gallic acid equivalents (GAE)/g of extract) and good IC50 values were detected for the inhibition of the radicals DPPH and ABTS (13.2 µg·mL-1 and 5.6 µg·mL-1). In the evaluation of the oxidative stability of the oils enriched with this extract, it was found that at 1% concentration it was possible to obtain values of induction period (IP) close to the samples with added BHT.Los aceites de soja y maíz se encuentran entre los aceites vegetales más populares, ingredientes ampliamente utilizados en la cocina y también en la industria alimentaria. Estos aceites contienen muchos ácidos grasos insaturados como los ácidos oleico, linoleico y linolénico que se oxidan fácilmente con el oxígeno. Se están realizando grandes esfuerzos para prevenir o minimizar la oxidación de los aceites vegetales mediante el desarrollo de antioxidantes. Los antioxidantes fenólicos presentes en algunos extractos se pueden utilizar como aditivos alimentarios para prevenir la oxidación de lípidos. En este estudio se realizó la obtención y análisis cromatográficos (HPLC y GC) del extracto hidroalcohólico de Pluchea quitoc. El contenido de compuestos fenólicos se evaluó por el método de Folin-Ciocalteau y las propiedades antioxidantes frente a radicales DPPH y ABTS. Se determinó el efecto de muestras preparadas con aceites de soja y maíz enriquecidas con extracto hidroalcohólico de Pluchea quitoc y se comparó con muestras de estos aceites libres de antioxidantes y con el antioxidante sintético BHT. Los resultados mostraron potencial para la aplicación del extracto. Se detectó un alto contenido de compuestos fenólicos (314 mg GAE) y buenos valores de IC50 para la inhibición de los radicales DPPH y ABTS (13.2 µg·mL-1 y 5.6 µg·mL-1). En la evaluación de la estabilidad oxidativa de los aceites enriquecidos con este extracto, se encontró que para la concentración del 1% es posible obtener valores de período de inducción (IP) cercanos a las muestras adicionadas con BHT

Stroke Etiology and Thrombus Computed Tomography Characteristics in Patients With Acute Ischemic Stroke:A MR CLEAN Registry Substudy

Background and Purpose - If a relationship between stroke etiology and thrombus computed tomography characteristics exists, assessing these characteristics in clinical practice could serve as a useful additional diagnostic tool for the identification of stroke subtype. Our purpose was to study the association of stroke etiology and thrombus computed tomography characteristics in patients with acute ischemic stroke due to a large vessel occlusion. Methods - For 1429 consecutive patients enrolled in the MR CLEAN Registry, we determined stroke cause as defined by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. The association of stroke etiology with the hyperdense artery sign, clot burden score, and thrombus location was estimated with univariable and multivariable binary and ordinal logistic regression. Additionally, for 367 patients with available thin-section imaging, we assessed the association of stroke etiology with absolute and relative thrombus attenuation, distance from internal carotid artery-terminus to thrombus, thrombus length, and thrombus attenuation increase with univariable and multivariable linear regression. Results - Compared with cardioembolic strokes, noncardioembolic strokes were associated with presence of hyperdense artery sign (odds ratio, 2.2 [95% CI, 1.6-3.0]), lower clot burden score (common odds ratio, 0.4 [95% CI, 0.3-0.6]), shift towards a more proximal thrombus location (common odds ratio, 0.2 [95% CI, 0.2-0.3]), higher absolute thrombus attenuation (β, 3.6 [95% CI, 0.9-6.4]), decrease in distance from the ICA-terminus (β, -5.7 [95% CI, -8.3 to -3.0]), and longer thrombi (β, 8.6 [95% CI, 6.5-10.7]), based on univariable analysis. Thrombus characteristics of strokes with undetermined cause were similar to those of cardioembolic strokes. Conclusions - Thrombus computed tomography characteristics of cardioembolic stroke are distinct from those of noncardioembolic stroke. Additionally, our study supports the general hypothesis that many cryptogenic strokes have a cardioembolic cause. Further research should focus on the use of thrombus computed tomography characteristics as a diagnostic tool for stroke cause in clinical practice

Abelian Hidden Sectors at a GeV

We discuss mechanisms for naturally generating GeV-scale hidden sectors in the context of weak-scale supersymmetry. Such low mass scales can arise when hidden sectors are more weakly coupled to supersymmetry breaking than the visible sector, as happens when supersymmetry breaking is communicated to the visible sector by gauge interactions under which the hidden sector is uncharged, or if the hidden sector is sequestered from gravity-mediated supersymmetry breaking. We study these mechanisms in detail in the context of gauge and gaugino mediation, and present specific models of Abelian GeV-scale hidden sectors. In particular, we discuss kinetic mixing of a U(1)_x gauge force with hypercharge, singlets or bi-fundamentals which couple to both sectors, and additional loop effects. Finally, we investigate the possible relevance of such sectors for dark matter phenomenology, as well as for low- and high-energy collider searches.Comment: 43 pages, no figures; v2: to match JHEP versio

Effective treatment of a case of pregnancy toxemia in sheep - case report

ABSTRACT Pregnancy toxemia has a high mortality rate and few cases with effective treatment are reported, especially when associated with secondary diseases. Therefore, the present work reports the case of a sheep, which was referred to the veterinary hospital of UFMG, in the last month of pregnancy, presenting apathy, hyporexia and sternal recumbency. After the diagnosis of pregnancy toxemia, the fetuses were removed while still alive, but did not survive. Monitoring was started with blood gas analysis, blood glucose assessments and laboratory tests. The results were consistent with liver damage, which was justified by the condition of lipolysis. Treatment consisted of electrolyte replacement plus 50% glucose and potassium chloride, along with administration of antibiotics (ceftiofur, 5mg/kg/SID/IM/7 days), flunixim meglumine (2.2mg/kg/SID/IM first day and 1.1mg/kg/SID/IM on the second and third days) and omeprazole (4mg/kg/SID/oral). The patient had secondarily clinical laminitis, which was treated with cryotherapy and anti-inflammatory drugs, in addition to mastitis, using a single dose of intramammary antibiotics. The work demonstrated the effectiveness of the treatment of pregnancy toxemia, when performed early and intensively, associated with daily clinical and laboratory monitoring of the animal

Seleno-functionalization of quercetin improves the non-covalent inhibition of mpro and its antiviral activity in cells against sars-cov-2

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro ) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 µM and 8 µM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile. © 2021 by the authors. Licensee MDPI, Basel, Switzerland