Tag Archives: angiotensin receptor blocker

br Author s Contributions br

Author\’s Contributions

Funding Sources

Acknowledgements

Introduction
First isolated in 1947 from the blood of a Rhesus monkey in the Zika forest, Uganda (Dick et al., 1952), Zika virus (ZIKV) was recently declared a global public health emergency by WHO (Heymann et al., 2016). After decades of confinement in Africa and Asia, the first large outbreak caused by the virus was recorded in French Polynesia in 2013 (Cao-Lormeau et al., 2014), leading to an unusual increase in the number of Guillain-Barré cases (Paixão et al., 2016). The current South-American epidemic which started in 2015 in Brazil revealed a strong correlation between infection with ZIKV and congenital angiotensin receptor blocker malformations, including microcephaly (Oliveira Melo et al., 2016).
Microcephaly is characterized by smaller head circumference, intellectual disability and seizures, and is due to reduced neuronal production or increased cell death (Barkovich et al., 2012). Recent data strongly supports the link between ZIKV and microcephaly, including detection of the virus in the amniotic fluid, placenta and brain of microcephalic fetuses, as well as in the blood of microcephalic newborns (Calvet et al., 2016; Mlakar et al., 2016; Martines et al., 2016). A retrospective study recently revealed a similar association between the French Polynesian 2013 outbreak and increased rates of microcephaly, supporting the implication of ZIKV (Cauchemez et al., 2016).
ZIKV belongs to the Flavivirus genus and is closely related to yellow fever virus (YFV), dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). Flaviviruses are arthropod-borne, single-stranded positive-sense RNA viruses, that cause infections in humans with a spectrum of clinical syndromes ranging from mild fever to hemorrhagic and encephalitic manifestations. Several infectious agents, belonging to the so-called TORCH complex, are responsible for congenital infections leading to brain developmental disorders, including microcephaly (Neu et al., 2015). However, neurotropic flaviviruses such as WNV and JEV, responsible for post-natal encephalitis, are rarely linked to congenital brain malformations, such as microcephaly (O\’Leary et al., 2006; Chaturvedi et al., 1980). Thus, neurovirulence of ZIKV in human fetuses must rely on mechanisms that are different from those involved in WNV or JEV neural infection, for example by infecting a particular set of fetal cells.
The cerebral cortex, a layered structure involved in higher cognitive functions, is strongly affected in microcephalic patients (Barkovich et al., 2012). During its normal development, all cortical neurons and most glial cells are generated, directly or indirectly, by the radial glial progenitor (RGP) cells (Kriegstein and Alvarez-Buylla, 2009). These cells are highly polarized and elongated, spanning the entire thickness of the developing neocortex. The apical process of RGP cells is in contact with the ventricular surface and the cerebro-spinal fluid (CSF), while their basal process is in contact with the pial surface and serves as a track for neuronal migration (Taverna et al., 2014). Genetic alterations leading to microcephaly are well known to affect RGP cell division, fate or survival (Fernández et al., 2016).
In vitro studies using induced Pluripotent Stem Cells (iPSCs)-derived brain cells, neurospheres and brain organoids have shown ZIKV infection of human neural stem and progenitor cells (Tang et al., 2016; Garcez et al., 2016; Qian et al., 2016; Dang et al., 2016). Recently, two different mouse models for ZIKV infection were developed and revealed a range of development defects including placental damage, developmental delay, ocular defects and embryonic death (Cugola et al., 2016; Miner et al., 2016). Another study described RGP cell infection and reduced cortical thickness after ZIKV injection into the lateral ventricle of embryonic brains (Li et al., 2016). It remains unclear if RGP cell infection was merely due to their location at the site of virus injection or if ZIKV has a specific tropism for these cells in the developing neocortex. This question is particularly important as it is still unknown if the virus reaches the developing brain via the cerebrospinal fluid (CSF), where ZIKV was detected (Rozé et al., 2016), or via blood vessels after crossing the placenta, as recently suggested (Miner et al., 2016). Another outstanding question is whether all flaviviruses share similar characteristics of infection in the developing brain, or if ZIKV, and especially microcephaly-associated ZIKV, exhibits a specific behavior in this tissue. In view of the rare congenital abnormalities associated with other flaviviruses, including following intrauterine WNV infection (O\’Leary et al., 2006), a comparative analysis between flaviviruses should provide a framework to identify ZIKV-specific mechanisms leading to microcephaly.

A renda familiar foi de

A renda familiar foi de até dois salários mínimos em 77,7% dos casos. Estudos mostram que angiotensin receptor blocker prevalência de crise febril não está associada com a classe social e a escolaridade dos pais. A tabela 3 mostra uma síntese das principais variáveis estudadas em artigos publicados até o momento, na qual podemos observar a escassez de dados relacionados ao período pré/perinatal e a heterogeneidade das variáveis pesquisadas, o que dificulta a comparação e até mesmo a feitura de metanálises relacionadas ao tema.

Conflitos de interesse

Agradecimentos

Introdução
A prevalência de obesidade e doenças crônicas não transmissíveis (DCNT) associadas à alimentação tem crescido em ritmo acelerado e chamado atenção para as taxas na população infantil. De acordo com a Pesquisa Nacional sobre Demografia e Saúde, de 2006, foi registrada uma prevalência nacional de sobrepeso de 6,6% em crianças de até cinco anos. Já os resultados da Pesquisa de Orçamento Familiar (POF) mostraram que a prevalência de excesso de peso variou de 25% a 40% em crianças entre cinco e nove anos.
As evidências científicas apontam que o aumento nas taxas de excesso de peso e DCNT é decorrente, entre outros fatores, da inversão dos padrões alimentares. Essa inversão caracteriza‐ se pela substituição cada vez maior da alimentação tradicional por alimentos e bebidas altamente processados e prontos para consumo.
Em geral, esses produtos ultraprocessados apresentam alta densidade energética, excesso de gorduras totais e saturadas, maiores concentrações de açúcar e/ou sódio e baixo teor de fibras. Ainda, têm por característica, devido a sua composição e a seu processamento, ser hiperpalatáveis, com maior durabilidade e prontos para o consumo. Dessa forma, têm uma ampla vantagem comercial quando comparados com os alimentos in natura ou minimamente processados, além de apresentar menor custo.
Os dados da POF indicaram que a alimentação das crianças brasileiras é deficiente em frutas, legumes e verduras. Ainda, apresenta excesso de consumo de biscoitos, embutidos, bebidas com adição de açúcar, sanduíches e salgados.
Dentre os fatores que estão condicionados à qualidade da alimentação das crianças, a Laurasia renda e a escolaridade dos pais merecem destaque. As pesquisas sugerem que uma alimentação de qualidade está diretamente relacionada ao maior nível de escolaridade e à maior renda.
Há evidências entre excesso de peso na infância e desenvolvimento precoce de diabetes mellitus, doenças cardiovasculares, dislipidemias e hipertensão na vida adulta. Assim, a infância é um período crucial para a prevenção das DCNT por meio do incentivo e da adoção de hábitos saudáveis que tendem a permanecer durante a fase adulta. Os pais exercem grande influência no desenvolvimento desses hábitos pela criança e devem ser exemplos positivos em relação à alimentação saudável associada à prática de exercício físico.

Métodos
O presente trabalho faz parte de um estudo maior intitulado “Obesidade e fatores de risco para doenças crônicas em crianças atendidas na Estratégia de Saúde da Família em uma unidade básica de saúde de Porto Alegre, RS.” Em termos de amostra, foram incluídas 204 crianças, o que forneceu a este estudo um poder estatístico de 90% para testar uma diferença de médias com magnitude de efeito (E/S) ≥0,5 desvio padrão para α= 0,05. Em dados categóricos, esse tamanho amostral forneceu um poder de 80% na comparação de proporções com diferenças iguais ou maiores do que 20% vs. 40% para α = 0,05.
A equipe de trabalho foi composta por nutricionistas e acadêmicas de nutrição previamente treinadas e a coleta dos dados ocorreu de setembro de 2012 a julho de 2013. As medidas antropométricas foram aferidas em duplicata com técnicas padronizadas conforme a Organização Mundial da Saúde. O peso (kg) foi obtido com balança digital com capacidade para 200kg e precisão de 50g e para aferir a altura (cm) foi usado estadiômetro fixo à parede. Foram consideradas com excesso de peso (sobrepeso e obesidade) as crianças menores de cinco anos com indicador de escore Z>2 e as com cinco a 10 anos com indicador de escore Z>+1 de acordo com o IMC para idade. Os dados antropométricos foram analisados com os softwares Anthro® e Anthro Plus® (Anthro®, WHO AnthroPlus, 2007, EUA).

As seguintes vari veis dos

As seguintes variáveis dos CFPs com relação ao controle glicêmico foram estudadas: idade, sexo, relação com o paciente, profissão, jornada de trabalho, escolaridade, ajuda de outra pessoa no cuidado do paciente e presença de ansiedade ou estresse. Também foram avaliadas a situação socioeconômica (questionário de Bronfman) e a funcionalidade familiar.
A depressão no CFP foi identificada por meio do questionário de Beck, instrumento autoadministrado validado para adultos falantes do espanhol. Os pacientes deprimidos foram definidos com um escore ≥ 10. A Escala de Estresse Percebido foi usada; essa escala consiste em 14 perguntas com cinco opções. Os escores variam de 0 (sem estresse ou estresse percebido mínimo) a 56 (estresse percebido máximo); os valores<30 caracterizaram indivíduos sem estresse. Essa escala também foi validada na população mexicana. O questionário familiar Apgar foi usado para determinar a funcionalidade familiar. Ele consiste em cinco componentes: adaptabilidade, cooperação, desenvolvimento, afeição e capacidade de resolução. Um escore ≥ 7 definiu boa funcionalidade familiar.
Resultados
Foram identificados no Serviço de Endocrinologia Pediátrica 63 pacientes elegíveis. Oito foram excluídos: três porque o CFP se recusou a participar, quatro por estarem em remissão e um porque recebia terapia com esteroides para colite eosinofílica. Portanto, foram incluídos 55 pacientes, entre dois e 11 anos. Havia mais pacientes do sexo feminino, com proporção de 2:1. A evolução temporal da DM1 variou de oito meses a 11 anos e nove meses. Somente oito pacientes apresentavam outra doença concomitante (três com hipotireoidismo primário, três com epilepsia e dois com depressão), que estava sob controle. Todos os CFPs eram mulheres; 53 (95%) eram as mães dos pacientes. Suas idades eram de 21 a 54 anos e a maioria (42%) havia concluído o ensino médio ou um ensino técnico. Com relação à composição familiar, a maioria era nuclear (n=43, 78%) e 20% tinham apenas um dos pais. O regime de insulina de todos os pacientes tinha como angiotensin receptor blocker várias injeções de insulina durante o dia. Nenhum paciente usa bomba de infusão de insulina. Além disso, a frequência geral de automonitoramento da glicemia era antes e duas horas depois de cada refeição.

Discussão
O controle metabólico da diabetes mellitus está associado ao desenvolvimento, à progressão e à gravidade de suas complicações. Em pacientes pediátricos, a administração abrangente dessa doença exige a participação ativa do paciente e de sua família. A saúde física e emocional do CFP e sua capacidade de tomar decisões podem influenciar o cuidado de crianças com diabetes. Até onde sabemos, este é o primeiro estudo feito com a população latino‐americana sobre o papel do CFP nos pacientes pediátricos com DM1; estudos semelhantes foram feitos com populações americanas ou europeias.
Consideramos que os resultados deste estudo são confiáveis, pois fatores diferentes foram controlados. Foram incluídos somente pacientes pré‐púberes porque o CFP tem um papel muito importante nessa faixa etária e para evitar confusão relacionada a mudanças hormonais que ocorrem em diversos estágios púberes. O controle glicêmico (de acordo com os níveis de HbA1c) foi a principal medida de resultado, pois quase nenhum dos pacientes apresentou alterações metabólicas adicionais, como esperado em pacientes pré‐púberes com esse tipo de diabetes. Para determinar os efeitos das variáveis diretamente relacionadas ao CFP, este estudo incluiu variáveis conhecidas por alterarem o controle glicêmico.
Cada paciente incluído neste estudo recebeu tratamento médico e consultas sobre dieta e exercícios gratuitos como parte dos serviços oferecidos pela instituição (IMSS). Essas famílias em geral têm uma situação socioeconômica que permite que sigam a orientação médica. As mães dos pacientes eram o CFP em 95% dos casos estudados; vale destacar que 42% trabalham fora de casa, mas essa situação não influenciou o controle glicêmico dos pacientes. Em países desenvolvidos, cerca de 15% dos CFPs de pacientes com DM1 são o pai, e não a mãe. Diferentemente de populações americanas ou europeias, em nosso estudo as mães não apenas declaram que a situação empregatícia de seus cônjuges não permite que eles participem do cuidado de crianças com diabetes, como também acreditam que o cuidado deve ser prestado exclusivamente pela mãe.

A concerned effort has been made

A concerned effort has been made to search out new highly efficient reactors that produce biodiesel while saving time and energy. Inefficient mass transfer is one of the main limitations in biphasic heterogeneous reactions, such as transesterification. Although many types of vigorous mixing have been investigated to address this requirement, most of them suffer from high angiotensin receptor blocker demands [13–15]. Optimal mass/heat transfer is doubtless the key to enhancing biodiesel production while cavitational effects may also play a significant role. The two main routes to acoustic cavitation are high-intensity ultrasound and HC (passage of liquid at high flow rates through a constriction), although rotating HC generators are the most recent innovation.
With the aim of reducing energy consumption in biodiesel production, we have thoroughly investigated the effect of cavitation on the transesterification reaction of triglycerides over the last few years [16]. We have also investigated combinations of different enabling technologies both in batch and in flow processes [17–19]. Hybrid processes for biodiesel production that function upon a combination of sonochemical reactors and other intensification techniques have been thoroughly reviewed [20] as have continuous flow technologies [21]. In 2005 Gogate and Pandit described HC as a technology for the future [22], and one year later, a Chinese group from the Zhejiang University of Technology compared US and HC conditions for biodiesel production [23]. The techniques displayed similar enhancement effects in the transesterification reaction of soybean oil, both giving shorter reaction times and lower energy consumption than the conventional mechanical stirring method. Several authors have confirmed these results [24,25] and have highlighted HC’s easier scale-up compared to US methods. The micro level turbulence created by HC may be able to overcome the mass transfer limitations of a triphasic reaction such as transesterification. With the best of our knowledge we could not find previous applications of rotor-stator type HC reactors for biodiesel production, however the commercially available SPR BD reactors equipped with a spinning rotor (a drum with hundreds of holes) from Hydro Dynamics, Inc. (USA) are successfully used in this field [26].
The high cost of vegetable oils and the ethical issues that surround competition with the food industry for oil crops means that much attention angiotensin receptor blocker has been focussed on non-edible oils and used frying oils which are a renewable source [27–29].
The recycling of waste cooking oil (WCO) that had been used for frying has been investigated under HC conditions [30–33]. HC has also been used as a pre-treatment for residual algal biomass’s conversion into cheap feedstock for yeast cells that produce lipids [34].

Material and methods

Results and discussion
We herein report a new, efficient HC protocol for biodiesel production from edible and waste oil. The latter feedstock contains FFA that may lead to soap formation via the undesirable saponification reaction, especially when homogeneous basic catalysts are employed in the transesterification reaction. Methods for reducing or removing FFA from oils are neutralization, extraction by alcohol, steam distillation and the esterification reaction [35]. Many limitations and drawbacks have been documented for all of these methods; however the esterification reaction makes best use of FFA in oils as it transforms FFA directly into FAME. Recent studies have described the adsorption of free fatty acids using an anion-exchange resin such as Dowex 550A [36], as a prior step to the transesterification reaction in order to replace the esterification reaction.
All the rapid tests on unwashed and washed biodiesel samples (from both types of vegetable oil) after the second step of the transesterification gave excellent conversions. The photo in Fig. 3 shows an example of the test on unwashed biodiesel from refined and bleached palm oil.

br Discussion The survey demonstrated that poultry is widely exposed

Discussion
The survey demonstrated that poultry is widely exposed to T. gondii in Israel (Fig. 1).
Importantly, and as has been mentioned in the results section, this MAT assay demonstrated high specificity as no cross-reaction was observed with sera obtained from Eimeria tenella-infected chickens used as controls.
The results of the survey present evidence that housing conditions which prevent oocyst-shedding cats to access premises have a significant impact on T. gondii seroprevalence of poultry (Fig. 1). Battery-raised egg layers (Group 2) had the highest cumulative seroprevalence of all 6 survey groups with 35.4% of angiotensin receptor blocker infected (Fig. 3.1). Housing egg-laying chickens in batteries above the ground did not change the level of T. gondii seroprevalence since they were initially housed on the ground until the age of 105days. A varying lack of strict biosecurity conditions in this group, which was personally observed, with rodents and cats occasionally gaining access to the housing facilities might be a possible explanation. It might also be related to differences in the age composition of these groups. Conditions of high bird concentrations in limited spaces where cats readily frequent may allow for easier T. gondii oocyst exposure allowing for these high seroprevalence rates to be achieved. Broilers in Israel are often raised on cement pens and on the ground under conditions of relatively high biosecurity with regard to access to cats and rodents. Broiler raising pens are thoroughly cleaned and disinfected with aldehydes after each batch of broilers is removed and before reintroduction of a new flock. This is probably also the reason why birds in Group 3 were seronegative. Even the relatively much older 2-year-old breeders (Group 4) were found to be seronegative and this can only be explained by an effective housing system where biosecurity is strictly enforced and feed/litter is not contaminated with oocysts. Zhu et al. (2008), Yan et al. (2009) and Maksimov et al. (2011) have reported similar findings amongst biosecurity-enforced, caged and free-range poultry in North East China and enclosed and free-range geese and ducks in Saxony, Germany. Both reports relate high T. gondii seroprevalence in free-range birds due to their exposure to feral cats. Unfortunately, these surveys compared only two types of housed poultry and did not include the possibility of housing birds above the ground exclusively in their investigations.
Although relatively few turkeys were sampled in the survey, close to 10% of those birds sampled (4/45) were seropositive for T. gondii anntibodies. In fact, three of 4 birds had antibody titers that were ≥50 (Results not shown). This finding should signal a warning to stakeholders in the poultry industry and officials involved in public health. Further surveys should be conducted in turkeys using larger sample groups in order to confirm the high seroprevalence of T. gondii in this poultry species since turkey meat is consumed extensively by the Israeli public (http://www.thepoultrysite.com/).
Housing conditions as a modifying mechanism for T. gondii prevalence in poultry is crucial, especially in a day and age whereby animal production systems that offer outdoor access to animals have become increasingly popular in the Western world, including Israel, due to the growing general discontent of consumers with conventional bio-industrial farming practices. These open production systems offer improved animal welfare but may create new problems for animal health, resulting in increased food safety risks from parasitic infections, like toxoplasmosis. In current organic husbandry systems, the animals are kept at lower stocking densities and have outdoor access. The design of new animal production systems with outdoor access requires both a thorough analysis of possible risks and optimal communication of these risks throughout the food chain and appropriate partitioning of responsibility concerning these risks. Some risks are inherent to the choice of keeping animals in a more natural environment and could be judged as an inherent responsibility of the consumer, whereas other risks may be mitigated by further refinement or adjustment of the housing or farm management system used.

Introduction Materials aging of Reinforced

Introduction
Materials aging of Reinforced Concrete (RC) structures, earthquake excitations, corrosion of steel reinforcement and fire exposure have been the cause of serious structural damage and of high costs in repair and maintenance. Concrete deterioration and damage in critical RC members adversely impact the ability of structures to withstand future operating conditions and increase risk to fatal failures and catastrophic collapses if not controlled. Recently developments of various non-destructive and Structural Health Monitoring (SHM) techniques have been made with respect to real-time surveillance, continuous inspection and in-situ testing techniques to help ensure continuous safe, functional and economical operation of RC structures. Even more, SHM is becoming extremely important in RC structures that withstand critical shear mechanisms which lead to fragile and abrupt failure modes. Even minor incipient shear damage in deficient shear-critical RC elements, such as beam-column joints, short columns and deep beams, could be the cause of catastrophic collapse [3,10,32,35,42].
The implementation of smart materials such as Piezoelectric lead Zirconate Titanate (PZT) in SHM techniques is a rather recent development with promising results. It has emerged due to the advantageous characteristics of these materials combined with the merits of the Electro-Mechanical Impedance (EMI) or its reverse admittance method that uses electro-mechanical signals extracted from PZT transducers mounted on RC members as damage indicators [33,36,39,46,48].
A PZT transducer produces electrical charges when subjected to a strain field and conversely it angiotensin receptor blocker produces mechanical strain when an electrical field is applied. The impedance-based SHM approach utilizes the electro-mechanical properties of these smart materials that are related with the mechanical impedance of the host structural members, which is affected by the presence of any structural damage. In this way, the impedance extracts and its inverse, the admittance, constitute the properties on which the PZT approach is based for the SHM of RC structures. The produced effects by the structural damage on the PZT electrical signals are vertical enlargement or/and lateral shifting of the baseline signals of the initially healthy structure [9,18,49]. Numerical studies that simulate electro-mechanical admittance monitoring procedures utilizing PZTs to detect and localize cracking in concrete beams have also been presented [15,24,28,43]. In addition, identification of damage due to the corrosion of steel reinforcing bars and debonding between bars and concrete have been investigated experimentally and analytically using bonded PZT transducers on the surface of the steel bars [16,29,30,40,41]. Furthermore, real-time monitoring of concrete compressive strength gain using bonded PZT patches showed promising results [25,26,28,34,45].
Failures in shear-deficient RC elements are associated with brittle catastrophic collapses. When principal tensile stresses exceed the tensile strength of concrete, diagonal cracking occurs in the shear span and the behaviour of a concrete element under shear stresses is mainly characterised by the tensile strength of the material [4,19,31]. It has been found that the ratio of the transverse shear reinforcement, the ratio of the tensional reinforcement and the span-to-depth ratio control the inclination of the shear diagonal cracking of shear-critical RC beams [14]. It is also known that the ultimate shear strength of RC beams is calculated by a superposition of the shear strength of beams without web reinforcement and the strength provided by the shear reinforcement [7,8]. However, the formation of critical shear diagonal cracking of RC beams without web reinforcement is crucial for the determination of the onset of diagonal cracking of common RC beams with bars and stirrups. Consequently, any improvement of the existing SHM techniques to detect in real-time the first appeared diagonal cracks in a RC beam and to assess their severity before the inevitable brittle shear failure of the element is essential. A first approach to diagnose damage at early cracking stages of shear-critical RC beams using the admittance measurements of embedded and surface attached PZTs through a non-portable EMI monitoring system has recently been attempted by Chalioris et al. [5] and Voutetaki et al. [44].

br Introduction Athletes hearts develop physiologic hypertrophy

Introduction
Athletes\’ hearts develop physiologic hypertrophy through intensive training, and manifests as an increase in cardiac mass, chamber enlargement, and wall thickening. Cardiac hypertrophy can be pathologic or physiologic. Pathologic hypertrophy results from chronic pressure or volume angiotensin receptor blocker overload due to disease and it is associated with cardiac dysfunction and an increased risk of angiotensin receptor blocker failure. By contrast, physiologic hypertrophy is a normal response to exercise, pregnancy, and sometimes normal growth and is associated with normal or enhanced cardiac function.
The effect of hypertrophy on cardiac function is typically evaluated non-invasively via Doppler echocardiography and magnetic resonance imaging (MRI). Using these techniques shows that, compared to normal sedentary subjects, athletes have enhanced left ventricular (LV) filling or diastolic function (DF) during exercise. The most commonly reported echocardiographic DF index is the E/A ratio, which is the ratio of the peak early transmitral flow (Doppler E-wave) to the peak late atrial filling (Doppler A-wave). Other indexes include the peak E-wave velocity (Epeak) and the deceleration time of the E-wave (DT). However, the various echocardiographic indexes have led to inconsistent conclusions regarding the LV DF at rest. Conventional E-wave parameters moreover are load-dependent and have not been derived from basic physiologic principles that govern filling. Indexes such as the E/A ratio are generated by the complex interplay of simultaneous physiologic determinants governed by chamber properties. In particular, the E-wave DT has been shown to explicitly depend on stiffness and relaxation/viscoelasticity.
Thus, to overcome the limitation associated with the nonspecificity of conventional indexes, it is advantageous to quantify the DF by using a model of filling that is derived in accordance with the mechanical suction-pump attribute of the LV. We accordingly assessed the DF by using the parametrized diastolic filling (PDF) formalism (Appendix 1). The PDF formalism has facilitated the prediction and validation of the load-independent index of diastolic function (LIIDF) in the form of the dimensionless parameter, M.

Methods

Results

Discussion
Exercise induces LV hypertrophy in competitive athletes. This physiologic hypertrophy is in response to the additional volume-pump/pressure-pump load to which the LV is subjected during exercise. In this study, we examined the differences in the DF at rest in athletes and controls by using conventional Doppler-derived indexes and a previously validated kinematic model (i.e., PDF formalism) of the DF. We used MRI to determine the LV mass and chamber size. Conventional filling parameters such as Epeak, E/A ratio, AT, and DT were determined from Doppler E-waves. An analysis of E-waves via PDF formalism provided the chamber stiffness, viscoelasticity/relaxation, preload parameters, and the LIIDF. In concordance with previous studies, we found that the LV chamber dimensions and mass were significantly higher in athletes. The resting HR was lower and the E-wave duration was greater in athletes than in the controls. The cardiac output (i.e., the product of the HR and the LVSV) was similar at rest in both groups. The PDF-derived kinematic parameters showed that the chamber stiffness was lower and the volumetric preload was higher in athletes.

Conclusion

Acknowledgments
This work was supported in part by the Alan A. and Edith L. Wolff Charitable Trust (St. Louis, MO) and the Barnes-Jewish Hospital Foundation. E. Ghosh is the recipient of a Heartland Affiliate predoctoral fellowship award (11PRE4950009) from the American Heart Association. T. Morrell and S. Zhu are recipients of Honorary Scholars Summer Research Grants from Washington University (Saint Louis, MO).

Introduction
Ambient temperature has a significant influence on human physiological responses to physical activity. A combination of high environmental temperatures and elevated relative humidity (R.H.) create substantial stress for athletes training and competing under such conditions. However, the effects of high environmental temperature and different relative humidity levels on aerobic and anaerobic exercise performance are an important question with no definitive answer. The answer could have important implications because athletes could use this information to prepare better or to anticipate potential changes in performance at athletic events in which the environmental conditions at the competition site differ from their training location.

br Introduction Porcine reproductive and respiratory syndrome

Introduction
Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important global viral diseases for over two decades. PRRS is characterized by reproductive failures in sows and respiratory distress in growing pigs (Zimmerman et al., 2012). The etiologic agent of PRRS is the PRRS virus (PRRSV), which is a member of the Arterivirus genus, Arteriviridae family and Nidovirales order (Snijder and Meulenberg, 1998). The PRRSV genome is approximately 15kb in length and contains at least ten open reading frames (ORFs) (Snijder et al., 2013). PRRSV can be divided into two genetically distinct genotypes: type 1 PRRSV, which is the major genotype circulating in Europe, and type 2 PRRSV, which is the major genotype found in North America and Asian countries (Allende et al., 1999; Murtaugh et al., 2010). Type 2 PRRSV is the most angiotensin receptor blocker and economically significant genotype in Korea. Type 2 PRRSV is further classified into 9 lineages based on global genotyping classification (Shi et al., 2010). Among those, type 2 PRRSV belonging to lineage 1 and 5 is commonly isolated in Korea (Shi et al., 2010).
PRRSV is considered one of the most rapidly evolving viruses on the planet (Normile, 2007). Mutation and recombination are two common evolutionary mechanisms for PRRSV, which can lead to enhanced fitness for survival or increased virulence (Gorbalenya et al., 2006; Domingo and Holland, 1997). Rapid evolution of PRRSV is an important driving force for the emergence of new strains capable of vaccine resistance (Chand et al., 2012). The commercial PRRS modified live vaccine (Ingelvac® PRRS MLV, Boehringer Ingelheim Vetmedica Inc., St. Joseph, Missouri, USA) has been used to control PRRSV for 20 years in Korean pig farms. After 20 years of use, some swine producers and practitioners have raised the concerns about the efficacy of this PRRS MLV due to genetic and antigenic change of field viruses. Therefore, the objective of this study was to evaluate this PRRS MLV against two recent PRRSV isolates.

Materials and methods

Results

Discussion
After 20 years of use in over 35 million pigs (http://www.bivkorea.com), PRRS MLV used in this study is still proven to be efficacious against recently isolated heterologous type 2 PRRSV strains. These results provide swine practitioners and producers with clinically significant information because there have been concerns about the efficacy of this PRRS MLV over the massive use for 20 years. Genetic variation of 1995–1999 and 2011–2015 Korean isolates was determined based on ORF5, which encodes for highly variable regions (Murtaugh et al., 1995). ORF5 of Korean PRRSV isolates showed 82.2–100% homology at nucleotide level and 83–100% at amino acid level. The prediction of protection has frequently been attributed to antigenic but not genetic similarity between vaccine and challenge strains (Lager et al., 1999; Prieto et al., 2008). Despite the fact that genetic variation may affect antigenic diversity (Frossard et al., 2012), present results suggest that PRRS MLV is still closely related antigenically to the recently isolated field strains.
The most common and representative strains of PRRSV were chosen to evaluate the PRRS MLV used in the present study. Two challenge viruses (SNUVR150004 and SNUVR150324) are local field isolates. The severity of experimentally reproduced clinical respiratory disease and lesions was generally consistent with the clinical respiratory disease observed on the farm from which each strain originated. Two challenge viruses are high virulent as other Korean type 2 PRRSV isolate (SNUVR090851, GenBank JN315685) based on levels of viremia and lung lesion (Han et al., 2013). Genetically, global type 2 diversity is dominated mainly by isolates of four lineages 1, 5, 8, and 9, which collectively constitute over 97% of all ORF5 sequences (Brar et al., 2015). Among those, type 2 PRRSV belonging to lineages 1 and 5 are the most commonly identified in Korea (Shi et al., 2010). Korean type 2 field strains belonging to lineage 5 shared a high degree of identity to the PRRS MLV vaccine virus which is based on the VR2332 isolate (Cheon and Chae, 2000). At the present time, the origin of Korean PRRS MLV-like type 2 PRRSV field strains has not been determined. It is possible that these field strains prevailed in Korea before the introduction of the PRRS MLV or may have originated from the vaccine virus.

Instead of determining cluster membership our goal in

Instead of determining cluster membership, our goal in this angiotensin receptor blocker paper is to develop an anomaly ranking method. To motivate, we first investigate information which is potentially present in the eigenvector components. Specifically we show next that optimization problem in (1) can be considered a relaxation to the unsupervised SVM.
Formally, given a feature mapping ϕ(x), we want to solve the following nested minimization problem:
Due to the integer constraints on y, (3) is a NP-hard problem.
Let K = (K), K = ϕ(x)ϕ(x),i,j = 1,⋯,m, be the kernel matrix and Y = diag(y). The inner convex optimization problem satisfies strong duality and has the equivalent dual formulation
Replacing the inner minimization by its dual problem, we have the following equivalent minmax problem
Let where
It immediately follows that
Moreover, for any α ≠ 0, we have
Consequently
Therefore, given y, solution to (4) is one of local maximizers of
Note that the objective function in (7) is no longer concave and (7) has many local maximizers. Let
Now consider the following simpler problem
We note that (8) remains an NP-hard problem due to the concave objective function and rectangular constraints. Assume K is positive definite in the space z:ez = 0 . Then all local minimizers of (8) are at the boundary of .
Intuitively, each maximizer of (7) is created by moving from the origin into a quadrant in , from the combined values of the first increasing term and the second decreasing term . For the unsupervised SVM, the main task is to assign the label y to determine the minimum of local maximums. In other words, we want to determine the quadrant at which the global optimal solution locates. Assuming moving away from the origin in contours of , the optimal label assignments y for the minmax objective function (5) corresponds to the quadrant along which the objective function decreases the fastest. This suggests we can obtain a reasonable approximation to the optimal label assignment by computing the minimum of under the same constraints, i.e., (8) is a reasonable approximation to the unsupervised SVM (5). Fig. 1 illustrates this motivation in the two dimensional case. Subplot (a), (b), and (c) graph possible shapes of functions , , and respectively.
Next we show that the spectral optimization (1) is a reasonable approximation to (8) (and consequently to unsupervised SVM (5)). Denoting , K = D−1WD−1, and ignoring the constant υ in the objective function, spectral optimization (1) is equivalent to
Assuming K is positive definite, the ellipsoidal equality constraint can be replaced by an inequality constraintbecause the ellipsoidal constraint in (9) should be active at a solution. Assuming K = D−1WD−1, , and approximating the rectangular constraint by the ellipsoidal constraint, problem (9) becomes an approximation to the optimization problem (8). This suggests that the normalized spectral optimization problem (1) can be regarded as an approximation to the unsupervised SVM problem (5).
The optimal separating hypothesis from an unsupervised SVM has the formwhere the coefficient of the bi-class separating optimal decision function represents a measure of support from the jth data point on the two class separation decision. Since the first non-principal eigenvector of the normalized spectral clustering z yields an approximation and also provides a measurement of the jth data point\’s support on the separation. However, because of the use of the ellipsoidal constraint rather than rectangular constraints and other approximations, the eigenvector components are mostly nonzero, yielding a continuous measure of support in this two clusters separation.

A new spectral ranking for anomaly
In the standard spectral analysis, k-means clustering is typically applied to non-principal eigenvectors to determine clustering memberships. Our discussion in Section 2 suggests that components of a non-principal eigenvector have meaning beyond indicating cluster membership. In fact provides a bi-class clustering strength measure in the optimal bi-class clustering in the high dimensional feature space according to the assumed similarity.

Numerous interstitial macrophages showed immunoreactivity for both antigen and

Numerous interstitial macrophages showed immunoreactivity for both antigen and COX-2, demonstrating that the pathogen is able to invade the mammary interstitium, exacerbating the inflammatory response. Expression of COX-2 at these sites of infection may be stimulated both directly by innate immune recognition of the mycoplasma organisms or indirectly by inflammatory mediators (). Although it has been described in human beings, primates and in porcine bronchial allografts (), COX-2 immunostaining of endothelial angiotensin receptor blocker and fibroblasts was somewhat unexpected, since antigen was not detected in these cell types. COX-2 expression by endothelial cells can impact on vascular permeability, whereas the presence of COX-2 in fibroblasts might be involved in the progressive fibrosis that occurs during infection ().
In conclusion, COX-2 expression was upregulated in mammary gland tissues exposed to infection. COX-2 was expressed by several cell types that might be involved in different biological processes that contribute to caprine contagious agalactia. Influx of inflammatory cells, phagocytosis, exudation and fibrosis could be associated with COX-2 expression by epithelial cells, macrophages, endothelial cells and fibroblasts, respectively.
Conflict of interest statement

Congenital myotonia (CM) is clinically characterised by a delay in muscular relaxation after a sudden contraction. The sustained muscle contraction is the result of abnormalities in the ion conductance leading to a reduced electrical threshold. In fact, muscle chloride conductance is decreased in CM affected individuals as a result of functional defects in a skeletal muscle chloride channel termed CLCN1 (). Although CM has been reported in sheep, the cause has not been previously disclosed in this species ().
An outbreak of anomalies during the movement of lambs in a flock of Rasa Aragonesa sheep was referred to the Ovine Clinics service at the Veterinary Faculty of the University of Zaragoza (Spain) in October 2012. The symptoms were visible only after sudden visual and/or auditory stimulation or fast movements during normal flock management. When other individuals in the lot started evasive movements, the affected lambs maintained a rigid position with extended limbs and frequently fell to the ground. After 6–25 s, the lambs were able to stand and move normally (see : ). Selenium treatment proved to be inefficient. Survival was not apparently impaired although affected animals were slaughtered. Reproducers in the flock did not show symptoms. According to the owner of the flock, the occurrence started in 2007 with a single animal (representing approximately 0.08% of the new-born animals in that year). The incidence increased progressively, and when the case was referred to us in 2012, 1% of the new-borns were affected (around 15 cases/year).
Clinical examination of two affected individuals at the School of Veterinary Sciences\’ facilities revealed a delay in muscle relaxation after a stimulation, preventing normal contraction and extension of muscular groups during running. The two lambs were euthanased and necropsied. The most remarkable post-mortem finding was muscular enlargement, particularly affecting the hind part musculature (see : ).
No environmental factors could explain the occurrence of these symptoms because veterinary care, feeding and reproductive management were similar to those of other flocks in the area. The lack of affected reproducers pointed to recessive inheritance. reported a similar myotonia outbreak in a flock producing show lambs in the United States and this was also consistent with autosomal recessive inheritance. The gene responsible for the anomaly remained undisclosed, however.
demonstrated that a genomic G > C single nucleotide variation (SNV) in the goat muscle chloride channel gene () leading to p.Ala855Pro substitution in a conserved domain was responsible for CM in kid goats. Mutations in the gene have also been found to be in the origin of CM in humans (), horses () and mice (). For this reason, we considered ovine to be the most suitable candidate gene for this pathology.