Management of nursing assistants' (NAs) emotional stress from relationship conflicts with residents, families, and coworkers is rarely the focus of educational programs. Our objective was to gather feedback from NAs and their nursing supervisors (NSs) about the utility of our e-learning program for managing relationship stress.
Cardiovascular disease in pregnancy is the leading cause of maternal mortality in North America. Although transthoracic echocardiography (TTE) is the most widely used imaging modality for the assessment of cardiovascular function during pregnancy, little is known on the role of cardiovascular magnetic resonance (CMR). The objective of the Cardiac Hemodynamic Imaging and Remodeling in Pregnancy (CHIRP) study was to compare TTE and CMR in the non-invasive assessment of maternal cardiac remodeling during the peripartum period.
Dysregulation of aldosterone or cortisol production can predispose to hypertension, as seen in aldosterone-producing adenoma, a form of primary aldosteronism. We investigated the role of microRNA (miRNA) in their production, with particular emphasis on the CYP11B1 (11?-hydroxylase) and CYP11B2 (aldosterone synthase) genes, which produce the enzymes responsible for the final stages of cortisol and aldosterone biosynthesis, respectively. Knockdown of Dicer1, a key enzyme in miRNA maturation, significantly altered CYP11B1 and CYP11B2 expression in a human adrenocortical cell line. Screening of nondiseased human adrenal and aldosterone-producing adenoma samples yielded reproducible but distinctive miRNA expression signatures for each tissue type, with levels of certain miRNA, including microRNA-24 (miR-24), differing significantly between the 2. Bioinformatic analysis identified putative binding sites for several miRNA, including miR-24, in the 3 untranslated region of CYP11B1 and CYP11B2 mRNAs. In vitro manipulation of miR-24 confirmed its ability to modulate CYP11B1 and CYP11B2 expression, as well as cortisol and aldosterone production. This study demonstrates that Dicer-dependent miRNA, including miR-24, can post-transcriptionally regulate expression of the CYP11B1 and CYP11B2 genes. Normal adrenal tissue and aldosterone-producing adenoma differ significantly and reproducibly in their miRNA expression profiles, with miR-24 significantly downregulated in the latter. Adrenal miRNA may, therefore, be a novel and valid target for the therapeutic manipulation of corticosteroid biosynthesis.
Membranous ventricular septum aneurysm (MVSA) is an uncommon cardiac abnormality primarily associated with the spontaneous closure of a small membranous ventricular septal defect in childhood. Diagnosis of an idiopathic MVSA in an adult is exceedingly rare. We report on a man, aged 38 years, with a bilobed MVSA diagnosed by transesophageal echocardiography and gated computed tomography, with separate aneurysm sacs extending into the right atrium and right ventricle.
Nutrient enrichment and loadings of pharmaceuticals and agrochemicals into freshwater systems are common concerns, especially for water bodies receiving wastewater inputs. In the rural communities of Morden and Winkler of Manitoba, Canada, sewage lagoons discharge their wastewater directly into Dead Horse Creek, a small tributary of the Red River that empties into Lake Winnipeg. This lagoon approach to managing rural wastewaters is common across the North American Prairies. Therefore, this study aimed to assess the hazards of lagoon treatment releases at this model site. This was done by characterizing the nutrients, organic micropollutants (i.e., pesticides, pharmaceuticals) and standard water quality parameters in the creek prior to and following lagoon discharge events over a number of years (2009-2011). Measured concentrations of nutrients were compared to regulatory expectations and micropollutants were assessed using hazard quotients. As expected, concentrations of nitrogen and phosphorus species were greatest in sites downstream of the sewage outfall immediately following discharge events. Pharmaceutical and agricultural chemicals were detected at concentrations between 0.5 and 90 ng/L. Detection frequencies and concentrations matched typical use patterns. Those compounds used predominately for human medicine were detected at downstream sites following discharge events, while those used in an agricultural setting were detected at relatively consistent levels over time at sites both upstream and downstream of the outfall location. Hazard quotients calculated for micropollutants of interest indicated minimal toxicological risk to aquatic biota in the creek, with only erythromycin and diazinon presenting a potential concern to aquatic algae and invertebrates. Concentrations of nutrients exceeded Canadian guideline thresholds during release, but returned to background levels once discharges ceased. Therefore, it is advisable that wastewater treatment and management strategies such as constructed wetlands and/or staggered releases be used in order to minimize the hazard posed by nutrient pulses in Dead Horse Creek and other similar systems.
Despite the concern that has been expressed about potential method biases, and the pervasiveness of research settings with the potential to produce them, there is disagreement about whether they really are a problem for researchers in the behavioral sciences. Therefore, the purpose of this review is to explore the current state of knowledge about method biases. First, we explore the meaning of the terms "method" and "method bias" and then we examine whether method biases influence all measures equally. Next, we review the evidence of the effects that method biases have on individual measures and on the covariation between different constructs. Following this, we evaluate the procedural and statistical remedies that have been used to control method biases and provide recommendations for minimizing method bias.
Advances in the sensitivity of molecular techniques during the 1990s led to a flurry of studies that supported the existence of extra-adrenal sites of aldosterone production in various tissues including the brain and the heart. Subsequent work was often conflicting or ambiguous, leading many to question whether extra-adrenal aldosterone was of any physiological importance, or whether it even existed. In this article, we review these studies and, in light of this evidence, discuss whether the current lack of interest in extra-adrenal aldosterone biosynthesis is justified.
Guidelines for the provision of echocardiography in Canada were jointly developed and published by the Canadian Cardiovascular Society and the Canadian Society of Echocardiography in 2005. Since their publication, recognition of the importance of echocardiography to patient care has increased, along with the use of focused, point-of-care echocardiography by physicians of diverse clinical backgrounds and variable training. New guidelines for physician training and maintenance of competence in adult echocardiography were required to ensure that physicians providing either focused, point-of-care echocardiography or comprehensive echocardiography are appropriately trained and proficient in their use of echocardiography. In addition, revision of the guidelines was required to address technological advances and the desire to standardize echocardiography training across the country to facilitate the national recognition of a physicians expertise in echocardiography. This paper summarizes the new Guidelines for Physician Training and Maintenance of Competency in Adult Echocardiography, which are considerably more comprehensive than earlier guidelines and address many important issues not previously covered. These guidelines provide a blueprint for physician training despite different clinical backgrounds and help standardize physician training and training programs across the country. Adherence to the guidelines will ensure that physicians providing echocardiography have acquired sufficient expertise required for their specific practice. The document will also provide a framework for other national societies to standardize their training programs in echocardiography and will provide a benchmark by which competency in adult echocardiography may be measured.
Serotonin 1B (5-HT(1B)) autoreceptors regulate release of serotonin from terminals of dorsal raphe nucleus (DRN) projections. Expression of 5-HT(1B) in the DRN inversely correlates with behavioral measures of emotion, and viral-mediated overexpression of 5-HT(1B) receptors in the middle DRN inversely reduces measures of fear and anxiety in unstressed rats. Because the caudal subregion of the DRN is important in translating stress into emotional dysregulation, we explored behavioral functions of 5-HT(1B) autoreceptors in the caudal DRN.
It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMP-dependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC.
SCOP (suprachiasmatic nucleus (SCN) circadian oscillatory protein) was originally identified in 1999 in a differential display screen of the rat SCN for genes whose expression were regulated in a circadian manner (K. Shimizu, M. Okada, A. Takano and K. Nagai, FEBS Lett., 1999, 458, 363-369). The SCN is the principle pacemaker of the circadian clock, and expression of SCOP protein in the SCN was found to oscillate, increasing during the subjective night, even when animals were housed in constant darkness. SCOP interacts with and inhibits multiple proteins important for intracellular signaling, either by directly binding to K-Ras or by dephosphorylating p-Akt and p-PKC. Since the functions of K-Ras, Akt, and PKC are considerably divergent, SCOP may have several roles. We recently discovered that SCOP participates in the formation of long-term hippocampus-dependent memories, and other investigators have examined its role in cell proliferation and survival. In this review, we introduce SCOP from its molecular structure to its physiological functions, focusing mainly on its role in ERK1/2 activation and memory consolidation.
Recent evidence highlighting the presence of cortico-steroid receptors in the central nervous system has prompted further investigation regarding their role in the pathogenesis of hypertension. The sympathetic nervous system, an important factor in the pathogenesis of hypertension, is influenced by sodium and volume status. Activation of central nervous system mineralocorticoid receptors is known to affect sympathetic activity, although the processes that underpin this phenomenon are incompletely understood. This article reviews some of the recent advances in this area, particularly mechanisms by which the mineralo-corticoid receptor maintains selectivity for its ligand within the central nervous system, its role in salt appetite, and the possibility of local production of corticosteroids. In addition, the links between central mineralocorticoid receptor activation, stress, sympathetic activity, and hypertension are discussed.
Aldosterone plays an important role in electrolyte and blood pressure homeostasis. Our studies have focused on the role of aldosterone in essential hypertension. We have shown that plasma aldosterone and ARR are heritable characteristics and that aldosterone concentrations in older subjects are inversely correlated with birthweight and positively correlated with blood pressure. Aldosterone levels are also associated with polymorphic variation in the CYP11B2 gene, which encodes aldosterone synthase, the enzyme responsible for aldosterone production. Interestingly, CYP11B2 polymorphisms are also associated with less efficient activity of 11beta-hydroxylase, encoded by the neighbouring, highly homologous CYP11B1 gene. We propose that a digenic effect leads to increased aldosterone production, with inefficient 11beta-hydroxylation causing a long-term increase in ACTH drive to the adrenal gland and enhanced expression of CYP11B2, thereby resulting in chronically raised aldosterone secretion in response to factors such as angiotensin II and potassium. In susceptible subjects this is likely, over many years, to result in hypertension with relative aldosterone excess.
Animal models suggest that explanations for the association of low birthweight with adult hypertension may include chronic activation of the hypothalamic-pituitary-adrenal or renin-angiotensin-aldosterone axes. In humans, low birthweight predicts elevated plasma cortisol, but associations with aldosterone have not been reported. We measured aldosterone in serum samples from 205 men and 106 women from 67 to 78 years of age, from Hertfordshire, UK, for whom birthweight was recorded. Participants underwent an overnight low-dose (0.25 mg) dexamethasone suppression test and a low-dose (1 mug) ACTH (corticotropin) stimulation test and were genotyped for the -344 C/T polymorphism of the CYP11B2 gene encoding aldosterone synthase. Median aldosterone was 6.22 ng/dL (range 0.15 to 38.74) and was higher in men than women (P<0.0001). Higher aldosterone levels after both dexamethasone and ACTH stimulation were associated with higher blood pressure (r=0.20, P=0.001; r=0.33, P<0.0001, respectively) and with lower birthweight (r=-0.16, P=0.008; r=-0.21, P=0.001, respectively). These associations remained significant after adjusting for age, gender, obesity, and genotype. Our findings supplement previous evidence that aldosterone is an important regulator of blood pressure and suggest that factors in early life that retard fetal growth and program activation of the hypothalamic-pituitary-adrenal axis in humans result not only in higher glucocorticoid activity but also in increased mineralocorticoid activity.
An intrinsic property of human motor behavior is a trade-off between speed and accuracy. This is classically described by Fitts law, a model derived by assuming that the human body has a limited capacity to transmit information in organizing motor behavior. However, Fitts law can also be realized as an emergent property of movements generated by delayed feedback. In this article, we describe the relationship between the Fitts law coefficients and the physiological parameters of the underlying delayed feedback circuit: the relaxation rate or time constant, and the psychomotor delay of the feedback process. This relationship is then used to estimate the motor circuit delay of several tasks for which Fitts law data are available in the literature. We consistently estimate the delay to be between 0 and 112 ms. A further consequence of this model is that not all combinations of slope and Y-intercept in Fitts law are possible when movements are generated by delayed feedback. In fact, it is only possible for an observed speed-accuracy trade-off to be generated by delayed feedback if the Fitts law coefficients satisfy -0.482 < or = a/b < or = 3.343 [bits] where b represents the slope in bits per second and a represents the Y-intercept in seconds. If we assume human movement is generated by delayed feedback, then the Fitts law coefficients should always be restricted to this range of values.
Retinoids play important roles in many diverse biological functions such as cell growth, morphogenesis, differentiation, and reproduction. Previous studies demonstrated that retinol administration to ewes, followed by natural service, resulted in embryos with improved competence to develop under standard in vitro conditions (5% CO(2) in air). Additional studies provided evidence that retinol may have some antioxidant effect by improving blastocyst development in cattle under atmospheric conditions (5% CO(2) in air). Glutathione is an important non-protein, sulphydryl compound found in oocytes and embryos, which acts to decrease oxidative stress. The purpose of the present study was to evaluate the effects of retinol administration to ewes on the content of glutathione and glutathione-related and antioxidant enzymes in in vivo matured sheep oocytes. Briefly, ewes were administered retinol or vehicle during superovulation, and after 60h the oviducts were removed and mature oocytes collected. Glutathione content did not differ significantly between oocytes collected from retinol-treated ewes (6.78+/-3.81pmol/oocyte) and control ewes (6.38+/-1.58pmol/oocyte). Transcripts encoding for manganese superoxide dismutase (Mn-SOD), copper zinc superoxide dismutase (Cu-Zn SOD), glutathione synthetase (GS), and glutathione transferase pi (GSTp) were detected in single ovine oocytes; however, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not reveal any significant differences in transcripts between oocytes from retinol-treated ewes and those from control ewes.
The perioperative management of patients undergoing cardiac surgery usually requires the accurate assessment of left ventricular filling pressures (LVFP). The gold standard for determining LVFP involves the use of pulmonary artery catheters (PAC). Using tissue Doppler indices (TDI) obtained by transthoracic echocardiography, the ratio of early transmitral filling velocity to the corresponding early mitral annular velocity (E/E) has a strong correlation with pulmonary capillary wedge pressure (PCWP). Little is known, however, on whether this relationship between E/E and PCWP is valid intraoperatively using transesophageal echocardiography (TEE) during cardiac surgery.
The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n=3340) and confirmation (n=2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conversion polymorphism showing strongest association with hypertension in both cohorts and in combined analysis (odds ratio=1.16, P=8.54×10(-5)). The CYP11B1 ACA haplotype associated with increased risk of hypertension relative to the alternative, GTC (odds ratio=1.11; P=7.4×10(-3)), whereas the CYP11B2 TWtC haplotype seemed protective relative to the contrasting CConvT (odds ratio=0.88, P=2.2×10(-3)). Analysis spanning the whole CYP11B1/CYP11B2 locus showed that haplotypes associated with raised risk of hypertension tend to coexist. Functional analysis of heterozygous human adrenal tissue demonstrated decreased CYP11B2 expression and increased CYP11B1 expression for those alleles associating with reduced risk of hypertension. These results confirm the hypertensive influence of this locus, with data suggesting a complex digenic mechanism whereby altered relative CYP11B1 and CYP11B2 gene expression could have a chronic effect on enzyme activity and corticosteroid synthesis.
The objectives of this consensus conference were to evaluate the evidence for the efficacy and safety of perioperative drugs, technologies, and techniques in reducing allogeneic blood transfusion for adults undergoing cardiac surgery and to develop evidence-based recommendations for comprehensive perioperative blood management in cardiac surgery, with emphasis on minimally invasive cardiac surgery.
Sensory hair cells in the zebrafish lateral line regenerate rapidly and completely after damage. Previous studies have used a variety of ototoxins to kill lateral line hair cells to study different phenomena including mechanisms of hair cell death and regeneration. We sought to directly compare these ototoxins to determine if they differentially affected the rate and amount of hair cell replacement. In addition, previous studies have found evidence of proliferative hair cell regeneration in zebrafish, but both proliferation and non-mitotic direct transdifferentiation have been observed during hair cell regeneration in the sensory epithelia of birds and amphibians. We sought to test whether a similar combination of regenerative mechanisms exist in the fish. We analyzed the time course of regeneration after treatment with different ototoxic compounds and also labeled dividing hair cell progenitors. Certain treatments, including cisplatin and higher concentrations of dissolved copper, significantly delayed regeneration by one or more days. However, cisplatin did not block all regeneration as observed previously in the chick basilar papilla. The particular ototoxin did not appear to affect the mechanism of regeneration, as we observed evidence of recent proliferation in the majority of new hair cells in all cases. Inhibiting proliferation with flubendazole blocked the production of new hair cells and prevented the accumulation of additional precursors, indicating that proliferation has a dominant role during regeneration of lateral line hair cells.
Several studies have correlated elevations in cardiac biomarkers of injury post marathon with transient and reversible right ventricular (RV) systolic dysfunction as assessed by both transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). Whether or not permanent myocardial injury occurs due to repeated marathon running in the aging population remains controversial.
Several researchers have persuasively argued that the most important evidence to consider when assessing construct validity is whether variations in the construct of interest cause corresponding variations in the measures of the focal construct. Unfortunately, the literature provides little practical guidance on how researchers can go about testing this. Therefore, the purpose of this article is to describe how researchers can use video techniques to test whether their scales measure what they purport to measure. First, we discuss how researchers can develop valid manipulations of the focal construct that they hope to measure. Next, we explain how to design a study to use this manipulation to test the validity of the scale. Finally, comparing and contrasting traditional and contemporary perspectives on validation, we discuss the advantages and limitations of video-based validation procedures.
The genetic mechanisms underlying hypertension are unclear, but relative aldosterone excess, present in ?10% of hypertensive patients, is known to be a heritable trait. This phenotype associates with a T/C single nucleotide polymorphism (SNP) at position -344 of the aldosterone synthase gene (CYP11B2). However, deletion of this SNP has no effect on gene transcription. We have identified another T/C SNP at -1651, in tight linkage disequilibrium with the -344 SNP and here investigate its functional effect on CYP11B2 transcription.
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