Machine learned interatomic potential for dispersion strengthened plasma facing components.

Tungsten (W) is a material of choice for the divertor material due to its high melting temperature, thermal conductivity, and sputtering threshold. However, W has a very high brittle-to-ductile transition temperature, and at fusion reactor temperatures (≥1000 K), it may undergo recrystallization and grain growth. Dispersion-strengthening W with zirconium carbide (ZrC) can improve ductility and limit grain growth, but much of the effects of the dispersoids on microstructural evolution and thermomechanical properties at high temperatures are still unknown. We present a machine learned Spectral Neighbor Analysis Potential for W-ZrC that can now be used to study these materials. In order to construct a potential suitable for large-scale atomistic simulations at fusion reactor temperatures, it is necessary to train on ab initio data generated for a diverse set of structures, chemical environments, and temperatures. Further accuracy and stability tests of the potential were achieved using objective functions for both material properties and high temperature stability. Validation of lattice parameters, surface energies, bulk moduli, and thermal expansion is confirmed on the optimized potential. Tensile tests of W/ZrC bicrystals show that although the W(110)-ZrC(111) C-terminated bicrystal has the highest ultimate tensile strength (UTS) at room temperature, observed strength decreases with increasing temperature. At 2500 K, the terminating C layer diffuses into the W, resulting in a weaker W-Zr interface. Meanwhile, the W(110)-ZrC(111) Zr-terminated bicrystal has the highest UTS at 2500 K.

Temporal endurance of exercise-induced benefits on hippocampus-dependent memory and synaptic plasticity in female mice.

Exercise facilitates hippocampal neurogenesis and neuroplasticity that in turn, promotes cognitive function. Our previous studies have demonstrated that in male mice, voluntary exercise enables hippocampus-dependent learning in conditions that are normally subthreshold for long-term memory formation in sedentary animals. Such cognitive enhancement can be maintained long after exercise has ceased and can be re-engaged by a subsequent subthreshold exercise session, suggesting exercise-induced benefits are temporally dynamic. In females, the extent to which the benefits of exercise can be maintained and the mechanisms underlying this maintenance have yet to be defined. Here, we examined the exercise parameters required to initiate and maintain the benefits of exercise in female C57BL/6J mice. Using a subthreshold version of the hippocampus-dependent task called object-location memory (OLM) task, we show that 14d of voluntary exercise enables learning under subthreshold acquisition conditions in female mice. Following the initial exercise, a 7d sedentary delay results in diminished performance, which can be re-facilitated when animals receive 2d of reactivating exercise following the sedentary delay. Assessment of estrous cycle reveals enhanced wheel running activity during the estrus phase relative to the diestrus phase, whereas estrous phase on training or test had no effect on OLM performance. Utilizing the same exercise parameters, we demonstrate that 14d of exercise enhances long-term potentiation (LTP) in the CA1 region of the hippocampus, an effect that persists throughout the sedentary delay and following the reactivating exercise session. Previous studies have proposed exercise-induced BDNF upregulation as the mechanism underlying exercise-mediated benefits on synaptic plasticity and cognition. However, our assessment of hippocampal Bdnf mRNA expression following memory retrieval reveals no difference between exercise conditions and control, suggesting that persistent Bdnf upregulation may not be required for maintenance of exercise-induced benefits. Together, our data indicate that 14d of voluntary exercise can initiate long-lasting benefits on neuroplasticity and cognitive function in female mice, establishing the first evidence on the temporal endurance of exercise-induced benefits in females.

HDAC3 Activity within the Nucleus Accumbens Regulates Cocaine-Induced Plasticity and Behavior in a Cell-Type-Specific Manner.

Epigenetic mechanisms regulate processes of neuroplasticity critical to cocaine-induced behaviors. This includes the Class I histone deacetylase (HDAC) HDAC3, known to act as a negative regulator of cocaine-associated memory formation within the nucleus accumbens (NAc). Despite this, it remains unknown how cocaine alters HDAC3-dependent mechanisms. Here, we profiled HDAC3 expression and activity in total NAc mouse tissue following cocaine exposure. Although chronic cocaine did not affect expression of Hdac3 within the NAc, chronic cocaine did affect promoter-specific changes in HDAC3 and H4K8Ac occupancy. These changes in promoter occupancy correlated with cocaine-induced changes in expression of plasticity-related genes. To causally determine whether cocaine-induced plasticity is mediated by HDAC3's deacetylase activity, we overexpressed a deacetylase-dead HDAC3 point mutant (HDAC3-Y298H-v5) within the NAc of adult male mice. We found that disrupting HDAC3's enzymatic activity altered selective changes in gene expression and synaptic plasticity following cocaine exposure, despite having no effects on cocaine-induced behaviors. In further assessing HDAC3's role within the NAc, we observed that chronic cocaine increases Hdac3 expression in Drd1 but not Drd2-cells of the NAc. Moreover, we discovered that HDAC3 acts selectively within D1R cell-types to regulate cocaine-associated memory formation and cocaine-seeking. Overall, these results suggest that cocaine induces cell-type-specific changes in epigenetic mechanisms to promote plasticity important for driving cocaine-related behaviors.SIGNIFICANCE STATEMENT Drugs of abuse alter molecular mechanisms throughout the reward circuitry that can lead to persistent drug-associated behaviors. Epigenetic regulators are critical drivers of drug-induced changes in gene expression. Here, we demonstrate that the activity of an epigenetic enzyme promotes neuroplasticity within the nucleus accumbens (NAc) critical to cocaine action. In addition, we demonstrate that these changes in epigenetic activity drive cocaine-seeking behaviors in a cell-type-specific manner. These findings are key in understanding and targeting cocaine's impact of neural circuitry and behavior.

Systemic HDAC3 inhibition ameliorates impairments in synaptic plasticity caused by simulated galactic cosmic radiation exposure in male mice.

Deep space travel presents a number of measurable risks including exposure to a spectrum of radiations of varying qualities, termed galactic cosmic radiation (GCR) that are capable of penetrating the spacecraft, traversing through the body and impacting brain function. Using rodents, studies have reported that exposure to simulated GCR leads to cognitive impairments associated with changes in hippocampus function that can persist as long as one-year post exposure with no sign of recovery. Whether memory can be updated to incorporate new information in mice exposed to GCR is unknown. Further, mechanisms underlying long lasting impairments in cognitive function as a result of GCR exposure have yet to be defined. Here, we examined whether whole body exposure to simulated GCR using 6 ions and doses of 5 or 30 cGy interfered with the ability to update an existing memory or impact hippocampal synaptic plasticity, a cellular mechanism believed to underlie memory processes, by examining long term potentiation (LTP) in acute hippocampal slices from middle aged male mice 3.5-5 months after radiation exposure. Using a modified version of the hippocampus-dependent object location memory task developed by our lab termed "Objects in Updated Locations" (OUL) task we find that GCR exposure impaired hippocampus-dependent memory updating and hippocampal LTP 3.5-5 months after exposure. Further, we find that impairments in LTP are reversed through one-time systemic subcutaneous injection of the histone deacetylase 3 inhibitor RGFP 966 (10 mg/kg), suggesting that long lasting impairments in cognitive function may be mediated at least in part, through epigenetic mechanisms.

Explicit Multielement Extension of the Spectral Neighbor Analysis Potential for Chemically Complex Systems.

A natural extension of the descriptors used in the Spectral Neighbor Analysis Potential (SNAP) method is derived to treat atomic interactions in chemically complex systems. Atomic environment descriptors within SNAP are obtained from a basis function expansion of the weighted density of neighboring atoms. This new formulation instead partitions the neighbor density into partial densities for each chemical element, thus leading to explicit multielement descriptors. For Nelem chemical elements, the number of descriptors increases as [Formula: see text], while the computational cost of the force calculation as implemented in LAMMPS is limited to [Formula: see text] and the favorable linear scaling in the number of atoms is retained. We demonstrate these chemically aware descriptors by producing an interatomic potential for indium phosphide capable of capturing high-energy defects that result from radiation damage cascades. This new explicit multielement SNAP method reproduces the relaxed defect formation energies with substantially greater accuracy than weighted-density SNAP, while retaining accurate representation of the bulk indium phosphide properties.

Microglial activation increases cocaine self-administration following adolescent nicotine exposure.

With the rise of e-cigarette use, teen nicotine exposure is becoming more widespread. Findings from clinical and preclinical studies show that the adolescent brain is particularly sensitive to nicotine. Animal studies have demonstrated that adolescent nicotine exposure increases reinforcement for cocaine and other drugs. However, the mechanisms that underlie these behaviors are poorly understood. Here, we report reactive microglia are critical regulators of nicotine-induced increases in adolescent cocaine self-administration. Nicotine has dichotomous, age-dependent effects on microglial morphology and immune transcript profiles. A multistep signaling mechanism involving D2 receptors and CX3CL1 mediates nicotine-induced increases in cocaine self-administration and microglial activation. Moreover, nicotine depletes presynaptic markers in a manner that is microglia-, D2- and CX3CL1-dependent. Taken together, we demonstrate that adolescent microglia are uniquely susceptible to perturbations by nicotine, necessary for nicotine-induced increases in cocaine-seeking, and that D2 receptors and CX3CL1 play a mechanistic role in these phenomena.

Pediatric endocrine society survey of diabetes practices in the United States: What is the current state?

BACKGROUND: The Practice Management Committee (PMC) of the Pediatric Endocrine Society (PES) conducted a survey of its membership in February/March, 2016 to assess the current state of pediatric diabetes care delivery across multiple practice types in the United States. METHODS: The PES distributed an anonymous electronic survey (Survey Monkey) via email to its membership and requested that only one survey be completed for each practice. RESULTS: Ninety-three unique entries from the US were entered into analysis. Care is predominantly delivered by multidisciplinary teams, based at academic institutions (65.6%), with >85% of the provider types being physicians. Each 1.0 full time equivalent certified diabetes educators serves on average 367 diabetic youth. Fee-for-service remains the standard method of reimbursement with 57% of practices reporting financial loss. Survey respondents identified under-reimbursement as a major barrier to improving patient outcomes and lack of behavioral health (BH) providers as a key gap in services provided. CONCLUSIONS: Our survey reveals wide variation in all aspects of pediatric diabetes care delivery in the United States. Pediatric Endocrinologists responding to the survey identified a lack of resources and the current fee for service payment model as a major impediment to practice and the lack of integrated BH staff as a key gap in service. The respondents strongly support its organizations' involvement in the dissemination of standards for care delivery and advocacy for a national payment model aligned with chronic diabetes care in the context of our emerging value-based healthcare system.

Computation of the Density Matrix in Electronic Structure Theory in Parallel on Multiple Graphics Processing Units.

The algorithm developed in Cawkwell, M. J. et al. J. Chem. Theory Comput. 2012 , 8 , 4094 for the computation of the density matrix in electronic structure theory on a graphics processing unit (GPU) using the second-order spectral projection (SP2) method [ Niklasson, A. M. N. Phys. Rev. B 2002 , 66 , 155115 ] has been efficiently parallelized over multiple GPUs on a single compute node. The parallel implementation provides significant speed-ups with respect to the single GPU version with no loss of accuracy. The performance and accuracy of the parallel GPU-based algorithm is compared with the performance of the SP2 algorithm and traditional matrix diagonalization methods on a multicore central processing unit (CPU).

Immature rat seminiferous tubules reconstructed in vitro express markers of Sertoli cell maturation after xenografting into nude mouse hosts.

Sertoli cells undergo a maturation process during post-natal testicular development that leads to the adult-type Sertoli cell, which is required for spermatogenesis. Understanding Sertoli cell maturation is therefore necessary to gain insight into the underlying causes of impaired spermatogenesis and male infertility. The present study characterized the cellular and molecular differentiation of Sertoli cells in a xenograft model of mammalian testicular development. Immature rat Sertoli cells were cultured in a three-dimensional culture system to allow the formation of cord-like structures. The in vitro Sertoli cell cultures were then grafted into nude mice. Sertoli cell proliferation, morphological differentiation and mRNA expression of Sertoli cell maturation markers were evaluated in xenografts. Sertoli cell proliferation significantly decreased between 1 and 4 weeks (6.7 +/- 0.9 versus 1.2+/- 0.1%, P < 0.001), and was maintained at low levels thereafter. Sertoli cell cord-like structures significantly decreased between 1 and 4 weeks (59.6 versus 21%, P < 0.05), whereas Sertoli cell tubules were more frequently observed after 4 weeks (13.3 versus 73.1%, P < 0.05). Furthermore, expression of androgen binding protein, transferrin and follicle stimulating hormone receptor, markers for mature Sertoli cells, was detected after 1 week of grafting and increased significantly thereafter. We conclude from these results that rat Sertoli cells continue maturation after xenografting to the physiological environment of a host. This model of in vitro tubule formation will be helpful in future investigations addressing testicular maturation in the mammalian testis.

Influence of isoflurane general anesthesia or anesthesia and surgery on thyroid function tests in dogs.

BACKGROUND: Anesthesia and surgery affect thyroid function tests in humans but have not been studied in dogs. HYPOTHESIS: Anesthesia and anesthesia with surgery will affect thyroid function tests in dogs. ANIMALS: Fifteen euthyroid dogs. METHODS: Prospective, controlled, interventional study. Dogs were assigned to one of 3 groups: control, general anesthesia, and general anesthesia plus abdominal exploratory surgery. Dogs in the anesthesia and surgery groups were premedicated with acepromazine and morphine, induced with propofol, and maintained on isoflurane. Samples for measurement of serum thyroxine (T4), free T4 (fT4) by equilibrium dialysis, triiodothyronine (T3), reverse T3 (rT3), and thyroid-stimulating hormone concentrations were collected from each dog immediately before premedication, at multiple times during anesthesia, surgery, 4, 8, 12, 24, 36, and 48 hours after anesthesia, once daily for an additional 5 days, and once 14 days after anesthesia. Sampling was performed at identical times in the control group. RESULTS: Serum T4 decreased significantly from baseline in the surgery and anesthesia groups compared with the control group at 0.33 (P= 0.043) and 1 hour (P= 0.018), and 2 (P= 0.031) and 4 hours (P= 0.037), respectively, then increased significantly in the surgery group compared with the control group at 24 hours (P= 0.005). Serum T3 decreased significantly from baseline in the anesthesia group compared with the control group at 1 hour (P= 0.034). Serum rT3 increased significantly from baseline in the surgery group compared with the control and anesthesia groups at 8 (P= 0.026) and 24 hours (P= 0.0001) and anesthesia group at 8, 12, 24, and 36 hours (P= 0.004, P= 0.016, P= 0.004, and P= 0.014, respectively). Serum fT4 increased significantly from baseline in the surgery group compared to the control at 24 hours (P= 0.006) and at day 7 (P= 0.037) and anesthesia group at 48 hours (P= 0.023). CONCLUSIONS AND CLINICAL IMPORTANCE: Surgery and anesthesia have a significant effect on thyroid function tests in dogs.

Complex temporal patterns of spontaneous initiation and termination of reentry in a loop of cardiac tissue.

A two-component model is developed consisting of a discrete loop of cardiac cells that circulates action potentials as well as a pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and the pacer's action are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability (T-bistability) of reentrant circulation and in some cases, also phase-resetting interactions with the pacer.

Correlating cell morphology and osteoid mineralization relative to strain profile for bone tissue engineering applications.

A number of bone tissue engineering strategies use porous three-dimensional scaffolds in combination with bioreactor regimes. The ability to understand cell behaviour relative to strain profile will allow for the effects of mechanical conditioning in bone tissue engineering to be realized and optimized. We have designed a model system to investigate the effects of strain profile on bone cell behaviour. This simplified model has been designed with a view to providing insight into the types of strain distribution occurring across a single pore of a scaffold subjected to perfusion-compression conditioning. Local strains were calculated at the surface of the pore model using finite-element analysis. Scanning electron microscopy was used in secondary electron mode to identify cell morphology within the pore relative to local strains, while backscattered electron detection in combination with X-ray microanalysis was used to identify calcium deposition. Morphology was altered according to the level of strain experienced by bone cells, where cells subjected to compressive strains (up to 0.61%) appeared extremely rounded while those experiencing zero and tensile strain (up to 0.81%) were well spread. Osteoid mineralization was similarly shown to be dose dependent with respect to substrate strain within the pore model, with the highest level of calcium deposition identified in the intermediate zones of tension/compression.

Supplemental algal meal alters the ruminal trans-18:1 fatty acid and conjugated linoleic acid composition in cattle.

The effects of dietary algal supplementation, a source of docosahexaenoic acid, on the fatty acid profile of rumen lipids in cattle were evaluated, with special emphasis on CLA and trans fatty acids produced by rumen microbes. A diet based on corn silage was fed with supplements containing the following: 1) no algal meal and fed at 2.1 kg of DM/d (control), 2) algal meal and fed at 1.1 kg of DM/d (low algal meal), 3) algal meal and fed at 2.1 kg of DM/d (medium algal meal), and 4) algal meal and fed at 4.2 kg of DM/d (high algal meal). A modified lipid extraction procedure was developed to analyze the lipid changes in rumen fluid. The percentage of stearic acid (18:0) in rumen fluid was decreased by algal meal supplementation (P < 0.001) compared with control and was linearly dependent on the level of algal meal supplementation (P = 0.005). Total trans-18:1 in rumen fluid of cattle fed the control diet was 19% of total fatty acids. Addition of algal meal increased (P < 0.001) total trans-18:1 up to 43%, mostly due to 18:1 trans-10 that increased (P = 0.002) to 29.5% of total rumen fatty acids. This increase in 18:1 trans-10 seems to suggest a change in the rumen microbial population. Vaccenic acid (18:1 trans-11) increased quadratically (P = 0.005) with increasing level of algal meal supplementation in the diets. The total CLA content was low in the control (<0.9%) and increased with dietary algal meal addition, although not significantly; the greatest level was 1.5% with the medium algal meal diet. The increase of rumenic acid (cis-9, trans-11 CLA) was quadratic (P = 0.05) with algal meal supplementation, whereas trans-10, cis-12 CLA increased linearly with increased level of algal meal from 0.08 to 0.13% (P = 0.03). The ratio of trans-11 (cis-9, trans-11 CLA + 18:1 trans-11) to trans-10 (trans-10, cis-12 CLA + 18:1 trans-10) decreased from 2.45 to 0.77, 0.87, and 0.21 for the control, low algal meal, medium algal meal, and high algal meal diets, respectively. The content of docosahexaenoic acid in rumen fluid increased (P = 0.002) from 0.3 to 1.4% of total fatty acids with increasing level of algal meal supplementation in the diets. Our results suggest that algal meal inhibits the reduction of trans-18:1 to 18:0, giving rise to the high trans-18:1 content. In conclusion, algal meal could be used to increase the concentration in rumen contents of trans-18:1 isomers that serve as precursors for CLA biosynthesis in the tissues of ruminants.

Does home-based exercise improve body mass index in patients with type 2 diabetes? Results of a feasibility trial.

AIMS: This feasibility trial evaluated the use, safety, and short-term benefits of a home-based exercise intervention designed to increase physical activity among adults with diabetes. METHODS: Participants with type 2 diabetes in a group practice were recruited and randomly assigned to the home-based exercise intervention or usual care. Participants were given diabetes self-management education, instructed to exercise 30 min 5 days/week, and were followed for 3 months. The intervention contained three exercise routines (aerobic and resistance exercises). Outcomes included changes from baseline at 3 months between groups in body mass index (BMI), quality of life, A1C, and blood pressure. RESULTS: Seventy-six sedentary adults completed the study: 49% intervention group, 68% women, 47% black, mean age 56.6+/-9.6 years. Using intention to treat analysis, a trend towards improvement between groups for BMI (mean change -0.4 versus 0.1, respectively; P=0.06) was identified. Thirty-eight percent of the intervention group adhered to 80% of the exercise recommendation and significantly improved BMI (-1.07; P<0.05). No other differences were detected between groups. CONCLUSIONS: Home-based exercise interventions have potential to reduce BMI in patients with diabetes. The results provide variance estimates necessary to power a larger study of longer duration.

Implementation of a mandatory rheumatology osteoporosis consultation in patients with low-impact hip fracture.

BACKGROUND: Osteoporosis remains an underdiagnosed and undertreated major health problem. The current treatment rate for patients who have experienced at least 1 osteoporotic fracture is 20%-25%. Therefore, the Rheumatology and Internal Medicine Departments of Ochsner Clinic Foundation New Orleans implemented a mandatory rheumatology osteoporosis consult as part of preprinted admission orders for all patients after hip fracture surgery on the Internal Medicine service. METHODS: We conducted a retrospective study of 78 patients admitted with a low-impact hip fracture between June 2004 and July 2005. These patients were seen by the rheumatology service in the hospital after hip fracture repair (exposed group). Osteoporosis evaluation was performed based on an interview questionnaire. Seventy-eight age-matched patients previously admitted for low-intensity or low-impact hip fracture in 2002-2003 but not exposed to the mandatory rheumatology consult served as our comparison group. Pearson chi2 test was used for statistical analysis. RESULTS: Mean patient age was 80 years. Of the 78 unexposed patients, 17 (22%) were on treatment (calcium, vitamin D, hormones or antiresorptive agents) before the hip fracture, and 18 (23%) were on treatment after fracture repair. Of the 78 patients exposed to the compulsory rheumatology consultation, 34 (44%) patients were receiving osteoporosis treatment before hip fracture and 75 (96%) patients were receiving treatment after fracture repair. Of the patients not treated before hip fracture repair, there was a significant increase in the percent treated for those patients exposed to the rheumatology consult versus those not exposed (97.6% vs. 2.4%, respectively, P < 0.0001). CONCLUSIONS: In our institution, we were successful in identifying and initiating appropriate therapy for osteoporosis patients through an automatic rheumatology osteoporosis consultation after hip fracture. The implementation of a mandatory osteoporosis consult resulted in a statistically significant increase in treatment of the exposed group compared with the unexposed group.

SMAC/Diablo mediates the proapoptotic function of PUMA by regulating PUMA-induced mitochondrial events.

p53-upregulated modulator of apoptosis (PUMA) is a BH3-only Bcl-2 family protein and an essential mediator of DNA damage-induced apoptosis. PUMA is localized in the mitochondria and induces apoptosis through the mitochondrial pathway. However, the mechanisms of PUMA-induced apoptosis remain unclear. In this study, we found that second mitochondria-derived activator of caspase (SMAC)/Diablo, a mitochondrial apoptogenic protein, mediates the proapoptotic function of PUMA by regulating PUMA-induced mitochondrial events. SMAC is consistently released into the cytosol in colon cancer cells undergoing PUMA-induced apoptosis. In SMAC-deficient cells, execution of PUMA-induced apoptosis is abrogated, in company with decreases in caspase activation, cytosolic release of cytochrome c and collapse of mitochondrial membrane potential. Reconstituting SMAC expression restored these events in the SMAC-deficient cells. Furthermore, SMAC and agents that mimic the inhibitor of apoptosis proteins (IAPs) inhibition function of SMAC significantly sensitize cells to PUMA-induced apoptosis. These results demonstrate an important role of SMAC in executing DNA damage-induced and PUMA-mediated apoptosis and suggest that SMAC participates in a feedback amplification loop to promote cytochrome c release and other mitochondrial events in apoptosis.

Colloidal lithography and current fabrication techniques producing in-plane nanotopography for biological applications.

Substrate topography plays a vital role in cell and tissue structure and function in situ, where nanometric features, for example, the detail on single collagen fibrils, influence cell behaviour and resultant tissue formation. In vitro investigations demonstrate that nanotopography can be used to control cell reactions to a material surface, indicating its potential application in tissue engineering and implant fabrication. Developments in the catalyst, optical, medical and electronics industries have resulted in the production of nanopatterned surfaces using a variety of methods. The general protocols for nanomanufacturing require high resolution and low cost for fabricating devices. With respect to biological investigations, nanotopographies should occur across a large surface area (ensuring repeatability of experiments and patterning of implant surfaces), be reproducible (allowing for consistency in experiments), and preferably, accessible (limiting the requirement for specialist equipment). Colloidal lithography techniques fit these criteria, where nanoparticles can be utilized in combination with a functionalized substrate to produce in-plane nanotopographies. Subsequent lithographic processing of colloidal substrates utilizing, for example, reactive ion etching allows the production of modified colloidal-derived nanotopographies. In addition to two-dimensional in-plane nanofabrication, functionalized structures can be dip coated in colloidal sols, imparting nanotopographical cues to cells within a three-dimensional environment.

[The efficiency (cost-effectiveness) of palivizumab as prophylaxis against respiratory syncytial virus infection in premature infants with a gestational age of 32-35 weeks in Spain]. / La eficiencia (coste-efectividad) de palivizumab como profilaxis para la infección por virus respiratorio sincitial en prematuros de 32-35 semanas en España.

OBJECTIVES: To evaluate the efficiency (cost-effectiveness) of palivizumab in preventing severe respiratory syncytial virus (RSV) infection in premature infants with a gestational age of 32-35 weeks (GA 32-35) and two or more risk factors (RF) in Spain. DESIGN: decision tree model using data from the scientific literature and the FLIP I and FLIP II studies (cohort of 326 infants with GA 32-35 and two or more RF who received palivizumab) sponsored by the Spanish Society of Neonatology. Main effectiveness measure: quality-adjusted life years (QALY) gained. PERSPECTIVES: the national health service (NHS), which includes direct costs (administration of palivizumab and hospital admissions), and the societal perspective, which also includes indirect costs (the child's future lost productivity). Discount: 3 % annually for effectiveness and indirect costs. Sensitivity analysis: construction of 37 scenarios modifying variables related to effectiveness and costs. RESULTS: Prophylaxis with palivizumab in premature infants with GA 32-35 and two or more RF produced an incremental cost-effectiveness ratio (ICER) of 13,849 euro/QALY from the NHS perspective, and an ICER of 4,605 euro/QALY from the societal perspective. In the sensitivity analysis, from the NHS perspective the ICER ranged from 5,351 euro/QALY (most favorable scenario) to 23,276 euro/QALY (least favorable scenario). CONCLUSIONS: Palivizumab is a cost-effective therapy as prophylaxis against RSV in infants with GA 32-35 and two or more RF. Its use is efficient from the NHS perspective, since the cost of a QALY, even in the least favorable scenarios, is lower than the threshold of 30,000 Euro/QALY considered socially acceptable in Spain.

Characterizing the efficacy of calcium channel agonist-release strategies for bone tissue engineering applications.

We have previously reported on the use of Bay K8644-release strategies in combination with perfusion-compression bioreactor systems for up regulating bone formation in three-dimensional PLLA scaffolds. Here we report on the analysis of Bay activity following its release from our PLLA scaffolds over the culture period imposed in our tissue engineering protocol using UV spectroscopy in combination with whole cell patch clamping techniques. Bay was released continually from scaffolds within the physiological range required for agonist activity (1-10 microM). Patch clamping allowed for the effects of Bay released from scaffolds to be monitored directly with respect to osteoblast electrophysiology. A characteristic shift in the current-voltage (I-V) relationship of L-type VOCC currents was observed in rat osteoblast sarcoma (ROS) cells patched in a solution with Bay released from scaffolds following 14 and 28 days incubation, with statistically significant differences observed in peak currents compared to non-Bay controls. An increase in the magnitude of the peak inward currents was also noted. The electrophysiological response of osteoblasts in the presence of Bay released from scaffolds demonstrates that the released Bay is stable and maintains its bioactivity following culture of up to 28 days.