Mechanical stimuli for left ventricular growth during pressure overload.

BACKGROUND: The mechanical stimulus (i.e. stress or stretch) for growth occurring in the pressure-overloaded left ventricle (LV) is not exactly known. OBJECTIVE: To address this issue, we investigate the correlation between local ventricular growth (indexed by local wall thickness) and the local acute changes in mechanical stimuli after aortic banding. METHODS: LV geometric data were extracted from 3D echo measurements at baseline and 2 weeks in the aortic banding swine model (n = 4). We developed and calibrated animal-specific finite element (FE) model of LV mechanics against pressure and volume waveforms measured at baseline. After the simulation of the acute effects of pressure-overload, the local changes of maximum, mean and minimum myocardial stretches and stresses in three orthogonal material directions (i.e., fiber, sheet and sheet-normal) over a cardiac cycle were quantified. Correlation between mechanical quantities and the corresponding measured local changes in wall thickness was quantified using the Pearson correlation number (PCN) and Spearman rank correlation number (SCN). RESULTS: At 2 weeks after banding, the average septum thickness decreased from 10.6 ± 2.92mm to 9.49 ± 2.02mm, whereas the LV free-wall thickness increased from 8.69 ± 1.64mm to 9.4 ± 1.22mm. The FE results show strong correlation of growth with the changes in maximum fiber stress (PCN = 0.5471, SCN = 0.5111) and changes in the mean sheet-normal stress (PCN= 0.5266, SCN = 0.5256). Myocardial stretches, however, do not have good correlation with growth. CONCLUSION: These results suggest that fiber stress is the mechanical stimuli for LV growth in pressure-overload.

Left ventricular geometry, tissue composition, and residual stress in High Fat Diet Dahl-Salt sensitive rats.

BACKGROUND: Hypertension drives myocardial remodeling, leading to changes in structure, composition and mechanical behavior, including residual stress, which are linked to heart disease progression in a gender-specific manner. Emerging therapies are also targeting constituent-specific pathological features. All previous studies, however, have characterized remodeling in the intact tissue, rather than isolated tissue constituents, and did not include sex as a biological variable. OBJECTIVE: In this study we first identified the contribution of collagen fiber network and myocytes to the myocardial residual stress/strain in Dahl-Salt sensitive rats fed with high fat diet. Then, we quantified the effect of hypertension on the remodeling of the left ventricle (LV), as well as the existence of sex-specific remodeling features. METHODS: We performed mechanical tests (opening angle, ring-test) and histological analysis on isolated constituents and intact tissue of the LV. Based on the measurements from the tests, we performed a stress analysis to evaluate the residual stress distribution. Statistical analysis was performed to identify the effects of constituent isolation, elevated blood pressure, and sex of the animal on the output of both experimental measures and modeling results. RESULTS: Hypertension leads to reduced residual stress/strain intact tissue, isolated collagen fibers, and isolated myocytes in male and female rats. Collagen remains the largest contributor to myocardial residual stress in both normotensive and hypertensive animals. We identified sex-differences in both hypertensive and normotensive animals. CONCLUSIONS: We observed both constituent- and sex-specific remodeling features in the LV of an animal model of hypertension.

Training-induced Increase in Bone Mineral Density between Growing Male and Female Rats.

The purpose of this study was to determine the existence of sex differences in the resistance training-induced elevation in bone mineral density (BMD) and bone strength (Fmax) during the growth period in rats. 16 male (M) and 16 female (F) rats (approx. 8 weeks old) were randomly divided into sedentary control (MC=8, FC=8), and resistance-trained (RT) groups (M-RT=8, F-RT=8). The RT groups were conditioned to climb a vertical ladder 4 consecutive times (per exercise session) with weights attached to their tail 3 days per week for a total of 6 weeks. After 6 weeks, there were no interaction effects (sex×exercise). The main effect of sex indicated no difference in tibial BMD (in g/cm(2)) for males (0.226±0.005) compared to females (0.221±0.004). However, Fmax (in Newtons) was significantly greater for males (131.3±5.3) compared to females (89.9±3.0). The main effect of exercise indicated that tibial BMD and Fmax were significantly greater for RT groups (0.234±0.004 g/cm(2) and 120.9±7.4 Newtons) compared to controls (0.212±0.003 g/cm(2) and 100.3±5.1 Newtons). The results indicate that during growth, there were no sex differences in the training-induced elevation in BMD and bone mechanical properties.

Elimination of subterranean termite (Isoptera: Rhinotermitidae) colonies using a refined cellulose bait matrix containing noviflumuron when monitored and replenished quarterly.

Using a quarterly (3-mo) monitoring and bait-replenishment interval, 122 subterranean termite colonies throughout the United States were baited with a refined cellulose bait matrix containing 0.5% noviflumuron. All colonies were eliminated in less than 1 yr after initiation of baiting as determined by long-term monitoring and genetic markers. Sixty-three percent of the colonies were eliminated during the first quarter after the initiation of baiting and 77% of colonies were eliminated after consuming two bait tubes or less. This suggests that a single baiting cycle and bait installed in response to a single active monitoring device were sufficient to eliminate the majority of colonies. Although termites temporarily abandoned stations after depleting bait, workers resumed feeding when baits were replenished. Colonies that consumed large amounts of bait before elimination foraged into multiple stations, thus allowing adequate amounts of bait to sustain feeding. The time to eliminate termite colonies with bait replenished quarterly was similar to that previously reported for laminated cellulose bait replenished monthly. Our data support the conclusion that extending the bait replenishment interval from monthly to quarterly for bait tubes with refined cellulose containing 0.5% noviflumuron did not adversely impact colony elimination.

Routine antiseptic baths and MRSA decolonization: diverse approaches across Singapore's acute-care hospitals.

To determine the variation in practices on meticillin-resistant Staphylococcus aureus (MRSA) surveillance and management of MRSA-colonized patients amongst 17 acute healthcare facilities in Singapore, the Ministry of Health convened a sharing session with Infection Prevention and Control Leads. All hospitals practised close to universal MRSA entry swabbing in keeping with national policy. There were, however, major variations in the response to both positive and negative surveillance swabs across facilities including the role of routine antiseptic bathing and MRSA decolonization. Most undertaking decolonization considered its role to be in 'bioburden reduction' rather than longer-term clearance.

Gigantic jets between a thundercloud and the ionosphere.

Transient luminous events in the atmosphere, such as lighting-induced sprites and upwardly discharging blue jets, were discovered recently in the region between thunderclouds and the ionosphere. In the conventional picture, the main components of Earth's global electric circuit include thunderstorms, the conducting ionosphere, the downward fair-weather currents and the conducting Earth. Thunderstorms serve as one of the generators that drive current upward from cloud tops to the ionosphere, where the electric potential is hundreds of kilovolts higher than Earth's surface. It has not been clear, however, whether all the important components of the global circuit have even been identified. Here we report observations of five gigantic jets that establish a direct link between a thundercloud (altitude approximately 16 km) and the ionosphere at 90 km elevation. Extremely-low-frequency radio waves in four events were detected, while no cloud-to-ground lightning was observed to trigger these events. Our result indicates that the extremely-low-frequency waves were generated by negative cloud-to-ionosphere discharges, which would reduce the electrical potential between ionosphere and ground. Therefore, the conventional picture of the global electric circuit needs to be modified to include the contributions of gigantic jets and possibly sprites.

Different training volumes yield equivalent increases in BMD.

The purpose of this study was to determine if an exercise threshold existed in stimulating an elevation in bone mineral density (BMD), via resistance training, during the growth period in male rats. 27 male rats were randomly divided into Â-Control (Con, n=9), 3 ladder climb resistance trained group (3LC, n=9), and 6 ladder climb resistance trained group (6LC, n=9). The 3LC and 6LC groups were conditioned to climb a vertical ladder with weights appended to their tail 3 days/wk for a total of 6 wks, but the 6LC group performed significantly more work than the 3LC group. After 6 weeks, left tibial BMD (mean±SD) was significantly greater for 3LC (0.225±0.006 g/cm (2)) and 6LC (0.234±0.008 g/cm (2)) when compared to Con (0.202±0.013 g/cm (2)). Further, bone strength (force to failure in Newtons) was significantly greater for 3LC (132.7±13.7) and 6LC (130.0±22.8) compared to Con (102.0±10.1). There was no significant difference in BMD or bone strength between 3LC and 6LC. The results indicate that both resistance training programs were equally effective in elevating BMD and bone strength in growing rats. These data suggest that during growth, there is a stimulation threshold where more work per exercise session is ineffective in promoting additional bone formation.

Kinetics and mechanism of the CN + NCO --> NCN + CO reaction studied by experiment and theory.

The rate coefficients for the CN + NCO --> NCN + CO reaction have been measured by a laser-photolysis/laser-induced fluorescence technique in the temperature range of 254-353 K and the He pressures of 123-566 Torr. The CN radical was produced from the photolysis of BrCN at 193 nm, and the NCO radical from the CN + O(2) reaction. The NCN radical was monitored by laser-induced fluorescence with a dye laser at 329.01 nm. The rate constants derived from kinetic modeling, with a negative temperature dependence but no pressure effect, can be expressed by k = (2.15 +/- 0.70) x 10(-11) exp[(155 +/- 92)/T] cm(3) molecule(-1) s(-1), where the quoted errors are two standard deviations. The reaction mechanism and rate constant have also been theoretically predicted for the temperature range of 200-3000 K at He pressures ranging from 10(-4) Torr to 1000 atm based on dual channel Rice-Ramsperger-Kassel-Marcus (RRKM) calculations with the potential energy surface evaluated at the G2M and CCSD(T) levels. The rate constant calculated by variational RRKM theory agrees reasonably with experimental data.

Population-based trend analysis of voiding cystourethrogram ordering practices in a single-payer healthcare system before and after the release of evaluation guidelines.

INTRODUCTION: While voiding cystourethrogram (VCUG) is a widely-accepted test, it is invasive and associated with radiation exposure. Most cases of primary vesicoureteral reflux (VUR) are low-grade and unlikely to be associated with acquired renal scarring. To select patients at greatest risk, in 2011 the American Academy of Pediatrics (AAP) published guidelines for evaluation of children ages 2 - 24 months with urinary tract infections (UTIs). Similarly, in 2010 the Society for Fetal Urology (SFU) published guidelines for patients with hydronephrosis. Herein a prospectively-collected database was queried through the Institute of Clinical Evaluative Sciences (ICES), exploring trends in VCUG ordering within the Ontario Health Insurance Program (OHIP), which guarantees universal access to care. MATERIAL AND METHODS: A dedicated ICES analyst extracted data on all patients younger than 18 years in Ontario, Canada, with billing codes for VCUG and ICD-9 codes for VUR, from 2004-2014. The baseline characteristics included patient age, gender, geographic region, specialty of ordering provider and previous diagnoses of UTI and/or antenatal hydronephrosis to determine the indication for ordering the test. Of these, patients were subsequently incurred OHIP procedure codes for endoscopic injection or ureteral reimplantation. Patients who had a VCUG in the setting of urethral trauma, posterior urethral valves, and neurogenic bladder were excluded. RESULTS AND DISCUSSION: Trend analysis demonstrated that the total number of VCUGs ordered in the province has decreased over a decade (Figure 1), with a concurrent decrease in VUR diagnosis. On multivariate regression analysis, the decrease in VCUG ordering could not be explained by changes in population demographics or other baseline patient variables. Most VCUGs obtained per year were ordered by pediatricians or family physicians (mean 2,022+523.8), compared with urologists and nephrologists (mean 616+358.3). Interestingly, while the rate of VCUG requests decreased, the annual number of surgeries performed for VUR (endoscopic or open) did not show a significant reduction over time. CONCLUSIONS: We present a large population-based analysis in a universal access to care system, reporting a decreasing trend in the number of cystograms and differences by primary care versus specialist providers. While it is reassuring to see practice patterns favorably impacted by guidelines, it is also encouraging to note that the number of surgeries has remained stable. This suggests that patients at risk continue to be detected and offered surgical correction. These data confirm previous institution-based assessments and affirm changes in VCUG ordering independent of variables not relevant to the healthcare system, such as the insurance status.

Kinetics and mechanism of the NCN + NO2 reaction studied by experiment and theory.

The rate constant for the NCN + NO 2 reaction has been measured by a laser photolysis/laser-induced fluorescence technique in the temperature range of 260-296 K at pressures between 100 and 500 Torr with He and N 2 as buffer gases. The NCN radical was produced from the photolysis of NCN 3 at 193 nm and monitored by laser-induced fluorescence with a dye laser at 329.01 nm. The rate constant was found to increase with pressure but decrease with temperature, indicating that the reaction occurs via a long-lived intermediate stabilized by collisions with buffer gas. The reaction mechanism and rate constant are also theoretically predicted for the temperature range of 200-2000 K and the He and N 2 pressure range of 10 (-4) Torr to 1000 atm based on dual-channel Rice-Ramsperger-Kassel-Marcus (RRKM) theory with the potential energy surface evaluated at the G2M//B3LYP/6-311+G(d) level. In the low-temperature range (<700 K), the most favorable reaction is the barrierless association channel that leads to the intermediate complex (NCN-NO 2). At high temperature, the direct O-abstraction reaction with a barrier of 9.8 kcal/mol becomes the dominant channel. The rate constant calculated by RRKM theory agrees reasonably well with experimental data.

Equilibrated warping: Finite element image registration with finite strain equilibrium gap regularization.

In this paper, we propose a novel continuum finite strain formulation of the equilibrium gap regularization for image registration. The equilibrium gap regularization essentially penalizes any deviation from the solution of a hyperelastic body in equilibrium with arbitrary loads prescribed at the boundary. It thus represents a regularization with strong mechanical basis, especially suited for cardiac image analysis. We describe the consistent linearization and discretization of the regularized image registration problem, in the framework of the finite elements method. The method is implemented using FEniCS & VTK, and distributed as a freely available python library. We show that the equilibrated warping method is effective and robust: regularization strength and image noise have minimal impact on motion tracking, especially when compared to strain-based regularization methods such as hyperelastic warping. We also show that equilibrated warping is able to extract main deformation features on both tagged and untagged cardiac magnetic resonance images.

Stent-related complications after hypospadias repair: a prospective trial comparing Silastic tubing and Koyle urethral stents.

INTRODUCTION: There is a paucity of data comparing urethral stents after hypospadias repair. The aim of this study is to compare Silastic tubing vs Koyle stents (Cook Medical), addressing outcomes related to stent-related complications, added visits to healthcare providers in the early postoperative period, and postoperative complications at clinic follow-up. MATERIALS AND METHODS: Following an alternate week allocation, 150 patients were prospectively assigned to have Silastic tubes (n = 76) and Koyle stents (n = 74) after hypospadias repair. Exclusion criteria included fistula repairs, drainage via alternative catheter, or stentless repairs. Silastic tubes were secured with 5-0 Prolene and removed during a planned clinic visit. Koyle stents were secured with 7-0 PDS and left to fall out spontaneously. Questionnaires capturing postoperative outcomes were completed. RESULTS AND DISCUSSION: Median age was 13 and 11 months in the Silastic and Koyle stent groups, respectively (P = 0.48). There was no statistically significant difference in hypospadias location. Blockage/kinking of stents occurred in 8% (n = 6) of the Silastic and 9% (n = 7) Koyle stent groups, P = 0.78. Although follow-up was short, there was no difference in fistula rate among the Silastic (21%, n = 14) versus Koyle stent group (17%, n = 11), P = 0.66. There was a twofold higher rate of emergency department (ED) visits in the Silastic (32%, n = 24) versus Koyle stent group (16%, n = 12), P = 0.03. Half of ED visits in the Silastic group were related to stents falling out before planned removal. The authors propose that Silastic stents falling out before the removal date may have led to increased parental anxiety and thus a visit to the ED. With improved parental education, the authors propose that many of these visits may have been preventable. CONCLUSIONS: There were no significant differences in stent-related complications or fistula rate between the Silastic and Koyle stent groups. Although there were a twofold higher number of visits to the ED in the Silastic stent group, the authors propose that this was due to parental education rather than the stent itself.

Cancer-related hypercalcemia in oral cancer.

Cancer-related hypercalcemia (CRH) is a critical paraneoplastic disorder in advanced cancer patients. In clinical practice, patients with CRH have a poor prognosis. The medical records of 3198 oral cancer patients with CRH diagnosed at Taichung Veterans General Hospital from 1 January 2003 to 31 December 2015 were reviewed. The criteria for patient enrolment were a diagnosis of hypercalcemia or the use of antihypercalcemia medication. Patients who met any of the following criteria were excluded: use of total parenteral nutrition, incomplete serum calcium data, and unknown date of death. The total incidence of CRH was 6.95‰ per year. A total of 91 patients were enrolled; their median survival time was 28 days. The patients were divided into two groups by survival time, with a cut-off point of 30 days. Reduced serum albumin, leucocytosis, and clodronate use had a statistically significant effect on survival in the univariate analysis (all P<0.05). Forty-five patients (49.5%) had recurrence of CRH, of whom nine died within 30days. These nine patients had a shorter interval to the first episode of CRH recurrence (median 13 days) than those who survived ≥30days (median 28 days) (P<0.001). It was observed that a short interval to the first episode of CRH recurrence is a poor prognostic factor.

Brief Report: Self-Injurious Behaviors in Preschool Children with Autism Spectrum Disorder Compared to Other Developmental Delays and Disorders.

We compared the prevalence of self-injurious behaviors (SIB) in preschoolers aged 30-68 months with autism spectrum disorder (ASD) (n = 691) versus other developmental delays and disorders (DD) (n = 977) accounting for sociodemographic, cognitive, and medical factors. SIB prevalence was higher in ASD versus all DD [adjusted odds-ratio (aOR) 2.13 (95% confidence interval (95% CI) 1.53, 2.97)]. In subgroup analyses, SIB prevalence was higher in ASD versus DD without ASD symptoms [aOR 4.42 (95% CI 2.66, 7.33)], but was similar between ASD and DD with ASD symptoms [aOR 1.09 (95% CI 0.68, 1.77)]. We confirmed higher prevalence of SIB in ASD versus DD, independent of confounders. In children with DD, SIB prevalence increased with more ASD symptoms. These findings are informative to clinicians, researchers, and policymakers.

"Full house" proliferative glomerulonephritis: an unreported presentation of subacute infective endocarditis.

A severely ill 65-year-old man presented with symptoms of shortness of breath, edema and vasculitidic purpura over his lower extremities. He had severe mitral regurgitation which had not been surgically treated. Hematologic examination demonstrated leukocytosis with profound anemia. Other blood tests revealed impaired renal function, hypoalbuminemia, hypocomplementemia and mixed-type cryoglobulinemia. Urinalysis showed proteinuria, hematuria and pyuria, typical of a nephritic sediment. Renal biopsy indicated diffuse proliferative glomerulonephritis and a "full house" deposition in immunofluorescence study (positive for C3, C4, C1q, IgG, IgA and IgM), resembling the pathologic findings in class IV lupus nephritis. Although subacute bacterial endocarditis was initially suspected owing to a history of a predisposing valvular heart disease, probable vegetation shown by cardiac sonography and a clinical picture suggestive of a chronic infection, it was thought unlikely due to the entire afebrile course and initial sterile blood cultures. However, the blood cultures repeated 2 weeks after admission grew 3 sets of viridans streptococci. Following a course of penicillin and gentamicin treatment, his renal function, anemia and abnormal urine sediments improved gradually. Diffuse proliferative glomerulonephritis is well known to occur in infective endocarditis. However, the "full house" immunostaining in immunofluorescence study has never been reported. This case adds a new entity to the differential diagnosis of "full house" immune complex-related glomerulonephritis and exemplifies the need to maintain a high index of suspicion for underlying infectious disorders when facing glomerulonephritic or vasculitic syndrome.

Solar Open Flux Migration from Pole to Pole: Magnetic Field Reversal.

Coronal holes are solar regions with low soft X-ray or low extreme ultraviolet intensities. The magnetic fields from coronal holes extend far away from the Sun, and thus they are identified as regions with open magnetic field lines. Coronal holes are concentrated in the polar regions during the sunspot minimum phase, and spread to lower latitude during the rising phase of solar activity. In this work, we identify coronal holes with outward and inward open magnetic fluxes being in the opposite poles during solar quiet period. We find that during the sunspot rising phase, the outward and inward open fluxes perform pole-to-pole trans-equatorial migrations in opposite directions. The migration of the open fluxes consists of three parts: open flux areas migrating across the equator, new open flux areas generated in the low latitude and migrating poleward, and new open flux areas locally generated in the polar region. All three components contribute to the reversal of magnetic polarity. The percentage of contribution from each component is different for different solar cycle. Our results also show that the sunspot number is positively correlated with the lower-latitude open magnetic flux area, but negatively correlated with the total open flux area.

Factors Associated with Self-Injurious Behaviors in Children with Autism Spectrum Disorder: Findings from Two Large National Samples.

In this study, we explored potential associations among self-injurious behaviors (SIB) and a diverse group of protective and risk factors in children with autism spectrum disorder from two databases: Autism and Developmental Disabilities Monitoring (ADDM) Network and the Autism Speaks-Autism Treatment Network (AS-ATN). The presence of SIB was determined from children's records in ADDM and a parent questionnaire in AS-ATN. We used multiple imputation to account for missing data and a non-linear mixed model with site as a random effect to test for associations. Despite differences between the two databases, similar associations were found; SIB were associated with developmental, behavioral, and somatic factors. Implications of these findings are discussed in relation to possible etiology, future longitudinal studies, and clinical practice.

Mathematical modeling of cardiac growth and remodeling.

This review provides an overview of the current state of mathematical models of cardiac growth and remodeling (G&R). We concisely describe the experimental observations associated with cardiac G&R and discuss existing mathematical models that describe this process. To facilitate the discussion, we have organized the G&R models in terms of (1) the physical focus (biochemical vs mechanical) and (2) the process that they describe (myocyte hypertrophy vs extracellular matrix remodeling). The review concludes with a discussion of some possible directions that can advance the existing state of cardiac G&R mathematical modeling. WIREs Syst Biol Med 2016, 8:211-226. doi: 10.1002/wsbm.1330 For further resources related to this article, please visit the WIREs website.

Modeling Pathologies of Diastolic and Systolic Heart Failure.

Chronic heart failure is a medical condition that involves structural and functional changes of the heart and a progressive reduction in cardiac output. Heart failure is classified into two categories: diastolic heart failure, a thickening of the ventricular wall associated with impaired filling; and systolic heart failure, a dilation of the ventricles associated with reduced pump function. In theory, the pathophysiology of heart failure is well understood. In practice, however, heart failure is highly sensitive to cardiac microstructure, geometry, and loading. This makes it virtually impossible to predict the time line of heart failure for a diseased individual. Here we show that computational modeling allows us to integrate knowledge from different scales to create an individualized model for cardiac growth and remodeling during chronic heart failure. Our model naturally connects molecular events of parallel and serial sarcomere deposition with cellular phenomena of myofibrillogenesis and sarcomerogenesis to whole organ function. Our simulations predict chronic alterations in wall thickness, chamber size, and cardiac geometry, which agree favorably with the clinical observations in patients with diastolic and systolic heart failure. In contrast to existing single- or bi-ventricular models, our new four-chamber model can also predict characteristic secondary effects including papillary muscle dislocation, annular dilation, regurgitant flow, and outflow obstruction. Our prototype study suggests that computational modeling provides a patient-specific window into the progression of heart failure with a view towards personalized treatment planning.