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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]

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.)

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).)

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.)

Background: Spot-check hemoglobin co-oximetry analyzers measure hemoglobin transcutaneously and offer the benefit of a hemoglobin measurement without phlebotomy. The objective of this study was to determine the validity of non-invasive spot-check hemoglobin co-oximetry testing for the detection of postpartum anemia (hemoglobin < 10 g/dL)., Methods: Five hundred eighty-four women aged 18 and over were recruited on postpartum day one following a singleton delivery. Two non-invasive spot-check hemoglobin co-oximetry monitors, Masimo Pronto Pulse CO-Oximeter (Pronto) and Masimo Rad-67 Pulse CO-Oximeter (Rad-67), were evaluated and compared to the postpartum phlebotomy hemoglobin value., Results: Of 584 participants, 31% (181) had postpartum anemia by phlebotomy hemoglobin measurement. Bland-Altman plots determined a bias of + 2.4 (± 1.2) g/dL with the Pronto and + 2.2 (± 1.1) g/dL with the Rad-67. Low sensitivity was observed: 15% for the Pronto and 16% for the Rad-67. Adjusting for the fixed bias, the Pronto demonstrated a sensitivity of 68% and specificity of 84%, while the Rad-67 demonstrated a sensitivity of 78% and specificity of 88%., Conclusion: A consistent overestimation of hemoglobin by the non-invasive spot-check hemoglobin co-oximetry monitors compared to phlebotomy hemoglobin result was observed. Even after adjusting for the fixed bias, the sensitivity for detecting postpartum anemia was low. Detection of postpartum anemia should not be based on these devices alone., (© 2023. The Author(s).)

For children and youth, the COVID-19 pandemic surfaced at a critical time in their development. Children have experienced extended disruptions to routines including in-person schooling, physical activities, and social interactions-things that bring meaning and structure to their daily lives. We estimated the prevalence of anxiety and depression symptoms of children and youth and their experiences of health-related quality of life (HRQoL), during the first year of the pandemic, and identified factors related to these outcomes. Further, we examined these effects among ethnocultural minority families. We conducted an online survey (March-July 2021) with 510 children and youth aged 8-18 years and their parents/caregivers. The sample was representative of the targeted population. We modelled the relationship between anxiety, depression (measured using the Revised Child Anxiety and Depression Scale), HRQoL (measured using KIDSCREEN-10), and sociodemographic, behavioural, and COVID-19-contributing factors using binary logistic regression. A priori-selected moderating effects of sociodemographic characteristics and self-identified ethnocultural minority groups on the outcomes were tested. The point-in-time prevalence of medium-to-high anxiety symptoms and depression symptoms was 10.19% and 9.26%, respectively. Almost half (49.15%) reported low-to-moderate HRQoL. Children reporting medium-to-high anxiety symptoms, depression symptoms, and low-to-moderate HRQoL were more likely to be aged 8-11 years, 16-18 years, ethnocultural minority participants, living in rural/urban areas, having good/fair MH before COVID-19, experiencing household conflicts, having less physical activity, and having ≥3 h of recreational screen time. Those who had more people living at home and ≥8 h of sleep reported low anxiety and depression symptoms. Ethnocultural minority 16-18-year-olds were more likely to report low-to-moderate HRQoL, compared to 12-15-year-olds. Additionally, 8-11-year-olds, 16-18-year-olds with immigrant parents, and 16-18-year-olds with Canadian-born parents were more likely to report low-moderate HRQoL, compared to 12-15-year-olds. Children and youth MH and HRQoL were impacted during the pandemic. Adverse MH outcomes were evident among ethnocultural minority families. Our results reveal the need to prioritize children's MH and to build equity-driven, targeted interventions.

Purpose: While excessive weight gain is highest during young adulthood, the extent to which specific dietary patterns are associated with changes in measures of body mass in this course of life remains unknown. We aimed to examine the associations of dietary patterns at 21 years with changes in body weight and body mass index (BMI) between 21 and 30 years., Methods: We used data on young adults from a long-running birth cohort in Australia. Western and prudent dietary patterns were identified applying principal component analysis to 33 food groups obtained by a food frequency questionnaire at 21 years. Body weight and height were measured at 21 and 30 years. Multivariable regression models, using generalized estimating equations, were adjusted for concurrent changes in sociodemographic and lifestyle variables in evaluating the effect of identified dietary patterns on changes in weight and BMI over time., Results: In the fully adjusted model, young adults in the highest tertile of the Western pattern had a mean weight gain of 9.9 (95% CI 8.5, 11.3) kg compared to those in the lowest that had a mean weight gain of 7.1 (95% CI 5.6, 8.5) kg, P-for linear trend = 0.0015. The corresponding values for mean gains in BMI were 3.1 (95% CI 2.7, 3.6) kg/m 2 for young adults in the highest tertile compared to 2.4 (95% CI 1.9, 2.9) kg/m 2 for those in lowest, P-for linear trend = 0.0164. There was no evidence of a significant association between the prudent pattern and mean changes in each outcome over time in this study., Conclusions: The findings of the current study show that greater adherence to the Western diet at 21 years was positively associated with increases in body weight and BMI from 21 to 30 years of age, whereas the prudent diet had no significant association with these outcomes. The findings provide evidence that the adverse effects of the Western diet on weight gain in young adulthood could partly be prevented through optimising diet in the early course of life., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Protein bound uremic toxins (PBUTs) are small substances binding to larger proteins, mostly human serum albumin (HSA), and are challenging to remove by hemodialysis (HD). Among different classes of PBUTs, p-cresyl sulfate (PCS) is the most widely used marker molecule and major toxin, as 95 % is bound to HSA. PCS has a pro-inflammatory effect and increases both the uremia symptom score and multiple pathophysiological activities. High-flux HD to clear PCS leads to serious loss of HSA, which results in a high mortality rate. The goal of the present study is to investigate the efficacy of PCS detoxification in serum of HD patients using a biocompatible laccase enzyme from Trametes versicolor. Molecular docking was used to gain an in-depth understanding of the interactions between PCS and the laccase to identify the functional group(s) responsible for ligand-protein receptor interactions. UV-Vis spectroscopy and gas chromatography-mass spectrometry (GC-MS) were used to assess the detoxification of PCS. GC-MS was used to identify the detoxification byproducts and their toxicity was assessed using docking commutations. In situ synchrotron radiation micro-computed tomography (SR-µCT) imaging available at the Canadian Light Source (CLS) was conducted to assess HSA binding with PCS before and after detoxification with laccase and undertake the corresponding quantitative analysis. GC-MS analyses confirmed the detoxification of PCS with laccase at a concentration of 500 mg/L. The potential pathway of PCS detoxification in the presence of the laccase was identified. Increasing laccase concentration led to the formation of m-cresol, as indicated by the corresponding absorption in the UV-Vis spectra and a sharp peak on the GC-MS spectra. Our analysis provides insight into the general features of PCS binding on Sudlow site II, as well as insights into PCS detoxification product interactions. The average affinity energy for detoxification products was lower than that of PCS. Even though some byproducts showed potential toxicity, the level was lower than for PCS based on toxicity indexes (e.g., LD50/LC50, carcinogenicity, neurotoxicity, mutagenicity). In addition, these small compounds can also be more easily removed by HD compared to PCS. SR-µCT quantitative analysis showed adhesion of the HSA to a significant reduced extent in the presence of the laccase enzyme in bottom sections of the polyarylethersulfone (PAES) clinical HD membrane tested. Overall, this study opens new frontiers for PCS detoxification., 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 Elsevier B.V. All rights reserved.)

Background and Aims: To examine a combined effect of dietary intakes, blood lipid and insulin resistance in young adulthood on the risk of predicted CVD through midlife., Methods and Results: Data of young adults from a birth cohort study in Australia were used. Reduced rank regression (RRR) and partial least squares (PLS) methods identified dietary patterns rich in meats, refined grains, processed and fried foods, and high-fat dairy and low in whole grains and low-fat dairy from dietary intakes obtained at 21-years, and blood lipids and measures of insulin resistance measured at 30-years of age. Using standard CVD risk factors measured at 30-years of age, the Framingham Heart Study risk-prediction algorithms were used to calculate the 30-year predicted Framingham CVD risk scores. The scores represent Hard CVD events; coronary death, myocardial infarction and stroke and Full CVD events; Hard CVD plus coronary insufficiency and angina pectoris, transient ischaemic attack, intermittent claudication, and congestive heart failure in midlife. Sex-specific upper quartiles of CVD risk scores were used to define high-risk groups. Modified Poisson regression models were used to estimate relative risks (RRs) with 95% CI. Greater adherence to the diet identified applying RRR in young adulthood was associated with higher risks of predicted Hard CVD (RR: 1.60; 1.14, 2.25) and Full CVD (RR: 1.46; 1.04, 2.05) events in midlife. The diet from PLS showed similar trend of association for the risk of predicted Hard CVD events (RR: 1.49; 1.03, 2.16) in adjusted models., Conclusion: Dietary patterns associated with variations in blood lipids and insulin resistance in young adulthood are associated with increased risks of predicted CVD events in midlife. The findings suggest that diet induced altered blood lipids and insulin resistance in the life course of young adulthood could increase the risks of CVD events in later life., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. All rights reserved.)

Circadian desynchrony with the external light-dark cycle influences the rhythmic secretion of melatonin which is among the first signs of circadian rhythm sleep disorders. An accurate dim light melatonin onset (established indicator of circadian rhythm sleep disorders) measurement requires lengthy assays, and antibody affinities alterations, especially in patients with circadian rhythm disorders whose melatonin salivary levels vary significantly, making antibodies detection mostly inadequate. In contrast, aptamers with their numerous advantages (e.g., target selectivity, structural flexibility in tuning binding affinities, small size, etc.) can become preferable biorecognition molecules for salivary melatonin detection with high sensitivity and specificity. This study thoroughly characterizes the structural property and binding mechanism of a single-stranded DNA aptamer full sequence (MLT-C-1) and its truncated versions (MLT-A-2, MLT-A-4) to decipher its optimal characteristics for saliva melatonin detection. We use circular dichroism spectroscopy to determine aptamers' conformational changes under different ionic strengths and showed that aptamers display a hairpin loop structure where few base pairs in the stem play a significant role in melatonin binding and formation of aptamer stabilized structure. Through microscale thermophoresis, aptamers demonstrated a high binding affinity in saliva samples (MLT-C-1F K d  = 12.5 ± 1.7 nM; MLT-A-4F K d  = 11.2 ± 1.6 nM; MLT-A-2F K d  = 2.4 ± 2.8 nM; limit-of-detection achieved in pM, highest sensitivity attained for MLT-A-2F aptamer with the lowest detection limit of 1.35 pM). Our data suggest that aptamers are promising as biorecognition molecules and provide the baseline parameters for the development of an aptamer-based point-of-care diagnostic system for melatonin detection and accurate profiling of its fluctuations in saliva., 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 Elsevier B.V. All rights reserved.)

Pea (Pisum sativum L.) is an important legume crop providing a good source of protein, vitamins, minerals and bioactive compounds with health benefits for humans. In this study, an improved method for simultaneous analysis of multiple phytoestrogens among 100 pea accessions was developed. Ipriflavone, (a synthetic isoflavone), was used as an internal standard for the semiquantitative analysis of 17 phytoestrogens including isoflavone aglycones and conjugates, allowing direct analysis of isoflavones in their naturally occurring forms. This comprehensive dataset demonstrated that the isoflavones varied greatly and some accessions tended to have high levels of multiple phytoestrogens among the 100 accessions analyzed. Isoliquiritigenin followed by glycitein were the predominant compounds detected in the accessions and showed the highest correlation with the total phytoestrogens content. Secoisolariciresinol content was consistently higher in yellow cotyledon peas than in green cotyledon peas, whereas the contents of coumestrol, genestein and secoisolariciresinol were significantly correlated with seed coat color. The total phenolics and saponins showed a wide range of variability among the accessions with higher concentrations of total phenolics observed in seeds with pigmented seed coat or yellow cotyledon seeds, suggesting the synthesis of saponins and phenolics are significantly affected by metabolic pathway genes controlling cotyledon color or seed coat color. This study profiled the variability of bioactive compounds of pea seed quality traits in diverse pea accessions and provides an immense resource for continued research, breeding and selection of genotypes for a wide range of applications., 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., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: People who inject drugs living with HIV (PWIDLH) suffer the lowest rates of HIV viral suppression due to episodic injection drug use and poor mental health coupled with poor retention in HIV care. Approximately 44% of PWIDLH along the US-Mexico border are retained in care and only 24% are virally suppressed. This underserved region faces a potential explosion of transmission of HIV due to highly prevalent injection drug use. This protocol describes an optimization trial to promote sustained viral suppression among Spanish-speaking Latinx PWIDLH., Methods: The multiphase optimization strategy (MOST) is an engineering-inspired framework for designing and building optimized interventions and guides this intervention. The primary aim is to conduct a 2 4 factorial experiment in which participants are randomized to one of 16 intervention conditions, with each condition comprising a different combination of four behavioral intervention components. The components are peer support for methadone uptake and persistence; behavioral activation therapy for depression; Life-Steps medication adherence counseling; and patient navigation for HIV care. Participants will complete a baseline survey, undergo intervention, and then return for 3-,6-,9-, and 12-month follow-up assessments. The primary outcome is sustained viral suppression, defined as viral loads of < 40 copies per mL at 6-,9-, and 12-month follow-up assessments. Results will yield effect sizes for each component and each additive and interactive combination of components. The research team and partners will make decisions about what constitutes the optimized multi-component intervention by judging the observed effect sizes, interactions, and statistical significance against real-world implementation constraints. The secondary aims are to test mediators and moderators of the component-to-outcome relationship at the 6-month follow-up assessment., Discussion: We are testing well-studied and available intervention components to support PWIDLH to reduce drug use and improve their mental health and engagement in HIV care. The intervention design will allow for a better understanding of how these components work in combination and can be optimized for the setting., Trial Registration: This project was registered at clinicaltrials.gov (NCT05377463) on May 17th, 2022., (© 2023. The Author(s).)

Comprehensive understanding of protein adsorption phenomenon on membrane surface during hemodialysis (HD) is one of the key moments for development of hemocompatible HD membrane. Though many mechanisms and kinetics of protein adsorption on some surface have been studied, we are still far away from complete understanding and control of this process, which results in a series of biochemical reactions that causes severe complications with health and even the death among HD patients. The aim of this study is to conduct quantitative analysis of competitive adsorption tendency of human serum protein on polyether sulfone (PES) clinical dialysis membrane. In situ synchrotron radiation micro-computed tomography (SR-µCT) imaging available at the Canadian Light Source (CLS) was conducted to assess human serum proteinbinding and undertake the corresponding quantitative analysis.The competitive adsorption of Human protein albumin (HSA), fibrinogen (FB) and transferrin (TRF) were tested from single and multiple protein solution. Furthermore, in-vitro human serum protein adsorption on clinical dialyzers was investigated using UV-Visible to confirm the competitive adsorption tendency. Results showed that when proteins were adsorbed from their mixture, FB content (among proteins) in the adsorbed layer increased from 3.6% mass (content in the initial solution) to 18% mass and 12%, in case of in situ quantitative and invitro analysis, respectively. The increase in FB content was accompanied by the decrease in the HSA content, while TRF remained on approximately on the same level for both cases. Overall, the percentage of HSA adsorption ratio onto the HD membrane has dropped approximately 10 times when HSA was adsorbed in competition with other proteins, compared to the adsorption from single HSA solution. The substitution of HSA with FB was especially noticeable when HSA adsorption from its single solution was compared with the case of the protein mixture. Moreover, SR-µCT has revealed that FB when adsorbed from a protein mixture solution is located predominately in the middle of the membrane, whereas the peak of the distribution is shifted to membrane bottom layers when adsorption from FB single solution takes place. Results showed that HSA FB and TRF adsorption behavior observations are similar on both in-situ small scale and clinical dialyzer of the PES membrane., (© 2023. The Author(s).)

Hemodialysis (HD) membrane fouling with human serum proteins is a highly undesirable process that results in blood activations with further severe consequences for HD patients. Polyvinylidene fluoride (PVDF) membranes possess a great extent of protein adsorption due to hydrophobic interaction between the membrane surface and non-polar regions of proteins. In this study, a PVDF membrane was modified with a zwitterionic (ZW) polymeric structure based on a poly (maleic anhydride-alt-1-decene), 3-(dimethylamino)-1-propylamine derivative and 1,3-propanesultone. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and zeta potential analyses were used to determine the membrane's characteristics. Membrane fouling with human serum proteins (human serum albumin (HSA), fibrinogen (FB), and transferrin (TRF)) was investigated with synchrotron radiation micro-computed tomography (SR-μCT), which allowed us to trace the protein location layer by layer inside the membrane. Both membranes (PVDF and modified PVDF) were detected to possess the preferred FB adsorption due to the Vroman effect, resulting in an increase in FB content in the adsorbed protein compared to FB content in the protein mixture solution. Moreover, FB was shown to only replace HSA, and no significant role of TRF in the Vroman effect was detected; i.e., TRF content was nearly the same both in the adsorbed protein layer and in the protein mixture solution. Surface modification of the PVDF membrane resulted in increased FB adsorption from both the protein mixture and the FB single solution, which is supposed to be due to the presence of an uncompensated negative charge that is located at the COOH group in the ZW polymer.

Purpose: Airway evaluation is a fundamental component of the preanesthetic examination. Virtual care has increased during the COVID-19 pandemic. We aimed to assess the reliability of a virtual preanesthetic airway evaluation compared with a traditional in-person airway evaluation., Methods: This prospective observational study compared the inter-rater agreement of an in-person airway evaluation performed by a consultant anesthesiologist with a virtual airway evaluation (VAE) performed by consultant anesthesiologists and medical students. The airway evaluation was completed using a comprehensive airway evaluation and scoring tool. The primary outcome was the inter-rater agreement of total scores between in-person anesthesiologist airway evaluations and the VAEs of both the anesthesiologists and medical students, assessed using Cohen's Kappa (CK). Secondary outcomes included the inter-rater agreement for each airway evaluation component between the in-person anesthesiologists and both the anesthesiologist and medical student VAEs, assessed using prevalence-adjusted and bias-adjusted Kappa., Results: One hundred out of 111 participants completed all three evaluations. The in-person anesthesiologist airway evaluations had fair and good levels of agreement of total scores with the VAEs of the anesthesiologists (CK, 0.21; 97.5% confidence interval [CI], 0.07 to 0.34) and the medical students (CK, 0.74; 97.5% CI, 0.62 to 0.86), respectively. One participant was reported to have a difficult intubation., Conclusion: Virtual airway evaluations performed by anesthesiologists and medical students had fair and good inter-rater agreement, respectively, with in-person anesthesiologist airway evaluations. Further study with a focus on patients with difficult airways is required to define the predictive value of VAEs regarding difficult intubations., (© 2022. Canadian Anesthesiologists' Society.)

Rationale: The female menstrual or estrous cycle and its associated fluctuations in circulating estradiol (E2), progesterone, and other gonadal hormones alter orexin or hypocretin peptide production and receptor activity. Depending on the estrous cycle phase, the transcription of prepro-orexin mRNA, post-translational modification of orexin peptide, and abundance of orexin receptors change in a brain region-specific manner. The most dramatic changes occur in the hypothalamus, which is considered the starting point of the hypothalamic-pituitary-gonadal axis as well as the hub of orexin-producing neurons. Thus, hypothalamus-regulated behaviors, including arousal, feeding, reward processing, and the stress response depend on coordinated efforts between E2, progesterone, and the orexin system. Given the rise of orexin therapeutics for various neuropsychiatric conditions including insomnia and affective disorders, it is important to delineate the behavioral outcomes of this drug class in both sexes, as well as within different time points of the female reproductive cycle., Objectives: Summarize how the menstrual or estrous cycle affects orexin system functionality in animal models in order to predict how orexin pharmacotherapies exert varying degrees of behavioral effects across the dynamic hormonal milieu., (© 2022. The Author(s).)

Tissue engineering offers a great potential in regenerative dentistry and to this end, three dimensional (3D) bioprinting has been emerging nowadays to enable the incorporation of living cells into the biomaterials (such a mixture is referred as a bioink in the literature) to create scaffolds. However, the bioinks available for scaffold bioprinting are limited, particularly for dental tissue engineering, due to the complicated, yet compromised, printability, mechanical and biological properties simultaneously imposed on the bioinks. This paper presents our study on the development of a novel bioink from carboxymethyl chitosan (CMC) and alginate (Alg) for bioprinting scaffolds for enamel tissue regeneration. CMC was used due to its antibacterial ability and superior cell interaction properties, while Alg was added to enhance the printability and mechanical properties as well as to regulate the degradation rate. The bioinks with three mixture ratios of Alg and CMC (2-4, 3-3 and 4-2) were prepared, and then printed into the calcium chloride crosslinker solution (100 mM) to form a 3D structure of scaffolds. The printed scaffolds were characterized in terms of structural, swelling, degradation, and mechanical properties, followed by their in vitro characterization for enamel tissue regeneration. The results showed that the bioinks with higher concentrations of Alg were more viscous and needed higher pressure for printing; while the printed scaffolds were highly porous and showed a high degree of printability and structural integrity. The hydrogels with higher CMC ratios had higher swelling ratios, faster degradation rates, and lower compressive modulus. Dental epithelial cell line, HAT-7, could maintain high viability in the printed constructs after 1, 7 and 14 d of culture. HAT-7 cells were also able to maintain their morphology and secrete alkaline phosphatase after 14 d of culture in the 3D printed scaffolds, suggesting the capacity of these cells for mineral deposition and enamel-like tissue formation. Among all combinations Alg4%-CMC2% and in a less degree 2%Alg-4%CMC showed the higher potential to promote ameloblast differentiation, Ca and P deposition and matrix mineralization in vitro . Taken together, Alg-CMC has been illustrated to be suitable to print scaffolds with dental epithelial cells for enamel tissue regeneration., (Creative Commons Attribution license.)