Alterations in vasomotor systems and mechanics of resistance-sized mesenteric arteries from SHR and WKY male rats following in vivo testosterone manipulation

<p>Abstract</p> <p>Background</p> <p>Testosterone (T) and the sympathetic nervous system each contribute to the pathology of hypertension. Altered blood vessel reactivity is also associated with the pathology of high blood pressure. The purpose of this study was to examine the effects of T manipulation in the regulation of resistance-sized blood vessel reactivity.</p> <p>Methods</p> <p>Adult spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) male rats at 8 weeks of age were used. The rats were divided into groups consisting of gonadally intact controls (CONT), castrate with sham implant (CAST) and castrate with T implant (CAST + T) (<it>n </it>= 6 to 12 per group). Following a short-term period of T treatment (approximately 4 weeks), plasma norepinephrine (NE) and plasma T were assessed by performing high-performance liquid chromatography and RIA, respectively. Resistance-sized mesenteric artery reactivity was assessed on a pressurized arteriograph for myogenic reactivity (MYO), phenylephrine (PE) responsiveness and passive structural mechanics.</p> <p>Results</p> <p>SHR and WKY males exhibited similar physiological trends in T manipulation, with castration significantly lowering plasma T and NE and T replacement significantly increasing plasma T and NE. T manipulation in general resulted in significant alterations in MYO of second-order mesenteric arteries, with T replacement decreasing MYO in SHR (<it>P </it>< 0.05) compared to CONT, T replacement increasing MYO, and CAST decreasing MYO in WKY rats (<it>P </it>< 0.001) compared to CONT rats. Additionally, PE-induced constriction was significantly altered in both strains following T treatment, with the effective concentration of PE to constrict the vessel to 50% of the total diameter significantly increased in the CAST + T SHR compared to CONT (<it>P </it>< 0.05). Comparisons of passive structural mechanics between SHR and WKY treatment groups indicated in SHR a significantly increased wall-to-lumen ratio and decreased circumferential wall stress compared to WKY treatment groups.</p> <p>Conclusions</p> <p>These data suggest that T and NE are involved in a complex interaction with both myogenic reactivity and structural alterations of resistance-sized blood vessels and that these factors likely contribute to the development and maintenance of hypertension.</p

A New Approach to Learning How to Teach: medical students as instructional designers

As students at the David Geffen School of Medicine at UCLA, the student authors were given the opportunity to develop their own creative projects which would be used to teach future medical students. They chose their own topics, planned and researched their projects, and then implemented the projects in interactive digital Adobe Flash files. In the first project they created interactive case-based radiology teaching files. In the second project they integrated photographic images into the existing illustrative anatomy files. Students in subsequent years have learned from these files on computers both at home and in the school's anatomy lab. The experience of creating the files served as an opportunity for hands-on learning for the student authors, both of the material and of the practice of teaching. In this paper they describe why they undertook these projects, what exactly they did, and the impact their creation had on them. The projects demonstrate that student-driven educational materials are both possible and beneficial. Furthermore, their experience has allowed them to conclude that faculty at other medical schools should consider providing students with opportunities to develop their own creative projects that contribute to the curriculum

Resonant Magnetization Tunneling in Mn12 Acetate: The Absence of Inhomogeneous Hyperfine Broadening

We present the results of a detailed study of the thermally-assisted-resonant-tunneling relaxation rate of Mn12 acetate as a function of an external, longitudinal magnetic field and find that the data can be fit extremely well to a Lorentzian function. No hint of inhomogeneous broadening is found, even though some is expected from the Mn nuclear hyperfine interaction. This inconsistency implies that the tunneling mechanism cannot be described simply in terms of a random hyperfine field.Comment: Some minor revisions, title changed, updated figures, two added notes, one added reference. RevTeX, 4 pages, 3 postscript figures. Submitted to Rapid Communication

Selection on stability across ecological scales

Much of the focus in evolutionary biology has been on the adaptive differentiation among organisms. It is equally important to understand the processes that result in similarities of structure among systems. Here, we discuss examples of similarities occurring at different ecological scales, from predator–prey relations (attack rates and handling times) through communities (food-web structures) to ecosystem properties. Selection among systemic configurations or patterns that differ in their intrinsic stability should lead generally to increased representation of relatively stable structures. Such nonadaptive, but selective processes that shape ecological communities offer an enticing mechanism for generating widely observed similarities, and have sparked new interest in stability properties. This nonadaptive systemic selection operates not in opposition to, but in parallel with, adaptive evolution

Merging Resource Availability with Isotope Mixing Models: The Role of Neutral Interaction Assumptions

Background: Bayesian mixing models have allowed for the inclusion of uncertainty and prior information in the analysis of trophic interactions using stable isotopes. Formulating prior distributions is relatively straightforward when incorporating dietary data. However, the use of data that are related, but not directly proportional, to diet (such as prey availability data) is often problematic because such information is not necessarily predictive of diet, and the information required to build a reliable prior distribution for all prey species is often unavailable. Omitting prey availability data impacts the estimation of a predator's diet and introduces the strong assumption of consumer ultrageneralism (where all prey are consumed in equal proportions), particularly when multiple prey have similar isotope values. Methodology: We develop a procedure to incorporate prey availability data into Bayesian mixing models conditional on the similarity of isotope values between two prey. If a pair of prey have similar isotope values (resulting in highly uncertain mixing model results), our model increases the weight of availability data in estimating the contribution of prey to a predator's diet. We test the utility of this method in an intertidal community against independently measured feeding rates. Conclusions: Our results indicate that our weighting procedure increases the accuracy by which consumer diets can be inferred in situations where multiple prey have similar isotope values. This suggests that the exchange of formalism for predictive power is merited, particularly when the relationship between prey availability and a predator's diet cannot be assumed for all species in a system.National Science Foundation (NSF) [DEB-0608178]U.S. Environmental Protection AgencyDepartment of EducationSigma XiUniversity of ChicagoFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)(CAPES) Coordenacao de Aperfeicoamento de Pessoal de Nivel Superiori

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD

Cost effectiveness of epidural steroid injections to manage chronic lower back pain

Background The efficacy of epidural steroid injections in the management of chronic low back pain is disputed, yet the technique remains popular amongst physicians and patients alike. This study assesses the cost effectiveness of injections administered in a routine outpatient setting in England. Methods Patients attending the Nottingham University Hospitals’ Pain Clinic received two injections of methylprednisolone plus levobupivacaine at different dosages, separated by at least 12 weeks. Prior to each injection, and every week thereafter for 12 weeks, participants completed the EQ-5D health-related quality of life instrument. For each patient for each injection, total health state utility gain relative to baseline was calculated. The cost of the procedure was modelled from observed clinical practice. Cost effectiveness was calculated as procedure cost relative to utility gain. Results 39 patients provided records. Over a 13-week period commencing with injection, mean quality adjusted life year (QALY) gains per patient for the two dosages were 0.028 (SD 0.063) and 0.021 (SD 0.057). The difference in QALYs gained by dosage was insignificant (paired t-test, CIs -0.019 – 0.033). Based on modelled resource use and data from other studies, the mean cost of an injection was estimated at £219 (SD 83). The cost utility ratio of the two injections amounted to £8,975 per QALY gained (CIs 5,480 – 22,915). However, at costs equivalent to the tariff price typically paid to providers by health care purchasers, the ratio increased to £27,459 (CIs 16,779 – 70,091). Conclusions When provided in an outpatient setting, epidural steroid injections are a short term, but nevertheless cost effective, means of managing chronic low back pain. However, designation of the procedure as a day case requires the National Health Service to reimburse providers at a price which pushes the procedure to the margin of cost effectiveness