Search

Louise GH Goh,1 Satvinder S Dhaliwal,1 Timothy A Welborn,2 Peter L Thompson,2–4 Bruce R Maycock,1 Deborah A Kerr,1 Andy H Lee,1 Dean Bertolatti,1 Karin M Clark,1 Rakhshanda Naheed,1 Ranil Coorey,1 Phillip R Della5 1School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia; 2Sir Charles Gairdner Hospital, Nedlands, Perth, WA, Australia; 3School of Population Health, University of Western Australia, Perth, WA, Australia; 4Harry Perkins Institute for Medical Research, Perth, WA, Australia; 5School of Nursing and Midwifery, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia Purpose: Although elevated cardiovascular disease (CVD) risk factors are associated with a higher risk of developing heart conditions across all ethnic groups, variations exist between groups in the distribution and association of risk factors, and also risk levels. This study assessed the 10-year predicted risk in a multiethnic cohort of women and compared the differences in risk between Asian and Caucasian women. Methods: Information on demographics, medical conditions and treatment, smoking behavior, dietary behavior, and exercise patterns were collected. Physical measurements were also taken. The 10-year risk was calculated using the Framingham model, SCORE (Systematic COronary Risk Evaluation) risk chart for low risk and high risk regions, the general CVD, and simplified general CVD risk score models in 4,354 females aged 20–69 years with no heart disease, diabetes, or stroke at baseline from the third Australian Risk Factor Prevalence Study. Country of birth was used as a surrogate for ethnicity. Nonparametric statistics were used to compare risk levels between ethnic groups. Results: Asian women generally had lower risk of CVD when compared to Caucasian women. The 10-year predicted risk was, however, similar between Asian and Australian women, for some models. These findings were consistent with Australian CVD prevalence. Conclusion: In summary, ethnicity needs to be incorporated into CVD risk assessment. Australian standards used to quantify risk and treat women could be applied to Asians in the interim. The SCORE risk chart for low-risk regions and Framingham risk score model for incidence are recommended. The inclusion of other relevant risk variables such as obesity, poor diet/nutrition, and low levels of physical activity may improve risk estimation. Keywords: cardiovascular disease prevention, risk assessment, epidemiology, Asia, female

Captive breeding and reintroduction can be effective conservation tools, but the origin of founders for such programs is key for success. The red siskin Spinus cucullatus, a bird from northern South America, is Critically Endangered in Venezuela due to decades of trapping for the illegal wildlife trade. As a result, many red siskins are held in captivity worldwide, but several potential problems with captive birds make considering founders from the wild more desirable. A recently discovered population of red siskins in Guyana presents such an opportunity, but, due to its disjunct distribution from the main range, the possibility of genetic differentiation is a concern. We used a variety of standard and novel analyses of amplified fragment length polymorphism (AFLP) and mitochondrial (mtDNA) markers to evaluate genetic divergence of the Guyana (GU) population, using 5 individuals from GU and 13 captive birds of presumed Venezuelan (‘VE’) origin. All analyses of nuclear loci revealed 2 clusters separating GU from ‘VE’ individuals, with FST values varying from 0.15 to 0.24, depending on assumptions about individual relatedness. Furthermore, all 5 GU birds shared an mtDNA haplotype that differed by 2 or more substitutions (0.11%) from the 3 ‘VE’ haplotypes. The GU population thus appears to be differentiated from the ‘VE’ population in both nuclear and mtDNA. While further genetic evidence is needed, these data suggest that the GU population is not an optimal source of founders for recovery efforts in Venezuela, and should be treated as a separate elemental conservation unit until additional data are available.

OBJECTIVE: Breast-feeding is associated with better child development outcomes, but uncertainty remains primarily due to the close relationship between breast-feeding and socioeconomic status. This study assesses the issue in a low socioeconomic status sample where breast-feeding was close to universal. METHODS: Seven hundred eighty-four Chilean children were followed longitudinally from infancy. All but four were initially breastfed, 40% nursed beyond 12 months, and infant growth was normal. Child development was assessed at 5(1/2) years by a cognitive, language, and motor test battery. The duration of breast-feeding as the sole milk source was analyzed as a continuous variable, adjusting for a comprehensive set of background factors. RESULTS: The relationship between breast-feeding and most 5(1/2)-year developmental outcomes was nonlinear, with poorer outcome for periods of breast-feeding as the sole milk source for <2 months or >8 months--statistically significant for language, motor, and one comprehensive cognitive test, with a suggestive trend for IQ. CONCLUSIONS: The observed nonlinear relationships showed that breast-feeding as the sole milk source for <2 months or >8 months, compared with 2-8 months, was associated with poorer development in this sample. The latter finding requires replication in other samples where long breast-feeding is common and socioeconomic status is relatively homogeneous. [ABSTRACT FROM AUTHOR]

Understanding the changes in genetic variance which may occur as populations move from nature into captivity has been considered important when populations in captivity are used as models of wild ones. However, the inherent significance of these changes has not previously been appreciated in a conservation context: are the methods aimed at founding captive populations with gene diversity representative of natural populations likely also to capture representative quantitative genetic variation? Here, I investigate changes in heritability and a less traditional measure, evolvability, between nature and captivity for the large milkweed bug, Oncopeltus fasciatus, to address this question. Founders were collected from a 100-km transect across the north-eastern US, and five traits (wing colour, pronotum colour, wing length, early fecundity and later fecundity) were recorded for founders and for their offspring during two generations in captivity. Analyses reveal significant heritable variation for some life history and morphological traits in both environments, with comparable absolute levels of evolvability across all traits (0-30%). Randomization tests show that while changes in heritability and total phenotypic variance were highly variable, additive genetic variance and evolvability remained stable across the environmental transition in the three morphological traits (changing 1-2% or less), while they declined significantly in the two life-history traits (5-8%). Although it is unclear whether the declines were due to selection or gene-by-environment interactions (or both), such declines do not appear inevitable: captive populations with small numbers of founders may contain substantial amounts of the evolvability found in nature, at least for some traits.Heredity (2004) 93, 51-61. doi:10.1038/sj.hdy.6800479 [ABSTRACT FROM AUTHOR]

The advent of wearable sensing platforms capable of continuously monitoring physiological parameters indicative of health status have resulted in a paradigm shift for clinical medicine. The accessibility and adaptability of such portable, unobtrusive devices enables proactive, personalized care based on real-time physiological insights. While wearable sensing platforms exhibit powerful capabilities for continuously monitoring physiological parameters, device fabrication often requires specialized facilities and technical expertise, restricting deployment opportunities and innovation potential. The recent emergence of rapid prototyping approaches to sensor fabrication, such as laser-induced graphene (LIG), provides a pathway for circumventing these barriers through low-cost, scalable fabrication. However, inherent limitations in laser processing restrict the spatial resolution of LIG-based flexible electronic devices to the minimum laser spot size. For a CO 2 laser-a commonly reported laser for device production-this corresponds to a feature size of ∼120 μm. Here, we demonstrate a facile, low-cost stencil-masking technique to reduce the minimum resolvable feature size of a LIG-based device from 120 ± 20 μm to 45 ± 3 μm when fabricated by CO 2 laser. Characterization of device performance reveals this stencil-masked LIG (s-LIG) method yields a concomitant improvement in electrical properties, which we hypothesize is the result of changes in macrostructure of the patterned LIG. We showcase the performance of this fabrication method via production of common sensors including temperature and multi-electrode electrochemical sensors. We fabricate fine-line microarray electrodes not typically achievable via native CO 2 laser processing, demonstrating the potential of the expanded design capabilities. Comparing microarray sensors made with and without the stencil to traditional macro LIG electrodes reveals the s-LIG sensors have significantly reduced capacitance for similar electroactive surface areas. Beyond improving sensor performance, the increased resolution enabled by this metal stencil technique expands capabilities for scalable fabrication of high-performance wearable sensors in low-resource settings without reliance on traditional fabrication pathways., Competing Interests: Declaration of competing interest The authors declare the following competing financial interest(s): T.R.R. is an inventor on patents and patent applications related to epidermal microfluidics and has a consulting and advisory relationship with Epicore Biosystems., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The purpose of this qualitative study was to evaluate the effects of curricular changes made to foster graduate students' understanding of how they can be catalysts of change. For more than a decade, the concept of the citizen nurse has been woven into coursework in nursing education, thus indicating an evaluation process was needed., Method: Ten oral history interviews were completed with current students or alumni. Data were analyzed for codes, allowing the final themes to emerge., Results: Two main themes emerged. Students reported (1) having a new understanding of what it means to be a nurse and (2) feeling more prepared to take action., Conclusion: Students felt more prepared to lead change as the result of curricular changes that supported their ongoing education. [ J Nurs Educ . 2024;63(9):626-629.] .

Background: Evidence-based practice is at the forefront of providing quality patient care by using the best available evidence and clinical expertise, while also considering patient needs and preferences for clinical decisions. However, evidence-based practice may not be consistently used even when the evidence supports the therapy. The purpose of this study was to assess the factors associated with the use of evidence-based practice among respiratory therapy faculty teaching in a large community college system and post-professional students enrolled in a university-based, respiratory therapy baccalaureate degree-advancement program., Methods: A non-probability, descriptive survey research design was used to develop and administer an online questionnaire., Results: All respondents demonstrated sufficient knowledge and understanding of introductory concepts of evidence-based practice but knowledge of specific components of the evidence-based practice process was not as strong. Self-efficacy in knowledge and the use of evidence-based practice among faculty and degree-advancement students varied. Faculty and students rated their self-efficacy high in assessing patients' needs, values, and treatment preferences but ratings were lower for using the PICO (patient/population/problem, intervention, comparison, outcome) technique and interpreting common statistical tests. Students viewed their previous evidence-based practice learning experiences more favorably compared with faculty ( P = .008). Faculty and students searched and read the research literature more often compared with critically appraising and using the research literature. Logistic regression analysis indicated no statistically significant relationship of knowledge, self-efficacy, and learning experiences to the use of evidence-based practice among respiratory therapy students, Χ 2 (4, N = 54) = 7.73; P = .10., Conclusions: Analysis of the results suggested that respiratory therapy faculty and students were knowledgeable and confident with regard to evidence-based practice but their use of evidence-based practice in clinical decisions was limited. Although the evidence-based practice knowledge, self-efficacy, and learning experiences had minimal influence on the use of evidence-based practice, the results of the study provide a foundation for future research., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Shortwave infrared (SWIR, 1000-1700 nm) and extended SWIR (ESWIR, 1700-2700 nm) absorbing materials are valuable for applications including fluorescence based biological imaging, photodetectors, and light emitting diodes. Currently, ESWIR absorbing materials are largely dominated by inorganic semiconductors which are often costly both in raw materials and manufacturing processes used to produce them. The development of ESWIR absorbing organic molecules is thus of interest due to the tunability, solution processability, and low cost of organic materials compared to their inorganic counterparts. Herein, through the combination of heterocyclic indolizine donors and an antiaromatic fluorene core, a series of organic chromophores with absorption maxima ranging from 1470-2088 nm (0.84-0.59 eV) and absorption onsets ranging from 1693-2596 nm (0.73-0.48 eV) are designed and synthesized. The photophysical and electrochemical properties of these chromophores, referred to as FluIndz herein, are described via absorption spectroscopy in 17 solvents, cyclic voltammetry, solution photostability, and transient absorption spectroscopy. Molecular orbital energies, predicted electronic transitions, and antiaromaticity are compared to higher energy absorbing chromophores using density functional theory. The presence of thermally accessible diradical states is demonstrated using density functional theory and EPR spectroscopy, while XRD crystallography confirms structural connectivity and existence as a single molecule. Overall, the FluIndz chromophore scaffold exhibits a rational means to access organic chromophores with extremely narrow optical gaps., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Chronic kidney disease (CKD) coexists in up to 50% of heart failure (HF) patients, affecting both those with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF). Although the efficacy of several guideline-directed medical therapies (GDMT) has been well established, the treatment recommendations are similar for those patients with HF with and without CKD. We aimed to investigate the efficacy of GDMT in patients with HF with versus those without CKD., Method: This systematic review and meta-analysis included randomised controlled trials that compared the efficacy of GDMT (angiotensin-converting enzyme inhibitor [ACE-I], beta blocker, sodium-glucose cotransporter-2 inhibitor, mineralocorticoid receptor antagonist, angiotensin receptor-neprilysin inhibitor) in patients with HF with and without CKD. The primary outcome was the composite of cardiovascular death and HF hospitalisation. Risk ratios (RR) were pooled using random-effects meta-analysis., Results: A total of 19 trials (15 trials in HFrEF and four trials in HFpEF) enrolling 63,677 (38% had CKD) participants were included. Among HFrEF patients, GDMT reduced the primary endpoint in those with CKD (RR 0.77, 95% confidence interval [CI] 0.72-0.82) and without CKD (RR 0.79, 95% CI 0.74-0.84). Among HFpEF patients, the pooled summary RR for GDMT reducing the primary endpoint was 0.82 (95% CI 0.74-0.91) among those with CKD and 0.88 (95% CI 0.77-0.99) among those without CKD. There was no significant difference in the efficacy of GDMT in head-to-head comparisons between those with and without CKD in HFrEF (ratio of RR 0.97, 95% CI 0.88-1.06) and HFpEF (ratio of RR 0.94, 95% CI 0.80-1.11)., Conclusions: Among patients with HF, GDMT had a consistent effect in reducing adverse cardiovascular events in those with and without CKD. Future studies should investigate the best strategy to ensure patients with HF with CKD receive and tolerate GDMT when indicated., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Premise: Intraspecific variation may play a key role in shaping the relationships between plants and their interactions with soil microbial communities. The soil microbes of individual plants can generate intraspecific variation in the responsiveness of the plant offspring, yet have been much less studied. To address this need, we explored how the relatedness of seedlings from established clones of Solidago altissima altered the plant-soil interactions of the seedlings., Methods: Seedlings of known parentage were generated from a series of 24 clones grown in a common garden. Seedlings from these crosses were inoculated with soils from maternal, paternal, or unrelated clones and their performance compared to sterilized control inocula., Results: We found that soil inocula influenced by S. altissima clones had an overall negative effect on seedling biomass. Furthermore, seedlings inoculated with maternal or paternal soils tended to experience larger negative effects than seedlings inoculated with unrelated soils. However, there was much variation among individual crosses, with not all responding to relatedness., Conclusions: Our data argue that genetic relatedness to the plant from which the soil microbial inoculum was obtained may cause differential impacts on establishing seedlings, encouraging the regeneration of non-kin adjacent to established clones. Such intraspecific variation represents a potentially important source of heterogeneity in plant-soil microbe interactions with implications for maintaining population genetic diversity., (© 2024 Botanical Society of America.)

While CD4 + T cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of "natural" hosts such as sooty mangabeys does not cause CD4 + depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T cell activation abolishes CARD8 function and increases permissiveness to infection. In humanized mice reconstituted with CARD8-deficient cells, CD4 + depletion is delayed despite high viremia. Finally, we discovered loss-of-function mutations in CARD8 from "natural hosts," which may explain the peculiarly non-pathogenic nature of these infections. Our study suggests that CARD8 drives CD4 + T cell depletion during pathogenic HIV/SIV infections., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Metabolic dysfunction is an important factor in the pathogenesis of motor neuron disease, but its prevalence and association with survival in this disorder is unknown. We hypothesized that patients with motor neuron disease would show a higher prevalence of metabolic syndrome compared to the general New Zealand population, and that metabolic syndrome would be associated with worsened survival. We undertook a retrospective analysis in 109 motor neuron disease patients diagnosed and treated at Waikato Hospital from 2013 to 2020. Demographic, clinical, and laboratory data were collected. Survival was defined as the date of initial symptom onset to the date of death. Of 104 eligible patients, 34 patients (33%) had metabolic syndrome (33% of Europeans, 46% of Māori). Mean survival in motor neuron disease patients with metabolic syndrome was significantly reduced compared to patients without metabolic syndrome (38 vs. 61 months, P = 0.044), with a 5-year survival rate of 21% for the former and 38% for the latter (P = 0.012). Compared with the general New Zealand population, metabolic syndrome is highly prevalent amongst motor neuron disease patients in the Waikato region and it is associated with worsened survival. Metabolic dysfunction may be a key factor underlying the pathogenesis of motor neuron disease., (© 2023. The Author(s).)

Recent advances in skin-interfaced wearable sweat sensors enable the noninvasive, real-time monitoring of biochemical signals associated with health and wellness. These wearable platforms leverage microfluidic channels, biochemical sensors, and flexible electronics to enable the continuous analysis of sweat-based biomarkers such as electrolytes, metabolites, and hormones. As this field continues to mature, the potential of low-cost, continuous personalized health monitoring enabled by such wearable sensors holds significant promise for addressing some of the formidable obstacles to delivering comprehensive medical care in under-resourced settings. This Perspective highlights the transformative potential of wearable sweat sensing for providing equitable access to cutting-edge healthcare diagnostics, especially in remote or geographically isolated areas. It examines the current understanding of sweat composition as well as recent innovations in microfluidic device architectures and sensing strategies by showcasing emerging applications and opportunities for innovation. It concludes with a discussion on expanding the utility of wearable sweat sensors for clinically relevant health applications and opportunities for enabling equitable access to innovation to address existing health disparities.

HIV-1 usually utilizes CCR5 as its coreceptor and rarely switches to a CXCR4-tropic virus until the late stage of infection. CCR5+CD4+ T cells are the major virus-producing cells in viremic individuals as well as SIV-infected nonhuman primates. The differentiation of CCR5+CD4+ T cells is associated with the availability of IL-15, which increases during acute HIV-1 infection. Here, we report that CCR5 was expressed by CD4+ T cells exhibiting effector or effector memory phenotypes with high expression levels of the IL-2/IL-15 receptor common β and γ chains. IL-15, but not IL-7, improved the survival of CCR5+CD4+ T cells, drove their expansion, and facilitated HIV-1 infection in vitro and in humanized mice. Our study suggests that IL-15 plays confounding roles in HIV-1 infection, and future studies on the IL-15-based boosting of anti-HIV-1 immunity should carefully examine the potential effects on the expansion of HIV-1 reservoirs in CCR5+CD4+ T cells.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) induce pyroptosis of HIV-1-infected CD4 + T cells through induction of intracellular HIV-1 protease activity, which activates the CARD8 inflammasome. Because high concentrations of NNRTIs are required for efficient elimination of HIV-1-infected cells, it is important to elucidate ways to sensitize the CARD8 inflammasome to NNRTI-induced activation. We show that this sensitization can be achieved through chemical inhibition of the CARD8 negative regulator DPP9. The DPP9 inhibitor Val-boroPro (VbP) can kill HIV-1-infected cells without the presence of NNRTIs and act synergistically with NNRTIs to promote clearance of HIV-1-infected cells in vitro and in humanized mice. More importantly, VbP is able to enhance clearance of residual HIV-1 in CD4 + T cells isolated from people living with HIV (PLWH). We also show that VbP can partially overcome NNRTI resistance. This offers a promising strategy for enhancing NNRTI efficacy in the elimination of HIV-1 reservoirs in PLWH., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The pattern recognition receptor CARD8 is an inflammasome sensor for intracellular HIV-1 protease activity. Previously, the only method for studying the CARD8 inflammasome has been through utilizing DPP8/DPP9 inhibitors including Val-boroPro (VbP) to modestly and nonspecifically activate the CARD8 inflammasome. The identification of HIV-1 protease as a target for sensing by CARD8 has opened the door for a new method of studying the underlying mechanism of CARD8 inflammasome activation. Additionally, triggering the CARD8 inflammasome offers a promising strategy for reducing HIV-1 latent reservoirs. Here we describe the methods to study CARD8 sensing of HIV-1 protease activity through non-nucleoside reverse transcriptase inhibitor (NNRTI)-mediated pyroptosis of HIV-1-infected immune cells and through an HIV and CARD8 co-transfection model., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The biggest challenge to immune control of HIV infection is the rapid within-host viral evolution, which allows selection of viral variants that escape from T cell and antibody recognition. Thus, it is impossible to clear HIV infection without targeting "immutable" components of the virus. Unlike the adaptive immune system that recognizes cognate epitopes, the CARD8 inflammasome senses the essential enzymatic activity of the HIV-1 protease, which is immutable for the virus. Hence, all subtypes of HIV clinical isolates can be recognized by CARD8. In HIV-infected cells, the viral protease is expressed as a subunit of the viral Gag-Pol polyprotein and remains functionally inactive prior to viral budding. A class of anti-HIV drugs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs), can promote Gag-pol dimerization and subsequent premature intracellular activation of the viral protease. NNRTI treatment triggers CARD8 inflammasome activation, which leads to pyroptosis of HIV-infected CD4 + T cells and macrophages. Targeting the CARD8 inflammasome can be a potent and broadly effective strategy for HIV eradication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic focused attention on a pressing need for fast, accurate, and low-cost diagnostic tests. This work presents an electrochemical capillary driven immunoassay (eCaDI) developed to detect SARS-CoV-2 nucleocapsid (N) protein. The low-cost flow device is made of polyethylene terephthalate (PET) and adhesive films. Upon addition of a sample, reagents and washes are sequentially delivered to an integrated screen-printed carbon electrode for detection, thus automating a full sandwich immunoassay with a single end-user step. The modified electrodes are sensitive and selective for SARS-CoV-2 N protein and stable for over 7 weeks. The eCaDI was tested with influenza A and Sindbis virus and proved to be selective. The eCaDI was also successfully applied to detect nine different SARS-CoV-2 variants, including Omicron., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: This study evaluated nursing students' learning at a nurse-led, faculty-organized, drop-in health care center that provided basic care to marginalized communities. Nursing students have engaged in practicum and coursework at this site for more than 30 years; thus, a review of learning outcomes was needed., Method: Using grounded theory as outlined by Strauss and Corbin, data were collected and then analyzed for patterns and themes to inform the research purpose., Results: Four main themes were identified from the data analysis regarding what students learned during their practicum at the community health care center. The themes included: connecting on a human scale, using self-reflection, building relationships with marginalized individuals, and developing skills to make needed changes., Conclusion: The findings supported the continuation of this educational opportunity to provide learning experiences that addressed health inequities and social determinants of health for nursing students. [ J Nurs Educ . 2022;61(9):525-527.] .

Huntington's disease (HD) is characterized by defective oligodendroglial differentiation and white matter disease. Here, we investigate the role of oligodendrocyte progenitor cell (OPC) dysfunction in adult myelin maintenance in HD. We first note a progressive, age-related loss of myelin in both R6/2 and zQ175 HD mice compared with wild-type controls. Adult R6/2 mice then manifest a significant delay in remyelination following cuprizone demyelination. RNA-sequencing and proteomic analysis of callosal white matter and OPCs isolated from both R6/2 and zQ175 mice reveals a systematic downregulation of genes associated with oligodendrocyte differentiation and myelinogenesis. Gene co-expression and network analysis predicts repressed Tcf7l2 signaling as a major driver of this expression pattern. In vivo Tcf7l2 overexpression restores both myelin gene expression and remyelination in demyelinated R6/2 mice. These data causally link impaired TCF7L2-dependent transcription to the poor development and homeostatic retention of myelin in HD and provide a mechanism for its therapeutic restoration., Competing Interests: Declaration of interests S.A.G. is a part-time employee and stockholder of Sana Biotechnology, a cell therapy company, and his lab receives sponsored research support from Sana. S.A.G. is also a co-founder and adviser to CNS2 Therapeutics, another cell therapy company. None of the work described in this paper overlaps with his work with those companies. D.C.-M. is also a consultant to Sana., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The COVID-19 pandemic increased economic, social, and health stressors for families, yet its impacts on families of youth with chronic conditions, such as type 1 diabetes (T1D), are not well understood. Self-regulation (SR)-or the capacities to control emotions, cognition, and behavior in response to challenge-is known to support T1D management and coping in the face of stress. Strong SR may have protected youth with T1D from the impacts of pandemic-related stressors. This study compared youth and parent emotional functioning and T1D management before and after the pandemic's onset in relation to family pandemic-related stress and youth SR., Methods: Parents of youth with T1D (N = 88) and a subset of these youth (N = 43; Mean age 15.3 years [SD 2.2]) completed surveys regarding SR, stress, emotional functioning, and T1D-related functioning prior to and after March 2020. Outcomes were compared using mixed effects models adjusting for covariates. Family pandemic-related stress experiences and youth SR were tested as moderators of change., Results: Parents' responsibility for T1D management increased across pandemic onset and their diabetes-related distress decreased. Family pandemic-related stress was associated with decreased emotional functioning over time. Youth SR, particularly emotional and behavioral aspects, predicted better emotional and T1D-related functioning., Discussion: While youth with T1D whose families experienced higher pandemic-related stress had poorer adjustment, strong emotional and behavioral SR appeared to protect against worsening youth mood and adherence across pandemic onset. Both social-contextual and individual factors are important to consider when working with families managing T1D., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Point-of-care (POC) methods currently available for detecting SARS-CoV-2 infections still lack accuracy. Here, we report the development of a highly sensitive electrochemical immunoassay capable of quantitatively detecting the presence of the SARS-CoV-2 virus in patient nasopharyngeal samples using stencil-printed carbon electrodes (SPCEs) functionalized with capture antibodies targeting the SARS-CoV-2 nucleocapsid protein (N protein). Samples are added to the electrode surface, followed by horseradish peroxidase (HRP)-conjugated detection antibodies also targeting the SARS-CoV-2 N protein. The concentration of the virus in samples is quantified using chronoamperometry in the presence of 3,3'5,5'-tetramethylbenzidine. Limits of detection equivalent to less than 50 plaque forming units/mL (PFU/mL) were determined with virus sample volumes of 20 μL. No cross-reactivity was detected with the influenza virus and other coronavirus N proteins. Patient nasopharyngeal samples were tested as part of a proof-of-concept clinical study where samples were also tested using the gold-standard real-time quantitative polymerase chain reaction (RT-qPCR) method. Preliminary results from a data set of 22 samples demonstrated a clinical specificity of 100% ( n = 9 negative samples according to RT-qPCR) and a clinical sensitivity of 70% for samples with RT-PCR cycle threshold (Ct) values under 30 ( n = 10) and 100% for samples with Ct values under 25 ( n = 5), which complies with the World Health Organization (WHO) criteria for POC COVID-19 diagnostic tests. Our functionalized SPCEs were also validated against standard plaque assays, and very good agreement was found between both methods ( R 2 = 0.9993, n = 6), suggesting that our assay could be used to assess patient infectivity. The assay currently takes 70 min from sampling to results.

Background: Cognitive impairment and neuropsychiatric symptoms are frequently reported in Relapsing-Remitting Multiple Sclerosis (RRMS). Natalizumab (NTZ) is usually administered on a 4-weekly Standard Interval Dosing (SID) schedule. However, Extended Interval Dosing (EID) at 6-8 weekly intervals has been proven non-inferior regarding relapse risk, with a lower risk of Progressive Multifocal Leukoencephalopathy (PML). The impact of EID NTZ on neuropsychological deficits in RRMS has not been studied. Objective: To determine if EID NTZ demonstrates an improvement in neuropsychological parameters in RRMS patients. Method: We performed a retrospective, observational analysis of 34 RRMS patients treated between August 2015-2017. Patients underwent baseline neuropsychological testing before commencing EID NTZ. A second evaluation was performed, on average 28 months after commencing treatment. Results: Z scores at the initial assessment showed baseline cognitive impairment in multiple domains. 14/20 Z-scores showed an improvement post-NTZ and 5/14 reached statistical significance; namely Trails A (visual attention/processing speed), Line-orientation (visual-spatial), Picture-naming (word finding), Digital-Span (attention, executive function and memory) and Story-recall (memory). The Hospital Anxiety and Depression Scale (HADS) data remained unchanged. Correlation matrix showed no association between HADS scores, the time between assessments and the changes in Z scores. Conclusion: This data suggests the efficacy of EID NTZ in improving cognitive impairment in RRMS. A prospective observational study is warranted., (© The Author(s), 2022.)

Despite advances in antimicrobial therapy and even the advent of some effective vaccines, Pseudomonas aeruginosa (P. aeruginosa) remains a significant cause of infectious disease, primarily due to antibiotic resistance. Although P. aeruginosa is commonly treatable with readily available therapeutics, these therapies are not always efficacious, particularly for certain classes of patients (e.g., cystic fibrosis (CF)) and for drug-resistant strains. Multi-drug resistant P. aeruginosa infections are listed on both the CDC's and WHO's list of serious worldwide threats. This increasing emergence of drug resistance and prevalence of P. aeruginosa highlights the need to identify new therapeutic strategies. Combinations of monoclonal antibodies against different targets and epitopes have demonstrated synergistic efficacy with each other as well as in combination with antimicrobial agents typically used to treat these infections. Such a strategy has reduced the ability of infectious agents to develop resistance. This manuscript details the development of potential therapeutic targets for polyclonal antibody therapies to combat the emergence of multidrug-resistant P. aeruginosa infections. In particular, potential drug targets for combinational immunotherapy against P. aeruginosa are identified to combat current and future drug resistance.

HIV-1 has high mutation rates and exists as mutant swarms within the host. Rapid evolution of HIV-1 allows the virus to outpace the host immune system, leading to viral persistence. Approaches to targeting immutable components are needed to clear HIV-1 infection. Here, we report that the caspase recruitment domain-containing protein 8 (CARD8) inflammasome senses HIV-1 protease activity. HIV-1 can evade CARD8 sensing because its protease remains inactive in infected cells before viral budding. Premature intracellular activation of the viral protease triggered CARD8 inflammasome-mediated pyroptosis of HIV-1-infected cells. This strategy led to the clearance of latent HIV-1 in patient CD4 + T cells after viral reactivation. Thus, our study identifies CARD8 as an inflammasome sensor of HIV-1, which holds promise as a strategy for the clearance of persistent HIV-1 infection., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Brain energy metabolism is impaired in Alzheimer's disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients., Methods: We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects., Results: We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild., Conclusions: This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia., Trial Registration: This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.

Background/objectives: The contribution of iron status at birth to iron status in infancy is not known. We used a physiologic framework to evaluate how iron status at birth related to iron status at 9 months, taking iron needs and sources into account., Subjects/methods: In a longitudinal birth cohort in China, iron status measures in cord blood and venous blood in infancy (9 months) and clinical data were prospectively collected in 545 healthy term maternal-infant dyads. We used structural equation modeling (SEM) to create a 9-month iron composite and to assess direct and indirect contributions of multiple influences on 9-month iron status. Logistic regression was used to calculate odds ratios for iron deficiency (ID), iron deficiency anemia (IDA), and anemia., Results: Approximately 15% (78/523) of infants were born with cord SF <75 µg/l, suggesting fetal-neonatal ID. At 9 months, 34.8% (186/535) and 19.6% (105/535) of infants had ID and IDA, respectively. The following factors were independently associated with poorer 9-month iron status: higher cord zinc protoporphyrin/heme (ZPP/H) (adjusted estimate -0.18, P < 0.001) and serum transferrin receptor (sTfR) (-0.11, P = 0.004), lower cord hemoglobin (Hb) (0.13, P = 0.004), lower birth weight (0.15, P < 0.001), male sex (0.10, P = 0.013), older age at testing (-0.26, P < 0.001), higher 9-month weight (-0.12, P = 0.006) and breastfeeding (0.38, P < 0.001). Breastfeeding at 9 months showed the strongest association, adjusting for all other factors. Compared to formula-fed infants, the odds of IDA were 19.1 (95% CI: 6.92, 52.49, P < 0.001) and 3.6 (95% CI: 1.04, 12.50, P = 0.043) times higher in breastfed and mixed-fed infants, respectively., Conclusions: Indicators of iron status at birth, postnatal iron needs, and iron sources independently related to iron status at 9 months. Sex was an additional factor. Public health policies to identify and protect infants at increased risk of ID should be prioritized.

Objectives: To determine which combinations of type 2 diabetes (T2D) and multiple chronic conditions (MCC) contribute to total spending and differences in spending between groups based on sex, race/ethnicity, and rural residency., Study Design: Retrospective cohort study using 2012 Medicare claims data from beneficiaries in Michigan with T2D., Methods: Zero-inflated Poisson regression models to estimate relationships of demographic characteristics and MCC combinations on hospital outpatient, acute inpatient, skilled nursing, hospice, and Part D drug spending., Results: Across most MCC combinations, there are lower odds of no spending, with a concurrent increase in the expected mean of actual spending when payments are made, except for hospital outpatient costs. For hospital outpatient services, we observed lower spending across all MCC combinations. When controlling for MCC, we generally found that compared with White beneficiaries, Black, Asian/Pacific Islander, and Hispanic beneficiaries experience increased odds of no spending, but when payments were made, payments generally increased. American Indian/Alaska Native beneficiaries are the exception; they experience decreased odds of no payments for hospital outpatient and acute inpatient services, with a concurrent decrease in mean expected payments., Conclusions: When considering a range of MCC combinations, we observed differences in total payments between racial/ethnic minority groups and White beneficiaries. Our results highlight the ongoing need to make changes in the health care system to make the system more accessible to racial/ethnic minority groups.

While thermal treatment of paper can lead to the formation of aromatic structures via hydrothermal treatment (low temperature) or pyrolysis (high temperature), neither of these approaches allow patterning the substrates. Somewhere in between these two extremes, a handful of research groups have used CO2 lasers to pattern paper and induce carbonization. However, none of the previously reported papers have focused on the possibility to form fluorescent derivatives via laser-thermal engraving. Exploring this possibility, this article describes the possibility of using a CO2 laser engraver to selectively treat paper, resulting in the formation of fluorescent compounds, similar to those present on the surface of carbon dots. To determine the most relevant variables controlling this process, 3 MM chromatography paper was treated using a standard 30 W CO2 laser engraver. Under selected experimental conditions, a blue fluorescent pattern was observed when the substrate was irradiated with UV light (365 nm). The effect of various experimental conditions (engraving speed, engraving power, and number of engraving steps) was investigated to maximize the fluorescence intensity. Through a comprehensive characterization effort, it was determined that 5-(hydroxymethyl)furfural and a handful of related compounds were formed (varying in amount) under all selected experimental conditions. To illustrate the potential advantages of this strategy, that could complement those applications traditionally developed from carbon dots (sensors, currency marking, etc.), a redox-based optical sensor for sodium hypochlorite was developed.

The quest for simple ligands that enable multi-electron metal-ligand redox chemistry is driven by a desire to replace noble metals in catalysis and to discover novel chemical reactivity. The vast majority of simple ligand systems display electrochemical potentials impractical for catalytic cycles, illustrating the importance of creating new strategies towards energetically aligned ligand frontier and transition metal d orbitals. We herein demonstrate the ability to chemically control the redox-activity of the ubiquitous acetylacetonate (acac) ligand. By employing the ligand field of high-spin Cr(ii) as a switch, we were able to chemically tailor the occurrence of metal-ligand redox events via simple coordination or decoordination of the labile auxiliary ligands. The mechanism of ligand field actuation can be viewed as a destabilization of the d z 2 orbital relative to the π* LUMO of acac, which proffers a generalizable strategy to synthetically engineer redox-activity with seemingly redox-inactive ligands., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Self-regulation (SR), or the capacity to control one's thoughts, emotions, and behaviors in order to achieve a desired goal, shapes health outcomes through many pathways, including supporting adherence to medical treatment regimens. Type 1 Diabetes (T1D) is one specific condition that requires SR to ensure adherence to daily treatment regimens that can be arduous and effortful (e.g., monitoring blood glucose). Adolescents, in particular, have poor adherence to T1D treatment regimens, yet it is essential that they assume increased responsibility for managing their T1D as they approach young adulthood. Adolescence is also a time of rapid changes in SR capacity and thus a compelling period for intervention. Promoting SR among adolescents with T1D may thus be a novel method to improve treatment regimen adherence. The current study tests a behavioral intervention to enhance SR among adolescents with T1D. SR and T1D medical regimen adherence will be examined as primary and secondary outcomes, respectively., Methods: We will use a randomized control trial design to test the impact of a behavioral intervention on three SR targets: Executive Functioning (EF), Emotion Regulation (ER), and Future Orientation (FO); and T1D medical regimen adherence. Adolescents with T1D (n = 94) will be recruited from pediatric endocrinology clinics and randomly assigned to treatment or control group. The behavioral intervention consists of working memory training (to enhance EF), biofeedback and relaxation training (to enhance ER), and episodic future thinking training (to enhance FO) across an 8-week period. SR and treatment regimen adherence will be assessed at pre- and post-test using multiple methods (behavioral tasks, diabetes device downloads, self- and parent-report). We will use an intent-to-treat framework using generalized linear mixed models to test our hypotheses that: 1) the treatment group will demonstrate greater improvements in SR than the control group, and 2) the treatment group will demonstrate better treatment regimen adherence outcomes than the control group., Discussion: If successful, SR-focused behavioral interventions could improve health outcomes among adolescents with T1D and have transdiagnostic implications across multiple chronic conditions requiring treatment regimen adherence., Trial Registration: ClinicalTrials.gov: NCT03688919; registered September 28, 2018.

β-Diketonates, such as acetylacetonate, are amongst the most common bidentate ligands towards elements across the entire periodic table and are considered wholly redox-inactive in their complexes. Herein we show that complexation of 1,1,1,5,5,5-hexafluoroacetylacetonate (hfac - ) to Cr II spontaneously affords Cr III and a reduced β-diketonate radical ligand scaffold, as evidenced by crystallographic analysis, magnetic measurements, optical spectroscopy, reactivity studies, and DFT calculations. The possibility of harnessing β-diketonates as electron reservoirs opens up possibilities for new metal-ligand concerted reactivity in the ubiquitous β-diketonate coordination chemistry., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Correction for 'Electrochemical paper-based devices: sensing approaches and progress toward practical applications' by Eka Noviana et al., Lab Chip, 2019, DOI: .

Paper-based sensors offer an affordable yet powerful platform for field and point-of-care (POC) testing due to their self-pumping ability and utility for many different analytical measurements. When combined with electrochemical detection using small and portable electronics, sensitivity and selectivity of the paper devices can be improved over naked eye detection without sacrificing portability. Herein, we review how the field of electrochemical paper-based analytical devices (ePADs) has grown since it was introduced a decade ago. We start by reviewing fabrication methods relevant to ePADs with more focus given to the electrode fabrication, which is fundamental for electrochemical sensing. Multiple sensing approaches applicable to ePADs are then discussed and evaluated to present applicability, advantages and challenges associated with each approach. Recent applications of ePADs in the fields of clinical diagnostics, environmental testing, and food analysis are also presented. Finally, we discuss how the current ePAD technologies have progressed to meet the analytical and practical specifications required for field and/or POC applications, as well as challenges and outlook.

Doxycycline is a tetracycline-class antimicrobial labeled by the United States (U.S.) Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline class antibiotics and tooth staining, although doxycycline may be used off-label in severe conditions. Accordingly, there is a paucity of pharmacokinetic (PK) data to guide dosing in children 8 years and younger. We leveraged opportunistically-collected plasma samples after intravenous (IV) and oral doxycycline doses received per standard of care to characterize the PK of doxycycline in children of different ages, and evaluated the effect of obesity and fasting status on PK parameters.We developed a population PK model of doxycycline using data collected from 47 patients 0-18 years of age, including 14 participants ≤8 years. We developed a 1 compartment PK model and found doxycycline clearance to be 3.32 L/h/70 kg and volume to be 96.8 L/70kg for all patients; comparable to values reported in adults. We estimated a bioavailability of 89.6%, also consistent with adult data. Allometrically scaled clearance and volume of distribution did not differ between children 2 to ≤8 years of age and children >8 to ≤18 years of age, suggesting that younger children may be given the same per kg dosing. Obese and fasting status were not selected for inclusion in the final model. Additional doxycycline PK samples collected in future studies may be used to improve model performance and maximize its clinical value., (Copyright © 2019 American Society for Microbiology.)

Combining electrochemistry with microfluidics is attractive for a wide array of applications including multiplexing, automation, and high-throughput screening. Electrochemical instrumentation also has the advantage of being low-cost and can enable high analyte sensitivity. For many electrochemical microfluidic applications, carbon electrodes are more desirable than noble metals because they are resistant to fouling, have high activity, and large electrochemical solvent windows. At present, fabrication of electrochemical microfluidic devices bearing integrated carbon electrodes remains a challenge. Here, a new system for integrating polycaprolactone (PCL) and carbon composite electrodes into microfluidics is presented. The PCL : carbon composites have excellent electrochemical activity towards a wide range of analytes as well as high electrical conductivity (∼1000 S m -1 ). The new system utilizes a laser cutter for fast, simple fabrication of microfluidics using PCL as a bonding layer. As a proof-of-concept application, oil-in-water and water-in-oil droplets are electrochemically analysed. Small-scale electrochemical organic synthesis for TEMPO mediated alcohol oxidation is also demonstrated.

Aedes aegypti is the primary vector of a number of viruses pathogenic to humans including dengue virus (DENV). DENV infection leads to widespread transcriptomic and proteomic alterations in mosquito cells. Here we identified alterations to the mosquito cell secretome during DENV infection by performing liquid chromatography tandem mass spectrometry. We found that an extracellular fragment of low-density lipoprotein receptor-related protein 1 (LRP-1) was present during infection. Previous literature suggests that LRP-1 regulates cholesterol homeostasis. Therefore, we hypothesized that DENV modifies LRP-1 protein expression to maintain host-derived intracellular cholesterol, which would facilitate virus replication within membrane-associated replication compartments. Accordingly, stimuli that are present during flavivirus infection reduced LRP-1 protein expression. We also found that dsRNA knockdown of LRP-1 increased intracellular cholesterol and DENV viral RNA. Further, depletion of intracellular lipids reduced infection. Together, these data suggest that DENV reduces LRP-1 protein expression, possibly through regulated intramembrane proteolysis (RIP), to increase intracellular cholesterol and facilitate replication in Ae. aegypti.

Purpose of Review: Interventions that aim to alter child eating behaviors often focus on parents as a proximal influence. Yet, parents can be difficult to engage. Therefore, intervention recommendations are often not implemented as designed. The goal of this review is to highlight factors at multiple contextual levels that are important to consider when developing interventions to address child eating, due to their implications for overcoming parent engagement challenges., Recent Findings: Intervention studies suggest that parents are often the key to successfully changing child eating behaviors, and many interventions focus on feeding. Factors such as child eating phenotypes, parent stress, family system dynamics, and sociodemographic constraints have also been identified as shaping food parenting. Challenges at multiple contextual levels can affect the likelihood of parent engagement. Addressing factors at the child-, parent-, family-, and broader social-contextual levels of influence is essential in order to promote best practices for parent-focused feeding interventions.

Nurses must learn essential skills based in transcultural nursing to address issues of equity and social justice. The development of a model for nursing practice for an urban nurse-led drop-in center for individuals experiencing marginalization provides an opportunity for student nurses to learn transcultural nursing skills that shifts care from acknowledging the need of others to accompanying others on their health journey. The practice model provides the opportunity for undergraduate and graduate nursing students at Augsburg University to de-emphasize tasks and build relationships. Students learn to listen to others' stories and acknowledge their struggles in the margins. Four stages of nursing practice skills, acknowledging others' needs, attending to their struggles, affirming strengths, and ultimately accompanying others, are taught and experienced. At the core of the nursing practice model is the concept of "hospitality." The nursing practice model serves as guide for student nurses to learn to suspend disbeliefs, withhold judgment, and ultimately reduce stereotypes and stigma to offer a safe space for individuals living in the margins seeking care. The future of nursing requires essential knowledge, skills, and attitudes that shift care from need-based care to accompaniment to address health inequities and provide culturally appropriate care.