Synthesis of Bioinspired Carbohydrate Amphiphiles that Promote and Inhibit Biofilms

The synthesis and characterization of a new class of bioinspired carbohydrate amphiphiles that modulate Pseudomonas aeruginosa biofilm formation are reported. The carbohydrate head is an enantiopure poly-amido-saccharide (PAS) prepared by a controlled anionic polymerization of β-lactam monomers derived from either glucose or galactose. The supramolecular assemblies formed by PAS amphiphiles are investigated in solution using fluorescence assays and dynamic light scattering. Dried samples are investigated using X-ray, infrared spectroscopy, and transmission electron microscopy. Additionally, the amphiphiles are evaluated for their ability to modulate biofilm formation by the Gram-negative bacterium Pseudomonas aeruginosa. Remarkably, from a library of eight amphiphiles, we identify a structure that promotes biofilm formation and two structures that inhibit biofilm formation. Using biological assays and electron microscopy, we relate the chemical structure of the amphiphiles to the observed activity. Materials that modulate the formation of biofilms by bacteria are important both as research tools for microbiologists to study the process of biofilm formation and for their potential to provide new drug candidates for treating biofilm-associated infections

Differences in Secure Messaging, Self-management, and Glycemic Control Between Rural and Urban Patients: Secondary Data Analysis

BACKGROUND: Rural patients with diabetes have difficulty accessing care and are at higher risk for poor diabetes management. Sustained use of patient portal features such as secure messaging (SM) can provide accessible support for diabetes self-management. OBJECTIVE: This study explored whether rural patients\u27 self-management and glycemic control was associated with the use of SM. METHODS: This secondary, cross-sectional, mixed methods analysis of 448 veterans with diabetes used stratified random sampling to recruit a diverse sample from the United States (rural vs urban and good vs poor glycemic control). Administrative, clinical, survey, and interview data were used to determine patients\u27 rurality, use of SM, diabetes self-management behaviors, and glycemic control. Moderated mediation analyses assessed these relationships. RESULTS: The sample was 51% (n=229) rural and 49% (n=219) urban. Mean participant age was 66.4 years (SD 7.7 years). More frequent SM use was associated with better diabetes self-management (P=.007), which was associated with better glycemic control (P \u3c .001). Among rural patients, SM use was indirectly associated with better glycemic control through improved diabetes self-management (95% CI 0.004-0.927). These effects were not observed among urban veterans with diabetes (95% CI -1.039 to 0.056). Rural patients were significantly more likely than urban patients to have diabetes-related content in their secure messages (P=.01). CONCLUSIONS: More frequent SM use is associated with engaging in diabetes self-management, which, in turn, is associated with better diabetes control. Among rural patients with diabetes, SM use is indirectly associated with better diabetes control. Frequent patient-team communication through SM about diabetes-related content may help rural patients with diabetes self-management, resulting in better glycemic control

Stretched Lens Array (SLA) for Collection and Conversion of Infrared Laser Light: 45% Efficiency Demonstrated for Near-Term 800 W/kg Space Power System

For the past 2% years, our team has been developing a unique photovoltaic concentrator array for collection and conversion of infrared laser light. This laser-receiving array has evolved from the solar-receiving Stretched Lens Array (SLA). The laser-receiving version of SLA is being developed for space power applications when or where sunlight is not available (e.g., the eternally dark lunar polar craters). The laser-receiving SLA can efficiently collect and convert beamed laser power from orbiting spacecraft or other sources (e.g., solar-powered lasers on the permanently illuminated ridges of lunar polar craters). A dual-use version of SLA can produce power from sunlight during sunlit portions of the mission, and from beamed laser light during dark portions of the mission. SLA minimizes the cost and mass of photovoltaic cells by using gossamer-like Fresnel lenses to capture and focus incoming light (solar or laser) by a factor of 8.5X, thereby providing a cost-effective, ultra-light space power system

Secure Messaging, Diabetes Self-management, and the Importance of Patient Autonomy: a Mixed Methods Study

BACKGROUND: Diabetes is a complex, chronic disease that requires patients\u27 effective self-management between clinical visits; this in turn relies on patient self-efficacy. The support of patient autonomy from healthcare providers is associated with better self-management and greater diabetes self-efficacy. Effective provider-patient secure messaging (SM) through patient portals may improve disease self-management and self-efficacy. SM that supports patients\u27 sense of autonomy may mediate this effect by providing patients ready access to their health information and better communication with their clinical teams. OBJECTIVE: We examined the association between healthcare team-initiated SM and diabetes self-management and self-efficacy, and whether this association was mediated by patients\u27 perceptions of autonomy support from their healthcare teams. DESIGN: We surveyed and analyzed content of messages sent to a sample of patients living with diabetes who use the SM feature on the VA\u27s My HealtheVet patient portal. PARTICIPANTS: Four hundred forty-six veterans with type 2 diabetes who were sustained users of SM. MAIN MEASURES: Proactive (healthcare team-initiated) SM (0 or \u3e /= 1 messages); perceived autonomy support; diabetes self-management; diabetes self-efficacy. KEY RESULTS: Patients who received at least one proactive SM from their clinical team were significantly more likely to engage in better diabetes self-management and report a higher sense of diabetes self-efficacy. This relationship was mediated by the patient\u27s perception of autonomy support. The majority of proactive SM discussed scheduling, referrals, or other administrative content. Patients\u27 responses to team-initiated communication promoted patient engagement in diabetes self-management behaviors. CONCLUSIONS: Perceived autonomy support is important for diabetes self-management and self-efficacy. Proactive communication from clinical teams to patients can help to foster a patient\u27s sense of autonomy and encourage better diabetes self-management and self-efficacy

Study design and rationale for a randomized controlled trial to assess effectiveness of stochastic vibrotactile mattress stimulation versus standard non-oscillating crib mattress for treating hospitalized opioid-exposed newborns

The incidence of Neonatal Abstinence Syndrome (NAS) continues to rise and there remains a critical need to develop non-pharmacological interventions for managing opioid withdrawal in newborns. Objective physiologic markers of opioid withdrawal in the newborn remain elusive. Optimal treatment strategies for improving short-term clinical outcomes and promoting healthy neurobehavioral development have yet to be defined. This dual-site randomized controlled trial (NCT02801331) is designed to evaluate the therapeutic efficacy of stochastic vibrotactile stimulation (SVS) for reducing withdrawal symptoms, pharmacological treatment, and length of hospitalization, and for improving developmental outcomes in opioid-exposed neonates. Hospitalized newborns (n = 230) receiving standard clinical care for prenatal opioid exposure will be randomly assigned within 48-hours of birth to a crib with either: 1) Intervention (SVS) mattress: specially-constructed SVS crib mattress that delivers gentle vibrations (30-60 Hz, ~12 mum RMS surface displacement) at 3-hr intervals; or 2) Control mattress (treatment as usual; TAU): non-oscillating hospital-crib mattress. Infants will be studied throughout their hospitalization and post discharge to 14-months of age. The study will compare clinical measures (i.e., withdrawal scores, cumulative dose and duration of medications, velocity of weight gain) and characteristic progression of physiologic activity (i.e., limb movement, cardio-respiratory, temperature, blood-oxygenation) throughout hospitalization between opioid-exposed infants who receive SVS and those who receive TAU. Developmental outcomes (i.e., physical, social, emotional and cognitive) within the first year of life will be evaluated between the two study groups. Findings from this randomized controlled trial will determine whether SVS reduces in-hospital severity of NAS, improves physiologic function, and promotes healthy development

Work-Related Mental Health and Job Performance: Can Mindfulness Help?

Work-related mental health issues such as work-related stress and addiction to work impose a significant health and economic burden to the employee, the employing organization, and the country of work more generally. Interventions that can be empirically shown to improve levels of work-related mental health – especially those with the potential to concurrently improve employee levels of work performance – are of particular interest to occupational stakeholders. One such broad-application interventional approach currently of interest to occupational stakeholders in this respect is mindfulness-based interventions (MBIs). Following a brief explication of the mindfulness construct, this paper critically discusses current research directions in the utilization of mindfulness in workplace settings and assesses its suitability for operationalization as an organization-level work-related mental health intervention. By effecting a perceptual-shift in the mode of responding and relating to sensory and cognitive-affective stimuli, employees that undergo mindfulness training may be able to transfer the locus of control for stress from external work conditions to internal metacognitive and attentional resources. Therefore, MBIs may constitute cost-effective organization-level interventions due to not actually requiring any modifications to human resource management systems and practises. Based on preliminary empirical findings and on the outcomes of MBI studies with clinical populations, it is concluded that MBIs appear to be viable interventional options for organizations wishing to improve the mental health of their employees

Meditation Awareness Training (MAT) for Work-related Wellbeing and Job Performance: A Randomised Controlled Trial

Due to its potential to concurrently improve work-related wellbeing (WRW) and job performance, occupational stakeholders are becoming increasingly interested in the applications of meditation. The present study conducted the first randomized controlled trial to assess the effects of meditation on outcomes relating to both WRW and job performance. Office-based middle-hierarchy managers (n = 152) received an eight-week meditation intervention (Meditation Awareness Training; MAT) or an active control intervention. MAT participants demonstrated significant and sustainable improvements (with strong effect sizes) over control-group participants in levels of work-related stress, job satisfaction, psychological distress, and employer-rated job performance. There are a number of novel implications: (i) meditation can effectuate a perceptual shift in how employees experience their work and psychological environment and may thus constitute a cost-effective WRW intervention, (ii) meditation-based (i.e., present-moment-focussed) working styles may be more effective than goal-based (i.e., future-orientated) working styles, and (iii) meditation may reduce the separation made by employees between their own interests and those of the organizations they work for

Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer.

BACKGROUND: High mitotic activity is associated with the genesis and progression of many cancers. Small molecule inhibitors of mitotic apparatus proteins are now being developed and evaluated clinically as anticancer agents. With clinical trials of several of these experimental compounds underway, it is important to understand the molecular mechanisms that determine high mitotic activity, identify tumor subtypes that carry molecular aberrations that confer high mitotic activity, and to develop molecular markers that distinguish which tumors will be most responsive to mitotic apparatus inhibitors. METHODS: We identified a coordinately regulated mitotic apparatus network by analyzing gene expression profiles for 53 malignant and non-malignant human breast cancer cell lines and two separate primary breast tumor datasets. We defined the mitotic network activity index (MNAI) as the sum of the transcriptional levels of the 54 coordinately regulated mitotic apparatus genes. The effect of those genes on cell growth was evaluated by small interfering RNA (siRNA). RESULTS: High MNAI was enriched in basal-like breast tumors and was associated with reduced survival duration and preferential sensitivity to inhibitors of the mitotic apparatus proteins, polo-like kinase, centromere associated protein E and aurora kinase designated GSK462364, GSK923295 and GSK1070916, respectively. Co-amplification of regions of chromosomes 8q24, 10p15-p12, 12p13, and 17q24-q25 was associated with the transcriptional upregulation of this network of 54 mitotic apparatus genes, and we identify transcription factors that localize to these regions and putatively regulate mitotic activity. Knockdown of the mitotic network by siRNA identified 22 genes that might be considered as additional therapeutic targets for this clinically relevant patient subgroup. CONCLUSIONS: We define a molecular signature which may guide therapeutic approaches for tumors with high mitotic network activity

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.Cancer Research UK Clinician Scientist Fellowship C53779/A20097 (M.L.B), Leukaemia Foundation Australia Senior Fellowship and Howard Hughes Medical Institute International Research Scholarship 55008729 (M.A.D), Peter and Julie Alston Centenary fellowship (K.D.S.), Wellcome Trust Principal Research Fellowship 101835/Z/13/Z (P.J.L), Peter MacCallum Postgraduate Scholarship (C.E.S), NHMRC Postgraduate Scholarship (K.L.C.), Maddie Riewoldt's Vision 064728 (Y-C.C), Victorian Cancer Agency (E.Y.N.L), CSL Centenary fellowship (S-J.D), National Breast Cancer Foundation Fellowship ECF-17-005 (P.A.B.), Addenbrooke’s Charitable Trust and NIHR Cambridge BRC (M.L.B., P.J.L), NHMRC grant 1085015, 1106444 (M.A.D) and 1128984 (M.A.D, S-J.D)

Doing descriptive phenomenological data collection in sport psychology research

Researchers in the field of sport psychology have begun to highlight the potential of phenomenological ap-proaches in recognising subjective experience and the essential structure of experience. Despite this, phenom-enology has been used inconsistently in the sport psychology literature thus far. Therefore, the aim of this paper is to provide theoretically informed practical guidelines for researchers who wish to employ the descrip-tive phenomenological interview in their studies. The recommended guidelines will be supported by under-pinning theory and brief personal accounts. An argument will also be presented for the potential that descrip-tive phenomenology holds in creating new knowledge through rich description. In doing so, it is hoped that this method will be utilised appropriately in future sport psychology research to not only strengthen and diver-sify the existing literature, but also the knowledge of practitioners working within the applied world of profes-sional sport