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In this commentary on the J-AIM Special Issue 'Integrative Approaches to Health', we argue for plural narratives of health to balance and to reconnect human populations with their environments, to foster a renewed culture of health and wellbeing. Integration of our inner and outer ecosystems with pluralistic health systems requires ‘movement’ and ‘change’ and the special issue provides papers on integration and health from multiple disciplinary perspectives that study humans, non-human, animals, and plants in relation to clinical trials, individual and population studies and health systems. All these perspectives provide new insights to map integrative approaches in health, illness and wellbeing in times of the climate emergency.To ameliorate the biomedical and biopharmaceutical industries 'medicalisation of life' as the hegemonic and thus totalising human and more-than-human health systems and approach, the special issue acknowledges, situates and authorises broader visions and epistemologies of health and disease. These complementary epistemologies, their words, their movements (Ayu) and their health (Swastya) and balance (Soukya) are contained within indigenous health systems that include Ayurveda and Traditional Chinese Medicine (TCM) amongst a vast array of local health cultures across the globe. In contrast with the narrower approach of medicalisation; integrative, inclusive, plural and sustainable approaches to health involve the respect for a population’s self-reliance in health (the 4th Tier) and the dignity of the Sanskrit word for health, ‘Swastya’ which means ‘being rooted within’. These perspective and epistemologies will help to create a vision for health and health systems that encourage integration through the dignity of the individual (Atmasnman/Anubhuti), respect for the other (Pratiksa/Adara), trust in community (Nyasa) and the creation of systems of equity (Samata) and social justice for all (Nyaya).

BackgroundThe generation of research evidence and knowledge in primary health care (PHC) is crucial for informing the development and implementation of interventions and innovations and driving health policy, health service improvements, and potential societal changes. PHC research has broad effects on patients, practices, services, population health, community, and policy formulation. The in-depth exploration of the definition and measures of research impact within PHC is essential for broadening our understanding of research impact in the discipline and how it compares to other health services research. ObjectiveThe objectives of the study are (1) to understand the conceptualizations and measures of research impact within the realm of PHC and (2) to identify methodological frameworks for evaluation and research impact and the benefits and challenges of using these approaches. The forthcoming review seeks to guide future research endeavors and enhance methodologies used in assessing research impact within PHC. MethodsThe protocol outlines the rapid review and environmental scan approach that will be used to explore research impact in PHC and will be guided by established frameworks such as the Canadian Academy of Health Sciences Impact Framework and the Canadian Health Services and Policy Research Alliance. The rapid review follows scoping review guidelines (PRISMA-ScR; Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Reviews). The environmental scan will be done by consulting with professional organizations, academic institutions, information science, and PHC experts. The search strategy will involve multiple databases, citation and forward citation searching, and manual searches of gray literature databases, think tank websites, and relevant catalogs. We will include gray and scientific literature focusing explicitly on research impact in PHC from high-income countries using the World Bank classification. Publications published in English from 1978 will be considered. The collected papers will undergo a 2-stage independent review process based on predetermined inclusion criteria. The research team will extract data from selected studies based on the research questions and the CRISP (Consensus Reporting Items for Studies in Primary Care) protocol statement. The team will discuss the extracted data, enabling the identification and categorization of key themes regarding research impact conceptualization and measurement in PHC. The narrative synthesis will evolve iteratively based on the identified literature. ResultsThe results of this study are expected at the end of 2024. ConclusionsThe forthcoming review will explore the conceptualization and measurement of research impact in PHC. The synthesis will offer crucial insights that will guide subsequent research, emphasizing the need for a standardized approach that incorporates diverse perspectives to comprehensively gauge the true impact of PHC research. Furthermore, trends and gaps in current methodologies will set the stage for future studies aimed at enhancing our understanding and measurement of research impact in PHC. International Registered Report Identifier (IRRID)PRR1-10.2196/55860

IntroductionExertional tests have become a promising tool to assist clinicians in the management of concussions, however require expensive equipment, extensive spaces, and specialized clinician expertise. As such, we developed a test with minimal resource requirements encompassing key elements of sport and physical activity. The purpose of this study was to pilot test the Multimodal Exertional Test (MET) protocol in a sample of healthy interuniversity athletes.MethodsThe MET comprises four stages, each featuring three distinct tasks. The test begins with engaging in squats, alternating reverse lunges, and hip hinges (Stage 1). The next stage progressively evolves into executing these tasks within specified time limits (Stage 2). Following this, the test advances to a stage that incorporates cognitive tasks (Stage 3), and the final stage demands greater levels of physical exertion, cognition, and multi-directional movements (Stage 4). Heart rate (HR) was obtained during each stage of the MET and participants’ symptom severity scores were recorded following each task.ResultsFourteen healthy interuniversity athletes (n = 8 female, n = 6 male) participated in the study. HR was obtained for 10 of the 14 athletes (females: n = 6, males: n = 4). Increases in average and maximum HR were identified between pre-MET and Stage 1, and between Stages 3 and 4. Consistent with the tasks in each stage, there were no increases in average and maximum HR observed between MET Stages 1 to 3. Female athletes exhibited higher average and maximum HRs compared to male athletes during all four stages. All 14 athletes reported minimal changes in symptom severity following each task.ConclusionAmong healthy athletes, the MET elicits an increase in average and maximum HR throughout the protocol without symptom provocation. Female athletes exhibit higher HRs during all four stages in comparison to male athletes.

X-ray Free Electron Lasers (XFELs) allow the collection of high-quality serial femtosecond crystallography data. The next generation of megahertz superconducting FELs promises to drastically reduce data collection times, enabling the capture of more structures with higher signal-to-noise ratios and facilitating more complex experiments. Currently, gas dynamic virtual nozzles (GDVNs) stand as the sole delivery method capable of best utilizing the repetition rate of megahertz sources for crystallography. However, their substantial sample consumption renders their use impractical for many protein targets in serial crystallography experiments. Here, we present a novel application of a droplet-on-demand injection method, which allowed operation at 47 kHz at the European XFEL (EuXFEL) by tailoring a multi-droplet injection scheme for each macro-pulse. We demonstrate a collection rate of 150 000 indexed patterns per hour. We show that the performance and effective data collection rate are comparable to GDVN, with a sample consumption reduction of two orders of magnitude. We present lysozyme crystallographic data using the Large Pixel Detector at the femtosecond x-ray experiment endstation. Significant improvement of the crystallographic statistics was made by correcting for a systematic drift of the photon energy in the EuXFEL macro-pulse train, which was characterized from indexing the individual frames in the pulse train. This is the highest resolution protein structure collected and reported at the EuXFEL at 1.38 Å resolution.

BackgroundRecent developments in CRISPR/Cas9 genome-editing tools have facilitated the introduction of precise alleles, including genetic intervals spanning several kilobases, directly into the embryo. However, the introduction of donor templates, via homology directed repair, can be erroneous or incomplete and these techniques often produce mosaic founder animals. Thus, newly generated alleles must be verified at the sequence level across the targeted locus. Screening for the presence of the desired mutant allele using traditional sequencing methods can be challenging due to the size of the interval to be sequenced, together with the mosaic nature of founders.Methodology/principal findingsIn order to help disentangle the genetic complexity of these animals, we tested the application of Oxford Nanopore Technologies long-read sequencing at the targeted locus and found that the achievable depth of sequencing is sufficient to offset the sequencing error rate associated with the technology used to validate targeted regions of interest. We have assembled an analysis workflow that facilitates interrogating the entire length of a targeted segment in a single read, to confirm that the intended mutant sequence is present in both heterozygous animals and mosaic founders. We used this workflow to compare the output of PCR-based and Cas9 capture-based targeted sequencing for validation of edited alleles.ConclusionTargeted long-read sequencing supports in-depth characterisation of all experimental models that aim to produce knock-in or conditional alleles, including those that contain a mix of genome-edited alleles. PCR- or Cas9 capture-based modalities bring different advantages to the analysis.

BackgroundEncapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls.MethodsLinear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients.ResultsEPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p

Among existing water electrolysis (WE) technologies, anion-exchange-membrane water electrolyzers (AEMWEs) show promise for low-cost operation enabled by the basic solid-polymer electrolyte used to conduct hydroxide ions. The basic environment within the electrolyzer, in principle, allows the use of non-platinum-group metal catalysts and less-expensive cell components compared to acidic-membrane systems. Nevertheless, AEMWEs are still underdeveloped, and the degradation and failure modes are not well understood. To improve performance and durability, supporting electrolytes such as KOH and K2CO3 are often added to the water feed. The effect of the anion interactions with the ionomer membrane (particularly other than OH-), however, remains poorly understood. We studied three commercial anion-exchange ionomers (Aemion, Sustainion, and PiperION) during oxygen evolution (OER) at oxidizing potentials in several supporting electrolytes and characterized their chemical stability with surface-sensitive techniques. We analyzed factors including the ionomer conductivity, redox potential, and pH tolerance to determine what governs ionomer stability during OER. Specifically, we discovered that the oxidation of Aemion at the electrode surface is favored in the presence of CO32-/HCO3- anions perhaps due to the poor conductivity of that ionomer in the carbonate/bicarbonate form. Sustainion tends to lose its charge-carrying groups as a result of electrochemical degradation favored in basic electrolytes. PiperION seems to be similarly negatively affected by a pH drop and low carbonate/bicarbonate conductivity under the applied oxidizing potential. The insight into the interactions of the supporting electrolyte anions with the ionomer/membrane helps shed light on some of the degradation pathways possible inside of the AEMWE and enables the informed design of materials for water electrolysis.

Background. Droplet simulation often requires expensive and inaccessible equipment. Herein, we develop and assess a low-cost droplet simulation model using easily accessible materials, open-source software, and a smartphone-based cobalt blue light. Methods. The simulation model was developed using commercial-grade materials and fluorescein dye. A clear face shield was assessed ten times following a simulated cough using fluorescein dye. A conventional ultraviolet Woods lamp was compared to a smartphone-based cobalt blue light to detect fluorescein illumination. Results. The simulation platform and smartphone-based cobalt blue light cost $20.18. A Wilcoxon signed rank test revealed that the median droplet area of fluorescence under the UV Wood's lamp was not significantly different than that of the smartphone-based cobalt blue light (2.89 vs 2.94, P = .386). Conclusions. This simulation model is inexpensive and easily reproducible. The smartphone application may be a convenient alternative to standard ultraviolet lights. This model has great potential for use in financially restricted academic centers during the COVID-19 pandemic and beyond.

Adolescents may be more vulnerable to COVID-19-related impacts and require long-term mental health care. Services that bolster emotion regulation, such as mindfulness-based interventions (MBIs) promote positive impacts on psychosocial outcomes and have high acceptability. No studies have assessed feasibility, treatment perceptions and satisfaction of online MBIs with adolescents. 56 moderate- and high-risk adolescent (m = 14.5 years, 66.1% female, 26.8% LatinX) participants tested the feasibility, treatment perceptions and satisfaction of an 8-session online MBI focused on observing non-judgmentally, attending to positivity, and self-soothing. The study achieved acceptable feasibility with high attendance (m = 5.75) and retention rates (87.5%). The moderate- vs. high-risk group reported significantly higher ratings of treatment perceptions (t = 2.03, p < .05, d = 0.60). Significant associations were found between increased pre-test depression and anxiety symptomology and reduced intervention utility (rs = -0.34 and -0.32, ps < .05). This study demonstrated feasibility, treatment perceptions and satisfaction of an online MBI for adolescents presenting with two risk levels. Higher-risk adolescents may need a higher-touch intervention than moderate-risk, who may be more likely to find online MBIs acceptable. The impact of adjunctive MBIs for adolescents on treatment attendance and mental health outcomes over longer periods is necessary to understand patterns in effective adolescent treatment options., Author(s): Morica Hutchison [sup.1] [sup.3] , Beth S. Russell [sup.1] [sup.3] , Kim M. Gans [sup.1] [sup.3] , Angela R. Starkweather [sup.2] Author Affiliations: (1) grid.63054.34, 0000 0001 0860 4915, [...]

Abstract Introduction Incontinence and urgency are common after prostatectomy. The University of Virginia prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimise continence outcomes following robotic‐assisted laparoscopic prostatectomy (RALP). Patients are prospectively evaluated by a Female Pelvic Medicine and Reconstructive Surgery specialist. This study assessed for predictors of 3‐ and 6‐month stress urinary incontinence (SUI) and urgency symptom outcomes following RALP. Methods We performed a post hoc review of patients from our PFOP receiving a minimum of 6‐month follow‐up. Urinary symptoms are prospectively assessed using the validated International Consultation on Incontinence Questionnaire‐Male Lower Urinary Tract Symptoms (ICIQ‐MLUTS) questionnaire and daily pad use (pads per day [PPD]). Primary study outcomes included ICIQ‐MLUTS SUI and urgency domain scores and PPD. Multivariable linear regression was performed to identify variables associated with outcomes at 3 and 6 months postoperatively. Variables included patient, oncologic and surgical factors. Each variable was run in a separate model with pelvic floor muscle therapy and surgeon to reduce confounding and prevent overfitting. Results Forty men were included. In assessment of ICIQ‐MLUTS SUI domain score, at 3 months, body mass index (BMI) was associated with worse scores, and at 6 months, BMI, hypertension and estimated blood loss (EBL) were associated with worse scores, whereas bilateral nerve‐sparing technique was associated with better scores. For ICIQ‐MLUTS Urgency domain score, at 3 months, preoperative use of benign prostatic hyperplasia (BPH) medication was associated with better scores. No covariates predicted 6‐month ICIQ‐MLUTS Urgency domain scores. For PPD use, at both 3 and 6 months, BMI was a positive predictor, while preoperative use of BPH medication was a negative predictor. Conclusion Increased BMI, EBL and hypertension are associated with worsened SUI outcomes following RALP, whereas bilateral nerve‐sparing technique and preoperative BPH medication are associated with improved SUI outcomes. These data may inform patient counselling and help identify patients who may benefit from closer surveillance and earlier anti‐incontinence intervention.

Abstract Nature provides a rich source of information for the design of novel materials; yet there remain significant challenges in the design and manufacture of materials that replicate the form, function, and sustainability of biological solutions. Here, we identify key challenges and promising approaches to the development of materials informed by biology. These challenges fall into two main areas; the first relates to harnessing biological information for materials innovation, including key differences between biological and synthetic materials, and the relationship between structure and function. We propose an approach to materials innovation that capitalizes on biodiversity, together with high-throughput characterization of biological material architectures and properties, linked to environmental and ecological context. The second area relates to the design and manufacture of bioinformed materials, including the physical scale of material architectures and manufacturing scale up. We suggest ways to address these challenges and promising prospects for a bioinformed approach to materials innovation.

Abstract Background A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity. Methods This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at high risk, including those with comorbidities (hypertension, diabetes, obesity, reactive airway disease, smokers), racial and ethnic minorities, elderly, teachers, police, restaurant wait-staff, delivery personnel, health care workers who are defined as personnel working in a healthcare setting, at a hospital, medical center or clinic (veterinary, dental, ophthalmology), and first responders (paramedics, firefighters, or law enforcement), will be randomly assigned to two treatment groups. The treatment groups will receive intradermal administration of BCG vaccine or placebo (saline) with groups at a 1:1 ratio. Individuals will be tracked for evidence of SARS-CoV-2 infection and severity as well as obtaining whole blood to track immunological markers, and a sub-study will include cognitive function and brain imaging. The majority of individuals will be followed for 6 months, with an option to extend for another 6 months, and the cognitive sub-study duration is 2 years. We will plot Kaplan-Meier curves that will be plotted comparing groups and hazard ratios and p-values reported using Cox proportional hazard models. Discussion It is expected this trial will allow evaluation of the effects of BCG vaccination at a population level in high-risk healthcare individuals through a mitigated clinical course of SARS-CoV-2 infection and inform policy making during the ongoing epidemic. Trial registration ClinicalTrials.gov NCT04348370. Registered on April 16, 2020.

Abstract Meaningful engagement and partnerships with people who use drugs are essential to conducting research that is relevant and impactful in supporting desired outcomes of drug consumption as well as reducing drug-related harms of overdose and COVID-19. Community-based participatory research is a key strategy for engaging communities in research that directly affects their lives. While there are growing descriptions of community-based participatory research with people who use drugs and identification of key principles for conducting research, there is a gap in relation to models and frameworks to guide research partnerships with people who use drugs. The purpose of this paper is to provide a framework for research partnerships between people who use drugs and academic researchers, collaboratively developed and implemented as part of an evaluation of a provincial prescribed safer supply initiative introduced during dual public health emergencies (overdose and COVID-19) in British Columbia, Canada. The framework shifts from having researchers choose among multiple models (advisory, partnership and employment) to incorporating multiple roles within an overall community-based participatory research approach. Advocacy by and for drug users was identified as a key role and reason for engaging in research. Overall, both academic researchers and Peer Research Associates benefited within this collaborative partnerships approach. Each offered their expertise, creating opportunities for omni-directional learning and enhancing the research. The shift from fixed models to flexible roles allows for a range of involvement that accommodates varying time, energy and resources. Facilitators of involvement include development of trust and partnering with networks of people who use drugs, equitable pay, a graduate-level research assistant dedicated to ongoing orientation and communication, technical supports as well as fluidity in roles and opportunities. Key challenges included working in geographically dispersed locations, maintaining contact and connection over the course of the project and ensuring ongoing sustainable but flexible employment.

Late-term abortions cause significant economic loss and are of great concern for dairy herds. Late-term abortions >152 d and 50% reliability. For late-term abortion as a trait, estimated heritability was only 0.001 and PTA had a standard deviation of only 0.1% for recent sires with high reliability (>75%). Young animal genomic PTA have near 50% reliability but range only from −0.5 to +0.4 because of the low incidence and heritability. Genetic trend was slightly favorable and late-term abortion PTA were correlated favorably by 0.27 with net merit, 0.49 with productive life, 0.33 with livability, 0.23 with CCR, 0.20 with HCR, 0.26 with DPR, −0.31 with somatic cell score, −0.24 with daughter stillbirth, and −0.26 with daughter dystocia. Thus, PTA for late-term abortions should not be needed as a separate fertility trait and instead these minor edit changes should suffice. The PTA for late-term abortions would add little value because national evaluations for current fertility traits already account for those economic losses.

Pemphigus vulgaris (PV) is an IgG autoantibody-mediated, potentially fatal mucocutaneous disease manifested by progressive non-healing erosions and blisters. Beyond acting to inhibit adhesion molecules, PVIgGs elicit a unique process of programmed cell death and detachment of epidermal keratinocytes termed apoptolysis. Mitochondrial damage by antimitochondrial antibodies (AMA) has proven to be a critical link in this process. AMA act synergistically with other autoantibodies in the pathogenesis of PV. Importantly, absorption of AMA inhibits the ability of PVIgGs to induce blisters. Pharmacologic agents that protect mitochondrial function offer a new targeted approach to treating this severe immunoblistering disease.