Field evaluation of a volatile pyrethroid spatial repellent and etofenprox treated clothing for outdoor protection against forest malaria vectors in Cambodia.

Cambodia's goal to eliminate malaria by 2025 is challenged by persistent transmission in forest and forest fringe areas, where people are exposed to Anopheles mosquito bites during the day and night. Volatile pyrethroid spatial repellents (VPSRs) and insecticide-treated clothing (ITC) could address these gaps. This study evaluated the outdoor application of one passive transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. A 7 × 7 Latin-square study was conducted over 49 collection nights in temporary open structures in Mondulkiri Province. All interventions substantially reduced Anopheles landing, with protective efficacy ranging from 61 to 95%. Mathematical modeling showed significant reductions in vectoral capacity, especially with the combined ITC and VPSR and VPSR alone, albeit with decreased effectiveness over time. These interventions have the potential to reduce outdoor and daytime Anopheles biting, offering valuable contributions to malaria elimination efforts in Cambodia and the Greater Mekong Subregion, contingent upon achieving effective coverage and adherence.

Additional blood meals increase sporozoite infection in Anopheles mosquitoes but not Plasmodium falciparum genetic diversity.

The availability of nutrients from mosquito blood meals accelerates the development of Plasmodium falciparum laboratory strains in artificially infected Anopheles gambiae mosquitoes. The impact of multiple blood meals on the number of P. falciparum genotypes developing from polyclonal natural human malaria infections (field-isolates) remains unexplored. Here, we experimentally infect An. gambiae with P. falciparum field-isolates and measure the impact of an additional non-infectious blood meal on parasite development. We also assess parasite genetic diversity at the blood stage level of the parasite in the human host and of the sporozoites in the mosquito. Additional blood meals increase the sporozoite infection prevalence and intensity, but do not substantially affect the genetic diversity of sporozoites in the mosquito. The most abundant parasite genotypes in the human blood were transmitted to mosquitoes, suggesting that there was no preferential selection of specific genotypes. This study underlines the importance of additional mosquito blood meals for the development of parasite field-isolates in the mosquito host.

Occupational exposure to malaria, leishmaniasis and arbovirus vectors in endemic regions: A systematic review.

Vector-borne diseases, including dengue, leishmaniasis and malaria, may be more common among individuals whose occupations or behaviours bring them into frequent contact with these disease vectors outside of their homes. A systematic review was conducted to ascertain at-risk occupations and situations that put individuals at increased risk of exposure to these disease vectors in endemic regions and identify the most suitable interventions for each exposure. The review was conducted in accordance with PRISMA guidelines on articles published between 1945 and October 2021, searched in 16 online databases. The primary outcome was incidence or prevalence of dengue, leishmaniasis or malaria. The review excluded ecological and qualitative studies, abstracts only, letters, commentaries, reviews, and studies of laboratory-acquired infections. Studies were appraised, data extracted, and a descriptive analysis conducted. Bite interventions for each risk group were assessed. A total of 1170 articles were screened and 99 included. Malaria, leishmaniasis and dengue were presented in 47, 41 and 24 articles, respectively; some articles presented multiple conditions. The most represented populations were soldiers, 38% (43 of 112 studies); refugees and travellers, 15% (17) each; migrant workers, 12.5% (14); miners, 9% (10); farmers, 5% (6); rubber tappers and missionaries, 1.8% (2) each; and forest workers, 0.9% (1). Risk of exposure was categorised into round-the-clock or specific times of day/night dependent on occupation. Exposure to these vectors presents a critical and understudied concern for outdoor workers and mobile populations. When devising interventions to provide round-the-clock vector bite protection, two populations are considered. First, mobile populations, characterized by their high mobility, may find potential benefits in insecticide-treated clothing, though more research and optimization are essential. Treated clothing offers personal vector protection and holds promise for economically disadvantaged individuals, especially when enabling them to self-treat their clothing to repel vectors. Secondly, semi-permanent and permanent settlement populations can receive a combination of interventions that offer both personal and community protection, including spatial repellents, suitable for extended stays. Existing research is heavily biased towards tourism and the military, diverting attention and resources from vulnerable populations where these interventions are most required like refugee populations as well as those residing in sub-Saharan Africa.

Germline ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition.

The genomics era has facilitated discovery of new genes predisposing to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ERG as a novel autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor critical for definitive hematopoiesis, stem cell function and platelet maintenance. ERG colocalizes with other transcription factors including RUNX1 and GATA2 on promoters/enhancers of genes orchestrating hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 thrombocytopenic individuals from one family and 14 additional ERG variants in unrelated individuals with BMF/HM including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germline ERG variants included cytopenias (thrombocytopenia, neutropenia, pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense, 1 truncating) including 3 missense population variants were functionally characterized. Thirteen potentially pathogenic ETS domain missense variants displayed loss-of-function characteristics disrupting transcriptional transactivation, DNA-binding and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture, and to promote acute erythroleukemia when transplanted into mice, concordant with these variants being loss-of-function. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germline ERG variants has clinical implications for patient/family diagnosis, counselling, surveillance, and treatment strategies including selection of bone marrow donors or cell/gene therapy.

Comparison of the Trapping Efficacy of Locally Modified Gravid Aedes Trap and Autocidal Gravid Ovitrap for the Monitoring and Surveillance of Aedes aegypti Mosquitoes in Tanzania.

The study assessed the trapping efficacy of locally modified (1) Gravid Aedes Trap (GAT) lined with insecticide-treated net (ITN) as a killing agent and (2) Autocidal Gravid Ovitrap (AGO) with sticky board in the semi-field system (SFS) and field setting. Fully balanced Latin square experiments were conducted to compare GAT lined with ITN vs. AGO, both with either yeast or grass infusion. Biogent-Sentinel (BGS) with BG-Lure and no CO2 was used as a standard trap for Aedes mosquitoes. In the SFS, GAT outperformed AGO in collecting both nulliparous (65% vs. 49%, OR = 2.22, [95% CI: 1.89-2.60], p < 0.001) and gravid mosquitoes (73% vs. 64%, OR = 1.67, [95% CI: 1.41-1.97], p < 0.001). Similar differences were observed in the field. Yeast and grass infusion did not significantly differ in trapping gravid mosquitoes (OR = 0.91, [95% CI: 0.77-1.07], p = 0.250). The use of ITN improved mosquito recapture from 11% to 70% in the SFS. The same trend was observed in the field. Yeast was chosen for further evaluation in the optimized GAT due to its convenience and bifenthrin net for its resistance management properties. Mosquito density was collected when using 4× GATs relative to BGS-captured gravid mosquitoes 64 vs. 58 (IRR = 0.82, [95% CI: 0.35-1.95], p = 0.658) and showed no density dependence. Deployment of multiple yeast-baited GAT lined with bifenthrin net is cost-effective (single GAT < $8) compared to other traps such as BGS ($160).

Screening of malaria infections in human blood samples with varying parasite densities and anaemic conditions using AI-Powered mid-infrared spectroscopy.

BACKGROUND: Effective testing for malaria, including the detection of infections at very low densities, is vital for the successful elimination of the disease. Unfortunately, existing methods are either inexpensive but poorly sensitive or sensitive but costly. Recent studies have shown that mid-infrared spectroscopy coupled with machine learning (MIRs-ML) has potential for rapidly detecting malaria infections but requires further evaluation on diverse samples representative of natural infections in endemic areas. The aim of this study was, therefore, to demonstrate a simple AI-powered, reagent-free, and user-friendly approach that uses mid-infrared spectra from dried blood spots to accurately detect malaria infections across varying parasite densities and anaemic conditions. METHODS: Plasmodium falciparum strains NF54 and FCR3 were cultured and mixed with blood from 70 malaria-free individuals to create various malaria parasitaemia and anaemic conditions. Blood dilutions produced three haematocrit ratios (50%, 25%, 12.5%) and five parasitaemia levels (6%, 0.1%, 0.002%, 0.00003%, 0%). Dried blood spots were prepared on Whatman™ filter papers and scanned using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) for machine-learning analysis. Three classifiers were trained on an 80%/20% split of 4655 spectra: (I) high contrast (6% parasitaemia vs. negative), (II) low contrast (0.00003% vs. negative) and (III) all concentrations (all positive levels vs. negative). The classifiers were validated with unseen datasets to detect malaria at various parasitaemia levels and anaemic conditions. Additionally, these classifiers were tested on samples from a population survey in malaria-endemic villages of southeastern Tanzania. RESULTS: The AI classifiers attained over 90% accuracy in detecting malaria infections as low as one parasite per microlitre of blood, a sensitivity unattainable by conventional RDTs and microscopy. These laboratory-developed classifiers seamlessly transitioned to field applicability, achieving over 80% accuracy in predicting natural P. falciparum infections in blood samples collected during the field survey. Crucially, the performance remained unaffected by various levels of anaemia, a common complication in malaria patients. CONCLUSION: These findings suggest that the AI-driven mid-infrared spectroscopy approach holds promise as a simplified, sensitive and cost-effective method for malaria screening, consistently performing well despite variations in parasite densities and anaemic conditions. The technique simply involves scanning dried blood spots with a desktop mid-infrared scanner and analysing the spectra using pre-trained AI classifiers, making it readily adaptable to field conditions in low-resource settings. In this study, the approach was successfully adapted to field use, effectively predicting natural malaria infections in blood samples from a population-level survey in Tanzania. With additional field trials and validation, this technique could significantly enhance malaria surveillance and contribute to accelerating malaria elimination efforts.

Clinical research self-efficacy in academic veterinary clinicians in the United States.

OBJECTIVE: Clinical research is a growing part of the academic clinician's job, and documenting areas of low self-efficacy can inform training initiatives. SAMPLE: 182 US academic veterinary clinicians. METHODS: A survey of academic veterinary clinicians was distributed to 31 US institutions. Self-efficacy was assessed with a modified Clinical Research Appraisal Instrument-12. The relationship between research self-efficacy and completion of formal research training and years of experience was evaluated. RESULTS: Respondents were predominantly junior to midcareer faculty. The lowest reported confidence was in performing advanced statistical analyses (3; 0 to 10). Other low-confidence tasks included designing a qualitative methods study (4; 0 to 10), terminating a collaboration that isn't working (5; 0 to 10), describing a funding agency's review/award process (5; 0 to 10), establishing a timeline for a grant application (5; 0 to 10), establishing collaborator and consultant agreements (5; 0 to 10), and asking staff to leave the project team (5; 0 to 10). Completion of a formal research training program was significantly associated with improved self-efficacy in many tasks. Years of experience was also associated, especially in project management and interpersonal interactions. CLINICAL RELEVANCE: These results highlight the need for targeted training opportunities for academic veterinary clinicians in biostatistical support, qualitative study design methods, and aspects of communication and interpersonal skills that are important for developing and leading effective research teams. Range of confidence suggests that development opportunities in all domains will improve self-efficacy for some clinicians. Future studies should focus on the impact of formal training sessions on various domains of self-efficacy and on targeted mentoring in supporting confidence in more experiential learning domains.

The acceptability of group B streptococcal bacteria (GBS) testing to women, including self-swabbing procedures: A qualitative study.

BACKGROUND: Group B streptococcus (GBS) is a bacterium carried by 20-25 % of pregnant women in the UK, which can be transmitted from pregnant women to their babies at the time of birth. Women can be tested for GBS in pregnancy using a vaginal-rectal swab, however, this testing is currently not routinely offered in the UK. A large clinical trial is underway to determine the clinical and cost-effectiveness of routine testing (ISRCTN reference number ISRCTN49639731). A crucial part of understanding whether this type of test should be implemented is women's views on the acceptability of being offered GBS tests, their preferences towards testing procedures and their willingness to receive these tests. AIM: To explore women's views on the acceptability of different methods of Group B streptococcal bacteria (GBS) testing in pregnancy, including self-swabbing procedures. METHODS: A convenience sample of 19 women (5 pregnant and 14 postpartum) were interviewed using a semi-structured interview guide. Interviews were transcribed and analysed using systematic thematic analysis. RESULTS: Findings show that many of the women interviewed were not concerned about being offered a GBS test, were willing to provide a sample and felt positive towards samples being taken to detect GBS. Women varied in their preferences on the best time for sampling. Some thought being approached during pregnancy gave them time to understand the purpose of testing, prepare for what may happen next and ask questions about potential treatment if needed. Others thought labour was a good time to provide accurate results on GBS carriage at birth and reduce unnecessary worry during pregnancy. However, women were concerned that they may be unable to make an informed decision in labour due to time, pain and the prospect of birthing quickly. Women perceived clinician swabbing as more accurate than self-sampling; however, many thought clinician swabbing might be embarrassing so self-swabs should be available to increase uptake for some women. CONCLUSIONS: Overall, women thought both pregnancy and labour were acceptable times to test for GBS. The majority found both clinician and self-swabbing procedures acceptable; however, many had a preferred swabbing option and thought women should be given the choice of the swabbing procedure most acceptable to them. It is important that women are given information about GBS testing and its procedures in pregnancy regardless of when the GBS swabbing is performed.

A photoaging smartphone application to promote sun safety behaviors among youth in late childhood and adolescence.

BACKGROUND: Ultraviolet (UV)-exposure behaviors can directly impact an individual's skin cancer risk, with many habits formed during childhood and adolescence. We explored the utility of a photoaging smartphone application to motivate youth to improve sun safety practices. METHODS: Participants completed a preintervention survey to gather baseline sun safety perceptions and behaviors. Participants then used a photoaging mobile application to view the projected effects of chronic UV exposure on participants' self-face image over time, followed by a postintervention survey to assess motivation to engage in future sun safety practices. RESULTS: The study sample included 87 participants (median [interquartile (IQR)] age, 14 [11-16] years). Most participants were White (50.6%) and reported skin type that burns a little and tans easily (42.5%). Preintervention sun exposure behaviors among participants revealed that 33 (37.9%) mostly or always used sunscreen on a sunny day, 48 (55.2%) experienced at least one sunburn over the past year, 26 (30.6%) engaged in outdoor sunbathing at least once during the past year, and zero (0%) used indoor tanning beds. Non-skin of color (18 [41.9%], p = .02) and older (24 [41.4%], p = .007) participants more often agreed they felt better with a tan. Most participants agreed the intervention increased their motivation to practice sun-protective behaviors (wear sunscreen, 74 [85.1%]; wear hats, 64 [74.4%]; avoid indoor tanning, 73 [83.9%]; avoid outdoor tanning, 68 [79%]). CONCLUSION: The findings of this cross-sectional study suggest that a photoaging smartphone application may serve as a useful tool to promote sun safety behaviors from a young age.

Segmental Shielding: A Rare Case of Acute Respiratory Distress Syndrome with Middle Lobe Sparing.

Acute respiratory distress syndrome (ARDS) presents a formidable challenge in critical care, often resulting in high mortality rates, particularly in severe cases or those compounded by preexisting conditions. Despite substantial advancements in critical care, the heterogeneous nature of ARDS necessitates nuanced clinical approaches. ARDS is generally diagnosed through clinical evaluation, radiographic imaging, and laboratory tests, as well as acute onset, bilateral lung infiltrates on imaging, and a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspiratory oxygen concentration (FiO2) ratio of less than 300 mmHg. Management involves measurements to improve oxygenation and provide mechanical ventilation to assist breathing. The typical manifestation of ARDS is diffuse lung involvement, which affects multiple lobes symmetrically. Here, we report an unusual case of ARDS in a 53-year-old female who was brought into the hospital in an unresponsive state, exhibiting hypoxic and hypotension requiring intubation. Subsequent imaging revealed a distinctive pattern: the preservation of the right middle lobe, diverging from the conventional diffuse pulmonary affliction. This case underscores the need for clinical vigilance and adaptability, as such atypical presentations can confound diagnosis and management, posing unique clinical challenges. This case highlights the importance of recognizing ARDS' diverse presentations. Moreover, understanding the mechanisms behind the lobar sparing could provide greater insight into the disease heterogeneity and guide tailored therapeutic approaches. The imperative for further research into these uncommon presentations is clear, as it may be vital to improving outcomes for a broader spectrum of ARDS patients.

Evaluating human landing catches as a measure of mosquito biting and the importance of considering additional modes of action.

Entomological evaluations of vector control tools often use human landing catches (HLCs) as a standard measure of a direct human-vector contact. However, some tools have additional characteristics, such as mortality, and HLCS are not sensitive for measuring other effects beyond landing inhibition. Therefore, additional measures may need to be considered when evaluating these tools for public health use. This study has two main aims (1) the evaluate the accuracy of HLCs as a proxy for feeding and (2) to compare the predicted reduction in vectorial capacity when we do and do not consider these additional characteristics. To achieve this, we analyse previously published semi-field data from an experiment which used HLCs and another where mosquitoes were allowed to feed in the presence of different dosages of the volatile pyrethroid spatial repellent, transfluthrin. We compare results for two mathematical models: one which only considers the reduction in feeding effect and one which also considers mortality before and after feeding (using data gathered by the aspiration of mosquitoes after the semi-field feeding/landing period and 24 h survival monitoring). These Bayesian hierarchical models are parameterised using Bayesian inference. We observe that, for susceptible mosquitoes, reduction in landing is underestimated by HLCs. For knockdown resistant mosquitoes the relationship is less clear; with HLCs sometimes appearing to overestimate this characteristic. We find HLCs tend to under-predict the relative reduction in vectorial capacity in susceptible mosquitoes while over-predicting this impact in knockdown-resistant mosquitoes. Models without secondary effects have lower predicted relative reductions in vectorial capacities. Overall, this study highlights the importance of considering additional characteristics to reduction in biting of volatile pyrethroid spatial repellents. We recommend that these are considered when evaluating novel vector control tools.

Complete series method (CSM): a convenient method to reduce daily heterogeneity when evaluating the regeneration time (RT) of insecticide-treated nets (ITNs).

BACKGROUND: "Regeneration time" (RT) denotes the time required to obtain a stable mortality rate for mosquitoes exposed to insecticide-treated nets (ITNs) after three consecutive washes of a net in a day. The RT informs the wash interval used to artificially age ITNs to simulate their lifetime performance under user conditions (20 washes). RT was estimated following World Health Organization (WHO) longitudinal method (LM) procedures. Longitudinal evaluation may introduce heterogeneity due to mosquito batch variability, complicating RT determination. To overcome this, nets at each stage of regeneration (i.e., 1, 2, 3, 5 and 7 days post wash) were prepared in advance and refrigerated; then, a complete regeneration series was tested with a single mosquito batch on 1 testing day, completing four series over 4 days. This study compared the complete series method (CSM) against the LM. METHODS: The overall heterogeneity in the methods for estimating RT of one incorporated alpha-cypermethrin and piperonyl butoxide (PBO) and one incorporated permethrin with PBO ITNs was determined using laboratory-reared resistant Anopheles arabiensis under standard laboratory conditions. LM methods and CSM were compared in two experiments with refrigerated nets acclimated for (i) 2 h (test 1) and (ii) 3 h (test 2). Four regeneration replicates per day were tested per ITN product with 50 mosquitoes exposed per replicate (equivalent sample size to LM). The heterogeneity from these methods was compared descriptively. RESULTS: The intra-method variability for unwashed pieces was minimal, with variance of 1.26 for CSM and 1.18 for LM. For unwashed nets, LM had substantially greater variance and ratio of LM:CSM was 2.66 in test 1 and 2.49 in test 2. The magnitude of mortality measured in bioassays depended on sample acclimation after refrigeration. CONCLUSIONS: The CSM is a convenient method for determining the regeneration times. ITNs are prepared in advance, reducing pressure to prepare all samples to start on a single day. A complete regeneration series of samples is removed from the refrigerator, defrosted and evaluated on a single day with one mosquito batch reducing the influence of mosquito batch heterogeneity on results. Replicates can be conducted over several days but do not have to be conducted on consecutive days, allowing easy facility scheduling.

Risk of Cesarean Delivery Among People With Inflammatory Bowel Disease According to Disease Characteristics: A Population-Based Study.

OBJECTIVES: It is unclear if use of cesarean delivery in people with inflammatory bowel disease (IBD) is guideline-concordant. We compared the odds of cesarean delivery among primiparous individuals with IBD versus without, overall, and by disease characteristics, as well as time to subsequent delivery. METHODS: Retrospective matched population-based cohort study between 1 April 1994 and 31 March 2020. Primiparous individuals aged 15-55 years with IBD were matched to those without IBD on age, year, hospital, and number of newborns delivered. Primary outcome was cesarean delivery versus vaginal delivery. Multivariable conditional logistic regression analyses were performed to estimate the odds of cesarean delivery among individuals with and without IBD as a binary exposure, and a categorical exposure based on IBD-related indications for cesarean delivery. Time to subsequent delivery was evaluated using a Cox proportional hazard model. RESULTS: We matched 7472 individuals with IBD to 37 360 individuals without (99.02% match rate). Individuals with IBD were categorised as having perianal (PA) disease (IBD-PA, n = 764, 10.2%), prior ileal pouch-anal anastomosis (n = 212, 2.8%), or IBD-Other (n = 6496, 86.9%). Cesarean delivery rates were 35.4% in the IBD group versus 30.4% in their controls (adjusted odds ratio 1.27; 95% CI 1.20-1.34). IBD-ileal pouch-anal anastomosis had a cesarean delivery rate of 66.5%, compared to 49.9% in IBD-PA and 32.7% in IBD-Other. There was no significant difference in the rate of subsequent delivery in those with and without IBD (adjusted hazard ratio 1.03; 95% CI 1-1.07). CONCLUSIONS: The higher risk of cesarean delivery in people with IBD reflects guideline-concordant use. Individuals with and without IBD were equally likely to have a subsequent delivery with similar timing.

Impact of hindlimb length variation on jumping dynamics in the Longshanks mouse.

Distantly related mammals (e.g. jerboa, tarsiers, kangaroos) have convergently evolved elongated hindlimbs relative to body size. Limb elongation is hypothesized to make these species more effective jumpers by increasing their kinetic energy output (through greater forces or acceleration distances), thereby increasing take-off velocity and jump distance. This hypothesis, however, has rarely been tested at the population level, where natural selection operates. We examined the relationship between limb length, muscular traits and dynamics using Longshanks mice, which were selectively bred over 22 generations for longer tibiae. Longshanks mice have approximately 15% longer tibiae and 10% longer femora compared with random-bred Control mice from the same genetic background. We collected in vivo measures of locomotor kinematics and force production, in combination with behavioral data and muscle morphology, to examine how changes in bone and muscle structure observed in Longshanks mice affect their hindlimb dynamics during jumping and clambering. Longshanks mice achieved higher mean and maximum lunge-jump heights than Control mice. When jumping to a standardized height (14 cm), Longshanks mice had lower maximum ground reaction forces, prolonged contact times and greater impulses, without significant differences in average force, power or whole-body velocity. While Longshanks mice have longer plantarflexor muscle bodies and tendons than Control mice, there were no consistent differences in muscular cross-sectional area or overall muscle volume; improved lunge-jumping performance in Longshanks mice is not accomplished by simply possessing larger muscles. Independent of other morphological or behavioral changes, our results point to the benefit of longer hindlimbs for performing dynamic locomotion.

Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk.

Background: Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Methods: Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. Results: CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells. Conclusion: There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

Modic changes in the lumbar vertebral column of chondrodystrophic and non-chondrodystrophic dogs with intervertebral disc disease.

Introduction: Modic changes (MC) are signs of vertebral pathology visible on magnetic resonance (MR) images that have been associated with low back pain (LBP) and disc degeneration in people. Multiple breeds of dogs also develop MCs and coincident back pain. However, the association between breed, MC, and spinal pathologies has yet to be fully elucidated. This study aimed to identify the prevalence of MC that occur spontaneously in the lumbar vertebral column of dogs diagnosed with intervertebral disc disease (IVDD) and examine their association with demographic criteria and the disc width index (DWI). Methods: Medical records and lumbar vertebral column MR images were examined from 104 dogs (831 intervertebral disc spaces and adjacent vertebrae), which were divided into three groups: chondrodystrophic dogs (CD; n =54) and non-chondrodystrophic dogs (NCD; n =30) with IVDD as the primary diagnosis, and control dogs (n =20) with other spinal diseases as their primary diagnosis. Results: Increasing age and a diagnosis of IVDD were significantly associated with MC in dogs (p < 0.001 and p = 0.0062, respectively). In CD dogs with IVDD, Type 2 MC were most prevalent, whereas, in NCD dogs, Type 3 MC were the most prevalent type. Type 2 MC were distributed nearly equally across the lumbar vertebral column, while Type 3 MC were primarily detected at the level of L7-S1. Discussion: This study demonstrated that MC developed spontaneously in dogs, are common in dogs diagnosed with IVDD, and the type observed varies by breed. Further research is needed to understand the pathogenesis of MC; however, the increased presence of Type 2 MC in CD dogs, similar to what is found in people with disc degeneration, suggests that CD dogs could serve as models for MC in people.

Building CapaCITY/É for sustainable transportation: protocol for an implementation science research program in healthy cities.

INTRODUCTION: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not. METHODS AND ANALYSIS: Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities. ETHICS AND DISSEMINATION: This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.

Implementing a pharmacist-integrated collaborative model of medication treatment for opioid use disorder in primary care: study design and methodological considerations.

BACKGROUND: Pharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care. METHODS: This study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site's capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber). DISCUSSION: This study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients' access to MOUD and treatment outcomes. TRIAL REGISTRATION: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www. CLINICALTRIALS: gov/study/NCT05310786?id=NCT05310786&rank=1.