Electrocardiographic Identification of Abnormal Ventricular Depolarization and Repolarization in Patients With Idiopathic Ventricular Fibrillation 11This study was supported by Grant 93.080 from The Netherlands Heart Foundation.22All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.

AbstractObjectives. We sought to gain more insight into the arrhythmogenic etiology of idiopathic ventricular fibrillation (VF) by assessing ventricular depolarization and repolarization properties by means of various electrocardiographic (ECG) techniques.Background. Idiopathic VF occurs in the absence of demonstrable structural heart disease. Abnormalities in ventricular depolarization or repolarization have been related to increased vulnerability to VF in various cardiac disorders and are possibly also present in patients with idiopathic VF.Methods. In 17 patients with a first episode of idiopathic VF, 62-lead body surface QRST integral maps, QT dispersion on the 12-lead ECG and XYZ-lead signal-averaged ECGs were computed.Results. All subjects of a healthy control group had a normal dipolar QRST integral map. In patients with idiopathic VF, either a normal dipolar map (29%), a dipolar map with an abnormally large negative area on the right side of the thorax (24%) or a nondipolar map (47%) were recorded. Only four patients (24%) had increased QT dispersion on the 12-lead ECG and late potentials could be recorded in 6 (38%) of 16 patients. During a median follow-up duration of 56 months (range 9 to 136), a recurrent arrhythmic event occurred in 7 patients (41%), all of whom had an abnormal QRST integral map. Five of these patients had late potentials, and three showed increased QT dispersion on the 12-lead ECG.Conclusions. In patients with idiopathic VF, ventricular areas of slow conduction, regionally delayed repolarization or dispersion in repolarization can be identified. Therefore, various electrophysiologic conditions, alone or in combination, may be responsible for the occurrence of idiopathic VF. Body surface QRST integral mapping may be a promising method to identify those patients who do not show a recurrent episode of VF

Magnetism of small V clusters embedded in a Cu fcc matrix: an ab initio study

We present extensive first principles density functional theory (DFT) calculations dedicated to analyze the magnetic and electronic properties of small V$_{n}$ clusters (n=1,2,3,4,5,6) embedded in a Cu fcc matrix. We consider different cluster structures such as: i) a single V impurity, ii) several V$_{2}$ dimers having different interatomic distance and varying local atomic environment, iii) V$_{3}$ and iv) V$_{4}$ clusters for which we assume compact as well as 2- and 1-dimensional atomic configurations and finally, in the case of the v) V$_{5}$ and vi) V$_{6}$ structures we consider a square pyramid and a square bipyramid together with linear arrays, respectively. In all cases, the V atoms are embedded as substitutional impurities in the Cu network. In general, and as in the free standing case, we have found that the V clusters tend to form compact atomic arrays within the cooper matrix. Our calculated non spin-polarized density of states at the V sites shows a complex peaked structure around the Fermi level that strongly changes as a function of both the interatomic distance and local atomic environment, a result that anticipates a non trivial magnetic behavior. In fact, our DFT calculations reveal, in each one of our clusters systems, the existence of different magnetic solutions (ferromagnetic, ferrimagnetic, and antiferromagnetic) with very small energy differences among them, a result that could lead to the existence of complex finite-temperature magnetic properties. Finally, we compare our results with recent experimental measurements.Comment: 7 pages and 4 figure

Production of structured lipids by acidolysis of an EPA-enriched fish oil and caprylic acid in a packed bed reactor: analysis of three different operation modes.

Structured triacylglycerols (ST) enriched in eicosapentaenoic acid (EPA) in position 2 of the triacylglycerol (TAG) backbone were synthesized by acidolysis of a commercially available EPA-rich oil (EPAX4510, 40% EPA) and caprylic acid (CA), catalyzed by the 1,3-specific immobilized lipase Lipozyme IM. The reaction was carried out in a packed bed reactor (PBR) operating in two ways: (1) by recirculating the reaction mixture from the exit of the bed to the substrate reservoir (discontinuous mode) and (2) in continuous mode, directing the product mixture leaving the PBR to a product reservoir. By operating in these two ways and using a simple kinetic model, representative values for the apparent kinetic constants (k X ) for each fatty acid (native, L i or odd, M) were obtained. The kinetic model assumes that the rate of incorporation of a fatty acid into TAG per amount of enzyme, r X (mole/(h g lipase)) is proportional to the extent of the deviation from the equilibrium for each fatty acid (i.e., the difference of concentration between the fatty acid in the triacylglycerol and the concentration of the same fatty acid in the triacylglycerol once the equilibrium of the acidolysis reaction is reached). The model allows comparing the two operating modes through the processing intensity, defined as m L t/(V[TG] 0 ) and m L /(q[TG] 0 ), for the discontinuous and continuous operation modes, respectively. In discontinuous mode, ST with 59.5% CA and 9.6% EPA were obtained. In contrast, a ST with 51% CA and 19.6% EPA were obtained when using the continuous operation mode. To enhance the CA incorporation when operating in continuous mode, a two-step acidolysis reaction was performed (third operation mode). This continuous two-step process yields a ST with a 64% CA and a 15% EPA. Finally, after purifying the above ST in a preparative silica gel column, impregnated with boric acid, a ST with 66.9% CA and 19.6% EPA was obtained. The analysis by reverse phase and Ag + liquid chromatography of the EPA-enriched ST demonstrated that the CA was placed in positions 1 and 3 and the EPA was occupying position 2 of the final ST

Asociaciones de larvas de peces en relación a cambios ambientales en las Bahías Chamela, Jalisco y Santiago-Manzanillo, Colima (2001-2002)

Spatial and temporal structure of fish larvae associations and their relationship to the environmental variability were studied at Bahía Chamela, Jalisco, and Santiago-Manzanillo complex, Colima, during 2001-2002. Two spatial aggregations were found, related to the coastal physiography and to the adult habitat. The first was observed at Bahía Chamela, which integrated a combination of species belonging to coastal, demersal and inshore habitats (Bregmaceros bathymaster, Bairdiella sp., Cynoscion sp., Engraulis mordax, and Labrisomidae type 1) and the other in Santiago-Manzanillo composed by species from lagoon and inshore areas (Eucinostomus sp., Abudefduf troschelii, Haemulidae type 2 and 3, and Enneanectes sexmaculatus). Temporal organization was influenced by the environmental shift between two periods (warm and temperate) defined by the regional environmental variability. The warm period was characterized by tropical species (Harengula thrissina, Eucinostomus sp., Auxis sp., and Haemulidae type 3), related to high temperature and rainfall, while temperate period was dominated by species with a tropical-subtropical affinity (B. bathymaster, Bairdiella sp., Cynoscion sp., and E. mordax) and related to lower temperature and elevated nutrients, chlorophyll a and plankton concentrations.Se analizó la influencia de los factores ambientales sobre las asociaciones espacio-temporales de larvas de peces frente a Bahía Chamela, Jalisco y el conjunto de bahías Santiago-Manzanillo, Colima, durante un ciclo anual (2001-2002). Se identificaron dos agrupaciones relacionadas con la fisiografía de la costa y el hábitat de los adultos, una frente a Bahía Chamela integrada por una mezcla de especies de hábitats costero, demersal e intermareal-submareal (Bregmaceros bathymaster, Bairdiella sp., Cynoscion sp., Engraulis mordax y Labrisomidae tipo 1) y otra en Santiago-Manzanillo compuesta por especies de origen lagunar e intermareal-submareal (Eucinostomus sp., Abudefduf troschelii, Haemulidae tipos 2 y 3, así como Enneanectes sexmaculatus). La organización temporal estuvo influenciada por la alternancia entre dos periodos (cálido y templado) definidos por la variabilidad ambiental regional. El periodo cálido estuvo caracterizado por especies principalmente tropicales (Harengula thrissina, Eucinostomus sp., Auxis sp. y Haemulidae tipo 3), relacionadas con una mayor temperatura y precipitación pluvial, en cambio durante el periodo templado dominaron las especies de afinidad tropical-subtropical (B. bathymaster, Bairdiella sp., Cynoscion sp. y E. mordax), relacionadas con una menor temperatura e incrementos en las concentraciones de nutrimentos, clorofila-a y zooplancton

Clinical characteristics and outcome of drug-induced liver injury in the older patients: from the young-old to the oldest-old

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (<65y); “young-old” (65-74y); “middle-old” (75-84y); and “oldest-old” (≥85y). All elderly groups had increasingly higher comorbidity burden (p<0.001) and polypharmacy (p<0.001). There was a relationship between jaundice and hospitalization (p<0.001), and both were more prevalent in the elderly age groups, especially in the oldest-old (88% and 69%, respectively) and the DILI episode was more severe (p=0.029). The proportion of females decreased across age groups from the young to the middle-old, yet in the oldest-old there was a distinct female predominance. Pattern of liver injury shifted towards cholestatic with increasing age among top culprit drugs amoxicillin- clavulanate, atorvastatin, levofloxacin, ibuprofen, and ticlopidine. The best cut-off point for increased odds of cholestatic DILI was 65y. Older patients had increased non-liver related mortality (p=0.030) as shown by the predictive capacity of MELD (OR=1.116; p<0.001), and comorbidity burden (OR=4.188; p=0.001) in the 6-month mortality. Older patients with DILI exhibited an increasingly predominant cholestatic phenotype across a range of culprit drugs other that amoxicillin-clavulanate, with increased non-liver related mortality and require a different approach to predict outcome. The oldest DILI patients exhibited a particular phenotype with more severe DILI episodes and need to be considered when stratifying older DILI populations.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI 18/01804; PT17/0017/0020) and Agencia Española del Medicamento. SCReN and CIBERehd are funded by ISCIII. JSC holds a Rio Hortega (CM17/00243) and MR a “Joan Rodes” (JR16/00015) research contract from the National Health System, ISCIII. RAW held a University of Málaga visiting scientist scholarship

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed