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Examination of the extent to which time and place affect people's health has been constrained by the resources available to answer this question. A British longitudinal, nationally representative survey of 8301 adults aged 16 years and older living in private households was used to consider the influence of household membership, area of residence and time using multilevel logistic regression. Self-rated health was assessed by general health and limiting illness during periods characterized by economic decline (1992), economic improvement (1996) and prosperity (2000). There was modest evidence of clustering of poor general health within areas and stronger support for within household similarities in general health which increased over time. Individual, household and area level deprivation accounted for almost all the area-level variability but had little effect on household variance. There was greater evidence of clustering of limiting illness within areas: deprivation did not account for this to any great extent. Area differences in general health reduced as the economy improved but time trends in differences in limiting illness lagged behind the timing of economic recovery. Both time and place are shown to affect self-rated health although the processes may differ depending on the health outcome. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate whether longstanding illnesses, social context, and current socioeconomic circumstances predict quality of life. DESIGN: Secondary analysis of wave 1 of the English longitudinal study of aging. Missing data were imputed and multiple regression analyses conducted. SETTING: England, 2002 PARTICIPANTS: Nationally representative sample of non-institutionalised adults living in England (n = 11 234, 54.5% women, age 65.1 (SD 10.2) years). MAIN OUTCOME MEASURE: Quality of life as measured by CASP-19, a 19 item Likert scaled index. RESULTS: The quality of life was reduced by depression (beta -0.265), poor perceived financial situation (beta -0.157), limitations in mobility (beta -0.124), difficulties with everyday activities (beta -0.112), and limiting longstanding illness (beta -0.112). The quality of life was improved by trusting relationships with family (beta 0.105) and friends (beta 0.078), frequent contacts with friends (beta 0.059), living in good neighbourhoods (beta 0.103), and having two cars (beta 0.066). The regression models explained 48% variation in CASP-19 scores. There were slight differences between age groups and between men and women. CONCLUSIONS: Efforts to improve quality of life in early old age need to address financial hardships, functionally limiting disease, lack of at least one trusting relationship, and inability to move out of a disfavoured neighbourhood. There is the potential for improved quality of life in early old age (the third age) if these factors are controlled. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To study how social inequalities change as people age, this paper presents a growth curve model of self assessed health, which accommodates changes in occupational class and individual health with age. DESIGN: Nationally representative interview based longitudinal survey of adults in Great Britain. SETTING: Representative members of private households of Great Britain in 1991. PARTICIPANTS: Survey respondents (n = 6705), aged 21-59 years in 1991 and followed up annually until 2001. MAIN OUTCOME MEASURE: Self assessed health. RESULTS: On average, self assessed health declines slowly from early adulthood to retirement age. No significant class differences in health were observed at age 21. Health inequalities emerged later in life with the gap between mean levels of self assessed health of those in managerial and professional occupations and routine occupations widening approaching retirement. Individual variability in health trajectories increased between ages 40 and 59 years so that this widening of mean differences between occupational classes was not significant. When the analysis is confined to people whose occupational class remained constant over time, a far greater difference in health trajectories between occupational classes was seen. CONCLUSIONS: The understanding of social inequalities in health at the population level is enriched by an analysis of individual variation in age related declines by social position. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVE: To examine social inequalities in minor psychiatric morbidity as measured by the GHQ-12 using lagged models of psychiatric morbidity and changing job status. DESIGN: GHQ scores were modelled using two level hierarchical regression models with measurement occasions nested within individuals. The paper compares and contrasts three different ways of describing social position: income, social advantage and lifestyle (the Cambridge scale), and social class (the new National Statistics Socio-Economic Classification), and adjusts for attrition. SETTING: Survey interviews for a nationally representative sample of adults of working age living in Britain. PARTICIPANTS: 8091 original adult respondents in 1991 who remain of working age during 1991-1998 from the British Household Panel Survey (BHPS). MAIN RESULTS: There was a relation of GHQ-12 to social position when social position was combined with employment status. This relation itself varied according to a person's psychological health in the previous year. CONCLUSIONS: The relation between social position and minor psychiatric morbidity depended on whether or not a person was employed, unemployed, or economically inactive. It was stronger in those with previously less good psychological health. Among employed men and women in good health, GHQ-12 varied little according to social class, status, or income. There was a 'classic' social gradient in psychiatric morbidity, with worse health in less advantaged groups, among the economically inactive. Among the unemployed, a 'reverse' gradient was found: the impact of unemployment on minor psychiatric morbidity was higher for those who were previously in a more advantaged social class position. [ABSTRACT FROM AUTHOR]

BACKGROUND: In health inequalities research there is a growing impetus to examine the development of inequalities in health over time. However, many of the sources of longitudinal data in Britain are not designed specifically for health research. Typically, health status is assessed by self-reported problems and the use of symptom checklists. METHODS: The British Household Panel Survey (BHPS) is an annual survey of approximately 5500 private households containing 9000 men and women, which began in 1991. Each year, the BHPS contains a checklist of 13 health problems and symptoms. The findings presented here are based on adult participants aged 16 years and over in 1991. Using eight waves of data from the BHPS, we use latent class analysis (LCA) to model latent health status from a set of observed binary variables. Individuals are assigned to a latent health class on the basis of LCA estimated probabilities of class membership given their response patterns and the estimated unconditional class frequencies. The predictive value of latent health class membership is assessed for self-reported health status and functioning, health and welfare service use, and mortality 1 year later. RESULTS: The LCA supported a suitable four-class model of health status representing good health, psychosomatic health problems, physical health problems and comorbid health problems. Members of the good latent health class were predicted to have better self-reported health and functioning, less health and welfare service use, and lower risk of mortality 1 year later than members of the three problem health classes. Those with comorbid health problems were predicted to have particularly poor outcomes. CONCLUSIONS: A latent class approach to modelling self-reported health problems and symptoms has allowed for both quantitative and qualitative dimensions of health status to be captured. This may motivate better informed models of health by users of general population surveys. [ABSTRACT FROM AUTHOR]

Quality of life is the subject of much research. However it lacks an agreed theoretical basis. In studies with older populations(ill) health has been used as a proxy measure for quality of life (QoL). We have developed a needs satisfaction measure of QoL in early old age. Our measure has four ontologically grounded domains: conal, autonomy, pleasure, and self-realization. The measure was piloted with focus groups, a self-completion pilot, and cognitive interview testing.This produced a 22-item scale that was included in a postal questionnaire and sent to 286 people aged 65-75 years.A 92% response rate was achieved. The scale was reduced to 19 items on the basis of statistical analysis. The domains have Cronbach's alphas between 0.6 and 0.8. Correlations between the four domains range from 0.4 to 0.7. A second order factor analysis revealed a single latent QoL factor. The scores for the 19-item scale are well distributed along the range although they exhibit a slight negative skew. Concurrent validity was assessed using the Life Satisfaction Index--wellbeing. A strong and positive association was found between the two scales (r= 0.6, p = 0.01). The CASP-19 appears to be a useful scale for measuring QoL in older people. [ABSTRACT FROM AUTHOR]

This paper investigates geographical variations in women's reports of limiting long-term illness in terms of individual inequalities and the contribution of area characteristics among wards and county districts. We use multilevel modelling of linked census data from the Office for National Statistics Longitudinal Study for England and Wales. We follow a random sample of 76.374 women aged between 16 and 45 at the time of the 1971 Census for 20 years to observe their reported limiting long-term illness (LLTI) at the 1991 Census. Car and home ownership were useful markers of social and material advantage, apparently protecting against the risk of reporting LLTI. Migration into the South-East region appeared beneficial, but otherwise there was little difference between those who moved home and those who did not. Differences between county districts persist after adjustment for individual circumstances (education and ethnicity), but almost all of these differences are explained by the social profile of wards in these areas. Geographical differences in LLTI are not, therefore, entirely explained by the distribution of individual characteristics: a woman with the same history may face a different risk of illness in different kinds of area. For women, the social composition of the locality (using the ward as a proxy) is more relevant than the broader economic and industrial classification of the surrounding county district, which is more important for health inequalities among men. [ABSTRACT FROM AUTHOR]

AIM: The aim of this study was to investigate the nature and organization of maternal needs and priorities in a neonatal unit. BACKGROUND: The relationship between maternal needs and priorities appears to be an under studied area in neonatal nursing. METHODS: A quantitative survey was carried out based on 209 mothers with premature infants. Two self-assessment schedules were used: critical care maternal needs inventory (J. Leske, Heart and Lung 15, 27-42) and a ranking scale. The data were analysed with multivariate analysis. FINDINGS: Data analysis revealed clear priorities in maternal needs. In particular the need for accurate infant related information was a priority for 93% of the mothers. Good communication practices with professionals were also valued. The mothers displayed altruistic behaviour, and self-related needs took second place. It is proposed that maternal needs demonstrate a hierarchical organization. CONCLUSION: It is important for nurses to consider the individual needs of the mothers, simply because the satisfaction of these needs is essential for maternal well-being. [ABSTRACT FROM AUTHOR]

Proteins are fundamental to biochemical processes and critical in hemodialysis. This study investigates the impact of pH on human serum albumin (HSA), fibrinogen (FB), and transferrin (TRF) interactions with polyarylethersulfone (PAES) hemodialysis membranes. A multi-method approach was utilized, including protein crystallography for structural insights, hydration layer analysis to explore solvation and interaction potentials, molecular docking using AutoDock 4.0 for binding affinity simulations, and in-situ X-ray synchrotron SR-μCT imaging to observe protein deposition dynamics. Molecular docking revealed that PAES demonstrated superior binding energies and interaction patterns with FB and TRF compared to cellulose triacetate (CTA), facilitated by specific hydrogen bonding within a water shell. CTA displayed weaker, hydration-sensitive interactions varying with pH. Imaging studies indicated that FB showed higher adsorption at pH 6 than at pH 7.2, predominantly in the middle membrane regions. Similarly, HSA and TRF exhibited increased adsorption at pH 6, suggesting a stronger affinity under acidic conditions. Mixed protein solutions also indicated higher adsorption at pH 6, emphasizing an increased risk of membrane fouling. These findings highlight the crucial role of pH in modulating protein-membrane interactions and enhancing the efficacy of hemodialysis. A deeper understanding of hydration environments and their effects on protein binding affinities provides valuable insights for optimizing membrane design and performance. Clinically, this research suggests that fine-tuning pH during hemodialysis could mitigate protein fouling on membranes, thereby improving procedural efficiency and potentially leading to better patient outcomes through enhanced dialysis effectiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Many attempts have been made to integrate medicinal chemistry knowledge into therapeutic decision-making in pharmacy programs across North America. Examples include the use of Structure-Based Therapeutic Evaluations, alignment of medicinal chemistry content with courses in pharmacology, pharmaceutics and pharmacotherapeutics, and team-based or problem-based learning methods. The majority of these approaches indicate that students have greater confidence or comfort with medicinal chemistry, but there remain few cases where an improvement in performance has been measured. This is especially challenging for assessing a student's ability to implement medicinal chemistry learning in pharmacotherapeutic decision-making. Building upon our national special interest group's recent environmental scan of medicinal chemistry instruction in Canadian Pharmacy programs, we are investigating strategies for integration of medicinal chemistry learning in therapeutic decision-making. This commentary will discuss methods and evidence to support medicinal chemistry integration, relevant assessment strategies, and potential paths forward., Competing Interests: Declaration of competing interest The authors listed above have no conflict of interest to declare and no affiliations with or involvement in any organization or entity with any financial interest in this submission., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Endpoint Adjudication Committees (EACs) benefit the quality of randomized control trials (RCTs) where outcomes depend on subjective interpretations. However, assembling a committee to adjudicate large datasets is cumbersome. In a recent RCT, the primary outcome was time to union following operative fixation of scaphoid non-union, with real or placebo adjunctive ultrasound treatment. Union status was determined with computed tomography (CT) scans interpreted by treating surgeons and radiologists. An EAC was established to deliberate discrepancies between radiologists' and surgeons' interpretations of union status., Methods: Three hundred sixty-four CT scans from 142 participants were collected in the RCT. The treating surgeon and an MSK radiologist categorized images by percent-union (0 %, 1-24 %, 25-49 %, 50-74 %, 75-99 %, 100 %). Union was defined as at least 50 % trabecular bridging. The EAC adjudicated those images that were deemed major discrepancies. The committee was composed of three members assembled by the committee chair, an MSK radiologist. A charter was established to guide the adjudication process. Ten minutes were allotted to each scan, including 2-3 min of an independent adjudicator's review, followed by 5-7 min of committee discussion to reach a diagnosis., Results: Adjudicators spent an average of seven minutes on each scan. The EAC assessed 101 CT scans from 69 patients collected across five study sites: four scans from the agreed upon group as practice interpretations, 75 major discrepancies, and 22 missing interpretations from either the initial MSK radiologist, the treating orthopaedic surgeon, or both. These were adjudicated for final union status. Twenty-eight of the images with major discrepancies were adjudicated to union, and 47 to non-union. Adjudication changed the primary outcome of time to union in 40/142 (28 %) of study participants., Conclusion: This adjudication process provides a valuable research tool for reference by other clinical investigators whose RCTs' outcomes are dependent on interpretation of radiographic images., Competing Interests: Declaration of competing interest For the clinical trial for which this adjudication panel was implemented, NJW received funding from Bioventus LLC. The authors declare no other potential conflicts of interest with respect to the research and publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Bulk-fill, monochromatic, and ORMOCER composites were introduced in restorative dentistry with the aim of reducing clinical time and/or alleviating contraction stresses at the interface between the tooth and restoration. While the conversion and immediate properties of these materials are comparable to conventional composites, studies evaluating their long-term properties and the structure of the polymer matrix are lacking. The objective of this study was to evaluate the degree of conversion and, indirectly, the crosslink density of conventional, bulk-fill, monochromatic, and ORMOCER resin composites. The degree of conversion was measured using Fourier-transform infrared spectroscopy (FTIR). Flexural strength, elastic modulus, and hardness were measured both dry (24 h) and after ethanol storage (24 h) using three-point bending and Knoop microhardness testing, respectively. Sorption and solubility were determined by changes in mass before and after immersion in water and drying. Data were analyzed using one-way or two-way ANOVA (material or material/storage conditions). The degree of conversion was statistically similar across all materials. For composites from the same manufacturer, no significant differences were observed in the reduction of mechanical properties after ethanol storage between bulk-fill and monochromatic composites, although differences were noted for the ORMOCER material. Sorption and solubility varied among most composites from the same manufacturer, suggesting subtle differences in composition. Therefore, it can be concluded that, for composites from the same manufacturer, the degree of crosslinking was similar between bulk-fill and monochromatic composites, indicating comparable polymeric structures. The same was not observed for the ORMOCER material, although it exhibits properties similar to other conventional composites., Competing Interests: Declaration of competing interest There is no conflict of interest, (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Arterial endothelial cells (ECs) reside in a complex biomechanical environment. ECs sense and respond to wall shear stress. Low and oscillatory wall shear stress is characteristic of disturbed flow and commonly found at arterial bifurcations and around atherosclerotic plaques. Disturbed flow is pro-inflammatory to ECs. Arteries also stiffen with aging and/or the onset of vascular disease. ECs sense and respond to stiffening in a pro-fibrotic manner. Thus, flow and stiffening disturbances elicit EC responses that promote pathologic arterial remodeling. However, the pathways elicited by ECs under pathologic stiffening and disturbed flow are not well understood. The objective of this work was to discover and test the modifiability of key pathways in ECs. To do this we used the partial carotid ligation model to impose disturbed flow onto the precociously stiffened fibulin-5 knockout (Fbln5 -/- ) mouse carotid arteries. Biomechanical testing demonstrated that Fbln5 -/- arteries under disturbed flow approximate the stiffness ratio of diseased human arteries, and the ECs in these Fbln5 -/- arteries underwent rapid reprogramming via endothelial to mesenchymal transition (EndMT). Under atherogenic conditions, disturbed flow Fbln5 -/- arteries developed more vulnerable plaques than the wild type (WT) mouse arteries. Connective tissue growth factor/cellular communication network factor 2 (Ctgf/Ccn2) was upregulated in vivo in ECs with aging, with stiffening in the Fbln5 -/- arteries, and increased again by disturbed flow under stiffened conditions, supporting CTGF as a key biomarker for flow and stiffening. This was validated by immunohistochemistry, which demonstrated increased CTGF deposition in areas of disturbed flow in patient carotid endarterectomy and peripheral artery disease (PAD) specimens. Finally, to test the role of CTGF in regulating and combining these processes, we created an EC-specific Ctgf knockout (Ctgf ecko ). We identified that carotid arteries under disturbed flow and atherogenic conditions in male Ctgf ecko , but not female, mice had decreased plaque area compared to WT control mice. We then tested the Ctgf expression in the carotid endothelium exposed to disturbed or stable flow in WT and Fbln5 -/- mice. Here we found that under disturbed flow male mice had greater Ctgf expression than female mice. This work demonstrates that stiffened + disturbed flow conditions drive EC reprogramming, that CTGF is increased by these conditions, and that this increase is more prominent in male carotid arteries. Future exploration of sex-based differences in these fibrotic pathways are warranted to develop targeted therapeutics to limit pathologic arterial remodeling under pathologically stiffened + disturbed flow environments., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2025. Published by Elsevier B.V.)

Introduction: Overdose response hotlines and apps are novel virtual harm reduction technologies that allow remote monitoring of individuals while they use substances (especially if they use alone) through electronic means. The authors explored partner perspectives to determine which groups of people who use substances (PWUS) these services would be most appropriate for, with the aim of better informing service providers on how to target their use to maximize benefit for clients., Methods: The study conducted 64 semi-structured interviews with participants from a variety of backgrounds (individuals with lived or living experience of substance use, lay persons, health care providers, harm reduction workers, and operational experts). All information from interviews was kept confidential, de-identified, and stored on a secure server. Inductive thematic analysis identified major themes and subthemes. Two evaluators coded transcripts using Dedoose software. Once initial coding was complete, transcript coders selected quotes and shared them with a consulting project manager to cross-validate themes. The study conducted interviews until thematic saturation across all participants was reached based on the consensus of the two evaluators and the primary investigator., Results: Overall, the study determined that overdose response hotlines and apps would potentially have at least some utility for any PWUS. However, some were found to have a varying level of appropriateness for specific subgroups of PWUS. There were 11 different subgroups identified in this study and of these subgroups, the majority were identified as groups for whom virtual harm reduction services would be appropriate interventions., Conclusions: Overdose response hotlines and apps are helpful and potentially life-saving adjunctive options which may be more appropriate for some subgroups of PWUS than others. These results may help service providers to target groups with the most potential to benefit., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Objective: Technology can be combined with psychological interventions to support older adults with memory concerns. Using a bi-phasic design, cognitive rehabilitation (CR) was integrated with off-the-shelf technology and delivered to two people with cognitive impairment, and one care partner., Method: Pre- and post-intervention assessments were completed for all participants. Individuals with memory problems received pre- and post-intervention remote neuropsychological assessment (i.e., Rey auditory verbal learning test; mental alternations test; animal fluency), and the hospital anxiety and depression scale (HADS). The care partner completed the HADS, Zarit burden interview, and neuropsychiatric inventory questionnaire. Change metrics incorporated reliable change indices where possible. Goals were tracked using the Canadian occupation performance measure; these data were analyzed through visual inspection. A research journal (used to document intervention process) was analyzed thematically., Results: Results cautiously suggested our integration was feasible and acceptable across several technologies and varying goals. Across participants, significant changes in goal progress suggested the integration of technology with CR successfully facilitated goal performance and satisfaction. The research journal underscored the importance of a visual component, intervention flexibility, and a strong therapeutic alliance in integrating technology and CR., Conclusions: CR and technology present a promising avenue for supporting people living with cognitive impairment. Further exploration of technology and CR with a range of etiologies and target goals is warranted., (© The Author(s) 2024. Published by Oxford University Press.)

The aim of this study was to investigate the scientific evidence regarding the effectiveness of modified-ILIB (intravascular laser irradiation of blood) in the control of systemic conditions and/or oral changes during dental care. This systematic literature review study aimed to answer the question, "Is modified-ILIB an effective adjuvant therapy in the control of systemic conditions and/or oral changes in children and adults during dental treatment?". The protocol for this systematic review was registered in the PROSPERO database under number CRD42023493800. The search was carried out in the PubMed, Web of Science, LILACS, SCOPUS and EMBASE databases on June 10, 2024. Google Scholar was used as a search source for gray literature. Randomized clinical trials were included, without restrictions on language or year of publication. The RoB 2.0 tool was used to assess the risk of bias and GRADE was used to check the quality of the evidence. A total of 750 articles were retrieved and five studies were selected for this review. All studies were in English and were carried out in Brazil. The outcomes were periodontal parameters and glycemic control in patients with periodontitis and type II diabetes, anxiety control in pediatric dentistry, postoperative pain after third molar extraction and improving taste in post-COVID-19 patients. The majority of studies had a low risk of bias, while only one study was considered to have some concerns. The quality of evidence from the studies was considered very low. The current evidence does not overwhelmingly support the effectiveness of modified-ILIB in controlling oral and/or systemic conditions in dentistry., Competing Interests: Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: Not applicable. Conflicts of interest: The authors declare no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Purpose: We report the preclinical evaluation of potent long-acting [ 225 Ac]Ac-EBTATE against SSTR2-positive small cell lung cancer (SCLC) and pancreatic neuroendocrine tumors (pan-NETs)., Methods: The pharmacokinetic, biodistribution, and safety studies were evaluated in healthy female and/or male BALB/c mice after intravenous injections of [ 225 Ac]Ac-EBTATE. Further biodistribution and radioligand therapy were investigated in female athymic BALB/c nude mice bearing high or low SSTR2-expressing subcutaneous SCLC models NCI-H524 or NCI-H727, respectively, and in a pan-NET model QGP1.SSTR2., Results: Pharmacokinetics confirmed a prolonged clearance half-life (40.27 ± 9.23 h) while biodistribution in healthy male and female BALB/c mice was similar, with prolonged blood circulation that peaked at 6 h. Biodistribution in subcutaneous xenograft models of NCI-H524 and NCI-H727 showed consistent tumor-uptake with SSTR2-overexpression while the projected human effective doses for males and females were 61.7 and 83.7 millisievert/megabecquerel, respectively. 2 × 34 kBq of [ 225 Ac]Ac-EBTATE administered 10 days (d) apart, was generally tolerated for 28 days in healthy BALB/c mice as revealed by blood biochemistry, complete blood count, and histopathological examination of H&E-stained organs. Targeted alpha therapy at 2 × 30 kBq of [ 225 Ac]Ac-EBTATE, injected 10 days apart, resulted in 100% survivals and 80% and 20% complete remissions for NCI-H524 and QGP1.SSTR2 models, respectively. Additionally, [ 225 Ac]Ac-EBTATE had a dose-dependent response in the NCI-H727 model, with median survivals for 2 × 30 kBq and 2 × 15 kBq groups being 63 d (p < 0.0007), and 47 d (p = 0.0148), respectively., Conclusions: [ 225 Ac]Ac-EBTATE is safe and effective against SCLC and pan-NET and therefore warrants clinical investigation., Competing Interests: Declarations. Ethical approval: All animal experiments were approved, supervised, and maintained following the guidelines of the University of Saskatchewan Animal Care Committee (UACC). Ethical approval reference 20220021. Consent to publish: The authors have consent to publish all the data presented in the manuscript. Disclosure: Koon Y. Pak and Brian D. Gray are executives and shareholders of Molecular Targeting Technologies Inc., which owns the IP and has commercial interests in [225Ac]Ac-EBTATE. Competing interests: B. Gray and K. Pak are employees of Molecular Targeting Technologies Inc that owns the licence for EB-TATE. All other authors have declared no competing conflicts of interest., (© 2024. Crown.)

The emergence and re-emergence of pathogens with pandemic potential has been a persistent issue throughout history. Recent decades have seen significant outbreaks of zoonotic viruses from members of the Coronaviridae , Filoviridae , Paramyxoviridae , Flaviviridae , and Togaviridae families, resulting in widespread infections. The continual emergence of zoonotic viral pathogens and associated infections highlights the need for prevention strategies and effective treatments. Central to this effort is the availability of suitable animal models, which are essential for understanding pathogenesis and assessing transmission dynamics. These animals are also critical for evaluating the safety and efficacy of novel vaccines or therapeutics and are essential in facilitating regulatory approval of new products. Rapid development of animal models is an integral aspect of pandemic response and preparedness; however, their establishment is fraught by several rate-limiting steps, including selection of a suitable species, the logistical challenges associated with sharing and disseminating transgenic animals (e.g., the time-intensive nature of breeding and maintaining colonies), the availability of technical expertise, as well as ethical and regulatory approvals. A method for the rapid development of relevant animal models that has recently gained traction, in large part due to the COVID-19 pandemic, is the use of gene therapy vectors to express human viral receptors in readily accessible laboratory animals to enable virus infection and development of clinical disease. These models can be developed rapidly on any genetic background, making mechanistic studies and accelerated evaluation of novel countermeasures possible. In this review, we will discuss important considerations for the effective development of animal models using viral vector approaches and review the current vector-based animal models for studying viral pathogenesis and evaluating prophylactic and therapeutic strategies, with an emphasis on models of SARS-CoV-2 infection based on the vectorized expression of human angiotensin-converting enzyme 2.

Background: Fibrotic responses in the gingiva are characterized by their hyperproliferative nature instead of scar tissue formation. Clinically, these conditions appear as "gingival overgrowth" (GO), which can be of drug-induced or genetic origin. Despite surgical removal, GO can recur. Therefore, non-invasive methods of treating GO are required. In other fibrotic systems, the matricellular protein CCN2 represents a potential therapeutic target. However, CCN2 has been relatively understudied in the context of GO., Highlight: Herein, we describe what is known regarding CCN2 expression in GO and gingival fibroblasts. Specifically, CCN2 is induced by agents that promote fibrogenesis in the oral cavity, such as transforming growth factor-β, and drugs that promote GO, such as cyclosporine, nifedipine, and phenytoin., Conclusion: Although little is known regarding the possible function of CCN2 in GO, given the correlation between CCN2 expression and GO recurrence, we hope that this review will inspire further research on this topic., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This study aims to review the escalating prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) among Canada's Indigenous population, focusing on risk factors, hospitalization and mortality rates, and disparities in kidney transplantation. The study explores how these factors contribute to the health outcomes of this population and examines the influence of genetic variations on CKD progression., Methods: The review synthesizes data on prevalence rates, hospitalization and mortality statistics, and transplantation disparities among Indigenous individuals. It also delves into the complexities of healthcare access, including geographical, socioeconomic, and psychological barriers. Additionally, the manuscript investigates the impact of racial factors on blood characteristics relevant to dialysis treatment and the genetic predispositions influencing disease progression in Indigenous populations., Results: Indigenous individuals exhibit a higher prevalence of CKD and ESRD risk factors such as diabetes and obesity, particularly in regions like Saskatchewan. These patients face a 77% higher risk of death compared to their non-Indigenous counterparts and are less likely to receive kidney transplants. Genetic analyses reveal significant associations between CKD and specific genomic variations. Through analyses, we found that healthy Indigenous individuals may have higher levels of circulating inflammatory markers, which could become further elevated for those with CKD. In particular, they may have higher levels of C-reactive protein (CRP) fibrinogen, as well as genomic variations that affect IL-6 production and the function of von Willebrand Factor (vWF) which has critical potential influence on the compatibility with dialysis membranes contributing to complications in dialysis., Conclusion: Indigenous people in Canada are disproportionately burdened by CKD and ESRD due to socioeconomic factors and potential genetic predispositions. While significant efforts have been made to assess the socioeconomic conditions of the Indigenous population, the genetic factors and their potential critical influence on compatibility with dialysis membranes, contributing to treatment complications, remain understudied. Further investigation into these genetic predispositions is essential., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Verify whether hypervigilance to pain (HP) and sleep quality (SQ) are confounding variables in the infrared thermography (IT) examination of the temporomandibular joint and temporal and masseter muscles., Methods: A cross-sectional and analytical study was conducted, collecting HP and SQ data from 80 participants without temporomandibular disorders (TMD), performing their IT and another 40 participants with TMD. For the selection of participants with and without TMD, the TMD Pain Screener questionnaire and axis I of the Diagnostic Criteria for Temporomandibular Disorders were applied. SQ was verified using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. For the HP assessment the Pain Vigilance and Awareness Questionnaire (PVAQ) was applied. And the IT was performed through a FLIR infrared sensor camera, model T650 Infrared., Results: No significant correlations were found between SQ and the temperatures of the areas of interest (P > .05), and regarding HP, a statistically significant positive correlation was found with the dimensionless (ρ = 0.289) and non-dimensionless (ρ = 0.223) asymmetries of temporal muscle temperatures. In the temperature comparisons between the participants without TMD and the participants with TMD, significant differences were found (P < .05), also when the group without TMD was controlled according to both HP and SQ (P < .05), with higher temperatures found in the TMD group., Conclusions: HP and SQ can be considered confounding variables in IT examination of the temporomandibular region., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This paper presents a novel centrifugal microfluidic approach (so-called lab-on-a-CD) for magnetic circulating tumor cell (CTC) separation from the other healthy cells according to their physical and acquired chemical properties. This study enhances the efficiency of CTC isolation, crucial for cancer diagnosis, prognosis, and therapy. CTCs are cells that break away from primary tumors and travel through the bloodstream; however, isolating CTCs from blood cells is difficult due to their low numbers and diverse characteristics. The proposed microfluidic device consists of two sections: a passive section that uses inertial force and bifurcation law to sort CTCs into different streamlines based on size and shape and an active section that uses magnetic forces along with Dean drag, inertial, and centrifugal forces to capture magnetized CTCs at the downstream of the microchannel. The authors designed, simulated, fabricated, and tested the device with cultured cancer cells and human cells. We also proposed a cost-effective method to mitigate the surface roughness and smooth surfaces created by micromachines and a unique pulsatile technique for flow control to improve separation efficiency. The possibility of a device with fewer layers to improve the leaks and alignment concerns was also demonstrated. The fabricated device could quickly handle a large volume of samples and achieve a high separation efficiency (93%) of CTCs at an optimal angular velocity. The paper shows the feasibility and potential of the proposed centrifugal microfluidic approach to satisfy the pumping, cell sorting, and separating functions for CTC separation.

Background: Human relationships with and connections to nature and the "land" are a commonly accepted Social Determinant of Health. Greater knowledge about these relationships can inform public health policies and interventions focused on health equity among Indigenous populations. Two research questions were explored: (1) what are the experiences of meaningful human-nature relationships among Indigenous youth within central Canada; and (2) how do these relationships function as a determinant of health and wellness within their lives., Methods: Drawing from three community-based participatory research (CBPR) projects within two urban centers in Saskatchewan and Manitoba, the integrated qualitative findings presented here involved 92 interviews with 52 Indigenous youth that occurred over a period of nine years (2014-2023). Informed by "two-eyed seeing," this analysis combined Indigenous Methodologies and a Constructivist Grounded Theory approach., Results: Our integrative analysis revealed three cross-cutting themes about meaningful human-nature relationships: (1) promoting cultural belonging and positive identity; (2) connecting to community and family; and (3) supporting spiritual health and relationships. The experiences of young people also emphasized barriers to land and nature access within their local environments., Discussion: Policies, practices, and interventions aimed at strengthening urban Indigenous young peoples' relationships to and connections with nature and the land can have a positive impact on their health and wellness. Public Health systems and healthcare providers can learn about leveraging the health benefits of human-nature relationships at individual and community levels, and this is particularly vital for those working to advance health equity among Indigenous populations., (© 2024. The Author(s).)

Background: We conducted a scoping review of the evidence for the use of the Pediatric Assessment Triangle (PAT) tool in emergency pediatric patients, in hospital and prehospital settings. We focused on the psychometric properties of the PAT, the reported impact, the setting and circumstances for tool implementation in clinical practice, and the evidence on teaching the PAT., Methods: We followed the Joanna Briggs Institute methodology for scoping reviews and registered the review protocol. We searched MEDLINE, PubMed Central, the Cochrane Library, Epistemonikos, Scopus, CINAHL, Grey literature report, Lens.org, and the web pages of selected emergency pediatrics organizations in August 2022. Two reviewers independently screened and extracted data from eligible articles., Results: Fifty-five publications were included. The evidence suggests that the PAT is a valid tool for prioritizing emergency pediatric patients, guiding the selection of interventions to be undertaken, and determining the level of care needed for the patient in both hospital and prehospital settings. The PAT is reported to be fast, practical, and useful potentially impacting overcrowded and understaff emergency services. Results highlighted the importance of instruction prior using the tool. The PAT is included in several curricula and textbooks about emergency pediatric care., Conclusions: This scoping review suggests there is a growing volume of evidence on the use of the PAT to assess pediatric emergency patients, some of which might be amenable to a systematic review. Our review identified research gaps that may guide the planning of future research projects. Further research is warranted on the psychometric properties of the PAT to provide evidence on the tool's quality and usefulness. The simplicity and accuracy of the tool should be considered in addressing the current healthcare shortages and overcrowding in emergency services., Review Registration: Open Science Framework; 2022. https://osf.io/vkd5h/., (© 2024. The Author(s).)

Introduction: Medicinal chemistry instruction in PharmD programs at Canadian universities is considered an important foundational science. However, with few guidelines for the required content most programs have observed a decrease in hours of medicinal chemistry instruction. A Medicinal Chemistry Special Interest Group (SIG) was formed to address these issues nationally and initiated a pan-Canadian environmental scan to better understand the depth and breadth of medicinal chemistry instruction., Methods: The SIG carried out an environmental scan to identify medicinal chemistry content, delivery and assessments in PharmD programs in Canada., Results: Core medicinal chemistry concepts across the PharmD programs are in general agreement with those listed by the Accreditation Council for Pharmacy Education. Medicinal chemistry was typically taught as didactic lectures either as a standalone course or within a pharmacology course, although one program integrated some medicinal chemistry within therapeutics focused problem-based learning. There was no consistent time in program where medicinal chemistry occurred., Conclusions: The SIG found that similar medicinal chemistry content is taught across all Canadian PharmD programs, but incorporation of medicinal chemistry in therapeutics courses was minimal. Core concepts within six high-level overarching themes that guide our collective instruction were identified. The core concepts require developing high-level cognitive processes such as knowledge application and synthesis that practicing pharmacists are expected to possess for entry to practice. We the authors posit that in addition to providing a unique tool for pharmacists to employ in therapeutic decision-making, medicinal chemistry also provides early practice of important problem-solving and critical thinking skills., Competing Interests: Declaration of competing interest The authors listed above have no conflict of interest to declare and no affiliations with or involvement in any organization or entity with any financial interest in this submission., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Adhesion to zirconia remains a significant dental challenge. This study is aimed at assessing the bond strength of zirconia based on surface treatment with pre or postsintering sandblasting associated with different chemical treatments and resin cements. Methods: Zirconia blocks were divided into 12 experimental groups based on the surface treatment (presintering sandblasting or postsintering sandblasting/tribochemical abrasion treatment), chemical treatment (none, Single Bond Universal, or Signum Zirconia Bond), and choice of cement (Panavia F or RelyX™ U200). The bond strength was measured by shear tests using a universal testing machine. The fracture analysis was performed using stereomicroscopy. Data were analyzed using three-way ANOVA and Tukey's test ( α = 5%). Results: Triple and double factor's interactions were not significant ( p > 0.05). Regarding the surface treatment factor, the bond strength following postsintering sandblasting treatment associated with tribochemical abrasion (9.15 ± 3.62 MPa) was significantly higher than presintering sandblasting treatment (5.24 ± 3.53 MPa). Concerning the chemical treatment factor, bond strengths were ranked as follows: Signum Zirconia Bond > Single Bond Universal > no treatment. The bond strength of the resin cements did not differ among them. Most fractures (67%) were classified as adhesive, and 32% were categorized as mixed fractures. Conclusion: Surface treatment via postsintering sandblasting combined with tribochemical abrasion demonstrated superior efficacy than in presintering sandblasting. Additionally, chemical treatment with zirconia primer increased the bond strength of zirconia irrespective of the surface physical treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Flávia Gonçalves et al.)

Human space exploration expansion from Low-Earth Orbit to deep space is accelerating the need to monitor and address the known health concerns related to deep space radiation. The human musculoskeletal system is vulnerable to these risks (alongside microgravity) and its health reflects the well-being of other body systems. Multiparametric magnetic resonance imaging (MRI) is an important approach for assessing temporal physiological changes in the musculoskeletal system. We propose that ultra-low-field MRI provides an optimal low Size Weight and Power (SwaP) solution for non-invasively monitoring muscle and bone changes on the planned Gateway lunar space station. Our proposed ultra-low-field Gateway MRI meets low SWaP design specifications mandated by limited room in the lunar space station. This review summarizes the current state of our knowledge on musculoskeletal consequences of spaceflight, especially with respect to radiation, and then elaborates how MRI can be used to monitor the deleterious effects of space travel and the efficacy of putative countermeasures. We argue that an ultra-low-field MRI in cis-lunar space on the Gateway can provide valuable research and medical insights into the effects of deep space radiation exposure on astronauts. Such an MRI would also allow the development of imaging protocols that would facilitate Earth-bound teams to monitor space personnel musculoskeletal changes during future interplanetary spaceflight. It will especially have a role in monitoring countermeasures, such as the use of melanin, in protecting space explorers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Canadian Space Agency (CSA) funding was provided to Pelican MRI, Inc. of which author GES is sole owner., (Copyright © 2024 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

Background: We conducted a review of topical medications available for alleviation of diabetic neuropathic pain (DNP) and compared their efficacy with oral medications for pain relief. We also explored the feasibility of compounding topical medications., Methods: Searches on PubMed, Medline Ovid, and Embase databases were conducted and findings were presented as a narrative review., Results and Discussion: 8% Capsaicin patches and 5% Lidocaine patches had the most evidence. The literature also showed evidence for topical clonidine, gabapentin, and amitriptyline., Conclusion: Topical formulations are a potential substitute to oral medications in patients suffering from DNP. Potential options include 8% Capsaicin patch, 5% Lidocaine patch, Clonidine gel, Topical gabapentin, and an amitriptyline and ketamine combination. A promising area of research that requires further study is the effect of a combination of topicals in alleviated DNP., Competing Interests: Conflict of interestThe authors declared that they have no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Interactions of graphene oxide (GO) with an ex vivo rat heart and its coronary vessels have not been studied yet. Moreover, the conflicting data on the "structure-properties" relationships do not allow for biomedical applications of GO. Herein, we study the impact of GO on the ex vivo isolated rat heart, normotensive and hypertensive, under the working heart and the constant-pressure perfusion (Langendorff) regimes. Four structural GO variants of the following initial morphology were used: few-layer (below 10-layer) GO1, O < 49%; predominantly single-layer GO2, O = 41-50%; 15-20-layer GO3, O < 11%; and few-layer (below 10-layer) NH 4 + -functionalized GO4, O < 44%, N = 3-6%. The aqueous GO dispersions, sonicated and stabilized with bovine serum albumin in Krebs-Henseleit-like solution-uniformized in terms of the particle size-were eventually size-monodisperse as revealed by dynamic light scattering. To study the cardiotoxicity mechanisms of GO, histopathology, Raman spectroscopy, analysis of cardiac parameters (coronary and aortic flows, heart rate, aortic pressure), and nitric oxide (NO-)-dependent coronary flow response to bradykinin (blood-vessel-vasodilator) were used. GO1 (10 mg/L) exerted no effects on cardiac function and preserved an increase in coronary flow in response to bradykinin. GO2 (10 mg/L) reduced coronary flow, aortic pressure in normotensive hearts, and coronary flow in hypertensive hearts, and intensified the response to bradykinin in normal hearts. GO3 (10 mg/L) reduced all parameters in hypertensive hearts and coronary response to bradykinin in normal hearts. At higher concentrations (normotensive hearts, 30 mg/L), the coronary response to bradykinin was blocked. GO4 (10 mg/L) reduced the coronary flow in normal hearts, while for hypertensive hearts, all parameters, except the coronary flow, were reduced and the coronary response to bradykinin was blocked. The results showed that a low number of GO layers and high O-content were safer for normal and hypertensive rat hearts. Hypertensive hearts deteriorated easier upon perfusion with low-O-content GOs. Our findings support the necessity of strict control over the GO structure during organ perfusion and indicate the urgent need for personalized medicine in biomedical applications of GO., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: To evaluate the imaging and therapeutic properties (theranostic) of 67 Cu-labeled anti-human epidermal growth factor receptor II (HER2) monoclonal antibody trastuzumab against HER2-positive breast cancer (BC)., Methods: We conjugated trastuzumab with p-SCN-Bn-NOTA, 3p-C-NETA-NCS, or p-SCN-Bn-DOTA, and radiolabeled with [ 67 Cu]CuCl 2 . Immunoconjugate internalization was evaluated in BT-474, JIMT-1 and MCF-7 BC cells. In vitro stability was studied in human serum (HS) and Phosphate Buffered Saline (PBS). Flow cytometry, radioligand binding and immunoreactive fraction assays were carried out. ImmunoSPECT imaging of [ 67 Cu]Cu-NOTA-trastuzumab was done in mice bearing BT-474, JIMT-1 and MCF-7 xenografts. Pharmacokinetic was studied in healthy Balb/c mice while dosimetry was done in both healthy Balb/c and in athymic nude mice bearing JIMT-1 xenograft. The therapeutic effectiveness of [ 67 Cu]Cu-NOTA-trastuzumab was evaluated in mice bearing BT-474 and JIMT-1 xenografts after a single intravenous (i.v.) injection of ~ 16.8 MBq., Results: Pure immunoconjugates and radioimmunoconjugates (> 95%) were obtained. Internalization was HER2 density-dependent with highest internalization observed with NOTA-trastuzumab. After 5 days, in vitro stabilities were 97 ± 1.7%, 31 ± 6.2%, and 28 ± 4% in HS, and 79 ± 3.5%, 94 ± 1.2%, and 86 ± 2.3% in PBS for [ 67 Cu]Cu-NOTA-trastuzumab, [ 67 Cu]Cu-3p-C-NETA-trastuzumab and [ 67 Cu]Cu-DOTA-trastuzumab, respectively. [ 67 Cu]Cu-NOTA-trastuzumab was chosen for further evaluation. BT-474 flow cytometry showed low K D , 8.2 ± 0.2 nM for trastuzumab vs 26.5 ± 1.6 nM for NOTA-trastuzumab. There were 2.9 NOTA molecules per trastuzumab molecule. Radioligand binding assay showed a low K D of 2.1 ± 0.4 nM and immunoreactive fraction of 69.3 ± 0.9. Highest uptake of [ 67 Cu]Cu-NOTA-trastuzumab was observed in JIMT-1 (33.9 ± 5.5% IA/g) and BT-474 (33.1 ± 10.6% IA/g) xenograft at 120 h post injection (p.i.). Effectiveness of the radioimmunoconjugate was also expressed as percent tumor growth inhibition (%TGI). [ 67 Cu]Cu-NOTA-trastuzumab was more effective than trastuzumab against BT-474 xenografts (78% vs 54% TGI after 28 days), and JIMT-1 xenografts (90% vs 23% TGI after 19 days). Mean survival of [ 67 Cu]Cu-NOTA-trastuzumab, trastuzumab and saline treated groups were > 90, 77 and 72 days for BT-474 xenografts, while that of JIMT-1 were 78, 24, and 20 days, respectively., Conclusion: [ 67 Cu]Cu-NOTA-trastuzumab is a promising theranostic agent against HER2-positive BC., (© 2024. Crown.)

Dialysis membranes are not hemocompatible with human blood, as the patients are suffering from the blood-membrane interactions' side effects. Zwitterionic structures have shown improved hemocompatibility; however, their complicated synthesis hinders their commercialization. The goal of the study is to achieve fast functionalization for carboxybetaine and sulfobetaine zwitterionic immobilization on PES membranes while comparing the stability and the targeted hemocompatibility. The chemical modification approach is based on an aminolysis reaction. Characterization, computational simulations, and clinical analysis were conducted to study the modified membranes. Atomic force microscopy (AFM) patterns showed a lower mean roughness for carboxybetaine-modified (6.3 nm) and sulfobetaine-modified (7.7 nm) membranes compared to the neat membrane (52.61 nm). The pore size of the membranes was reduced from values above 50 nm for the neat PES to values between 2 and 50 nm for zwitterionized membranes, using Brunauer-Emmett-Teller (BET) analysis. More hydrophilic surfaces led to a growth equilibrium water content (EWC) of nearly 6% for carboxybetaine and 10% for sulfobetaine-modified membranes. Differential scanning calorimetry (DSC) measurements were 12% and 16% stable water for carboxybetaine- and sulfobetaine-modified membranes, respectively. Sulfobetaine membranes showed better compatibility with blood with respect to C5a, IL-1a, and IL-6 biomarkers. Aminolysis-based zwitterionization was found to be suitable for the improvement of hemodialysis membranes. The approach introduced in this paper could be used to modify the current dialysis membranes with minimal change in the production facilities.

Dust is a sink for many semi-volatile compounds including flame retardants of the organophosphate ester (OPE) and brominated flame-retardant (BFR) classes. Given the large amount of time that we spend indoors, our exposure to these compounds via dust is of significant interest. Here, we present a novel microextraction approach to determine quantitative levels of selected OPEs and BFRs sampled from residential air filters from HVAC systems using a small volume of solvent. Dust samples (25 mg) is extracted with 1 mL of hexane/acetone (50/50, v/v). Upon solvent extraction of these HVAC dust samples, the analytes (TCPP, TDCPP, TPHP, T24DtBPP, TBBPA, and TriBBPA) were quantified via gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-mass spectrometry (LC/MS). The methods for extracting these compounds from HVAC dust samples are detailed here with extensive method validation data to demonstrate accuracy and precision of these methods. •Dust is a sink for many semi-volatile compounds, including novel or emerging indoor pollutants like the organophosphate ester flame retardant T24DtBPP.•Here, a small amount of dust (25 mg) is extracted with a small volume of solvent (1 mL hexane and acetone) prior to analysis via chromatographic separation and mass spectrometric detection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Background: In response to the exacerbated rates of morbidity and mortality associated with the overlapping overdose and COVID-19 epidemics, novel strategies have been developed, implemented, operationalized and scaled to reduce the harms resulting from this crisis. Since the emergence of mobile overdose response services (MORS), two strategies have aimed to help reduce the mortality associated with acute overdose including staffed hotline-based services and unstaffed timer-based services. In this article, we aim to gather the perspectives of various key interest groups on these technologies to determine which might best support service users., Methods: Forty-seven participants from various interested groups including people who use substances who have and have not used MORS, healthcare workers, family members, harm reduction employees and MORS operators participated in semi-structured interviews. Transcripts were coded and analyzed using a thematic analysis approach., Results: Four major themes emerged regarding participant perspectives on the differences between services, namely differences in connection, perceived safety, privacy and accessibility, alongside features that are recommended for MORS in the future., Conclusions: Overall, participants noted that individuals who use substances vary in their desire for connection during a substance use session offered by hotline and timer-based service modalities. Participants perceived hotline-based approaches to be more reliable and thus potentially safer than their timer-based counterparts but noted that access to technology is a limitation of both approaches., (© 2024. Crown.)

To determine multifaceted determinants of household vulnerability to food insecurity in Afghanistan before and after the Taliban takeover, we randomly selected 555 households from 13 provinces, conducted in-person surveys, and applied the Household Food Insecurity Assess Scale (HFIAS) and Structural Equation Modeling (SEM). We collected data from January to April 2022. We observed an increase in both prevalence and severity of food insecurity among Afghan households after the Taliban takeover. Approximately, 98% and 70% of interviewed households were food insecure after and before the Taliban takeover, respectively. Similarly, households were more likely to be severely food insecure (81%) than before (40%). Our results showed that policy and political conditions contributed substantially to the food insecurity of Afghan households after the Taliban takeover. We recommend that the Taliban forces facilitate the presence of humanitarian organizations and NGOs to improve low-income households' food security, especially for women and children. We also recommend that international organizations enhance their attempts to negotiate with the Taliban to ensure freedom for women., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Cannabis sativa has gained popularity as a "natural substance", leading many to falsely assume that it is not harmful. This assumption has been documented amongst pregnant mothers, many of whom consider Cannabis use during pregnancy as benign. The purpose of this study was to validate a Cannabis smoke exposure model in pregnant rats by determining the plasma levels of cannabinoids and associated metabolites in the dams after exposure to either Cannabis smoke or injected cannabinoids. Maternal and fetal cytokine and chemokine profiles were also assessed after exposure. Pregnant Sprague-Dawley rats were treated daily from gestational day 6-20 with either room air, i.p. vehicle, inhaled high-Δ 9 -tetrahydrocannabinol (THC) (18% THC, 0.1% cannabidiol [CBD]) smoke, inhaled high-CBD (0.7% THC, 13% CBD) smoke, 3 mg/kg i.p. THC, or 10 mg/kg i.p. CBD. Our data reveal that THC and CBD, but not their metabolites, accumulate in maternal plasma after repeated exposures. Injection of THC or CBD was associated with fewer offspring and increased uterine reabsorption events. For cytokines and chemokines, injection of THC or CBD up-regulated several pro-inflammatory cytokines compared to control or high-THC smoke or high-CBD smoke in placental and fetal brain tissue, whereas smoke exposure was generally associated with reduced cytokine and chemokine concentrations in placental and fetal brain tissue compared to controls. These results support existing, but limited, knowledge on how different routes of administration contribute to inconsistent manifestations of cannabinoid-mediated effects on pregnancy. Smoked Cannabis is still the most common means of human consumption, and more preclinical investigation is needed to determine the effects of smoke inhalation on developmental and behavioural trajectories., (© 2023. The Author(s).)

Background: Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases that are characterized by muscle injury. These disorders can cause cardiomyopathy and heart failure, myocarditis, and arrhythmias. However, only a few cases of cardiac arrest as a result of IIMs have been previously reported., Case Summary: A 46-year-old male presented with an out-of-hospital ventricular fibrillation cardiac arrest. A diagnosis of IIM had been made through a muscle biopsy performed 2 years before presentation. The patient had a positive anti-nuclear antibody but negative myositis-specific antibodies. His initial symptoms of IIM were mild and consisted of myalgias. His only cardiac symptoms were minor palpitations that occurred 3 years prior to the cardiac arrest, with a negative Holter monitor test result at that time. His cardiac catheterization was normal. He was suspected to have myocarditis, and a rheumatologist was consulted, following which the patient was initiated on intravenous immunoglobulin (IVIG). Cardiac magnetic resonance imaging demonstrated evidence of chronic myocarditis and an ejection fraction of 44%. He was initiated on goal-directed medical therapy for heart failure. A VVI implantable cardioverter defibrillator was implanted for secondary prevention. He was discharged and prescribed additional immunosuppression including further IVIG infusions, prednisone taper and rituximab infusions., Discussion: Our case demonstrates that cardiac arrest in IIM is not only plausible, but can be the first major cardiac manifestation of the disease. When a diagnosis of IIM is made, patients require a thorough assessment of cardiac symptomatology and a low threshold for additional cardiac investigations., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Salivary melatonin is a clinically used biomarker for diagnosing circadian rhythm sleep disorders. Current melatonin detection assays are complex, expensive, and in many cases do not adequately measure low levels of salivary melatonin. Precisely measuring melatonin levels at multiple time points is crucial for determining dim light melatonin onset to evaluate its circadian fluctuation as well as the extent of circadian disruption and consequently adapt treatment regimens. Moreover, melatonin low levels in saliva challenges the reliability of routine clinical testing. This paper presents the development of a novel, highly sensitive, yet cost-effective, colorimetric assay for the rapid detection of salivary melatonin utilizing aptamer-AuNPs. Among several types of the aptamer tested, the 36-mer MLT-A-2 aptamer-AuNP probe showed the highest sensitivity with a melatonin limit of detection of 0.0011 nM along with a limit of quantification of 0.0021 nM in saliva. Moreover, our assay showed preferential interaction with melatonin when tested in presence of other structurally similar counter-targets. Taken together, this study provides new parameters for a melatonin assay that meets adequate levels of sensitivity and selectivity. The developed colorimetric assay could be adapted in a point-of-care system for profiling salivary melatonin levels at multiple time points during 24 h, crucial for accurately diagnosing and monitoring circadian rhythm sleep disorders and beyond., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

To determine the number of patients with acute respiratory distress syndrome (ARDS) who would be eligible to receive veno-venous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective observational study of ARDS patients admitted to Regina General Hospital Intensive Care Unit (ICU). VV-ECMO eligibility was assessed using selection criteria from the Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Syndrome trial (EOLIA), the Extracorporeal Life Support Organization (ELSO), New South Wales (NSW), Critical Care Services Ontario (CCSO) and a Regina-restrictive criteria. Of 415 patients admitted between October 16, 2018, and January 21, 2021, 103 (25%) had mild, 175 (42%) had moderate, and 64 (15%) had severe ARDS. Of the cohort, 144 (35%) had bacterial pneumonia, 86 (21%) had viral pneumonia (including COVID-19), and 72 (17%) had aspiration pneumonia. Using the EOLIA, ELSO, NSW, CCSO and Regina-restrictive criteria, 7/415 (1.7%), 6/415 (1.5%), 19/415 (4.6%), 26/415 (6.3%) and 12/415 (2.9%) were eligible for VV-ECMO, respectively. Of all ECMO-eligible patients, only one (2.4%) actually received VV-ECMO, 20/42 (48%) received prone positioning and 21/42 (50%) received neuromuscular blockade. There is potential for service expansion of VV-ECMO in Regina; however, there is still a need to improve the delivery of evidence-based ARDS therapies., (© 2023. Springer Nature Limited.)

It is important to know the mineral distribution in cereal grains for nutritional improvement or genetic biofortification. Distributions and intensities of micro-elements (Mn, Fe, Cu, and Zn) and macro-elements (P, S, K and Ca) in Arborg oat were investigated using synchrotron-based on X-ray fluorescence imaging (XFI). Arborg oat provided by the Crop Development Center (CDC, Aaron Beattie) of the University of Saskatchewan for 2D X-ray fluorescence scans were measured at the BioXAS-Imaging beamline at the Canadian Light Source. The results show that the Ca and Mn were mainly localized in the aleurone layer and scutellum. P, K, Fe, Cu, and Zn were mainly accumulated in the aleurone layer and embryo. Particularly the intensities of P, K, Cu, and Zn in the scutellum were higher compared to other areas. S was also distributed in each tissue and its abundance in the sub-aleurone was the highest. In addition, the intensities of S and Cu were highest in the nucellar projection of the crease region. All these elements were also found in the pericarp but they were at lower levels than other tissues. Overall, the details of these experimental results can provide important information for micronutrient biofortification and processing strategies on oat through elemental mapping in Arborg oat., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Generally, pandemics such as COVID-19 take an enormous toll on people's lives. As the pandemic now turns to an endemic state, growing attention has been paid to the multiple adverse mental health and behavioral issues, such as suicidal ideation and substance use. However, the interplay of suicidality and substance misuse during the pandemic has been limited. We aimed to investigate the prevalence of co-occurrence of suicide ideation, alcohol and cannabis misuse, and the factors that are associated with these co-occurrences in the province of Saskatchewan during the COVID-19 pandemic., Methods: We performed a multivariable trivariate probit regression on a sample of 666 Saskatchewan adolescents and adults (16 years or older), drawn from the cycle 10 data collection (March 2022) of the Mental Health Commission of Canada, and Canadian Centre on Substance Use and Addiction (MHCC-CCSA) dataset., Results: The prevalence of suicidal ideation was higher among respondents who reported both problematic cannabis and alcohol use (25.8%) than single users of alcohol (23.2%) and cannabis (18.7%). Younger respondents (16-34 years) and those who reported recent changes in other substance use were independent factors that were associated with the common experience of suicide ideation, problematic cannabis, and alcohol use. Having a diagnosis of mental health disorders either before or during the pandemic, and the perceived inability to bounce back after the pandemic (low resilience) are strong correlates of suicidal ideation. Those who lived alone, between 35 and 55 years of age were more likely to report problematic alcohol use. Those who reported changes in alternative activities, who reported pandemic stress, and declared a LGBTQIA2S + identity had higher probability of problematic cannabis use., Conclusions: As the pandemic persists, improving access to suicide and substance use interventions for the vulnerable groups identified in this study may be impactful., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The goal of the current study is to enhance the hemocompatibility of polyethersulfone (PES) membranes using heparin immobilization. Heparin was immobilized covalently and via electrostatic interaction with the positively charged PES surface (pseudo-zwitterionic (pZW) complex) to investigate the influence of each method on the membrane hemocompatibility. In situ synchrotron radiation micro-computed tomography (SR-µCT) imaging, available at the Canadian Light Source (CLS), was used to critically assess the fibrinogen adsorption to the newly synthesized membranes qualitatively and quantitatively using an innovative synchrotron-based X-ray tomography technique. The surface roughness of the synthesized membranes was tested using atomic force microscopy (AFM) analysis. The membrane hemocompatibility was examined through the ex vivo clinical interaction of the membranes with patients' blood to investigate the released inflammatory biomarkers (C5a, IL-1α, IL-1β, IL-6, vWF, and C5b-9). The presence and quantitative analysis of a stable hydration layer were assessed with DSC analysis. Surface modification resulted in reduced surface roughness of the heparin-PES membrane. Both types of heparin immobilization on the PES membrane surface resulted in a decrease in the absolute membrane surface charge from -60 mV (unmodified PES) to -13 mV for the pZW complex and -9.16 mV for the covalently attached heparin, respectively. The loss of human serum fibrinogen (FB) was investigated using UV analysis. The PES membrane modified with the heparin pseudo-ZW complex showed increased FB retention (90.5%), while the unmodified PES membrane and the heparin covalently attached PES membrane exhibited approximately the same level of FB retention (81.3% and 79.8%, respectively). A DSC analysis revealed an improvement in the content of the hydration layer (32% of non-freezable water) for the heparin-coated membranes compared to the unmodified PES membrane (2.84%). An SR-µCT analysis showed that the method of heparin immobilization significantly affects FB adsorption distribution across the membrane thickness. A quantitative analysis using SR-µCT showed that when heparin is attached covalently, FB tends to be deposited inside the membrane pores at the top (layer index 0-40) membrane regions, although its content peak distribution shifted to the membrane surface, whereas the unmodified PES membrane holds 90% of FB in the middle (layer index 40-60) of the membrane. The ex vivo hemocompatibility study indicates an improvement in reducing the von Willebrand factor (vWF) for the heparin pseudo-ZW PES membrane compared to the covalently attached heparin and the untreated PES.

Background: HER2 is overexpressed in 25-30% of breast cancer. Multiple domains targeting of a receptor can have synergistic/additive therapeutic effects., Methods: Two domain-specific ADCs trastuzumab-PEG 6 -DM1 (domain IV) and pertuzumab-PEG 6 -DM1 (domain II) were developed, characterised and radiolabeled to obtain [ 89 Zr]Zr-trastuzumab-PEG 6 -DM1 and [ 67 Cu]Cu-pertuzumab-PEG 6 -DM1 to study their in vitro (binding assay, internalisation and cytotoxicity) and in vivo (pharmacokinetics, biodistribution and immunoPET/SPECT imaging) characteristics., Results: The ADCs had an average drug-to-antibody ratio of 3. Trastuzumab did not compete with [ 67 Cu]Cu-pertuzumab-PEG 6 -DM1 for binding to HER2. The highest antibody internalisation was observed with the combination of ADCs in BT-474 cells compared with single antibodies or ADCs. The combination of the two ADCs had the lowest IC 50 compared with treatment using the single ADCs or controls. Pharmacokinetics showed biphasic half-lives with fast distribution and slow elimination, and an AUC that was five-fold higher for [ 89 Zr]Zr-trastuzumab-PEG 6 -DM1 compared with [ 67 Cu]Cu-pertuzumab-PEG 6 -DM1. Tumour uptake of [ 89 Zr]Zr-trastuzumab-PEG 6 -DM1 was 51.3 ± 17.3% IA/g (BT-474), and 12.9 ± 2.1% IA/g (JIMT-1) which was similarly to [ 67 Cu]Cu-pertuzumab-PEG 6 -DM1. Mice pre-blocked with pertuzumab had [ 89 Zr]Zr-trastuzumab-PEG 6 -DM1 tumour uptakes of 66.3 ± 33.9% IA/g (BT-474) and 25.3 ± 4.9% IA/g (JIMT-1) at 120 h p.i., Conclusion: Using these biologics simultaneously as biparatopic theranostic agents has additive benefits., (© 2023. Crown.)