Phenotypically plastic responses to environmental variation are more complex than life history theory predicts.

For insects that exhibit wing polyphenic development, abiotic and biotic signals dictate the adult wing morphology of the insect in an adaptive manner such that in stressful environments the formation of a flight-capable morph is favored and in low stress environments a flightless morph is favored. While there is a relatively large amount known about the environmental cues that dictate morph formation in wing polyphenic hemipterans like planthoppers and aphids, whether those cues dictate the same morphs in non-hemipteran (i.e. cricket) wing polyphenic species has not been explicitly investigated. To experimentally test the generality of environmental cue determination of wing polyphenism across taxa with diverse life histories, in this study we tested the importance of food quantity, parasitic infection, and tactile cues on wing morph determination in the wing polyphenic sand field cricket, Gryllus firmus. Our results also show that certain stress cues, such as severe diet quantity limitation and parasitic infection, actually led to an increase in the production of flightless morph. Based on these findings, our results suggest that physiological and genetic constraints are important to an organism's ability to respond to environmental variation in an adaptive manner beyond simple life history trade-offs.

Strategies to reduce out-of-pocket medication costs for Canadians with peripheral arterial disease.

BACKGROUND: Given that peripheral arterial disease (PAD) disproportionately affects people of lower socioeconomic status, out-of-pocket expenses for preventive medications are a major barrier to their use. We carried out a cost comparison of drug therapies for PAD to identify prescribing strategies that minimize out-of-pocket expenses for these medications. METHODS: Between March and June 2019, we contacted outpatient pharmacies in Hamilton, Ontario, Canada, to assess pricing of pharmacologic therapies at dosages included in the 2016 American College of Cardiology/American Heart Association guideline for management of lower extremity PAD. We also gathered pricing information for supplementary charges, including delivery, pill splitting and blister packaging. We calculated prescription prices with and without dispensing fees for 30-day brand-name and generic prescriptions, and 90-day generic prescriptions. RESULTS: Twenty-four pharmacies, including hospital-based, independent and chain, were included in our sample. In the most extreme scenario, total 90-day medication costs could differ by up to $1377.26. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee and delivery cost, if any. CONCLUSION: By opting for prescriptions for 90 days or as long as possible, selecting the lowest-cost generic drugs available in each drug class, and identifying dispensing locations with lower fees, prescribers can minimize out-of-pocket patient medication expenses. This may help improve adherence to guideline-recommended therapies for the secondary prevention of vascular events in patients with PAD.

The effects of dietary nitrate supplementation on endurance exercise performance and cardiorespiratory measures in healthy adults: a systematic review and meta-analysis.

BACKGROUND: Nitrate supplementation is thought to improve performance in endurance sports. OBJECTIVE: To meta-analyze studies evaluating the effect of nitrate supplementation on endurance sports performance among adults. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science and CINAHL without language restrictions. METHODS: We included studies that: 1) compared nitrate supplementation with placebo; 2) enrolled adults engaging in an endurance-based activity; and 3) reported a performance measure or surrogate physiologic outcome. We evaluated risk of bias using the Cochrane Collaboration tool and pooled data with a random-effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate confidence in estimates. RESULTS: We included 73 studies (n = 1061). Nitrate supplementation improved power output (MD 4.6 watts, P < 0.0001), time to exhaustion (MD 25.3 s, P < 0.00001), and distance travelled (MD 163.7 m, P = 0.03). We found no significant difference on perceived exertion, time trial performance and work done. Nitrate supplementation decreased VO2 (MD - 0.04 L/min, P < 0.00001) but had no significant effect on VO2max or blood lactate levels. CONCLUSION: The available evidence suggests that dietary nitrate supplementation benefits performance-related outcomes for endurance sports.

Strategies to Reduce Out-of-Pocket Medication Costs for Canadians Living with Heart Failure.

INTRODUCTION: Daily medication is the cornerstone of evidence-based therapy to reduce mortality and morbidity in patients with heart failure (HF). Up to 20% of Canadian patients pay for medications out of pocket. We sought to identify strategies that patients and prescribers can employ to reduce these costs. METHODS: We collected data from outpatient pharmacies in Hamilton, Ontario. We determined prices for different medications in each of the drug classes recommended for HF with reduced ejection fraction in the Canadian Cardiovascular Society's guidelines. We examined differences in dispensing and delivery fees and inquired about other cost-saving strategies. RESULTS: We collected data from 24 different pharmacies, including a selection of hospital-based, independent, and larger chain pharmacies. In the most extreme scenario (i.e., 90-day prescription instead of a 30-day prescription and the least expensive generic drug instead of the most expensive brand name drug), total medication costs can differ by up to $495.56 per month. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee, and delivery cost. CONCLUSIONS: Prescription content, dispensing practice, and pharmacy choice can remarkably impact out-of-pocket costs for HF medications. Prescribers can reduce costs by writing 90-day prescriptions and choosing the lowest-cost generic drugs in each therapeutic class. Patients should consider the services received for their pharmacy dispensing fees, use free delivery services where needed, and request inexpensive generic drugs. Pharmacists can facilitate cost minimization without compromising therapeutic efficacy.

Synergisms in Science: Climate Change and Integrated Pest Management Through the Lens of Communication-2019 Student Debates.

Every year, the Student Debates Subcommittee (SDS) of the Student Affairs Committee (SAC) for the annual Entomological Society of America (ESA) meeting organizes the Student Debates. This year, the SAC selected topics based on their synergistic effect or ability to ignite exponential positive change when addressed as a whole. For the 2019 Student Debates, the SAC SDS identified these topic areas for teams to debate and unbiased introduction speakers to address: 1) how to better communicate science to engage the public, particularly in the area of integrated pest management (IPM), 2) the influential impacts of climate change on agriculturally and medically relevant insect pests, and 3) sustainable agriculture techniques that promote the use of IPM to promote food security. Three unbiased introduction speakers gave a foundation for our audience to understand each debate topic, while each of six debate teams provided a strong case to support their stance or perspective on a topic. Debate teams submitted for a competitive spot for the annual ESA Student Debates and trained for the better part of a year to showcase their talents in presenting logical arguments for a particular topic. Both the debate teams and unbiased introduction speakers provided their insight toward a better understanding of the complexities of each topic and established a foundation to delve further into the topics of science advocacy and communication, climate change, and the many facets of integrated pest management.

The Insulin Signaling Substrate Chico and the Ecdysone Response Element Broad Both Regulate Growth of the Head Horns in the Asian Rhinoceros Beetle, Trypoxylus dichotomus.

Males of the Asian rhinoceros beetle, Trypoxylus dichotomus, possess exaggerated head and thoracic horns that scale dramatically out of proportion to body size. While RNAi-mediated knockdowns of the insulin receptor suggest that the insulin signaling pathway regulates nutrition-dependent growth including exaggerated horns, the genes that regulate disproportionate growth have yet to be identified. We used RNAi-mediated knockdown of several genes to investigate their potential role in growth and scaling of the sexually dimorphic, exaggerated head horns of T. dichotomus. Knockdown of the insulin signaling substrate chico and the ecdysone response element broad caused significant decreases in head horn length, while having no or minimal effects on other structures such as elytra and tibiae. However, scaling of horns to body size was not affected by either knockdown. In addition, knockdown of phosphatase and tensin homolog, a negative regulator of the insulin signaling pathway, had no significant effects on any trait. Our results do not identify any candidate genes that may specifically mediate the allometric aspect of horn growth, but they do confirm the insulin signaling pathway as a mediator of conditional trait expression, and importantly implicate the ecdysone signaling pathway, possibly in conjunction with insulin signaling, as an additional mediator of horn growth.

Dnmt1, Dnmt3a and Dnmt3b cooperate in photoreceptor and outer plexiform layer development in the mammalian retina.

Characterizing the role of epigenetic regulation in the mammalian retina is critical for understanding fundamental mechanisms of retinal development and disease. DNA methylation, an epigenetic modifier of genomic DNA, plays an important role in modulating networks of tissue and cell-specific gene expression. However, the impact of DNA methylation on retinal development and homeostasis of retinal neurons remains unclear. Here, we have created a tissue-specific DNA methyltransferase (Dnmt) triple mutant mouse in an effort to characterize the impact of DNA methylation on retinal development and homeostasis. An Rx-Cre transgene was used to drive targeted mutation of all three murine Dnmt genes in the mouse retina encoding major DNA methylation enzymes DNMT1, DNMT3A and DNMT3B. The triple mutant mice represent a hypomorph model since Dnmt1 catalytic activity was still present and excision of Dnmt3a and Dnmt3b had only about 90% efficiency. Mutation of all three Dnmts resulted in global genomic hypomethylation and dramatic reorganization of the photoreceptor and synaptic layers within retina. Transcriptome and proteomic analyses demonstrated enrichment of dysregulated phototransduction and synaptic genes. The 5 mC signal in triple mutant retina was confined to the central heterochromatin but reduced in the peripheral heterochromatin region of photoreceptor nuclei. In addition, we found a reduction of the 5 mC signal in ganglion cell nuclei. Collectively, this data suggests cooperation of all three Dnmts in the formation and homeostasis of photoreceptors and other retinal neurons within the mammalian retina, and highlight the relevance of epigenetic regulation to sensory retinal disorders and vision loss.

Viral-mediated vision rescue of a novel AIPL1 cone-rod dystrophy model.

Defects in aryl hydrocarbon receptor interacting protein-like1 (AIPL1) are associated with blinding diseases with a wide range of severity in humans. We examined the mechanism behind autosomal dominant cone-rod dystrophy (adCORD) caused by 12 base pair (bp) deletion at proline 351 of hAIPL1 (P351Δ12) mutation in the primate-specific region of human AIPL1. Mutant P351Δ12 human isoform, aryl hydrocarbon receptor interacting protein-like 1 (hAIPL1) mice demonstrated a CORD phenotype with early defects in cone-mediated vision and subsequent photoreceptor degeneration. A dominant CORD phenotype was observed in double transgenic animals expressing both mutant P351Δ12 and normal hAIPL1, but not with co-expression of P351Δ12 hAIPL1 and the mouse isoform, aryl hydrocarbon receptor interacting protein-like 1 (mAipl1). Despite a dominant effect of the mutation, we successfully rescued cone-mediated vision in P351Δ12 hAIPL1 mice following high over-expression of WT hAIPL1 by adeno-associated virus-mediated gene delivery, which was stable up to 6 months after treatment. Our transgenic P351Δ12 hAIPL1 mouse offers a novel model of AIPL1-CORD, with distinct defects from both the Aipl1-null mouse mimicking LCA and the Aipl1-hypomorphic mice mimicking a slow progressing RP.