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Open Access
Development of microfluidic passive flow assays for point-of-care quantification of chronic kidney disease biomarkers in urine and serum
(2025-06-01) Tomsa, Dumitru; Salimi, Elham (Electrical and Computer Engineering); Rigatto, Claudio (Internal Medicine); Lin, Francis
Chronic kidney disease (CKD) significantly affects people's health and life quality and presents a high economic burden worldwide. However, the existing diagnostic test methods remain complicated and cost-prohibitive.
This research addresses critical gaps in CKD diagnostics through the development of innovative microfluidic platforms for point-of-care (PoC) testing. We present complementary approaches targeting key CKD biomarkers: a passive flow microreactor for urinary creatinine measurement (uCR-Chip) and microfluidic devices for serum cystatin C (CYS-C) quantification.
The uCR-Chip employs a 2-phase pressure compensation technique, optimized observation window (OW), and channel network design to control fluidic mixing and chemical reactions precisely. A stable signal is achieved within 7 minutes, with the dynamic range up to 40 mM and a lower limit of detection of 0.521 mM. This performance meets clinical precision requirements and demonstrates acceptable recovery rates in artificial urine matrices, particularly at lower creatinine concentrations, making it highly amenable to integration with previously developed microfluidic urine albumin assays.
For CYS-C, recommended as a superior estimated glomerular filtration rate (eGFR) biomarker due to minimal influence from non-filtration factors like muscle mass, we developed a PDMS-based immunoturbidity chip enabling side-scattering optical measurement. We demonstrated that the CYS-C chip meets the clinical requirements for detection range and limits while integrated into a custom-developed reader for PoC applications. Validation studies using CKD patient samples demonstrated comparable agreement levels with the traditional well plate-based immunoturbidity assay test results, determining eGFR range across clinically relevant group criteria.
Together, these microfluidic platforms offer viable solutions for decentralized CKD assessment, providing potential technology for measuring various disease biomarkers with advantages in accessibility, speed, and precision compared to existing clinical methods.
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Open Access
Development of a microfluidic paper-based device for point-of-care measurement of serum Cystatin C in chronic kidney disease
(2025-06-03) Abolfathi, Amir Hossein; Sokoro, AbdulRazaq A. H. (Pathology); Liu, Song (Biosystems Engineering); Lin, Francis
In clinical practice of chronic kidney disease (CKD), Cystatin C (CYS-C) is recommended as a superior serum biomarker for the estimated glomerular filtration rate (eGFR) compared to the traditional sole creatinine-based eGFR equation, owing to its minimal influence by non-filtration-specific factors such as muscle mass, age, and gender. However, the current CYS-C test is limited to specialized diagnostic labs and no point-of-care (POC) tools are clinically available. To address this gap, we leveraged the enabling power of microfluidic devices for POC tests of CYS-C. Among the various types of microfluidic devices, paper-based dry chips have been widely used for disease biomarker measurements with their respective advantages and limitations. Therefore, in this study, we developed a paper-based microfluidic lateral flow immunoassay chip with a unique channel design and a novel electric field-assisted antibody loading protocol for quantitative CYS-C tests. We demonstrated that paper chips meet the clinical requirements of the serum CYS-C detection range and limit. Importantly, this microfluidic chip is packaged into a special housing cartridge integrated with a custom-developed portable reader. The reader is wirelessly controlled by a smartphone app as a POC test prototype. In validation studies using serum samples from CKD patients across different disease stages, the proposed chip tests showed a similar agreement level with the traditional well plate-based immunoturbidity assay test results. As an integrated POC test system, the microfluidic CYS-C paper chip test showed high accuracy to determine the eGFR range based on several clinically relevant grouping criteria. Collectively, this integrated microfluidic assay offers practical solutions for decentralized POC diagnostic tests of CKD with competitive advantages over existing methods.
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Open Access
Identifying promising or priority effective adolescent, sexual and reproductive health interventions in Ghana: what frameworks should guide the selection of interventions?
(BMC, 2025-05-31) Achala, Daniel M.; Fenny, Ama P.; Atim, Chris; Ataguba, John Ele-Ojo
Abstract Background Adolescent sexual and reproductive health (ASRH) is an integral part of the global health agenda. It is strongly featured in the universal health coverage (UHC) agenda of the sustainable development goals (SDGs). The need to expand ASRH services to accelerate progress on UHC is urgent in Africa, compared to other regions, given its youthful population and unmet ASRH needs. Limited access to ASRH services increases the risk and vulnerability of adolescents to poor health outcomes such as unintended pregnancies, high adolescent birth rate, poor birth outcomes, high maternal and neonatal mortalities and high exposure to sexually transmitted infections. The unavailability and inaccessibility of ASRH interventions to adolescents and young adults in most African countries, including Ghana, arise from several limitations, including inadequate funding of interventions, cultural barriers and norms, lack of education, and inadequate supplies of ASRH services and commodities, among others. However, gains from investments in ASRH interventions, especially following the implementation of the Millennium Development Goals, highlight the importance of identifying and prioritising adequate funding for effective ASRH interventions. This paper identifies priority ASRH interventions that can potentially advance the sexual and reproductive health (SRH) needs of adolescents in Ghana to accelerate progress towards UHC. Methods Qualitative descriptive methods, combining literature review and stakeholder engagement, were used for this study. A literature review complemented by stakeholder engagement ensured the listing, ranking and validation of interventions. Results Adapting an established framework designed by the West African Health Organization (WAHO) through stakeholders’ engagement process, the paper identifies four of seven priority interventions ranked and validated by stakeholders for addressing the SRH needs of adolescents in Ghana. Consistent with the literature, several interventions exist to address ASRH needs. The most effective priority or promising four interventions in Ghana, according to stakeholders, include adolescent health clubs programmes, girls’ empowerment programmes through comprehensive sexuality education, national capacity-building programmes to deliver high-quality integrated family planning and comprehensive maternal health services, and electronic health (eHealth)/digital health programmes. Conclusion Identifying effective priority interventions for addressing the SRH needs of adolescents is a consultative process facilitated by proven and valid frameworks adapted to align with specific country contexts.
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Open Access
Impact of discontinuation of lactation consultant program on early infant feeding in Manitoba
(BMC, 2025-05-26) Hui, Amy L; Yamamoto, Jennifer; Dragan, Roxana; Poliquin, Vanessa; Birk, Patricia; Kearns, Katherine; Decaire, Elizabeth; Omarr, Vivian; Onyiuke, Chukwudumebi; Friesen, Kira; Raimondi Dattero, Christina; Wicklow, Brandy; Dyck, Carol; Shen, Garry X
Abstract Background Lactation Consultants (LC) at Health Sciences Centre (HSC) and St Boniface General Hospitals (SBGH) supported the lactation of 2/3 of Manitoba newborns since 1994. The LC program in HSC was discontinued in 2018. Its impact on infant feeding in the province remains unclear. Methods To assess the influence of the LC program cessation on the feeding of newborns in postpartum wards via a retrospective administrative database cohort. Results A total of 126,285 infants were delivered in all Manitoban hospitals during 2014–2021 [First Nations (FN): 21%, all others: 79%, urban: 55%, rural: 41% and remote: 4%]. The rates of breastfeeding were lower and formula feeding were higher in FN and all other newborns after the program cessation (2018–2021) compared to that during 2014–2017 (p < 0.01). The intensity of the changes in infant feeding among FN or remote-living newborns during 2018–2021 were 2–threefold greater than that among all others or urban/rural-living newborns delivered in HSC (p < 0.01). In contrast, infant feeding status stayed stable for those delivered at SBGH where the LC program did not withdraw. The cessation of LC program decreased adjusted odds ratio (aOR) for exclusive breastfeeding in FN infants (aOR 0.93, 95% CI: 0.88–0.98) and urban-living infants (aOR 0.96, 95% CI: 0.94–0.98), but not in all others, rural- or remote-living infants. Increased odds for formula feeding was detected in FN and all other infants living in various regions in the province during 2018–2021 compared to that during 2014–2017 (p < 0.05). Conclusion The findings suggest that the discontinuation of LC program decreased breastfeeding and increased formula feeding, and the unfavorable changes in infant feeding was most profound among FN and remote-living infants.
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Open Access
Evaluating zooplankton community responses to aquaculture wastewater using eDNA metabarcoding and morphological identification
(2025-04-23) Dickenson, Leah; Loseto, Lisa (Environment and Geography); Docker, Margaret (Biological Sciences); Palace, Vince; Hanson, Mark
Inland aquaculture wastewater (AWW) is nutrient-rich due to the high stocking densities of cultivated organisms and intensive feeding inputs. Finding sustainable wastewater management strategies is critical as aquaculture is the fastest-growing food production system globally. Using aquaculture wastewater as a fertilizer for wild rice cultivation presents a potential solution since wild rice requires high nitrogen and phosphorus for sufficient growth. However, this raises concerns about possible impacts on aquatic ecosystems within the wild rice system or on receiving environments of the flooded paddy drainage. For instance, the high nutrient concentration of AWW can contribute to eutrophication and deterioration of water quality, and ammonia and metals within the AWW can result in significant toxicological effects. This research assessed the ecological effects of AWW on ecosystem health, using zooplankton communities as biological indicators within mesocosms planted with wild rice. Three experiments were conducted in different simulated Northern wild rice (Zizania palustris) ecosystems: established wild rice wetlands (UM-EW), natural wild rice stands (UM-WR), and commercial paddies (R&L). AWW was applied to treatment mesocosms across a gradient of loadings. Environmental DNA (eDNA) metabarcoding was used to analyze the zooplankton communities and was compared to standard morphological identifications to determine the efficacy of this emerging method. At environmentally relevant AWW loadings, the effects on zooplankton communities were minimal. However, calanoid copepods in the R&L study exhibited a significant sensitivity to AWW exposure. In high AWW loading treatments, increased eutrophication and declining water quality led to shifts in zooplankton community dynamics. Ammonia and metal toxicity were not identified as primary drivers of these changes. Using eDNA metabarcoding proved highly effective in achieving significant taxonomic depth of the zooplankton taxa present. While community composition results did vary between methods, similar trends and responses were observed. Additionally, using designed targeted primer sets rather than a universal primer provided a more comprehensive assessment of the zooplankton community. This research advances our understanding of AWW impacts on aquatic ecosystems and demonstrates the potential of eDNA metabarcoding for biodiversity monitoring. These findings will help inform future wild rice-AWW systems of acceptable nutrient loadings to minimize ecosystem impacts.
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Open Access
LL-37 and citrullinated-LL-37 modulate IL-17A/F-mediated responses and selectively suppress Lipocalin-2 in bronchial epithelial cells
(BMC, 2025-05-23) Altieri, Anthony; Lloyd, Dylan; Ramotar, Padmanie; van der Does, Anne M.; Hemshekhar, Mahadevappa; Mookherjee, Neeloffer
Abstract Background Levels of the human cationic antimicrobial host defence peptide LL-37 are enhanced in the lungs during neutrophilic airway inflammation. LL-37 drives Th17 differentiation, and Th17 cells produce IL-17A and IL-17F which form the biologically active heterodimer IL-17A/F. While IL-17 is a critical mediator of neutrophilic airway inflammation, LL-37 exhibits contradictory functions; LL-37 can both promote and mitigate neutrophil recruitment depending on the inflammatory milieu. The impact of LL-37 on IL-17-induced responses in the context of airway inflammation remains largely unknown. Therefore, we examined signaling intermediates and downstream responses mediated by the interplay of IL-17A/F and LL-37 in human bronchial epithelial cells (HBEC). As LL-37 can become citrullinated during airway inflammation, we also examined LL-37-mediated downstream responses compared to that with citrullinated LL-37 (citLL-37) in HBEC. Results Using an aptamer-based proteomics approach, we identified proteins that are altered in response to IL-17A/F in HBEC. Proteins enhanced in response to IL-17A/F were primarily neutrophil chemoattractants, including chemokines and proteins associated with neutrophil migration such as lipocalin-2 (LCN-2). We showed that selective depletion of LCN-2 mitigates neutrophil migration, functionally demonstrating LCN-2 as a critical neutrophil chemoattractant. We further demonstrated that LL-37 and citLL-37 selectively suppress IL-17A/F-induced LCN-2 abundance in HBEC. Mechanistic studies revealed that LL-37 and citLL-37 suppresses IL-17 A/F-mediated enhancement of C/EBPβ, a transcription factor required for LCN-2 production. In contrast, LL-37 and citLL-37 enhance the abundance of ribonuclease Regnase-1, which is a negative regulator of IL-17 and LCN-2 in HBEC. In an animal model of allergen-challenged airway inflammation with elevated IL-17A/F and neutrophil elastase in the lungs, we demonstrated that CRAMP (mouse orthologue of LL-37) negatively correlates with LCN-2. Conclusions Overall, our findings showed that LL-37 and citLL-37 can selectively suppress the abundance of IL-17A/F-mediated LCN-2, a protein that is critical for neutrophil migration in HBEC. These results suggest that LL-37, and its modified citrullinated form, have the potential to negatively regulate IL-17-mediated neutrophil migration during airway inflammation. To our knowledge, this is the first study to report that the immunomodulatory function of LL-37 enhances the RNA binding protein Regnase-1, suggesting that a post-transcriptional mechanism of action is mediated by the peptide.
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Open Access
IADL for identifying cognitive impairment in Chinese older adults: insights from cross-lagged panel network analysis
(BMC, 2025-05-22) Zhai, Xiaotong; Wang, Ruizhe; Liu, Ran; Jiang, Depeng; Yu, Xiaojin
Abstract Background As China has entered an aging society, the prevention of cognitive impairment is of great importance. The progression of cognitive impairment is usually a slow and continuous process, with Instrumental Activities of Daily Living (IADL) serving as a sensitive indicator for early prediction of cognitive decline. The objective of this study was to utilize longitudinal network analysis to pinpoint the most sensitive indicators of IADLs to identify cognitive impairment in different populations, and to offer practical recommendations for preventing cognitive impairment among older adults in China. Methods A total of 2,781 participants were selected from the Chinese Longitudinal Healthy Longevity Survey (CLHLS 2014–2018). Cognitive function and IADLs were assessed by Mini-mental State Examination (MMSE) and Chinese modified Lawton scale, respectively. In this study, the cross-lagged panel network (CLPN) model was employed to construct three separate networks for all Chinese older adults, male Chinese older adults, and female Chinese older adults, respectively. Two centrality indices were used to quantify symptom centrality in directed CLPN: In-Expected-Influence (IEI) and Out-Expected-Influence (OEI). Results In the IADLs and cognitive function networks, “Use public transit,” “Make food” and “Walk 1 km” emerged as the most influential and important indicators. The edge “Use public transit → Attention and Calculation” was the strongest edge connection in all three networks. Among older adult males, “General ability” exhibited the most influence on other cognitive domains, followed by “Language,” while “Attention and Calculation” had a weaker influence. Conversely, among older adult females, “Attention and Calculation” was the most influential factor, followed by “General ability” and “Language.” Conclusions This study provides new insights into the associations between specific IADL activities and cognitive function domains among Chinese older adults. Concentrate on monitoring limitations related to “Use public transit,” “Make food” and “Walk 1 km,” and promoting broader life-space mobility may be beneficial to preventing the decline of cognitive function. The findings underscore the importance of targeting interventions not only by specific cognitive domains, but also potentially by gender. Clinical trial number Not applicable.
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Open Access
Healthcare providers' perspectives on the Canadian Caries Risk Assessment Tool implementation in Indigenous pediatric primary care: a qualitative study
(BMC, 2025-05-10) Olatosi, Olubukola O.; Schroth, Robert; DeMaré, Daniella; Mittermuller, Betty-Anne; Manigque, Maria; Edwards, Jeanette; Amin, Maryam S.; Nicolae, Alexandra; Lavoie, Josée G.; Sanguins, Julianne; Chelikani, Prashen; Wong, Peter D.; Lamoureux, Jesse; Bertone, Mary; Yerex, Katherine; Campbell, Rhonda
Abstract Background Early childhood caries remains a significant public health concern among Indigenous children in Canada. Integrating caries risk assessment (CRA) into primary care settings could improve early detection and intervention. Objectives This qualitative study explored the barriers to implementing and integrating the Canadian CRA tool into the primary care of First Nations and Métis children in Manitoba, based on the perspectives of non-dental primary care providers (NDPCPs). Methods Fifty NDPCPs providing care to Indigenous children under six years of age were purposefully selected from ten Indigenous communities in Manitoba, including Winnipeg, Selkirk, St. Laurent, Swan River, Pine Creek, Camperville, and Pine Falls. The study employed an exploratory design, with data collected through eight focus groups and twelve in-depth key informant interviews conducted between April 2023 and September 2024. All interviews were audio-recorded, transcribed verbatim, and analyzed using inductive thematic analysis with NVivo software. Results Participants included pediatricians, family physicians, public health nurses, nurse practitioners, physician assistants, dietitians, and child development workers, with an average age of 41 years (range: 24–61) and 13 years of practice experience (range: 1–40). Thematic analysis identified four major barriers to integrating the CRA tool: (1) Service provider level – time constraint, scope of practice, documentation/referral pathways, and funding; (2) Community level – oral care not priority, separation of dental and general health, lack of transportation, and healthcare distrust; (3) Caregiver and child level – lack of dental insurance, parental willingness, substituting CRA for dental visit; and (4) Provider training and skills – lack of training on fluoride varnish application and dental screening. Despite these challenges, participants expressed a positive attitude toward receiving training on early childhood caries prevention, fluoride application, and the use of the Canadian CRA tool. Conclusion This study highlights that NDPCPs in Manitoba recognize the Canadian CRA tool as a valuable resource for improving access to early preventive dental care for First Nations and Métis children. The identified barriers provide critical insights for dental, medical, and allied healthcare providers, offering a foundation for developing strategies, guidelines, and policies to enhance preventive oral health services for Indigenous children in Manitoba.
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Open Access
Estimation and evaluation of protein metabolism in a freshwater snail Planorbella duryi
(2025-05-30) Wang, Chenyi; Silva, Robin da (Physiology and pathophysiology); Detwiler, Jillian T (Biological science); Treberg, Jason
Animal bioenergetics can be defined as the conversion chemical energy from food into forms that can be used in vivo for maintenance, development and growth as well as reproduction. Thus, metabolic strategies that maximize the efficiency of energy assimilation may be beneficial to animals, especially under changing environmental conditions like elevated temperatures. Protein metabolism is a major contributor to resting energetic costs in ectotherms and protein accretion is a central component of growth. Proteins are responsible as cellular catalysts, essential structural elements and are core to defense against heat damages. Hence, a thorough understanding of protein turnover can provide insights to how energy metabolism interacts with growth dynamics under temperature change. In this thesis, two developed methods are used to assess protein metabolism in adult as well as embryonic stages of the freshwater snail Planorbella duryi. Using a novel D5-phenylalanine tracer approach to protein metabolism to flood endogenous phenylalanine pools we measure protein metabolism in the adult snails and test the effect of temperature acclimation on both the kinetics of protein synthesis and degradation. A novel open-chambered respirometer was utilized for the estimation of protein metabolism cost during embryonic development. While biochemical processes are often associated with a 2-fold to 3-fold change per 10°C change in temperature, protein metabolism following acclimation suggests marked compensation for temperature effects in the adults. Embryonic snails showed a higher commitment of energy metabolism to protein synthesis, as may be expected given the rapid cellular turnover and growth during this life-stage.
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Open Access
Hollow cone dark field imaging: automatic acquisition, and its contrast for magnesium
(2025-05-27) Parsa, Farhang; Liang, Xihui (Mechanical Engineering); Guyot, Meghan (Mechanical Engineering); Zhu, Guozhen
Hollow Cone Dark Field (HCDF) imaging is a powerful technique, yet it remains under-used for contrast-orientation studies—particularly when rapid, well-timed illumination adjustments are required and, up to the present time of authoring this thesis, no dedicated simulation protocols exist.
The key obstacle is software fragmentation: conical-illumination simulation, beam-tilt control, automatic acquisition, and quantitative validation reside in separate programs. Researchers must therefore stitch together ad-hoc scripts and file conversions, hampering usability, reproducibility, and high-throughput studies.
This study addresses the challenge by presenting a single, automated framework that unifies the entire HCDF workflow. A common scripting layer (i) generates orientation grids and supercells, (ii) performs multi-slice simulations, (iii) drives the microscope through continuous hollow-cone tilts while capturing images autonomously, and (iv) overlays experimental and simulated patterns with full parameter logging—eliminating manual data hand-offs at every stage.
Demonstrated on magnesium crystals, the system simulates several hundred HCDF images, with experimental contrast matching simulation closely enough to validate both model and instrument settings. By fusing simulation, real-time acquisition, and validation into one cohesive environment, the framework transforms HCDF from a specialist method into a practical, high-throughput technique helpful for routine orientation mapping and in-situ deformation studies in both academic and industrial contexts.