'If I don't Do It, I'm Out of Rhythm and I Can't Focus As Well': Positive and Negative Adult Interpretations of Therapies Aimed at 'Fixing' Their Restricted and Repetitive Behaviours in Childhood.

Restricted and repetitive behaviours (RRBs) are observed in many children presenting with characteristics of autism and are frequently the targets of psychological interventions. This study used Interpretative Phenomenological Analysis (IPA) to identify positive and negative interpretations from four young adults who received behavioural interventions in their childhood designed to 'fix' RRBs. Two superordinate themes were identified: (1) Doubt, stigma and being fixed according to others, and (2) Embracing Authenticity. They highlighted juxtaposed positions from exclusion, rejection, criticism, and self-doubt in childhood, to rejecting societal censure and embracing authentic growth in adult life. As adults, though the participants recognised themselves as neurologically different from others, they redefined themselves through a lens of neurodiversity, and therefore as not needing to be fixed.

Intranasal Delivery of Recombinant S100A8 Protein Delays Lung Cancer Growth by Remodeling the Lung Immune Microenvironment.

Lung cancer is the leading cause of cancer-related death worldwide. Increasing evidence indicates a critical role for chronic inflammation in lung carcinogenesis. S100A8 is a protein with reported pro- and anti-inflammatory functions. It is highly expressed in myeloid-derived suppressor cells (MDSC) that accumulate in the tumor microenvironment and abrogate effective anti-cancer immune responses. Mechanisms of MDSC-mediated immunosuppression include production of reactive oxygen species and nitric oxide, and depletion of L-arginine required for T cell function. Although S100A8 is expressed in MDSC, its role in the lung tumor microenvironment is largely unknown. To address this, mouse recombinant S100A8 was repeatedly administered intranasally to mice bearing orthotopic lung cancers. S100A8 treatment prolonged survival from 19 days to 28 days (p < 0.001). At midpoint of survival, whole lungs and bronchoalveolar lavage fluid (BALF) were collected and relevant genes/proteins measured. We found that S100A8 significantly lowered expression of cytokine genes and proteins that promote expansion and activation of MDSC in lungs and BALF from cancer-bearing mice. Moreover, S100A8 enhanced activities of antioxidant enzymes and suppressed production of nitrite to create a lung microenvironment conducive to cytotoxic lymphocyte expansion and function. In support of this, we found decreased MDSC numbers, and increased numbers of CD4+ T cells and natural killer T (NK-T) cells in lungs from cancer-bearing mice treated with S100A8. Ex-vivo treatment of splenocytes with S100A8 protein activated NK cells. Our results indicate that treatment with S100A8 may favourably modify the lung microenvironment to promote an effective immune response in lungs, thereby representing a new strategy that could complement current immunotherapies in lung cancer.

Reversible reconfiguration of high-order DNA nanostructures by employing G-quartet toeholds as adhesive units.

G-quadruplex structures are becoming useful alternative interaction modules for the assembly of DNA nanomaterials because of their unique inducibility by cations. In this study, we demonstrated a new strategy for the assembly of polymeric DNA nanoarchitectures in the presence of cations, such as K+ and Na+, by employing G-quartet toeholds at the edges of discrete mini-square DNA building blocks as adhesive units. In comparison with the Watson-Crick base-paired duplex linkers, G-quadruplex arrays embedded in the self-assembled DNA system exhibit higher thermal stability. The morphology of these doughnut-shaped or spherical-shaped DNA nanostructures is highly regulated by the orientation of the folded G-quadruplexes either in parallel or antiparallel orientation in response to different cations. Furthermore, this G-quadruplex-mediated assembly strategy is able to manipulate the cycling of DNA assemblies between discrete and polymeric states by means of introducing cations and chelating agents sequentially. This property enables the reversible manipulation of the DNA-based nanosystems for at least 4 cycles. The G-quadruplex array embedded in this self-assembled DNA system can become a scaffold for functional molecules, as a number of organic molecules and proteins exhibit specific binding to these G-quadruplex structures. Besides, embedded G-quadruplexes are also considered as functional components of nanoscale electronic materials due to their electron transport through the stacked orientation of the G-quartet. Therefore, this work is an important step towards obtaining reversible, responsive G-quadruplex-induced DNA-based nanomaterials with versatile functionalities which will be highly useful in further electronic, biomedical and drug-delivery applications.

Photoresponsive Self-Assembled DNA Nanomaterials: Design, Working Principles, and Applications.

Photoresponsive DNA nanomaterials represent a new class of remarkable functional materials. By adjusting the irradiation wavelength, light intensity, and exposure time, various photocontrolled DNA-based systems can be reversibly or irreversibly regulated in respect of their size, shape, conformation, movement, and dissociation/association. This Review introduces the most updated progress in the development of photoresponsive DNA-based system and emphasizes their advantages over other stimuli-responsive systems. Their design and mechanisms to trigger the photoresponses are shown and discussed. The potential application of these photon-responsive DNA nanomaterials in biology, biomedicine, materials science, nanophotonic and nanoelectronic are also covered and described. The challenges faced and further directions of the development of photocontrolled DNA-based systems are also highlighted.

Exploring Community Smokers' Perspectives for Developing a Chat-Based Smoking Cessation Intervention Delivered Through Mobile Instant Messaging: Qualitative Study.

BACKGROUND: Advances in mobile communication technologies provide a promising avenue for the delivery of tobacco dependence treatment. Although mobile instant messaging (IM) apps (eg, WhatsApp, Facebook messenger, and WeChat) are an inexpensive and widely used communication tool, evidence on its use for promoting health behavior, including smoking cessation, is scarce. OBJECTIVE: This study aims to explore the perception of using mobile IM as a modality to deliver a proposed chat intervention for smoking cessation in community smokers in Hong Kong, where the proportion of smartphone use is among the highest in the world. METHODS: We conducted 5 focus group, semistructured qualitative interviews on a purposive sample of 15 male and 6 female current cigarette smokers (age 23-68 years) recruited from the community in Hong Kong. All interviews were audiotaped and transcribed. Two investigators independently analyzed the transcripts using thematic analyses. RESULTS: Participants considered mobile IM as a feasible and acceptable platform for the delivery of a supportive smoking cessation intervention. The ability to provide more personalized and adaptive behavioral support was regarded as the most valued utility of the IM-based intervention. Other perceived utilities included improved perceived psychosocial support and identification of motivator to quit. In addition, participants provided suggestions on the content and design of the intervention, which may improve the acceptability and usability of the IM-based intervention. These include avoiding health warning information, positive messaging, using former smokers as counselors, and adjusting the language style (spoken vs written) according to the recipients' preference. CONCLUSIONS: This qualitative study provides the first evidence that mobile IM may be an alternative mobile health platform for the delivery of a smoking cessation intervention. Furthermore, the findings inform the development of a chat-based, IM smoking cessation program being evaluated in a community trial.

Facile construction of a DNA tetrahedron in unconventional ladder-like arrangements at room temperature.

A DNA tetrahedron as the most classical and simplest three-dimensional DNA nanostructure has been widely utilized in biomedicine and biosensing. However, the existing assembly approaches usually require harsh thermal annealing conditions, involve the formation of unwanted by-products, and have poor size control. Herein, a facile strategy to fabricate a discrete DNA tetrahedron as a single, thermodynamically stable product in a quantitative yield at room temperature is reported. This system does not require a DNA trigger or thermal annealing treatment to initiate self-assembly. This DNA tetrahedron was made of three chemically ligated triangular-shaped DNAs in unconventional ladder-like arrangements, with measured heights of ∼4.16 ± 0.04 nm, showing extra protections for enzymatic degradation in biological environment. They show substantial cellular uptake in different cell lines via temperature, energy-dependent and clathrin-mediated endocytosis pathways. These characteristics allow our DNA tetrahedron to be used as vehicles for the delivery of very small and temperature-sensitive cargos. This novel assembly strategy developed for DNA tetrahedra could potentially be extended to other highly complex polyhedra; this indicated its generalizability.

Chat-based instant messaging support combined with brief smoking cessation interventions for Chinese community smokers in Hong Kong: Rationale and study protocol for a pragmatic, cluster-randomized controlled trial.

BACKGROUND: Novel approaches to engage community smokers in smoking cessation are needed as smokers typically lack motivation to quit or use evidence-based tobacco dependence treatment. Mobile instant messaging apps (e.g., WhatsApp, Facebook Messenger) are widely used but under-studied as a mobile health modality for delivering smoking cessation support. This paper presents the rationale and study design of a trial which aims to evaluate the effectiveness of a chat-based intervention using mobile instant messaging combined with brief interventions for community smokers. METHODS: This is a two-arm, parallel, accessor-blinded, pragmatic cluster-randomized controlled trial on an estimated 1172 daily cigarette smokers aged ≥18 years proactively recruited from 68 community sites (cluster) throughout Hong Kong. Subjects in intervention group received three months of chat-based, instant messaging support guided by acceptance and commitment therapy and other behavioural change techniques, integrated with brief advice and active referral to a smoking cessation service using the AWARD (Ask, Warn, Advise, Refer, Do-it-again) intervention model. Control group received brief advice to quit plus a self-help booklet at baseline. Outcomes were assessed at 1-, 2-, 3- and 6-month after baseline. The primary outcome is abstinence validated by exhaled carbon monoxide (<4 ppm) and salivary cotinine (<10 ng/mL) at 6-month after baseline. Primary analyses will be based on intention-to-treat. COMMENTS: This is the first trial examining the effectiveness of a chat-based cessation support programme combined with brief interventions in promoting abstinence. The intervention model can be adapted for other behavioural change treatments and more advanced digital smoking cessation intervention.

α-l-Threose Nucleic Acids as Biocompatible Antisense Oligonucleotides for Suppressing Gene Expression in Living Cells.

Because of the chemical simplicity of α-l-threose nucleic acid (TNA) and its ability to exchange genetic information between itself and RNA, it has attracted significant interest as the RNA ancestor. We herein explore the biological properties and evaluate the potency of sequence-designed TNA polymers to suppress the gene expression in living environments. We found that sequence-specific TNA macromolecules exhibit strong affinity and specificity toward the complementary RNA targets, are highly biocompatible and nontoxic in a living cell system, and readily enter a number of cell lines without using transfecting agents. Particularly, TNA exhibited much stronger enzymatic resistance toward fetal bovine serum or human serum as compared to traditional antisense oligonucleotides, which means that the intrinsic structure of TNA is thoroughly resistant to biological degradation. Importantly, the efficacy of the TNA molecule with green fluorescent protein (GFP) target sequence (anti-GFP TNAs) as antisense agents was first demonstrated in living cells in which these polymers revealed high antisense activity in terms of the degree of inhibition of GFP gene expression. The GFP gene inhibition studies in HeLa and HEK293 cells characterize sequence-controlled TNA as a functional biomaterial and a valuable alternative to traditional antisense oligonucleotides such as peptide nucleic acids, phosphorodiamidate morpholino oligomers, and locked nucleic acids for a wide range of applications in drug discovery and life science research. Additionally, we also first reported the cost-efficient approach to synthesize the four TNA phosphoramidite monomers using 2-cyanoethyl N, N, N', N'-tetraisopropylphosphoramidite as a key reagent. Furthermore, by increasing the frequency of the deblocking and coupling reactions together with extending their reaction time in each synthesis cycle, sequence-controlled TNAs can be easily synthesized in a quantitative yield and high purity.

Fulfilling the psychological and information need of the family members of critically ill patients using interactive mobile technology: A randomised controlled trial.

BACKGROUND: Intensive care nurses may have an important role in empowering families by providing psychological support and fulfilling the family's pivotal need for information. AIM: To determine whether 'education of families by tab' about the patient's condition was more associated with improved anxiety, stress, and depression levels than the 'education of families by routine'. RESEARCH DESIGN: A randomized control trial of 74 main family caregivers (intervention: 39; control: 35). SETTING: An adult intensive care unit. MAIN OUTCOME MEASURES: Depression Anxiety Stress Scale, and Communication and Physical Comfort Scale. RESULTS: Although information need satisfaction was not significantly different between intervention and control groups, the former reported significantly better depression score on Depression Anxiety Stress Scale comparing to the control group (p<0.01; η2=0.09) with a medium effect size. Reduction of anxiety in the intervention group were clinically significant. CONCLUSION: The results suggest that use of 'education of family by tab' is promising for intensive care nurses to provide psychological support for family members. More studies are needed to investigate this aspect of family care for better psychological support and information need satisfaction that contributes to the evidence-based practice of intensive care nursing.

S100A8/A9 and S100A9 reduce acute lung injury.

S100A8 and S100A9 are myeloid cell-derived proteins that are elevated in several types of inflammatory lung disorders. Pro- and anti-inflammatory properties are reported and these proteins are proposed to activate TLR4. S100A8 and S100A9 can function separately, likely through distinct receptors but a systematic comparison of their effects in vivo are limited. Here we assess inflammation in murine lung following S100A9 and S100A8/A9 inhalation. Unlike S100A8, S100A9 promoted mild neutrophil and lymphocyte influx, possibly mediated in part, by increased mast cell degranulation and selective upregulation of some chemokine genes, particularly CXCL-10. S100 proteins did not significantly induce proinflammatory mediators including TNF-α, interleukin-1ß (IL-1ß), IL-6 or serum amyloid A3 (SAA3). In contrast to S100A8, neither preparation induced S100A8 or IL-10 mRNA/protein in airway epithelial cells, or in tracheal epithelial cells in vitro. Like S100A8, S100A9 and S100A8/A9 reduced neutrophil influx in acute lung injury provoked by lipopolysaccharide (LPS) challenge but were somewhat less inhibitory, possibly because of differential effects on expression of some chemokines, IL-1ß, SAA3 and IL-10. Novel common pathways including increased induction of an NAD+-dependent protein deacetylase sirtuin-1 that may reduce NF-κB signalling, and increased STAT3 activation may reduce LPS activation. Results suggest a role for these proteins in normal homeostasis and protective mechanisms in the lung.

Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.

RATIONALE: Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. OBJECTIVE: To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. METHODS: 18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. RESULTS: Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. CONCLUSION: Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust. TRIAL REGISTRATION NUMBER: NCT01792232.

On-line application of near-infrared spectroscopy for monitoring water levels in parts per million in a manufacturing-scale distillation process.

An on-line analytical method based on transmission near-infrared spectroscopy (NIRS) for the quantitative determination of water concentrations (in parts per million) was developed and applied to the manufacture of a pharmaceutical intermediate. Calibration models for water analysis, built at the development site and applied at the manufacturing site, were successfully demonstrated during six manufacturing runs at a 250-gallon scale. The water measurements will be used as a forward-processing control point following distillation of a toluene product solution prior to use in a Grignard reaction. The most significant impact of using this NIRS-based process analytical technology (PAT) to replace off-line measurements is the significant reduction in the risk of operator exposure through the elimination of sampling of a severely lachrymatory and mutagenic compound. The work described in this report illustrates the development effort from proof-of-concept phase to manufacturing implementation.