Search

BackgroundSecondary prevention is an important strategy to reduce the burden of cardiovascular disease (CVD), a leading cause of death worldwide. Despite the growing evidence for the effectiveness of digital health interventions (DHIs) for the secondary prevention of CVD, the majority are designed with minimal input from target end users, resulting in poor uptake and usage. ObjectiveThis study aimed to optimize the acceptance and effectiveness of a DHI for the secondary prevention of CVD through co-design, integrating end users’ perspectives throughout. MethodsA theory-driven, person-based approach using co-design was adopted for the development of the DHI, known as INTERCEPT. This involved a 4-phase iterative process using online workshops. In phase 1, a stakeholder team of health care professionals, software developers, and public and patient involvement members was established. Phase 2 involved identification of the guiding principles, content, and design features of the DHI. In phase 3, DHI prototypes were reviewed for clarity of language, ease of navigation, and functionality. To anticipate and interpret DHI usage, phase 4 involved usability testing with participants who had a recent cardiac event (

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Long-read sequencing is driving rapid progress in genome assembly across all major groups of life, including species of the family Drosophilidae, a longtime model system for genetics, genomics, and evolution. We previously developed a cost-effective hybrid Oxford Nanopore (ONT) long-read and Illumina short-read sequencing approach and used it to assemble 101 drosophilid genomes from laboratory cultures, greatly increasing the number of genome assemblies for this taxonomic group. The next major challenge is to address the laboratory culture bias in taxon sampling by sequencing genomes of species that cannot easily be reared in the lab. Here, we build upon our previous methods to perform amplification-free ONT sequencing of single wild flies obtained either directly from the field or from ethanol-preserved specimens in museum collections, greatly improving the representation of lesser studied drosophilid taxa in whole-genome data. Using Illumina Novaseq X Plus and ONT P2 sequencers with R10.4.1 chemistry, we set a new benchmark for inexpensive hybrid genome assembly at US $150 per genome while assembling genomes from as little as 35 ng of genomic DNA from a single fly. We present 183 new genome assemblies for 179 species as a resource for drosophilid systematics, phylogenetics, and comparative genomics. Of these genomes, 62 are from pooled lab strains and 121 from single adult flies. Despite the sample limitations of working with small insects, most single-fly diploid assemblies are comparable in contiguity (>1 Mb contig N50), completeness (>98% complete dipteran BUSCOs), and accuracy (>QV40 genome-wide with ONT R10.4.1) to assemblies from inbred lines. We present a well-resolved multi-locus phylogeny for 360 drosophilid and 4 outgroup species encompassing all publicly available (as of August 2023) genomes for this group. Finally, we present a Progressive Cactus whole-genome, reference-free alignment built from a subset of 298 suitably high-quality drosophilid genomes. The new assemblies and alignment, along with updated laboratory protocols and computational pipelines, are released as an open resource and as a tool for studying evolution at the scale of an entire insect family.

Abstract The brain derived‐neurotrophic factor (BDNF) Val66Met polymorphism causes functional changes in BDNF, and is associated with obesity and some psychiatric disorders, but its relationship to health‐related quality of life (HRQoL) remains unknown. This study examined, in youth with obesity, whether carriers of the BDNF Val66met polymorphism Met‐alleles (A/A or G/A) differed from noncarriers (G/G) on HRQoL. The participants were 187 adolescents with obesity. Ninety‐nine youth were carriers of the homozygous Val/Val (G/G) alleles, and 88 were carriers of the Val/Met (G/A) or Met/Met (A/A) alleles. Blood samples were drawn in the morning after an overnight fast for genotyping. HRQoL was measured using the Pediatric‐Quality of Life core version. Compared to carriers of the Val66Met Val (G/G) alleles, carriers of the Met‐Alleles reported significantly higher physical –HRQoL (p = 0.02), school‐related HRQoL, (p = 0.05), social‐related HRQoL (p = 0.05), and total HRQoL (p = 0.03), and a trend for Psychosocial‐HRQoL. Research is needed to confirm our findings and determine whether carriers of the BDNF Val66Met homozygous Val (G/G) alleles may be at risk of diminished HRQoL, information that can influence interventions in a high‐risk population of inactive youth with obesity.

Abstract Background Wolbachia is a widespread bacterial endosymbiont that can inhibit vector competency when stably transinfected into the mosquito, Aedes aegypti, a primary vector of the dengue virus (DENV) and other arboviruses. Although a complete mechanistic understanding of pathogen blocking is lacking, it is likely to involve host immunity induction and resource competition between Wolbachia and DENV, both of which may be impacted by microbiome composition. The potential impact of Wolbachia transinfection on host fitness is also of importance given the widespread release of mosquitos infected with the Drosophila melanogaster strain of Wolbachia (wMel) in wild populations. Here, population-level genomic data from Ae. aegypti was surveyed to establish the relationship between the density of wMel infection and the composition of the host microbiome. Results Analysis of genomic data from 172 Ae. aegypti females across six populations resulted in an expanded and quantitatively refined, species-level characterization of the bacterial, archaeal, and fungal microbiome. This included 844 species of bacteria across 23 phyla, of which 54 species were found to be ubiquitous microbiome members across these populations. The density of wMel infection was highly variable between individuals and negatively correlated with microbiome diversity. Network analyses revealed wMel as a hub comprised solely of negative interactions with other bacterial species. This contrasted with the large and highly interconnected network of other microbiome species that may represent members of the midgut microbiome community in this population. Conclusion Our bioinformatic survey provided a species-level characterization of Ae. aegypti microbiome composition and variation. wMel load varied substantially across populations and individuals and, importantly, wMel was a major hub of a negative interactions across the microbiome. These interactions may be an inherent consequence of heightened pathogen blocking in densely infected individuals or, alternatively, may result from antagonistic Wolbachia-incompatible bacteria that could impede the efficacy of wMel as a biological control agent in future applications. The relationship between wMel infection variation and the microbiome warrants further investigation in the context of developing wMel as a multivalent control agent against other arboviruses. Video Abstract

Abstract Globally invasive Aedes aegypti disseminate numerous arboviruses that impact human health. One promising method to control Ae. aegypti populations is transinfection with Wolbachia pipientis, which naturally infects ~40–52% of insects but not Ae. aegypti. Transinfection of Ae. aegypti with the wMel Wolbachia strain induces cytoplasmic incompatibility (CI), allows infected individuals to invade native populations, and inhibits transmission of medically relevant arboviruses by females. Female insects undergo post-mating physiological and behavioral changes—referred to as the female post-mating response (PMR)—required for optimal fertility. PMRs are typically elicited by male seminal fluid proteins (SFPs) transferred with sperm during mating but can be modified by other factors, including microbiome composition. Wolbachia has modest effects on Ae. aegypti fertility, but its influence on other PMRs is unknown. Here, we show that Wolbachia influences female fecundity, fertility, and re-mating incidence and significantly extends the longevity of virgin females. Using proteomic methods to examine the seminal proteome of infected males, we found that Wolbachia moderately affects SFP composition. However, we identified 125 paternally transferred Wolbachia proteins, but the CI factor proteins (Cifs) were not among them. Our findings indicate that Wolbachia infection of Ae. aegypti alters female PMRs, potentially influencing control programs that utilize Wolbachia-infected individuals.

Abstract Background There are well‐recognized benefits of behavioral interventions that include exercise for children and adolescents with obesity. However, such behavioral weight management programs may precipitate unintended consequences. It is unclear if different exercise modalities impact eating behaviors differently in youth with obesity. Objectives The purpose of this study was to examine the effects of aerobic, resistance, and combined aerobic and resistance exercise training on eating attitudes and behaviors (uncontrolled eating, restrained eating, emotional eating, external eating and food craving) among adolescents with overweight and obesity. Methods N = 304 (70% female) adolescents with overweight and obesity participated in the 6‐month Healthy Eating Aerobic and Resistance Training in Youth (HEARTY) randomized controlled trial. All participants were inactive post‐pubertal adolescents (15.6 ± 1.4 years) with a mean BMI = 34.6 ± 4.5 kg/m2. The Food Craving Inventory (food cravings), Dutch Eating Behavior Questionnaire (restrained eating, emotional eating, external eating), and the Three‐Factor Eating Questionnaire (uncontrolled eating) were used to assess eating attitudes and behaviors. Results All exercise groups showed within‐group decreases in external eating and food cravings. Participants randomized to the Combined training group and were more adherent showed the greatest improvements in eating behaviors and cravings. Conclusions A 6‐month exercise intervention produced improvements in disordered eating behaviors and food cravings, but effects may be gender and modality‐specific. Findings highlight the need to tailor exercise intervention to participant characteristics for the promotion of healthier eating and weight management outcomes in youth with obesity. Clinical Trial Registration # and Date: ClinicalTrials.Gov NCT00195858, September 12, 2005

According to The Organization for Economic Co-operation and Development (OECD), demand for poultry meat and eggs consumption is growing consistently since poultry meat and eggs are readily available and cheap source for nutritional protein. As such, there is pressing demand from industry for improved protocols to determine chicken sex, especially in layer industry since only females can lay eggs. Extensive efforts are being dedicated to avoiding male chicks culling by developing in-ovo sexing detection methods. Any established in-ovo detection method will need to be validated by embryo genotyping. Therefore, there is a growing demand for fast, inexpensive, and precise method for proper discrimination between males and females in the poultry science community. Our aim with this study was to develop an accurate, high-throughput protocol for sex determination using small volumes of blood. We designed primers targeting the Hint-W gene within the W chromosome clearly distinguishing between males and females. In the interest of establishing an efficient protocol without the need for gel electrophoresis, crude DNA extraction without further purification was coupled with qPCR. We validated the accuracy of our method using established protocols and gonad phenotyping and tested our protocol with four different chicken breeds, day-nine embryos, day-old chicks and adult chicken. In summary, we developed a fast, cost-effective, and accurate method for the genotyping of sex chromosomes in chicken.

Background: We examined the characteristics and outcomes in a contemporary ambulatory population of patients with atrial fibrillation (AF), comparing rate control with rhythm control. Methods: This is a post hoc analysis of a cluster-randomized trial (Integrated Management Program Advancing Community Treatment of Atrial Fibrillation [IMPACT-AF]) in ambulatory AF patients from 2016 to 2018, which compared use of a clinical decision support tool for general practitioners to usual care. This analysis compared patients managed with rate vs rhythm control, at entry into the study. Outcomes included AF-related emergency department (ED) visits, unplanned cardiovascular hospitalizations, and bleeding events at 12 months. Results: A total of 870 patients were included in this analysis, 99 (11.4%) in the rhythm-control group, and 40% women. In the rhythm-control group, the mean age was younger (70 ± 11.4 vs 72.7 ± 9.5 years, P = 0.03), a higher number were paroxysmal (80% vs 43%, P < 0.001), and CHADS2 scores were lower. The rate of AF-related ED visits was higher in the rhythm-control group (17.2 vs 7.3%, P = 0.003), and repeat visits (rate ratio 3.03, 95% confidence interval [1.99-4.52], P < 0.001). The number of repeat ED visits was independently associated with female sex and being in the rhythm-control group. Conclusions: Both rate- and rhythm-control patients have recurrent ED visits, with a higher rate in patients treated with rhythm control. These findings are observational, but taken in the context of current guidelines could help develop further therapies aimed at improving symptom burden in both rhythm- and rate-control patients to broadly improve healthcare utilization in the AF population. Résumé: Contexte: Nous avons examiné les caractéristiques et le devenir de patients ambulatoires contemporains atteints de fibrillation auriculaire (FA) dans le cadre d’une comparaison entre la maîtrise de la fréquence cardiaque et la maîtrise du rythme cardiaque. Méthodologie: Nous avons effectué une analyse a posteriori d’un essai à répartition aléatoire par grappes (Integrated Management Program Advancing Community Treatment of Atrial Fibrillation [IMPACT-AF]) mené de 2016 à 2018 chez des patients ambulatoires atteints de FA en vue de comparer un outil d’aide à la décision clinique destiné aux omnipraticiens avec les soins habituels. Notre analyse a permis d’établir une comparaison entre les patients pris en charge par une maîtrise de la fréquence cardiaque et ceux pris en charge par une maîtrise du rythme cardiaque lors de leur inscription à l’essai. Les paramètres d’évaluation comprenaient les consultations aux urgences liées à la FA, les hospitalisations imprévues ayant des causes cardiovasculaires et les épisodes hémorragiques à 12 mois. Résultats: Au total, 870 patients ont été inclus dans cette analyse; 99 (11,4 %) faisaient partie du groupe pris en charge par une maîtrise du rythme cardiaque, et 40 % étaient de femmes. Dans le groupe pris en charge par une maîtrise du rythme cardiaque, l’âge moyen était moindre (70 ± 11,4 ans vs 72,7 ± 9,5 ans, P = 0,03), un plus grand nombre de patients présentaient une FA paroxystique (80 % vs 43 %, P

Background: Major societal guidelines recommend a 5-day stop interval before cardiac surgery for patients with acute coronary syndrome receiving clopidogrel. Yet, many such patients present with high acuity, generating surgeon inclination toward use of shorter stop intervals. Thus, this study aimed to determine the impact of the duration and timing of the interval of clopidogrel cessation on adverse bleeding events. Methods: Patients who underwent cardiac surgery between 2009 and 2016 at a tertiary-care centre were included in this retrospective cohort study. Multivariable logistic regression models adjusted for clopidogrel stop interval, age, urgency of procedure, and procedure type were used to quantify the effect of clinically relevant baseline demographic characteristics on incidence of massive transfusion as well as hemorrhagic complication outcomes. Results: A total of 5748 patients underwent cardiac surgery. In this cohort, 1743 patients (30.3%) received clopidogrel preoperatively, and 884 (50.7%) of these patients discontinued clopidogrel 5 days before presenting to the operating room. The administration of clopidogrel 1-2 days before surgery (odds ratio 1.97; 95% confidence interval: 1.18 to 3.29) was an independent predictor for massive transfusions and hemorrhagic complications (odds ratio 1.85; 95% confidence interval: 1.01 to 3.37). The 3-4 day group did not have an increased risk of major bleeding complications. The risk for both massive transfusions and hemorrhagic complications also increased with the urgency and complexity of surgery. Conclusion: A clopidogrel stop interval of 3-4 days preoperatively was not associated with an increased risk for major bleeding complications. Résumé: Introduction: Les grandes lignes directrices sociétales recommandent une interruption de cinq jours avant l’intervention chirurgicale du cœur des patients atteints d’un syndrome coronarien aigu qui prennent du clopidogrel. Toutefois, comme il s’agit pour plusieurs d’entre eux de patients de haute acuité, le chirurgien penche vers l’utilisation d’une interruption plus courte. Par conséquent, la présente étude avait pour objectif de déterminer les conséquences de la durée et du moment de la cessation du clopidogrel sur les événements hémorragiques indésirables. Méthodes: La présente étude de cohorte rétrospective portait sur les patients qui avaient subi une intervention chirurgicale au cœur entre 2009 et 2016 dans un centre de soins tertiaires. Nous avons utilisé les modèles multivariés de régression logistique ajustés à l’interruption du clopidogrel, à l’âge, à l’urgence de l’intervention chirurgicale et au type d’intervention chirurgicale pour quantifier les effets des caractéristiques démographiques initiales cliniquement pertinentes sur la fréquence des transfusions massives ainsi que sur les issues des complications hémorragiques. Résultats: Un total de 5 748 patients ont subi une intervention chirurgicale au cœur. Dans cette cohorte, parmi les 1 743 patients (30,3 %) qui avaient reçu du clopidogrel avant l’opération, 884 (50,7 %) avaient cessé le clopidogrel cinq jours avant leur admission à la salle d’opération. L’administration du clopidogrel un à deux jours avant l’intervention chirurgicale (ratio d’incidence approché 1,97; intervalle de confiance [IC] à 95 % : de 1,18 à 3,29) était un prédicteur indépendant des transfusions massives et des complications hémorragiques (ratio d’incidence approché 1,85; [IC] à 95 % : de 1,01 à 3,37). Le groupe de l’interruption de trois à quatre jours n’a pas montré de risque accru de complications hémorragiques graves. Le risque de transfusions massives et de complications hémorragiques a aussi contribué à l’augmentation de l’urgence et de la complexité de l’intervention chirurgicale. Conclusion: Une interruption du clopidogrel de trois à quatre jours avant l’opération n’a pas été associée à un risque accru de complications hémorragiques graves.

Abstract Background Emotional disorders in young people are increasing but studies have found that this age group do not always recognise the signs and symptoms of mental health problems in themselves or others. The Mental Health Foundation’s school-based Peer Education Project (PEP) has the potential to improve young people’s understanding of their own mental health at a critical developmental stage (early adolescence) using a peer teaching method. This study is a process evaluation to understand: the mechanisms through which PEP might improve young people’s mental health literacy, any challenges with delivery, how the project can be embedded within wider school life and how it can be improved to be of most benefit to the widest number of young people. We will also validate a bespoke mental health literacy questionnaire, and test the feasibility of using it to measure outcomes in preparation for a future study evaluating effectiveness. Methods All schools recruited to the study will receive the PEP intervention. The process evaluation will be informed by realist evaluation approaches to build understanding regarding key mechanisms of change and the impact of different school contexts. The evaluation will test and revise an existing intervention logic model which has been developed in partnership with the Mental Health Foundation. Process evaluation data will be collected from newly recruited schools (n = 4) as well as current PEP user schools (n = 2) including training and lesson delivery observations, staff interviews and student focus groups. Baseline and follow-up data will be collected in all newly recruited intervention schools (n = 4) from all students in Year 7/8 (who receive the PEP) and recruited peer educators in Year 12 via a self-report survey. Discussion This study will enable us to refine the logic model underpinning the peer education project and identify areas of the intervention that can be improved. Findings will also inform the design of a future effectiveness study which will test out the extent to which PEP improves mental health literacy.

Aims: Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning and blood banking requirements. Methods: We performed a retrospective cohort study of adult patients who underwent orthopaedic surgery at four Canadian hospitals between 2014 and 2016. We studied all patients admitted to hospital for nonarthroscopic joint surgeries, amputations, and fracture surgeries. For each surgery and surgical subgroup, we characterized the proportion of patients who received red blood cell (RBC) transfusion, the mean/median number of RBC units transfused, and exposure to platelets and plasma. Results: Of the 14,584 included patients, the most commonly performed surgeries were knee arthroplasty (24.8%), hip arthroplasty (24.6%), and hip fracture surgery (17.4%). A total of 10.3% of patients received RBC transfusion; the proportion of patients receiving RBC transfusions varied widely based on the surgical subgroup (0.0% to 33.1%). Primary knee arthroplasty and hip arthroplasty, the two most common surgeries, were associated with in-hospital transfusion frequencies of 2.8% and 4.5%, respectively. RBC transfusion occurred in 25.0% of hip fracture surgeries, accounting for the greatest total number of RBC units transfused in our cohort (38.0% of all transfused RBC units). Platelet and plasma transfusions were uncommon. Conclusion: Orthopaedic surgeries were associated with variable rates of transfusion. The rate of RBC transfusion is highly dependent on the surgery type. Identifying surgeries with the highest transfusion rates, and further evaluation of factors that contribute to transfusion in identified at-risk populations, can serve to inform perioperative planning and blood bank requirements, and facilitate pre-emptive transfusion mitigation strategies.

Identifying ecological indicators and management factors that influence sustainability and resilience, both ecologically and economically, is key to restoring grassland landscapes' ecological function. We examine soil and vegetation responses to different combinations of adaptive multi-paddock grazing (AMP) managed to improve soil and ecological function as the foundation to improve the provision of ecosystem services and economic benefits, relative to heavy continuous grazing (HCG) and moderate continuous grazing (MCG).We used multidimensional scaling (MDS) and analysis of similarities (ANOSIM) to indicate associations among soil, soil biota and vegetation parameters to indicate associations in response to the different grazing management strategies. AMP grazing improved total herbaceous biomass, C4 tallgrasses, native perennial summer growing forbs, and vegetation cover while decreasing bare ground cover and less productive or invasive herbaceous species. AMP also had higher biomass of total soil microbes, actinomycetes, and gram-positive and gram-negative bacteria associated with improved soil aggregation and nutrient cycling than HCG, with MCG having intermediate responses. Arbuscular mycorrhizal fungi crucial for enhanced water and nutrient acquisition by plants were higher with AMP and were lower with HCG, with MCG intermediate between the two. AMP also outperformed HCG and usually MCG in the critical soil physical elements such as soil aggregation fostering improved ecological function. These are substantive improvements, achieved despite AMP having double the stocking rate of MCG. These positive outcomes were generally not compromised with the BURN and HAY treatments as both were managed with AMP grazing. The exception was HAY, which showed increased soil penetration resistance compared to AMP but less than with HCG or MCG. AMP grazing also compared favorably with the grazing Exclosures for most parameters measured. The presence of low densities of trees had predominantly positive results relative to treeless AMP and MCG, particular for soil temperature, soil organic matter and cation exchange capacity. These findings provide evidence that AMP grazing is a powerful management strategy to positively alter plant composition and soil physical, chemical, and microbial properties relative to season-long continuous grazing to enhance the provision of ecosystem services and economic benefits in Southern Tallgrass prairie.

Abstract Precursor messenger RNA (pre-mRNA) splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions (introns) and ligates coding regions (exons) into a continuous message (mature mRNA). This process is highly regulated and can be highly flexible through a process known as alternative splicing, which allows for several transcripts to arise from a single gene, thereby greatly increasing genetic plasticity and the diversity of proteome. Alternative splicing is particularly prevalent in neuronal cells, where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis, migration and synaptic function. The continuous changes in splicing patterns and a high demand on many cis- and trans-splicing factors contribute to the susceptibility of neuronal tissues to splicing defects. The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function. Several of the most common neurodegenerative diseases involve some form of splicing defect(s), such as Alzheimer’s disease, Parkinson’s disease and spinal muscular atrophy. Our growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide therapeutics. Here we review our current understanding of the effects alternative splicing has on neuronal differentiation, neuronal migration, synaptic maturation and regulation, as well as the impact on neurodegenerative diseases. We will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.

Background: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. Methods: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. Results: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. Conclusions: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients. Résumé: Introduction: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d’un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d’optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L’objectif de la présente étude était d’examiner les obstacles réels et perçus à l’utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d’optimiser les modèles de soins à distance. Méthodes: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. Résultats: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d’uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l’utilisation optimale et l’adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l’ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d’information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. Conclusions: L’absence d’une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l’implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l’utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l’utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

The advent of the Internet of Things (IoT) has triggered an increased demand for sensing devices with multiple integrated wireless transceivers. These platforms often support the advantageous use of multiple radio technologies to exploit their differing characteristics. Intelligent radio selection techniques allow these systems to become highly adaptive, ensuring more robust and reliable communications under dynamic channel conditions. In this paper, we focus on the wireless links between devices equipped by deployed operating personnel and intermediary access-point infrastructure. We use multi-radio platforms and wireless devices with multiple and diverse transceiver technologies to produce robust and reliable links through the adaptive control of available transceivers. In this work, the term ‘robust’ refers to communications that can be maintained despite changes in the environmental and radio conditions, i.e., during periods of interference caused by non-cooperative actors or multi-path or fading conditions in the physical environment. In this paper, a multi-objective reinforcement learning (MORL) framework is applied to address a multi-radio selection and power control problem. We propose independent reward functions to manage the trade-off between the conflicting objectives of minimised power consumption and maximised bit rate. We also adopt an adaptive exploration strategy for learning a robust behaviour policy and compare its online performance to conventional methods. An extension to the multi-objective state–action–reward–state–action (SARSA) algorithm is proposed to implement this adaptive exploration strategy. When applying adaptive exploration to the extended multi-objective SARSA algorithm, we achieve a 20% increase in the F1 score in comparison to one with decayed exploration policies.

Abstract Oocyte composition can directly influence offspring fitness, particularly in oviparous species such as most insects, where it is the primary form of parental investment. Oocyte production is also energetically costly, dependent on female condition and responsive to external cues. Here, we investigated whether mating influences mature oocyte composition in Drosophila melanogaster using a quantitative proteomic approach. Our analyses robustly identified 4,485 oocyte proteins and revealed that stage-14 oocytes from mated females differed significantly in protein composition relative to oocytes from unmated females. Proteins forming a highly interconnected network enriched for translational machinery and transmembrane proteins were increased in oocytes from mated females, including calcium binding and transport proteins. This mating-induced modulation of oocyte maturation was also significantly associated with proteome changes that are known to be triggered by egg activation. We propose that these compositional changes are likely to have fitness consequences and adaptive implications given the importance of oocyte protein composition, rather than active gene expression, to the maternal-to-zygotic transition and early embryogenesis.

Central nervous system (CNS) infections are a major cause of human morbidity and mortality worldwide. Even patients that survive, CNS infections can have lasting neurological dysfunction resulting from immune and pathogen induced pathology. Developing approaches to noninvasively track pathology and immunity in the infected CNS is crucial for patient management and development of new therapeutics. Here, we develop novel MRI-based approaches to monitor virus-specific CD8+ T cells and their relationship to cerebrovascular pathology in the living brain. We studied a relevant murine model in which a neurotropic virus (vesicular stomatitis virus) was introduced intranasally and then entered the brain via olfactory sensory neurons – a route exploited by many pathogens in humans. Using T2*-weighted high-resolution MRI, we identified small cerebral microbleeds as an early form of pathology associated with viral entry into the brain. Mechanistically, these microbleeds occurred in the absence of peripheral immune cells and were associated with infection of vascular endothelial cells. We monitored the adaptive response to this infection by developing methods to iron label and track individual virus specific CD8+ T cells by MRI. Transferred antiviral T cells were detected in the brain within a day of infection and were able to reduce cerebral microbleeds. These data demonstrate the utility of MRI in detecting the earliest pathological events in the virally infected CNS as well as the therapeutic potential of antiviral T cells in mitigating this pathology.

Abstract Background There is clear evidence that patients with prior myocardial infarction and a reduced ejection fraction benefit from implantation of a cardioverter-defibrillator (ICD). It is unclear whether this benefit is altered by whether or not revascularization is performed prior to ICD implantation. Methods This was a retrospective cohort study following patients who underwent ICD implantation from 2002 to 2014. Patients with ischemic cardiomyopathy and either primary or secondary prevention ICDs were selected for inclusion. Using the electronic medical record, cardiac catheterization data, revascularization status (percutaneous coronary intervention or coronary bypass surgery) were recorded. The outcomes were mortality and ventricular arrhythmia. Results There were 606 patients included in the analysis. The mean age was 66.3 ± 10.1 years, 11.9% were women, and the mean LVEF was 30.5 ± 12.0, 58.9% had a primary indication for ICD, 82.0% of the cohort had undergone coronary catheterization prior to ICD implantation. In the overall cohort, there were fewer mortality and ventricular arrhythmia events in patients who had undergone prior revascularization. In patients who had an ICD for secondary prevention, revascularization was associated with a decrease in mortality (HR 0.46, 95% CI (0.24, 0.85) p = 0.015), and a trend towards fewer ventricular arrhythmia (HR 0.62, 95% CI (0.38, 1.00) p = 0.051). There was no association between death or ventricular arrhythmia with revascularization in patients with primary prevention ICDs. Conclusion Revascularization may be beneficial in preventing recurrent ventricular arrhythmia, and should be considered as adjunctive therapy to ICD implantation to improve cardiovascular outcomes.

Islands can be powerful demonstrations of how destructive invasive species can be on endemic faunas and insular ecologies. Oceanic islands in the eastern Indian Ocean have suffered dramatically from the impact of one of the world’s most destructive invasive species, the black rat, causing the loss of endemic terrestrial mammals and ongoing threats to ground-nesting birds. We use molecular genetic methods on both ancient and modern samples to establish the origins and minimum invasion frequencies of black rats on Christmas Island and the Cocos-Keeling Islands. We find that each island group had multiple incursions of black rats from diverse geographic and phylogenetic sources. Furthermore, contemporary black rat populations on these islands are highly admixed to the point of potentially obscuring their geographic sources. These hybridisation events between black rat taxa also pose potential dangers to human populations on the islands from novel disease risks. Threats of ongoing introductions from yet additional geographic sources is highlighted by genetic identifications of black rats found on ships, which provides insight into how recent ship-borne human smuggling activity to Christmas Island can negatively impact its endemic species.

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is functionally related to BDNF, and is associated with obesity and metabolic complications in adults, but limited research exists among adolescents. This study comparatively examined carriers and non-carriers of the BDNF Val66Met polymorphism on body composition, energy intake, and cardiometabolic profile among adolescents with obesity. The sample consisted of 187 adolescents with obesity; 99 were carriers of the homozygous Val (G/G) alleles and 88 were carriers of the Val/Met (G/A) or Met (A/A) alleles. Cardiometabolic profile and DNA were quantified from fasted blood samples. Body composition was assessed by magnetic resonance imaging (MRI). Compared to carriers of the homozygous Val (G/G) allele, carriers of the Val/Met (G/A) or Met/Met (A/A) variants exhibited significantly higher protein (p = 0.01) and fat (p = 0.05) intake, C-Reactive protein (p = 0.05), and a trend toward higher overall energy intake (p = 0.07), fat-free mass (p = 0.07), and lower HDL-C (p = 0.07) Results showed for the first time that among youth with obesity, carriers of the Val66Met BDNF Met-alleles exhibited significantly higher C-reactive protein and energy intake in the form of fat and protein compared to Val-allele carriers, thereby providing support for the possible role of BDNF in appetite, weight, and metabolic regulation during adolescence.Clinical Trial Registration:http://clinicaltrials.gov/, identifier NCT00195858.

Background: Prior studies have demonstrated an association between appropriate implantable cardioverter defibrillator (ICD) shocks and mortality in clinical trials. The effect of shock burden on heart failure and mortality has not been previously studied in a large population-based cohort. Methods: The cohort was derived using a comprehensive prospective ICD registry in the province of Nova Scotia with a mean follow-up of 4 ± 2.3 years. With the use of time-varying analysis, the relationship among shock burden, mortality, and heart failure hospitalization was determined. Results: A total of 776 patients (mean age of 64.8 years) were included in the study, of whom 37% received appropriate therapy during follow-up. A single ICD shock did not confer an increased mortality risk compared with no therapy (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.84-1.79; P = 0.3), but mortality risk was significantly increased with ≥ 2 shocks (HR, 3.23; 95% CI, 2.04-5.09; P < 0.0001). There was a significant increase in heart failure hospitalization associated with receiving 1 ICD shock (HR, 2.05; 95% CI, 1.46-2.89; P < 0.0001) or more than 1 ICD shock (HR, 4.36; CI, 2.53-7.52; P < 0.0001) compared with patients receiving no ICD therapy. Patients who received antitachycardia pacing alone showed no difference in heart failure hospitalization (HR, 0.93; CI, 0.67-1.29; P = 0.7) and improved survival (HR, 0.69; CI, 0.5-0.96; P = 0.03) compared with those receiving no ICD therapy. Conclusion: Ventricular arrhythmia treated with appropriate ICD shocks is associated with an increased risk of heart failure hospitalization, whereas recurrent episodes of ventricular arrhythmia requiring shocks are associated with both higher mortality and higher heart failure hospitalization rates. Résumé: Contexte: Des études menées antérieurement ont révélé l’existence d’un lien entre l’administration appropriée de décharges électriques au moyen d’un défibrillateur cardioverteur implantable (DCI) et la mortalité au cours des essais cliniques. L’effet de telles décharges sur l’insuffisance cardiaque et la mortalité n’avait encore jamais été étudié au sein d’une cohorte d’envergure représentative de la population. Méthodologie: La cohorte a été établie au moyen d’un registre prospectif exhaustif des DCI implantés chez des patients de la Nouvelle-Écosse ayant fait l’objet d’un suivi moyen de 4 ± 2,3 ans. La relation entre le fardeau imposé par les décharges, la mortalité et l’hospitalisation pour insuffisance cardiaque a été déterminée au moyen d’une analyse en fonction du temps. Résultats: Au total, 776 patients (âge moyen : 64,8 ans) ont été admis dans l’étude; 37 % d’entre eux avaient reçu un traitement approprié au cours de la période de suivi. Une seule décharge délivrée par un DCI n’augmentait pas le risque de mortalité par rapport à l’absence de traitement (rapport des risques instantanés [RRI] de 1,23; intervalle de confiance [IC] à 95 %, de 0,84 à 1,79; p = 0,3), mais le risque de mortalité était significativement accru chez les patients ayant reçu ≥ 2 décharges (RRI de 3,23; IC à 95 %, de 2,04 à 5,09; p < 0,0001). Le risque d’hospitalisation pour insuffisance cardiaque s’est révélé significativement supérieur chez les sujets ayant reçu 1 décharge par DCI (RRI de 2,05; IC à 95 %, de 1,46 à 2,89; p < 0,0001) ou plus de 1 décharge par DCI (RRI de 4,36; IC à 95 %, de 2,53-7,52; p < 0,0001), comparativement à ceux n’ayant reçu aucun traitement par DCI. On n’a observé aucune différence quant à l’hospitalisation pour insuffisance cardiaque (RRI de 0,93; IC à 95 %, de 0,67 à 1,29; p = 0,7) et à l’amélioration de la survie (RRI de 0,69; IC à 95 %, de 0,5 à 0,96; p = 0,03) chez les patients qui ont reçu uniquement une stimulation antitachycardie comparativement à ceux qui n’ont reçu aucun traitement par DCI. Conclusion: L’arythmie ventriculaire traitée de façon appropriée au moyen de décharges électriques délivrées par un DCI est associée à un risque accru d’hospitalisation pour insuffisance cardiaque, tandis que des épisodes récurrents d’arythmie ventriculaire exigeant un traitement par décharge électrique sont associés à des taux supérieurs de mortalité et d’hospitalisation pour insuffisance cardiaque.

Background: Cardiac resynchronization therapy (CRT) is effective in treating advanced heart failure (HF), but data describing benefits and long-term outcomes for upgrades from a preexisting device are limited. This study sought to compare long-term outcomes in de novo CRT implants with those eligible for CRT with a prior device. Methods: This is a retrospective cohort study using data from a provincial registry (2002-2015). Patients were included if they had mild-moderate HF, left ventricular ejection fraction ≤ 35%, and QRS duration ≥ 130 ms. Patients were classified as de novo CRT or upgraded to CRT from a prior device. Outcomes were mortality and composite mortality and HF hospitalization. Results: There were 342 patients included in the study. In a multivariate model, patients in the upgraded cohort (n = 233) had a higher 5-year mortality rate (adjusted hazard ratio, 2.86; 95% confidence interval, 1.59-5.15; P = 0.0005) compared with the de novo cohort (n = 109) and higher composite mortality and HF hospitalization (adjusted hazard ratio, 2.60; 95% confidence interval, 1.54-4.37; P = 0.0003). Conclusions: Implantation of de novo CRTs was associated with lower mortality and HF hospitalization compared with upgraded CRTs from preexisting devices. It is unknown whether these differences are due to the timing of CRT implementation or other clinical factors. Further work in this area may be helpful to determine how to improve outcomes for these patients. Résumé: Contexte: La thérapie de resynchronisation cardiaque (TRC) est efficace pour traiter l’insuffisance cardiaque avancée, mais les données décrivant les bienfaits et les résultats à long terme de la mise à niveau d’un implant déjà en place sont limitées. La présente étude visait à comparer les résultats à long terme chez les patients recevant un implant de TRC de novo et chez ceux ayant déjà un implant qui sont admissibles à une TRC. Méthodologie: Il s’agit d’une étude de cohorte rétrospective reposant sur les données issues d’un registre provincial (2002-2015). Les patients ont été inclus dans l’étude s’ils présentaient une insuffisance cardiaque légère ou modérée, une fraction d’éjection ventriculaire gauche ≤ 35 % et un intervalle QRS ≥ 130 ms. Les patients ont été classés dans le groupe TRC de novo ou dans le groupe TRC remplaçant un implant antérieur. Les paramètres d’évaluation étaient la mortalité et le critère regroupant la mortalité et l’hospitalisation pour insuffisance cardiaque. Résultats: En tout, 342 patients ont été inclus dans l’étude. Après analyse selon un modèle multivarié, le taux de mortalité à 5 ans était plus élevé (rapport des risques instantanés [RRI] corrigé de 2,86; intervalle de confiance [IC] à 95 % de 1,59 à 5,15], p = 0,0005) dans la cohorte TRC remplaçant un implant antérieur (n = 233) que dans la cohorte TRC de novo (n = 109), tout comme le taux pour le critère regroupant la mortalité et l’hospitalisation pour insuffisance cardiaque (RRI corrigé de 2,60; IC à 95 % de 1,54 à 4,37], p = 0,0003). Conclusions: L’implantation d’une TRC de novo était associée à un taux de mortalité et d’hospitalisation pour insuffisance cardiaque inférieur comparativement à l’implantation d’une TRC chez des patients ayant déjà un implant. On ne sait pas si ces différences sont attribuables au moment choisi pour l’implantation de la TRC ou à d’autres facteurs cliniques. D’autres études sur cette question pourraient être utiles afin de déterminer comment améliorer les résultats chez ces patients.

AbstractSexual reproduction in internally fertilizing species requires complex coordination between female and male reproductive systems and among the diverse tissues of the female reproductive tract (FRT). Here, we report a comprehensive, tissue-specific investigation of Drosophila melanogaster

Background: Understanding how frailty affects patients listed for transplantation has been identified as a priority research need. Frailty may be associated with a high risk of death or wait-list withdrawal, but this has not been evaluated in a large multicenter cohort of Canadian wait-listed patients. Objective: The primary objective is to evaluate whether frailty is associated with death or permanent withdrawal from the transplant wait list. Secondary objectives include assessing whether frailty is associated with hospitalization, quality of life, and the probability of being accepted to the wait list. Design: Prospective cohort study. Setting: Seven sites with established renal transplant programs that evaluate patients for the kidney transplant wait list. Patients: Individuals who are being considered for the kidney transplant wait list. Measurements: We will assess frailty using the Fried Phenotype, a frailty index, the Short Physical Performance Battery, and the Clinical Frailty Scale at the time of listing for transplantation. We will also assess frailty at the time of referral to the wait list and annually after listing in a subgroup of patients. Methods: The primary outcome of the composite of time to death or permanent wait-list withdrawal will be compared between patients who are frail and those who are not frail and will account for the competing risks of deceased and live donor transplantation. Secondary outcomes will include number of hospitalizations and length of stay, and in a subset, changes in frailty severity over time, change in quality of life, and the probability of being listed. Recruitment of 1165 patients will provide >80% power to identify a relative hazard of ≥1.7 comparing patients who are frail to those who are not frail for the primary outcome (2-sided α = .05), whereas a more conservative recruitment target of 624 patients will provide >80% power to identify a relative hazard of ≥2.0. Results: Through December 2019, 665 assessments of frailty (inclusive of those for the primary outcome and all secondary outcomes including repeated measures) have been completed. Limitations: There may be variation across sites in the processes of referral and listing for transplantation that will require consideration in the analysis and results. Conclusions: This study will provide a detailed understanding of the association between frailty and outcomes for wait-listed patients. Understanding this association is necessary before routinely measuring frailty as part of the wait-list eligibility assessment and prior to ascertaining the need for interventions that may modify frailty. Trial Registration: Not applicable as this is a protocol for a prospective observational study.

We introduce the rationale for, and architecture of, the European Space Agency Climate Change Initiative (CCI) Open Data Portal (http://cci.esa.int/data/). The Open Data Portal hosts a set of richly diverse datasets – 13 “Essential Climate Variables” – from the CCI programme in a consistent and harmonised form and to provides a single point of access for the (>100 TB) data for broad dissemination to an international user community. These data have been produced by a range of different institutions and vary across both scientific and spatio-temporal characteristics. This heterogeneity of the data together with the range of services to be supported presented significant technical challenges. An iterative development methodology was key to tackling these challenges: the system developed exploits a workflow which takes data that conforms to the CCI data specification, ingests it into a managed archive and uses both manual and automatically generated metadata to support data discovery, browse, and delivery services. It utilises both Earth System Grid Federation (ESGF) data nodes and the Open Geospatial Consortium Catalogue Service for the Web (OGC-CSW) interface, serving data into both the ESGF and the Global Earth Observation System of Systems (GEOSS). A key part of the system is a new vocabulary server, populated with CCI specific terms and relationships which integrates OGC-CSW and ESGF search services together, developed as part of a dialogue between domain scientists and linked data specialists. These services have enabled the development of a unified user interface for graphical search and visualisation – the CCI Open Data Portal Web Presence.

Dynamic mechanical interactions between adhesion complexes and the cytoskeleton are essential for axon outgrowth and guidance. Whether planar cell polarity (PCP) proteins, which regulate cytoskeleton dynamics and appear necessary for some axon guidance, also mediate interactions with membrane adhesion is still unclear. Here we show that Vangl2 controls growth cone velocity by regulating the internal retrograde actin flow in an N-cadherin-dependent fashion. Single molecule tracking experiments show that the loss of Vangl2 decreased fast-diffusing N-cadherin membrane molecules and increased confined N-cadherin trajectories. Using optically manipulated N-cadherin-coated microspheres, we correlated this behavior to a stronger mechanical coupling of N-cadherin with the actin cytoskeleton. Lastly, we show that the spatial distribution of Vangl2 within the growth cone is selectively affected by an N-cadherin-coated substrate. Altogether, our data show that Vangl2 acts as a negative regulator of axonal outgrowth by regulating the strength of the molecular clutch between N-cadherin and the actin cytoskeleton.

Purpose: Sellar masses may present either with clinical manifestations of mass effect/hormonal dysfunction (CMSM) or incidentally on imaging (pituitary incidentaloma (PI)). This novel population-based study compares these two entities. Methods: Retrospective analysis of all patients within a provincial pituitary registry between January 2006 and June 2014. Results: Nine hundred and three patients were included (681 CMSM, 222 PI). CMSM mainly presented with secondary hormone deficiencies (SHDs) or stalk compression (29.7%), whereas PIs were found in association with neurological complaints (34.2%) (P < 0.0001). PIs were more likely to be macroadenomas (70.7 vs 49.9%; P < 0.0001). The commonest pathologies among CMSM were prolactinomas (39.8%) and non-functioning adenomas (NFAs) (50%) in PI (P < 0.0001). SHDs were present in 41.3% CMSM and 31.1% PI patients (P < 0.0001) and visual field deficit in 24.2 and 29.3%, respectively (P = 0.16). CMSM were more likely to require surgery (62.9%) than PI (35.8%) (P < 0.0005). The commonest surgical indications were impaired vision and radiological evidence of optic nerve compression. Over a follow-up period of 5.7 years for CMSM and 5.0 years for PI, tumour growth/recurrence occurred in 7.8% of surgically treated CMSM and 2.6% without surgery and PI, 0 and 4.9%, respectively (P = 1.0). There were no significant differences in the risk of new-onset SHD in CMSM vs PI in those who underwent surgery (P = 0.7) and those who were followed without surgery (P = 0.58). Conclusions: This novel study compares the long-term trends of PI with CMSM, highlighting the need for comprehensive baseline and long-term radiological and hormonal evaluations in both entities.

Postcopulatory sexual selection is credited as a principal force behind the rapid evolution of reproductive characters, often generating a pattern of correlated evolution between interacting, sex-specific traits. Because the female reproductive tract is the selective environment for sperm, one taxonomically widespread example of this pattern is the co-diversification of sperm length and female sperm-storage organ dimension. In Drosophila, having testes that are longer than the sperm they manufacture was believed to be a universal physiological constraint. Further, the energetic and time costs of developing long testes have been credited with underlying the steep evolutionary allometry of sperm length and constraining sperm length evolution in Drosophila. Here, we report on the discovery of a novel spermatogenic mechanism—sperm cyst looping—that enables males to produce relatively long sperm in short testis. This phenomenon (restricted to members of the saltans and willistoni species groups) begins early during spermatogenesis and is potentially attributable to heterochronic evolution, resulting in growth asynchrony between spermatid tails and the surrounding spermatid and somatic cyst cell membranes. By removing the allometric constraint on sperm length, this evolutionary innovation appears to have enabled males to evolve extremely long sperm for their body mass while evading delays in reproductive maturation time. On the other hand, sperm cyst looping was found to exact a cost by requiring greater total energetic investment in testes and a pronounced reduction in male lifespan. We speculate on the ecological selection pressures underlying the evolutionary origin and maintenance of this unique adaptation.

Abstract Background Rapid evolution is a hallmark of reproductive genetic systems and arises through the combined processes of sequence divergence, gene gain and loss, and changes in gene and protein expression. While studies aiming to disentangle the molecular ramifications of these processes are progressing, we still know little about the genetic basis of evolutionary transitions in reproductive systems. Here we conduct the first comparative analysis of sperm proteomes in Lepidoptera, a group that exhibits dichotomous spermatogenesis, in which males produce a functional fertilization-competent sperm (eupyrene) and an incompetent sperm morph lacking nuclear DNA (apyrene). Through the integrated application of evolutionary proteomics and genomics, we characterize the genomic patterns potentially associated with the origination and evolution of this unique spermatogenic process and assess the importance of genetic novelty in Lepidopteran sperm biology. Results Comparison of the newly characterized Monarch butterfly (Danaus plexippus) sperm proteome to those of the Carolina sphinx moth (Manduca sexta) and the fruit fly (Drosophila melanogaster) demonstrated conservation at the level of protein abundance and post-translational modification within Lepidoptera. In contrast, comparative genomic analyses across insects reveals significant divergence at two levels that differentiate the genetic architecture of sperm in Lepidoptera from other insects. First, a significant reduction in orthology among Monarch sperm genes relative to the remainder of the genome in non-Lepidopteran insect species was observed. Second, a substantial number of sperm proteins were found to be specific to Lepidoptera, in that they lack detectable homology to the genomes of more distantly related insects. Lastly, the functional importance of Lepidoptera specific sperm proteins is broadly supported by their increased abundance relative to proteins conserved across insects. Conclusions Our results identify a burst of genetic novelty amongst sperm proteins that may be associated with the origin of heteromorphic spermatogenesis in ancestral Lepidoptera and/or the subsequent evolution of this system. This pattern of genomic diversification is distinct from the remainder of the genome and thus suggests that this transition has had a marked impact on lepidopteran genome evolution. The identification of abundant sperm proteins unique to Lepidoptera, including proteins distinct between specific lineages, will accelerate future functional studies aiming to understand the developmental origin of dichotomous spermatogenesis and the functional diversification of the fertilization incompetent apyrene sperm morph.

Mutations inGPSM2cause a rare disease characterized by deafness and brain abnormalities. Here the authors show that Gpsm2 forms a molecular complex with a heterotrimeric G-protein subunit, whirlin and a myosin motor to regulate actin dynamics in neurons and auditory hair cell stereocilia.

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite ("seesaw") transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome.

Obesity in youth increases the risk of type 2 diabetes (T2D), and both are risk factors for neurocognitive deficits. Exercise attenuates the risk of obesity and T2D while improving cognitive function. In adults, these benefits are associated with the actions of the brain-derived neurotrophic factor (BDNF), a protein critical in modulating neuroplasticity, glucose regulation, fat oxidation, and appetite regulation in adults. However, little research exists in youth. This study examined the associations between changes in diabetes risk factors and changes in BDNF levels after 6 months of exercise training in adolescents with obesity. The sample consisted of 202 postpubertal adolescents with obesity (70% females) aged 14–18 years who were randomized to 6 months of aerobic and/or resistance training or nonexercise control. All participants received a healthy eating plan designed to induce a 250/kcal deficit per day. Resting serum BDNF levels and diabetes risk factors, such as fasting glucose, insulin, homeostasis model assessment (HOMA-B—beta cell insulin secretory capacity) and (HOMA-IS—insulin sensitivity), and hemoglobin A1c (HbA1c), were measured after an overnight fast at baseline and 6 months. There were no significant intergroup differences on changes in BDNF or diabetes risk factors. In the exercise group, increases in BDNF were associated with reductions in fasting glucose (β = −6.57, SE = 3.37, p=0.05) and increases in HOMA-B (β = 0.093, SE = 0.03, p=0.004) after controlling for confounders. No associations were found between changes in diabetes risk factors and BDNF in controls. In conclusion, exercise-induced reductions in some diabetes risk factors were associated with increases in BDNF in adolescents with obesity, suggesting that exercise training may be an effective strategy to promote metabolic health and increases in BDNF, a protein favoring neuroplasticity. This trial is registered with ClinicalTrials.gov NCT00195858, September 12, 2005 (funded by the Canadian Institutes of Health Research).