The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSION: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Bacterial lipopolysaccharide induces apoptosis in the trout ovary

BACKGROUND: In mammals it is well known that infections can lead to alterations in reproductive function. As part of the innate immune response, a number of cytokines and other immune factors is produced during bacterial infection or after treatment with lipopolysaccharide (LPS) and acts on the reproductive system. In fish, LPS can also induce an innate immune response but little is known about the activation of the immune system by LPS on reproduction in fish. Therefore, we conducted studies to examine the in vivo and in vitro effects of lipopolysaccharide (LPS) on the reproductive function of sexually mature female trout. METHODS: In saline- and LPS -injected brook trout, we measured the concentration of plasma steroids as well as the in vitro steroidogenic response (testosterone and 17alpha-hydroxyprogesterone) of ovarian follicles to luteinizing hormone (LH), the ability of 17alpha,20beta-dihydroxy-4-pregnen-3-one to induce germinal vesicle breakdown (GVBD) in vitro, and that of epinephrine to stimulate follicular contraction in vitro. We also examined the direct effects of LPS in vitro on steroid production, GVBD and contraction in brook trout ovarian follicles. The incidence of apoptosis was evaluated by TUNEL analysis. Furthermore, we examined the gene expression pattern in the ovary of saline- and LPS-injected rainbow trout by microarray analysis. RESULTS: LPS treatment in vivo did not affect plasma testosterone concentration or the basal in vitro production of steroids, although a small but significant potentiation of the effects of LH on testosterone production in vitro was observed in ovarian follicles from LPS-treated fish. In addition, LPS increased the plasma concentration of cortisol. LPS treatment in vitro did not affect the basal or LH-stimulated steroid production in brook trout ovarian follicles. In addition, we did not observe any effects of LPS in vivo or in vitro on GVBD or follicular contraction. Therefore, LPS did not appear to impair ovarian steroid production, oocyte final maturation or follicular contraction under the present experimental conditions. Interestingly, LPS administration in vivo induced apoptosis in follicular cells, an observation that correlated with changes in the expression of genes involved in apoptosis, as evidenced by microarray analysis. CONCLUSION: These results indicate that female trout are particularly resistant to an acute administration of LPS in terms of ovarian hormone responsiveness. However, LPS caused a marked increase in apoptosis in follicular cells, suggesting that the trout ovary could be sensitive to the pro-apoptotic effects of LPS-induced inflammatory cytokines.

Cellular and molecular evidence for a role of tumor necrosis factor alpha in the ovulatory mechanism of trout

Background: The relevance of immune-endocrine interactions to the regulation of ovarian function in teleosts is virtually unexplored. As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor alpha (TNF alpha) and other immune factors, are produced and act on the reproductive system. However, TNF alpha is also an important physiological player in the ovulatory process in mammals. In the present study, we have examined for the first time the effects of TNF alpha in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta). Methods: To determine the in vivo regulation of TNF alpha expression in the ovary, preovulatory brook trout (Salvelinus fontinalis) were injected intraperitoneally with either saline or bacterial lipopolysaccharide (LPS). In control and recombinant trout TNF alpha (rtTNF alpha)-treated brown trout granulosa cells, we examined the percentage of apoptosis by flow cytometry analysis and cell viability by propidium iodide (PI) staining. Furthermore, we determined the in vitro effects of rtTNF alpha on follicle contraction and testosterone production in preovulatory brown trout ovarian follicles. In addition, we analyzed the gene expression profiles of control and rtTNF alpha-treated ovarian tissue by microarray and real-time PCR (qPCR) analyses. Results: LPS administration in vivo causes a significant induction of the ovarian expression of TNF alpha. Treatment with rtTNF alpha induces granulosa cell apoptosis, decreases granulosa cell viability and stimulates the expression of genes known to be involved in the normal ovulatory process in trout. In addition, rtTNF alpha causes a significant increase in follicle contraction and testosterone production. Also, using a salmonid-specific microarray platform (SFA2.0 immunochip) we observed that rtTNF alpha induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling. Furthermore, the expression of kallikrein, TOP-2, serine protease 23 and ADAM 22, genes that have been postulated to be involved in proteolytic and tissue remodeling processes during ovulation in trout, increases in follicles incubated in the presence of rtTNF alpha. Conclusions In view of these results, we propose that TNF alpha could have an important role in the biomechanics of follicle weakening, ovarian rupture and oocyte expulsion during ovulation in trout, primarily through its stimulation of follicular cell apoptosis and the expression of genes involved in follicle wall proteolysis and contraction.

Eficiencia de las reglas de asignación de agua en el regadío: asignación a través de mercados, de la regla proporcional y de la regla uniforme

En el presente trabajo se simula la introducción de diferentes métodos de reparto del agua en la agricultura, y se aplican a una zona de regadío del valle central del Ebro. En concreto, se han escogido tres métodos diferentes de asignación con el fin de comparar su eficiencia económica. Además del actual sistema proporcional y el sistema de mercado, se simulará la introducción de la regla de reparto uniforme, desarrollada en la teoría de la elección social. Los resultados permiten concluir que aunque el mercado de agua conduzca a mejores resultados globales en todos los casos, la regla uniforme puede resultar una alternativa interesante cuando las dotaciones de agua se encuentran en el intervalo habitual, mientras que en situaciones de escasez severa de agua, el mercado presenta una ventaja más clara con respecto a cualquier otro sistema de asignación. Asimismo, los resultados demuestran que los niveles superiores de heterogeneidad entre los usuarios y altos precios administrativos del agua representan situaciones más ventajosas para la aplicación de la regla de asignación uniforme en comparación con el actual sistema proporcional

Desempenho, fibras musculares e carne de bovinos jovens de três grupos genéticos

O objetivo deste trabalho foi avaliar as características de desempenho, carcaça, qualidade de carne e das fibras musculares esqueléticas de bovinos jovens de três grupos genéticos, Angus x Nelore, Canchim x Nelore e Simental x Nelore. Noventa bovinos inteiros mestiços jovens, com idade média de oito meses, sendo 30 de cada grupo genético, foram distribuídos em delineamento experimental inteiramente casualizado, com três tratamentos (grupos genéticos) e seis repetições. Nas análises das fibras musculares, foram utilizados seis animais por tratamento e na avaliação de desempenho e características de carcaça, foram utilizados todos os animais. Em relação a ganho de peso diário, rendimentos de carcaça e cortes cárneos, área do músculo longissimus dorsi e proteínas e lipídeos totais na carne, não houve diferença entre os grupos genéticos, porém os mestiços Angus apresentaram maior espessura de gordura subcutânea. A maciez da carne não variou entre os grupos genéticos e entre os períodos de 7 e 14 dias de maturação. A semelhança da maciez da carne de 7 e 14 dias permite que o tempo de maturação das carnes seja reduzido, quando se utiliza animais jovens.

Efficacy and safety of a phospholipid emulsion (GR270773) in Gram-negative severe sepsis: results of a phase II multicenter, randomized, placebo-controlled, dose-finding clinical trial.

OBJECTIVE: To assess the survival benefit and safety profile of low-dose (850 mg/kg) and high-dose (1350 mg/kg) phospholipid emulsion vs. placebo administered as a continuous 3-day infusion in patients with confirmed or suspected Gram-negative severe sepsis. Preclinical and ex vivo studies show that lipoproteins bind and neutralize endotoxin, and experimental animal studies demonstrate protection from septic death when lipoproteins are administered. Endotoxin neutralization correlates with the amount of phospholipid in the lipoprotein particles. DESIGN: A three-arm, randomized, blinded, placebo-controlled trial. SETTING: Conducted at 235 centers worldwide between September 2004 and April 2006. PATIENTS: A total of 1379 patients participated in the study, 598 patients received low-dose phospholipid emulsion, and 599 patients received placebo. The high-dose phospholipid emulsion arm was stopped, on the recommendation of the Independent Data Monitoring Committee, due to an increase in life-threatening serious adverse events at the fourth interim analysis and included 182 patients. MEASUREMENTS AND MAIN RESULTS: A 28-day all-cause mortality and new-onset organ failure. There was no significant treatment benefit for low- or high-dose phospholipid emulsion vs. placebo for 28-day all-cause mortality, with rates of 25.8% (p = .329), 31.3% (p = .879), and 26.9%, respectively. The rate of new-onset organ failure was not statistically different among groups at 26.3%, 31.3%, 20.4% with low- and high-dose phospholipid emulsion, and placebo, respectively (one-sided p = .992, low vs. placebo; p = .999, high vs. placebo). Of the subjects treated, 45% had microbiologically confirmed Gram-negative infections. Maximal changes in mean hemoglobin levels were reached on day 10 (-1.04 g/dL) and day 5 (-1.36 g/dL) with low- and high-dose phospholipid emulsion, respectively, and on day 14 (-0.82 g/dL) with placebo. CONCLUSIONS: Treatment with phospholipid emulsion did not reduce 28-day all-cause mortality, or reduce the onset of new organ failure in patients with suspected or confirmed Gram-negative severe sepsis.

Nonpoint source pollution, space, time and asymetric information - a deposit refund approach

The incorporation of space allows the establishment of a more precise relationship between a contaminating input, a contaminating byproduct and emissions that reach the final receptor. However, the presence of asymmetric information impedes the implementation of the first-best policy. As a solution to this problem a site specific deposit refund system for the contaminating input and the contaminating byproduct are proposed. Moreover, the utilization of a successive optimization technique first over space and second over time enables definition of the optimal intertemporal site specific deposit refund system

Dieta com alto teor de gordura e desempenho de tourinhos de grupos genéticos diferentes em confinamento

O objetivo deste trabalho foi avaliar o desempenho em confinamento de tourinhos de quatro grupos genéticos distintos tratados com dietas com diferentes teores de gordura. Foram utilizados nove animais Nelore, nove Caracu, dez ½ Caracu ¼ Angus ¼ Nelore e dez ½ Red Angus ¼ Caracu ¼ Nelore, com massa corporal inicial de 227±33 kg e dez meses de idade, distribuídos aleatoriamente em dois tratamentos nutricionais: baixo teor de gordura (3,15% de extrato etéreo) e alto teor de gordura (7,28% de extrato etéreo). A ingestão de matéria seca (IMS) foi quantificada durante 208 dias e as pesagens dos animais foram realizadas a cada 28 dias. Os animais alimentados com as dietas de alto e de baixo teor de gordura apresentaram resultados similares de ganho médio diário de peso (1,511x1,487 kg por dia, respectivamente) e de eficiência alimentar (194x180 g de ganho por quilograma de MS ingerida, respectivamente); a IMS, em percentagem do peso vivo, foi menor nos animais alimentados com dieta de alto teor de gordura (2,25x2,40, respectivamente). Os animais cruzados apresentaram maior ganho de massa corporal e IMS que os Nelore. A dieta com alto teor de gordura pode ser utilizada em confinamento para melhorar o desempenho de tourinhos ½ Caracu ¼ Angus ¼ Nelore, pois é eficiente para reduzir a ingestão de matéria seca e não prejudica o ganho de massa corporal dos animais.

Características de carcaça e qualidade de carne de novilhos superprecoces de três grupos genéticos

O objetivo deste trabalho foi avaliar parâmetros de carcaça, características físico-químicas e de qualidade de carne de novilhos machos superprecoces. Foram avaliados três grupos raciais com 8 animais Nelore (N), 18 ¼ Abeerden Angus ½ Nelore (AN) e 18 ½ Limousin ¼ Abeerden Angus ¼ Nelore (LAN), com idade entre 7,5 e 11,5 meses no início do experimento, abatidos após 143 dias de confinamento. Os animais AN apresentaram maior peso ao abate, ganho médio diário de peso, peso de carcaça e comprimento de carcaça; os animais LAN apresentaram maior rendimento de carcaça e área de olho de lombo. Os animais LAN apresentaram 72% de carcaças convexas, enquanto 83% das carcaças dos animais AN e 100% das carcaças dos animais N foram classificadas como subconvexas. Os grupos LAN e AN não apresentaram diferença significativa nos valores de força de cisalhamento, o que indica a possibilidade de utilização da proporção de 50% do genótipo Bos indicus sem prejuízo para a maciez da carne. As características de carcaça e carne dos animais dos grupos genéticos NA, LAN e N estão em conformidade com as especificações de consumo e adequadas para abate aos 15 meses de idade, o que viabiliza o sistema de produção de novilhos superprecoces.

Eficiências biológica e econômica de bovinos em terminação alimentados com dieta suplementar em pastagem de capim-marandu

O objetivo deste trabalho foi avaliar as eficiências biológica e econômica de novilhos em terminação, em pastagem, que receberam suplementação durante o período seco. Trinta novilhos ½ Braford ¼ Angus ¼/ Nelore, separados em dois lotes com pesos corporais médios (PC) de 365 e 410 kg, foram distribuídos em seis piquetes de capim-marandu, em delineamento experimental inteiramente casualizado, com três tratamentos e dez repetições. Os tratamentos foram constituídos pelos suplementos: sal-amireia; 0,6 e 1% do PC de concentrado. A cada 28 dias, os animais foram pesados, e a cobertura de gordura foi avaliada. Mensalmente, todos os piquetes foram amostrados para determinação da massa de forragem dos componentes morfológicos e do valor nutritivo. Os animais com suplementação de 1% do PC de concentrado ganharam mais peso do que aqueles com 0,6% do PC, e estes últimos mais do que aqueles que receberam sal-amireia. Consequentemente, houve relação inversa entre a dose de suplementação e o tempo necessário para os animais atingirem o ponto de acabamento. Independentemente do tratamento, os animais mais leves apresentaram margens líquidas superiores. Para os dois lotes, a maior margem líquida esteve associada à suplementação apenas com sal-amireia.

Genetic polymorphisms related to meat traits in purebred and crossbred Nelore cattle

The objective of this work was to estimate the allelic and genotypic frequencies of CAST/XmnI, a calpastatin gene polymorphism, and CAPN530, a calpain 1 large subunit gene polymorphism, in different beef genetic groups (Nelore and Nelore x Bos taurus), and to investigate associations between these polymorphisms and carcass and meat traits. Three hundred animals - comprising 114 Nelore, 67 Angus x Nelore, 44 Rubia Gallega x Nelore, 41 Canchim, 19 Brangus three-way cross and 15 Braunvieh three-way cross- were genotyped by PCR-RFLP and phenotyped for rib-eye area (REA), back-fat thickness (BT), intramuscular fat (IF), shear force (SF) and myofibrillar fragmentation index (MFI). The occurrence of the two alleles of the CAST/XmnI and CAPN530 single nucleotide polymorphisms (SNPs) in a B. indicus breed, which permitted association studies in purebred and crossbred Nelore cattle, was first shown in the present work. No relationship was found between the CAST or CAPN1 SNPs and growth-related traits (REA) or fat deposition (BT and IF), since calpastatin and µ-calpain are not physiologically involved with these traits. Moreover, the association results between genotypes and aged meat tenderness (assessed by SF and MFI) showed that these markers are useless in assisted selection for purebred Nelore and their crosses with B. taurus.

Insulin-like growth factor and growth hormone receptor in postpartum lactating beef cows

The objective of this study was to evaluate the plasma concentrations of insulin-like growth factor-I (IGF-I), and the mRNA hepatic expression of IGF-I and of the growth hormone receptors GHR and GHR 1A, in postpartum beef cows. Four Angus and four crossbred (Angus x Nelore) postpartum suckled beef cows were used. Liver and blood samples were collected every 10 days, from calving to 40 days postpartum, for gene expression and for β-hydroxybutyrate and IGF-I assays, respectively. Samples for progesterone assay were collected every other day, from day 10 to 40 postpartum. Three cows ovulated before 40 days postpartum. IGF-I concentration was higher in Angus x Nelore than in Angus cows. There was no difference in the expression of GHR, GHR 1A and IGF-I according to breed or ovulatory status. IGF-I concentrations were higher in crossbred cows, but have not changed according to postpartum ovulatory status. Moreover, changes in postpartum IGF-I concentrations are not associated with changes in liver GHR, GHR 1A and IGF-I mRNA expression in either breed.

Curvas de crescimento em vacas de corte de diferentes tipos biológicos

O objetivo deste trabalho foi selecionar o modelo de curvas de crescimento mais adequado e avaliar a influência de efeitos de ambiente e de grupo genético sobre os parâmetros estimados do modelo. Cinco modelos não lineares, Brody, Gompertz, Logístico, Von Bertalanffy e Richards, foram ajustados a dados de peso-idade coletados de 316 vacas, de quatro grupos genéticos: G (Nelore, ½Canchim + ½Nelore, ½Angus + ½Nelore e ½Simental + ½Nelore), do nascimento até 100 meses de idade; em duas estações do ano: E (primavera e outono). As vacas foram submetidas a dois níveis de concentrado (S) durante quatro meses, pós-desmama. O ajuste dos modelos foi realizado por mínimos quadrados ordinários, usando os pesos ponderado e não ponderado pelo inverso da variância. Os modelos Brody e Von Bertalanffy convergiram para todos os grupos genéticos; porém, o Brody foi o mais adequado. As estimativas do peso assintótico (A) e da taxa de maturação (k) do modelo Brody ponderado pelo inverso da variância foram analisadas por modelo misto, que incluiu efeito médio global e efeitos principais de G, E e S, e suas interações. O parâmetro A foi influenciado pelo efeito de G e E, enquanto k foi influenciado por S, o que indica que melhorias no manejo alimentar resultam em menor variação na forma das curvas de crescimento e em altas taxas de maturação.

Sepsis: a roadmap for future research.

Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research.