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Colloidal single-walled carbon nanotubes (SWCNTs) offer a promising platform for the nanoscale engineering of molecular recognition. Optical sensors have been recently designed through the modification of noncovalent corona phases (CPs) of SWCNTs through a phenomenon known as corona phase molecular recognition (CoPhMoRe). In CoPhMoRe constructs, DNA CPs are of great interest due to the breadth of the design space and our ability to control these molecules with sequence specificity at scale. Utilizing these constructs for metal ion sensing is a natural extension of this technology due to DNA's well-known coordination chemistry. Additionally, understanding metal ion interactions of these constructs allows for improved sensor design for use in complex aqueous environments. In this work, we study the interactions between a panel of 9 dilute divalent metal cations and 35 DNA CPs under the most controlled experimental conditions for SWCNT optical sensing to date. We found that best practices for the study of colloidal SWCNT analyte responses involve mitigating the effects of ionic strength, dilution kinetics, laser power, and analyte response kinetics. We also discover that SWCNT with DNA CPs generally offers two unique sensing states at pH 6 and 8. The combined set of sensors in this work allowed for the differentiation of Hg 2+ , Pb 2+ , Cr 2+ , and Mn 2+ . Finally, we implemented Hg 2+ sensing in the context of portable detection within fish tissue extract, demonstrating nanomolar level detection.

Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in transduction of IL-1R/TLR signaling which is responsible for innate immune response. From HTS campaign, bicyclic-pyrimidine compounds have been identified as potent IRAK4 inhibitors, exhibiting good potency in both IRAK4 biochemical and LPS induced IL-23 inhibition cell-based assays. The SAR efforts were focused on further improving on-target potency, reducing PAD activities of HTS hit molecule and improving in vivo PK profiles of early lead compounds. When different aromatic rings were fused to the pyrimidine core, and with various substituents at 2- or 4-position of the pyrimidine, the impact on potency and PK properties were observed and are discussed. Selected compounds were further evaluated in IL-1β induced IL-6 inhibition acute animal model and rodent arthritis disease model, of which compounds 33 and 39 showed good efficacy in both studies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Hydralazine has been known to cause multiple side effects, both localized and systemic. The literature includes case reports of systemic vasculitis caused by hydralazine. Case Report: A 79-year-old male with stage 3 chronic kidney disease attributable to hypertension and type 2 diabetes was started on hydralazine to control his hypertension. Three weeks after starting hydralazine, the patient developed nephrotic syndrome and acute kidney injury with progressively worsening proteinuria. Pathologic evaluation of the kidney tissue revealed that the patient had lupus nephritis. Immunologic markers confirmed hydralazine-induced lupus nephritis with positive antihistone antibodies. No evidence of systemic vasculitis was found. The patient's hydralazine was stopped, and the patient was treated with immunosuppressive therapy. After 7 months of immunosuppressive therapy, the patient achieved complete remission of lupus nephritis. Conclusion: Isolated renal disease induced by hydralazine as part of drug-induced lupus is uncommon. Our patient developed isolated classic lupus nephritis after hydralazine therapy with no associated systemic vasculitis. Treatment required stopping the hydralazine and initiating systemic immunosuppressive therapy to achieve complete remission., (©2020 by the author(s); Creative Commons Attribution License (CC BY).)

Purpose: Canagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor which received U.S. Food and Drug Administration approval in 2013 for the treatment of type 2 diabetes mellitus. Fanconi syndrome is a rare acquired disorder which typically occurs in adults as an adverse effect of medications. The literature includes few case reports of Fanconi syndrome caused by the use of canagliflozin. Here, we present a case of Fanconi syndrome in a patient with type 1 diabetes previously miscategorized as type 2 diabetes., Summary: A 32-year-old woman with a 6-year history of type 2 diabetes was started on canagliflozin. Within 2 months of therapy initiation, she began to develop symptoms of high anion gap metabolic acidosis. Further laboratory test results showed severe life-threatening hypophosphatemia. Further investigation by nephrology revealed the presence of Fanconi syndrome. During the admission, she was found to have clinical and laboratory features of type 1 (insulin-dependent) diabetes. After discontinuation of canagliflozin, she was treated with intravenous (i.v.) fluids for hydration, subcutaneous insulin, and i.v. potassium phosphate. She recovered from all metabolic acidosis and electrolyte abnormalities., Conclusion: Fanconi syndrome is a rare, exogenously acquired disorder in adults that often develops as an adverse effect of medication therapy. Our patient presented with Fanconi syndrome as a complication of canagliflozin use for the treatment of presumed type 2 diabetes. She was then started on subcutaneous insulin monotherapy for the treatment of type 1 diabetes mellitus., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Coronary heart disease is rapidly increasing in developing countries, but access to cardiac rehabilitation and secondary prevention remains low. In this study, we aimed to assess the effectiveness of a smartphone-based cardiac rehabilitation and secondary prevention programme delivered via the social media platform WeChat (SMART-CR/SP)., Methods: In this parallel-group, single-blind, randomised controlled trial, we recruited patients aged 18 years or older with coronary heart disease who had received percutaneous coronary interventions from a large tertiary hospital in Shanghai, China. Participants were randomly assigned (1:1) by block randomisation to either a 2-month intensive programme followed by a 4-month step-down phase of SMART-CR/SP or to usual care. In the SMART-CR/SP group, participants received comprehensive cardiac rehabilitation and secondary prevention via WeChat. The usual care group received standard outpatient cardiology follow-up but without formal cardiac rehabilitation and secondary prevention. Assessments were done at baseline, 2 months, 6 months, and 12 months. The primary outcome was change in functional capacity from baseline, measured by 6-min walk distance, at 2 months and 6 months. Analysis was by intention to treat. Research personnel involved in assessments were blinded to group allocation. Adverse-event analysis was based on percentage of patients who discontinued the study owing to adverse events. SMART-CR/SP programme-related safety issues were also recorded. This study was registered with the Chinese Clinical Trial Registry, number ChiCTR-INR-16009598., Findings: Between Nov 17, 2016, and March 18, 2017, 312 patients (mean age 60·5 years [SD 9·2]), of whom 58 (19%) were female and 254 (81%) were male, were recruited and subsequently randomly assigned to SMART-CR/SP (n=156) or usual care (n=156). The improvement in 6-min walk distance at 2 months was significantly greater in the SMART-CR/SP group (from 489·2 m [99·4] at baseline to 539·1 m [68·0]) than in the control group (from 485·0 m [93·5] at baseline to 517·8 m [74.6]), with an adjusted mean difference of 20·64 m (95% CI 7·50-33·77; p=0·034). This improvement was maintained at 6 months (mean 6-min walk distance 543·4 m [67·5] in the SMART-CR/SP group vs 523·5 m [60·2] in the control group), with a mean between-group difference of 22·29 m (8·19-36·38; p=0·027). No adverse events or SMART-CR/SP programme-related safety issues were reported by participants during the study., Interpretation: SMART-CR/SP was found to be a cardiac rehabilitation and secondary prevention service model with high efficacy and accessibility and to be easy to use. These results justify the implementation of similar models of care on a broader scale., Funding: Curtin University., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The burden of cardiovascular disease (CVD) is rapidly increasing in developing countries, however access to cardiac rehabilitation and secondary prevention (CR/SP) in these countries is limited. Alternative delivery models that are low-cost and easy to access are urgently needed to address this service gap. The objective of this study is to investigate whether a smartphone and social media-based (WeChat) home CR/SP programme can facilitate risk factor monitoring and modification to improve disease self-management and health outcomes in patients with coronary heart disease (CHD), after percutaneous coronary intervention (PCI) therapy., Methods and Analysis: We propose a single-blind, randomised controlled trial of 300 patients post-PCI with follow-up over 12 months. The intervention group will receive a smartphone-based and WeChat-based CR/SP programme providing education and support for risk factor monitoring and modification. SMART-CR/SP incorporates core components of modern CR/SP: physical activity tracking with interactive feedback and goal setting; education modules addressing CHD understanding and self-management; remote blood pressure monitoring and strategies to improve medication adherence. Furthermore, a dedicated data portal and a CR/SP coach will facilitate individualised supervision and counselling. The control group will receive usual care but no formal CR/SP programme. The primary outcome is change in exercise capacity measured by 6 minute walk test distance. Secondary outcomes include knowledge and awareness of CHD, risk factor status, medication adherence, psychological well-being and quality of life, major cardiovascular events, re-hospitalisations and all-cause mortality. To assess the feasibility and patients' acceptance of the intervention, a process evaluation will be performed at the conclusion of the study., Ethics and Dissemination: Ethics approval was granted by both the Human Research Ethics Committee of Fudan University Zhongshan Hospital (HREC B2016-058) and Curtin University Human Research Ethics Office (HRE2016-0120). Results will be disseminated via peer-reviewed publications and presentations at conferences., Clinical Trial Registration Number: ChiCTR-INR-16009598; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Allogeneic hematopoietic cell transplantation (HCT) is the most effective therapy for hematopoietic malignancies through T-cell-mediated graft-vs-leukemia (GVL) effects but often leads to severe graft-vs-host disease (GVHD). Given that protein kinase Cθ (PKCθ), in cooperation with PKCα, is essential for T-cell signaling and function, we have evaluated PKCθ and PKCα as potential therapeutic targets in allogeneic HCT using genetic and pharmacologic approaches. We found that the ability of PKCα(-/-)/θ(-/-) donor T cells to induce GVHD was further reduced compared with PKCθ(-/-) T cells in relation with the relevance of both isoforms to allogeneic donor T-cell proliferation, cytokine production, and migration to GVHD target organs. Treatment with a specific inhibitor for both PKCθ and PKCα impaired donor T-cell proliferation, migration, and chemokine/cytokine production and significantly decreased GVHD in myeloablative preclinical murine models of allogeneic HCT. Moreover, pharmacologic inhibition of PKCθ and PKCα spared T-cell cytotoxic function and GVL effects. Our findings indicate that PKCα and θ contribute to T-cell activation with overlapping functions essential for GVHD induction while less critical to the GVL effect. Thus, targeting PKCα and PKCθ signaling with pharmacologic inhibitors presents a therapeutic option for GVHD prevention while largely preserving the GVL activity in patients receiving HCT.

Objectives: To examine parent perception of child behaviour problems and parenting stress in Hong Kong, and to assess the extent to which they are related to socio-demographic factors and the availability of social support., Design: Cross-sectional survey by using a questionnaire., Setting: Maternal and Child Health Centres, Hong Kong., Participants: Parents of children aged 4 years who were registered with Maternal and Child Health Centres and were living in Hong Kong between September 2002 and February 2003., Main Outcome Measures: Child behaviour problems and parenting stress., Results: A total of 1009 questionnaires were returned giving a participation rate of 67.0%. About one tenth of parents were experiencing difficulties with their children's behaviour. Parenting stress and children's behaviour problems were associated with presence or absence of social support. Parenting stress was also associated with household income., Conclusions: The prevalence of child behaviour problems in Hong Kong is comparable with international figures. Intervention programmes should be targeted at parents who experience difficulties with their children's behaviour and parenting.