Energy Minimization of Discrete Protein Titration State Models Using Graph Theory

There are several applications in computational biophysics which require the optimization of discrete interacting states; e.g., amino acid titration states, ligand oxidation states, or discrete rotamer angles. Such optimization can be very time-consuming as it scales exponentially in the number of sites to be optimized. In this paper, we describe a new polynomial-time algorithm for optimization of discrete states in macromolecular systems. This algorithm was adapted from image processing and uses techniques from discrete mathematics and graph theory to restate the optimization problem in terms of "maximum flow-minimum cut" graph analysis. The interaction energy graph, a graph in which vertices (amino acids) and edges (interactions) are weighted with their respective energies, is transformed into a flow network in which the value of the minimum cut in the network equals the minimum free energy of the protein, and the cut itself encodes the state that achieves the minimum free energy. Because of its deterministic nature and polynomial-time performance, this algorithm has the potential to allow for the ionization state of larger proteins to be discovered

(Z)-2,2,2-Trichloro-N 2-cyano­acetamidine

The title compound, C3H2Cl3N3, crystallizes as the Z isomer with respect to the C=N bond. The –C(NH2)=NCN functional group is effectively planar (r.m.s. deviation = 0.016 Å), with only the three Cl atoms out of the mol­ecular plane. A strong network of N—H⋯N hydrogen bonds forms dimers which are associated into ribbons in the crystal structure. Hydrogen bonding is suspected to be the cause of the near-equivalence of the formal C—N and C=N bonds (ΔCN = 0.008 Å

Variability of Pain Outcomes and Physical Activity Among a Diverse Sample of Older Men: Is It More Than Just Race?

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.There is a compendium of data documenting the increasing number of older adults. This suggests the continued need to understand identified health outcomes across domains of pain and physical activity, particularly among older men. Therefore, the aim of this study was to evaluate race similarities and/or differences in pain and rates of physical activity among White, Black, and Hispanic men 60+ years of age. Data were taken from the Health and Retirement Study, a longitudinal panel study surveying a representative sample of people in the United States. Logistic regression analysis was used to examine associations between race and pain and the odds of regular physical activity. Results showed that Black men were less likely to participate in light or moderate/vigorous physical activity. Similarly, pain increased the odds of physical activity among Hispanics, but decreased the odds of physical activity among White men. Findings may reflect a number of factors that impact the well-being of what it means to experience pain and physical functioning, while also assuming a masculine identity. This perspective may allow for a better understanding of short- and long-term implications of the pain experience and the pain and physical functioning dyad among this group of men

Exploring intentional medication non-adherence in patients with systemic lupus erythematosus: The role of physician-patient interactions

OBJECTIVE: Medication non-adherence contributes to worse health outcomes among SLE patients. The underlying mechanisms that drive medication non-adherence are poorly understood. The purpose of this study was to explore possible mechanisms of medication non-adherence by eliciting patient experiences. METHODS: Consented adult patients with ACR- or SLICC-classified SLE were recruited. Ten semi-structured interviews were conducted across six participants. Interviews were audio recorded, transcribed, and analysed using an iterative process. The findings were presented to an interactive public forum with SLE patients, family members and friends of patients, and health-care professionals to assess validity and for elaboration of the concepts developed. RESULTS: The following three interrelated themes emerged from the interviews. First, why do rheumatologists not know more about lupus or share what they do know with their patients? Second, why do I have to take so many drugs and why do the drugs not work? Third, if my rheumatologist cannot communicate with me, why should I follow the prescribed medication regimen? CONCLUSION: Our exploratory findings lay out a possible underlying logic by which patients might choose intentionally to engage with medication non-adherence behaviours. Patients suggested that poor communication with their rheumatologists along with a lack of validation of their symptoms contributed to them not valuing the recommendations of physicians. This also contributed to development of a cynical outlook and little belief that medication would improve their condition. Although further work is needed to validate these findings, our preliminary work suggests that interventions focusing on the development of communication skills among both patients and rheumatologists are necessary to reduce medication non-adherence

Patients' perceptions of a NHS Health Check in the primary care setting

The NHS Health Checks is a cardiovascular disease (CVD) risk assessment and management programme for individuals in England aged between 40 and 74 with the aim of identifying previously unassessed individuals that are at high risk of CVD. Little research to date has explored patient perceptions and opinions of Health Checks. This paper aims to investigate the perceptions and opinions of patients who had attended a Health Check appointment within a cohort of 83 General Practices in Gloucestershire. A cross sectional survey of patients who had completed a Health Check appointment during the period May to June 2012 within a single county in England. Quantitative and qualitative data were acquired from 1,011 standardised and anonymised patient surveys sent out by a Health Check Commissioner and GPs. Data gathered included perceptions concerning all aspects of the Health Checks process and actual appointment. Descriptive analysis was used to interrogate the quantitative data. Inductive content analysis was used to analyse qualitative data. Concerns about health were a principal driver of attendance. Reassurance, access to health information and guidance, and the identification of CVD risk and CVD diagnosis were perceived as key benefits of attending the appointment. Principal disadvantages included inconsistencies in the Health Check process, administration of appointments and a lack of appropriate follow up advice. Health Checks are popular with patients and provide useful outcomes but greater consistency is needed in engaging patients and describing its purpose

CB1 Receptor Antagonism Blocks Stress-Potentiated Reinstatement of Cocaine Seeking in Rats

Rationale Under some conditions, stress, rather than directly triggering cocaine seeking, potentiates reinstatement to other stimuli, including a subthreshold cocaine dose. The mechanisms responsible for stress-potentiated reinstatement are not well defined. Endocannabinoid signaling is increased by stress and regulates synaptic transmission in brain regions implicated in motivated behavior. Objectives The objective of this study was to test the hypothesis that cannabinoid type 1 receptor (CB1R) signaling is required for stress-potentiated reinstatement of cocaine seeking in rats. Methods Following i.v. cocaine self-administration (2 h access/day) and extinction in male rats, footshock stress alone does not reinstate cocaine seeking but reinstatement is observed when footshock is followed by an injection of an otherwise subthreshold dose of cocaine (2.5 mg/kg, i.p.). CB1R involvement was tested by systemic administration of the CB1R antagonist AM251 (0, 1, or 3 mg/kg, i.p.) prior to testing for stress-potentiated reinstatement. Results Stress-potentiated reinstatement was blocked by both 1 and 3 mg/kg AM251. By contrast, AM251 only attenuated food-reinforced lever pressing at the higher dose (i.e., 3 mg/kg) and did not affect locomotor activity at either dose tested. Neither high-dose cocaine-primed reinstatement (10 mg/kg, i.p.) nor footshock stress-triggered reinstatement following long-access cocaine self-administration (6 h access/day) was affected by AM251 pretreatment. Footshock stress increased concentrations of both endocannabinoids, N-arachidonylethanolamine and 2-arachidonoylglycerol, in regions of the prefrontal cortex. Conclusions These findings demonstrate that footshock stress increases prefrontal cortical endocannabinoids and stress-potentiated reinstatement is CB1R-dependent, suggesting that CB1R is a potential therapeutic target for relapse prevention, particularly in individuals whose cocaine use is stress-related

Development of a digital toolkit to improve quality of life of patients with systemic lupus erythematosus

OBJECTIVE: The purpose of this manuscript is to detail development and initial usability testing of an e-toolkit designed to provide skills and knowledge around self-management behaviors for individuals living with systemic lupus erythematosus. METHODS: Researchers worked with a steering committee of patients and providers to (1) develop a clickable prototype of an e-toolkit and (2) conduct alpha (individuals not affiliated with an academic clinic as patient or provider) and beta (individual patients with systemic lupus erythematosus as well as members of the clinic healthcare team and individuals who work in patient advocacy organizations) usability testing through semistructured interviews. RESULTS: During the review of the e-toolkit, the feedback provided by participants in both alpha and beta groups centered on two overarching themes: (1) improving user interface and materials and (2) integration of information and supports between toolkit and clinical personnel. CONCLUSION: Digital approaches that are tailored to individual symptom variation and integrated with a clinical system have the opportunity to enhance ongoing clinical care. These findings support movement toward integrated, team-based care models, tailored digital resources, and use of expanded virtual interaction options to ensure on-going engagement between healthcare providers and systemic lupus erythematosus patients

Training needs and supports for evidence-based decision making among the public health workforce in the United States

BACKGROUND: Preparing the public health workforce to practice evidence-based decision making (EBDM) is necessary to effectively impact health outcomes. Few studies report on training needs in EBDM at the national level in the United States. We report competency gaps to practice EBDM based on four U.S. national surveys we conducted with the state and local public health workforce between 2008 and 2013. METHODS: We compared self-reported data from four U.S. national online surveys on EBDM conducted between 2008 and 2013. Participants rated the importance of each EBDM competency then rated how available the competency is to them when needed on a Likert scale. We calculated a gap score by subtracting availability scores from importance scores. We compared mean gaps across surveys and utilized independent samples t tests and Cohen’s d values to compare state level gaps. In addition, participants in the 2013 state health department survey selected and ranked three items that “would most encourage you to utilize EBDM in your work” and items that “would be most useful to you in applying EBDM in your work”. We calculated the percentage of participants who ranked each item among their top three. RESULTS: The largest competency gaps were consistent across all four surveys: economic evaluation, communicating research to policymakers, evaluation designs, and adapting interventions. Participants from the 2013 state level survey reported significantly larger mean importance and availability scores (p <0.001, d =1.00, and p <0.001, d = .78 respectively) and smaller mean gaps (p <0.01, d = .19) compared to the 2008 survey. Participants most often selected “leaders prioritizing EBDM” (67.9%) among top ways to encourage EBDM use. “EBDM training for specific areas” was most commonly ranked as important in applying EBDM (64.3%). CONCLUSION: Perceived importance and availability of EBDM competencies may be increasing as supports for EBDM continue to grow through trends in funding, training, and resources. However, more capacity building is needed overall, with specific attention to the largest competency gaps. More work with public health departments to both situate trainings to boost competency in these areas and continued improvements for organizational practices (leadership prioritization) are possible next steps to sustain EBDM efforts

Enhancing evidence-based diabetes and chronic disease control among local health departments: A multi-phase dissemination study with a stepped-wedge cluster randomized trial component

Examples of Intervention Dissemination Strategies and Description. (DOCX 22 kb