Development of a mammalian neurosensory full‐thickness skin equivalent and its application to screen sensitizing stimuli

Human skin equivalents (HSEs) are an increasingly popular research tool due to limitations associated with animal testing for dermatological research. They recapitulate many aspects of skin structure and function, however, many only contain two basic cell types to model dermal and epidermal compartments, which limits their application. We describe advances in the field skin tissue modeling to produce a construct containing sensory-like neurons that is responsive to known noxious stimuli. Through incorporation of mammalian sensory-like neurons, we were able to recapitulate aspects of the neuroinflammatory response including secretion of substance P and a range of pro-inflammatory cytokines in response to a well-characterized neurosensitizing agent: capsaicin. We observed that neuronal cell bodies reside in the upper dermal compartment with neurites extending toward the keratinocytes of the stratum basale where they exist in close proximity to one another. These data suggest that we are able to model aspects of the neuroinflammatory response that occurs during exposure to dermatological stimuli including therapeutics and cosmetics. We propose that this skin construct can be considered a platform technology with a wide range of applications including screening of actives, therapeutics, modeling of inflammatory skin diseases, and fundamental approaches to probe underlying cell and molecular mechanisms

Does Predation Influence the Seasonal and Diel Timing of Moose Calving in Central Ontario, Canada?

Birth synchrony is well documented among ungulates and is hypothesised to maximize neonate survival, either by minimizing the risk of predation through predator swamping or by synchronising birthing with increased seasonal food availability. We used encapsulated vaginal implant transmitters to locate and capture neonatal moose calves and document the seasonal and diel timing of parturition in two adjacent study areas with different predation pressure in central Ontario, Canada. We tested the hypothesis that predation promotes earlier and more synchronous birth of moose calves. Across both areas, proportionately more births occurred during the afternoon and fewer than expected occurred overnight. Mean date of calving averaged 1.5 days earlier and calving was also more synchronous in the study area with heavier predation pressure, despite average green-up date and peak Normalized Difference Vegetation Index date occurring 2 days later in this study area than in the area receiving lighter predation pressure. We encourage analysis of data on timing of parturition from additional study areas experiencing varying degrees of predation pressure to better clarify the influence of predation in driving seasonal and diel timing of parturition in temperate ungulate

Political conservatism predicts asymmetries in emotional scene memory

Variation in political ideology has been linked to differences in attention to and processing of emotional stimuli, with stronger responses to negative versus positive stimuli (negativity bias) the more politically conservative one is. As memory is enhanced by attention, such findings predict that memory for negative versus positive stimuli should similarly be enhanced the more conservative one is. The present study tests this prediction by having participants study 120 positive, negative, and neutral scenes in preparation for a subsequent memory test. On the memory test, the same 120 scenes were presented along with 120 new scenes and participants were to respond whether a scene was old or new. Results on the memory test showed that negative scenes were more likely to be remembered than positive scenes, though, this was true only for political conservatives. That is, a larger negativity bias was found the more conservative one was. The effect was sizeable, explaining 45% of the variance across subjects in the effect of emotion. These findings demonstrate that the relationship between political ideology and asymmetries in emotion processing extend to memory and, furthermore, suggest that exploring the extent to which subject variation in interactions among emotion, attention, and memory is predicted by conservatism may provide new insights into theories of political ideology

Thermal Links for the Implementation of an Optical Refrigerator

Optical refrigeration has been demonstrated by several groups of researchers, but the cooling elements have not been thermally linked to realistic heat loads in ways that achieve the desired temperatures. The ideal thermal link will have minimal surface area, provide complete optical isolation for the load, and possess high thermal conductivity. We have designed thermal links that minimize the absorption of fluoresced photons by the heat load using multiple mirrors and geometric shapes including a hemisphere, a kinked waveguide, and a tapered waveguide. While total link performance is dependent on additional factors, we have observed net transmission of photons with the tapered link as low as 0.04%. Our optical tests have been performed with a surrogate source that operates at 625 nm and mimics the angular distribution of light emitted from the cooling element of the Los Alamos solid state optical refrigerator. We have confirmed the optical performance of our various link geometries with computer simulations using CODE V optical modeling software. In addition we have used the thermal modeling tool in COMSOL MULTIPHYSICS to investigate other heating factors that affect the thermal performance of the optical refrigerator. Assuming an ideal cooling element and a nonabsorptive dielectric trapping mirror, the three dominant heating factors are (1) absorption of fluoresced photons transmitted through the thermal link, (2) blackbody radiation from the surrounding environment, and (3) conductive heat transfer through mechanical supports. Modeling results show that a 1 cm3 load can be chilled to 107 K with a 100Wpump laser. We have used the simulated steady-state cooling temperatures of the heat load to compare link designs and system configurations

Benthic fluxes of trace metals in the Chukchi Sea and their transport into the Arctic Ocean

Highlights • Frequent sediment resuspension may have buffered D-Fe released from shelf sediments. • 228Ra was used to estimate trace element fluxes from the Chukchi shelf sediments. • The estimated sediment 228Ra flux ranks among the highest reported globally. • About 10–25% of the Chukchi shelf sediment Fe flux is exported to the Arctic Ocean. The Chukchi Sea is a primary site for shelf-ocean exchange in the Arctic region and modifies Pacific-sourced water masses as they transit via the Bering Strait into the Arctic Ocean. The aim of this study was to use radium and trace metal distributions to improve our understanding of biogeochemical cycles in the Bering and Chukchi Seas, and evaluate their potential response to future changes in the Arctic. We investigated the distributions of dissolved and total dissolvable trace metals (Cd, Fe, Ni, Cu, Zn, Mn, Co, and Pb) in the Bering and Chukchi Seas during spring. In addition, the long-lived radium isotopes (226Ra and 228Ra) were measured as tracers of benthic trace metal inputs. Trace metal concentrations, especially Fe and Mn, were highly elevated in Chukchi shelf waters compared with the open Arctic Ocean and Bering Strait. Trace metal, nutrient, and Ra patterns suggested that Fe, Mn, and Co concentrations were predominantly controlled by reductive benthic inputs, whereas the other trace metals were influenced by biological uptake and release processes. We propose that Fe, Mn, and Co in the Chukchi Sea are supplied from shelf sediments during winter overturning, and we combine the 228Ra fluxes with the distributions of Fe, Mn, and Co to provide a first estimate of their benthic fluxes in the region. The average benthic flux of 228Ra was 1.49 × 108 atoms m−2 d−1, which is among the highest rates reported globally. Estimated dissolved Fe (D-Fe) flux from the sediments was 2.5 μmol m−2 d−1, whereas D-Mn and D-Co fluxes were 8.0 μmol m−2 d−1 and 0.2 μmol m−2 d−1, respectively. The off-shelf transport of D-Fe to the Arctic Ocean is estimated to be about 10–25% of the benthic Fe flux, with the remainder retained on the shelf due to scavenging and/or phytoplankton uptake. Our results highlight the importance of the Chukchi Sea as a major source of the micro-nutrients to the Arctic Ocean, thereby supporting primary production. Long-term changes in factors that affect cross-shelf mixing, such as the observed reduction in ice cover, may therefore enhance shelf nutrient inputs and primary productivity in the Arctic

Rasch analysis of the hospital anxiety and depression scale (hads) for use in motor neurone disease

<p>Abstract</p> <p>Background</p> <p>The Hospital Anxiety and Depression Scale (HADS) is commonly used to assess symptoms of anxiety and depression in motor neurone disease (MND). The measure has never been specifically validated for use within this population, despite questions raised about the scale's validity. This study seeks to analyse the construct validity of the HADS in MND by fitting its data to the Rasch model.</p> <p>Methods</p> <p>The scale was administered to 298 patients with MND. Scale assessment included model fit, differential item functioning (DIF), unidimensionality, local dependency and category threshold analysis.</p> <p>Results</p> <p>Rasch analyses were carried out on the HADS total score as well as depression and anxiety subscales (HADS-T, D and A respectively). After removing one item from both of the seven item scales, it was possible to produce modified HADS-A and HADS-D scales which fit the Rasch model. An 11-item higher-order HADS-T total scale was found to fit the Rasch model following the removal of one further item.</p> <p>Conclusion</p> <p>Our results suggest that a modified HADS-A and HADS-D are unidimensional, free of DIF and have good fit to the Rasch model in this population. As such they are suitable for use in MND clinics or research. The use of the modified HADS-T as a higher-order measure of psychological distress was supported by our data. Revised cut-off points are given for the modified HADS-A and HADS-D subscales.</p

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-{alpha}-aminoadipic semialdehyde/L-{Delta}1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-{alpha}-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-{alpha}-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios

Residential Segregation and Overweight/Obesity Among African-American Adults: A Critical Review

The relationship between residential segregation and overweight/obesity among African-American adults remains unclear. Elucidating that relationship is relevant to efforts to prevent and to reduce racial disparities in obesity. This article provides a critical review of the 11 empirical studies of segregation and overweight/obesity among African-American adults. Results revealed that most studies did not use a valid measure of segregation, many did not use a valid measure of overweight/obesity, and many did not control for neighborhood poverty. Only four (36% of the) studies used valid measures of both segregation and overweight/obesity and also controlled for area-poverty. Those four studies suggest that segregation contributes to overweight and obesity among African-American adults, but that conclusion cannot be drawn with certainty in light of the considerable methodologic problems in this area of research. Suggestions for improving research on this topic are provided