Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation.

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans. Here we present novel neuroimaging data from these animals to further explore the translational potential of the nonhuman primate MIA model. Nine male MIA-treated offspring and 4 controls from our original cohort underwent in vivo positron emission tomography (PET) scanning at approximately 3.5-years of age using [18F] fluoro-l-m-tyrosine (FMT) to measure presynaptic dopamine levels in the striatum, which are consistently elevated in individuals with schizophrenia. Analysis of [18F]FMT signal in the striatum of these nonhuman primates showed that MIA animals had significantly higher [18F]FMT index of influx compared to control animals. In spite of the modest sample size, this group difference reflects a large effect size (Cohen's d = 0.998). Nonhuman primates born to MIA-treated dams exhibited increased striatal dopamine in late adolescence-a hallmark molecular biomarker of schizophrenia. These results validate the MIA model in a species more closely related to humans and open up new avenues for understanding the neurodevelopmental biology of schizophrenia and other neurodevelopmental disorders associated with prenatal immune challenge

The effect of an emergency department clinical “triggers” program based on abnormal vital signs

AbstractObjectiveTo determine the effect of a clinical triggers program in the Emergency Department (ED) setting that utilized predetermined abnormal vital signs to activate a rapid assessment by an emergency physician led multidisciplinary team.MethodsA retrospective, separate sample, pre-post intervention study following implementation of an ED triggers program. Abnormal vital sign criteria that warranted a trigger response included: heart rate <40 or >130 beats/min, respiratory rate <8 or >30 respirations/min, systolic blood pressure <90 mm Hg, or oxygen saturation <90% on room air. The primary outcome investigated was time to physician evaluation with secondary outcomes being the time to disposition decision and time to first critical therapeutic intervention.ResultsThe median time to physician evaluation was reduced by 25% from 28 min to 21 min (P<0.05). The median time to disposition decision was decreased by 12% from 154 minutes to 135 minutes (P<0.05). The median time to first intervention was 46 min and 43 min (P=0.33) in the before and after groups, which did not represent a statistically significant difference.ConclusionsIn our model, the implementation of an ED triggers program resulted in a modest decreased time to physician evaluation and disposition decision but not time to intervention

Primary total knee arthroplasty in a patient with a chronic extensor mechanism deficiency

AbstractA 44-year-old female presented with a chief complaint of left knee pain and dysfunction. The patient had a complex surgical history including patellar fracture repair, subsequent patellar ligament repair, and ultimately allograft reconstruction which was complicated by septic arthritis requiring graft resection. On presentation to our clinic, she was noted to have significant degenerative disease in addition to chronic extensor mechanism deficiency. She underwent primary total knee arthroplasty with concomitant tibial tubercle osteotomy and advancement. The patient has had an excellent result postoperatively including return of full range of motion without residual extensor lag

Low density lipoprotein cholesterol control status among Canadians at risk for cardiovascular disease: findings from the Canadian Primary Care Sentinel Surveillance Network Database

Background To determine the prevalence of uncontrolled LDL-C in patients with high cardiovascular disease (CVD) risks across Canada and to examine its related factors. Methods Non-pregnant adults >20 years-old, who had a lipid test completed between January 1, 2009 and December 31, 2011 and were included in the Canadian Primary Care Surveillance Network (CPCSSN) database were studied. The Framingham-Risk-Score was calculated to determine the risk levels. A serum LDL-C level of >2.0 mmol/L was considered as being poorly controlled. Patients with a previous record of a cerebrovascular accident, peripheral artery disease, or an ischemic heart disease were regarded as those under secondary prevention. Logistic regression modeling was performed to examine the factors associated with the LDL-C control. Results A total of 6,405 high-risk patients were included in the study and, of this population, 68 % had a suboptimal LDL-C, which was significantly associated with the female gender (OR: 3.26; 95 % CI: 2.63–4.05, p < 0.0001) and no medication therapy (OR: 6.31, 95 % CI: 5.21–7.65, p < 0.0001). Those with comorbidities of diabetes, hypertension, obesity, and smokers had a better LDL-C control. Rural residents (OR: 0.64, 95 % CI: 0.52–0.78, p < 0.0001), and those under secondary prevention (OR: 0.42; 95 % CI: 0.35–0.51, p < 0.0001), were also more likely to have a better LDL-C control. Conclusion A high proportion of high-cardiac risk patients in Canadian primary care settings have suboptimal LDL-C control. A lack of medication therapy appears to be the major contributing factor to this situation

A foundation for provitamin A biofortification of maize: genome-wide association and genomic prediction models of carotenoid levels.

Efforts are underway for development of crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency. As a global staple crop with considerable variation in kernel carotenoid composition, maize (Zea mays L.) could have a widespread impact. We performed a genome-wide association study (GWAS) of quantified seed carotenoids across a panel of maize inbreds ranging from light yellow to dark orange in grain color to identify some of the key genes controlling maize grain carotenoid composition. Significant associations at the genome-wide level were detected within the coding regions of zep1 and lut1, carotenoid biosynthetic genes not previously shown to impact grain carotenoid composition in association studies, as well as within previously associated lcyE and crtRB1 genes. We leveraged existing biochemical and genomic information to identify 58 a priori candidate genes relevant to the biosynthesis and retention of carotenoids in maize to test in a pathway-level analysis. This revealed dxs2 and lut5, genes not previously associated with kernel carotenoids. In genomic prediction models, use of markers that targeted a small set of quantitative trait loci associated with carotenoid levels in prior linkage studies were as effective as genome-wide markers for predicting carotenoid traits. Based on GWAS, pathway-level analysis, and genomic prediction studies, we outline a flexible strategy involving use of a small number of genes that can be selected for rapid conversion of elite white grain germplasm, with minimal amounts of carotenoids, to orange grain versions containing high levels of provitamin A

Controlling trapping potentials and stray electric fields in a microfabricated ion trap through design and compensation

Recent advances in quantum information processing with trapped ions have demonstrated the need for new ion trap architectures capable of holding and manipulating chains of many (>10) ions. Here we present the design and detailed characterization of a new linear trap, microfabricated with scalable complementary metal-oxide-semiconductor (CMOS) techniques, that is well-suited to this challenge. Forty-four individually controlled DC electrodes provide the many degrees of freedom required to construct anharmonic potential wells, shuttle ions, merge and split ion chains, precisely tune secular mode frequencies, and adjust the orientation of trap axes. Microfabricated capacitors on DC electrodes suppress radio-frequency pickup and excess micromotion, while a top-level ground layer simplifies modeling of electric fields and protects trap structures underneath. A localized aperture in the substrate provides access to the trapping region from an oven below, permitting deterministic loading of particular isotopic/elemental sequences via species-selective photoionization. The shapes of the aperture and radio-frequency electrodes are optimized to minimize perturbation of the trapping pseudopotential. Laboratory experiments verify simulated potentials and characterize trapping lifetimes, stray electric fields, and ion heating rates, while measurement and cancellation of spatially-varying stray electric fields permits the formation of nearly-equally spaced ion chains.Comment: 17 pages (including references), 7 figure

Demonstration of integrated microscale optics in surface-electrode ion traps

In ion trap quantum information processing, efficient fluorescence collection is critical for fast, high-fidelity qubit detection and ion-photon entanglement. The expected size of future many-ion processors require scalable light collection systems. We report on the development and testing of a microfabricated surface-electrode ion trap with an integrated high numerical aperture (NA) micromirror for fluorescence collection. When coupled to a low NA lens, the optical system is inherently scalable to large arrays of mirrors in a single device. We demonstrate stable trapping and transport of 40Ca+ ions over a 0.63 NA micromirror and observe a factor of 1.9 enhancement in photon collection compared to the planar region of the trap.Comment: 15 pages, 8 figure

A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice.

It is well known that the ω-3 fatty acids (ω-3-FAs; also known as n-3 fatty acids) can exert potent anti-inflammatory effects. Commonly consumed as fish products, dietary supplements and pharmaceuticals, ω-3-FAs have a number of health benefits ascribed to them, including reduced plasma triglyceride levels, amelioration of atherosclerosis and increased insulin sensitivity. We reported that Gpr120 is the functional receptor for these fatty acids and that ω-3-FAs produce robust anti-inflammatory, insulin-sensitizing effects, both in vivo and in vitro, in a Gpr120-dependent manner. Indeed, genetic variants that predispose to obesity and diabetes have been described in the gene encoding GPR120 in humans (FFAR4). However, the amount of fish oils that would have to be consumed to sustain chronic agonism of Gpr120 is too high to be practical, and, thus, a high-affinity small-molecule Gpr120 agonist would be of potential clinical benefit. Accordingly, Gpr120 is a widely studied drug discovery target within the pharmaceutical industry. Gpr40 is another lipid-sensing G protein-coupled receptor, and it has been difficult to identify compounds with a high degree of selectivity for Gpr120 over Gpr40 (ref. 11). Here we report that a selective high-affinity, orally available, small-molecule Gpr120 agonist (cpdA) exerts potent anti-inflammatory effects on macrophages in vitro and in obese mice in vivo. Gpr120 agonist treatment of high-fat diet-fed obese mice causes improved glucose tolerance, decreased hyperinsulinemia, increased insulin sensitivity and decreased hepatic steatosis. This suggests that Gpr120 agonists could become new insulin-sensitizing drugs for the treatment of type 2 diabetes and other human insulin-resistant states in the future