Integrating informal and formal care: An innovative, scalable program blueprint.

People have infinite needs, including illness prevention, wellness, self-care, practical support, and quality of life. This article describes community-based, informal care programs that help people identify their needs, set goals, and organize networks of care to address their needs holistically in a way that can also significantly reduce healthcare costs. Approaches can be customized for primary care, home and community, hospice, and other care sectors to facilitate low-cost, high impact adoption.

Rural Sanitation Sustainability Dynamics: Gaining Insight through Participatory and Simulation Modeling.

Improved sanitation provides many benefits to human health and well-being and is integral to achieving Sustainable Development Goal Six. However, many nations, including most of sub-Saharan Africa, are not on track to meeting sanitation targets. Recognizing the inherent complexity of environmental health, we used systems thinking to study sanitation sustainability in Uganda.

Skeletal phenotype amelioration in mucopolysaccharidosis VI requires intervention at the earliest stages of postnatal development.

Mucopolysaccharidosis VI (MPS VI) is a rare lysosomal disease arising from impaired function of the enzyme arylsulfatase B (ARSB). This impairment causes aberrant accumulation of dermatan sulfate, a glycosaminoglycan (GAG) abundant in cartilage. While clinical severity varies along with age at first symptom manifestation, MPS VI usually presents early and strongly affects the skeleton.

Oral β-lactams vs fluoroquinolones and trimethoprim/sulfamethoxazole for step-down therapy for Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae bacteremia.

Purpose: To compare rates of treatment failure for patients with bloodstream infections (BSIs) due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis who received oral step-down antibiotic therapy with either a fluoroquinolone (FQ) or trimethoprim/sulfamethoxazole (SXT) to rates for those who received an oral β-lactam (BL).

Methods: This retrospective, multicenter, cohort study included 397 unique adult hospitalized patients with a BSI due to E. coli, K.

Systems Thinking for Effective Interventions in Global Environmental Health.

Environmental health risks such as household air pollution due to burning solid fuels, inadequate water, sanitation, and hygiene, and chemical pollution disproportionately affect the poorest and most marginalized populations. While billions of dollars and countless hours of research have been applied toward addressing these issues in both development and humanitarian contexts, many interventions fail to achieve or sustain desired outcomes over time. This pattern points to the perpetuation of linear thinking, despite the complex nature of environmental health within these contexts.

Phosphorylation-dependent BRD4 dimerization and implications for therapeutic inhibition of BET family proteins.

Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and oncology drug target that regulates gene transcription through binding to acetylated chromatin via bromodomains. Phosphorylation by casein kinase II (CK2) regulates BRD4 function, is necessary for active transcription and is involved in resistance to BRD4 drug inhibition in triple-negative breast cancer. Here, we provide the first biophysical analysis of BRD4 phospho-regulation.

A Comparison of the United States and Austrian Healthcare Needs and Systems.

Austria and the United States have very different healthcare systems with Austria following a social insurance model and the United States following an out of pocket model however;gross domestic product on healthcare expenditures. There is a current gap in literature on how the United States and Austrian healthcare systems comparatively impact patient outcomes, especially when considering the mediating effects of societal norms such as exercise and mental self-care habits. The information presented could benefit the United States healthcare system if they adopted Austria's model, which expands access, and the Austrian healthcare system regulators could look to American standards of communication and care coordination to improve their healthcare system overall.

Complexities of a protonatable substrate in measurements of Hoechst 33342 transport by multidrug transporter LmrP.

Multidrug transporters can confer drug resistance on cells by extruding structurally unrelated compounds from the cellular interior. In transport assays, Hoechst 33342 (referred to as Hoechst) is a commonly used substrate, the fluorescence of which changes in the transport process. With three basic nitrogen atoms that can be protonated, Hoechst can exist as cationic and neutral species that have different fluorescence emissions and different abilities to diffuse across cell envelopes and interact with lipids and intracellular nucleic acids.

Use of an Instrumented Ankle Arthrometer and External Strain Gauge to Assess Ankle Dorsiflexion Motion and Plantarflexor Stiffness.

Background: Ankle dorsiflexion motion and plantarflexor stiffness measurement offer clinical insight into the assessment and treatment of musculoskeletal and neurologic disorders. We aimed to determine reliability and concurrent validity of an ankle arthrometer in quantifying dorsiflexion motion and plantarflexor stiffness.

Methods: Ten healthy individuals were assessed for dorsiflexion motion and plantarflexor stiffness using an ankle arthrometer with a 6 degree-of-freedom kinematic linkage system and external strain gauge to apply dorsiflexion torque.

Overcoming hurdles: measurement of health-related outcomes associated with national level medicines usage in Ireland.

Public discourse on medicine provision predominantly focuses on overall expenditure. However, current literature suggests measurement of alternative indicators can provide a method to benchmark or ameliorate medicine provision. Previous research has investigated the viability of using health-related outcome metrics, such as the number of patients treated, quality-adjusted life-year gain and life-year gain, to provide macro-level estimates on medicines' societal contributions.

Appalachian Environmental Health Literacy: Building Knowledge and Skills to Protect Health.

Environmental health literacy (EHL) is an emerging, multidisciplinary field that promotes understanding of how environmental exposures can affect human health. After discussing the regional relevance of environmental health knowledge and skills, this article describes three ongoing Appalachian projects that are focused on measuring and building EHL.

Potent and selective bivalent inhibitors of BET bromodomains.

Proteins of the bromodomain and extraterminal (BET) family, in particular bromodomain-containing protein 4 (BRD4), are of great interest as biological targets. BET proteins contain two separate bromodomains, and existing inhibitors bind to them monovalently. Here we describe the discovery and characterization of probe compound biBET, capable of engaging both bromodomains simultaneously in a bivalent, in cis binding mode.

Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain.

Angelman syndrome (AS) is a neurological genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain. Due to brain-specific genetic imprinting at this locus, the paternal UBE3A is silenced by a long antisense transcript. Inhibition of the antisense transcript could lead to unsilencing of paternal UBE3A, thus providing a therapeutic approach for AS.

Completing the structural family portrait of the human EphB tyrosine kinase domains.

The EphB receptors have key roles in cell morphology, adhesion, migration and invasion, and their aberrant action has been linked with the development and progression of many different tumor types. Their conflicting expression patterns in cancer tissues, combined with their high sequence and structural identity, present interesting challenges to those seeking to develop selective therapeutic molecules targeting this large receptor family. Here, we present the first structure of the EphB1 tyrosine kinase domain determined by X-ray crystallography to 2.

Stability and solubility engineering of the EphB4 tyrosine kinase catalytic domain using a rationally designed synthetic library.

The inability to generate soluble, correctly folded recombinant protein is often a barrier to successful structural and functional studies. Access to affordable synthetic genes has, however, made it possible to design, make and test many more variants of a target protein to identify suitable constructs. We have used rational design and gene synthesis to create a controlled randomised library of the EphB4 receptor tyrosine kinase, with the aim of obtaining soluble, purifiable and active catalytic domain material at multi-milligram levels in Escherichia coli.

Biochemical and biophysical characterization of four EphB kinase domains reveals contrasting thermodynamic, kinetic and inhibition profiles.

The Eph (erythropoietin-producing hepatocellular carcinoma) B receptors are important in a variety of cellular processes through their roles in cell-to-cell contact and signalling; their up-regulation and down-regulation has been shown to have implications in a variety of cancers. A greater understanding of the similarities and differences within this small, highly conserved family of tyrosine kinases will be essential to the identification of effective therapeutic opportunities for disease intervention. In this study, we have developed a route to production of multi-milligram quantities of highly purified, homogeneous, recombinant protein for the kinase domain of these human receptors in Escherichia coli.

Structures of the human poly (ADP-ribose) glycohydrolase catalytic domain confirm catalytic mechanism and explain inhibition by ADP-HPD derivatives.

Poly(ADP-ribose) glycohydrolase (PARG) is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers, thereby reversing the effects of poly(ADP-ribose) polymerases. PARG deficiency leads to cell death whilst PARG depletion causes sensitisation to certain DNA damaging agents, implicating PARG as a potential therapeutic target in several disease areas. Efforts to develop small molecule inhibitors of PARG activity have until recently been hampered by a lack of structural information on PARG.

Nutritional Effects on the Growth, Cell Size, and Resistance to Stress of Acholeplasma laidlawii.

Due to their lack of a cell wall, mycoplasmas are useful models for the study of biological membranes. However, they are much less appreciated by cell culture laboratories due to their unfortunate tendency to contaminate cell culture lines (1-5). One of the primary protections of a cell line is through filtration of cell culture media.

Paradigm shift: shaping policy to meet the needs of our aging population.

The extent to which our aging population impacts the health system is, as Chappell and Hollander suggest, dependent on (1) how that system is defined and organized and (2) our attitudes as a society to aging and the elderly. The Canadian Home Care Association supports the policy prescription described by Chappell and Hollander and believes that a paradigm shift from a reactive and episodic system to one that is proactive and supportive is required. This article expands upon the lead essay by further discussing the role of home care and the need for its integration into the healthcare system.

Nutritional effects of culture media on mycoplasma cell size and removal by filtration.

Careful media filtration prior to use is an important part of a mycoplasma contamination prevention program. This study was conducted to increase our knowledge of factors that influence efficient filtration of mycoplasma. The cell size of Acholeplasma laidlawii was measured after culture in various nutritional conditions using scanning electron microscopy.

Point-of-use water filtration reduces healthcare-associated infections in bone marrow transplant recipients.

Outbreaks of infection with gram-negative bacteria (GNB) have been linked to hospital water. We sought to determine whether point-of-use (POU) water filtration might result in decreased risk of infection in hospitalized bone marrow transplant (BMT) recipients in the absence of any recognized outbreak. Unfiltered water was sampled from taps in the BMT unit of a major US teaching hospital, and cultured at a reference laboratory.