Cross-sectional relations of urinary sodium excretion to cardiac structure and hypertrophy. The Framingham Heart Study

BACKGROUND: Increased sodium intake has been positively associated with high blood pressure (BP) and hypertensive target organ damage, but associations with cardiac structure in nonhypertensive individuals have yielded inconsistent results. We tested the hypothesis that sodium intake is associated with left ventricular (LV) mass and left ventricular hypertrophy (LVH), independent of BP, in the community. METHODS: We analyzed the cross-sectional relationships between urinary sodium excretion and LV measurements in a community-based sample of 2660 Framingham Offspring Study participants (mean age 58 years, 56% women and 44% men). Participants with known coronary artery disease, congestive heart failure, or renal failure as well as those using diuretics were excluded. Urinary sodium excretion was measured on a spot urine sample and was indexed to urinary creatinine. RESULTS: In sex-specific, multivariable linear regression models adjusting for covariates known to influence LV measurements, log urinary sodium was not associated with LV mass, wall thickness, end-diastolic dimensions, or left atrial size in either sex. Urinary sodium was not related to LVH defined as LV mass >/= sex-specific 80th percentile value. In analyses restricted to hypertensive individuals (n = 983, 470 women), urinary sodium was not associated with LV mass or LVH. CONCLUSIONS: In our large community-based sample, urinary sodium excretion was not related to LV mass, function, or hypertrophy.     

Safety and potential cost savings of same-setting electrophysiologic testing and placement of transvenous implantable cardioverter-defibrillators

BACKGROUND: Separately, electrophysiologic study (EPS) and placement of a transvenous implantable cardioverter-defibrillator (ICD) can be performed safely in the majority of patients. The safety and potential cost savings of same-setting procedures have not been evaluated. HYPOTHESIS: Electrophysiologic study and placement of transvenous ICDs can be performed safely in the same setting at reduced cost. METHODS: In all. 160 (mean age 65 +/- 10 years, 75% men) and 41 (mean age 66 +/- 11 years, 73% men) consecutive patients who underwent same- versus separate-setting procedures, respectively, were prospectively evaluated. RESULTS: The two groups had similar clinical characteristics and indications for EPS and ICD therapy. Complications occurred in eight patients (5.0%, 95% confidence interval [CI] 2.3-10.3) who had same-setting procedures (one hypotension during ICD testing, one pocket hematoma, two lead dislodgments, two pneumothoraces, one stroke, and one infection) and in two (4.9%, CI 0.60-16.5) who had separate-setting procedures (one pocket hematoma and one infection). There were no procedure-related deaths or long-term ICD-related complications in either group. The mean time from ICD implantation to hospital discharge was similar in the two groups (2.5 +/- 2.4 vs. 2.7 +/- 2.2 days, p = NS). The combined procedure cost was higher in patients who had separate-setting procedures ($12,403 +/- 1,386 vs. $10,242 +/- 2.256, p = < 0.001). who incurred an additional hospital cost of $2,121 +/- $2,125 for the waiting period (1.7 +/- 1.6 days) between EPS and ICD implantation. CONCLUSIONS: In patients deemed candidates for ICD therapy based on EPS results, placement of transvenous defibrillators in the same setting as EPS is as safe as separate-setting procedures and, if adopted, could further reduce the cost of providing ICD therapy.     

Ulcerogenicity devoid novel non-steroidal anti-inflammatory agents (NSAIDS): syntheses,computational studies,and activity of 5-aryliden-2-imino-4-thiazolidinones

A series of new 5-aryliden-2-imino-4-thiazolidinones (5a–e and 6a–e) were synthesized via a three-step reaction and characterized by physicochemical and spectral data. The uniqueness of the derivatives lies in the fact that none of them had an acidic group, like conventional NSAIDS, but exhibited significant in vivo activity in acute inflammation models. In particular, 5-(3-chlorobenzyliden)-2-(pyridin-2-yl-imino)-4-thiazolidinone(5a) and 5-(3-chlorobenzyliden)-2-(5-methylisoxazol-3-yl-imino)-4-thiazolidinone (6a) showed remarkable paw oedema inhibition (67.76 and 74.47 % oedema inhibition, respectively, after 3 h) comparable to that of Ibuprofen (74.56 % oedema inhibition, after 3 h) at half of the dose of the standard drug. Also, compounds 5a (72.86 %) and 6a (80.20 %) were found to possess significant inhibition of albumin denaturation when screened for in vitro anti-inflammatory activity. In addition, these compounds were docked into the known active site of COX-2 protein using Glide XP and QPLD algorithms, and the binding-free energy was calculated using Prime MM/GBSA simulation methods. The combined use of molecular docking and MM/GBSA methods gave a good correlation between the predicted binding-free energy and experimentally determined biological activities. It was also evident from the docking results that 2-methylisoxazolylimino or 2-(pyridin-2-yl-imino substitution and 3-chloro moiety on 5-benzylidin nucleus of these 4-thiazolidinone derivatives can easily occupy the COX-2 binding pocket, considered as the critical interaction for COX-2 inhibition. Moreover, pharmacokinetic properties of all the synthesized compounds were predicted, with good results. Further, the synthesized derivatives showed neither acute toxicity nor symptoms of gastric ulceration, at extended doses, owing to the absence of an acidic group.     

From the Cover: Bumblebees perceive the spatial layout of their environment in relation to their body size and form to minimize inflight collisions

Animals that move through complex habitats must frequently contend with obstacles in their path. Humans and other highly cognitive vertebrates avoid collisions by perceiving the relationship between the layout of their surroundings and the properties of their own body profile and action capacity. It is unknown whether insects, which have much smaller brains, possess such abilities. We used bumblebees, which vary widely in body size and regularly forage in dense vegetation, to investigate whether flying insects consider their own size when interacting with their surroundings. Bumblebees trained to fly in a tunnel were sporadically presented with an obstructing wall containing a gap that varied in width. Bees successfully flew through narrow gaps, even those that were much smaller than their wingspans, by first performing lateral scanning (side-to-side flights) to visually assess the aperture. Bees then reoriented their in-flight posture (i.e., yaw or heading angle) while passing through, minimizing their projected frontal width and mitigating collisions; in extreme cases, bees flew entirely sideways through the gap. Both the time that bees spent scanning during their approach and the extent to which they reoriented themselves to pass through the gap were determined not by the absolute size of the gap, but by the size of the gap relative to each bee’s own wingspan. Our findings suggest that, similar to humans and other vertebrates, flying bumblebees perceive the affordance of their surroundings relative their body size and form to navigate safely through complex environments.

Avoiding collisions with obstacles is a requirement for successful locomotion through most natural habitats, where the physical environment is often cluttered and complex. At the most elemental level, animals moving through their environments need to identify gaps between obstacles and assess their passability. In this context, whether a gap between obstacles “affords” passing is determined by the fit between the spatial layout of the environment and the properties of the organism’s form and action system, as described in classical theses on affordances (1–3). In humans and other highly cognitive vertebrates, the perception of affordances for performing visually guided actions such as grasping, passing through apertures, and climbing is actively shaped throughout ontogeny, as body size, configuration, and experience change (2, 4–7). However, the strategies used by animals with much smaller brains, such as insects, to contend with the challenges of navigating environmental clutter and spatial heterogeneity are unclear.We used bumblebees to investigate whether flying insects take into account their own size during interactions with their surroundings. Bumblebees and other volant insects that travel long distances (8) and frequently encounter regions of dense clutter can be expected to exhibit strategies to avoid collisions, because damage to sensitive structures such as the wings is irreparable and adversely impacts flight performance and lifespan (9, 10). For an animal attempting to navigate through tight spaces, perceiving the relationship between the layout of the environment and its own size can help inform the animal of its potential for collision-free passage. Bumblebee workers naturally display large variation in body size within a given colony (11, 12), and thus are particularly suitable models for testing the effects of insect body size on aerial navigation and for determining whether insects perceive the external environment in relation to their own spatial dimensions.To elicit repeatable flight behavior, we trained foraging bumblebees to fly within a 1.6 × 0.3 × 0.3 m (l × w × h) flight tunnel that separated the hive from a foraging arena (Materials and Methods, SI Appendix, Fig. S1, and Movie S1). After bees were habituated to the setup and began foraging normally, we placed an unexpected obstacle within the tunnel, consisting of a thin vertical wall (5-mm thickness) spanning the tunnel’s width and height. The obstructing wall contained a rectangular gap starting midway up and extending to the top of the wall (Materials and Methods, SI Appendix, Fig. S1, and Movie S1). The width of the gap was varied between 20 and 60 mm over different trials, with the presenting order of gap sizes chosen randomly. A high-speed camera placed above the tunnel was used to record bees’ instantaneous positions, heading/yaw orientations (Fig. 1A), and trajectories as they approached the obstructing wall and passed through the gap. To prevent bees from becoming familiar with the experimental paradigm, the obstructing wall was removed after each flight recording. In total, we recorded and analyzed over 400 flights of bees of varying body sizes flying through seven different gap sizes (SI Appendix, Table S1). For the population of bees recorded, wingspan was the longest dimension of the body and it varied linearly by a factor of 1.9 compared to their longitudinal body length while in flight (SI Appendix, Fig. S2A).Open in a separate windowFig. 1.Bumblebees can safely fly through gaps that are smaller than their wingspan. (A and B) Illustrations indicating the wingspan of bees (Ws), the size of the gap (Gs), and the positive and negative yaw (heading) angles for bees flying in the tunnel, respectively. (C) Schematic illustration of the flight of a bee flying through a gap that is much wider than its wingspan. (D) The instantaneous yaw angle of bee shown in C. (E) Schematic illustrationof the flightofabeeflying through a gap that is smaller than its wingspan. (F) The instantaneous yaw angle of bee shown in E. Flights, in both cases (C and E), consisted of approach, lateral peering, and—for the smaller gap size (E)—body reorientation (an increase in yaw angle) while passing through the gap. The differences in reorientation behavior can be noted at x = 0 (location of the gap), whereas in F the bee displays a large increase in yaw angle that reorients its body to pass through the small gap, and body reorientation in D is minimal. For the flight shown in C and D, Ws = 27.5 mm and Gs = 50 mm, while for the flight shown in E and F, Ws = 27 mm and Gs = 25 mm.