Traffic Noise Impacts Glucocorticoid Response, Activity, and Growth in Two Species of Tadpoles.

There is a large body of evidence linking increased noise to negative health effects for animals. Anthropogenic noise induces behavioral and physiological reactions across a range of taxa and increased traffic noise affects glucocorticoid (GC) hormones associated with the stress response in amphibians. GCs help to maintain homeostasis while balancing energetic trade-offs between reproduction, growth, and activity. Stressors during early development can impact fitness at later life stages. We measured growth, activity, and GCs in response to high levels of traffic noise in two tadpole species that differ in life history: Acris crepitans and Rana berlandieri. We predicted that earlier exposures to traffic noise will slow down the development and alter the behavior and GC concentrations differently than later exposures. Subjects were initially either exposed to natural levels of traffic noise for 8 days (early exposure) or a white noise control (later exposure), then the treatment was switched. Activity was measured via focal sampling and tadpoles were categorized as active if movement was detected. Tadpoles exposed to white noise initially maintained mass and activity throughout the experiment and early exposure to traffic noise had a greater impact on mass, activity, and GCs. Tadpoles exposed to traffic noise initially lost mass, with A. crepitans regaining mass but not R. berlandieri. When exposed earlier to traffic noise, R. berlandieri increased movement when shifted to the white noise treatment while A. crepitans did not significantly change activity. Acris creptians had higher corticosterone release rates compared to R. berlandieri, and in both species, release rates were higher for tadpoles exposed to noise earlier. The longer-lived R. berlandieri allocated more of their energetic resources into activity, while the shorter-lived A. crepitans allocated energy toward growth. Rana berlandieri and A. crepitans utilized different coping strategies to contend with early exposure to traffic noise, potentially due to differences in life histories. Our findings suggest that these tadpoles employ different coping mechanisms to modulate stress responses in noise-polluted environments, and these mechanisms could influence their fitness later in life. Further study is needed to understand the impact in more sensitive tadpole species.

An in vivo accelerated developmental myelination model for testing promyelinating therapeutics.

BACKGROUND: Therapeutic agents stimulating the process of myelination could be beneficial for the treatment of demyelinating diseases, such as multiple sclerosis. The efficient translation of compounds promoting myelination in vitro to efficacy in vivo is inherently time-consuming and expensive. Thyroid hormones accelerate the differentiation and maturation of oligodendrocytes, thereby promoting myelination. Systemic administration of the thyroid hormone thyroxine (T4) accelerates brain maturation, including myelination, during early postnatal development. The objective of this study was to validate an animal model for rapid testing of promyelinating therapeutic candidates for their effects on early postnatal development by using T4 as a reference compound. METHODS: Daily subcutaneous injections of T4 were given to Sprague Dawley rat pups from postnatal day (PND) 2 to PND10. Changes in white matter were determined at PND10 using diffusion tensor magnetic resonance imaging (DTI). Temporal changes in myelination from PND3 to PND11 were also assessed by quantifying myelin basic protein (MBP) expression levels in the brain using the resonance Raman spectroscopy/enzyme-linked immunosorbent assay (RRS-ELISA) and quantitative immunohistochemistry. RESULTS: DTI of white matter tracts showed significantly higher fractional anisotropy in the internal capsule of T4-treated rat pups. The distribution of total FA values in the forebrain was significantly shifted towards higher values in the T4-treated group, suggesting increased myelination. In vivo imaging data were supported by in vitro observations, as T4 administration significantly potentiated the developmental increase in MBP levels in brain lysates starting from PND8. MBP levels in the brain of animals that received treatment for 9 days correlated with the FA metric determined in the same pups in vivo a day earlier. Furthermore, accelerated developmental myelination following T4 administration was confirmed by immunohistochemical staining for MBP in coronal brain sections of treated rat pups. CONCLUSIONS: T4-treated rat pups had increased MBP expression levels and higher MRI fractional anisotropy values, both indications of accelerated myelination. This simple developmental myelination model affords a rapid test of promyelinating activity in vivo within several days, which could facilitate in vivo prescreening of candidate therapeutic compounds for developmental hypomyelinating diseases. Further research will be necessary to assess the utility of this platform for screening promyelination compounds in more complex demyelination disease models, such us multiple sclerosis.

Zero Preventable Deaths by 2020: Analysis of Prehospital and Emergency Department Deaths Following Penetrating Trauma Stratified by Anatomic Location.

INTRODUCTION: Preventable deaths following trauma are high and unchanged over the last two decades. The objective of this study was to describe the location of death in patients with penetrating trauma, stratified by anatomic location of injury, in order to better tailor our approach to reducing preventable deaths from trauma. METHODS: This retrospective analysis of a prospectively maintained trauma registry included consecutive adult trauma activations with penetrating trauma at a level 1 trauma center between 07/2012 and 03/2018. Injuries were categorized as extremity, junctional, and torso. Head and neck injuries were excluded. Patients injured in >1 defined location were categorized as "multiple." Location of death was defined as on-scene, emergency department (ED), or hospital. Two-sided χ2 tests were used to compare groups. Multivariate analysis was performed using logistic regression. RESULTS: A total of 1024 patients were included with an overall case fatality rate (CFR) of 7.8%. The CFR following extremity injury (3.0%) was significantly lower than all other injury sites (P = .02).There were no significant differences in CFR for junctional (10.4%), torso (8.3%), or multiple injuries (9.6%). Forty percent of fatalities following junctional injury occurred on-scene and an additional 20% occurred in the ED. DISCUSSION: To our knowledge, this is the first study to describe location of death stratified by anatomic location of injury. There was no difference in the CFRs of junctional and torso injuries, and a large proportion of deaths occurred prior to reaching the hospital or in the trauma bay. These findings support reevaluating the classical algorithms and care pathways for patients with proximal penetrating trauma.

A role for dopamine in the peripheral sensory processing of a gastropod mollusc.

Histological evidence points to the presence of dopamine (DA) in the cephalic sensory organs of multiple gastropod molluscs, suggesting a possible sensory role for the neurotransmitter. We investigated the sensory function of DA in the nudipleuran Pleurobranchaea californica, in which the central neural correlates of sensation and foraging behavior have been well characterized. Tyrosine hydroxylase-like immunoreactivity (THli), a signature of the dopamine synthetic pathway, was similar to that found in two other opisthobranchs and two pulmonates previously studied: 1) relatively few (<100) THli neuronal somata were observed in the central ganglia, with those observed found in locations similar to those documented in the other snails but varying in number, and 2) the vast majority of THli somata were located in the peripheral nervous system, were associated with ciliated, putative primary sensory cells, and were highly concentrated in chemotactile sensory organs, giving rise to afferent axons projecting to the central nervous system. We extended these findings by observing that applying a selective D2/D3 receptor antagonist to the chemo- and mechanosensory oral veil-tentacle complex of behaving animals significantly delayed feeding behavior in response to an appetitive stimulus. A D1 blocker had no effect. Recordings of the two major cephalic sensory nerves, the tentacle and large oral veil nerves, in a deganglionated head preparation revealed a decrease of stimulus-evoked activity in the former nerve following application of the same D2/D3 antagonist. Broadly, our results implicate DA in sensation and engender speculation regarding the foraging-based decisions the neurotransmitter may serve in the nervous system of Pleurobranchaea and, by extension, other gastropods.

Genetic analysis through OtoSeq of Pakistani families segregating prelingual hearing loss.

OBJECTIVE: To identify the genetic cause of prelingual sensorineural hearing loss in Pakistani families using a next-generation sequencing (NGS)-based mutation screening test named OtoSeq. STUDY DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS AND METHODS: We used 3 fluorescently labeled short tandem repeat (STR) markers for each of the known autosomal recessive nonsyndromic (DFNB) and Usher syndrome (USH) locus to perform a linkage analysis of 243 multigenerational Pakistani families segregating prelingual hearing loss. After genotyping, we focused on 34 families with potential linkage to MYO7A, CDH23, and SLC26A4. We screened affected individuals from a subset of these families using the OtoSeq platform to identify underlying genetic variants. Sanger sequencing was performed to confirm and study the segregation of mutations in other family members. For novel mutations, normal hearing individuals from ethnically matched backgrounds were also tested. RESULTS: Hearing loss was found to co-segregate with locus-specific STR markers for MYO7A in 32 families, CDH23 in 1 family, and SLC26A4 in 1 family. Using the OtoSeq platform, a microdroplet PCR-based enrichment followed by NGS, we identified mutations in 28 of the 34 families including 11 novel mutations. Sanger sequencing of these mutations showed 100% concordance with NGS data and co-segregation of the mutant alleles with the hearing loss phenotype in the respective families. CONCLUSION: Using NGS-based platforms like OtoSeq in families segregating hearing loss will contribute to the identification of common and population-specific mutations, early diagnosis, genetic counseling, and molecular epidemiology.

Pervasive seismic wave reflectivity and metasomatism of the Tonga mantle wedge.

Subduction zones play critical roles in the recycling of oceanic lithosphere and the generation of continental crust. Seismic imaging can reveal structures associated with key dynamic processes occurring in the upper-mantle wedge above the sinking oceanic slab. Three-dimensional images of reflecting interfaces throughout the upper-mantle wedge above the subducting Tonga slab were obtained by migration of teleseismic recordings of underside P- and S-wave reflections. Laterally continuous weak reflectors with tens of kilometers of topography were detected at depths near 90, 125, 200, 250, 300, 330, 390, 410, and 450 kilometers. P- and S-wave impedances decreased at the 330-kilometer and 450-kilometer reflectors, and S-wave impedance decreased near 200 kilometers in the vicinity of the slab and near 390 kilometers, just above the global 410-kilometer increase. The pervasive seismic reflectivity results from phase transitions and compositional zonation associated with extensive metasomatism involving slab-derived fluids rising through the wedge.