Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

This thesis aims to explore how a critical reading of the novel Things Fall Apart (1958) can provide valuable perspective for educators and students when examining socio-economic issues in  a colonial context in the ESL classroom. The main issues being analysed are how the novel reveals and explores socio-economic forms of exploitation under colonialism, and how a critical reading of the novel can be used in teaching to inform and persuade learners about social injustices. To show this, the essay examines the novel from a marxist perspective, and more specifically by drawing on the concept of primitive accumulation to understand and explain the changes brought about by the introduction of colonial rule. The changes in this context include the Igbo community's relation to land, its socio-economic and cultural aspects as well as the introduction of trade. The discussion and analysis of the novel centre on social injustices due to land expropriation, breakdown of traditional values and customs, and economic changes brought about by the arrival of Europeans in the context of colonialism. Expanding on this, the essay also reflects on the pedagogical implications of its arguments by showing how a critical reading of Things Fall Apart might provide an opportunity for teachers to underline issues of social injustice, material, and economic forms of exploitation under colonialism and beyond. This literary analysis also discusses and reflects on the practical challenges and possibilities of teaching such issues in the ESL classroom by using the concept of critical literacy.

Doctor Educationis / This study was a cephalometric and dental investigation of the treatment outcomes of UCLP children treated at the Red Cross Children's Hospital (RCCH) with respect to craniofacial morphology and dental arch relationship. The quality of the outcome for the RCCH group was compared with the outcomes reported for the Six-Centre International Study (Melsted et al., 1992; Mars et al., 1992). The sample consisted of 20 (11 females, 9 males) consecutively treated UCLP children who had cephalometric and dental records taken between the ages of8 to 11years (mean 10.13 ± 1.2 years). The cephalometric analysis described by Melsted et al. (1992) was used to evaluate the skeletal and soft tissue morphology. The quality of the dental arch relationship was measured according to the Gosion Yardstick (Mars et al., 1987). The treatment outcome of children treated at the RCCH was evaluated with respect to craniofacial form and dental arch relationship. When comparing the mean cephalometric skeletal parameters of the RCCH to the six centres in the Eurocleft study, a significant difference was found between the RCCH group and centre D for most of the variables. A significant increase in the upper incisor inclination and maxillary inclination was found in the RCCH patients compared to the European centres. The difference in the soft tissue parameters was limited to the relative protrusion of the nose and the sagittal soft tissue variable sss-ns-pgs. The analysis of the Goslon scores showed a significant difference between the RCCH group and centres C, D, and F. According to the Goslon score, 85% of the RCCH patients had good to satisfactory dental arch relationship, which was comparable to that recorded for centres A(92%), B(89%) and C(94). In conclusion, the results of the cephalometric analysis and the Goslon Yardstick showed a significant difference between the RCCH group and centre D. The GosIon score indicated good quality of the dental arch relationship, which faired favourably with the better centres in the Six Centre Study.

<p>Sepsis and septic shock are life-threating conditions, which resulted from a continuum of the body’s response to overwhelming infection. Elimination of bacteria through antibiotics is not sufficient, because the host is still left with a large amount of lipopolysaccharide (LPS) that prevents the host immune system from returning to normal homeostasis. Synthetic LPS antagonists that can bind to LPS via electrostatic and/or hydrophobic interactions cause systemic toxicities. Moreover, LPS elimination alone may not address already established complications of sepsis. To address these challenges, we propose to develop nanoparticle formulations of LPS antagonists (D-TZP) that can be delivered systemically. Specifically, cholecalciferol (vitamin D) was encapsulated in a self-assembly of tannic acid/Fe³⁺ coordination complex (pTA) capsule, forming a core that could be surface-modified with LPS adsorbents, such as low molecular weight succinylated chitosan (LMZWC) and polymyxin B (PMB). D-TZP suppressed pro-inflammatory effects of LPS on the engineered human monocytes with significantly less cytotoxicity than free PMB at the equivalent dose. D-TZP increased the maximum tolerated dose of PMB by both intraperitoneal and intravenous administration. In the LPS-induced mouse model of sepsis, systemic administration of D-TZP immediately after LPS challenge neutralized the lethal effect of LPS. D-TZP also reduced the mortality of mice when given 2 h after the LPS challenge. D-TZP inhibited the mortality in the cecal ligation and puncture (CLP)-induced bacteremia mouse model when given IV 2 h after the insult. In the CLP model, the D-TZP-treated animals also showed lower levels of both TNF-α and IL-10 cytokines as well as D-dimer levels, reflecting the attenuation of disseminated intravascular coagulation, compared to the vehicle-treated control group. Collectively, these results support that the D-TZP is a safe and effective systemic intervention of sepsis.<br></p>

Este trabalho investiga a evolução espacial da Camada Limite Planetária (CLP) na região do Canal de São Sebastião (CSS) - SP, uma das áreas mais impactadas por derramamentos acidentais de óleo das regiões sul e sudeste do Brasil. Para tanto, foi feito levantamento da topografia e cobertura do solo para uma região de 12 km x 12 km no CSS com o intuito de levantar parâmetros essenciais para a estimativa do balanço de energia sobre o continente. Foram utilizados dados médios horários de vento, temperatura e umidade específica do ar coletados pelo Centro de Biologia Marinha (CEBIMar), e temperatura do oceano obtida de um fundeio ancorado próximo ao centro do canal. Os dados médios foram utilizados para estimar o balanço de energia sobre o continente, utilizando o método proposto por Deardorff (1978), e sobre o oceano através de parametrização do tipo bulk para as condições de verão e inverno. Com os resultados obtidos foi determinada a altura da CLP para ambas as superfícies e, em seguida, aplicada uma média móvel com advecção destas alturas no sentido do vento zonal - a componente mais intensa do vento ao longo do dia segundo análise de dados para ambas estações estudadas - para investigar sua evolução espacial ao longo de duas linhas de latitude: uma interceptando o CEBIMar e outra, mais ao sul, numa região composta por água e continente em igual proporção. / This work investigates the spatial evolution of the Planetary Boundary Layer in the region of São Sebastião Channel (SSC) - SP, one of the most impacted area by accidental oil spilling in the South and Southeast regions of Brazil. It was performed a topographic and soil cover survey for a region of 12 km x 12 km in the SSC region in order to obtain the essential parameters to estimate the energy balance over the continent. Hourly averaged data of wind, air temperature and specific humidity collected by the Marine Biologic Center (CEBIMar) and ocean temperature obtained by a mooring near the center of the channel were used in this work to estimate the energy balance over the continent using the routine proposed by Deardorff (1978) and over the ocean using bulk parameterizations for winter and summer conditions. The obtained results were used to determine the PBL height for both surfaces. To investigate the PBL spatial evolution in the transition continent-water-continent it was applied a movable average with advection of the PBL height in the zonal wind direction the wind component more intense during winter and summer, according to the data analysis- to investigate the PBL spatial evolution through two latitude lines: one intercepting the CEBIMar and another in an region southward with equal water and continent proportion.

Die Tetrapyrrolbiosynthese (TBS) führt zu wichtigen Endprodukten wie Häm und Chlorophyll. Das gemeinsame Vorstufenmolekül aller Tetrapyrrole ist die 5-Aminolävulinsäure (ALA), die in Pflanzen über den C5-Weg aus Glutamat synthetisiert wird. Das erste spezifische Enzym der ALA-Synthese und somit auch der TBS ist die Glutamyl-tRNA Reduktase (GluTR). Sie unterliegt als Schlüsselenzym einer strengen Regulation. Aufgrund der unterschiedlichen Expression der HEMA-Gene in Arabidopsis wird ein differenzieller Beitrag der GluTR-Isoformen zu den Endprodukten der TBS vermutet. Analysen von knockout-Mutanten gaben Aufschluss darüber, inwiefern die Isoformen den Verlust des jeweils anderen kompensieren können. Die knockout-Mutante von HEMA1 zeigte einen blassgrünen Phänotyp, war nicht mehr in der Lage photoautotroph zu wachsen und demonstrierte eine essentielle Rolle der GluTR1 gegenüber GluTR2, wohingegen hema2-Mutanten einen wildtypartigen Phänotyp aufzeigten. Die Bedeutung der N-terminalen GluTR-Domäne in der posttranslationalen Regulation der ALA-Synthese wurde durch BiFC-Analysen und Komplementationsversuche aufgeklärt. BiFC-Analysen zeigten eine Interaktion der N-terminalen Domäne der GluTR1 mit Proteinen der Clp Proteasen und dem GluTR-Bindeprotein (GBP). Veränderte GluTR-Stabilitäten in gbp-Mutanten lassen eine schützende Funktion des GBP gegenüber dem Abbau des Proteins postulieren. Die Expression einer N-terminal verkürzten GluTR1 komplementierte hema1-Mutanten vollständig. Die in diesen Pflanzen und in clp-Mutanten beobachteten erhöhten GluTR1-Proteinstabilitäten im Dunkeln lassen einen Abbau der GluTR durch Clp Proteasen vermuten, bei dem der N-Terminus des Enzyms für die Substraterkennung notwendig zu sein scheint. Die Detektion von erhöhten Pchlid-Mengen als Folge der erhöhten Proteinstabilität in Linien, die die verkürzte GluTR1 exprimierten, demonstriert erstmals die Bedeutung einer kontrollierten Proteolyse der GluTR in der Regulation der ALA-Synthese. / In plants 5-aminolevulinic acid (ALA) is the common precursor of all tetrapyrrols and formed from glutamate via the C5 pathway. Glutamyl-tRNA reductase (GluTR) is the initial enzyme of ALA synthesis and thus tetrapyrrole biosynthesis (TBS). The most important control point of the TBS is the synthesis of ALA and GluTR is the key enzyme, that is tightly regulated. Due to the different expression of HEMA genes in Arabidopsis, a differential contribution to endproducts of the TBS is proposed for GluTR isoforms. Analysis of knockout mutants gave some indications of how the isoforms can compensate each other. I introduced a new knockout mutant of HEMA1 that was pale-green and not able to grow photoautotrophically, indicating that the remaining GluTR2 does not sufficiently compensate ALA synthesis for the extensive needs of chlorophyll. In contrast, hema2 mutants were wild-type-like. The function of the N-terminal region of GluTR1 in posttranslational regulation has been analyzed by BiFC analysis and complementation experiments of hema1. BiFC analysis showed an interaction of the N-terminal region of GluTR1 with the GluTR binding protein (GBP) and with proteins of the Clp proteases. Mutants of GBP revealed a decreased GluTR1 stability during the dark period, indicating a protective role of GBP against proteolysis of GluTR1 in darkness. The expression of a GluTR1 lacking the N-terminal amino acid residues successfully complemented hema1. These plants as well as clp mutants revealed an increased GluTR1 stability in darkness, suggesting a degradation of the protein through Clp proteases. Thereby, the N-terminal region of GluTR1 seems to be necessary for the recognition by Clp proteins. The observed high amount of truncated GluTR1 in transformed hema1 mutants was caused by the increased GluTR1 stability and lead to an accumulation of Pchlide in prolonged dark periods, demonstrating the importance of a controlled proteolysis of GluTR in the regulation of ALA synthesis.

Este trabalho investiga a evolução espacial da Camada Limite Planetária (CLP) na região do Canal de São Sebastião (CSS) - SP, uma das áreas mais impactadas por derramamentos acidentais de óleo das regiões sul e sudeste do Brasil. Para tanto, foi feito levantamento da topografia e cobertura do solo para uma região de 12 km x 12 km no CSS com o intuito de levantar parâmetros essenciais para a estimativa do balanço de energia sobre o continente. Foram utilizados dados médios horários de vento, temperatura e umidade específica do ar coletados pelo Centro de Biologia Marinha (CEBIMar), e temperatura do oceano obtida de um fundeio ancorado próximo ao centro do canal. Os dados médios foram utilizados para estimar o balanço de energia sobre o continente, utilizando o método proposto por Deardorff (1978), e sobre o oceano através de parametrização do tipo bulk para as condições de verão e inverno. Com os resultados obtidos foi determinada a altura da CLP para ambas as superfícies e, em seguida, aplicada uma média móvel com advecção destas alturas no sentido do vento zonal - a componente mais intensa do vento ao longo do dia segundo análise de dados para ambas estações estudadas - para investigar sua evolução espacial ao longo de duas linhas de latitude: uma interceptando o CEBIMar e outra, mais ao sul, numa região composta por água e continente em igual proporção. / This work investigates the spatial evolution of the Planetary Boundary Layer in the region of São Sebastião Channel (SSC) - SP, one of the most impacted area by accidental oil spilling in the South and Southeast regions of Brazil. It was performed a topographic and soil cover survey for a region of 12 km x 12 km in the SSC region in order to obtain the essential parameters to estimate the energy balance over the continent. Hourly averaged data of wind, air temperature and specific humidity collected by the Marine Biologic Center (CEBIMar) and ocean temperature obtained by a mooring near the center of the channel were used in this work to estimate the energy balance over the continent using the routine proposed by Deardorff (1978) and over the ocean using bulk parameterizations for winter and summer conditions. The obtained results were used to determine the PBL height for both surfaces. To investigate the PBL spatial evolution in the transition continent-water-continent it was applied a movable average with advection of the PBL height in the zonal wind direction the wind component more intense during winter and summer, according to the data analysis- to investigate the PBL spatial evolution through two latitude lines: one intercepting the CEBIMar and another in an region southward with equal water and continent proportion.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / With the globalization and the competitiveness in all the levels of the industrial sector, the final product quality search became higher. On the other hand, energy saving became another important factor in modern industry. The consumption of electric energy in the industrial sector represents 45.5% of the total consumption of the country. The motor force represents most of this consumption, arriving to be superior of 80% in the textile, paper and cellulose sectors. This work presents two strategies of control, auto-adjustable PID and fuzzy controller, the objectives are a better final product quality and the energy saving. Ventilation and compression industrials process are used in this work. An analysis of limit cyclesâ presence through the descriptive function of the fuzzy controller is carried through, providing a previously validation of fuzzy controllerâs parameters by simulations, saving time in the adjust phase. Set-point changes are easily made and on-line, still the process is running, in the two considered controllers. Comparisons of energy consumption are made between the conventional strategies and the two strategies considered in this work. / Com a globalizaÃÃo e a competitividade em todos os nÃveis do setor industrial, a qualidade do produto final se tornou de importÃncia crescente. Por outro lado, a conservaÃÃo de energia no setor industrial se tornou outro fator importante na indÃstria moderna. O consumo de energia elÃtrica do setor industrial representa 45,5% do consumo total do paÃs. A forÃa motriz representa a maior parte deste consumo, chegando a ser superior a 80% nos setores tÃxtil, de papel e celulose. Este trabalho apresenta duas estratÃgias de controle, PID auto-ajustÃvel e controlador nebuloso, e tÃm como objetivos tanto a qualidade do produto final quanto a eficiÃncia energÃtica. SÃo utilizados processos de ventilaÃÃo e de compressÃo em escala industriais. Uma anÃlise da presenÃa dos ciclos limites atravÃs da funÃÃo descritiva do controlador nebuloso à realizada, de forma que os parÃmetros do controlador nebuloso podem ser previamente validados atravÃs de simulaÃÃes, poupando tempo na fase de ajuste dos parÃmentros do controlador. MudanÃas de set-point sÃo facilmente realizadas de forma online e sem que o funcionamento do processo seja descontinuado, nos dois controladores propostos. ComparaÃÃes quanto ao consumo de energia sÃo realizadas usando as estratÃgias de controle convencionais e as proposta neste trabalho.

A sépsis e o choque séptico representam uma síndrome complexa de intensa resposta inflamatória sistêmica, com múltiplas anormalidades fisiológicas e imunológicas, comumente causadas por infecção bacteriana. A principal conseqüência dessa resposta é o comprometimento de muitos órgãos e tecidos. A disfunção cardíaca, decorrente de um prejuízo na contratilidade miocárdica, tem sido reconhecida como um fator importante que contribui para os altos índices de mortalidade observados na sépsis. Dados recentes do nosso laboratório indicam que alterações estruturais no miocárdio podem ser responsáveis pela disfunção cardíaca observada na sépsis. Considerando que a maquinaria contrátil interna das miofibras deve permanecer intimamente conectada com a membrana e a matriz extracelular, o presente estudo foi proposto para avaliar alterações nas comunicações intercelulares e acoplagem mecânica entre os cardiomiócitos vizinhos e avaliar a expressão de proteínas do arcabouço celular e da matriz extracelular (especificamente a laminina-?2) durante a sépsis grave. Nossos resultados mostraram que há uma diminuição na expressão das proteínas envolvidas na formação das gap junctions (conexina43) e junções aderentes (N-caderina), o que resultaria na perda da integridade estrutural dos discos intercalares, alterando o acoplamento mecânico e eletro-químico entre os cardiomiócitos vizinhos. Além disso, demonstramos que há redução na expressão de distrofina e das proteínas que constituem o complexo de glicoproteínas associadas a distrofina (CGD) durante a sépsis experimental. A redução ou perda da expressão de distrofina é o evento primário que ocorre seguido pela degeneração miofilamentar, caracterizada pela lise dos filamentos de actina e miosina. A diminuição na expressão das glicoproteínas associadas à distrofina: -distroglicana e laminina foram considerados eventos secundários. Os resultados sugerem que durante a sépsis induzida por ligação e perfuração do ceco (CLP), há perda de proteínas importantes envolvidas tanto no remodelamento do disco intercalar quanto na expressão de glicoproteínas envolvidas na ligação mecânica entre o citoesqueleto intracelular e a matriz extracelular. Embora estudos funcionais sejam necessários para determinar o efeito direto dessas alterações sobre o miocárdio podemos sugerir que as alterações estruturais são parcialmente responsáveis pela depressão miocárdica observada na sépsis. / Sepsis and septic shock represent a complex syndrome of systemic inflammatory response, with multiple physiological and immunological abnormalities, commonly caused by bacterial infection. The most important consequence of the response is the involvement of many organs and tissues. Cardiac dysfunction, caused by impairment in myocardial contractility, has been recognized as an important factor that contributes to the high mortality observed in sepsis. Evidence from our laboratory indicates that myocardial structural changes could be responsible for sepsis-induced myocardial dysfunction. Taking into account that the contractile machinery inside the myofibers must remain intimately connected with the membrane and extracellular matrix, the present investigation sought to evaluate changes in intercellular communications and mechanical coupling between the neighbor cardiomyocytes and the expression of the cell scaffold protein and extracellular matrix (specifically merosin laminin-2 chain) during the severe sepsis. Our results showed a decrease in the expression of proteins involved in formation of gap junctions (connexin-43) and adherens junctions (N-cadherin). These alterations may result in the loss of intercalated disc structural integrity, changing the mechanical and electrical-chemical coupling between neighboring cardiomyocytes. Additionally, we demonstrated the decrease of dystrophin and dystrophin-glycoprotein complex (DGC) components resulting from severe septic injury. The reduction or loss of dystrophin is the primary event that occurs followed by miofilamentar degeneration characterized by actin and myosin lysis. The decrease of glycoproteins associated with dystrophin: -dystroglican and laminin were considered secondary events. The results suggest that during experimental severe sepsis induced by cecal ligation and puncture (CLP), there is loss of important proteins involved in both the remodeling of the intercalated disc and the glycoproteins expression implicated in the mechanical link between the intracellular cytoskeleton and extracellular matrix. Although the functional studies are needed to determine the direct effect of these alterations on myocardium, we can suggest that myocardial structural changes may be partly responsible for sepsis-induced cardiac depression.

A sépsis e o choque séptico representam uma síndrome complexa de intensa resposta inflamatória sistêmica, com múltiplas anormalidades fisiológicas e imunológicas, comumente causadas por infecção bacteriana. A principal conseqüência dessa resposta é o comprometimento de muitos órgãos e tecidos. A disfunção cardíaca, decorrente de um prejuízo na contratilidade miocárdica, tem sido reconhecida como um fator importante que contribui para os altos índices de mortalidade observados na sépsis. Dados recentes do nosso laboratório indicam que alterações estruturais no miocárdio podem ser responsáveis pela disfunção cardíaca observada na sépsis. Considerando que a maquinaria contrátil interna das miofibras deve permanecer intimamente conectada com a membrana e a matriz extracelular, o presente estudo foi proposto para avaliar alterações nas comunicações intercelulares e acoplagem mecânica entre os cardiomiócitos vizinhos e avaliar a expressão de proteínas do arcabouço celular e da matriz extracelular (especificamente a laminina-?2) durante a sépsis grave. Nossos resultados mostraram que há uma diminuição na expressão das proteínas envolvidas na formação das gap junctions (conexina43) e junções aderentes (N-caderina), o que resultaria na perda da integridade estrutural dos discos intercalares, alterando o acoplamento mecânico e eletro-químico entre os cardiomiócitos vizinhos. Além disso, demonstramos que há redução na expressão de distrofina e das proteínas que constituem o complexo de glicoproteínas associadas a distrofina (CGD) durante a sépsis experimental. A redução ou perda da expressão de distrofina é o evento primário que ocorre seguido pela degeneração miofilamentar, caracterizada pela lise dos filamentos de actina e miosina. A diminuição na expressão das glicoproteínas associadas à distrofina: -distroglicana e laminina foram considerados eventos secundários. Os resultados sugerem que durante a sépsis induzida por ligação e perfuração do ceco (CLP), há perda de proteínas importantes envolvidas tanto no remodelamento do disco intercalar quanto na expressão de glicoproteínas envolvidas na ligação mecânica entre o citoesqueleto intracelular e a matriz extracelular. Embora estudos funcionais sejam necessários para determinar o efeito direto dessas alterações sobre o miocárdio podemos sugerir que as alterações estruturais são parcialmente responsáveis pela depressão miocárdica observada na sépsis. / Sepsis and septic shock represent a complex syndrome of systemic inflammatory response, with multiple physiological and immunological abnormalities, commonly caused by bacterial infection. The most important consequence of the response is the involvement of many organs and tissues. Cardiac dysfunction, caused by impairment in myocardial contractility, has been recognized as an important factor that contributes to the high mortality observed in sepsis. Evidence from our laboratory indicates that myocardial structural changes could be responsible for sepsis-induced myocardial dysfunction. Taking into account that the contractile machinery inside the myofibers must remain intimately connected with the membrane and extracellular matrix, the present investigation sought to evaluate changes in intercellular communications and mechanical coupling between the neighbor cardiomyocytes and the expression of the cell scaffold protein and extracellular matrix (specifically merosin laminin-2 chain) during the severe sepsis. Our results showed a decrease in the expression of proteins involved in formation of gap junctions (connexin-43) and adherens junctions (N-cadherin). These alterations may result in the loss of intercalated disc structural integrity, changing the mechanical and electrical-chemical coupling between neighboring cardiomyocytes. Additionally, we demonstrated the decrease of dystrophin and dystrophin-glycoprotein complex (DGC) components resulting from severe septic injury. The reduction or loss of dystrophin is the primary event that occurs followed by miofilamentar degeneration characterized by actin and myosin lysis. The decrease of glycoproteins associated with dystrophin: -dystroglican and laminin were considered secondary events. The results suggest that during experimental severe sepsis induced by cecal ligation and puncture (CLP), there is loss of important proteins involved in both the remodeling of the intercalated disc and the glycoproteins expression implicated in the mechanical link between the intracellular cytoskeleton and extracellular matrix. Although the functional studies are needed to determine the direct effect of these alterations on myocardium, we can suggest that myocardial structural changes may be partly responsible for sepsis-induced cardiac depression.