Search

The pressure dependence of the static magnetic susceptibility χ(T) of the heavy-electron superconductor UBe13 was investigated over temperatures ranging from 1.5 to 300 K and at pressures from 1 bar to 8 kbar. It is linear in pressure over the full temperature range, having a small constant pressure dependence at higher temperatures that increases rapidly below about T=150 K. The maximal value of the relative susceptibility change [1/χ(dχ/dP)] is about 1% per kbar. The Curie-Weiss law is obeyed in the temperature range 100 to 300 K with the effective magnetic moment peff=3.46μB independent of pressure, while the paramagnetic Curie temperature FTHETA∼-100 K becomes more negative with pressure. The lattice parameter of cubic UBe13 was measured as a function of pressure, permitting a determination of a compressibility value of -9.2×10-4 kbar-1 near ambient pressure. The pressure dependence of χ(T) is significantly weaker than that of the specific-heat coefficient C(T)/T; we discuss whether this can be resolved by (i) consideration of intersite antiferromagnetic interactions, or (ii) the quadrupolar Kondo-effect model, and conclude that the latter provides a stronger explanation of the results. © 1993 The American Physical Society.

We undertook this narrative analysis study to explore the complexities of women's relationships with other women within the sociocultural milieu of beautyism and ageism. Using an open-ended narrative framework, four focus groups of women living in different regions throughout the U.S. were conducted and analyzed to identify thematic categories within and across group sessions. We discuss four of the six key themes discovered in response to the primary research question: How does beauty culture shape women's experiences of aging and their relationships with women of all ages? We conclude that Western idealized beauty standards exert a divisive impact on women's relationships with each other across the life span, negatively affecting their socioemotional well-being, especially in old age. [ABSTRACT FROM AUTHOR]

Isocycloseram is a new insecticide in the isoxazoline class that targets insect GABA-gated chloride channels. In this study, we evaluated a cockroach gel bait formulation containing 1% isocycloseram against a susceptible strain (UCR) and 5 field-collected strains (WM, RG386, Ryan, CDR, and SY) of the German cockroach, Blattella germanica (L.) (Blattodea: Ectobiidae), and compared it with several commercial insecticide baits in the laboratory. Using the Ebeling choice box method, we also tested a residual deposit of an SC formulation of isocycloseram against the UCR, RG386, and Ryan strains. The isocycloseram bait was among the fastest-performing treatments against adult males (mean survival time: 0.9-2.7 days) and mixed stages and sexes (mean survival time: 1.4-5.4 days) across all strains. Secondary transfer effects of the bait were demonstrated in the UCR strain by exposing new adult males to individuals killed by direct bait treatment. Physiological resistance was not detected in the WM, CDR, and RG386 strains with topical treatment of a diagnostic dose (3× LD95) of isocycloseram developed using the UCR strain. However, topical assays revealed resistance ratios (RR50) of 1.6 and 3.0× in the Ryan and SY strains, respectively. The performance of a 0.05% isocycloseram residual application against the Ryan strain was improved with the addition of piperonyl butoxide., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The recent emergence of the omicron variant of the SARS-CoV-2 virus with large numbers of mutations has raised concern about a potential new surge in infections. Here we use molecular dynamics to study the biophysics of the interface of the BA1 and BA2 omicron spike protein binding to (i) the ACE2 receptor protein, (ii) antibodies from all known binding regions, and (iii) the furin binding domain. Our simulations suggest that while there is a significant reduction of antibody (Ab) binding strength corresponding to escape, the omicron spikes pay a cost in terms of weaker receptor binding as measured by interfacial hydrogen bonds (H-bond). The furin cleavage domain (FCD) is the same or weaker binding than the delta variant, suggesting lower fusogenicity resulting in less viral load and disease intensity than the delta variant. IMPORTANCE The BA1 and BA2 and closely related BA2.12.2 and BA.5 omicron variants of SARS-CoV-2 dominate the current global infection landscape. Given the high number of mutations, particularly those which will lead to antibody escape, it is important to establish accurate methods that can guide developing health policy responses that identify at a fundamental level whether omicron and its variants are more threatening than its predecessors, especially delta. The importance of our work is to demonstrate that simple in silico simulations can predict biochemical binding details of the omicron spike protein that have epidemiological consequences, especially for binding to the cells and for fusing the viral membrane with the cells. In each case, we predicted weaker binding of the omicron spike, which agreed with subsequent experimental results. Future virology experiments will be needed to test these predictions further.

Establishing the host range for novel viruses remains a challenge. Here, we address the challenge of identifying non-human animal coronaviruses that may infect humans by creating an artificial neural network model that learns from spike protein sequences of alpha and beta coronaviruses and their binding annotation to their host receptor. The proposed method produces a human-Binding Potential (h-BiP) score that distinguishes, with high accuracy, the binding potential among coronaviruses. Three viruses, previously unknown to bind human receptors, were identified: Bat coronavirus BtCoV/133/2005 and Pipistrellus abramus bat coronavirus HKU5-related (both MERS related viruses), and Rhinolophus affinis coronavirus isolate LYRa3 (a SARS related virus). We further analyze the binding properties of BtCoV/133/2005 and LYRa3 using molecular dynamics. To test whether this model can be used for surveillance of novel coronaviruses, we re-trained the model on a set that excludes SARS-CoV-2 and all viral sequences released after the SARS-CoV-2 was published. The results predict the binding of SARS-CoV-2 with a human receptor, indicating that machine learning methods are an excellent tool for the prediction of host expansion events., (© 2023. The Author(s).)

Plant cytokinesis, a fundamental process of plant life, involves de novo formation of a "cell plate" partitioning the cytoplasm of dividing cells. Cell plate formation is directed by orchestrated delivery, fusion of cytokinetic vesicles, and membrane maturation to form a nascent cell wall by timely deposition of polysaccharides. During cell plate maturation, the fragile membrane network transitions to a fenestrated sheet and finally a young cell wall. Here, we approximated cell plate sub-structures with testable shapes and adopted the Helfrich-free energy model for membranes, including a stabilizing and spreading force, to understand the transition from a vesicular network to a fenestrated sheet and mature cell plate. Regular cell plate development in the model was possible, with suitable bending modulus, for a two-dimensional late stage spreading force of 2-6 pN/nm, an osmotic pressure difference of 2-10 kPa, and spontaneous curvature between 0 and 0.04 nm-1. With these conditions, stable membrane conformation sizes and morphologies emerged in concordance with stages of cell plate development. To reach a mature cell plate, our model required the late-stage onset of a spreading/stabilizing force coupled with a concurrent loss of spontaneous curvature. Absence of a spreading/stabilizing force predicts failure of maturation. The proposed model provides a framework to interrogate different players in late cytokinesis and potentially other membrane networks that undergo such transitions. Callose, is a polysaccharide that accumulates transiently during cell plate maturation. Callose-related observations were consistent with the proposed model's concept, suggesting that it is one of the factors involved in establishing the spreading force., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Established technology, operational infrastructure, and nursing resources were leveraged to develop a remote patient monitoring (RPM) program for ambulatory management of patients with COVID-19. The program included two care-delivery models with different monitoring capabilities supporting variable levels of patient risk for severe illness. The primary objective of this study was to determine the feasibility and safety of a multisite RPM program for management of acute COVID-19 illness. We report an evaluation of 7074 patients served by the program across 41 US states. Among all patients, the RPM technology engagement rate was 78.9%. Rates of emergency department visit and hospitalization within 30 days of enrollment were 11.4% and 9.4%, respectively, and the 30-day mortality rate was 0.4%. A multisite RPM program for management of acute COVID-19 illness is feasible, safe, and associated with a low mortality rate. Further research and expansion of RPM programs for ambulatory management of other acute illnesses are warranted., (© 2021. The Author(s).)

Background: The Mayo Clinic Center for Connected Care has an established organizational framework for telehealth care delivery. It provides patients, consumers, care teams, and referring providers access to clinical knowledge through technologies and integrated practice models. Central to the framework are teams that support product management and operational functions. They work together across the asynchronous, synchronous video telemedicine, remote patient monitoring (RPM), and mobile core service lines. Methods: The organizational framework of the Center for Connected Care and Mayo Clinic telehealth response to the COVID-19 pandemic is described. Barriers to telehealth delivery that were addressed by the public health emergency are also reported. This report was deemed exempt from full review by the Mayo Clinic IRB. Results: After declaration of the COVID-19 pandemic, there was rapid growth in established telehealth offerings, including patient online services account creation, secure messaging, inpatient eConsults, express care online utilization, and video visits to home. Census for the RPM program for patients with chronic conditions remained stable; however, its framework was rapidly adapted to develop and implement a COVID-19 RPM service. In addition to this, other new telehealth and virtual care services were created to support the unique needs of patients with COVID-19 symptoms or disease and the health care workforce, including a digital COVID-19 self-assessment tool and video telemedicine solutions for ambulances, emergency departments, intensive care units, and designated medical-surgical units. Conclusion: Rapid growth, adoption, and sustainability of telehealth services through the COVID-19 pandemic were made possible by a scalable framework for telehealth and alignment of regulatory and reimbursement models., Competing Interests: No competing financial interests exist., (© Tufia C. Haddad et al., 2021; Published by Mary Ann Liebert, Inc.)

Biomolecular self-assembly is an emerging bottom-up approach for the synthesis of novel nanomaterials. DNA and viruses have both been used to create scaffolds but the former lacks chemical diversity and the latter lack spatial control. To date, the use of protein scaffolds to template materials on the nanoscale has focused on amyloidogenic proteins that are known to form fibrils or two-protein systems where a second protein acts as a cross-linker. We previously developed a unique approach for self-assembly of nanomaterials based on engineering β-solenoid proteins (BSPs) to polymerize into micrometer-length fibrils. BSPs have highly regular geometries, tunable lengths, and flat surfaces that are amenable to engineering and functionalization. Here, we present a newly engineered BSP based on the antifreeze protein of the beetle Rhagium inquisitor (RiAFP-m9), which polymerizes into stable fibrils under benign conditions. Gold nanoparticles were used to functionalize the RiAFP-m9 fibrils as well as those assembled from the previously described SBAFP-m1 protein. Cysteines incorporated into the sequences provide site-specific gold attachment. Additionally, silver was deposited on the gold-labelled fibrils by electroless plating to create nanowires. These results bolster prospects for programable self-assembly of BSPs to create scaffolds for functional nanomaterials., Competing Interests: The authors have declared that no competing interests exist.

The mortality rate of a field population of house fly (Musca domestica L.) was determined for a granular fly bait containing the active ingredient indoxacarb, which was compared to two commercially available granular fly baits containing either dinotefuran or cyantraniliprole. Indoxacarb was applied at three different application rates 0.498, 0.986, and 1.972 g/m2 (low, medium, and high). Time to 50% mortality was fastest for dinotefuran (5.7 h) and slowest for the low application rate of indoxacarb (10.3 h). Time to 90% mortality was fastest for the high application rate of indoxacarb (27.7 h) and slowest for dinotefuran (51.0 h) and cyantraniliprole (45.9 h). Among the three indoxacarb application rates, the high rate reached both 50 and 90% fly mortality significantly faster than the low rate. The medium rate did not significantly differ from either the high or low application rates. Dinotefuran bait produced greater fly mortality than all other treatments at 30-min post-exposure, with mortality for remaining baits exceeding controls by 3- to 6-h post-exposure. All insecticidal baits produced similar fly mortality by 6-h post-exposure and >94% fly mortality by 96-h post-exposure, indicating that each may be effective in a fly management program. Flies consumed a similar amount of the indoxacarb (regardless of application rate) and dinotefuran baits, but consumed less of the cyantraniliprole bait, suggesting a feeding irritancy or toxicity effect manifested during consumption. Nevertheless, flies consumed enough cyantraniliprole bait to cause mortality similar to other baits by 6-h post-exposure., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess the impact of implementing bar-code medication administration (BCMA) technology on the rate of medication administration errors in the inpatient setting, specifically those that affect the patient and result in harm., Patients and Methods: Implementation of the new technology began in September 2008 in a staged rollout of 4 or 5 units at a time in 11 separate waves. All corresponding medication administrations and voluntarily reported medication-related adverse events from March 1, 2007, through September 30, 2013, were included for analyses. Adherence to the use of BCMA technology and the number of adverse events were tracked and compared across the preimplementation period through follow-up. Actual errors, not potential errors, were included in the analysis., Results: After the BCMA technology was introduced, reported medication administration errors decreased by 43.5%. More importantly, the rate of harmful medication errors decreased from 0.65 per 100,000 medications preintervention to 0.29 per 100,000 medications postintervention. This resulted in a 55.4% decrease in actual patient harm events. None of the errors at category E or higher was caused by BCMA factors., Conclusion: Consistent use of BCMA technology improves patient safety by decreasing the number of patients harmed by medication administration errors.

Due to their large mechanical strength and potential for functionalization, beta-solenoid proteins show promise as building blocks in biomaterials applications such as two- and three-dimensional scaffolds. We have designed simulation models of two-dimensional square and honeycomb protein lattices by covalently linking a beta-solenoid protein, the spruce budworm antifreeze protein (SBAFP), to symmetric protein multimers. Periodic boundary conditions applied to the simulation cell allow for the simulation of an infinite lattice. We use molecular dynamics to strain the lattice by deforming the simulation cell and measuring the resulting stress tensor. We evaluate the linear portion of stress-strain curves to extract the corresponding bulk and shear elastic moduli. When strained at a rate of 0.3 nm ps-1, the lattices yield a bulk modulus of approximately 3 GPa. This large elastic modulus demonstrates that 2-dimensional structures designed from beta-solenoid proteins can be expected to retain the exceptional material strength of their building blocks.

We present estimates of ultimate tensile strength (UTS) for two engineered β-solenoid protein mutant fibril structures (spruce budworm and Rhagium inquisitor antifreeze proteins) derived from sonication-based measurements and from force pulling molecular dynamics simulations, both in water. Sonication experiments generate limiting scissioned fibrils with a well-defined length-to-width correlation for the mutant spruce budworm protein and the resultant UTS estimate is 0.66 ± 0.08 GPa. For fibrils formed from engineered R. inquisitor antifreeze protein, depending upon geometry, we estimate UTSs of 3.5 ± 3.2-5.5 ± 5.1 GPa for proteins with interfacial disulfide bonds, and 1.6 ± 1.5-2.5 ± 2.3 GPa for the reduced form. The large error bars for the R. inquisitor structures are intrinsic to the broad distribution of limiting scission lengths. Simulations provide pulling velocity-dependent UTSs increasing from 0.2 to 1 GPa in the available speed range, and 1.5 GPa extrapolated to the speeds expected in the sonication experiments. Simulations yield low-velocity values for the Young's modulus of 6.0 GPa. Without protein optimization, these mechanical parameters are similar to those of spider silk and Kevlar, but in contrast to spider silk, these proteins have a precisely known sequence-structure relationship., (Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty's views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected.

This paper focuses on the occupational experiences of five men living within a forensic mental health unit over a year. This study used a descriptive qualitative case study methodology to explore the meaning and value placed on daily life (activities, occupations and routines), and how this changed over time. The men's stories showed a complex picture of their experiences of daily life. This study demonstrated the impact of the environment on the men and the ongoing challenge of the need to balance treatment/therapy with security demands and opportunities. Three interrelated themes were identified: (1) Power and Occupation; (2) Therapy or Punishment; (3) Occupational Opportunities within Restrictions. These findings serve as a reminder to clinical teams to reassess the value of occupations attributed by their patients and the impact of the secure environment, whilst also acknowledging the potential for occupations to have a negative impact on well-being.

Barcode medication administration (BCMA) implementation represents a change in a complex process requiring significant modifications in the work of nurses. Nurses' voices are critical for successfully implementing BCMA technology to support this change in nursing practice. Feedback from nurses who administered medications was critical to selecting and refining a BCMA system that supported their practice needs. Feedback regarding implementation status was critical for keeping key stakeholders across the institution informed of the progress and initial impact of the implementation. Nursing leadership engagement throughout the process supported the successful adoption of new workflow processes and technology.

Circle dance, which derives from the tradition of folk dances, is practised worldwide. This article explores the meanings participants attribute to it. In-depth interviews with 39 participants, teachers and coordinators of teacher training programmes from the circle dance network in the United Kingdom were undertaken. Applying a constructivist grounded theory approach, major categories, representing respectively the experiences of circle dance participants, teachers and coordinators, were developed. This article specifically focuses on the first major category, termed "I can't imagine life without it", which relates to the experience of 22 dancers. From an occupational perspective, the study reveals how participants realise a sense of meaning and satisfaction through engagement in circle dance and the potential contribution of this occupation to well-being.

We compute potentials of mean force for bend and twist deformations via force pulling and umbrella sampling experiments for four β-solenoid proteins (BSPs) that show promise in nanotechnology applications. In all cases, we find quasi-Hooke's law behavior until the point of rupture. Bending moduli show modest anisotropy for two-sided and three-sided BSPs, and little anisotropy for a four-sided BSP. There is a slight clockwise/counterclockwise asymmetry in the twist potential of mean force, showing greater stiffness when the applied twist follows the intrinsic twist. When we extrapolate to beam theory appropriate for amyloid fibrils of the BSPs, we find bend/twist moduli which are somewhat smaller than those in the literature for other amyloid fibrils. Twist persistence lengths are on the order of a micron, and bend persistence lengths are several microns. Provided the intrinsic twist can be reversed, these results support the usage of BSPs in biomaterials applications.

Uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) catalyzes a reversible reaction for adding an O-acyl group to the GlcNAc in UDP-GlcNAc in the first step of lipid A biosynthesis. Lipid A constitutes a major component of lipopolysaccharides, also referred to as endotoxins, which form the outer monolayer of the outer membrane of Gram-negative bacteria. Ligand-free and UDP-GlcNAc-bound crystal structures of LpxA from Bacteroides fragilis NCTC 9343, the most common pathogenic bacteria found in abdominal abscesses, have been determined and are presented here. The enzyme crystallizes in a cubic space group, with the crystallographic threefold axis generating the biological functional homotrimer and with each monomer forming a nine-rung left-handed β-helical (LβH) fold in the N-terminus followed by an α-helical motif in the C-terminus. The structure is highly similar to LpxA from other organisms. Yet, despite sharing a similar LβH structure with LpxAs from Escherichia coli and others, previously unseen calcium ions are observed on the threefold axis in B. fragilis LpxA to help stabilize the trimeric assembly.

Background: To establish whether the current training of student sonographers in both academic and clinical settings is sufficient for educating about the dangers of work-related musculoskeletal disorders (WRMSDs)., Methods: A dual method of data collection was undertaken. Initially, a focus group was set up, involving a small group of practicing sonographers from a hospital in the United Kingdom, with the results of that survey being used to design a postal survey questionnaire. The questionnaire focused on ergonomics, scanning technique, training in physical techniques, personal general health, risk, stress, and task management. It was sent to seven participating universities across the United Kingdom. Approvals were obtained from the local ethics committees, the hospital Trust, and the academic institution., Results: The focus group highlighted several areas in which improvements could be made in educating sonographers on the reduction of WRMSDs. The questionnaire results indicated that students are being taught about certain aspects of WRMSD prevention by both their university and clinical mentors. Respondents received training on the prevention of WRMSDs: 97% in the university setting and 81% from clinical mentors., Conclusions: Improvements need to be made in terms of educating students to perform muscle-strengthening exercises during the workday; to have a system of reporting injury; to consider personal health, well-being, and stress management in the workplace; and to evaluate the ergonomics of computer workstations., (© 2014 Wiley Periodicals, Inc.)

Nature provides numerous examples of self-assembly that can potentially be implemented for materials applications. Considerable attention has been given to one-dimensional cross-β or amyloid structures that can serve as templates for wire growth or strengthen materials such as glue or cement. Here, we demonstrate controlled amyloid self-assembly based on modifications of β-solenoid proteins. They occur naturally in several contexts (e.g., antifreeze proteins, drug resistance proteins) but do not aggregate in vivo due to capping structures or distortions at their ends. Removal of these capping structures and regularization of the ends of the spruce budworm and rye grass antifreeze proteins yield micron length amyloid fibrils with predictable heights, which can be a platform for biomaterial-based self-assembly. The design process, including all-atom molecular dynamics simulations, purification, and self-assembly procedures are described. Fibril formation with the predicted characteristics is supported by evidence from thioflavin-T fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy. Additionally, we find evidence for lateral assembly of the modified spruce budworm antifreeze fibrils with sufficient incubation time. The kinetics of polymerization are consistent with those for other amyloid formation reactions and are relatively fast due to the preformed nature of the polymerization nucleus.

We present a coarse-grained two dimensional mechanical model for the microtubule-tau bundles in neuronal axons in which we remove taus, as can happen in various neurodegenerative conditions such as Alzheimers disease, tauopathies, and chronic traumatic encephalopathy. Our simplified model includes (i) taus modeled as entropic springs between microtubules, (ii) removal of taus from the bundles due to phosphorylation, and (iii) a possible depletion force between microtubules due to these dissociated phosphorylated taus. We equilibrate upon tau removal using steepest descent relaxation. In the absence of the depletion force, the transverse rigidity to radial compression of the bundles falls to zero at about 60% tau occupancy, in agreement with standard percolation theory results. However, with the attractive depletion force, spring removal leads to a first order collapse of the bundles over a wide range of tau occupancies for physiologically realizable conditions. While our simplest calculations assume a constant concentration of microtubule intercalants to mediate the depletion force, including a dependence that is linear in the detached taus yields the same collapse. Applying percolation theory to removal of taus at microtubule tips, which are likely to be the protective sites against dynamic instability, we argue that the microtubule instability can only obtain at low tau occupancy, from 0.06-0.30 depending upon the tau coordination at the microtubule tips. Hence, the collapse we discover is likely to be more robust over a wide range of tau occupancies than the dynamic instability. We suggest in vitro tests of our predicted collapse.

Background: Clinical decision support (CDS) has been shown to be effective in improving medical safety and quality but there is little information on how telephone triage benefits from CDS. The aim of our study was to compare triage documentation quality associated with the use of a clinical decision support tool, ExpertRN©., Methods: We examined 50 triage documents before and after a CDS tool was used in nursing triage. To control for the effects of CDS training we had an additional control group of triage documents created by nurses who were trained in the CDS tool, but who did not use it in selected notes. The CDS intervention cohort of triage notes was compared to both the pre-CDS notes and the CDS trained (but not using CDS) cohort. Cohorts were compared using the documentation standards of the American Academy of Ambulatory Care Nursing (AAACN). We also compared triage note content (documentation of associated positive and negative features relating to the symptoms, self-care instructions, and warning signs to watch for), and documentation defects pertinent to triage safety., Results: Three of five AAACN documentation standards were significantly improved with CDS. There was a mean of 36.7 symptom features documented in triage notes for the CDS group but only 10.7 symptom features in the pre-CDS cohort (p < 0.0001) and 10.2 for the cohort that was CDS-trained but not using CDS (p < 0.0001). The difference between the mean of 10.2 symptom features documented in the pre-CDS and the mean of 10.7 symptom features documented in the CDS-trained but not using was not statistically significant (p = 0.68)., Conclusions: CDS significantly improves triage note documentation quality. CDS-aided triage notes had significantly more information about symptoms, warning signs and self-care. The changes in triage documentation appeared to be the result of the CDS alone and not due to any CDS training that came with the CDS intervention. Although this study shows that CDS can improve documentation, further study is needed to determine if it results in improved care.

Purpose: Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (CFS/ME), has a significant impact upon daily functioning. Most recommended treatments aim to alter activity patterns based upon assumptions of activity avoidance. However, as there is limited research on the experience of activity and occupational beliefs in people with CFS/ME, this study took a qualitative approach to understand the meaning of activity in people with this disabling condition., Method: This study applied a social constructivist grounded theory methodology. Semi-structured interviews took place with 14 participants attending a Specialist CFS/ME Service in England., Findings: The emergent themes described a premorbid state of constant action with difficulty stopping an activity once it had commenced. When this pattern was interrupted by illness, participants attempted to maintain their previous level of occupational engagement. Negative associations and emotions were described in response to the concept of doing nothing or limited activity. A recurring cycle was reported of increasing activity levels when symptoms improved, followed by post exertional symptoms., Conclusions: Consequently, participants' beliefs about concepts of both activity and inactivity need to be considered within the application of rehabilitation programmes for CFS/ME that aim to modify activity related behaviours., Implications for Rehabilitation: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is commonly treated in the UK using activity modification. In this small qualitative study, patients expressed negative feelings and beliefs towards the concept of doing nothing and therefore sought to push their activity levels when this was available, leading to recurring cycles of symptoms and activity. Rehabilitation programmes need to consider how people with CFS/ME engaged with activity and inactivity before the condition and how this may impact upon engagement with activity-based rehabilitation programmes.

The implementation of a behavioral emergency response team (BERT) at a large midwestern health care organization is described. The BERT is a resource supporting nurses and other health care staff in managing behavioral emergencies. The Joint Commission (2010) reported an increasing rate of violence by patients toward health care staff, reinforcing a need for the BERT. No published reports were found in the literature of a BERT utilizing multidisciplinary mental health experts and security officers as responders. Development strategies, response data, and outcomes of this successful initiative are highlighted.

We employ all-atom structure-based models with a force field with multiple energetic basins for the C-terminal (residues 166-226) of the mammalian prion protein. One basin represents the known alpha-helical (αH) structure while the other represents the same residues in a left-handed beta-helical (LHBH) conformation. The LHBH structure has been proposed to help describe one class of in vitro grown fibrils, as well as possibly self-templating the conversion of normal cellular prion protein to the infectious form. Yet, it is unclear how the protein may make this global rearrangement. Our results demonstrate that the conformation changes are not strongly limited by large-scale geometry modification and that there may exist an overall preference for the LHBH conformation. Furthermore, our model presents novel intermediate trapping conformations with twisted LHBH structure., (Copyright © 2012 Wiley Periodicals, Inc.)

The left-handed β-helix (LHBH) is an intriguing, rare structural pattern in polypeptides that has been implicated in the formation of amyloid aggregates. We used accurate all-atom replica-exchange molecular dynamics (REMD) simulations to study the relative stability of diverse sequences in the LHBH conformation. Ensemble-average coordinates from REMD served as a scoring criterion to identify sequences and threadings optimally suited to the LHBH, as in a fold recognition paradigm. We examined the repeatability of our REMD simulations, finding that single simulations can be reliable to a quantifiable extent. We find expected behavior for the positive and negative control cases of a native LHBH and intrinsically disordered sequences, respectively. Polyglutamine and a designed hexapeptide repeat show remarkable affinity for the LHBH motif. A structural model for misfolded murine prion protein was also considered, and showed intermediate stability under the given conditions. Our technique is found to be an effective probe of LHBH stability, and promises to be scalable to broader studies of this and potentially other novel or rare motifs. The superstable character of the designed hexapeptide repeat suggests theoretical and experimental follow-ups., (Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

We have combined graphics processing unit-accelerated all-atom molecular dynamics with parallel tempering to explore the folding properties of small peptides in implicit solvent on the time scale of microseconds. We applied this methodology to the synthetic β-hairpin, trpzip2, and one of its sequence variants, W2W9. Each simulation consisted of over 8 μs of aggregated virtual time. Several measures of folding behavior showed good convergence, allowing comparison with experimental equilibrium properties. Our simulations suggest that the intramolecular interactions of tryptophan side chains are responsible for much of the stability of the native fold. We conclude that the ff99 force field combined with ff96 φ and ψ dihedral energies and an implicit solvent can reproduce plausible folding behavior in both trpzip2 and W2W9.

Introduction: the H1N1 (subtype hemagglutinin 1 neuraminidase 1) influenza pandemic of 2009 was associated with a large increase in demand for primary care office visits. However, many patients with H1N1 symptoms or exposure could be assessed and treated with telephone protocols., Methods: specific H1N1 influenza telephone protocols were developed by Mayo Clinic physicians using Centers for Disease Control recommendations. Using symptom calls to a primary care practice in the United States, we captured nurse telephone triage recommendations, telephone antiviral prescriptions, and what callers would have done without telephone advice. We retrospectively analyzed all symptom calls from July 2009 through January 2010., Results: call volume was 5,596 calls monthly during the peak influenza months, which was 56% above the monthly average of 3,595 calls for the nonpeak months (p  <  0.001). The calls during October 2009 were 111% over the nonpeak months (p  <  0.001). In October 2009, telephone triage nurses gave 412 prescriptions for antivirals accounting for 5.4% of calls and 39% of all telephonic prescriptions for that month. In the peak H1N1 month of October, there were 1,522 callers who intended to stay home for their care. For the same month, triage nurses suggested 3,250 of the callers stay home. For an October 2009 appointment capacity of 35,126 visit slots, a potential 5% capacity was preserved., Conclusions: a telephone triage solution for the acute demands of influenza H1N1 demonstrated how patients had needs met telephonically while preserving medical access for others.

Treponema pallidum reacts poorly with the antibodies present in rabbit and human syphilitic sera, a property attributed to the paucity of proteins in its outer membrane. To better understand the basis for the syphilis spirochete's "stealth pathogenicity," we used a dual-label, 3-step amplified assay in which treponemes encapsulated in gel microdroplets were probed with syphilitic sera in parallel with anti-FlaA antibodies. A small (approximately 5 to 10%) but reproducible fraction of intact treponemes bound IgG and/or IgM antibodies. Three lines of evidence supported the notion that the surface antigens were likely β-barrel-forming outer membrane proteins (OMPs): (i) surface labeling with anti-lipoidal (VDRL) antibodies was not observed, (ii) immunoblot analysis confirmed prior results showing that T. pallidum glycolipids are not immunoreactive, and (iii) labeling of intact organisms was not appreciably affected by proteinase K (PK) treatment. With this method, we also demonstrate that TprK (TP0897), an extensively studied candidate OMP, and TP0136, a lipoprotein recently reported to be surface exposed, are both periplasmic. Consistent with the immunolabeling studies, TprK was also found to lack amphiphilicity, a characteristic property of β-barrel-forming proteins. Using a consensus computational framework that combined subcellular localization and β-barrel structural prediction tools, we generated ranked groups of candidate rare OMPs, the predicted T. pallidum outer membrane proteome (OMPeome), which we postulate includes the surface-exposed molecules detected by our enhanced gel microdroplet assay. In addition to underscoring the syphilis spirochete's remarkably poor surface antigenicity, our findings help to explain the complex and shifting balance between pathogen and host defenses that characterizes syphilitic infection.

The purpose of this study was to determine the impact of a genomic educational session by measuring participants' application of the class content to their nursing care. A sample of 65 psychiatric nurses participated in a staff development activity and completed a survey. Every respondent reported use of a genomic assessment or intervention with a patient from their clinical practice. The mean use of genomic assessment and intervention items was 5.5 out of the possible 10 which were identified and described in the educational session, providing evidence that nurses are able to include genomic assessments and interventions when caring for a patient with a psychiatric disorder.

Backscattering interferometry enables the detection of syphilis antibody-antigen interactions in the presence of human serum, showing promise as a diagnostic tool for the serological diagnosis of infectious disease with potentially quantitative capabilities.

The objective of this study was to evaluate lufenuron termite bait (1,500 ppm) for the elimination of colonies of Reticulitermes hesperus Banks (Isoptera: Rhinotermitidae). Dispersion of colonies in six baited and six unbaited sites near Placerville, CA, was determined by genetic (microsatellite) analyses. Twenty-one colonies of R. hesperus inhabited the six baited sites and eight colonies of R. hesperus occurred in the six unbaited sites. Five criteria provided a cause-and-effect link between the deployment of lufenuron termite bait and elimination of baited colonies: 1) association of foragers, as members of the same colony, in the independent monitoring stations and bait stations; 2) quantity of bait consumed; 3) abnormal physical appearance of foragers in bait stations; 4) disappearance of foragers from, and cessation of feeding in, independent monitoring stations visited by baited colonies; and 5) presence of foragers from, and continuation of feeding in, independent monitors visited by unbaited colonies. Baited colonies were devoid of foraging termites within a mean of 70.6 d (range, 37-93 d) of bait deployment. Colonies consumed a mean of 8.0 g of bait (range, 2.2-16.0 g). Wood consumption by baited and unbaited colonies was not significantly different during the 2 mo before baiting, 281.4 versus 590.5 mg/d per colony, respectively, nor during the 3 mo immediately after baiting, 112.5 versus 436.8 mg/d per colony, respectively. However, from 10 to 16 mo after baiting, wood consumption by baited colonies essentially ceased and was significantly less than the unbaited colonies, 7.9 versus 470.1 mg/d per colony, respectively.

Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18-68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer > or = 1 : 4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5-240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.

Little is known about the mechanisms by which Treponema pallidum (Tp), the causative agent of syphilis, copes with oxidative stress as it establishes persistent infection within its obligate human host. The Tp genomic sequence indicates that the bacterium's antioxidant defenses do not include glutathione and are limited to just a few proteins, with only one, TP0509, offering direct defense against peroxides. Although this Tp peroxiredoxin (Prx) closely resembles AhpC-like Prxs, Tp lacks AhpF, the typical reductant for such enzymes. Functionally, TpAhpC resembles largely eukaryotic, nonAhpC typical 2-Cys Prx proteins in using thioredoxin (Trx, TP0919) as an efficient electron donor and exhibiting broad specificity toward hydroperoxide substrates. Unlike many of the eukaryotic Prxs, however, TpAhpC is relatively resistant to inactivation during turnover with hydroperoxide substrates. As is often observed in typical 2-Cys Prxs, TpAhpC undergoes redox-sensitive oligomer formation. Quantitative immunoblotting revealed that TpTrx and TpAhpC are present at very high levels (over 100 and 300 microM, respectively) in treponemes infecting rabbit testes; their redox potentials, at -242 +/- 1 and -192 +/- 2 mV, respectively, are consistent with the role of TpTrx as the cellular reductant of TpAhpC. Transcriptional analysis of select antioxidant genes confirmed the presence of high mRNA levels for ahpC and trx which diminish greatly when spirochetes replicate under in vitro growth conditions. Thus, T. pallidum has evolved an extraordinarily robust, broad-spectrum AhpC as its sole mechanism for peroxide defense to combat this significant threat to treponemal growth and survival during infection.

Cryo-electron tomography (CET) was used to examine the native cellular organization of Treponema pallidum, the syphilis spirochete. T. pallidum cells appeared to form flat waves, did not contain an outer coat and, except for bulges over the basal bodies and widening in the vicinity of flagellar filaments, displayed a uniform periplasmic space. Although the outer membrane (OM) generally was smooth in contour, OM extrusions and blebs frequently were observed, highlighting the structure's fluidity and lack of attachment to underlying periplasmic constituents. Cytoplasmic filaments converged from their attachment points opposite the basal bodies to form arrays that ran roughly parallel to the flagellar filaments along the inner surface of the cytoplasmic membrane (CM). Motile treponemes stably attached to rabbit epithelial cells predominantly via their tips. CET revealed that T. pallidum cell ends have a complex morphology and assume at least four distinct morphotypes. Images of dividing treponemes and organisms shedding cell envelope-derived blebs provided evidence for the spirochete's complex membrane biology. In the regions without flagellar filaments, peptidoglycan (PG) was visualized as a thin layer that divided the periplasmic space into zones of higher and lower electron densities adjacent to the CM and OM, respectively. Flagellar filaments were observed overlying the PG layer, while image modeling placed the PG-basal body contact site in the vicinity of the stator-P-collar junction. Bioinformatics and homology modeling indicated that the MotB proteins of T. pallidum, Treponema denticola, and Borrelia burgdorferi have membrane topologies and PG binding sites highly similar to those of their well-characterized Escherichia coli and Helicobacter pylori orthologs. Collectively, our results help to clarify fundamental differences in cell envelope ultrastructure between spirochetes and gram-negative bacteria. They also confirm that PG stabilizes the flagellar motor and enable us to propose that in most spirochetes motility results from rotation of the flagellar filaments against the PG.

We combine molecular dynamics simulations and density functional theory to analyze the electrical structure and transmission probability in four different DNA sequences under physiological conditions. The conductance in these sequences is primarily controlled by interstrand and intrastrand coupling between low-energy guanine orbitals. Insertion of adenine-thymine base pairs between the guanine-cytosine rich domains acts as a tunneling barrier. Our theory explains recent length dependent conductance data for individual DNA molecules in water.

The mechanism of site-specific recognition of DNA by proteins has been a long-standing issue. The DNA glycosylase MutY, for instance, must find the rare 8-oxoguanine-adenine mismatches among the large number of basepairs in the DNA. This protein has a [4Fe-4S] cluster, which is highly conserved in species as diverse as Escherichia Coli and Homo sapiens. The mixed-valent nature of this cluster suggests that charge transfer may play a role in MutY's function. We have studied the energetics of the charge transfer in Bacillus stearothermophilus MutY-DNA complex using multiscale calculation including density functional theory and molecular dynamics. The [4Fe-4S] cluster in MutY is found to undergo 2+ to 3+ oxidation when coupling to DNA through hole transfer, especially when MutY is near an oxoguanine modified base (oxoG). Employing the Marcus theory for electron transfer, we find near optimal Frank-Condon factors for electron transfer from MutY to oxoguanine modified base. MutY has modest selectivity for oxoguanine over guanine due to the difference in oxidation potential. The tunneling matrix element is significantly reduced with the mutation R149W, whereas the mutation L154F reduces the tunneling matrix element as well as the Frank-Condon factor. Both L154F and R149W mutations are known to dramatically reduce or eliminate repair efficiency. We suggest a scenario where the charge transfer leads to a stabilization of the specific binding conformation, which is likely the recognition mode, thus enabling it to find the damaged site efficiently.

We propose models for in vitro grown mammalian prion protein fibrils based upon left handed beta helices formed both from the N-terminal and C-terminal regions of the proteinase resistant infectious prion core. The C-terminal threading onto a beta-helical structure is almost uniquely determined by fixing the cysteine disulfide bond on a helix corner. In comparison to known left handed helical peptides, the resulting model structures have similar stability attributes including relatively low root mean square deviations in all atom molecular dynamics, substantial side-chain-to-side-chain hydrogen bonding, good volume packing fraction, and low hydrophilic/hydrophobic frustration. For the N-terminus, we propose a new threading of slightly more than two turns, which improves upon the above characteristics relative to existing three turn beta-helical models. The N-terminal and C-terminal beta helices can be assembled into eight candidate models for the fibril repeat units, held together by large hinge (order 30 residues) domain swapping, with three amenable to fibril promoting domain swapping via a small (five residue) hinge on the N-terminal side. Small concentrations of the metastable C-terminal beta helix in vivo might play a significant role in templating the infectious conformation and in enhancing conversion kinetics for inherited forms of the disease and explain resistance (for canines) involving hypothesized coupling to the methionine 129 sulfur known to play a role in human disease.

Acquisition of transition metals is central to the struggle between a bacterial pathogen and its mammalian host. Previous studies demonstrated that Treponema pallidum encodes a cluster-9 (C9) ABC transporter (troABCD) whose solute-binding protein component (TroA) ligands Zn(2+) and Mn(2+) with essentially equal affinities. Bioinformatic analysis revealed that T. pallidum encodes an additional C9 transporter (tp0034-36) orthologous to Zn(2+)-uptake (Znu) systems in other bacteria; the binding protein component, ZnuA, contains a His-rich tract characteristic of C9 Zn(2+)-binding proteins. Metal analysis and metal-reconstitution studies demonstrated that ZnuA is a Zn(2+)-binding protein; parallel studies confirmed that TroA binds Zn(2+), Mn(2+) and Fe. Circular dichroism showed that ZnuA, but not TroA, undergoes conformational changes in the presence of Zn(2+). Using isothermal titration calorimetry (ITC), we demonstrated that TroA binds Zn(2+) and Mn(2+) with affinities approximately 100-fold greater than those previously reported. ITC analysis revealed that ZnuA contains multiple Zn(2+)-binding sites, two of which are high-affinity and presumed to be located within the binding pocket and His-rich loop. Quantitative reverse transcription polymerase chain reaction of tro and znu transcripts combined with immunoblot analysis of TroA and ZnuA confirmed that both transporters are simultaneously expressed in T. pallidum and that TroA is expressed at much greater levels than ZnuA. Collectively, our findings indicate that T. pallidum procures transition metals via the concerted utilization of its general metal (Tro) and Zn(2+) (Znu) transporters. Sequestration of periplasmic Zn(2+) by ZnuA may free up TroA binding capacity for the importation of Fe and Mn(2+).