Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure

Inoue BH, dos Santos L, Pessoa TD, Antonio EL, Pacheco BPM, Savignano FA, Carraro-Lacroix LR, Tucci PJF, Malnic G, Girardi ACC. Increased NHE3 abundance and transport activity in renal proximal tubule of rats with heart failure. Am J Physiol Regul Integr Comp Physiol 302: R166-R174, 2012. First published October 26, 2011; doi:10.1152/ajpregu.00127.2011.-Heart failure (HF) is associated with a reduced effective circulating volume that drives sodium and water retention and extracellular volume expansion. We therefore hypothesized that Na(+)/H(+) exchanger isoform 3 (NHE3), the major apical transcellular pathway for sodium reabsorption in the proximal tubule, is upregulated in an experimental model of HF. HF was induced in male rats by left ventricle radiofrequency ablation. Sham-operated rats (sham) were used as controls. At 6 wk after surgery, HF rats exhibited cardiac dysfunction with a dramatic increase in left ventricular end-diastolic pressure. By means of stationary in vivo microperfusion and pH-dependent sodium uptake, we demonstrated that NHE3 transport activity was significantly higher in the proximal tubule of HF compared with sham rats. Increased NHE3 activity was paralleled by increased renal cortical NHE3 expression at both protein and mRNA levels. In addition, the baseline PKA-dependent NHE3 phosphorylation at serine 552 was reduced in renal cortical membranes of rats with HF. Collectively, these results suggest that NHE3 is upregulated in the proximal tubule of HF rats by transcriptional, translational, and posttranslational mechanisms. Enhanced NHE3-mediated sodium reabsorption in the proximal tubule may contribute to extracellular volume expansion and edema, the hallmark feature of HF. Moreover, our study emphasizes the importance of undertaking a cardiorenal approach to contain progression of cardiac disease.

Velocity recovery cycles of human muscle action potentials in chronic renal failure

To test the hypothesis that muscle fibers are depolarized in patients with chronic renal failure, by measuring velocity recovery cycles of muscle action potentials as indicators of muscle membrane potential.

Group Stereotypes and The Self: How Social Status and Interaction Expectation Affect Self-Stereotyping

This study examined how ingroup status affects the tendency for people to internalize ingroup stereotypes (i.e. self-stereotype) when expecting to interact with another individual who holds stereotypic views of them. Past research has demonstrated that people self-stereotype when they want to affiliate with another individual who holds stereotypic views of them. By self-stereotyping, individuals create a common bond or shared set of beliefs with the other individual. This line of research has not yet examinedif there are any moderators in the relationship between affiliation motivation and self-stereotyping. However, there is reason to believe that members of lower-status groups are more likely to feel the need to create this common bond through self-stereotyping because 1) they identify more closely with their social group, 2) their group identity is more salient 3) they are more aware of the expectations of others, 4) and they care more about the quality of an interaction with a member from a higher-status group. For this experiment, I recruited twenty-seven members of Alpha Chi Omega andtwenty-eight members of Delta Gamma, two sororities that are perceived to be middle-ranked (as determined by a pre-test survey). Upon arriving to the study, half the participants were informed that they would be interacting with a member of Kappa Kappa Gamma, a higher-ranked sorority (as determined by a pre-test survey) and half the participants were informed that they would be interacting with a member of a Chi Omega, a lower-ranked sorority (as determined by a pre-test survey). Participants were also informed that this partner held stereotypic views of their (i.e. the participant’s)sorority. After, participants were given the Self-Stereotyping Measure in which they rated how well sixteen characteristics described themselves. The results of the series of analyses performed on participants’ ratings on the Self-Stereotyping Measure indicated that when expecting to interact with another individual, members of low-status groups self-stereotype more than members of high-statusgroups and those who do not expect to interact. Furthermore, unexpectedly, among members of high-status groups, those who expected to interact with a member of a low-status group self-stereotyped less than those who did not expect to interact. Thus, this research provides support for the hypothesis that group status is a moderator in the relationship between self-stereotyping and affiliation motivation.

Adjacent vertebral failure after vertebroplasty: a biomechanical study of low-modulus PMMA cement

PMMA is the most common bone substitute used for vertebroplasty. An increased fracture rate of the adjacent vertebrae has been observed after vertebroplasty. Decreased failure strength has been noted in a laboratory study of augmented functional spine units (FSUs), where the adjacent, non-augmented vertebral body always failed. This may provide evidence that rigid cement augmentation may facilitate the subsequent collapse of the adjacent vertebrae. The purpose of this study was to evaluate whether the decrease in failure strength of augmented FSUs can be avoided using low-modulus PMMA bone cement. In cadaveric FSUs, overall stiffness, failure strength and stiffness of the two vertebral bodies were determined under compression for both the treated and untreated specimens. Augmentation was performed on the caudal vertebrae with either regular or low-modulus PMMA. Endplate and wedge-shaped fractures occurred in the cranial and caudal vertebrae in the ratios endplate:wedge (cranial:caudal): 3:8 (5:6), 4:7 (7:4) and 10:1 (10:1) for control, low-modulus and regular cement group, respectively. The mean failure strength was 3.3 +/- 1 MPa with low-modulus cement, 2.9 +/- 1.2 MPa with regular cement and 3.6 +/- 1.3 MPa for the control group. Differences between the groups were not significant (p = 0.754 and p = 0.375, respectively, for low-modulus cement vs. control and regular cement vs. control). Overall FSU stiffness was not significantly affected by augmentation. Significant differences were observed for the stiffness differences of the cranial to the caudal vertebral body for the regular PMMA group to the other groups (p < 0.003). The individual vertebral stiffness values clearly showed the stiffening effect of the regular cement and the lesser alteration of the stiffness of the augmented vertebrae using the low-modulus PMMA compared to the control group (p = 0.999). In vitro biomechanical study and biomechanical evaluation of the hypothesis state that the failure strength of augmented functional spine units could be better preserved using low-modulus PMMA in comparison to regular PMMA cement.

Estimating and quantifying uncertainties on level sets using the Vorob'ev expectation and deviation with Gaussian process models

Several methods based on Kriging have recently been proposed for calculating a probability of failure involving costly-to-evaluate functions. A closely related problem is to estimate the set of inputs leading to a response exceeding a given threshold. Now, estimating such a level set—and not solely its volume—and quantifying uncertainties on it are not straightforward. Here we use notions from random set theory to obtain an estimate of the level set, together with a quantification of estimation uncertainty. We give explicit formulae in the Gaussian process set-up and provide a consistency result. We then illustrate how space-filling versus adaptive design strategies may sequentially reduce level set estimation uncertainty.

Prevalence of Premature Ovarian Failure in Women with Tuberous Sclerosis

Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor disorder characterized by hamartomas, or benign growths, in various organ systems. Inactivating mutations in either the TSC1 or the TSC2 gene cause most cases of TSC. Recently, the use of ovarian specific conditional knock-out mouse models has demonstrated a crucial role of the TSC genes in ovarian function. Mice with complete deletion of Tsc1 or Tsc2 showed accelerated ovarian follicle activation and subsequent premature follicular depletion, consistent with the human condition premature ovarian failure (POF). POF is defined in women as the cessation of menses before the age of 40 and elevated levels of follicle stimulating hormone (FSH). The prevalence of POF is estimated to be 1%, affecting a substantial number of women in the general population. Nonetheless, the etiology of most cases of POF remains unknown. Based on the mouse model results, we hypothesized that the human TSC1 and TSC2 genes are likely to be crucial for ovarian development and function. Moreover, since women with TSC already have one inactivated TSC gene, we further hypothesized that they may show a higher prevalence of POF. To test this hypothesis, we surveyed 1000 women with TSC belonging to the Tuberous Sclerosis Alliance, a national support organization. 182 questionnaires were analyzed for information on menstrual and reproductive function, as well as TSC. This self-reported data revealed 8 women (4.4%) with possible POF, as determined by menstrual history report and additional supportive data. This prevalence is much higher than 1% in the general population. Data from all women suggested other reproductive pathology associated with TSC such as a high rate of miscarriage (41.2%) and menstrual irregularity of any kind (31.2%). These results establish a previously unappreciated effect of TSC on women’s reproductive health. Moreover, these data suggest that perturbations in the cellular pathways regulated by the TSC genes may play an important role in reproductive function.

US Corporate Default Swap Valuation: The Market Liquidity Hypothesis and Autonomous Credit Risk

This paper develops a reduced form three-factor model which includes a liquidity proxy of market conditions which is then used to provide implicit prices. The model prices are then compared with observed market prices of credit default swaps to determine if swap rates adequately reflect market risks. The findings of the analysis illustrate the importance of liquidity in the valuation process. Moreover, market liquidity, a measure of investors. willingness to commit resources in the credit default swap (CDS) market, was also found to improve the valuation of investors. autonomous credit risk. Thus a failure to include a liquidity proxy could underestimate the implied autonomous credit risk. Autonomous credit risk is defined as the fractional credit risk which does not vary with changes in market risk and liquidity conditions.

Ultimate and failure strengths of normal muds and serpentinite muds of ODP Leg 125 samples

Serpentinite seamounts in the Mariana forearc have been explained as diapirs rising from the Benioff zone. This hypothesis predicts that the serpentinites should have low strengths as well as low densities relative to the surrounding rocks. Drilling during Leg 125 showed that the materials forming Conical Seamount in the Mariana forearc and Torishima Forearc Seamount in the Izu-Bonin forearc are water-charged serpentinite muds of density <2 g/cm**3. Wykeham-Farrance torsion-vane tests showed that they are plastic solids with a rheology that bears many similarities to the idealized Cam clay soil model and is well described by critical-state soil mechanics. The serpentinite muds have ultimate strengths of 1.3 to 273.7 kPa and yield strengths of approximately 1.0 to 50 kPa. These muds thus are orders of magnitude weaker than salt and are, in fact, comparable in density and strength to common deep-sea clay muds. Such weak and low-density materials easily become diapiric. Serpentinite muds from the summit of Conical Seamount are weaker and more ductile than those on its flanks or on Torishima Forearc Seamount. Moreover, the summit muds do not contain the pronounced pure- and simple-shear fabrics that characterize those on the seamount flanks. The seamounts are morphologically similar to shield volcanoes, and anastomosing serpentinite debris flows descending from their summits are similar in map view to pahoehoe flows. These morphologic features, together with the physical properties of the muds and their similarities to other oceanic muds and the geochemistry of the entrained waters, suggest that many forearc serpentinite seamounts are gigantic (10-20 km wide, 1.5-2.0 km high) mud volcanoes that formed by the eruption of highly liquid serpentinite muds. Torishima Forearc Seamount, which is blanketed by more ìnormalî pelagic/volcaniclastic sediment, has probably been inactive since the Miocene. Conical Seamount, which seems to consist entirely of serpentinite mud and is venting fresh water of unusual chemistry from its summit, is presently active. Muds from the flanks of Conical Seamount are stronger and more brittle than those from the summit site, and muds from Torishima Forearc Seamount are stronger yet; this suggests that the serpentinite debris flows are compacted and dewatered as they mature. The shear fabrics probably result from downslope creep and flow, but may also be inherited.

Analysis of the operator action and the single failure criteria in a SGTR sequence using best estimate assumptions with TRACE 5.0

Steam Generator Tube Rupture (SGTR) sequences in Pressurized Water Reactors are known to be one of the most demanding transients for the operating crew. SGTR are a special kind of transient as they could lead to radiological releases without core damage or containment failure, as they can constitute a direct path from the reactor coolant system to the environment. The first methodology used to perform the Deterministic Safety Analysis (DSA) of a SGTR did not credit the operator action for the first 30 min of the transient, assuming that the operating crew was able to stop the primary to secondary leakage within that period of time. However, the different real SGTR accident cases happened in the USA and over the world demonstrated that the operators usually take more than 30 min to stop the leakage in actual sequences. Some methodologies were raised to overcome that fact, considering operator actions from the beginning of the transient, as it is done in Probabilistic Safety Analysis. This paper presents the results of comparing different assumptions regarding the single failure criteria and the operator action taken from the most common methodologies included in the different Deterministic Safety Analysis. One single failure criteria that has not been analysed previously in the literature is proposed and analysed in this paper too. The comparison is done with a PWR Westinghouse three loop model in TRACE code (Almaraz NPP) with best estimate assumptions but including deterministic hypothesis such as single failure criteria or loss of offsite power. The behaviour of the reactor is quite diverse depending on the different assumptions made regarding the operator actions. On the other hand, although there are high conservatisms included in the hypothesis, as the single failure criteria, all the results are quite far from the regulatory limits. In addition, some improvements to the Emergency Operating Procedures to minimize the offsite release from the damaged SG in case of a SGTR are outlined taking into account the offsite dose sensitivity results.

Atrial-like phenotype is associated with embryonic ventricular failure in retinoid X receptor alpha -/- mice.

We have recently characterized a cardiac model of ventricular chamber defects in retinoid X receptor alpha (RXR alpha) homozygous mutant (-/-) gene-targeted mice. These mice display generalized edema, ventricular chamber hypoplasia, and muscular septal defects, and they die at embryonic day 15. To substantiate our hypothesis that the embryos are dying of cardiac pump failure, we have used digital bright-field and fluorescent video microscopy and in vivo microinjection of fluorescein-labeled albumin to analyze cardiac function. The affected embryos showed depressed ventricular function (average left ventricular area ejection fraction, 14%), ventricular septal defects, and various degrees of atrioventricular block not seen in the RXR alpha wild-type (+/+) and heterozygous (+/-) littermates (average left ventricular area ejection fraction, 50%). The molecular mechanisms involved in these ventricular defects were studied by evaluating expression of cardiac-specific genes known to be developmentally regulated. By in situ hybridization, aberrant, persistent expression of the atrial isoform of myosin light chain 2 was identified in the ventricles. We hypothesize that retinoic acid provides a critical signal mediated through the RXR alpha pathway that is required to allow progression of development of the ventricular region of the heart from its early atrial-like form to the thick-walled adult ventricle. The conduction system disturbances found in the RXR alpha -/- embryos may reflect a requirement of the developing conduction system for the RXR alpha signaling pathway, or it may be secondary to the failure of septal development.

Nephron number, hypertension, renal disease, and renal failure

Essential hypertension is one of the most common diseases in the Western world, affecting about 26.4% of the adult population, and it is increasing (1). Its causes are heterogeneous and include genetic and environmental factors (2), but several observations point to an important role of the kidney in its genesis (3). In addition to variations in tubular transport mechanisms that could, for example, affect salt handling, structural characteristics of the kidney might also contribute to hypertension. The burden of chronic kidney disease is also increasing worldwide, due to population growth, increasing longevity, and changing risk factors. Although single-cause models of disease are still widely promoted, multideterminant or multihit models that can accommodate multiple risk factors in an individual or in a population are probably more applicable (4,5). In such a framework, nephron endowment is one potential determinant of disease susceptibility. Some time ago, Brenner and colleagues (6,7) proposed that lower nephron numbers predispose both to essential hypertension and to renal disease. They also proposed that hypertension and progressive renal insufficiency might be initiated and accelerated by glomerular hypertrophy and intraglomerular hypertension that develops as nephron number is reduced (8). In this review, we summarize data from recent studies that shed more light on these hypotheses. The data supply a new twist to possible mechanisms of the Barker hypothesis, which proposes that intrauterine growth retardation predisposes to chronic disease in later life (9). The review describes how nephron number is estimated and its range and some determinants and morphologic correlates. It then considers possible causes of low nephron numbers. Finally, associations of hypertension and renal disease with reduced nephron numbers are considered, and some potential clinical implications are discussed.

Birth weight and age at menopause in Australian female twin pairs: exploration of the fetal origin hypothesis

In a twin sample where duration of gestation can be controlled, a specific example of the fetal origins hypothesis concerning association between low birth weight and early age at menopause is explored. The hypothesis is based on the physiologically plausible path from intrauterine growth retardation and reduced numbers of primary follicles to an earlier menopause. The sample comprised 323 Australian female twin pairs where both co-twins had reached menopause naturally and reported on their weight at birth. Regression analysis showed no linear association between the two variables (P = 0.371, r(2) = 0.0009). Intra-pair differences in age at menopause were investigated in the context of relative birth weight of co-twins. In 265 pairs an intra-pair birth a eight difference was reported. In monozygotic (MZ) pairs (n = 168) this allowed for control of genetic effects as well as gestation duration. No significant differences dependent on birth weight relative to co-twin were found for age at natural menopause in either MZ or dizygotic (DZ) twin pairs, even in pairs whose birth weights differed markedly. There was some indication that twins with premature ovarian failure were heavier at birth than twins with normal or later menopausal age. We conclude that the hypothesis that lower birth weight is associated with earlier menopause is not supported by our data.

The temporal binding deficit hypothesis of autism

Frith has argued that people with autism show “weak central coherence,” an unusual bias toward piecemeal rather than configurational processing and a reduction in the normal tendency to process information in context. However, the precise cognitive and neurological mechanisms underlying weak central coherence are still unknown. We propose the hypothesis that the features of autism associated with weak central coherence result from a reduction in the integration of specialized local neural networks in the brain caused by a deficit in temporal binding. The visuoperceptual anomalies associated with weak central coherence may be attributed to a reduction in synchronization of high-frequency gamma activity between local networks processing local features. The failure to utilize context in language processing in autism can be explained in similar terms. Temporal binding deficits could also contribute to executive dysfunction in autism and to some of the deficits in socialization and communication.

A Customer's Expectation and Perception of Hotel Service Quality in Cyprus

In recent years, hotels in Cyprus have encountered difficult economic times due to increasing customer demands and strong internal industry development competition. The hospitality industry’s main concern globally is to serve its customer S needs and desires, most of which are addressed through personal services. Hence, the hotel businesses that are able to provide quality services to its ever-demanding customers in a warm and efficient manner are those businesses which will be more likely to obtain a long term competitive advantage over their rivals. Ironically, the quality of services frequently cannot fully appreciated until something goes wrong, and then, the poor quality of services can have long lasting lingering effects on the customer base and, hence, often is translated into a loss of business. Nevertheless, since the issue of delivery of hospitality services always involves people, this issue must center around the management of the human resource factor, and in particular, on the way which interacts with itself and with guests, as service encounters. In the eyes of guests, hospitality businesses will be viewed successful or failure, depending on [he cumulative impact of the service encounters they have experienced on a personal level. Finally, since hotels are offering intangible and perishable personal service encounters, managing these services must be a paramount concern of any hotel business. As a preliminary exercise, visualize when you have last visited a hotel, or a restaurant, and then, ask yourself these questions: What did you feel about the quality of the experience? Was it a memorable one, which you would recommend it to others, or there were certain things, which could have made the difference? Thus, the way personalized services are provided can make the deference in attracting arid retaining long-term customers

The impact of gestational age and fetal weight on the risk of failure of spinal anesthesia for cesarean delivery.

BACKGROUND: There are limited data about spinal dosing for cesarean delivery in preterm parturients. We investigated the hypothesis that preterm gestation is associated with an increased incidence of inadequate spinal anesthesia for cesarean delivery compared with term gestation. METHODS: We searched our perioperative database for women who underwent cesarean delivery under spinal or combined spinal-epidural anesthesia with hyperbaric bupivacaine ⩾10.5mg. The primary outcome was the incidence of inadequate surgical anesthesia needing conversion to general anesthesia or repetition or supplementation of the block. We divided patients into four categories: <28, 28 to <32, 32 to <37 and ⩾37weeks of gestation. The chi-square test was used to compare failure rates and a multivariable regression analysis was performed to investigate potential confounders of the relationship between gestational age and failure. RESULTS: A total of 5015 patients (3387 term and 1628 preterm) were included. There were 278 failures (5.5%). The incidence of failure was higher in preterm versus term patients (6.4% vs. 5.1%, P=0.02). Failure rates were 10.8%, 7.7%, 5.3% and 5% for <28, 28 to <32, 32 to <37 and ⩾37weeks of gestation, respectively. In the multivariable model, low birth weight (P<0.0001), gestational age (P=0.03), ethnicity (P=0.02) and use of combined spinal-epidural anesthesia (P<0.0001) were significantly associated with failure. CONCLUSIONS: At standard spinal doses of hyperbaric bupivacaine used in our practice (⩾10.5mg), there were higher odds of inadequate surgical anesthesia in preterm parturients. When adjusting for potential confounders, low birth weight was the main factor associated with failure.