Publications by authors named "J Michael Henderson"

3,420 Publications

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Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation.

J Biol Chem 2021 Apr 3:100631. Epub 2021 Apr 3.

Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, U.K. Electronic address:

TREM2 is a pattern recognition receptor, expressed on microglia and myeloid cells, detecting lipids and Aβ, and inducing an innate immune response. Missense mutations (e.g. R47H) of TREM2 increase risk of Alzheimer's disease (AD). The soluble ectodomain of wild-type TREM2 (sTREM2) has been shown to protect against AD in vivo, but the underlying mechanisms are unclear. We show that Aβ oligomers bind to cellular TREM2, inducing shedding of the sTREM2 domain. Wild-type sTREM2 bound to Aβ oligomers (measured by single-molecule imaging, dot blots and Bio-Layer Interferometry), inhibited Aβ oligomerization and disaggregated preformed Aβ oligomers and protofibrils (measured by transmission electron microscopy, dot blots and size exclusion chromatography). Wild-type sTREM2 also inhibited Aβ fibrillization (measured by imaging and thioflavin T fluorescence) and blocked Aβ-induced neurotoxicity (measured by permeabilization of artificial membranes and by loss of neurons in primary neuronal-glial co-cultures). In contrast, the R47H AD-risk variant of sTREM2 is less able to bind and disaggregate oligomeric Aβ, but rather promotes Aβ protofibril formation and neurotoxicity. Thus, in addition to inducing an immune response, wild-type TREM2 may protect against amyloid pathology by the Aβ-induced release of sTREM2, which blocks Aβ aggregation and neurotoxicity. In contrast, R47H sTREM2 promotes Aβ aggregation into protofibril that may be toxic to neurons. These findings may explain how wild-type sTREM2 apparently protects against AD in vivo, and why a single copy of the R47H variant gene is associated with increased AD risk.
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http://dx.doi.org/10.1016/j.jbc.2021.100631DOI Listing
April 2021

Brain Dynamics and Structure-Function Relationships via Spectral Factorization and the Transfer Function.

Neuroimage 2021 Apr 2:117989. Epub 2021 Apr 2.

School of Physics, University of Sydney, New South Wales 2006, Australia; ARC Center for Integrative Brain Function, University of Sydney, New South Wales 2006, Australia. Electronic address:

It is shown how the brain's linear transfer function provides a means to systematically analyze brain connectivity and dynamics, and to infer connectivity, eigenmodes, and activity measures such as spectra, evoked responses, coherence, and causality, all of which are widely used in brain monitoring. In particular, the Wilson spectral factorization algorithm is outlined and used to efficiently obtain linear transfer functions from experimental two-point correlation functions. The algorithm is tested on a series of brain-like structures of increasing complexity which include time delays, asymmetry, two-dimensionality, and complex network connectivity. These tests are used to verify the algorithm is suitable for application to brain dynamics, specify sampling requirements for experimental time series, and to verify that its runtime is short enough to obtain accurate results for systems of similar size to current experiments. The results can equally well be applied to inference of the transfer function in complex linear systems other than brains.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117989DOI Listing
April 2021

Beyond Self-Recycling: Cell-Specific Role of Autophagy in Atherosclerosis.

Cells 2021 Mar 11;10(3). Epub 2021 Mar 11.

Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximillians-Universität (LMU), D-80336 Munich, Germany.

Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall and underlies the development of cardiovascular diseases, such as myocardial infarction and ischemic stroke. As such, atherosclerosis stands as the leading cause of death and disability worldwide and intensive scientific efforts are made to investigate its complex pathophysiology, which involves the deregulation of crucial intracellular pathways and intricate interactions between diverse cell types. A growing body of evidence, including in vitro and in vivo studies involving cell-specific deletion of autophagy-related genes (ATGs), has unveiled the mechanistic relevance of cell-specific (endothelial, smooth-muscle, and myeloid cells) defective autophagy in the processes of atherogenesis. In this review, we underscore the recent insights on autophagy's cell-type-dependent role in atherosclerosis development and progression, featuring the relevance of canonical catabolic functions and emerging noncanonical mechanisms, and highlighting the potential therapeutic implications for prevention and treatment of atherosclerosis and its complications.
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http://dx.doi.org/10.3390/cells10030625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998923PMC
March 2021

Postsecondary Student Engagement With a Mental Health App and Online Platform (Thought Spot): Qualitative Study of User Experience.

JMIR Ment Health 2021 Apr 2;8(4):e23447. Epub 2021 Apr 2.

Office of Education, Centre for Addiction and Mental Health, Toronto, ON, Canada.

Background: There is growing interest in using mobile apps and online tools to support postsecondary student mental health, but most of these solutions have suboptimal user engagement in real-world settings. Poor engagement can limit long-term effectiveness and usefulness of these tools. Previous literature has proposed several theories that link factors such as low usability and poor user-centered design to app disengagement. However, few studies provide direct evidence showing what factors contribute to suboptimal user engagement in the context of mobile mental health apps for postsecondary students.

Objective: This study focuses on understanding postsecondary students' attitudes and behaviors when using Thought Spot, a co-designed mental health app and online platform, to understand factors related to engagement and user experience.

Methods: Students who were given access to Thought Spot for 6 months during a randomized trial of the intervention were invited to participate in one-on-one semistructured interviews. The interviews explored participants' overall experiences and perceptions of the app, along with factors that affected their usage of various features. All interviews were recorded, and template analysis was used to analyze transcripts.

Results: User satisfaction was mixed among users of Thought Spot. The degree of engagement with the app appeared to be affected by factors that can be grouped into 5 themes: (1) Students valued detailed, inclusive, and relevant content; (2) Technical glitches and a lack of integration with other apps affected the overall user experience and satisfaction with the app; (3) Using the app to support peers or family can increase engagement; (4) Crowdsourced information from peers about mental health resources drove user engagement, but was difficult to obtain; and (5) Users often turned to the app when they had an immediate need for mental health information, rather than using it to track mental health information over time.

Conclusions: Content, user experience, user-centeredness, and peer support are important determinants of user engagement with mobile mental health apps among postsecondary students. In this study, participants disengaged when the app did not meet their expectations on these determinants. Future studies on user engagement should further explore the effectiveness of different features and the relative importance of various criteria for high-quality apps. Further focus on these issues may inform the creation of interventions that increase student engagement and align with their mental health needs.

Trial Registration: ClinicalTrials.gov NCT03412461; https://clinicaltrials.gov/ct2/show/NCT03412461.

International Registered Report Identifier (irrid): RR2-10.2196/resprot.6446.
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http://dx.doi.org/10.2196/23447DOI Listing
April 2021

Assessment of serological assays for identifying high titer convalescent plasma.

medRxiv 2021 Mar 28. Epub 2021 Mar 28.

The COVID-19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose-response data using the Ortho VITROS IgG assay. The proliferation of SARS-CoV-2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between commercially available serological tests (Ortho, Abbott, Roche), a spike ELISA, and a virus neutralization assay using convalescent plasma from a cohort of 79 donors from April 2020. Relationships relative to FDA-approved cutoffs under the CCP EUA were identified by linear regression and receiver operator characteristic curves. Relative to the Ortho VITROS assay, the r of the Abbott, Roche, the anti-Spike ELISA and the neutralizing assay were 0.58, 0.5, 0.82, and 0.44, respectively. The best correlative index for establishing high-titer units was 3.82 S/C for the Abbott, 10.89 COI for the Roche, 1:1,202 for the anti-Spike ELISA, and 1:200 by the neutralization assay. The overall agreement using derived cutoffs compared to the CCP EUA Ortho VITROS cutoff of 9.5 was 92.4% for Abbott, 84.8% for Roche, 87.3% for the anti-S ELISA and 78.5% for the neutralization assay. Assays based on antibodies against the nucleoprotein (Roche, Abbott) and neutralizing antibody tests were positively associated with the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic.
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http://dx.doi.org/10.1101/2021.03.26.21254427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010743PMC
March 2021

Home Use of a Percutaneous Wireless Intracortical Brain-Computer Interface by Individuals With Tetraplegia.

IEEE Trans Biomed Eng 2021 Mar 30;PP. Epub 2021 Mar 30.

Objective: Individuals with neurological disease or injury such as amyotrophic lateral sclerosis, spinal cord injury or stroke may become tetraplegic, unable to speak or even locked-in. For people with these conditions, current assistive technologies are often ineffective. Brain-computer interfaces are being developed to enhance independence and restore communication in the absence of physical movement. Over the past decade, individuals with tetraplegia have achieved rapid on-screen typing and point-and-click control of tablet apps using intracortical brain-computer interfaces (iBCIs) that decode intended arm and hand movements from neural signals recorded by implanted microelectrode arrays. However, cables used to convey neural signals from the brain tether participants to amplifiers and decoding computers and require expert oversight, severely limiting when and where iBCIs could be available for use. Here, we demonstrate the first human use of a wireless broadband iBCI.

Methods: Based on a prototype system previously used in pre-clinical research, we replaced the external cables of a 192-electrode iBCI with wireless transmitters and achieved high-resolution recording and decoding of broadband field potentials and spiking activity from people with paralysis. Two participants in an ongoing pilot clinical trial completed on-screen item selection tasks to assess iBCI-enabled cursor control.

Results: Communication bitrates were equivalent between cabled and wireless configurations. Participants also used the wireless iBCI to control a standard commercial tablet computer to browse the web and use several mobile applications. Within-day comparison of cabled and wireless interfaces evaluated bit error rate, packet loss, and the recovery of spike rates and spike waveforms from the recorded neural signals. In a representative use case, the wireless system recorded intracortical signals from two arrays in one participant continuously through a 24-hour period at home.

Significance: Wireless multi-electrode recording of broadband neural signals over extended periods introduces a valuable tool for human neuroscience research and is an important step toward practical deployment of iBCI technology for independent use by individuals with paralysis. On-demand access to high-performance iBCI technology in the home promises to enhance independence and restore communication and mobility for individuals with severe motor impairment.
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http://dx.doi.org/10.1109/TBME.2021.3069119DOI Listing
March 2021

Quali sono le ragioni delle Missed Care? Risultato di uno studio bilaterale. Ragioni delle Missed Care.

Ig Sanita Pubbl 2020 Nov-Dec;76(6):355-369

Department of Nursing, School of Health Sciences, Cyprus University of Technology.

Background: Evidence of missed nursing care in clinical practice has been well documented; however, fewer studies highlighting why care is missed have been conducted and this prevents effective interventions aimed at minimizing the missed care.

Methods: A secondary analysis of two cross-sectional study designs was performed to capture the direction and strength of 1,114 Italian and Australian nurses' perceptions about why care was missed in their hospitals. The MISSCARE survey was used to collect data and the specific section aimed at estimating the reasons for missed nursing care was used. Data were analysed using structural equation modelling.

Results: Six significant variables emerged as predictors of why care is missed, and these were: workplace miscommunication; increased work intensity; inadequate physical and human resources for care work; nurses' age; and years of clinical experience.

Conclusions: Australian and Italian findings contribute to growing international studies as to why nursing care is missed and provides a framework for understanding precipitating factors, such as incomplete workplace communication, unpredictable workflows, staffing and material resources issues might contribute to why care is missed and must thus be addressed/improved.
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April 2021

Fetal heart rate during maternal sleep.

Dev Psychobiol 2021 Mar 25. Epub 2021 Mar 25.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Despite prolonged and cumulative exposure during gestation, little is known about the fetal response to maternal sleep. Eighty-four pregnant women with obesity (based on pre-pregnancy BMI) participated in laboratory-based polysomnography (PSG) with continuous fetal electrocardiogram monitoring at 36 weeks gestation. Multilevel modeling revealed both correspondence and lack of it in maternal and fetal heart rate patterns. Fetal heart rate (fHR) and variability (fHRV), and maternal heart rate (mHR) and variability (mHRV), all declined during the night, with steeper rates of decline prior to 01:00. fHR declined upon maternal sleep onset but was not otherwise associated with maternal sleep stage; fHRV differed during maternal REM and NREM. There was frequent maternal waking after sleep onset (WASO) and fHRV and mHRV were elevated during these episodes. Cross-correlation analyses revealed little temporal coupling between maternal and fetal heart rate, except during WASO, suggesting that any observed associations in maternal and fetal heart rates during sleep are the result of other physiological processes. Implications of the maternal sleep context for the developing fetus are discussed, including the potential consequences of the typical sleep fragmentation that accompanies pregnancy.
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http://dx.doi.org/10.1002/dev.22118DOI Listing
March 2021

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

medRxiv 2021 Mar 20. Epub 2021 Mar 20.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.
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http://dx.doi.org/10.1101/2021.03.19.21253986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987050PMC
March 2021

Braided absorbable sutures for traumatic wounds.

JPRAS Open 2021 Jun 20;28:64-65. Epub 2021 Feb 20.

Department of Plastic and Reconstructive Surgery, Southmead Hospital, Southmead Road, BS10 5NB, United Kingdom.

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http://dx.doi.org/10.1016/j.jpra.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960679PMC
June 2021

Maternal and child health in Seychelles.

Neurotoxicology 2020 12 12;81:238-245. Epub 2020 Oct 12.

Ministry of Health, Republic of Seychelles; Seychelles Medical and Dental Association, Republic of Seychelles.

Services aimed at improving the health of infants, children and mothers have developed over the years since the initiation of the Seychelles Child Development Study. This paper describes the policies, procedures and facilities and how they have impacted on service provision. The utilisation of antenatal, perinatal and child health services, both in the hospital and community settings, are described. The successes and challenges are illustrated by describing fertility, abortion, teenage pregnancy and infant mortality. This overview of maternal and child services provides a perspective on an important aspect of health care development and the context in which the SCDS is conducted.
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http://dx.doi.org/10.1016/j.neuro.2020.09.011DOI Listing
December 2020

Variants associated with expression have sex-differential effects on lung function.

Wellcome Open Res 2020 1;5:111. Epub 2020 Jun 1.

Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.

Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 ) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV ) (P=3.15x10 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV more in males (untransformed FEV β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( ) gene and was previously associated with lung function and lung expression. We found expression was significantly different between the sexes (P=6.90x10 ), but we could not detect sex differential effects of rs7697189 on expression. We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the gene. Establishing the mechanism by which SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
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http://dx.doi.org/10.12688/wellcomeopenres.15846.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938335PMC
June 2020

Considerations for evaluating digital mental health tools remotely- reflections after a randomized trial of Thought Spot.

Gen Hosp Psychiatry 2021 Feb 28;70:76-77. Epub 2021 Feb 28.

Office of Education, Centre for Addiction and Mental Health, Toronto, Canada; UHN Digital, University Health Network, Toronto, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.genhosppsych.2021.02.010DOI Listing
February 2021

Perspectives on Motivation and Change in an Intervention for Men Who Use Substances and Perpetrate Intimate Partner Abuse: Findings From a Qualitative Evaluation of the Advance Intervention.

J Interpers Violence 2021 Mar 9:886260521997436. Epub 2021 Mar 9.

King's College London, UK.

Despite consistent evidence that substance use is a contributory risk factor for perpetration of intimate partner abuse (IPA), little evidence exists for effective interventions for male IPA perpetrators who use substances. The Advance intervention aimed to meet this need. This 16-week intervention addressed both IPA and substance use, and was for men accessing substance use treatment who had perpetrated IPA toward a female (ex-)partner within the last 12 months. Two key theories underpinned the intervention: goal theory and self-regulation theory. In this article, we aim to illustrate the views of men and substance use treatment staff on men's motivations to change, the ways in which men and staff said that men had changed their behavior, and the aspects of the intervention that they reported were key in the process of change. Using framework analysis, we analyzed data from 12 men who took part in the intervention as well as 31 staff members from substance use treatment services. Our five overarching themes were personal goal setting and motivation; recognition of IPA and the substance using lifestyle; improved self-regulation; considering the impact on others; and learning together in a group. Men and staff valued having a program that integrated IPA and substance use and thought the program was unique and much needed. Moreover, our findings suggest that goal theory, self-regulation, and more broadly, motivational and strengths-based approaches with practice-based activities, may be beneficial for effecting change in the substance using perpetrator population. However, further research is needed to determine the effectiveness of the intervention. Overall, our findings highlight the value of using qualitative outcome measures of perpetrator programs to complement quantitative measures of impact.
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http://dx.doi.org/10.1177/0886260521997436DOI Listing
March 2021

Exploring the transformability of polymer-lipid hybrid nanoparticles and nanomaterial-biology interplay to facilitate tumor penetration, cellular uptake and intracellular targeting of anticancer drugs.

Expert Opin Drug Deliv 2021 Mar 30:1-14. Epub 2021 Mar 30.

Advanced Pharmaceutics & Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

Background: Successful delivery of anticancer drugs to intracellular targets requires different properties of the nanocarrier to overcome multiple transport barriers. However, few nanocarrier systems, to date, possess such properties, despite knowledge about the biological fate of inorganic and polymeric nanocarriers in relation to their fixed size, shape and surface properties. Herein, a polymer-lipid hybrid nanoparticle (PLN) system is described with size and shape transformability and its mechanisms of cellular uptake and intracellular trafficking are studied.

Methods: Pharmaceutical lipids were screened for use in transformable PLN. Mechanisms of cellular uptake and the role of fatty acid-binding proteins in intracellular trafficking of PLN were investigated in breast cancer cells. Intra-tumoral penetration and retention of doxorubicin (DOX) were evaluated by confocal microscopy.

Results: The lead PLNs showed time-dependent size reduction and shape change from spherical to spiky shape. This transformability of PLNs and lipid trafficking pathways facilitated intracellular transport of DOX-loaded PLN (DOX-PLN) into mitochondria and nuclei. DOX-PLN significantly increased DOX penetration and retention over free DOX or non-transformable liposomal DOX particles at 4 h post-intravenous administration.

Conclusion: Transformability of PLN and lipid-biology interplay can be exploited to design new nanocarriers for effective drug delivery to tumor cells and intracellular targets.
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http://dx.doi.org/10.1080/17425247.2021.1902984DOI Listing
March 2021

Review of Wearable Sensor-Based Health Monitoring Glove Devices for Rheumatoid Arthritis.

Sensors (Basel) 2021 Feb 24;21(5). Epub 2021 Feb 24.

School of Computing, Engineering and Intelligent System, Ulster University Magee Campus, Northland Rd, Londonderry BT48 7JL, Ireland.

Early detection of Rheumatoid Arthritis (RA) and other neurological conditions is vital for effective treatment. Existing methods of detecting RA rely on observation, questionnaires, and physical measurement, each with their own weaknesses. Pharmaceutical medications and procedures aim to reduce the debilitating effect, preventing the progression of the illness and bringing the condition into remission. There is still a great deal of ambiguity around patient diagnosis, as the difficulty of measurement has reduced the importance that joint stiffness plays as an RA identifier. The research areas of medical rehabilitation and clinical assessment indicate high impact applications for wearable sensing devices. As a result, the overall aim of this research is to review current sensor technologies that could be used to measure an individual's RA severity. Other research teams within RA have previously developed objective measuring devices to assess the physical symptoms of hand steadiness through to joint stiffness. Unfamiliar physical effects of these sensory devices restricted their introduction into clinical practice. This paper provides an updated review among the sensor and glove types proposed in the literature to assist with the diagnosis and rehabilitation activities of RA. Consequently, the main goal of this paper is to review contact systems and to outline their potentialities and limitations. Considerable attention has been paid to gloved based devices as they have been extensively researched for medical practice in recent years. Such technologies are reviewed to determine whether they are suitable measuring tools.
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http://dx.doi.org/10.3390/s21051576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956752PMC
February 2021

Reliability and Validity of Clinically Accessible Smart Glove Technologies to Measure Joint Range of Motion.

Sensors (Basel) 2021 Feb 24;21(5). Epub 2021 Feb 24.

School of Computing, Engineering and Intelligent System, Ulster University Magee Campus, Northland Rd, BT48 7JL Londonderry, Ireland.

Capturi ng hand motions for hand function evaluations is essential in the medical field. For many allied health professionals, measuring joint range of motion (ROM) is an important skill. While the universal goniometer (UG) is the most used clinical tool for measuring joint ROM, developments in current sensor technology are providing clinicians with more measurement possibilities than ever. For rehabilitation and manual dexterity evaluations, different data gloves have been developed. However, the reliability and validity of sensor technologies when used within a smart device remain somewhat unclear. This study proposes a novel electronically controlled sensor monitoring system (ECSMS) to obtain the static and dynamic parameters of various sensor technologies for both data gloves and individual sensor evaluation. Similarly, the ECSMS was designed to closely mimic a human finger joint, to have total control over the joint, and to have an exceptionally high precision. In addition, the ECSMS device can closely mimic the movements of the finger from hyperextension to a maximum ROM beyond any person's finger joint. Due to the modular design, the ECSMS's sensor monitoring board is independent and extensible to include various technologies for examination. Additionally, by putting these sensory devices through multiple tests, the system accurately measures the characteristics of any rotary/linear sensor in and out of a glove. Moreover, the ECSMS tracks the movement of all types of sensors with respect to the angle values of finger joints. In order to demonstrate the effectiveness of sensory devices, the ECSMS was first validated against a recognised secondary device with an accuracy and resolution of 0.1°. Once validated, the system simultaneously determines real angles alongside the hand monitoring device or sensor. Due to its unique design, the system is independent of the gloves/sensors that were tested and can be used as a gold standard to realise more medical equipment/applications in the future. Consequently, this design greatly enhances testing measures within research contact and even non-contact systems. In conclusion, the ECSMS will benefit in the design of data glove technologies in the future because it provides crucial evidence of sensor characteristics. Similarly, this design greatly enhances the stability and maintainability of sensor assessments by eliminating unwanted errors. These findings provide ample evidence for clinicians to support the use of sensory devices that can calculate joint motion in place of goniometers.
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http://dx.doi.org/10.3390/s21051555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956630PMC
February 2021

Research Note: Evaluation of the incidence of white striping and underlying myopathic abnormalities affected by fast weight gain in commercially fed broiler chickens.

Poult Sci 2021 Apr 27;100(4):101020. Epub 2021 Jan 27.

Department of Animal Science, University of California Davis, Davis, California, USA. Electronic address:

Significant improvements in genetics, nutrition, and food efficiency have had a great impact on the rapid growth of broilers, notably with increases in muscle mass. However, with rapid growth, the broiler industry has been negatively impacted by the increased incidence of myopathies, including white striping. White striping affects the pectoralis major muscle of broilers, particularly the larger breasts of rapidly growing modern commercial broiler lines. In this study, we documented the growth process of commercial broiler chickens from hatching to market weight at 6 wk. Gross pathology and histopathology analyses were performed on pectoralis major muscle collected weekly from birds culled from 1 to 6 wk. The severity of both gross and histologic pathologies in the breast muscle increased over time. White striping was initially observed at week 2, with a rise in the incidence and severity through the sixth week. Mild histopathology was noted in week 2, characterized by macrophage infiltration and limited phagocytosis of the muscle. Muscle condition deteriorated with age and weight gain, with more prevalent macrophages, phagocytosis, and interstitial fibroblasts. By week 5 and 6, there was severe myopathy including regions of obliterated muscle tissue. Linear regression models show a positive correlation between white striping, gross pathology, and histopathology relative to weight and age.
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http://dx.doi.org/10.1016/j.psj.2021.101020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937744PMC
April 2021

Commentary: Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Deep Brain Stimulations for Obsessive Compulsive Disorder: Update of the 2014 Guidelines.

Neurosurgery 2021 Feb 27. Epub 2021 Feb 27.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.

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http://dx.doi.org/10.1093/neuros/nyab035DOI Listing
February 2021

The Wellness Quest: A health literacy and self-advocacy tool developed by youth for youth mental health.

Health Expect 2021 Feb 26. Epub 2021 Feb 26.

Centre for Addiction and Mental Health, Toronto, ON, Canada.

Background: Less than 20% of youth who experience mental health difficulties access and receive appropriate treatment. This is exacerbated by barriers such as stigma, confidentiality concerns and lack of mental health literacy. A youth team developed the Wellness Quest: a health literacy tool to enable help-seeking youth to advocate for themselves.

Objective: To evaluate the content, presentation and utility of the Wellness Quest tool among youth.

Participants: Participants aged 14 to 26.

Methods: A youth research team conducted five focus groups and one online survey to evaluate the Wellness Quest tool. Thematic analysis was used to analyse the qualitative data, and descriptive statistics were used to explore the survey results.

Main Results: Overall evaluations of the Wellness Quest were positive: participants felt it would be useful during their mental health help-seeking journey. Participants expressed the need for information about services for specific populations, such as Indigenous, immigrants, refugees and 2SLGBTQ + youth. They expressed that the tool should be available in complementary online and print versions.

Discussion: Improving mental health literacy may improve mental health by enabling youth and those who support them to recognize and respond to signs of distress and understanding where and how to get help. The Wellness Quest tool may equip youth with the knowledge to make informed decisions and advocate for their own mental health, thereby facilitating help-seeking among youth.

Patient Or Public Contribution: Youth as service users led all stages of the project, from designing and conducting the study and analysing the data to writing the manuscript.
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http://dx.doi.org/10.1111/hex.13214DOI Listing
February 2021

Evaluating the effectiveness of the Family Connections program for caregivers of youth with mental health challenges, part II: A qualitative analysis.

Health Expect 2021 Feb 24. Epub 2021 Feb 24.

Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Background: The Family Connections™ (FC) program is a 12-week support and skill-training program for caregivers of youth with mental health challenges. The intervention was originally developed with a focus on borderline personality disorder (BPD). It is important to understand the experiences of caregivers in such interventions, as well as its applicability beyond BPD, for the purposes of evaluation and ongoing program improvement.

Objective: To explore and analyse the experiences of caregivers of youth with diverse mental health challenges and who participated in FC.

Design: Semi-structured interviews with thirteen FC-participating caregivers of youth with mental health challenges.

Results: Thematic analysis uncovered three major themes regarding caregivers' experience with FC: (a) FC increased the caregivers' ability to manage their youth's mental health challenges; (b) participating in FC impacted their intra- and interpersonal spheres; and (c) improvements to the program were proposed. Following participation in FC, caregivers felt they learned a new approach to understanding themselves, their youth and mental health, and were better able to manage their youth's mental health challenges.

Discussion And Conclusion: FC is a promising intervention for caregivers of youth with mental health challenges, beyond the traditional BPD focus. The intervention has the potential to provide broad-based benefits for caregivers and should be considered for implementation and scale-up across youth- and caregiver-serving organizations. Potential areas of intervention flexibility and improvement are discussed.

Patient/public Contribution: Caregivers were involved in the program development and facilitation of FC. A person with lived experience was involved with the analysis.
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http://dx.doi.org/10.1111/hex.13220DOI Listing
February 2021

Remote Hemodynamic-Guided Therapy of Patients With Recurrent Heart Failure Following Cardiac Resynchronization Therapy.

J Am Heart Assoc 2021 Feb 25;10(5):e017619. Epub 2021 Feb 25.

The Ohio State University Columbus OH.

Background Patients with recurring heart failure (HF) following cardiac resynchronization therapy fare poorly. Their management is undecided. We tested remote hemodynamic-guided pharmacotherapy. Methods and Results We evaluated cardiac resynchronization therapy subjects included in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association Class III Heart Failure Patients) trial, which randomized patients with persistent New York Heart Association Class III symptoms and ≥1 HF hospitalization in the previous 12 months to remotely managed pulmonary artery (PA) pressure-guided management (treatment) or usual HF care (control). Diuretics and/or vasodilators were adjusted conventionally in control and included remote PA pressure information in treatment. Annualized HF hospitalization rates, changes in PA pressures over time (analyzed by area under the curve), changes in medications, and quality of life (Minnesota Living with Heart Failure Questionnaire scores) were assessed. Patients who had cardiac resynchronization therapy (n=190, median implant duration 755 days) at enrollment had poor hemodynamic function (cardiac index 2.00±0.59 L/min per m), high comorbidity burden (67% had secondary pulmonary hypertension, 61% had estimated glomerular filtration rate <60 mL/min per 1.73 m), and poor Minnesota Living with Heart Failure Questionnaire scores (57±24). During 18 months randomized follow-up, HF hospitalizations were 30% lower in treatment (n=91, 62 events, 0.46 events/patient-year) versus control patients (n=99, 93 events, 0.68 events/patient-year) (hazard ratio, 0.70; 95% CI, 0.51-0.96; =0.028). Treatment patients had more medication up-/down-titrations (847 versus 346 in control, <0.001), mean PA pressure reduction (area under the curve -413.2±123.5 versus 60.1±88.0 in control, =0.002), and quality of life improvement (Minnesota Living with Heart Failure Questionnaire decreased -13.5±23 versus -4.9±24.8 in control, =0.006). Conclusions Remote hemodynamic-guided adjustment of medical therapies decreased PA pressures and the burden of HF symptoms and hospitalizations in patients with recurring Class III HF and hospitalizations, beyond the effect of cardiac resynchronization therapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00531661.
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http://dx.doi.org/10.1161/JAHA.120.017619DOI Listing
February 2021

SARS-CoV-2 variants and convalescent plasma: reality, fallacies, and opportunities.

J Clin Invest 2021 04;131(7)

Departments of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA.

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http://dx.doi.org/10.1172/JCI148832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011895PMC
April 2021

Control of Podocyte and Glomerular Capillary Wall Structure and Elasticity by WNK1 Kinase.

Front Cell Dev Biol 2020 2;8:618898. Epub 2021 Feb 2.

Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, United States.

Cytoskeletal structure and its regulation are essential for maintenance of the differentiated state of specific types of cells and their adaptation to physiologic and pathophysiologic conditions. Renal glomerular capillaries, composed of podocytes, endothelial cells, and the glomerular basement membrane, have distinct structural and biophysical properties and are the site of injury in many glomerular diseases. Calcineurin inhibitors, immunosuppressant drugs used for organ transplantation and auto-immune diseases, can protect podocytes and glomerular capillaries from injury by preserving podocyte cytoskeletal structure. These drugs cause complications including hypertension and hyperkalemia which are mediated by WNK (With No Lysine) kinases as well as vasculopathy with glomerulopathy. WNK kinases and their target kinases oxidative stress-responsive kinase 1 (OSR1) and SPS1-related proline/alanine-rich kinase (SPAK) have fundamental roles in angiogenesis and are activated by calcineurin inhibitors, but the actions of these agents on kidney vasculature, and glomerular capillaries are not fully understood. We investigated WNK1 expression in cultured podocytes and isolated mouse glomerular capillaries to determine if WNK1 contributes to calcineurin inhibitor-induced preservation of podocyte and glomerular structure. WNK1 and OSR1/SPAK are expressed in podocytes, and in a pattern similar to podocyte synaptopodin in glomerular capillaries. Calcineurin inhibitors increased active OSR1/SPAK in glomerular capillaries, the Young's modulus (E) of glomeruli, and the F/G actin ratio, effects all blocked by WNK inhibition. In glomeruli, WNK inhibition caused reduced and irregular synaptopodin-staining, abnormal capillary and foot process structures, and increased deformability. In cultured podocytes, FK506 activated OSR1/SPAK, increased lamellipodia, accelerated cell migration, and promoted traction force. These actions of FK506 were reduced by depletion of WNK1. Collectively, these results demonstrate the importance of WNK1 in regulation of the podocyte actin cytoskeleton, biophysical properties of glomerular capillaries, and slit diaphragm structure, all of which are essential to normal kidney function.
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http://dx.doi.org/10.3389/fcell.2020.618898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884762PMC
February 2021

When more is more: redundant modifiers can facilitate visual search.

Cogn Res Princ Implic 2021 Feb 17;6(1):10. Epub 2021 Feb 17.

Department of Psychology, University of California, One Shields Ave, Davis, CA, 95616-5270, USA.

According to the Gricean Maxim of Quantity, speakers provide the amount of information listeners require to correctly interpret an utterance, and no more (Grice in Logic and conversation, 1975). However, speakers do tend to violate the Maxim of Quantity often, especially when the redundant information improves reference precision (Degen et al. in Psychol Rev 127(4):591-621, 2020). Redundant (non-contrastive) information may facilitate real-world search if it narrows the spatial scope under consideration, or improves target template specificity. The current study investigated whether non-contrastive modifiers that improve reference precision facilitate visual search in real-world scenes. In two visual search experiments, we compared search performance when perceptually relevant, but non-contrastive modifiers were included in the search instruction. Participants (N = 48, N = 48) searched for a unique target object following a search instruction that contained either no modifier, a location modifier (Experiment 1: on the top left, Experiment 2: on the shelf), or a color modifier (the black lamp). In Experiment 1 only, the target was located faster when the verbal instruction included either modifier, and there was an overall benefit of color modifiers in a combined analysis for scenes and conditions common to both experiments. The results suggest that violations of the Maxim of Quantity can facilitate search when the violations include task-relevant information that either augments the target template or constrains the search space, and when at least one modifier provides a highly reliable cue. Consistent with Degen et al. (2020), we conclude that listeners benefit from non-contrastive information that improves reference precision, and engage in rational reference comprehension. SIGNIFICANCE STATEMENT: This study investigated whether providing more information than someone needs to find an object in a photograph helps them to find that object more easily, even though it means they need to interpret a more complicated sentence. Before searching a scene, participants were either given information about where the object would be located in the scene, what color the object was, or were only told what object to search for. The results showed that providing additional information helped participants locate an object in an image more easily only when at least one piece of information communicated what part of the scene the object was in, which suggests that more information can be beneficial as long as that information is specific and helps the recipient achieve a goal. We conclude that people will pay attention to redundant information when it supports their task. In practice, our results suggest that instructions in other contexts (e.g., real-world navigation, using a smartphone app, prescription instructions, etc.) can benefit from the inclusion of what appears to be redundant information.
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http://dx.doi.org/10.1186/s41235-021-00275-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889780PMC
February 2021

'It reshaped how I will do research': A qualitative exploration of team members' experiences with youth and family engagement in a randomized controlled trial.

Health Expect 2021 Feb 15. Epub 2021 Feb 15.

Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Background: Engaging youth and family members as active partners in research and service design offers great promise in improving projects. In youth mental health, recent research has highlighted the value of youth and family engagement. However, research on the experience and impacts of engagement is sparse.

Objective: This study explores the project team's experience of youth and family engagement in the design and development of the YouthCan IMPACT randomized controlled trial and clinical service pathway design.

Design: Qualitative data collected using semi-structured interviews and a focus group as part of the YouthCan IMPACT clinical trial were analysed to understand the impacts of engagement. Twenty-eight team members were interviewed, including youth and family members. A qualitative content analysis was conducted, with a member checking process.

Results: Team members reported facilitators, barriers and impacts of youth and family engagement. Facilitators included a safe environment and strong procedures conducive to inclusion in co-design. Barriers included logistical, structural and institutional constraints. Overall, team members found youth and family engagement to be valuable and to positively impact the research and service design process.

Discussion And Conclusions: Youth and family engagement played a critical role in research and clinical service pathway design. The team found that their involvement improved the quality of the research and service pathway through sustained and multifaceted engagement. Facilitators and barriers to engagement may serve to guide future engagement initiatives. Future research should evaluate the long-term impact of early engagement and further focus on family engagement.

Patient/public Contribution: Youth and family members were engaged in the data analysis and interpretation process.
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http://dx.doi.org/10.1111/hex.13206DOI Listing
February 2021

Evaluating the effectiveness of the Family Connections program for caregivers of youth with mental health challenges, part I: A quantitative analysis.

Health Expect 2021 Feb 13. Epub 2021 Feb 13.

Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Introduction: Caregivers of youth with mental health (MH) challenges are often faced with complex problems in relation to caring for their youth. Family Connections™ (FC) is a 12-week skills training program for families of individuals with MH challenges, developed originally for Borderline Personality Disorder. Research is needed to examine the effectiveness of FC for caregivers of youth with diverse MH challenges.

Objective: To examine the effectiveness of FC for caregivers of youth with MH challenges.

Methods: A total of 94 caregivers of youth with MH challenges participated in FC, across three sites in Ontario, Canada. Assessments occurred at baseline, 6 weeks, 12 weeks and follow-up. Primary outcomes include the Burden Assessment Scale and The Stress Index for Parents of Adolescents. Secondary outcomes included the caregiver's report of child behaviour, affect, mastery, coping and grief. Linear mixed model analyses were conducted, where time and the time × site interaction were defined as the fixed effects.

Results: Statistically significant improvements over time were observed across outcome measures, including caregiver burden, grief, coping, and other measures. The time × site interaction was only significant for burden (P = .005).

Conclusion: This study demonstrates the effectiveness of FC for caregivers of youth with MH challenges. Future research should focus on differences across geographical sites and facilitation models.

Patient Or Public Contribution: Caregivers were involved in the facilitation of FC. A person with lived experience was involved in analysing the data, reporting the results, and drafting the manuscript.
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http://dx.doi.org/10.1111/hex.13205DOI Listing
February 2021

Predictive Modeling of Virus Inactivation by UV.

Environ Sci Technol 2021 03 12;55(5):3322-3332. Epub 2021 Feb 12.

Department of Civil & Environmental Engineering, University of Michigan, Ann Arbor, MI 48109, United States.

UV disinfection strategies are commonly applied to inactivate pathogenic viruses in water, food, air, and on surfaces. There is a need for methods that rapidly predict the kinetics of virus inactivation by UV, particularly for emerging and difficult-to-culture viruses. We conducted a systematic literature review of inactivation rate constants for a wide range of viruses. Using these data and virus characteristics, we developed and evaluated linear and nonlinear models for predicting inactivation rate constants. Multiple linear regressions performed best for predicting the inactivation kinetics of (+) ssRNA and dsDNA viruses, with cross-validated root mean squared relative prediction errors similar to those associated with experimental rate constants. We tested the models by predicting and measuring inactivation rate constants of a (+) ssRNA mouse coronavirus and a dsDNA marine bacteriophage; the predicted rate constants were within 7% and 71% of the experimental rate constants, respectively, indicating that the prediction was more accurate for the (+) ssRNA virus than the dsDNA virus. Finally, we applied our models to predict the UV rate constants of several viruses for which high-quality UV inactivation data are not available. Our models will be valuable for predicting inactivation kinetics of emerging or difficult-to-culture viruses.
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http://dx.doi.org/10.1021/acs.est.0c07814DOI Listing
March 2021

Natron glass beads reveal proto-Silk Road between the Mediterranean and China in the 1st millennium BCE.

Sci Rep 2021 Feb 11;11(1):3537. Epub 2021 Feb 11.

Xinjiang Institute of Cultural Relics and Archaeology, Urumqi, 830001, China.

Natron-based glass was a vital part of material culture in the Mediterranean and Europe for nearly two millennia, but natron glass found elsewhere on the Eurasian Continent has not received adequate discussion, despite its influence on ancient Asian glass. Here we present a new interpretation of natron glass finds from both the West and the East. After establishing the compositional types and technological sequence of Mediterranean natron glass (eighth-second century BCE) using trace elements, we report the analysis of a mid-1st millennium BCE glass bead from Xinjiang, China, which was likely made with Levantine raw glass, and identify common types of stratified eye beads in Eurasia based on a compositional and typological comparison. Combining these findings, we propose that a considerable number of Mediterranean natron glass products had arrived in East Asia at least by the fifth century BCE, which may have been a contributing factor in the development of native Chinese glass-making. The swift diffusion of natron glass across Eurasia in the 1st millennium BCE was likely facilitated by a three-stage process involving maritime and overland networks and multiple forms of trade and exchange, indicating a highly adaptable and increasingly efficient transcontinental connection along the 'Proto-Silk Road'.
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http://dx.doi.org/10.1038/s41598-021-82245-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878486PMC
February 2021

Antisense oligonucleotides and nucleic acids generate hypersensitive platelets.

Thromb Res 2021 Apr 18;200:64-71. Epub 2021 Jan 18.

Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, Medical University of Vienna, Vienna, Austria. Electronic address:

Introduction: Despite the great promise for therapies using antisense oligonucleotides (ASOs), their adverse effects, which include pro-inflammatory effects and thrombocytopenia, have limited their use. Previously, these effects have been linked to the phosphorothioate (PS) backbone necessary to prevent rapid ASO degradation in plasma. The main aim of this study was to assess the impact of the nucleic acid portion of an ASO-type drug on platelets and determine if it may contribute to thrombosis or thrombocytopenia.

Methods: Platelets were isolated from healthy donors and men with advanced prostate cancer. Effects of antisense oligonucleotides (ASO), oligonucleotides, gDNA, and microRNA on platelet activation and aggregation were evaluated. A mouse model of lung thrombosis was used to confirm the effects of PS-modified oligonucleotides in vivo.

Results: Platelet exposure to gDNA, miRNA, and oligonucleotides longer than 16-mer at a concentration above 8 mM resulted in the formation of hypersensitive platelets, characterized by an increased sensitivity to low-dose thrombin (0.1 nM) and increase in p-Selectin expression (6-8 fold greater than control; p < 0.001). The observed nucleic acid (NA) effects on platelets were toll-like receptor (TLR) -7 subfamily dependent. Injection of a p-Selectin inhibitor significantly (p = 0.02) reduced the formation of oligonucleotide-associated pulmonary microthrombosis in vivo.

Conclusion: Our results suggest that platelet exposure to nucleic acids independent of the presence of a PS modification leads to a generation of hypersensitive platelets and requires TLR-7 subfamily receptors. ASO studies conducted in cancer patients may benefit from testing the ASO effects on platelets ex vivo before initiation of patient treatment.
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http://dx.doi.org/10.1016/j.thromres.2021.01.006DOI Listing
April 2021