Engrailed transcription factors direct excitatory cerebellar neuron diversity and survival.

The excitatory neurons of the three cerebellar nuclei (eCN) form the primary output for the cerebellum. The medial eCN (eCNm) were recently divided into molecularly defined subdomains in the adult, however how they are established during development is not known. We define molecular subdomains of the embryonic eCNm using scRNA-seq and spatial expression analysis, showing they evolve during embryogenesis to prefigure the adult. Furthermore, the medial eCN are transcriptionally divergent from the other nuclei by E14.5. We previously showed that loss of the homeobox genes En1 and En2 leads to loss of approximately half of embryonic eCNm. We demonstrate that mutation of En1/2 in embryonic eCNm results in death of specific posterior eCNm molecular subdomains and down regulation of TBR2 (EOMES) in an anterior embryonic subdomain, as well as reduced synaptic gene expression. We further reveal a similar function for EN1/2 in mediating TBR2 expression, neuron differentiation and survival in the other excitatory neurons (granule and unipolar brush cells). Thus, our work defines embryonic eCNm molecular diversity and reveals conserved roles for EN1/2 in the cerebellar excitatory neuron lineage.

Selective transformations of friedelanes isolated from cork smoker wash solids.

Friedelin (1) and 3-acetoxyfriedel-3-en-2-one (4), commonly known as friedelane triterpenoids, have been isolated from cork smoker wash solids (also known as black wax) on a multi-gram scale. These compounds are valuable starting materials for the synthesis of new friedelane derivatives. Stereoselective reduction of friedelin by treatment with LiAlH4, sodium, or catalytic hydrogenation results in the formation of both isomers of friedelinol (5 and 7) in excellent yields. Similarly, the reduction of 3-acetoxyfriedel-3-en-2-one gave epi-cerin (14) and a series of isomeric 2,3-diols or α-hydroxyketones. These transformations provide the most straightforward and convenient methods for the synthesis of A-ring functionalised friedelane derivatives using easily accessible starting materials.

Engrailed 2 serves as a master regulator of the super-enhancer in the TNC gene locus in non-small cell lung cancer.

Engrailed 2 (EN2) is a homeodomain-containing protein that is dysregulated in many types of cancer. However, the role of EN2 in non-small cell lung cancer (NSCLC) and the mechanism underlying its biological function are largely unclear. Here, we showed that EN2 played an oncogenic function in NSCLC and greatly enhanced the malignant phenotype of NSCLC cells. Meanwhile, EN2 was able to boost the expression of a well-studied oncogenic Tenascin-C (TNC) gene, which in turn activated the AKT signaling pathway. Interestingly, we found that EN2 directly bound to the super-enhancer (SE) region in the TNC locus. The histone marker H3K27ac was also enriched in the region, indicating the activation of the SE. Treatment of the cells with JQ1, an inhibitor of SE activity, abrogated the effect of EN2 on the expression of TNC and phosphorylation of AKT-Ser473. Collectively, our work unveils a novel mode of EN2 function, in which EN2 governs the SE in the TNC locus, consequently activating the oncogenic TNC-AKT axis in NSCLC.

Circ_0071589 contributes to growth, angiogenesis, and metastasis of colorectal cancer through regulating miR-296-5p/EN2 axis.

To explore the function and regulation mechanism of circ_0071589 in colorectal cancer (CRC). The expression levels of circ_0071589, microRNA-296-5p (miR-296-5p), and Engrailed-2 (EN2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to check the protein levels of EN2 and apoptosis-related proteins. Cell colony formation and 5-Ethynyl-29-deoxyuridine (EdU) assay were used to exhibit cell proliferation. Cell apoptosis was shown by flow cytometry. Tube formation assay manifested the angiogenesis ability of CRC cells. Transwell assay demonstrated cell migration and invasion. The interaction between miR-296-5p and circ_0071589 or EN2 was identified by dual-luciferase reporter assay. The effect of circ_0071589 on tumor formation was demonstrated by in vivo tumor formation experiments. Immunohistochemical (IHC) assay was used to detect the positive cell rate of Ki67 in tumor tissue. Circ_0071589 was upregulated in CRC tissue and cells. Circ_0071589 knockdown repressed CRC cells proliferation, angiogenesis, migration, invasion, and promoted cell apoptosis. MiR-296-5p was downregulated in CRC tissue and cells. And miR-296-5p inhibitor could reverse the malignant phenotypes and angiogenesis inhibition of CRC cells caused by circ_0071589 knockdown. Additionally, miR-296-5p decreased CRC cell colony formation, EdU-positive cells, angiogenesis, and increased cell apoptosis through reducing the expression level of EN2. Finally, circ_0071589 silencing inhibited tumor formation in vivo. Circ_0071589 upregulated EN2 expression through sponging miR-296-5p, thereby promoting the malignant phenotype and angiogenesis of CRC cells, which provided a new target for the treatment of CRC.

Antiproliferative and Tubulin-Destabilising Effects of 3-(Prop-1-en-2-yl)azetidin-2-Ones and Related Compounds in MCF-7 and MDA-MB-231 Breast Cancer Cells.

A series of novel 3-(prop-1-en-2-yl)azetidin-2-one, 3-allylazetidin-2-one and 3-(buta-1,3-dien-1-yl)azetidin-2-one analogues of combretastatin A-4 (CA-4) were designed and synthesised as colchicine-binding site inhibitors (CBSI) in which the ethylene bridge of CA-4 was replaced with a ß-lactam (2-azetidinone) scaffold. These compounds, together with related prodrugs, were evaluated for their antiproliferative activity, cell cycle effects and ability to inhibit tubulin assembly. The compounds demonstrated significant in vitro antiproliferative activities in MCF-7 breast cancer cells, particularly for compounds 9h, 9q, 9r, 10p, 10r and 11h, with IC50 values in the range 10-33 nM. These compounds were also potent in the triple-negative breast cancer (TBNC) cell line MDA-MB-231, with IC50 values in the range 23-33 nM, and were comparable with the activity of CA-4. The compounds inhibited the polymerisation of tubulin in vitro, with significant reduction in tubulin polymerization, and were shown to interact at the colchicine-binding site on tubulin. Flow cytometry demonstrated that compound 9q arrested MCF-7 cells in the G2/M phase and resulted in cellular apoptosis. The antimitotic properties of 9q in MCF-7 human breast cancer cells were also evaluated, and the effect on the organization of microtubules in the cells after treatment with compound 9q was observed using confocal microscopy. The immunofluorescence results confirm that ß-lactam 9q is targeting tubulin and resulted in mitotic catastrophe in MCF-7 cells. In silico molecular docking supports the hypothesis that the compounds interact with the colchicine-binding domain of tubulin. Compound 9q is a novel potent microtubule-destabilising agent with potential as a promising lead compound for the development of new antitumour agents.

Peer review of the pesticide risk assessment of the active substance (3E)-dec-3-en-2-one.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, the Netherlands, for the pesticide active substance (3E)-dec-3-en-2-one and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative post-harvest use of (3E)-dec-3-en-2-one on potato as a sprouting inhibitor applied by hot fogging in potato storage rooms. The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Protein kinase C beta relieves autism-like behavior in EN2 knockout mice via upregulation of the FTO/PGC-1α/UCP1 axis.

Increasing evidence suggests that disruption of neuron activity contributes to the autistic phenotype. Thus, we aimed in this study to explore the role of protein kinase C beta (PKCß) in the regulation of neuron activity in an autism model. The expression of PKCß in the microarray data of autism animal models was obtained from the Gene Expression Omnibus database. Then, mice with autism-like behavior were prepared in EN2 knockout (-/- ) mice. The interaction between PKCß on fat mass and obesity-associated protein (FTO) as well as between PGC-1α and uncoupling protein 1 (UCP1) were characterized. The effect of FTO on the N6 -methyladenosine (m6A) modification level of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) was assayed. Following transfection of overexpressed PKCß and/or silenced UCP1, effects of PKCß and UCP1 in autism-like behaviors in EN2-/- mice were analyzed. Results showed that PKCß was downregulated in EN2-/- mouse brain tissues or neurons. PKCß promoted the expression and stability of FTO, which downregulated the m6A modification level of PGC-1α to promote its expression. Moreover, PGC-1α positively targeted the expression of UCP1. PKCß knockdown enhanced sociability and spatial exploration ability, and reduced neuron apoptosis in EN2-/- mouse models of autism, which was reversed by UCP1 overexpression. Collectively, PKCß overexpression leads to activation of the FTO/m6A/PGC-1α/UCP1 axis, thus inhibiting neuron apoptosis and providing neuroprotection in mice with autism-like behavior.

MiR-33a targets FOSL1 and EN2 as a clinical prognostic marker for sarcopenia by glioma.

To determine the relationship between glioma and muscle aging and to predict prognosis by screening for co-expressed genes, this study examined the relationship between glioma and sarcopenia. The study identified eight co-downregulated miRNAs, three co-upregulated miRNAs, and seven genes associated with overall glioma survival, namely, KRAS, IFNB1, ALCAM, ERBB2, STAT3, FOSL1, and EN2. With a multi-factor Cox regression model incorporating FOSL1 and EN2, we obtained ROC curves of 0.702 and 0.709, respectively, suggesting that glioma prognosis can be predicted by FOSL1 and EN2, which are differentially expressed in both cancer and aged muscle. FOSL1 and EN2 were analyzed using Gene Set Enrichment Analysis to identify possible functional pathways. RT-qPCR and a dual-luciferase reporter gene system verified that hsa-miR-33a targets FOSL1 and EN2. We found that hsa-mir-33a co-targeting FOSL1 and EN2 has a good predictive value for glioblastoma and skeletal muscle reduction.

An Open-Framework Structured Material: [Ni(en)2]3[Fe(CN)6]2 as a Cathode Material for Aqueous Sodium- and Potassium-Ion Batteries.

Open-framework structured materials such as Prussian blue analogues and sodium superionic conductor (NASICON) materials have been regarded as promising electrode candidates for aqueous batteries. These materials exhibit outstanding long cycle stability and high rate capacity retention, due to their high ion diffusive rate in the crystal and the stable structure maintenance in the electrochemical reaction process. Herein, an open-framework structured material [Ni(en)2]3[Fe(CN)6]2 (NienHCF) is prepared and first used as a cathode material for aqueous sodium- and potassium-ion batteries. The resultant material exhibits a high output potential and outstanding cycle performance (93.4% after 500 cycles at 1 A g-1) in K-ion batteries. Meanwhile, the electrochemical reaction mechanism is investigated. After coupling with the activated carbon anode, the K-ion full cell has 91.5% capacity retention at 5 A g-1 and retains 77.2% after 1000 cycles at 0.5 A g-1, exhibiting the potential as an electrode material for rechargeable aqueous K-ion and Na-ion batteries.

What a difference a gas makes: Effect of foaming on dynamic aroma release and perception of a model dairy matrix.

When we are trying to decrease caloric intake by reducing fat content, aroma perception of the food is changed as well. Since previous studies indicated that foaming changes the aroma release, it was our goal to understand the physico-chemical background of this effect. Therefore, ten aroma compounds were added to a foamed acidified dairy matrix (4% milk protein, 1% gelatin, 60% gas volume). We simulated oral temperature conditions in a simplistic way through incubation at 40 °C and analyzed aroma release using headspace-solid phase microextraction-gas chromatography-ion mobility spectrometry. Significantly more highly hydrophobic aroma compounds were released from the foamed matrix than the unfoamed matrix, while compounds of intermediate hydrophobicity were released more from unfoamed matrix. The effect was independent from foam collapse and persisted for hours afterwards. Analytical results were complemented by orthonasal and retronasal sensory perception studies, which confirmed significant differences between aroma release behavior from foamed foods.

Regioselective asymmetric bioreduction of trans-4-phenylbut-3-en-2-one by whole-cell of Weissella cibaria N9 biocatalyst.

There is a considerable interest in the asymmetric production of chiral allylic alcohols, the main building blocks of many functional molecules. The asymmetric reduction of α,ß-unsaturated ketones is difficult with traditional chemical protocols in a regioselective and stereoselective manner. In this study, the reductive capacity of whole cell of Leuconostoc mesenteroides N6, Weissella paramesenteroides N7, Weissella cibaria N9, and Leuconostoc pseudomesenteroides N13 was investigated as whole-cell biocatalysts in the enantioselective reduction of (E)-4-phenylbut-3-en-2-one (1). The biocatalytic reduction of 1 to (S,E)-4-phenylbut-3-en-2-ol ((S,E)-2) using the whole cell of W. cibaria N9 isolated from Turkish sourdough was developed in a regioselective fashion, occurring with excellent conversion and recovering the product in good yield. In biocatalytic reduction reactions, the conversion of the substrate and the enantiomeric excess (ee) of the product are significantly affected by optimization parameters such as temperature, agitation rate, pH, and incubation time. Effects of these parameters on ee and conversion were investigated comprehensively. In addition, to our knowledge, this is the first report on production of (S,E)-2 using whole-cell biocatalyst in excellent yield, conversion with enantiopure form and at gram scale. These findings pave the way for the use of whole cell of W. cibaria N9 for challenging higher substrate concentrations of different α,ß-unsaturated ketones for regioselective reduction at industrial scale.

Engrailed 2 deficiency and chronic stress alter avoidance and motivation behaviors.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impairments in social interaction, cognition, and communication, as well as the presence of repetitive or stereotyped behaviors and interests. ASD is most often studied as a neurodevelopmental disease, but it is a lifelong disorder. Adults with ASD experience more stressful life events and greater perceived stress, and frequently have comorbid mood disorders such as anxiety and depression. It remains unclear whether adult exposure to chronic stress can exacerbate the behavioral and neurodevelopmental phenotypes associated with ASD. To address this issue, we first investigated whether adult male and female Engrailed-2 deficient (En2-KO, En2-/-) mice, which display behavioral disturbances in avoidance tasks and dysregulated monoaminergic neurotransmitter levels, also display impairments in instrumental behaviors associated with motivation, such as the progressive ratio task. We then exposed adult En2-KO mice to chronic environmental stress (CSDS, chronic social defeat stress), to determine if stress exacerbated the behavioral and neuroanatomical effects of En2 deletion. En2-/- mice showed impaired instrumental acquisition and significantly lower breakpoints in a progressive ratio test, demonstrating En2 deficiency decreases motivation to exert effort for reward. Furthermore, adult CSDS exposure increased avoidance behaviors in En2-KO mice. Interestingly, adult CSDS exposure also exacerbated the deleterious effects of En2 deficiency on forebrain-projecting monoaminergic fibers. Our findings thus suggest that adult exposure to stress may exacerbate behavioral and neuroanatomical phenotypes associated with developmental effects of genetic En2 deficiency.

Synthesis of pyrazoline fatty chain derivatives and its effects on melanoma cells.

Skin cancer is the most common type of cancer in Brazil, representing 30% of all cases. Among these, melanoma represents only 3% of malignant neoplasms; however, it is the most serious and has a high capacity for metastasis. For this reason, it is extremely important to identify more efficient compounds and treatments that stop or decrease the proliferation of melanoma, even in its more advanced stages. This work reports the synthesis and biological evaluation of two homologous series of pyrazoline fatty chain derivatives as potent antitumoral agents in the melanoma B16F10 cell line. Cells were treated with pyrazoline fatty chain compounds (3, 30, 300, and 3000 µM) for 0, 24, 48, and 72 h. Decreased cell viability was observed when using most compounds at different concentrations and times. The structure-activity relationship (SAR) between antitumoral activity and the number of carbons and lipophilicity, as well as the oxygen-sulfur bioisosteric exchange, was evaluated. Among the tested derivatives, the lipophilic compounds 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-carboxamide (2d) and 5-hydroxy-5-(trifluoromethyl)-3-undecyl-4,5-dihydro-1H-pyrazole-1-thiocarboxamide (3d) showed the best results in the B16F10 cell line, as they produced the best cell viability decrease effects. The presence of fatty unbranched undecyl chain in the molecular structure appears to be important for its antimelanoma properties.

Circular RNA circ_0000467 regulates colorectal cancer development via miR-382-5p/EN2 axis.

Circular RNAs (CircRNAs), belonging to non-coding RNAs, exert a crucial modulatory role in cancer progression. In this study, circRNA microarray analysis was utilized to screen differentially expressed circRNA in colorectal cancer (CRC) and circ_0000467 was identified as one circRNA whose expression was significantly upregulated in CRC. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) indicated that circ_0000467 and engrailed-2 (EN2) expression levels were up-modulated, while the expression level of miR-382-5p was down-modulated in CRC tissues. The depletion of circ_0000467 expression was found to impede the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) processes in CRC cells, which were examined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Transwell experiments. Dual-luciferase reporter assay was used to verify the targeting relationship between circ_0000467 and miR-382-5p. It was also revealed that circ_0000467 could up-regulate EN2 expression via repressing miR-382-5p in CRC cells. Furthermore, EN2 overexpression counteracted the suppressing effects of circ_0000467 knockdown on the malignant behaviors of CRC cells. To sum up, circ_0000467 facilitates CRC development by modulating the miR-382-5p/EN2 axis, and circ_0000467 is a promising target for CRC therapy.

A Selective Ratiometric Receptor 2-((E)-(3-(prop-1-en-2-yl)phenylimino)methyl)-4-nitrophenol for the Detection of Cu2+ ions Supported By DFT Studies.

A Schiff-base 2-((E)-(3-(prop-1-en-2-yl)phenylimino)methyl)-4-nitrophenol (Receptor 1) colorimetric probe was synthesized and its UV-visible and fluorescence spectral properties for the sensing of Cu+ 2 ions in CH3OH/H2O (60:40,v/v) solvent system was explored. The Receptor 1 showed the discriminating spectral behavior with the addition of Cu2+ ions solution. The other metal ions showed no significant effect towards Receptor 1. Moreover, the addition of Cu2+ ions to the Receptor 1 demonstrated the shift in the peak towards longer wavelength of 405 nm due to the ligand to metal charge transfer (LMCT) effect. The red-shift and new peak at 405 nm are due to the deprotonation of the -OH group and formation of complex and O-Cu covalent bond, respectively. A slight increase in the Cu2+ ion concentration exhibited strong absorption and fluorescence properties, leading to the spontaneous change in color from pale yellow to orange. Additionally, Density Functional Theory (DFT) studies were performed to investigate the interaction of Cu2+ ions with Receptor 1. The decrease in the energies (3.59062 kcal/mol to 0.36028 kcal/mol) of Cu2+-Receptor-1 complex compared to Receptor 1 confirms the strong interaction with high stability. The association constant (Ka) of Cu2+-Receptor-1 complex was found as 175000 M- 1. The limit of detection (LOD) was calculated and noted as 179 nM.

microRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2.

BACKGROUND: Bladder cancer is considered a malignant tumour characterised by great heterogeneity. Engrailed-2 may be a gene implicated in bladder cancer. Bioinformatics analysis found base pair complementation between microRNA-27b and engrailed-2. The present study aimed to investigate the reciprocal association between microRNA-27b and engrailed-2 in bladder cancer. METHODS: The microRNA-27b and the protein of engrailed-2 in the tissues and cells of the bladder were detected. The processes of apoptosis, proliferation, invasion, and migration of tumour cells were evaluated. The co-action between microRNA-27b and engrailed-2 was detected by a luciferase reporter system. Finally, the interaction between microRNA-27b and engrailed-2 was further verified in vivo. RESULTS: The study found that the expression level of microRNA-27b is lower in bladder cancer tissues and cells than that in neighbouring ordinary tissues, whereas the opposite outcome was observed regarding the expression level of engrailed-2. Furthermore, microRNA-27b expression level is not significantly linked to the age of patients with bladder cancer; however, it is significantly associated with the clinicopathological grade of bladder cancer. Notably, engrailed-2 is negatively regulated by microRNA-27b. Transfection with microRNA-27b was associated with a significant reduction in the activity of bladder cancer cells and promoted apoptosis, while engrailed-2 restoration effectively reversed the above effects of microRNA-27b on bladder cancer in vitro and in vivo. CONCLUSIONS: In conclusion, engrailed-2 is engaged in the development and process of bladder cancer through the negative mediation of microRNA-27b; additionally, microRNA-27b/engrailed-2 could form a signalling pathway with a significant effect on the process of bladder cancer.

Down-Regulation of miR-181a-5p Prevents Cerebral Ischemic Injury by Upregulating En2 and Activating Wnt/ß-catenin Pathway.

PURPOSE: Cerebral ischemic injury contributes to severe dysfunction of the brain, which triggers extremely high mortality and disability. The role of microRNA (miR)-181a-5p is documented in cerebral ischemic injury. Therefore, this study intended to further figure out the mechanism of miR-181a-5p in cerebral ischemic injury. METHODS: miR-181a-5p expression in middle cerebral artery occlusion (MCAO) mouse model, oxygen-glucose-deprivation/reoxygenation (OGD/R) N2a cell model, and serum from acute ischemic injury (ACI) patients was evaluated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Gain- and loss-of-function assays were implemented in MCAO mice and OGD/R-induced N2a cells. In mice, the cerebral infarction area was assessed with 2,3,5-triphenyltetrazolium chloride staining, the number of damaged neurons by Nissl staining, and apoptosis by TdT-mediated dUTP-biotin nick end-labeling staining. Moreover, N2a cell apoptosis and proliferation were determined with flow cytometry or 5-ethynyl-2'-deoxyuridine staining, respectively. The expression of En2 and Wnt/ß-catenin pathway-related factors was determined with RT-qPCR and Western blot analysis. The targeting relationship between miR-181a-5p and En2 was evaluated by dual luciferase reporter gene assay. RESULTS: miR-181a-5p was highly expressed in serum of ACI patients, MCAO mice, and OGD/R-induced N2a cells. En2, lowly expressed in MCAO mice, was targeted by miR-181a-5p, and miR-181a-5p down-regulation activated the Wnt/ß-catenin pathway. Furthermore, miR-181a-5p inhibition or En2 overexpression reduced cerebral infarction area, the number of damaged neurons, and apoptosis in MCAO mice, and also diminished apoptosis and accelerated proliferation of OGD/R-induced N2a cells. CONCLUSION: miR-181a-5p suppression activated Wnt/ß-catenin pathway and sequentially attenuated cerebral ischemic injury by targeting En2.

(3E)-4-[(Naphthalen-1-yl)amino]-pent-3-en-2-one hemihydrate.

The title compound, C15H15NO·0.5H2O, was prepared from α-naphthyl-amine and 2,4-penta-nedione in a 1:1 ratio. An intra-molecular N-H⋯O hydrogen bond in the N-naphthyl-pent-3-en-2-one mol-ecule involving the amine and carbonyl groups strengthens the structure. The water mol-ecule interacts with two symmetry-related N-naphthyl-pent-3-en-2-one mol-ecules viaby O-H⋯O hydrogen bonds.

Association Between Systolic Blood Pressure and Cardiovascular Inpatient Cost Moderated by Peer-Support Intervention Among Adult Patients With Type 2 Diabetes: A 2-Cohort Study.

OBJECTIVES: People with type 2 diabetes and increased systolic blood pressure (SBP) are at high risk of cardiovascular disease (CVD). In this study, we aimed to investigate the association between CVD-related hospital payments and SBP and tested whether this association is influenced by diabetes peer support. METHODS: Two cohorts comprising people with type 2 diabetes were included in the study. The first cohort comprised 4,704 patients with type 2 diabetes assessed between 2008 and 2009 from 18 general practices in Cambridgeshire and followed up to 2009-2011. The second cohort comprised 1,121 patients with type 2 diabetes from post-trial follow-up data, recruited between 2011 and 2012 and followed up to 2015. SBP was measured at baseline. Inpatient payments for CVD hospitalization within 2 years since baseline was the main outcome. The impact of 1:1, group or combined diabetes peer support and usual care were investigated in the second cohort. Adjusted mean CVD inpatient payments per person were estimated using a 2-part model after adjusting for baseline characteristics. RESULTS: A "hockey-stick" relationship between baseline SBP and estimated CVD inpatient payment was identified in both cohorts, with a threshold at 133 to 141 mmHg, suggesting increased payments for patients with SBP below and above the threshold. The combined peer-support intervention altered the aforementioned association, with no increased payment with SBP above the threshold, and payment slightly decreased with SBP beyond the threshold. CONCLUSIONS: SBP maintained between 133 and 141 mmHg is associated with the lowest CVD disease management costs for patients with type 2 diabetes. Combined peer-support intervention could significantly decrease CVD-related hospital payments.

Verbenone Inhibits Attraction of Ips pini (Coleoptera: Curculionidae) to Pheromone-Baited Traps in Northern Arizona.

Recent outbreaks of engraver beetles, Ips spp. De Geer (Coleoptera: Curculionidae; Scolytinae), in ponderosa pine, Pinus ponderosa var. scopulorum Engelm. (Pinales: Pinaceae), forests of northern Arizona have resulted in widespread tree mortality. Current treatment options, such as spraying individual P. ponderosa with insecticides or deep watering of P. ponderosa in urban and periurban settings, are limited in applicability and scale. Thinning stands to increase tree vigor is also recommended, but appropriate timing is crucial. Antiaggregation pheromones, widely used to protect high-value trees or areas against attacks by several species of Dendroctonus Erichson (Coleoptera: Curculionidae; Scolytinae), would provide a feasible alternative with less environmental impacts than current treatments. We evaluated the efficacy of the antiaggregation pheromone verbenone (4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one) in reducing attraction of pine engraver, I. pini (Say), to funnel traps baited with their aggregation pheromone in two trapping assays. Treatments included 1) unbaited control, 2) aggregation pheromone (bait), 3) bait with verbenone deployed from a pouch, and 4) bait with verbenone deployed from a flowable and biodegradable formulation (SPLAT Verb, ISCA Technologies Inc., Riverside, CA). Unbaited traps caught no beetles. In both assays, baited traps caught significantly more I. pini than traps with either formulation of verbenone, and no significant difference was observed between the verbenone pouch and SPLAT Verb. In the second assay, we also examined responses of Temnochila chlorodia (Mannerheim) (Coleoptera: Trogositidae), a common bark beetle predator. Traps containing verbenone pouches caught significantly fewer T. chlorodia than the baited control and SPLAT Verb treatments. We conclude that verbenone shows promise for reducing tree mortality from I. pini.