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Abstract Background Digital technologies allow users to engage in health-related behaviors associated with positive outcomes. We aimed to identify classes of US adults with distinct digital technologies access and health use patterns and characterize class composition. Data came from Health Information National Trends Survey Wave 5 Cycles 1–4, a nationally representative cross-sectional survey of US adults (N = 13,993). We used latent class analysis to identify digital technologies access and health use patterns based on 32 ternary variables of behaviors and access to requisite technologies and platforms, including the internet, internet-enabled devices, health monitors, and electronic health records (EHRs). We ran a multinomial logistic regression to identify sociodemographic and health correlates of class membership (n = 10,734). Results Ten classes captured patterns of digital technology access and health use among US adults. This included a digitally isolated, a mobile-dependent, and a super user class, which made up 8.9%, 7.8%, and 13.6% of US adults, respectively, and captured access patterns from only basic cellphones and health monitors to near complete access to web-, mobile-, and EHR-based platforms. Half of US adults belonged to classes that lacked access to EHRs and relied on alternative web-based tools typical of patient portals. The proportion of class members who used digital technologies for health purposes varied from small to large. Older and less educated adults had lower odds of belonging to classes characterized by access or engagement in health behaviors. Hispanic and Asian adults had higher odds of belonging to the mobile-dependent class. Individuals without a regular healthcare provider and those who had not visited a provider in the past year were more likely to belong to classes with limited digital technologies access or health use. Discussion Only one third of US adults belonged to classes that had near complete access to digital technologies and whose members engaged in almost all health behaviors examined. Sex, age, and education were associated with membership in classes that lacked access to 1 + digital technologies or exhibited none to limited health uses of such technologies. Results can guide efforts to improve access and health use of digital technologies to maximize associated health benefits and minimize disparities.

Abstract Ventilatory thresholds (VTs) are key physiological parameters used to evaluate physical performance and determine aerobic and anaerobic transitions during exercise. Current assessment of these parameters requires ergospirometry, limiting evaluation to laboratory or clinical settings. In this work, we introduce a wearable respiratory system that continuously tracks breathing during exercise and estimates VTs during ramp tests. We validate the respiratory rate and VTs predictions in 17 healthy adults using ergospirometry analysis. In addition, we use the wearable system to evaluate VTs in 107 recreational athletes during ramp tests outside the laboratory and show that the mean population values agree with physiological variables traditionally used to exercise prescription. We envision that respiratory wearables can be useful in determining aerobic and anaerobic parameters with promising applications in health telemonitoring and human performance.

ABSTRACT In the era of antimicrobial resistance, phage-antibiotic combinations offer a promising therapeutic option, yet research on their synergy and antagonism is limited. This study aims to assess these interactions, focusing on protein synthesis inhibitors and cell envelope-active agents against multidrug-resistant bacterial strains. We evaluated synergistic and antagonistic interactions in multidrug-resistant Staphylococcus aureus, Enterococcus faecium, and Pseudomonas aeruginosa strains. Phages were combined with protein synthesis inhibitors [linezolid (LZD), minocycline (MIN), gentamicin (GEN), and azithromycin (AZM)] or cell envelope-active agents [daptomycin (DAP), ceftaroline (CPT), and cefepime (FEP)]. Modified checkerboard minimum inhibitory concentration assays and 24-h time-kill analyses were conducted, alongside one-step growth curves to analyze phage growth kinetics. Statistical comparisons used one-way analysis of variance (ANOVA) and the Tukey test (P < 0.05). In the checkerboard and 24-h time-kill analyses (TKA) of S. aureus and E. faecium, phage-LZD and phage-MIN combinations were antagonistic (FIC > 4) while phage-DAP and phage-CPT were synergistic (FIC 0.5) (ANOVA range of mean differences 0.52–2.59 log10 CFU/mL; P < 0.001). For P. aeruginosa, phage-AZM was antagonistic (FIC > 4), phage-GEN was additive (FIC = 1), and phage-FEP was synergistic (ANOVA range of mean differences 1.04–1.95 log10 CFU/mL; P < 0.001). Phage growth kinetics were altered in the presence of LZD and MIN against S. aureus and in the presence of LZD against a single E. faecium strain (HOU503). Our findings indicate that select protein synthesis inhibitors may induce phage-antibiotic antagonism. However, this antagonism may not solely stem from changes in phage growth kinetics, warranting further investigation into the complex interplay among strains, phage attributes, and antibiotic mechanisms affecting bacterial inhibition.IMPORTANCEIn the face of escalating antimicrobial resistance, combining phages with antibiotics offers a promising avenue for treating infections unresponsive to traditional antibiotics. However, while studies have explored synergistic interactions, less attention has been given to potential antagonism and its impact on phage growth kinetics. This research evaluates the interplay between phages and antibiotics, revealing both synergistic and antagonistic patterns across various bacterial strains and shedding light on the complex dynamics that influence treatment efficacy. Understanding these interactions is crucial for optimizing combination therapies and advancing phage therapy as a viable solution for combating antimicrobial resistance.

Abstract Mesenchymal stromal cells (MSCs) are promising regenerative therapeutics that primarily exert their effects through secreted extracellular vesicles (EVs). These EVs – being small and non‐living – are easier to handle and possess advantages over cellular products. Consequently, the therapeutic potential of MSC‐EVs is increasingly investigated. However, due to variations in MSC‐EV manufacturing strategies, MSC‐EV products should be considered as highly diverse. Moreover, the diverse array of EV characterisation technologies used for MSC‐EV characterisation further complicates reliable interlaboratory comparisons of published data. Consequently, this study aimed to establish a common method that can easily be used by various MSC‐EV researchers to characterise MSC‐EV preparations to facilitate interlaboratory comparisons. To this end, we conducted a comprehensive inter‐laboratory assessment using a novel multiplex bead‐based EV flow cytometry assay panel. This assessment involved 11 different MSC‐EV products from five laboratories with varying MSC sources, culture conditions, and EV preparation methods. Through this assay panel covering a range of mostly MSC‐related markers, we identified a set of cell surface markers consistently positive (CD44, CD73 and CD105) or negative (CD11b, CD45 and CD197) on EVs of all explored MSC‐EV preparations. Hierarchical clustering analysis revealed distinct surface marker profiles associated with specific preparation processes and laboratory conditions. We propose CD73, CD105 and CD44 as robust positive markers for minimally identifying MSC‐derived EVs and CD11b, CD14, CD19, CD45 and CD79 as reliable negative markers. Additionally, we highlight the influence of culture medium components, particularly human platelet lysate, on EV surface marker profiles, underscoring the influence of culture conditions on resulting EV products. This standardisable approach for MSC‐EV surface marker profiling offers a tool for routine characterisation of manufactured EV products in pre‐clinical and clinical research, enhances the quality control of MSC‐EV preparations, and hopefully paves the way for higher consistency and reproducibility in the emerging therapeutic MSC‐EV field.

Abstract Prey metabarcoding has become a popular tool in molecular ecology for resolving trophic interactions at high resolution, from various sample types and animals. To date, most predator–prey studies of small‐sized animals (

Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth.

The aim of the article is to study the role and significance of brand management as the basis for the development of State values in the market. In modern marketing and in the conditions of competition in the market, topical issues are the development of the brand as an important marketing tool that plays a leading role for companies and the State in general in the Ukrainian and international markets. The visual appeal of products and services makes a primary impression on consumers, and therefore the priorities of the brand development strategy are obvious. Understanding the terms «brand» and «brand management» allows you to effectively apply these marketing tools in practice. In the new global digital economy, brands, in cooperation with management, make up a large part of the value of the company itself and a significant source of income. The brand is a challenge of the present and the future and is a mechanism for managing several areas at once: marketing, social, and economic. In today’s international environment, the interaction of brand and management is developing intensively, adapting to rapid changes in the world market and the introduction of information and communication technologies. For the effective functioning of marketing and development of Ukrainian companies that are focused on the market and influence the economy, it is necessary to consider in detail the issue of the functioning of the brand as an innovative tool both at the theoretical and practical levels. In particular, important components are the direct implementation of this mechanism, the list and content of the main stages of application, signs and types, the use of the dynamics of growth of indicators in both the domestic and the international markets. This study presents the features of the use of an innovative brand tool, which are the needs of modern companies, their specifics, overall impact, and also makes forecasts for the future. The use of brand management has a positive effect on the functioning and presentation of Ukraine in the market.

Adaptation of new employees is an important component of personnel management in Ukrainian business. The introduction and optimization of staff adaptation systems are a necessary link in ensuring the long-term stability and success of the company. In recent years, it has become clear that there is a need not only to attract talented employees, but also to successfully integrate them into the corporate culture. The carried out analysis of tools for assessing the efficiency of the staff adaptation systems in Ukraine allows to identify the main trends and highlight prospects for further research in this direction. It should be noted that the concept of adaptation goes beyond formal procedures and covers issues of interpersonal relationships, development of key skills and ensuring the psychological comfort of new employees. In the course of the study, it was found that the success of adaptation is directly related to the quality of the assessment tools used. Training programs, questionnaires, employee satisfaction and soft skills development become the basic tools on which the stability and efficiency of human resources are based. In particular, training programs become a midpoint for the transfer of not only professional knowledge, but also corporate values and culture. Questionnaires and feedback collection determine the current needs of employees and the effectiveness of the introduced changes, and the development of soft skills takes into account the human factor, which is essential for successful adaptation. The main idea is for business leaders and executives to understand that investing in proactive and innovative approaches to staff adaptation leads to real positive results and changes in the company. This is not just a strategy to prevent the loss of talents, but also to recognize human capital as a key resource for achieving business goals. The development and improvement of the adaptation system is an ongoing process that should be taken into account in the organization’s development strategy. Effective staff adaptation is not only a means of preventing the outflow of talents, but also an investment in the stability, development and success of the company in the long run.

We provide an overview of the World Amphipoda Database (WAD), a global species database that is part of the World Register of Marine Species (WoRMS). Launched in 2013, the database contains entries for over 10,500 accepted species names. Edited currently by 31 amphipod taxonomists, following WoRMS priorities, the WAD has at least one editor per major group. All accepted species are checked by the editors, as is the authorship available for all of the names. The higher classification is documented for every species and a type species is recorded for every genus name. This constitutes five of the 13 priorities for completion, set by WoRMS. In 2015, five LifeWatch grants were allocated for WAD activities. These included a general training workshop in 2016, together with data input for the superfamily Lysianassoidea and for a number of non-marine groups. Philanthropy grants in 2019 and 2021 covered more important gaps across the whole group. Further work remains to complete the linking of unaccepted names, original descriptions, and environmental information. Once these tasks are completed, the database will be considered complete for 8 of the 13 priorities, and efforts will continue to input new taxa annually and focus on the remaining priorities, particularly the input of type localities. We give an overview of the current status of the order Amphipoda, providing counts of the number of genera and species within each family belonging to the six suborders currently recognized.

A new stenothoid species is described from a hydroid polyp in British Columbia, Canada. The new species is provisionally assigned to Metopa as M. insolita sp. nov., pending revision of this genus.

Abstract Extracellular vesicles (EVs) are cell derived membranous nanoparticles. EVs are important mediators of cell–cell communication via the transfer of bioactive content and as such they are being investigated for disease diagnostics as biomarkers and for potential therapeutic cargo delivery to recipient cells. However, existing methods for isolating EVs from biological samples suffer from challenges related to co‐isolation of unwanted materials such as proteins, nucleic acids, and lipoproteins. In the pursuit of improved EV isolation techniques, we introduce multimodal flowthrough chromatography (MFC) as a scalable alternative to size exclusion chromatography (SEC). The use of MFC offers significant advantages for purifying EVs, resulting in enhanced yields and increased purity with respect to protein and nucleic acid co‐isolates from conditioned 3D cell culture media. Compared to SEC, significantly higher EV yields with similar purity and preserved functionality were also obtained with MFC in 2D cell cultures. Additionally, MFC yielded EVs from serum with comparable purity to SEC and similar apolipoprotein B content. Overall, MFC presents an advancement in EV purification yielding EVs with high recovery, purity, and functionality, and offers an accessible improvement to researchers currently employing SEC.

Abstract At high latitudes, strong seasonal differences in light availability affect marine organisms and regulate the timing of ecosystem processes. Marine protists are key players in Arctic aquatic ecosystems, yet little is known about their ecological roles over yearly cycles. This is especially true for the dark polar night period, which up until recently was assumed to be devoid of biological activity. A 12 million transcripts catalogue was built from 0.45 to 10 μm protist assemblages sampled over 13 months in a time series station in an Arctic fjord in Svalbard. Community gene expression was correlated with seasonality, with light as the main driving factor. Transcript diversity and evenness were higher during polar night compared to polar day. Light-dependent functions had higher relative expression during polar day, except phototransduction. 64% of the most expressed genes could not be functionally annotated, yet up to 78% were identified in Arctic samples from Tara Oceans, suggesting that Arctic marine assemblages are distinct from those from other oceans. Our study increases understanding of the links between extreme seasonality and biological processes in pico- and nanoplanktonic protists. Our results set the ground for future monitoring studies investigating the seasonal impact of climate change on the communities of microbial eukaryotes in the High Arctic.

Abstract Background Patients who identify as 2SLGBTQIA + report negative experiences with physiotherapy. The objectives were to evaluate student attitudes, beliefs and perceptions related to 2SLGBTQIA + health education and working with individuals who identify as 2SLGBTQIA + in entry-level physiotherapy programs in Canada and to evaluate physiotherapy program inclusiveness towards 2SLGBTQIA + persons. Methods We completed a nationwide, cross-sectional survey of physiotherapy students from Canadian institutions. We recruited students via email and social media from August-December 2021. Frequency results are presented with percentages. Logistic regression models (odds ratios [OR], 95%CI) were used to evaluate associations between demographics and training hours with feelings of preparedness and perceived program 2SLGBTQIA + inclusiveness. Results We obtained 150 survey responses (mean age = 25 years [range = 20 to 37]) from students where 35 (23%) self-identified as 2SLGBTQIA + . While most students (≥ 95%) showed positive attitudes towards working with 2SLGBTQIA + patients, only 20 students (13%) believed their physiotherapy program provided sufficient knowledge about 2SLGBTQIA + health and inclusiveness. Students believed more 2SLGBTQIA + training is needed (n = 137; 92%), believed training should be mandatory (n = 141; 94%) and were willing to engage in more training (n = 138; 92%). Around half believed their physiotherapy program (n = 80, 54%) and clinical placements (n = 75, 50%) were 2SLGBTQIA + -inclusive and their program instructors (n = 69, 46%) and clinical instructors (n = 47, 31%) used sex/gender-inclusive language. Discrimination towards 2SLGBTQIA + persons was witnessed 56 times by students and most (n = 136; 91%) reported at least one barrier to confronting these behaviours. Older students (OR = 0.89 [0.79 to 0.99]), individuals assigned female at birth (OR = 0.34 [0.15 to 0.77]), and students self-identifying as 2SLGBTQIA + (OR = 0.38 [0.15 to 0.94]) were less likely to believe their program was 2SLGBTQIA + inclusive. Older students (OR = 0.85 [0.76 to 0.94]) and 2SLGBTQIA + students (OR = 0.42 [0.23 to 0.76]) felt the same about their placements. Students who reported > 10 h of 2SLGBTQIA + training were more likely to believe their program was inclusive (OR = 3.18 [1.66 to 6.09]). Conclusions Entry-level physiotherapy students in Canada show positive attitudes towards working with 2SLGBTQIA + persons but believe exposure to 2SLGBTQIA + health and inclusiveness is insufficient in their physiotherapy programs. This suggests greater attention dedicated to 2SLGBTQIA + health would be valued.

Abstract Extracellular vesicles (EVs) are cell-derived lipid bilayer-enclosed particles that play a role in intercellular communication. Cardiac progenitor cell (CPC)-derived EVs have been shown to protect the myocardium against ischemia-reperfusion injury via pro-angiogenic effects. However, the mechanisms underlying CPC-EV-induced angiogenesis remain elusive. Here, we discovered that the ability of CPC-EVs to induce in vitro angiogenesis and to stimulate pro-survival pathways was lost upon EV donor cell exposure to calcium ionophore. Proteomic comparison of active and non-active EV preparations together with phosphoproteomic analysis of activated endothelial cells identified the contribution of candidate protein PAPP-A and the IGF-R signaling pathway in EV-mediated cell activation, which was further validated using in vitro angiogenesis assays. Upon further purification using iodixanol gradient ultracentrifugation, EVs partly lost their activity, suggesting a co-stimulatory role of co-isolated proteins in recipient cell activation. Our increased understanding of the mechanisms of CPC-EV-mediated cell activation will pave the way to more efficient EV-based therapeutics.

Abstract Background Chronic pain management is challenging for health systems worldwide. Clinical practice guidelines recommend interprofessional chronic pain management, but chronic pain clinics often have lengthy wait-lists. Advanced practice physiotherapists (APP) in orthopedic clinics and emergency departments have provided effective care and reduced wait times. The purpose of this study is to determine the feasibility of a clinical trial to evaluate the effects of integrating an APP into a chronic pain clinic setting. The primary objectives are as follows: (1) determine the feasibility of implementing trial methods by evaluating participant recruitment rates, retention, and assessment completion; (2) determine the feasibility of implementing the APP model of care by monitoring care provided and treatment fidelity; and (3) assess contextual factors that may influence implementation of the APP model of care by exploring the perspectives of patient participants and healthcare providers related to the model of care. Methods This will be a single-arm feasibility study with embedded qualitative interviews to assess contextual factors influencing implementation by exploring participant and provider perspectives. Approximately 40 adults with chronic musculoskeletal pain referred for care at an interprofessional chronic pain clinic will be invited to participate in the feasibility study. Approximately 10–12 patient participants and 5–10 health professionals from the interprofessional team will be interviewed using an interpretive description approach. The APP model of care will involve participants seeing a physiotherapist as the first point of contact within the interprofessional team. The APP will complete an initial assessment and make care recommendations. Outcome measures planned for the full trial will be reported descriptively, including pain severity, pain interference, health-related quality of life, psychosocial risk factors for chronic pain, treatment satisfaction, perceived change, healthcare utilization, and healthcare costs over one year. Discussion This study will inform plans to implement a full-scale study to evaluate the impact of an APP model of care in an interprofessional chronic pain management program. The results of the full study are intended to inform stakeholders considering this model to improve patient-centered and health system outcomes in interprofessional pain management program settings. Trial registration ClinicalTrials.gov, NCT05336903 (Registered April 5, 2022).

Abstract Background Individuals who identify as 2SLGBTQIA+ report worse health outcomes than heterosexual/cisgender counterparts, in part due to poor experiences with healthcare professionals. This may stem from inadequate 2SLGBTQIA+ health and inclusiveness training in health professional student education. The purpose of the study was to evaluate knowledge, behaviours, and training related to 2SLGBTQIA+ health education and inclusiveness for entry-level physiotherapy students in Canada. Methods We conducted a nationwide, cross-sectional survey with physiotherapy students from accredited Canadian physiotherapy programs. We administered the survey through Qualtrics and recruited students through targeted recruitment emails and social media posts on Twitter and Instagram between August and December 2021. Survey responses are reported as frequencies (percentage). We also completed multivariable logistic regressions to evaluate associations among question responses related to working with 2SLGBTQIA+ individuals (i.e., communication, feeling prepared and assessment competency). Covariates included training hours (

Abstract Extracellular vesicles (EVs) are thought to mediate intercellular communication by transferring cargoes from donor to acceptor cells. The EV content-delivery process within acceptor cells is still poorly characterized and debated. CD63 and CD9, members of the tetraspanin family, are highly enriched within EV membranes and are respectively enriched within multivesicular bodies/endosomes and at the plasma membrane of the cells. CD63 and CD9 have been suspected to regulate the EV uptake and delivery process. Here we used two independent assays and different cell models (HeLa, MDA-MB-231 and HEK293T cells) to assess the putative role of CD63 and CD9 in the EV delivery process that includes uptake and cargo delivery. Our results suggest that neither CD63, nor CD9 are required for this function.

Despite efforts to promote inclusivity in schools, ethnic bullying is a pervasive issue. Recent studies have highlighted the potential of empathy and cultural self efficacy within cross-cultural friendships to mitigate ethnic bullying. Violence prevention programs in the United States rely on didactic approaches and few include embodied approaches. Our goal was to examine the impact of dance/movement therapy (DMT) on empathy, peer relationships, and cultural self-efficacy among racially/ethnically diverse groups of middle school students using a mixed methods research design. Quantitative data did not demonstrate significant change in empathy, peer relationships, and cultural self-efficacy. Qualitative data described an increase in participants’ emotional intelligence including empathy, cultural self-efficacy, and positive cross-cultural relationships. Additional research is needed to determine the definitive impact of DMT on these outcomes.

Abstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding the distinct mechanisms underlying their regenerative abilities. Here, a dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied to isolate and separate CPC‐derived sEV subpopulations to study the functional differences related to cardiac repair responses. Three distinct sEV subpopulations were identified with unique protein profiles. Functional cell assays for cardiac repair‐related processes demonstrated that the middle‐sized and smallest‐sized sEV subpopulations exhibited the highest pro‐angiogenic and anti‐fibrotic activities. Proteasome activity was uniquely seen in the smallest‐sized subpopulation. The largest‐sized subpopulation showed no effect in any of the functional assays. This research uncovers the existence of sEV subpopulations, each characterized by a distinct composition and biological function. Enhancing our understanding of sEV heterogeneity will provide valuable insights into sEV mechanisms of action, ultimately accelerating the translation of sEV therapeutics.

Abstract The loss‐of‐function of the proprotein convertase subtilisin–kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low‐density lipoprotein cholesterol (LDL‐C) levels. Both CRISPR/Cas9 and CRISPR‐based editor‐mediated Pcsk9 inactivation have successfully lowered plasma LDL‐C and PCSK9 levels in preclinical models. Despite the promising preclinical results, these studies did not report how vehicle‐mediated CRISPR delivery inactivating Pcsk9 affected low‐density lipoprotein receptor recycling in vitro or ex vivo. Extracellular vesicles (EVs) have shown promise as a biocompatible delivery vehicle, and CRISPR/Cas9 ribonucleoprotein (RNP) has been demonstrated to mediate safe genome editing. Therefore, we investigated EV‐mediated RNP targeting of the Pcsk9 gene ex vivo in primary mouse hepatocytes. We engineered EVs with the rapamycin‐interacting heterodimer FK506‐binding protein (FKBP12) to contain its binding partner, the T82L mutant FKBP12‐rapamycin binding (FRB) domain, fused to the Cas9 protein. By integrating the vesicular stomatitis virus glycoprotein on the EV membrane, the engineered Cas9 EVs were used for intracellular CRISPR/Cas9 RNP delivery, achieving genome editing with an efficacy of ±28.1% in Cas9 stoplight reporter cells. Administration of Cas9 EVs in mouse hepatocytes successfully inactivated the Pcsk9 gene, leading to a reduction in Pcsk9 mRNA and increased uptake of the low‐density lipoprotein receptor and LDL‐C. These readouts can be used in future experiments to assess the efficacy of vehicle‐mediated delivery of genome editing technologies targeting Pcsk9. The ex vivo data could be a step towards reducing animal testing and serve as a precursor to future in vivo studies for EV‐mediated CRISPR/Cas9 RNP delivery targeting Pcsk9.

In glioblastoma, a malignant primary brain tumor, liposomes have shown promise in pre-clinical and early phase clinical trials as delivery vehicles for therapeutics. However, external factors influencing cellular uptake of liposomes in glioma cells are poorly understood. Heparin and heparin analogues are commonly used in glioma patients to decrease the risk of thrombo-embolic events. Our results show that heparin inhibits pegylated liposome uptake by U87 glioma and GL261 cells in a dose dependent manner in vitro, and that heparin-mediated inhibition of uptake required presence of fetal bovine serum in the media. In a subcutaneous model of glioma, Cy5.5 labeled liposomes could be detected with in vivo imaging after direct intra-tumoral injection. Ex-vivo analysis with flow cytometry showed a decreased uptake of liposomes into tumor cells in mice treated systemically with heparin compared to those treated with vehicle only.

Resilience to adverse events is increasingly recognized as important for human health. Socio-economic status (SES) is also frequently identified as a predictor of resilience. However, it is not well-understood how people define resilience in their everyday lives, and whether individuals have different experiences of resilience based on their SES. This study sought to fill these gaps, in the context of the COVID-19 pandemic and pandemic mitigation policies in the Netherlands.We interviewed high (n = 38) and low (n = 37) SES participants about their understanding and experiences of resilience during this period. Participants took part in individual interviews and focus groups in September 2021. Transcripts were analyzed thematically.A key theme was coping with adversity, in line with commonly-used definitions of resilience. However, we found that resilience was often defined more broadly. Resilience also encompassed aspects of self-reflection and improvement, and faith in oneself, the community and the nation. There were also key differences by SES background: elaborate and optimistic definitions and experiences of resilience were more often described by high SES individuals. For instance, high SES participants more frequently defined resilience as growing and improving. In contrast, low SES participants more commonly experienced resilience as enduring until better times arrived.Having a higher SES seemed to support resilience during the COVID-19 pandemic. This indicates that adverse events may exacerbate pre-existing financial and material difficulties among low SES individuals. This finding underscores the importance of addressing financial precarity prior to adverse events.

ABSTRACTBackground Chronic low back pain (LBP) is a prevalent and disabling health issue. Team-based models of primary care are ideally positioned to provide comprehensive care for patients with chronic LBP. A better understanding of primary care team perspectives can inform future efforts to improve how team-based care is provided for patients with chronic LBP in this practice setting.Aims The aim of this study was to understand health care providers’ experiences, perceived barriers and facilitators, and recommendations when providing team-based primary care for the management of chronic LBP.Methods We conducted an interpretive description qualitative study based on focus group discussions with health care providers from team-based primary care settings in Ontario, Canada. Data were analyzed using thematic analysis.Results We conducted five focus groups with five different primary care teams, including a total of 31 health care providers. We constructed four themes (each with subthemes) related to experiences, perceived barriers and facilitators, and recommendations to providing team-based primary care for the management of chronic LBP, including (1) care pathways and models of service delivery, (2) team processes and organization, (3) team culture and environment, and (4) patient needs and readiness.Conclusions Primary care teams are implementing diverse care pathways and models of service delivery for the management of patients with chronic LBP, which can be influenced by patient, team, and organizational factors. Results have potential implications for future research and practice innovations to improve how team-based primary care is delivered for patients with chronic LBP.

Abstract Background Women have a higher life expectancy than men but experience more years with physical disabilities in daily life at older ages, especially women with a migration background. This pinpoints older women as an important target group for strategies that stimulate healthy lifestyle, which benefits healthy aging. Our study investigates motivators and barriers for healthy lifestyles and perspectives on determinants of healthy aging of older women. This provides essential information for developing targeted strategies. Methods Data was collected by semi-structured digital interviews from February till June 2021. Women aged 55 years and older living in the Netherlands (n = 34) with a native Dutch (n = 24), Turkish (n = 6) or Moroccan (n = 4) migration background were included. Two main subjects were investigated: (1) motivators and barriers on their current lifestyles regarding smoking, alcohol consumption, physical activity, diet and sleep and (2) perspectives on determinants of healthy aging. Interviews were analyzed using Krueger’s framework. Results Personal health was the most common motivator for a healthy lifestyle. In addition, peer pressure and being outdoors were specific motivators for physical activity. Bad weather conditions and personal dislike to be active were specific barriers. The social environment, personal preferences and personal belief to compensate with other healthy lifestyle behaviors were barriers for low alcohol consumption. Personal preferences (liking unhealthy food and not making time) were the main barriers for a healthy diet. Sleep was not perceived as a form of lifestyle behavior, but rather as a personal trait. Since there were no smokers, specific barriers were not mentioned. For Turkish-Dutch and Moroccan-Dutch women, additional barriers and motivators were culture and religion. These were strong motivators to abstain from alcohol consumption and smoking, but a barrier for a healthy diet. With regard to perspectives on determinants of healthy aging, positive views on aging and being physically active were perceived as most important. Women often wanted to increase their physical activity or healthy diet to stimulate healthy aging. Among Turkish-Dutch and Moroccan-Dutch women, healthy aging was also perceived as something in the hands of God. Conclusions Although motivators and barriers for a healthy lifestyle and perspectives on healthy aging vary for distinct lifestyles, personal health is a common motivator across all lifestyles. Having a migration background added culture and religion as distinct barriers and motivations. Strategies to improve lifestyle among older women should therefore have a tailored, culture sensitive approach (if applicable) for distinct lifestyle factors.

Abstract Extracellular vesicles (EVs) are nanoscale particles that facilitate intercellular communication. They are regarded as a promising natural drug delivery system for transporting and delivering bioactive macromolecules to target cells. Recently, researchers have engineered EVs with FKBP12/FRB heterodimerization domains that interact with rapamycin to load and deliver exogenous proteins for both in vitro and in vivo applications. In this study, we examined the tissue distribution of EVs using near‐infrared fluorescent imaging. We evaluated the effectiveness of EV‐mediated delivery of Cre recombinase specifically to hepatocytes in the livers of Ai9 Cre‐loxP reporter mice. Intravenous injection resulted in more efficient Cre protein delivery to the liver than intraperitoneal injections. Depleting liver‐resident macrophages with clodronate‐encapsulated liposome pre‐treatment did not enhance EV‐mediated Cre delivery to hepatocytes. Moreover, we demonstrated that multiple intravenous injections of Cre‐EVs facilitated functional Cre delivery to hepatocytes. To the best of our knowledge, this is the first study to simultaneously investigate the tissue distribution of FKBP12/FRB‐engineered EVs and their subsequent intracellular protein delivery in Ai9 Cre‐loxP reporter mice. These insights can inform preclinical research and contribute to developing next‐generation EV‐based platforms for delivering therapeutic proteins or genome editing technologies targeting the liver.

Background Patient engagement (PE) in research refers to partnering with people with lived experience (e.g., patients, caregivers, family) as collaborators in the research process. Although PE is increasingly being recognized as an important aspect of health research, the current state of PE among pain research trainees in Canada is unclear.Aims The aims of this study were to describe perspectives about and experiences with PE among trainees conducting pain research in Canada, to identify perceived barriers and facilitators, and to describe recommendations to improve its implementation.Methods A cross-sectional web-based survey (English and French) was administered to trainees at any level conducting pain research at any Canadian academic institution.Results A total of 128 responses were received; 115 responses were complete and included in the final analysis. The majority of respondents identified as women (90/115; 78.3%), in graduate school (83/115; 72.2%), and conducting clinical pain research (83/115; 72.2%). Most respondents (103/115; 89.6%) indicated that PE is “very” or “extremely” important. Despite this, only a minority of respondents (23/111; 20.7%) indicated that they “often” or “always” implement PE within their own research. The most common barrier identified was lack of knowledge regarding the practical implementation of PE, and understanding its positive value was the most commonly reported facilitator. Recommendations for improving the implementation of PE were diverse.Conclusions Despite viewing PE as important in research, a minority of pain research trainees regularly implement PE. Results highlight perceived barriers and facilitators to PE and provide insight to inform the development of future training and other enabling initiatives.

Abstract Background Low back pain (LBP) is one of the most common reasons for primary care visits and is the leading contributor to years lived with disability worldwide. The purpose of this study was to understand the perspectives of patients and primary care team members related to their experiences with a new physiotherapist-led primary care model for LBP. Methods We conducted an interpretive description qualitative study. Data were collected using a combination of semi-structured interviews and focus group discussions and analyzed using thematic analysis. Participants included adults (> 18 years of age) with LBP and primary care team members who participated in a physiotherapist-led primary care model for LBP in Kingston, Ontario, Canada. Results We conducted 18 semi-structured interviews with patients with LBP (10 women; median age of 52) as well as three focus group discussions with a total of 20 primary care team members representing three teams. Four themes (each with sub-themes) were constructed: 1) enhanced primary care delivery for LBP (improved access and engagement in physiotherapy care, improved communication and care integration between the physiotherapist and primary care team, less inappropriate use of healthcare resources); 2) positive patient experiences and perceived outcomes with the new model of care (physiotherapist built therapeutic alliance, physiotherapist provided comprehensive care, improved confidence in managing LBP, decreased impact of pain on daily life); 3) positive primary care team experiences with the new model of care (physiotherapist fit well within the primary care team, physiotherapist provided expertise on LBP for the primary care team, satisfaction in being able to offer a needed service for patients); and 4) challenges implementing the new model of care (challenges with prompt access to physiotherapy care, challenges making the physiotherapist the first contact for LBP, and opportunities to optimize communication between the physiotherapist and primary care team). Conclusions A new physiotherapist-led primary care model for LBP was described by patients and primary care team members as contributing to positive experiences and perceived outcomes for patients, primary care team members, and potentially the health system more broadly. Results suggest that this model of care may be a viable approach to support integrated and guideline adherent management of LBP in primary care settings.

The Barents Sea is a transition zone between the Atlantic and the Arctic Ocean. The ecosystem in this region is highly variable, and a seasonal baseline of biological factors is needed to monitor the effects of global warming. In this study, we report the results from the investigations of the bacterial and archaeal community in late winter, spring, summer, and early winter along a transect through the northern Barents Sea into the Arctic Ocean east of Svalbard using 16S rRNA metabarcoding. Winter samples were dominated by members of the SAR11 clade and a community of nitrifiers, namely Cand. Nitrosopumilus and LS-NOB (Nitrospinia), suggest a prevalence of chemoautotrophic metabolisms. During spring and summer, members of the Gammaproteobacteria (mainly members of the SAR92 and OM60(NOR5) clades, Nitrincolaceae) and Bacteroidia (mainly Polaribacter, Formosa, and members of the NS9 marine group), which followed a succession based on their utilization of different phytoplankton-derived carbon sources, prevailed. Our results indicate that Arctic marine bacterial and archaeal communities switch from carbon cycling in spring and summer to nitrogen cycling in winter and provide a seasonal baseline to study the changes in these processes in response to the effects of climate change.

Both (biological) sex and (socio-cultural) gender are relevant for health but in large-scale studies specific gender measures are lacking. Using a masculine gender-score based on 'traditional masculine-connotated aspects of everyday life’, we explored how masculinity may affect sex differences in the prevalence of chronic health problems. We used cross-sectional data (2008–2012) from the Doetinchem Cohort Study to calculate a masculine gender-score (range 0–19) using information on work, informal care, lifestyle and emotions. The sample consisted of 1900 men and 2117 women (age: 40–80). Multivariable logistic regressions including age and SES were used to examine the role of masculine gender on sex differences in the prevalence of diabetes, coronary heart disease, CVA, arthritis, chronic pain and migraine. Men had higher masculine gender-scores than women (12.2 vs 9.1). For both sexes, a higher masculine gender-score was associated with lower prevalence of chronic health problems. Diabetes, CHD, and CVA were more prevalent in men, and gender-adjustment resulted in greater sex differences: e.g. for diabetes the ORsex changed from 1.21 (95 %CI 0.93–1.58) to 1.60 (95 %CI 1.18–2.17). Arthritis, chronic pain, and migraine were more prevalent in women, and gender-adjustment resulted in smaller sex differences: e.g. for chronic pain the ORsex changed from 0.53 (95 %CI 0.45–0.60) to 0.73 (95 %CI 0.63–0.86). Gender measured as ‘everyday masculinity’ is associated with lower prevalence of chronic health problems in both men and women. Our findings also suggest that the commonly found sex differences in the prevalence of chronic health problems have a large gender component.

Faster cryo specimen preparation can advance cryo electron microscopy (cryoEM). Here, the authors present a vitrification device with automated sample handling for cryoEM of proteins, suspensions and cells, enabling blot-free sample thinning, dew-point control and characterization of cryo grids prior to data acquisition.

Abstract Under very cold conditions, delicate ice‐crystal structures called frost flowers emerge on the surface of newly formed sea ice. These understudied, ephemeral structures include saline brine, organic material, inorganic nutrients, and bacterial and archaeal communities in their brine channels. Hitherto, only a few frost flowers have been studied during spring and these have been reported to be dominated by Rhizobia or members of the SAR11 clade. Here we report on the microbiome of frost flowers sampled during the winter and polar night in the Barents Sea. There was a distinct difference in community profile between the extracted DNA and RNA, but both were dominated by members of the SAR11 clade (78% relative abundance and 41.5% relative activity). The data further suggested the abundance and activity of Cand. Nitrosopumilus, Nitrospinia, and Nitrosomonas. Combined with the inference of marker genes based on the 16S rRNA gene data, this indicates that sulfur and nitrogen cycling are likely the major metabolism in these ephemeral structures.

Background Evidence about the impact of the COVID-19 pandemic on existing health inequalities is emerging. This study explored dif-ferences in mental health, sense of coherence (SOC), sense of community coherence (SOCC), sense of national coherence (SONC), and social support between low and high socioeconomic (SES) groups, and the predictive value of these predictors for mental health. Material and methods A cross-sectional study was conducted using an online survey in the Netherlands in October 2021, comprising a total of 91 respondents (n = 41, low SES; n = 50, high SES). Results There were no differences in mental health, SOC, SOCC, SONC, and social support between the groups. SOC was a predictor for mental health in both groups and SOCC for the low SES group. Conclusions We found that both SOC and SOCC predict mental health during the pandemic. In the article we reflect on possible path-ways for strengthening these resources for mental health.

Cardiac progenitor cell-derived extracellular vesicles (CPC-EVs) have been successfully applied via different delivery routes for treating post-myocardial infarction injury in several preclinical models. Hence, understanding the in vivo fate of CPC-EVs after systemic or local, i.e. myocardial, delivery is of utmost importance for the further therapeutic application of CPC-EVs in cardiac repair. Here, we studied the tissue- and cell distribution and retention of CPC-EVs after intramyocardial and intravenous injection in mice by employing different EV labeling and imaging techniques. In contrast to progenitor cells, CPC-EVs demonstrated no immediate flush-out from the heart upon intramyocardial injection and displayed limited distribution to other organs over time, as determined by near-infrared imaging in living animals. By employing CUBIC tissue clearing and light-sheet fluorescent microscopy, we observed CPC-EV migration in the interstitial space of the myocardium shortly after EV injection. Moreover, we demonstrated co-localization with cTnI and CD31-positive cells, suggesting their interaction with various cell types present in the heart. On the contrary, after intravenous injection, most EVs accumulated in the liver. To potentiate such a potential systemic cardiac delivery route, targeting the cardiac endothelium could provide openings for directed CPC-EV therapy. We therefore evaluated whether decorating EVs with targeting peptides (TPs) RGD-4C or CRPPR connected to Lamp2b could enhance EV delivery to endothelial cells. Expression of both TPs enhanced CPC-EV uptake under in vitro continuous flow, but did not affect uptake under static cell culture conditions. Together, these data demonstrate that the route of administration influences CPC-EV biodistribution pattern and suggest that specific TPs could be used to target CPC-EVs to the cardiac endothelium. These insights might lead to a better application of CPC-EV therapeutics in the heart.

The CRISPR-Cas9 technology represents a powerful tool for genome engineering in eukaryotic cells, advancing both fundamental research and therapeutic strategies. Despite the enormous potential of the technology, efficient and direct intracellular delivery of Cas9 ribonucleoprotein (RNP) complexes in target cells poses a significant hurdle, especially in refractive primary cells. In the present work, vapor nanobubble (VNB) photoporation was explored for Cas9 RNP transfection in a variety of cell types. Proof of concept was first demonstrated in H1299-EGFP cells, before proceeding to hard-to-transfect stem cells and T cells. Gene knock-out levels over 80% and up to 60% were obtained for H1299 cells and mesenchymal stem cells, respectively. In these cell types, the unique possibility of VNB photoporation to knock out genes according to user-defined spatial patterns was demonstrated as well. Next, effective targeting of the programmed cell death 1 receptor and Wiskott-Aldrich syndrome gene in primary human T cells was demonstrated, reaching gene knock-out levels of 25% and 34%, respectively. With a throughput of >200,000 T cells per second, VNB photoporation is a scalable and versatile intracellular delivery method that holds great promise for CRISPR-Cas9-mediated ex vivo engineering of cell therapy products.

Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth.