Demographic Clusters Identified within the Northern Gulf of Mexico Common Bottlenose Dolphin (Tursiops truncates) Unusual Mortality Event: January 2010 - June 2013

A multi-year unusual mortality event (UME) involving primarily common bottlenose dolphins (Tursiops truncates) was declared in the northern Gulf of Mexico (GoM) with an initial start date of February 2010 and remains ongoing as of August 2014. To examine potential changing characteristics of the UME over time, we compared the number and demographics of dolphin strandings from January 2010 through June 2013 across the entire GoM as well as against baseline (1990-2009) GoM stranding patterns. Years 2010 and 2011 had the highest annual number of stranded dolphins since Louisiana’s record began, and 2011 was one of the years with the highest strandings for both Mississippi and Alabama. Statewide, annual numbers of stranded dolphins were not elevated for GoM coasts of Florida or Texas during the UME period. Demographic, spatial, and temporal clusters identified within this UME included increased strandings in northern coastal Louisiana and Mississippi (March-May 2010); Barataria Bay, Louisiana (August 2010-December 2011); Mississippi and Alabama (2011, including a high prevalence and number of stranded perinates); and multiple GoM states during early 2013. While the causes of the GoM UME have not been determined, the location and magnitude of dolphin strandings during and the year following the 2010 Deepwater Horizon oil spill, including the Barataria Bay cluster from August 2010 to December 2011, overlap in time and space with locations that received heavy and prolonged oiling. There are, however, multiple known causes of previous GoM dolphin UMEs, including brevetoxicosis and dolphin morbillivirus. Additionally, increased dolphin strandings occurred in northern Louisiana and Mississippi before the Deepwater Horizon oil spill. Identification of spatial, temporal, and demographic clusters within the UME suggest that this mortality event may involve different contributing factors varying by location, time, and bottlenose dolphin populations that will be better discerned by incorporating diagnostic information, including histopathology.     

A Multicenter,Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

BackgroundDespite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes.ResultsA total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention.ConclusionsOsteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants.     

Characterization of the Cardiac Overexpression of HSPB2 Reveals Mitochondrial and Myogenic Roles Supported by a Cardiac HspB2 Interactome

Small Heat Shock Proteins (sHSPs) are molecular chaperones that transiently interact with other proteins, thereby assisting with quality control of proper protein folding and/or degradation. They are also recruited to protect cells from a variety of stresses in response to extreme heat, heavy metals, and oxidative-reductive stress. Although ten human sHSPs have been identified, their likely diverse biological functions remain an enigma in health and disease, and much less is known about non-redundant roles in selective cells and tissues. Herein, we set out to comprehensively characterize the cardiac-restricted Heat Shock Protein B-2 (HspB2), which exhibited ischemic cardioprotection in transgenic overexpressing mice including reduced infarct size and maintenance of ATP levels. Global yeast two-hybrid analysis using HspB2 (bait) and a human cardiac library (prey) coupled with co-immunoprecipitation studies for mitochondrial target validation revealed the first HspB2 “cardiac interactome” to contain many myofibril and mitochondrial-binding partners consistent with the overexpression phenotype. This interactome has been submitted to the Biological General Repository for Interaction Datasets (BioGRID). A related sHSP chaperone HspB5 had only partially overlapping binding partners, supporting specificity of the interactome as well as non-redundant roles reported for these sHSPs. Evidence that the cardiac yeast two-hybrid HspB2 interactome targets resident mitochondrial client proteins is consistent with the role of HspB2 in maintaining ATP levels and suggests new chaperone-dependent functions for metabolic homeostasis. One of the HspB2 targets, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), has reported roles in HspB2 associated phenotypes including cardiac ATP production, mitochondrial function, and apoptosis, and was validated as a potential client protein of HspB2 through chaperone assays. From the clientele and phenotypes identified herein, it is tempting to speculate that small molecule activators of HspB2 might be deployed to mitigate mitochondrial related diseases such as cardiomyopathy and neurodegenerative disease.     

Understanding Low-Acuity Visits to the Pediatric Emergency Department

Background

Canadian pediatric emergency department visits are increasing, with a disproportionate increase in low-acuity visits locally (33% of volume in 2008-09, 41% in 2011-12). We sought to understand: 1) presentation patterns and resource implications; 2) parents’ perceptions and motivations; and 3) alternate health care options considered prior to presenting with low-acuity problems.

Methods

We conducted a prospective cohort study at our tertiary pediatric emergency department serving two provinces to explore differences between patients with and without a primary care provider. During four, 2-week study periods over 1 year, parents of low-acuity visits received an anonymous survey. Presentation times, interventions, diagnoses and dispositions were captured on a data collection form linked to the survey by study number.

Results

Parents completed 2,443 surveys (74.1% response rate), with survey-data collection form pairs available for 2,146 visits. Overall, 89.7% of respondents had a primary care provider; 68% were family physicians. Surprisingly, 40% of visits occurred during weekday office hours and 27.3% occurred within 4 hours of symptom onset; 67.5% of those early presenters were for injuries. Few parents sought care from their primary care provider (25%), health information line (20.7%), or urgent care clinic (18.5%); 36% reported that they believed their child’s problem required the emergency department. Forty-five percent required only a history, physical exam and reassurance; only 11% required an intervention not available in an office setting. Patients without a primary care provider were significantly more likely to present during weekday office hours (p = 0.003), have longer symptom duration (p<0.001), and not know of other options (p = 0.001).

Conclusions

Many parents seek pediatric emergency department care for low-acuity problems despite their child having a primary care provider. Ensuring timely access to these providers may help reduce pediatric emergency department overuse. Educational initiatives should inform parents about low-acuity problems and where appropriate care can/should be accessed.     

Estimating striae of Retzius periodicity nondestructively using partial counts of perikymata

Accurate age estimations for enamel formation and the timing of enamel hypoplasia have traditionally only been available through histological analyses of dental thin sections, which is a difficult and destructive process. However, an association between striae of Retzius periodicity, crucial for accurate aging, and the total number of striae in imbricational enamel has been reported in the literature. This means periodicity can be estimated nondestructively but is reliant on all perikymata being visible along the crown surface. Therefore, crowns with worn or damaged surfaces may not be able to be assessed, potentially limiting sample sizes. We tested this relationship in a modern New Zealand sample and investigated whether reliable associations might be identified using only partial perikymata counts from the cervical half of the crown. Using mandibular canines (n = 11), the distribution of perikymata per decile was recorded using high definition replica surfaces. Thin sections of the same crowns were used to assess periodicity histologically along with striae of Retzius distributions. A strong correlation between total striae numbers and periodicity was also identified in our sample. Furthermore, we report strong correlations that allow periodicity to be estimated from perikymata counts using only 10% of crown height when certain deciles are used. Based on these findings, we propose a simple matrix that can be developed for nondestructively estimating periodicity based on the range of perikymata counts in the sixth to ninth deciles. Am J Phys Anthropol 154:251–258, 2014. © 2014 Wiley Periodicals, Inc.     

Visual deprivation suppresses L5 pyramidal neuron excitability by preventing the induction of intrinsic plasticity

In visual cortex monocular deprivation (MD) during a critical period (CP) reduces the ability of the deprived eye to activate cortex, but the underlying cellular plasticity mechanisms are incompletely understood. Here we show that MD reduces the intrinsic excitability of layer 5 (L5) pyramidal neurons and enhances long-term potentiation of intrinsic excitability (LTP-IE). Further, MD and LTP-IE induce reciprocal changes in K(v)2.1 current, and LTP-IE reverses the effects of MD on intrinsic excitability. Taken together these data suggest that MD reduces intrinsic excitability by preventing sensory-drive induced LTP-IE. The effects of MD on excitability were correlated with the classical visual system CP, and (like the functional effects of MD) could be rapidly reversed when vision was restored. These data establish LTP-IE as a candidate mechanism mediating loss of visual responsiveness within L5, and suggest that intrinsic plasticity plays an important role in experience-dependent refinement of visual cortical circuits.     

Assessment of genetic stability of two micropropagated wild olive species using flow cytometry and microsatellite markers

Micropropagated plants from two wild-olive species, Olea maderensis and O. europaea ssp. europaea var. sylvestris were screened for genetic stability. O. maderensis shoots were elongated/multiplied on OMG medium with zeatin (9.12 μM), and rooted on 1/2 OMG with NAA (3.22 μM). O. europaea var. sylvestris shoots were elongated/multiplied on OM medium with zeatin, and rooting was optimal after a hormonal shock (IBA 100 μM) followed by transfer to the same medium without growth regulators. In both species, acclimatization was successful and plants looked normal and morphologically identical to the donor field trees. Genetic variability was assessed at several stages of the micropropagation process using flow cytometry (FCM) and nuclear microsatellites (SSR). No changes in ploidy level were found among micropropagated plants, though small deviations, putatively due to the negative effects of cytosolic compounds on propidium iodide staining, between these and field plants were observed. In SSRs analyses, ten SSR markers were able to distinguish between genotypes. No mutations were found in these tested SSR loci among the donor tree and micropropagated plants, suggesting, for the tested markers, genetic uniformity throughout the process. The FCM and SSR results obtained do not exclude the occurrence of other changes in the nuclear genome but, considering the morphological stability of micropropagated plants, indicate that both protocols are suitable and efficient for large scale, true-to-type micropropagation of these two wild olive species.     

Study protocol of the YOU CALL - WE CALL TRIAL: impact of a multimodal support intervention after a "mild" stroke

Background

More than 60% of new strokes each year are "mild" in severity and this proportion is expected to rise in the years to come. Within our current health care system those with "mild" stroke are typically discharged home within days, without further referral to health or rehabilitation services other than advice to see their family physician. Those with mild stroke often have limited access to support from health professionals with stroke-specific knowledge who would typically provide critical information on topics such as secondary stroke prevention, community reintegration, medication counselling and problem solving with regard to specific concerns that arise. Isolation and lack of knowledge may lead to a worsening of health problems including stroke recurrence and unnecessary and costly health care utilization. The purpose of this study is to assess the effectiveness, for individuals who experience a first "mild" stroke, of a sustainable, low cost, multimodal support intervention (comprising information, education and telephone support) - "WE CALL" compared to a passive intervention (providing the name and phone number of a resource person available if they feel the need to) - "YOU CALL", on two primary outcomes: unplanned-use of health services for negative events and quality of life.

Method/Design

We will recruit 384 adults who meet inclusion criteria for a first mild stroke across six Canadian sites. Baseline measures will be taken within the first month after stroke onset. Participants will be stratified according to comorbidity level and randomised to one of two groups: YOU CALL or WE CALL. Both interventions will be offered over a six months period. Primary outcomes include unplanned use of heath services for negative event (frequency calendar) and quality of life (EQ-5D and Quality of Life Index). Secondary outcomes include participation level (LIFE-H), depression (Beck Depression Inventory II) and use of health services for health promotion or prevention (frequency calendar). Blind assessors will gather data at mid-intervention, end of intervention and one year follow up.

Discussion

If effective, this multimodal intervention could be delivered in both urban and rural environments. For example, existing infrastructure such as regional stroke centers and existing secondary stroke prevention clinics, make this intervention, if effective, deliverable and sustainable.

Trial Registration

ISRCTN95662526     

Interactions of the NPXY microdomains of the low density lipoprotein receptor‐related protein 1

The low density lipoprotein receptor‐related protein 1 (LRP1) mediates internalization of a large number of proteins and protein–lipid complexes and is widely implicated in Alzheimer's disease. The cytoplasmic domain of LRP1 (LRP1‐CT) can be phosphorylated by activated protein‐tyrosine kinases at two NPXY motifs in LRP1‐CT; Tyr 4507 is readily phosphorylated and must be phosphorylated before phosphorylation of Tyr 4473 occurs. Pull‐down experiments from brain lysate revealed numerous proteins binding to LRP1‐CT, but the results were highly variable. To separate which proteins bind to each NPXY motif and their phosphorylation dependence, each NPXY motif microdomain was prepared in both phosphorylated and non‐phosphorylated forms and used to probe rodent brain extracts for binding proteins. Proteins that bound specifically to the microdomains were identified by LC‐MS/MS, and confirmed by Western blot. Recombinant proteins were then tested for binding to each NPXY motif. The NPXY₄₅₀₇ (membrane distal) was found to interact with a large number of proteins, many of which only bound the tyrosine‐phosphorylated form. This microdomain also bound a significant number of other proteins in the unphosphorylated state. Many of the interactions were later confirmed to be direct with recombinant proteins. The NPXY₄₄₇₃ (membrane proximal) bound many fewer proteins and only to the phosphorylated form.