Author Correction: Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers.

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Incidence of Pediatric Cannabis Exposure Among Children and Teenagers Aged 0 to 19 Years Before and After Medical Marijuana Legalization in Massachusetts

Importance Pediatric health care contacts due to cannabis exposure increased in Colorado and Washington State after cannabis (marijuana) policies became more liberal, but evidence from other US states is limited. Objective To document the incidence of pediatric cannabis exposure cases reported to the Regional Center for Poison Control and Prevention (RPC) before and after medical marijuana legalization (MML) in Massachusetts. Design, Setting, and Participants Cross-sectional comparison of pediatric cannabis exposure cases 4 years before and after MML in Massachusetts. The exposure cases included those of 218 children and teenagers aged between 0 and 19 years, as reported to the RPC from 2009 to 2016. Census data were used to determine the incidence. Data analysis was performed from November 12, 2018, to July 20, 2019. Exposure Cannabis products. Main Outcomes and Measures Incidence of RPC-reported cannabis exposure cases, both single substance and polysubstance, for the age group of 0 to 19 years, and cannabis product type, coingestants, and clinical effects. Results During the 8-year study period (2009-2016), the RPC received 218 calls involving cannabis exposure (98 single substance, 120 polysubstance) in children and teenagers aged 0 to 19 years, representing 0.15% of all RPC calls in that age group for that period. Of the total exposure cases, males accounted for 132 (60.6%) and females 86 (39.4%). The incidence of single-substance cannabis calls increased from 0.4 per 100 000 population before MML to 1.1 per 100 000 population after (incidence rate ratio, 2.4; 95% CI, 1.5-3.9), a 140% increase. The age group of 15 to 19 years had the highest frequency of RPC-reported cannabis exposures (178 calls [81.7%]). The proportion of all RPC calls due to single-substance cannabis exposure increased overall for all age groups from 29 before MML to 69 afterward. Exposure to edible products increased after MML for most age groups. Conclusions and Relevance Pediatric cannabis exposure cases increased in Massachusetts after medical marijuana was legalized in 2012, despite using childproof packaging and warning labels. This study provides additional evidence suggesting that MML may be associated with an increase in cannabis exposure cases among very young children, and extends prior work showing that teenagers are also experiencing increased cannabis-related health system contacts via the RPC. Additional efforts are needed to keep higher-potency edible products and concentrated extracts from children and teenagers, especially considering the MML and retail cannabis sales in an increasing number of US states

Simple transporter trafficking model for amphetamine-induced dopamine efflux

Amphetamine and its derivatives are important drugs of abuse causing both short-term excitatory and long-term addictive effects. The short-term excitatory effects are linked to amphetamine's ability to maintain high levels of dopamine (DA) outside the cell both by inhibiting DA reuptake after synaptic transmission and by enhancing the efflux of DA from the dopaminergic cells. The molecular mechanisms by which amphetamine elicits the efflux of DA and similar monoamines are still unclear. Recent literature data suggest that trafficking of the monoamine transporters is a phenomenon that underlies observed changes in amphetamine-induced monoamine reuptake and efflux. We develop an ordinary differential equation model incorporating the diverse mechanistic details behind amphetamine-induced DA efflux and demonstrate its utility in describing our experimental data. We also demonstrate an experimental method to track the time-varying concentration of membrane-bound transporter molecules from the DA efflux data. The good fit between our model and the experimental data supports the hypothesis that amphetamine-induced transporter trafficking is necessary to produce extended efflux of DA. This model can explain the relative significance of different processes associated with DA efflux at different times and at different concentration ranges of amphetamine and DA. Synapse 61:500–514, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56075/1/20390_ftp.pd

Investigating the Psychosocial Determinants of Physical Activity in Older Adults: A Qualitative Approach

Objective: Despite the benefits of physical activity (PA), only one-third of older adults meet the recommended levels. The present study focused on psychosocial determinants of PA following retirement. Social cognitive theory (SCT) was used to better understand pre- and post-retirement adults’ thoughts about PA, the reasons why some individuals are more active than others, and how PA is incorporated into daily life after retirement. Design: Seven focus groups of older adults (N = 37, M = 64, SD = 5.20; males = 20) representing a range of PA levels and retirement length participated in one of seven focus groups. Results: Aligned with SCT, self-efficacy beliefs along with perceptions about barriers and benefits of PA were among the major determinants of PA. Findings highlighted the importance of social support, positive outcome expectations and self-regulatory strategies as motivators. The lack of structure in retirement was a hindrance to incorporating PA into daily routine but, when incorporated, PA provided a sense of purpose in the lives of retired individuals. Conclusion: It is important to understand the meaning of retirement as a life transition and how it affects beliefs about PA to inform SCT-based health promotion interventions targeting individuals in retirement age

Translating research into practice: Protocol for a community-engaged, stepped wedge randomized trial to reduce disparities in breast cancer treatment through a regional patient navigation collaborative

BACKGROUND: Racial and socioeconomic disparities in breast cancer mortality persist. In Boston, MA, Black, Non-Hispanic women and Medicaid-insured individuals are 2-3 times more likely to have delays in treatment compared to White or privately insured women. While evidence-based care coordination strategies for reducing delays exist, they are not systematically implemented across healthcare settings. METHODS: Translating Research Into Practice (TRIP) utilizes community engaged research methods to address breast cancer care delivery disparities. Four Massachusetts Clinical and Translational Science Institute (CTSI) hubs collaborated with the Boston Breast Cancer Equity Coalition (The Coalition) to implement an evidence-based care coordination intervention for Boston residents at risk for delays in breast cancer care. The Coalition used a community-driven process to define the problem of care delivery disparities, identify the target population, and develop a rigorous pragmatic approach. We chose a cluster-randomized, stepped-wedge hybrid type I effectiveness-implementation study design. The intervention implements three evidence-based strategies: patient navigation services, a shared patient registry for use across academic medical centers, and a web-based social determinants of health platform to identify and address barriers to care. Primary clinical outcomes include time to first treatment and receipt of guideline-concordant treatment, which are captured through electronic health records abstraction. We will use mixed methods to collect the secondary implementation outcomes of acceptability, adoption/penetration, fidelity, sustainability and cost. CONCLUSION: TRIP utilizes an innovative community-driven research strategy, focused on interdisciplinary collaborations, to design and implement a translational science study that aims to more efficiently integrate proven health services interventions into clinical practice

Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively).IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease

The effect of hypothermia on influx of leukocytes in the digital lamellae of horses with oligofructose-induced laminitis

Sepsis-related laminitis (SRL) is a common complication in the septic/endotoxemic critically-ill equine patient, in which lamellar injury and failure commonly lead to crippling distal displacement of the distal phalanx. Similar to organ injury in human sepsis, lamellar injury in SRL has been associated with inflammatory events, including the influx of leukocytes into the lamellar tissue and markedly increased expression of a wide array of inflammatory mediators at the onset of Obel grade 1 (OG1) laminitis. The only treatment reported both clinically and experimentally to protect the lamellae in SRL, local hypothermia (“cryotherapy”), has been demonstrated to effectively inhibit lamellar expression of multiple inflammatory mediators when initiated at the time of administration of a carbohydrate overload in experimental models of SRL. However, the effect of hypothermia on leukocyte influx into affected tissue has not been assessed. We hypothesized that cryotherapy inhibits leukocyte emigration into the digital lamellae in SRL. Immunohistochemical staining using leukocyte markers MAC387 (marker of neutrophils, activated monocytes) and CD163 (monocyte/macrophage-specific marker) was performed on archived lamellar tissue samples from an experimental model of SRL in which one forelimb was maintained at ambient temperature (AMB) and one forelimb was immersed in ice water (ICE) immediately following enteral oligofructose administration (10\ua0g/kg, n\ua0=\ua014 horses). Lamellae were harvested at 24\ua0h post-oligofructose administration (DEV, n\ua0=\ua07) or at the onset of OG1 laminitis (OG1, n\ua0=\ua07). Both MAC387-positive and CD163-positive cells were counted by a single blinded investigator on images [n\ua0=\ua010 (40× fields/digit for MAC387 and 20\ua0x fields/digit for CD163)] obtained using Aperio microscopy imaging analysis software. Data were assessed for normality and analyzed with a paired t-test and one-way ANOVA with significance set at p\ua

Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptormediated activation of PINK–Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility

Comparisons Between NO PLIF Imaging and CFD Simulations of Mixing Flowfields for High-Speed Fuel Injectors

The current work compares experimentally and computationally obtained nitric oxide (NO) planar laser-induced fluorescence (PLIF) images of the mixing flowfields for three types of high-speed fuel injectors: a strut, a ramp, and a rectangular flush-wall. These injection devices, which exhibited promising mixing performance at lower flight Mach numbers, are currently being studied as a part of the Enhanced Injection and Mixing Project (EIMP) at the NASA Langley Research Center. The EIMP aims to investigate scramjet fuel injection and mixing physics, and improve the understanding of underlying physical processes relevant to flight Mach numbers greater than eight. In the experiments, conducted in the NASA Langley Arc-Heated Scramjet Test Facility (AHSTF), the injectors are placed downstream of a Mach 6 facility nozzle, which simulates the high Mach number air flow at the entrance of a scramjet combustor. Helium is used as an inert substitute for hydrogen fuel. The PLIF is obtained by using a tunable laser to excite the NO, which is present in the AHSTF air as a direct result of arc-heating. Consequently, the absence of signal is an indication of pure helium (fuel). The PLIF images computed from the computational fluid dynamics (CFD) simulations are obtained by combining a fluorescence model for NO with the Reynolds-Averaged Simulation results carried out using the VULCAN-CFD solver to obtain a computational equivalent of the experimentally measured PLIF signal. The measured NO PLIF signal is mainly a function of NO concentration allowing for semi-quantitative comparisons between the CFD and the experiments. The PLIF signal intensity is also sensitive to pressure and temperature variations in the flow, allowing additional flow features to be identified and compared with the CFD. Good agreement between the PLIF and the CFD results provides increased confidence in the CFD simulations for investigations of injector performance

Elevated HbA1c levels and the accumulation of differentiated T cells in CMV+ individuals

Aims/hypothesis Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals. Methods A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. Results Among CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p \u3c 0.01) and EMRA (B = 2.90, p \u3c 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p \u3c 0.05) after applying similar adjustments. No associations were observed in CMV− individuals. Conclusions/interpretation The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users