Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation.

BACKGROUND: Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired. OBJECTIVE: To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation. STUDY DESIGN: This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8 ± 2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200 mg/day) or high dose (800 or 1000 mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose. RESULTS: Participants who consumed less than 150 mg/day DHA prior to 20 weeks' gestation (n = 810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp = 0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp = 0.97). CONCLUSION: The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice.

Validation of an abbreviated food frequency questionnaire for estimating DHA intake of pregnant women in the United States.

Docosahexaenoic acid (DHA) intake was estimated in pregnant women between 12- and 20-weeks' gestation using the National Cancer Institute's (NCI) Diet History Questionnaire-II (DHQ-II) and a 7-question screener designed to capture DHA intake (DHA Food Frequency Questionnaire, DHA-FFQ). Results from both methods were compared to red blood cell phospholipid DHA (RBC-DHA) weight percent of total fatty acids. DHA intake from the DHA-FFQ was more highly correlated with RBC-DHA (rs=0.528) than the DHQ-II (rs=0.352). Moreover, the DHA-FFQ allowed us to obtain reliable intake data from 1355 of 1400 participants. The DHQ-II provided reliable intake for only 847 of 1400, because many participants only partially completed it and it was not validated for Hispanic participants. Maternal age, parity, and socioeconomic status (SES) were also significant predictors of RBC-DHA. When included with estimated intake from the DHA-FFQ, the model accounted for 36% of the variation in RBC-DHA.

A customized framework for regional classification of conifers using automated feature extraction.

Pinyon and juniper expansion into sagebrush ecosystems is one of the major challenges facing land managers in the Great Basin. Effective pinyon and juniper treatment requires maps that accurately and precisely depict tree location and degree of woodland development so managers can target restoration efforts for early stages of pinyon and juniper expansion. However, available remotely sensed layers that cover a regional spatial extent lack the spatial resolution or accuracy to meet this need. Accuracy can be improved using object-based image analysis methods such as automated feature extraction, which has proven successful in accurately classifying land cover at the site-level but to date has yet to be applied to regional extents due to time and computational limitations. Using Feature Analyst™, we implement our framework with 1-m2 reference imagery provided by National Agricultural Imagery Program to classify conifers across Nevada and northeastern California. Our resulting binary conifer map has an overall accuracy of 86%. We discuss the advantages to accuracy and precision our framework provides compared to other classification methods. ● This framework allows automated feature extraction for large quantities of data and very high spatial resolution imagery ● It leverages supervised learning ● It results in high accuracy maps for regional spatial extents.

Higher maternal weight is related to poorer fetal autonomic function.

Maternal obesity is an established risk factor for poor infant neurodevelopmental outcomes; however, the link between maternal weight and fetal development in utero is unknown. We investigated whether maternal obesity negatively influences fetal autonomic nervous system (ANS) development. Fetal heart rate variability (HRV) is an index of the ANS that is associated with neurodevelopmental outcomes in the infant. Maternal-fetal magnetocardiograms were recorded using a fetal biomagnetometer at 36 weeks (n = 46). Fetal HRV was represented by the standard deviation of sinus beat-to-beat intervals (SDNN). Maternal weight was measured at enrollment (12-20 weeks) and 36 weeks. The relationships between fetal HRV and maternal weight at both time points were modeled using adjusted ordinary least squares regression models. Higher maternal weight at enrollment and 36 weeks were associated with lower fetal HRV, an indicator of poorer ANS development. Further study is needed to better understand how maternal obesity influences fetal autonomic development and long-term neurodevelopmental outcomes.

A conservation planning tool for Greater Sage-grouse using indices of species distribution, resilience, and resistance.

Managers require quantitative yet tractable tools that identify areas for restoration yielding effective benefits for targeted wildlife species and the ecosystems they inhabit. As a contemporary example of high national significance for conservation, the persistence of Greater Sage-grouse (Centrocercus urophasianus) in the Great Basin is compromised by strongly interacting stressors of conifer expansion, annual grass invasion, and more frequent wildfires occurring in sagebrush ecosystems. Associated restoration treatments to a sagebrush-dominated state are often costly and may yield relatively little ecological benefit to sage-grouse if implemented without estimating how Sage-grouse may respond to treatments, or do not consider underlying processes influencing sagebrush ecosystem resilience to disturbance and resistance to invasive species. Here, we describe example applications of a spatially explicit conservation planning tool (CPT) to inform prioritization of: (1) removal of conifers (i.e., pinyon-juniper); and (2) wildfire restoration aimed at improving habitat conditions for the Bi-State Distinct Population Segment of Sage-grouse along the California-Nevada state line. The CPT measures ecological benefits to sage-grouse for a given management action through a composite index comprised of resource selection functions and estimates of abundance and space use. For pinyon-juniper removal, we simulated changes in land-cover composition following the removal of sparse trees with intact understories, and ranked treatments on the basis of changes in ecological benefits per dollar-unit of cost. For wildfire restoration, we formulated a conditional model to simulate scenarios for land cover changes (e.g., sagebrush to annual grass) given estimated fire severity and underlying ecosystem processes influencing resilience to disturbance and resistance to invasion by annual grasses. For both applications, we compared CPT rankings to land cover changes along with sagebrush resistance and resilience metrics. Model results demonstrated how the CPT can be an important step in identifying management projects that yield the highest quantifiable benefit to Sage-grouse while avoiding costly misallocation of resources, and highlight the importance of considering changes in sage-grouse ecological response and factors influencing sagebrush ecosystem resilience to disturbance and resistance to invasion. This unique framework can be adopted to help inform other management questions aimed at improving habitat for other species across sagebrush and other ecosystems.

Integrating spatially explicit indices of abundance and habitat quality: an applied example for greater sage-grouse management.

Predictive species distributional models are a cornerstone of wildlife conservation planning. Constructing such models requires robust underpinning science that integrates formerly disparate data types to achieve effective species management.Greater sage-grouse Centrocercus urophasianus, hereafter 'sage-grouse' populations are declining throughout sagebrush-steppe ecosystems in North America, particularly within the Great Basin, which heightens the need for novel management tools that maximize the use of available information.Herein, we improve upon existing species distribution models by combining information about sage-grouse habitat quality, distribution and abundance from multiple data sources. To measure habitat, we created spatially explicit maps depicting habitat selection indices (HSI) informed by >35 500 independent telemetry locations from >1600 sage-grouse collected over 15 years across much of the Great Basin. These indices were derived from models that accounted for selection at different spatial scales and seasons. A region-wide HSI was calculated using the HSI surfaces modelled for 12 independent subregions and then demarcated into distinct habitat quality classes.We also employed a novel index to describe landscape patterns of sage-grouse abundance and space use (AUI). The AUI is a probabilistic composite of the following: (i) breeding density patterns based on the spatial configuration of breeding leks and associated trends in male attendance; and (ii) year-round patterns of space use indexed by the decreasing probability of use with increasing distance to leks. The continuous AUI surface was then reclassified into two classes representing high and low/no use and abundance. Synthesis and applications. Using the example of sage-grouse, we demonstrate how the joint application of indices of habitat selection, abundance and space use derived from multiple data sources yields a composite map that can guide effective allocation of management intensity across multiple spatial scales. As applied to sage-grouse, the composite map identifies spatially explicit management categories within sagebrush steppe that are most critical to sustaining sage-grouse populations as well as those areas where changes in land use would likely have minimal impact. Importantly, collaborative efforts among stakeholders guide which intersections of habitat selection indices and abundance and space use classes are used to define management categories. Because sage-grouse are an umbrella species, our joint-index modelling approach can help target effective conservation for other sagebrush obligate species and can be readily applied to species in other ecosystems with similar life histories, such as central-placed breeding.

Nondiffusive transport regimes for suprathermal ions in turbulent plasmas.

The understanding of the transport of suprathermal ions in the presence of turbulence is important for fusion plasmas in the burning regime that will characterize reactors, and for space plasmas to understand the physics of particle acceleration. Here, three-dimensional measurements of a suprathermal ion beam in the toroidal plasma device TORPEX are presented. These measurements demonstrate, in a turbulent plasma, the existence of subdiffusive and superdiffusive transport of suprathermal ions, depending on their energy. This result stems from the unprecedented combination of uniquely resolved measurements and first-principles numerical simulations that reveal the mechanisms responsible for the nondiffusive transport. The transport regime is determined by the interaction of the suprathermal ion orbits with the turbulent plasma dynamics, and is strongly affected by the ratio of the suprathermal ion energy to the background plasma temperature.

Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation.

Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.

Tradeoff between establishing an infection and killing the host: response of snails ( Physa acuta) to a gradient of trematode (Halipegus eccentricus) exposures.

Pond snails ( Physa acuta ) were exposed to a gradient (0, 1, 3, 5, 10, 15, 20, 25, 30, 35, 40, and 50) of trematode (Halipegus eccentricus) eggs and observed to determine egg dose effects on the survival of snails through the prepatent period, snail reproduction, and the production of cercariae. The probability of snail survival through the prepatent period significantly decreased with increasing egg exposures, where the odds of snail survival was 0.94 per trematode egg. Similarly, the probability of snail reproduction significantly decreased with increasing egg exposures, where the odds of snail reproduction was 0.85 per trematode egg. In contrast, the probability of a snail shedding cercariae significantly increased with increasing egg exposures, where the odds of reaching a patent infection were 1.64 per trematode egg. However, snails shedding cercariae that were exposed to higher doses of trematode eggs tended to die sooner. Thus, there appears to be a tradeoff between infecting a snail and killing the host.

Effects of docosahexaenoic acid supplementation during pregnancy on fetal heart rate and variability: a randomized clinical trial.

DHA (22:6n-3) supplementation during infancy has been associated with lower heart rate (HR) and improved neurobehavioral outcomes. We hypothesized that maternal DHA supplementation would improve fetal cardiac autonomic control and newborn neurobehavior. Pregnant women were randomized to 600 mg/day of DHA or placebo oil capsules at 14.4 (+/-4) weeks gestation. Fetal HR and HRV were calculated from magnetocardiograms (MCGs) at 24, 32 and 36 weeks gestational age (GA). Newborn neurobehavior was assessed using the Neonatal Behavioral Assessment Scale (NBAS). Post-partum maternal and infant red blood cell (RBC) DHA was significantly higher in the supplemented group as were metrics of fetal HRV and newborn neurobehavior in the autonomic and motor clusters. Higher HRV is associated with more responsive and flexible autonomic nervous system (ANS). Coupled with findings of improved autonomic and motor behavior, these data suggest that maternal DHA supplementation during pregnancy may impart an adaptive advantage to the fetus.

Nondiffusive suprathermal ion transport in simple magnetized toroidal plasmas.

We investigate suprathermal ion dynamics in simple magnetized toroidal plasmas in the presence of electrostatic turbulence driven by the ideal interchange instability. Turbulent fields from fluid simulations are used in the nonrelativistic equation of ion motion to compute suprathermal tracer ion trajectories. Suprathermal ion dispersion starts with a brief ballistic phase, during which particles do not interact with the plasma, followed by a turbulence interaction phase. In this one simple system, we observe the entire spectrum of suprathermal ion dynamics, from subdiffusion to superdiffusion, depending on beam energy and turbulence amplitude. We estimate the duration of the ballistic phase and identify basic mechanisms during the interaction phase that determine the dependencies of the character of suprathermal ion dispersion upon the beam energy and turbulence fluctuation amplitude.

Patient preferences for next generation neural prostheses to restore bladder function.

STUDY DESIGN: A survey administered to 66 individuals with spinal cord injury (SCI) implementing a choice-based conjoint (CBC) analysis. Six attributes with three levels each were defined and used to generate choice sets with treatment scenarios. Patients were asked to choose the scenario that they preferred most. OBJECTIVES: To determine the utility weights for treatment characteristics as well as the overall preference for the three types of neural prostheses (NP), that is Brindley, rhizotomy-free Brindley, and pudendal nerve stimulation. Earlier studies have revealed the importance of restoration of bladder function, but no studies have been performed to determine the importance of NP features. SETTING: Two academic affiliated medical systems' SCI outpatient and inpatient rehabilitation programs, Cleveland, OH. METHODS: CBC analysis followed by multinomial logit modeling. Individual part-worth utilities were estimated using hierarchical Bayes. RESULTS: Side effects had the greatest significant impact on subject choices, followed by the effectiveness on continence and voiding. NPs with rhizotomy-free sacral root stimulation were preferred (45% first choice) over pudendal afferent nerve stimulation (39% second choice) and sacral root stimulation with rhizotomy (53% third choice). Almost 20% did not want to have an NP at all times. CONCLUSION: CBC has shown to be a valuable tool to support design choices. The data showed that persons would prefer a bladder NP with minimally invasive electrodes, which would give them complete bladder function, with no side effects and that can be operated by pushing a button and they do not have to recharge themselves.

AMPA receptor subunit GluR1 downstream of D-1 dopamine receptor stimulation in nucleus accumbens shell mediates increased drug reward magnitude in food-restricted rats.

Previous findings suggest that neuroadaptations downstream of D-1 dopamine (DA) receptor stimulation in nucleus accumbens (NAc) are involved in the enhancement of drug reward by chronic food restriction (FR). Given the high co-expression of D-1 and GluR1 AMPA receptors in NAc, and the regulation of GluR1 channel conductance and trafficking by D-1-linked intracellular signaling cascades, the present study examined effects of the D-1 agonist, SKF-82958, on NAc GluR1 phosphorylation, intracranial electrical self-stimulation reward (ICSS), and reversibility of reward effects by a polyamine GluR1 antagonist, 1-NA-spermine, in ad libitum fed (AL) and FR rats. Systemically administered SKF-82958, or brief ingestion of a 10% sucrose solution, increased NAc GluR1 phosphorylation on Ser845, but not Ser831, with a greater effect in FR than AL rats. Microinjection of SKF-82958 in NAc shell produced a reward-potentiating effect that was greater in FR than AL rats, and was reversed by co-injection of 1-NA-spermine. GluR1 abundance in whole cell and synaptosomal fractions of NAc did not differ between feeding groups, and microinjection of AMPA, while affecting ICSS, did not exert greater effects in FR than AL rats. These results suggest a role of NAc GluR1 in the reward-potentiating effect of D-1 DA receptor stimulation and its enhancement by FR. Moreover, GluR1 involvement appears to occur downstream of D-1 DA receptor stimulation rather than reflecting a basal increase in GluR1 expression or function. Based on evidence that phosphorylation of GluR1 on Ser845 primes synaptic strengthening, the present results may reflect a mechanism via which FR normally facilitates reward-related learning to re-align instrumental behavior with environmental contingencies under the pressure of negative energy balance.

In vivo demonstration of a self-sustaining, implantable, stimulated-muscle-powered piezoelectric generator prototype.

An implantable, stimulated-muscle-powered piezoelectric active energy harvesting generator was previously designed to exploit the fact that the mechanical output power of muscle is substantially greater than the electrical power necessary to stimulate the muscle's motor nerve. We reduced to practice the concept by building a prototype generator and stimulator. We demonstrated its feasibility in vivo, using rabbit quadriceps to drive the generator. The generated power was sufficient for self-sustaining operation of the stimulator and additional harnessed power was dissipated through a load resistor. The prototype generator was developed and the power generating capabilities were tested with a mechanical muscle analog. In vivo generated power matched the mechanical muscle analog, verifying its usefulness as a test-bed for generator development. Generator output power was dependent on the muscle stimulation parameters. Simulations and in vivo testing demonstrated that for a fixed number of stimuli/minute, two stimuli applied at a high frequency generated greater power than single stimuli or tetanic contractions. Larger muscles and circuitry improvements are expected to increase available power. An implanted, self-replenishing power source has the potential to augment implanted battery or transcutaneously powered electronic medical devices.

The feline dorsal nerve of the penis arises from the deep perineal nerve and not the sensory afferent branch.

The cat has been used extensively as an animal model for urogenital studies involving the pudendal nerve. However, discrepancies persist in the literature regarding the origin of the dorsal nerve of the penis (DNP). This study used gross dissections and serial histological cross sections to demonstrate that the DNP arises from the deep perineal nerve and not the sensory afferent branch as previously reported. This finding indicates a better than previously appreciated neuroanatomical homology between the cat and human.

Non-nutritive sucking recorded in utero via fetal magnetography.

Several studies in term and pre-term infants have investigated the rhythmic pattern of non-nutritive sucking (NNS) indicating correlations between the quantitative measures derived from sucking pressure variation and/or electromyographic (EMG) recordings and a range of factors that include age, perinatal stress and sequelae. In the human fetus, NNS has been reported from 13 weeks of gestation and has been studied using real-time Doppler ultrasonography exclusively. The present study indicates that NNS in fetus can be reliably recorded and quantified using non-invasive biomagnetic measurements that have been recently introduced as an investigational tool for the assessment of fetal neurophysiologic development. We show that source separation techniques, such as independent component analysis, applied to the high-resolution multichannel recordings allow the segregation of an explicit waveform that represents the biomagnetic equivalent of the ororhythmic sucking pressure variation or EMG signal recorded in infants. This enables the morphological study of NNS patterning over different temporal scales, from the global quantitative measures to the within burst fine structure characterization, in correlation with the fetal cardiac rhythm.

Magnetographic assessment of fetal hiccups and their effect on fetal heart rhythm.

Fetal hiccups emerge as early as nine weeks post-conception, being the predominant diaphragmatic movement before 26 weeks of gestation. They are considered as a programmed isometric inspiratory muscle exercise of the fetus in preparation for the post-natal respiratory function, or a manifestation of a reflex circuitry underlying the development of suckling and gasping patterns. The present paper provides the first evidence of non-invasive biomagnetic measurements of the diaphragm spasmodic contractions associated with fetal hiccups. The magnetic field patterns generated by fetal hiccups exhibit well-defined morphological features, consisting of an initial high frequency transient waveform followed by a more prolonged low frequency component. This pattern is consistent across recordings obtained from two fetal subjects, and it is confirmed by signals recorded in a neonatal subject. These results demonstrate that fetal biomagnetometry can provide insights into the electrophysiological mechanisms of diaphragm motor function in the fetus. Additionally, we study the correlation between hiccup events and fetal cardiac rhythm and provide evidence that hiccups may modulate the fetal heart rate during the last trimester of pregnancy.

Design considerations for an implantable, muscle powered piezoelectric system for generating electrical power.

A totally implantable piezoelectric generator system able to harness power from electrically activated muscle would augment the power systems of implanted functional electrical stimulation devices by reducing the number of battery replacement surgeries or by allowing periods of untethered functionality. The generator design contains no moving parts and uses a portion of the generated power for system operation. A software model of the system was developed and simulations performed to predict the output power as the system parameters were varied within their constraints. Mechanical forces that mimic muscle forces were experimentally applied to a piezoelectric generator to verify the accuracy of the simulations and to explore losses due to mechanical coupling. Depending on the selection of system parameters, software simulations predict that this generator concept can generate up to 690 microW of power, which is greater than the power necessary to drive the generator, conservatively estimated to be 46 microW. These results suggest that this concept has the potential to be an implantable, self-replenishing power source and warrants further investigation.

Topography of spinal neurons active during hindlimb withdrawal reflexes in the decerebrate cat.

There exists a spatial organization of receptive fields and a modular organization of the flexion withdrawal reflex system. However, the three dimensional location and organization of interneurons interposed in flexion reflex pathways has not been systematically examined. We determined the anatomical locations of spinal neurons involved in the hindlimb flexion withdrawal reflex using expression of the immediate early gene c-fos and the corresponding FOS protein. The flexion withdrawal reflex was evoked in decerebrate cats via stimulation of the tibial or superficial peroneal nerve. Animals that received stimulation had significantly larger numbers of cells expressing FOS-like immunoreactivity (42.7+/-2.3 cells/section, mean+/-standard error of the mean) than operated unstimulated controls (18.6+/-1.4 cells/section). Compared with controls, cells expressing FOS-like immunoreactivity were located predominantly on the ipsilateral side, in laminae IV-VI, at L6 and rostral L7 segments, and between 20% and 60% of the distance from the midline to the lateral border of the ventral gray matter. Labeled neurons resulting from tibial nerve stimulation were medial to neurons labeled following superficial peroneal nerve stimulation in laminae I-VI, but not VII. The mean mediolateral positions of labeled neurons from both nerves shifted medially as the transverse plane in which they were viewed was moved from rostral to caudal and as the coronal plane in which they were viewed was moved from dorsal to ventral. The mediolateral separation between populations of labeled cells was consistent with primary afferent projections and the location of reflex encoders. This topographical segregation corresponding to different afferent inputs is a possible anatomical substrate for a modular organization of the flexion withdrawal reflex system.