Simple and convenient mapping of molecular dynamics mechanical property predictions of bisphenol-F epoxy for strain rate, temperature, and degree of cure.

It is well-known that all-atom molecular dynamics (MD) predictions of mechanical properties of thermoset resins suffer from multiple accuracy issues associated with their viscoelastic nature. The nanosecond simulation times of MD simulations do not allow for the direct simulation of the molecular conformational relaxations that occur under laboratory time scales. This adversely affects the prediction of mechanical properties at realistic strain rates, intermediate degrees of cure, and elevated temperatures. While some recent studies have utilized a time-temperature superposition approach to relate MD predictions to expected laboratory observations, such an approach becomes prohibitively difficult when simulating thermosets with a combination of strain rates, intermediate degrees of cure, and temperatures. In this study, a phenomenological approach is developed to map the predictions of Young's modulus and Poisson's ratio for a DGEBF/DETDA epoxy system to the corresponding laboratory-based properties for intermediate degrees of cure and temperatures above and below the glass transition temperature. The approach uses characterization data from dynamical mechanical analysis temperature sweep experiments. The mathematical formulation and experimental characterization of the mapping is described, and the resulting mapping of computationally-predicted to experimentally-observed elastic properties for various degrees of cure and temperatures are demonstrated and validated. This mapping is particularly important to mitigate the strain-rate effect associated with MD predictions, as well as to accurately predict mechanical properties at elevated temperatures and intermediate degrees of cure to facilitate accurate and efficient composite material process modeling.

Accurate predictions of thermoset resin glass transition temperatures from all-atom molecular dynamics simulation.

To enable the design and development of the next generation of high-performance composite materials, there is a need to establish improved computational simulation protocols for accurate and efficient prediction of physical, mechanical, and thermal properties of thermoset resins. This is especially true for the prediction of glass transition temperature (Tg), as there are many discrepancies in the literature regarding simulation protocols and the use of cooling rate correction factors for predicting values using molecular dynamics (MD) simulation. The objectives of this study are to demonstrate accurate prediction the Tg with MD without the use of cooling rate correction factors and to establish the influence of simulated conformational state and heating/cooling cycles on physical, mechanical, and thermal properties predicted with MD. The experimentally-validated MD results indicate that accurate predictions of Tg, elastic modulus, strength, and coefficient of thermal expansion are highly reliant upon establishing MD models with mass densities that match experiment within 2%. The results also indicate the cooling rate correction factors, model building within different conformational states, and the choice of heating/cooling simulation runs do not provide statistically significant differences in the accurate prediction of Tg values, given the typical scatter observed in MD predictions of amorphous polymer properties.

Maternal Choline Supplementation Modulates Placental Nutrient Transport and Metabolism in Late Gestation of Mouse Pregnancy.

Background: Fetal growth is dependent on placental nutrient supply, which is influenced by placental perfusion and transporter abundance. Previous research indicates that adequate choline nutrition during pregnancy improves placental vascular development, supporting the hypothesis that choline may affect placental nutrient transport.Objective: The present study sought to determine the impact of maternal choline supplementation (MCS) on placental nutrient transporter abundance and nutrient metabolism during late gestation.Methods: Female non-Swiss albino mice were randomly assigned to the 1×, 2×, or 4× choline diet (1.4, 2.8, and 5.6 g choline chloride/kg diet, respectively) 5 d before mating (n = 16 dams/group). The placentas and fetuses were harvested on gestational day (E) 15.5 and E18.5. The placental abundance of macronutrient, choline, and acetylcholine transporters and glycogen metabolic enzymes, and the placental concentration of glycogen were quantified. Choline metabolites and docosahexaenoic acid (DHA) concentrations were measured in the placentas and/or fetal brains. Data were stratified by gestational day and fetal sex and were analyzed by using mixed linear models.Results: At E15.5, MCS downregulated the placental transcript and protein abundance of glucose transporter 1 (GLUT1) (-40% to -73%, P < 0.05) and the placental transcript abundance of glycogen-synthesizing enzymes (-24% to -50%, P ≤ 0.05). At E18.5, MCS upregulated GLUT3 protein abundance (+55%, P = 0.016) and the transcript abundance of glycogen-synthesizing enzymes only in the female placentas (+36% to +60%, P < 0.05), resulting in a doubling (P = 0.01) of the glycogen concentration. A higher placental transcript abundance of the transporters for DHA, choline, and acetylcholine was also detected in response to MCS, consequently altering their concentrations in the placentas or fetal brains (P ≤ 0.05).Conclusions: These data suggest that MCS modulates placental nutrient transporter abundance and nutrient metabolism in late gestation of mouse pregnancy, with subsequent effects on nutrient supply for the developing fetus.

A physiological and behavioral system for hearing restoration with cochlear implants.

Cochlear implants are neuroprosthetic devices that provide hearing to deaf patients, although outcomes are highly variable even with prolonged training and use. The central auditory system must process cochlear implant signals, but it is unclear how neural circuits adapt-or fail to adapt-to such inputs. The knowledge of these mechanisms is required for development of next-generation neuroprosthetics that interface with existing neural circuits and enable synaptic plasticity to improve perceptual outcomes. Here, we describe a new system for cochlear implant insertion, stimulation, and behavioral training in rats. Animals were first ensured to have significant hearing loss via physiological and behavioral criteria. We developed a surgical approach for multichannel (2- or 8-channel) array insertion, comparable with implantation procedures and depth in humans. Peripheral and cortical responses to stimulation were used to program the implant objectively. Animals fitted with implants learned to use them for an auditory-dependent task that assesses frequency detection and recognition in a background of environmentally and self-generated noise and ceased responding appropriately to sounds when the implant was temporarily inactivated. This physiologically calibrated and behaviorally validated system provides a powerful opportunity to study the neural basis of neuroprosthetic device use and plasticity.

Latex barrier thin film formation on porous substrates.

Here we present the formation of thin layers of barrier polymers onto mesoporous and macroporous substrates via dip coating of latex solutions. We investigated four commercially available latex solutions: polytetrafluoroethylene (PTFE), perfluoroalkoxy fluorothermoplastic (PFA), polyvinylidene chloride (PVDC), and polyolefin-based latex (Hypod). We examined the latex film formation on porous polymeric and ceramic substrates with a broad range of pore sizes from 10 to 200 nm. Our results show that both characteristics of the latex solution [glass transition temperature (Tg), particle size, and crystallinity] and the characteristics of the porous substrate (pore size and hydrophobicity) impact the film formation. We confirmed the defect-free, barrier nature of our latex thin films through scanning electron microscopy (SEM), atomic force microscopy (AFM), and hydraulically driven water permeation tests. Additionally, we found that latex concentration (not dipping time) is the most important parameter determining ultimate latex film thickness. We obtained defect-free films from PVDC and Hypod, which are "soft" polymers (Tg < room temperature), on mesoporous substrates under the conditions of slow evaporation rate of the solvent from these latex solutions. PTFE and PFA, which are "hard" polymers (Tg > room temperature), did not form continuous films on porous substrates.

Behavioral Effects of Vaporized Delta-8 Tetrahydrocannabinol, Cannabidiol, and Mixtures in Male Rats.

Background: The popularity of delta-8 tetrahydrocannabinol (THC) and cannabidiol (CBD) products has seen a sharp increase in use during recent years. Despite the rise in use of these minor cannabinoids, there are little to no pre-clinical behavioral data on their effects, with most pre-clinical cannabis research focusing on the behavioral effects of delta-9 THC. The current experiments aimed to characterize the behavioral effects of delta-8 THC, CBD, and mixtures of these two drugs using a whole-body vapor exposure route of administration in male rats. Methods: Rats were exposed to vapor that contained different concentrations of delta-8 THC, CBD, or CBD/delta-8 THC mixtures during 10 min of exposure. Following 10 min of vapor exposure, locomotor behavior was monitored, or the warm-water tail withdrawal assay was conducted to measure the acute analgesic effects of the vapor exposure. Results: CBD and CBD/delta-8 THC mixtures resulted in a significant increase in locomotion across the entire session. Although delta-8 THC alone had no significant effect on locomotion across the session, the 10 mg concentration of delta-8 THC had a hyperlocomotion effect in the first 30 min of the session followed by a hypolocomotor effect later in the session. In the tail withdrawal assay, a 3/1 mixture of CBD/delta-8 THC resulted in an immediate analgesic effect compared to vehicle vapor. Finally, immediately following vapor exposure, all drugs had a hypothermic effect on body temperature compared to vehicle. Conclusion: This experiment is the first to characterize the behavioral effects of vaporized delta-8 THC, CBD, and CBD/delta-8 THC in male rats. While data were generally congruent with previous research investigating delta-9 THC, future studies should explore abuse liability and validate plasma blood concentrations of these drugs following administration through whole-body vapor exposure.

Salt sensitive purely zwitterionic physical hydrogel for prevention of postoperative tissue adhesion.

Abdominal adhesions are a class of serious complications following abdominal surgery, resulting in a complicated and severe syndrome and sometimes leading to a Gordian knot. Traditional therapies employ hydrogels synthesized using complicated chemical formulations-often with click chemistry or thermal responsive hydrogel. The complicated synthesis process and severe conditions limit the extent of the hydrogels' applications. In this work, poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) polymer was synthesized to self-assemble into physical hydrogels due to the inter- and intramolecular ion interactions. The strong static interaction bonding density has a substantial impact on the gelation and physicochemical properties, which is beneficial to clinical applications and offers a novel way to obtain the desired hydrogel for a specific biomedical application. Intriguingly, this PSBMA polymer can be customized into a transient network with outstanding antifouling capability depending on the ion concentration. As ion concentration increases, the PSBMA hydrogel dissociated completely, endowing it as a candidate for adhesion prevention. In the cecum-sidewall model, the PSBMA hydrogel demonstrated superior anti-adhesion properties than commercial HA hydrogel. Furthermore, we have demonstrated that this PSBMA hydrogel could inhibit the inflammatory response and encourage anti-fibrosis resulting in adhesion prevention. Most surprisingly, the recovered skins of cecum and sidewall are as smooth as the control skin without any scar and damage. In conclusion, a practical hydrogel was synthesized using a facile method based on purely zwitterionic materials, and this ion-sensitive, antifouling adjustable supramolecular hydrogel with great clinic transform potential is a promising barrier for preventing postoperative tissue adhesion. STATEMENT OF SIGNIFICANCE: The development of hydrogels with satisfactory coverage, long retention time, facile synthetic method, and good biocompatibility is vital for preventing peritoneal adhesions. Herein, we developed a salt sensitive purely zwitterionic physical hydrogel poly 3-[2-(methacryloyloxy)ethyl](dimethyl)-ammonio]-1-propanesulfonate (PSBMA) hydrogel to effectively prevent postoperative and recurrent abdominal adhesions. The hydrogel was simple to synthesize and easy to use. In the cecum-sidewall model, PSBMA hydrogel could instantaneously adhere and fix on irregular surfaces and stay in the wound for more than 10 days. The PSBMA hydrogel could inhibit the inflammatory response, encourage anti-fibrosis, and restore smoothness to damaged surfaces resulting in adhesion prevention. Overall, the PSBMA hydrogel is a promising candidate for the next generation of anti-adhesion materials to meet clinical needs.

Evolution of Glassy Carbon Derived from Pyrolysis of Furan Resin.

Glassy carbon (GC) material derived from pyrolyzed furan resin was modeled by using reactive molecular dynamics (MD) simulations. The MD polymerization simulation protocols to cure the furan resin precursor material are validated via comparison of the predicted density and Young's modulus with experimental values. The MD pyrolysis simulations protocols to pyrolyze the furan resin precursor is validated by comparison of calculated density, Young's modulus, carbon content, sp2 carbon content, the in-plane crystallite size, out-of-plane crystallite stacking height, and interplanar crystallite spacing with experimental results from the literature for furan resin derived GC. The modeling methodology established in this work can provide a powerful tool for the modeling-driven design of next-generation carbon-carbon composite precursor chemistries for thermal protection systems and other high-temperature applications.

Injectable Zwitterionic Physical Hydrogel with Enhanced Chemodynamic Therapy and Tumor Microenvironment Remodeling Properties for Synergistic Anticancer Therapy.

Surgical resection is the first-line therapy for breast cancer. However, residual tumor cells and the highly immunosuppressive tumor microenvironment (TME) continue to have a serious impact on tumor recurrence and metastasis postresection. Implantation of an in situ hydrogel system postresection has shown to be an effective treatment with great clinical potential. Herein, an injectable zwitterionic hydrogel system was developed for local drug delivery with enhanced immune activation and prevention of tumor recurrence. Driven by electrostatic interactions, poly(sulfobetaine methacrylate) (PSBMA) self-assembles into a hydrogel in saline, achieving low protein adsorption and tunable biodegradability. The chemotherapy drug doxorubicin (DOX) was loaded into copper peroxide nanoparticles (CuO2/DOX), which were coated with macrophage membranes to form tumor-targeting nanoparticles (M/CuO2/DOX). Next, M/CuO2/DOX and the stimulator of interferon genes (STING) agonist 2',3'-cGAMP were coloaded into PSBMA hydrogel (Gel@M/CuO2/DOX/STING). The hydrophilic STING agonist was first released by diffusion from hydrogel to activate the STING pathway and upregulate interferon (IFN) signaling related genes, remodeling the immunosuppressive TME. Then, M/CuO2/DOX targeted the residual tumor cells, combining with DOX-induced DNA damage, immunogenic tumor cell death, and copper death. Hence, this work combines chemodynamic therapy with STING pathway activation in TME, encouraging residual tumor cell death, promoting the maturation of dendritic cells, enhancing tumor-specific CD8+ T cell infiltration, and preventing postoperative recurrence and metastasis.

Mechanical Properties and Characterization of Epoxy Composites Containing Highly Entangled As-Received and Acid Treated Carbon Nanotubes.

Huntsman-Merrimack MIRALON® carbon nanotubes (CNTs) are a novel, highly entangled, commercially available, and scalable format of nanotubes. As-received and acid-treated CNTs were added to aerospace grade epoxy (CYCOM® 977-3), and the composites were characterized. The epoxy resin is expected to infiltrate the network of the CNTs and could improve mechanical properties. Epoxy composites were tested for flexural and viscoelastic properties and the as-received and acid treated CNTs were characterized using Field-Emission Scanning and Transmission Electron Microscopy, X-Ray Photoelectron Spectroscopy, and Thermogravimetric Analysis. Composites containing 0.4 wt% as-received CNTs showed an increase in flexural strength, from 136.9 MPa for neat epoxy to 147.5 MPa. In addition, the flexural modulus increased from 3.88 GPa for the neat epoxy to 4.24 GPa and 4.49 GPa for the 2.0 wt% and 3.0 wt% as-received CNT/epoxy composites, respectively. FE-SEM micrographs indicated good dispersion of the CNTs in the as-received CNT/epoxy composites and the 10 M nitric acid 6 h treatment at 120 °C CNT/epoxy composites. CNTs treated with 10 M nitric acid for 6 h at 120 °C added oxygen containing functional groups (C-O, C=O, and O=C-O) and removed iron catalyst present on the as-received CNTs, but the flexural properties were not improved compared to the as-received CNT/epoxy composites.

Applying a novel cost-evaluation framework to assess video-based neurosurgery education.

BACKGROUND: Analysis of comparative effectiveness uses different metrics to ensure that a new treatment is both effective and economical. However, there is a lack of financial frameworks to estimate the costs of introducing new technologies in medical and surgical education. METHODS: After conducting a literature review, we created and applied a framework ('REC') for the evaluation of three recent neurosurgery video modules aimed at medical students at Harvard Medical School. RESULTS: The most expensive component of these video-based education (VBE) modules was time cost. This cost was highly variable depending on the level of clinical seniority of the individuals involved in the video production process. CONCLUSION: Application of the REC framework to the three modules showed highly variable time and monetary cost differences between the modules. Usage of the REC framework will enable educators to institute effective planning, efficiently use resources, and clearly define a minimal viable education product to achieve desired learning outcomes.

Sarcopenia--mechanisms and treatments.

BACKGROUND: Sarcopenia is a consequence of aging. This atrophic event is responsible for decrease in strength and associated functional deficits seen in the aging adult. PURPOSE: This paper reviews: (1) the mechanisms contributing to sarcopenia, (2) the impact of age-related changes in muscle composition on 3 processes integral to muscle function, (3) the efficacy of pharmaceuticals and over-the-counter nutritional supplements in the management of sarcopenia, (4) experimental use of pharmaceutical regulation of myostatin to increase muscle mass and strength in animal models, and (5) efficacy of resistance training as a means of maintaining or recovering muscle mass and strength. METHODS: PubMed was searched for relevant research articles using the following descriptors: sarcopenia, aging, muscle mass, muscle performance, muscle strength, myostatin, testosterone, growth hormone, dehydroepiandrosterone, hormone replacement, nutrition, resistance training, and endurance training. RESULTS: Sarcopenia is mediated by multiple mechanisms, including alpha-motor neuron death, altered hormone concentrations, increased inflammation, and altered nutritional status. Age-related changes within muscle likely affect processes integral to muscle function. These changes negatively influence muscle performance directly or by contributing to sarcopenia. Pharmaceutical or supplement interventions to treat sarcopenia have not proved encouraging to date, either lacking or providing limited efficacy, along with the potential for negative health consequences. In contrast, resistance training has proven safe and highly effective for increasing muscle mass and strength in aging adults. CONCLUSION: Sarcopenia is a multifactorial consequence of aging that will affect many adults. Resistance training is the most effective and safe intervention to attenuate or recover some of the loss of muscle mass and strength that accompanies aging.

Maternal Choline Supplementation Modulates Placental Markers of Inflammation, Angiogenesis, and Apoptosis in a Mouse Model of Placental Insufficiency.

Dlx3 (distal-less homeobox 3) haploinsufficiency in mice has been shown to result in restricted fetal growth and placental defects. We previously showed that maternal choline supplementation (4X versus 1X choline) in the Dlx3+/- mouse increased fetal and placental growth in mid-gestation. The current study sought to test the hypothesis that prenatal choline would modulate indicators of placenta function and development. Pregnant Dlx3+/- mice consuming 1X (control), 2X, or 4X choline from conception were sacrificed at embryonic (E) days E10.5, E12.5, E15.5, and E18.5, and placentas and embryos were harvested. Data were analyzed separately for each gestational day controlling for litter size, fetal genotype (except for models including only +/- pups), and fetal sex (except when data were stratified by this variable). 4X choline tended to increase (p < 0.1) placental labyrinth size at E10.5 and decrease (p < 0.05) placental apoptosis at E12.5. Choline supplementation decreased (p < 0.05) expression of pro-angiogenic genes Eng (E10.5, E12.5, and E15.5), and Vegf (E12.5, E15.5); and pro-inflammatory genes Il1b (at E15.5 and 18.5), Tnfα (at E12.5) and Nfκb (at E15.5) in a fetal sex-dependent manner. These findings provide support for a modulatory effect of maternal choline supplementation on biomarkers of placental function and development in a mouse model of placental insufficiency.

Maternal choline supplementation alters vitamin B-12 status in human and murine pregnancy.

Despite participation in overlapping metabolic pathways, the relationship between choline and vitamin B-12 has not been well characterized especially during pregnancy. We sought to determine the effects of maternal choline supplementation on vitamin B-12 status biomarkers in human and mouse pregnancy, hypothesizing that increased choline intake would improve vitamin B-12 status. Associations between common genetic variants in choline-metabolizing genes and vitamin B-12 status biomarkers were also explored in humans. Healthy third-trimester pregnant women (n=26) consumed either 480 or 930 mg choline/day as part of a 12-week controlled feeding study. Wild-type NSA and Dlx3 heterozygous (Dlx3+/-) mice, which display placental insufficiency, consumed a 1×, 2× or 4× choline diet and were sacrificed at gestational days 15.5 and 18.5. Serum vitamin B-12, methylmalonic acid (MMA) and homocysteine were measured in all samples; holotranscobalamin (in humans) and hepatic vitamin B-12 (in mice) were also measured. The 2× choline supplementation for 12 weeks in pregnant women yielded higher serum concentrations of holotranscobalamin, the bioactive form of vitamin B-12 (~24%, P=.01). Women with genetic variants in choline dehydrogenase (CHDH) and betaine-homocysteine S-methyltransferase (BHMT) had higher serum MMA concentrations (~31%, P=.03) and lower serum holotranscobalamin concentrations (~34%, P=.03), respectively. The 4× choline dose decreased serum homocysteine concentrations in both NSA and Dlx3+/- mice (~36% and~43% respectively, P≤.015). In conclusion, differences in choline supply due to supplementation or genetic variation modulate vitamin B-12 status during pregnancy, supporting a functional relationship between these nutrients.

Maternal Choline Supplementation during Normal Murine Pregnancy Alters the Placental Epigenome: Results of an Exploratory Study.

The placental epigenome regulates processes that affect placental and fetal development, and could be mediating some of the reported effects of maternal choline supplementation (MCS) on placental vascular development and nutrient delivery. As an extension of work previously conducted in pregnant mice, the current study sought to explore the effects of MCS on various epigenetic markers in the placenta. RNA and DNA were extracted from placentas collected on embryonic day 15.5 from pregnant mice fed a 1X or 4X choline diet, and were subjected to genome-wide sequencing procedures or mass-spectrometry-based assays to examine placental imprinted gene expression, DNA methylation patterns, and microRNA (miRNA) abundance. MCS yielded a higher (fold change = 1.63-2.25) expression of four imprinted genes (Ampd3, Tfpi2, Gatm and Aqp1) in the female placentas and a lower (fold change = 0.46-0.62) expression of three imprinted genes (Dcn, Qpct and Tnfrsf23) in the male placentas (false discovery rate (FDR) ≤ 0.05 for both sexes). Methylation in the promoter regions of these genes and global placental DNA methylation were also affected (p ≤ 0.05). Additionally, a lower (fold change = 0.3; Punadjusted = 2.05 × 10-4; FDR = 0.13) abundance of miR-2137 and a higher (fold change = 1.25-3.92; p < 0.05) expression of its target genes were detected in the 4X choline placentas. These data demonstrate that the placental epigenome is responsive to maternal choline intake during murine pregnancy and likely mediates some of the previously described choline-induced effects on placental and fetal outcomes.

Maternal Choline Supplementation Alters Fetal Growth Patterns in a Mouse Model of Placental Insufficiency.

Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/- (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/- female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations of hepatic and placental betaine were detected in 4X versus 1X choline, and placental betaine was positively associated with embryo weight. Placental mRNA expression of Igf1 was downregulated by 4X (versus 1X) choline at E10.5. No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline. MCS improved fetal growth during early pregnancy in the Dlx3+/- mice with the compensatory downregulation of Igf1 to slow growth as gestation progressed. Placental betaine may be responsible for the growth-promoting effects of choline.

The metabolic fate of isotopically labeled trimethylamine-N-oxide (TMAO) in humans.

Trimethylamine-N-oxide (TMAO) is associated with chronic disease risk. However, little is known about the metabolic fate of dietary TMAO. This study sought to quantitatively elucidate the metabolic fate of orally consumed TMAO in humans. As part of a crossover feeding study, healthy young men (n=40) consumed 50-mg deuterium-labeled methyl d9-TMAO (d9-TMAO), and enrichments of TMAO and its derivatives were measured in blood for 6 h, urine and stool, as well as skeletal muscle in a subset of men (n=6). Plasma d9-TMAO was detected as early as 15 min, increased until 1 h and remained elevated through the 6-h period. TMAO exhibited an estimated turnover time of 5.3 h, and ~96% of the dose was eliminated in urine by 24 h, mainly as d9-TMAO. No d9-TMAO was detected in feces. Notably, d9-TMAO and d9-trimethylamine were detected in skeletal muscle (n=6) at 6 h, and the enrichment ratio of d9-TMAO to d9-trimethylamine was influenced by a genetic variant in flavin-containing monooxygenase isoform 3 (FMO3 G472A). These results suggest that the absorption of orally consumed TMAO is near complete and does not require processing by gut microbes. TMAO exhibits fast turnover in the circulation with the majority being eliminated in urine within 24 h. A small portion of the dose, however, is taken up by extrahepatic tissue in a manner that appears to be under the influence of FMO3 G472A polymorphism. This trial was registered at clinicaltrials.gov as NCT02558673.

Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner.

INTRODUCTION: Normal placental vascular development is influenced by inflammatory, angiogenic and apoptotic processes, which may be modulated by choline through its role in membrane biosynthesis, cellular signaling and gene expression regulation. The current study examined the effect of maternal choline supplementation (MCS) on placental inflammatory, angiogenic and apoptotic processes during murine pregnancy. METHOD: Pregnant dams were randomized to receive 1, 2 or 4 times (X) the normal choline content of rodent diets, and tissues were harvested on embryonic day (E) 10.5, 12.5, 15.5 or 18.5 for gene expression, protein abundance and immunohistochemical analyses. RESULTS: The choline-induced changes in the inflammatory and angiogenic markers were a function of fetal sex. Specifically, 4X (versus 1X) choline reduced the transcript (P ≤ 0.05) and protein (P ≤ 0.06) expression of TNF-a and IL-1ß in the male placentas at E10.5 and E18.5, respectively. In the female placentas, 4X (versus 1X) choline modulated the transcript expression of Il1b in a biphasic pattern with reduced Il1b at E12.5 (P = 0.045) and E18.5 (P = 0.067) but increased Il1b at E15.5 (P = 0.031). MCS also induced an upregulation of Vegfa expression in the female placentas at E15.5 (P = 0.034; 4X versus 2X) and E18.5 (P = 0.026; 4X versus 1X). MCS decreased (P = 0.011; 4X versus 1X) placental apoptosis at E10.5. Additionally, the luminal area of the maternal spiral arteries was larger (P ≤ 0.05; 4X versus 1X) in response to extra choline throughout gestation. DISCUSSION: MCS during murine pregnancy has fetal sex-specific effects on placental inflammation and angiogenesis, with possible consequences on placental vascular development.

In vitro flexural properties of hydroxyapatite and self-reinforced poly(L-lactic acid).

Poly(L-lactic acid) (PLLA) has been used for fracture fixation devices, but its use is limited because of its poor biocompatibility and mechanical properties. The effects of extrusion, incorporation of hydroxyapatite (HA) and self-reinforced composites (SRCs) on the resultant mechanical properties of PLLA were examined. Samples were conditioned for up to 52 weeks in PBS at 37 degrees C. Extrusion did not adversely affect the mechanical properties of PLLA. After in vitro conditioning, a slight but significant reduction in the strain to failure and modulus was seen. HA (10-40%) by weight was evenly distributed into PLLA using an intermeshing twin-screw extruder. As ceramic content increased, the initial modulus increased but flexural strength decreased. After immersion, the modulus of all HA-PLLA blends was lower than PLLA. HA particles did not form a strong bond with the PLLA, which promoted easier degradation of the HA-PLLA matrix. SRCs showed a higher modulus and strength when compared to all materials except the modulus of 30 and 40% HA-PLLA composites before immersion. Water preferentially attacked the matrix of the composite, leading to more fiber pullout, but the fiber orientation maintained the advantages in strength and modulus up to 24 weeks in vitro.

Nanoindentation of injection molded PLA and self-reinforced composite PLA after in vitro conditioning for three months.

Poly(lactic acid) (PLA) is used for medical devices such as sutures or orthopedic screws. A standard way to determine the loss of mechanical properties of a degradable polymer would be to soak the polymer in phosphate buffered saline (PBS) and test the desired property as a function of immersion time. This method is not sensitive enough to discern changes in mechanical properties through the cross-section of the polymer and neglects the degradation that is occurring at the molecular level. This article presents results of a nanoindentation study carried out with PLA. The modulus and hardness of PLA is characterized as a function of processing method, immersion time in PBS, and location of the indent. Measuring local properties with the nanoindenter allowed detection of differences in material properties as a function of all three of these variables. The mechanical properties on the edge were lower than the interior of the sample after in vitro degradation, and changes were seen earlier for nanoindentation than for traditional flexural or tensile tests. The nanoindenter is a valuable tool for quantifying changes in material properties and may have applicability for accelerated tests to screen biomaterials.