Novel valve-in-surgical bioprosthetic transcatheter aortic valve replacement: Undermining iatrogenic coronary obstruction with radiofrequency needle (UNICORN).

An 86-year-old female with history of surgical aortic valve replacement presented with clinical signs of heart failure. Echocardiography revealed a reduction in left ventricular systolic function and severe bioprosthetic aortic valve dysfunction. This is the first reported case of valve-in-valve transcatheter aortic valve replacement with concomitant undermining iatrogenic coronary obstruction with radiofrequency needle procedure in a surgical bioprosthetic valve.

Elucidating mobilization mechanisms of uranium during recharge of river water to contaminated groundwater.

The recharge of stream water below the baseflow water table can mobilize groundwater contaminants, particularly redox-sensitive and sorptive metals such as uranium. However, in-situ tracer experiments that simulate the recharge of stream water to uranium-contaminated groundwater are lacking, thus limiting the understanding of the potential mechanisms that control the mobility of uranium at the field scale. In this study, a field tracer test was conducted by injecting 100 gal (379 l) of oxic river water into a nearby suboxic and uranium-contaminated aquifer. The traced river water was monitored for 18 days in the single injection well and in the twelve surrounding observation wells. Mobilization of uranium from the solid to the aqueous phase was not observed during the tracer test despite its pre-test presence being confirmed on the aquifer sediments from lab-based acid leaching. However, strong evidence of oxidative immobilization of iron and manganese was observed during the tracer test and suggested that immobile uranium was likely in its oxidized state as U(VI) on the aquifer sediments; these observations ruled out oxidation of U(IV) to U(VI) as a potential mobilization mechanism. Therefore, desorption of U(VI) appeared to be the predominant potential mobilization mechanism, yet it was clearly not solely dependent on concentration as evident when considering that uranium-poor river water (<0.015 mg/L) was recharged to uranium-rich groundwater (≈1 mg/L). It was possible that uranium desorption was limited by the relatively higher pH and lower alkalinity of the river water as compared to the groundwater; both factors favor immobilization. However, it was likely that the immobile uranium was associated with a mineral phase, as opposed to a sorbed phase, thus desorption may not have been possible. The results of this field tracer study successfully ruled out two common mobilization mechanisms of uranium: (1) oxidative dissolution and (2) concentration-dependent desorption and ruled in the importance of advection, dispersion, and the mineral phase of uranium.

Allergy and the Heart: Eosinophilic Myocarditis With Biventricular Thrombi.

A 40-year-old woman with history of atopy and peripheral eosinophilia presented with clinical signs of heart failure. Echocardiography revealed a restrictive cardiomyopathy with biventricular thrombi. Hypereosinophilic syndrome resulting in eosinophilic myocarditis (Loeffler's syndrome) was diagnosed. This case highlights the workup, diagnosis, and management of hypereosinophilic syndrome with eosinophilic myocarditis. (Level of Difficulty: Advanced.).

Evolution of nectar spur length in a clade of Linaria reflects changes in cell division rather than in cell expansion.

Background and Aims: Nectar spurs (tubular outgrowths of a floral organ which contain, or give the appearance of containing, nectar) are hypothesized to be a 'key innovation' which can lead to rapid speciation within a lineage, because they are involved in pollinator specificity. Despite the ecological importance of nectar spurs, relatively little is known about their development. We used a comparative approach to investigate variation in nectar spur length in a clade of eight Iberian toadflaxes. Methods: Spur growth was measured at the macroscopic level over time in all eight species, and growth rate and growth duration compared. Evolution of growth rate was reconstructed across the phylogeny. Within the clade we then focused on Linaria becerrae and Linaria clementei, a pair of sister species which have extremely long and short spurs, respectively. Characterization at a micromorphological level was performed across a range of key developmental stages to determine whether the difference in spur length is due to differential cell expansion or cell division. Key Results: We detected a significant difference in the evolved growth rates, while developmental timing of both the initiation and the end of spur growth remained similar. Cell number is three times higher in the long spurred L. becerrae compared with L. clementei, whereas cell length is only 1.3 times greater. In addition, overall anisotropy of mature cells is not significantly different between the two species. Conclusions: We found that changes in cell number and therefore in cell division largely explain evolution of spur length. This contrasts with previous studies in Aquilegia which have found that variation in nectar spur length is due to directed cell expansion (anisotropy) over variable time frames. Our study adds to knowledge about nectar spur development in a comparative context and indicates that different systems may have evolved nectar spurs using disparate mechanisms.

Total parenteral nutrition in patients following pancreaticoduodenectomy: lessons from 1184 patients.

BACKGROUND: Total parenteral nutrition (TPN) has historically been used conservatively in the management of patients after pancreaticoduodenectomy (PD). Herein, we evaluate the indications for and outcomes associated with TPN use in a high-volume pancreatic surgery center. MATERIALS AND METHODS: We retrospectively queried our institution's pancreatic surgery database for patients who received TPN after PD from 2006 through 2015. RESULTS: Of 1184 patients who underwent PD, 232 (19.6%) received TPN perioperatively. The most common indications for TPN were delayed gastric emptying (DGE, n = 171, 73.7%), pancreatic fistula (n = 102, 44%), and generalized malnutrition (n = 25, 10.8%). The median day of TPN initiation was postoperative day 4 (range: -31 to 22), with a median usage of 9 days (range: 1-115). Forty-four (19%) patients received short-course TPN (≤3 days), primarily those diagnosed with isolated grade A DGE without associated complications (P = 0.0003). Multivariate analysis suggests the presence of deep surgical site infection (odds ratio: 3.09, [1.16-5.06], P = 0.018) or pancreatic fistula (odds ratio: 2.57, [1.03-6.41], P = 0.043) at the time of DGE presentation as predictive of long-term TPN requirement. Hyperglycemia (34.5%) was the most common complication resulting from TPN use, whereas central line-associated bloodstream infections (2.6%) were rare. Readmissions (35.3% TPN cohort; 15% historical institutional rate) were most commonly due to poor oral intake (26.8%). The 30-day mortality rate in the overall TPN cohort was 3.4% (0.8% historical institutional rate). CONCLUSIONS: TPN is a critical and safe adjunct for patients who develop PD-associated complications; however, it may be of limited utility for patients with isolated DGE.

Hypertension during Weight Lifting Reduces Flow-Mediated Dilation in Nonathletes.

PURPOSE: The purpose of this study was to determine whether increased intraluminal pressure is the damaging factor that reduces flow-mediated dilation (FMD) in young, healthy subjects after resistance exercise to maximal exertion. HYPOTHESIS: Attenuating the rise in brachial artery pressure during weight lifting by placing a blood pressure cuff on the upper arm prevents postexercise impairment of brachial artery FMD in sedentary individuals. METHODS: Nine sedentary individuals who exercise once a week or less and six exercise-trained individuals who exercise three times a week or more performed leg press exercise to maximal exertion on two separate occasions. During one visit, a blood pressure cuff, proximal to the site of brachial artery measurement, was inflated to 100 mm Hg to protect the distal vasculature from the rise in intraluminal pressure, which occurs during resistance exercise. Brachial artery FMD was determined using ultrasonography before and 30 min after weight lifting. RESULTS: Without the protective cuff, brachial artery FMD in sedentary individuals was reduced after weight lifting (9.0% ± 1.2% prelift vs 6.6% ± 0.8% postlift; P = 0.005), whereas in exercise-trained individuals, FMD was unchanged (7.4% ± 0.7% prelift vs 8.0% ± 0.9% postlift; P = 0.543). With the protective cuff, FMD no longer decreased but rather increased in sedentary individuals (8.7% ± 1.2% prelift vs 10.5% ± 1.0% postlift, P = 0.025). An increase in FMD was also seen in exercise-trained subjects when the cuff was present (6.6% ± 0.7% prelift vs 10.9% ± 1.5% postlift, P < 0.001). CONCLUSION: Protecting the brachial artery from exercise-induced hypertension enhances FMD in sedentary and exercise-trained individuals. These results indicate that increased intraluminal pressure in the artery contributes to the reduced FMD after heavy resistance exercise in sedentary individuals.

Response of 33 UK patients with infantile-onset Pompe disease to enzyme replacement therapy.

BACKGROUND: Enzyme replacement therapy (ERT) for infantile-onset Pompe disease has been commercially available for almost 10 years. We report the experience of its use in a cohort treated at three specialist lysosomal treatment centres in the UK. METHODS: A retrospective case-note review was performed, with additional data being gathered from two national audits on all such patients treated with ERT. The impact on the outcome of various characteristics, measured just prior to the initiation of ERT (baseline), was evaluated using logistic regression. RESULTS: Thirty-three patients were identified; 13/29 (45%) were cross-reactive immunological material (CRIM) negative, and nine were immunomodulated. At baseline assessment, 79% were in heart failure, 66% had failure to thrive and 70% had radiological signs of focal pulmonary collapse. The overall survival rate was 60%, ventilation-free survival was 40% and 30% of patients were ambulatory. Median follow-up of survivors was 4 years, 1.5 months (range 6 months to 13.5 years). As with previous studies, the CRIM status impacted on all outcome measures. However, in this cohort, baseline failure to thrive was related to death and lack of ambulation, and left ventricular dilatation was a risk factor for non-ventilator-free survival. CONCLUSION: The outcome of treated patients remains heterogeneous despite attempts at immunomodulation. Failure to thrive at baseline and left ventricular dilation appear to be associated with poorer outcomes.

One gene versus two: a regional study on the efficacy of single gene versus pyramided resistance for soybean aphid management.

The soybean aphid (Aphis glycines Matsumura) is a threat to soybean production in the Midwestern United States. Varieties containing the Rag1 soybean aphid resistance gene have been released with limited success in reducing aphid populations. Furthermore, virulent biotypes occur within North America and challenge the durability of single-gene resistance. Pyramiding resistance genes has the potential to improve aphid population suppression and increase resistance gene durability. Our goal was to determine if a pyramid could provide improved aphid population suppression across awide range of environments. We conducted a small-plot field experiment across seven states and three years. We compared soybean near-isolines for the Rag1 or Rag2 gene, and a pyramid line containing both genes for their ability to decrease aphid pressure and protect yield compared with a susceptible line. These lines were evaluated both with and without a neonicitinoid seed treatment. All aphid-resistant lines significantly decreased aphid pressure at all locations but one. The pyramid line experienced lower aphid pressure than both single-gene lines at eight of 23 location-years. Soybean aphids significantly reduced soybean yield for the susceptible line by 14% and for both single-gene lines by 5%; however, no significant yield decrease was observed for the pyramid line. The neonicitinoid seed treatment reduced plant exposure to aphids across all soybean lines, but did not provide significant yield protection for any of the lines. These results demonstrate that pyramiding resistance genes can provide sufficient and consistent yield protection from soybean aphid in North America.

Economic threshold for soybean aphid (Hemiptera: Aphididae).

Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), reached damaging levels in 2003 and 2005 in soybean, Glycine max (L.) Merrill, in most northern U.S. states and Canadian provinces, and it has become one of the most important pests of soybean throughout the North Central region. A common experimental protocol was adopted by participants in six states who provided data from 19 yield-loss experiments conducted over a 3-yr period. Population doubling times for field populations of soybean aphid averaged 6.8 d +/- 0.8 d (mean +/- SEM). The average economic threshold (ET) over all control costs, market values, and yield was 273 +/- 38 (mean +/- 95% confidence interval [CI], range 111-567) aphids per plant. This ET provides a 7-d lead time before aphid populations are expected to exceed the economic injury level (EIL) of 674 +/- 95 (mean +/- 95% CI, range 275-1,399) aphids per plant. Peak aphid density in 18 of the 19 location-years occurred during soybean growth stages R3 (beginning pod formation) to R5 (full size pod) with a single data set having aphid populations peaking at R6 (full size green seed). The ET developed here is strongly supported through soybean growth stage R5. Setting an ET at lower aphid densities increases the risk to producers by treating an aphid population that is growing too slowly to exceed the EIL in 7 d, eliminates generalist predators, and exposes a larger portion of the soybean aphid population to selection by insecticides, which could lead to development of insecticide resistance.

Femoral fractures in children, is early interventional treatment beneficial?

A protocol of early intervention (flexible intramedullary nails, early hip spica, and external fixation) was started in 1999 and during a 3-year period there were 25 children who sustained a femoral shaft fracture (early intervention group). These were prospectively reviewed with a minimum follow up of 24 months (Range 24-35 months). A historical control group of 41 children was used. These children were injured between February 1996 and February 1999 and were retrospectively reviewed. They had traditional in patient treatments with either Gallows or Thomas splint traction (traditional treatment group). Over the 6-year period from 1996 to 2002 there were a total of 66 femoral shaft fractures in the study that presented to our hospital. The mean length of hospital stay was 29 nights in the traditional group and 10 nights in the early intervention group. This difference is significant (p<0.001). The malunion rate was slightly higher in the early active group at radiological union but most of these remodelled over the 2 years of follow up. The protocol of early intervention used in our institution, of flexible nails, early hip spica or external fixation depended on the age of the child, and has resulted in a shorter hospital stay for the children. This has benefits for the child, the family and the hospital.

Engineering and public health at CDC.

Engineering is the application of scientific and technical knowledge to solve human problems. Using imagination, judgment, and reasoning to apply science, technology, mathematics, and practical experience, engineers develop the design, production, and operation of useful objects or processes. During the 1940s, engineers dominated the ranks of CDC scientists. In fact, the first CDC director, Assistant Surgeon General Mark Hollis, was an engineer. CDC engineers were involved in malaria control through the elimination of standing water. Eventually the CDC mission expanded to include prevention and control of dengue, typhus, and other communicable diseases. The development of chlorination, water filtration, and sewage treatment were crucial to preventing waterborne illness. Beginning in the 1950s, CDC engineers began their work to improve public health while developing the fields of environmental health, industrial hygiene, and control of air pollution. Engineering disciplines represented at CDC today include biomedical, civil, chemical, electrical, industrial, mechanical, mining, and safety engineering. Most CDC engineers are located in the National Institute for Occupational Safety and Health (NIOSH) and the Agency for Toxic Substances and Disease Registry (ATSDR). Engineering research at CDC has a broad stakeholder base. With the cooperation of industry, labor, trade associations, and other stakeholders and partners, current work includes studies of air contaminants, mining, safety, physical agents, ergonomics, and environmental hazards. Engineering solutions remain a cornerstone of the traditional "hierarchy of controls" approach to reducing public health hazards.

Efficacy of once-daily extended-release lovastatin as compared to immediate-release lovastatin in patients with hypercholesterolemia.

OBJECTIVE: to compare the efficacy and safety of 20 mg of lovastatin when administered once daily as an extended-release (ER) tablet or as an immediate-release (IR) tablet. RESEARCH DESIGN AND METHODS: Male or female patients aged 21-70 years with hypercholesterolemia who provided written informed consent and met the inclusion criteria were screened. A total of 179 patients were enrolled: 100 male and 79 female; 153 were Caucasian, eight Black and 18 other races; the mean age was 56 years. Patients were generally in good health as evidenced by medical history, physical and laboratory examination. Patients were required to not exceed specific low-density lipoprotein cholesterol (LDL-C) levels depending on their risk category. The trial was conducted as a multi-center, randomized, double-blind, positive-controlled, double-dummy, two-way crossover study. Patients were washed-out of any prior lipid-lowering medications (period 1) and then received one ER or one IR lovastatin tablet for 12 weeks (period 2) and then washed out with placebo for 6 weeks (period 3). They then received the alternate treatment for an additional 12 weeks (period 4). MAIN OUTCOME MEASURES: The primary efficacy variable was the combined mean percent change in LDL-C from baseline to endpoint for periods 2 and 4. Secondary variables included the mean percent change from baseline in high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) for periods 2 and 4 combined. Least-square mean differences between ER and IR treated groups were estimated at both treatments. All tests were two-sided and a p-value of < 0.05 was considered statistically significant. RESULTS: Both ER and IR lovastatin tablets produced statistically significant changes in the lipid profile from baseline. Differences in HDL-C (4.1% and 4.3% for ER and IR, respectively) and TG (7.4% and 10.4% for ER and IR, respectively) were not significant between treatments. TC (19.1% and 17.2% for ER and IR, respectively) and LDL-C (26.4% and 23.1% for ER and IR, respectively) were also reduced significantly from baseline by both treatments. However the ER lovastatin reduced TC by an additional 1.9% (p = 0.0355) and LDL-C by a further 3.3% decrease (p = 0.0028) as compared to the IR formulation. The increase in LDL-C efficacy is equivalent to an increase of 50% in the dose of IR lovastatin, suggesting that 20 mg ER is equivalent to about 30 mg IR in LDL-C-lowering capacity. No apparent difference in the safety profile between the two formulations was noted. CONCLUSIONS: The data show that 20 mg of ER lovastatin was about one and one-half times as effective at lowering LDL-C than the same dose of IR lovastatin. Both regimens were tolerated well.

Sex attractant pheromone of the red-shouldered stink bug Thyanta pallidovirens: a pheromone blend with multiple redundant components.

The male-produced sex pheromone of the red-shouldered stink bug, Thyanta pallidovirens (Stål) (Hemiptera: Pentatomidae) consists of a blend of methyl (E2,Z4,Z6)-decatrienoate (E2,Z4,Z6-10:COOMe), and the sesquiterpenes (+)-alpha-curcumene, (-)-zingiberene, and (-)-beta-sesquiphellandrene. In laboratory bioassays, sexually mature males attracted sexually mature females but not males, and females did not attract either sex. Extracts of volatiles collected from sexually mature males contained compounds not present in extracts from females or sexually immature males, and male-produced extract was attractive to females. Biological activity was lost when the extract was fractionated, indicating that the pheromone consisted of at least two components having different chemical properties. Individually, pheromone components were not attractive to females, but E2,Z4,Z6-10:COOMe in combination with at least one of the three male-produced sesquiterpenes was attractive. The presence of more than one sesquiterpene in the blend did not increase attraction, indicating redundancy in the pheromone signal. Male extract was as attractive as a blend reconstructed from synthesized compounds, indicating all biologically active components had been identified. In bioassays conducted at dusk in a 1- x 1- x 1-m screen field cage, females were attracted to synthetic pheromone lures. In field trials, adult female T pallidovirens were attracted to pheromone-baited traps in relatively low numbers. The profile of volatiles released by sexually mature males of a congeneric species, Thyanta accerra custator McAtee, was remarkably similar to that of male T. pallidovirens, with the exception that the former species produced (E)-2-decenal, a compound that was not found in T. pallidovirens extracts.

Treatment with controlled-release lovastatin decreases serum concentrations of human beta-amyloid (A beta) peptide.

The deposition of beta-amyloid (A beta) in neuronal plaques is believed to be crucial for the initiation and progression of Alzheimer's disease (AD). Studies in vitro have shown that inhibiting cholesterol metabolism with lovastatin, or its active metabolite lovastatin acid, lowers A beta production. To examine the effects of lovastatin on A beta in vivo, human subjects who had elevated low-density lipoprotein cholesterol were treated during a double-blind, randomized, placebo-controlled study with 10, 20, 40 or 60 mg once-daily doses of a controlled-release formulation of lovastatin, or matching placebo. Serum A beta concentrations were measured before and after up to 3 months of treatment. Mean and median changes from baseline in serum A beta concentrations showed a dose-dependent decrease, and analysis of variance indicated that treatment was statistically significant (p < 0.0348). Differences between the 40- and 60-mg dose groups and placebo were statistically significant (Dunnett's p < or = 0.05).

A Phase I study of raltitrexed, an antifolate thymidylate synthase inhibitor, in adult patients with advanced solid tumors.

The purpose of this study was to perform a Phase I trial of raltitrexed, a selective inhibitor of thymidylate synthase, and to determine the pharmacokinetic and toxicity profiles as a function of raltitrexed dose. Fifty patients with advanced solid tumors and good performance status were treated with raltitrexed as a 15-min i.v. infusion every 3 weeks, at doses escalating from 0.6 to 4.5 mg/m2. Asthenia, neutropenia, and hepatic toxicity were the most common dose-limiting toxicities in this largely pretreated patient population, but they occurred during the initial cycle in only one of nine patients treated with 4.0 mg/m2 and in two of nine patients treated with 4.5 mg/m2. Only 2 of 13 patients treated with 3.5 mg/m2 ultimately experienced unacceptable toxicity after three and seven cycles, compared with 42 and 56% of patients receiving 4.0 and 4.5 mg/m2 after medians of three and two cycles, respectively. The maximum raltitrexed plasma concentration and the area under the plasma concentration-time curve increased in proportion to dose. Raltitrexed clearance was independent of dose and was associated with the estimated creatinine clearance. Asthenia, neutropenia, and hepatic transaminitis were dose-related and tended to occur more frequently when patients received three or more cycles of therapy. A 3-week treatment interval was feasible in the majority of patients at all doses. Although 4.0 mg/m2 appeared to be a safe starting dose in this pretreated patient population, about half who received two or more courses ultimately experienced dose-limiting toxicity. A dose of 3.5 mg/m2 was well tolerated in most patients.