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Nicholas P Bent,1 Alison B Rushton,1 Chris C Wright,1 Emma-Jane Petherick,2 Mark E Batt3 1School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, 2School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, 3Centre for Sports Medicine, Nottingham University Hospitals, Nottingham, UK Background: The Anteromedial Reach Test is a performance-based outcome measure for evaluating dynamic knee stability in patients with anterior cruciate ligament injury. No previously published study has adequately evaluated intrarater or interrater reliability of the Anteromedial Reach Test, so the purpose of this study was to assess these measurement properties in healthy participants prior to their investigation in patients with anterior cruciate ligament injury. Methods: Two raters (A and B) tested 39 healthy university staff and students (20 men, 19 women). For the intrarater reliability investigation, rater A tested participants on three separate test occasions (days 1, 2, and 3) at the same time of day. For the interrater reliability investigation, raters A and B independently tested participants on the same test occasion (day 3). Results: There was no significant systematic bias between test occasions or raters. Values of the intraclass correlation coefficient (2,1) were 0.96 for intrarater reliability of both the dominant leg and nondominant leg and 0.97 (dominant leg) and 0.98 (nondominant leg) for interrater reliability. Values for the standard error of measurement were 1.46 (dominant leg) and 1.62 (nondominant leg) for the intrarater investigation, and 1.26 (dominant leg) and 1.04 (nondominant leg) for the interrater investigation. At the 90% confidence level, the minimum detectable change was 3.8% and the error in an individual's score at a given point in time was ±2.7%. Conclusion: The Anteromedial Reach Test demonstrated excellent intrarater and interrater reliability in healthy participants. This provides a basis for future investigation of the measurement properties of the Anteromedial Reach Test in patients with anterior cruciate ligament injury. Keywords: anterior cruciate ligament, injury, dynamic stability, rehabilitation, outcome measures

The anteromedial reach test (ART) is a new outcome measure for assessing dynamic knee stability in anterior cruciate ligament-injured patients. The effect of learning and leg length on distance reached in the ART was examined. Thirty-two healthy volunteers performed 15 trials of the ART on each leg. There was a moderate correlation (r = .44-.50) between reach distance and leg length, therefore reach distances were normalized for leg length. Normalized reach distance increased significantly over the 15 trials (p < .01), reaching a plateau after 8 trials, identified by a moving average graph. It is recommended that participants be afforded eight practice trials and that reach distances be normalized by expressing them as a percentage of leg length. [ABSTRACT FROM AUTHOR]

Using examples from the field of anterior cruciate ligament rehabilitation, this review provides sports and health practitioners with a comprehensive, user-friendly, guide to selecting outcome measures for use with active populations. A series of questions are presented for consideration when selecting a measure: is the measure appropriate for the intended use? (appropriateness); is the measure acceptable to patients? (acceptability); is it feasible to use the measure? (feasibility); does the measure provide meaningful results? (interpretability); does the measure provide reproducible values? (reliability); does the measure assess what it is supposed to assess? (validity); can the measure detect change? (responsiveness); do substantial proportions of patients achieve the worst or best scores? (floor and ceiling effects); is the measure structured and scored correctly? (dimensionality and internal consistency); has the measure been tested with the types of patients with whom it will be used? (sample characteristics). Evaluation of the measure using these questions will assist practitioners in making their judgements. [ABSTRACT FROM AUTHOR]

The re-education of spinal posture is an integral part of shoulder impingement management yet supporting evidence is limited. The purpose of this study was to evaluate the effect of slouched versus erect sitting posture on shoulder pain intensity and range of motion (ROM) in subjects with impingement. A same-subject repeated-measures design was utilized. Maximum active shoulder flexion and associated pain intensity were measured in 28 subjects in slouched and erect sitting postures, using video-analysis and visual analogue scales, respectively. An intra-tester reliability study of the video-analysis system was completed and intra-class correlation coefficients calculated. Shoulder flexion differences between slouched and erect sitting posture were analysed using a repeated-measures analysis of variance (ANOVA). The intra-tester reliability of the video-analysis method was found to be 'excellent' (ICC = 0.99). Flexion ROM was significantly greater in the erect sitting posture (F = 100.3, P < 0.0001); the mean ROM difference between postures was 17.67 degrees (+/- 9.17 degrees). There was no significant difference in pain intensity between postures (F = 1.9, P = 0.179). An erect sitting posture appeared to increase active shoulder flexion in subjects with shoulder impingement, although there were no differences in reported pain intensity. Further research is required to investigate the long-term effects of postural re-education. [ABSTRACT FROM AUTHOR]

Working Horizons is an intervention designed to prevent work disability by addressing the internal and external barriers faced by people with arthritis in their attempts to enter or maintain their positions in the employment arena. The aim of the pilot study was to determine whether Working Horizons influenced participants' self-efficacy and psychological well-being and to describe the experience of Working Horizons from the perspectives of participants and employment advisors (EAs). The study was a pre-test post-test design with an Intervention Group (n=22) and Comparison Control Group (n=22). Quantitative data were collected by self-completed questionnaires at baseline and at six-months follow-up. Qualitative data were collected via open questions on the questionnaires, interviews with a sub-sample of 10 participants, and a focus group with EAs at the end of the programme. Pilot data suggested that Working Horizons was effective in terms of increasing participants' job-seeking self-efficacy. In addition, the Intervention Group showed significant improvements on self-esteem and satisfaction with life. Qualitative findings confirmed that participants felt more 'confident' in relation to seeking employment, were more accepting of their condition, felt more positive and had greater awareness of the social model of disability. Participants valued the emotional and instrumental support provided by the EAs, who acted as successful 'work' role models. Interventions, such as Working Horizons, may be an effective means of addressing work disability, acting as a gateway to statutory services. The value of suitable role models in mentoring capacities was highlighted. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to describe the development of the 'Compliance of Hypertensive Patients' scale (=CHPS), and assessment of its reliability and validity. Previous scales incorporate only activity in health regimens as indicators of hypertensive patients' compliance. The 'Compliance of Hypertensive Patients' scale was developed to incorporate other indicators of compliance also, such as intention, responsibility and collaboration. Data were collected from a convenience sample of 103 patients, in five health care centres in Finland. Dimensionality was explored using principal component analysis and internal consistency was estimated according to a standard item analysis approach and Theta coefficient. Validity was assessed using face validity, content validity and criterion-related validity (through the use of concurrent validity). The data supported five subscales, labelled: lifestyle, intention, attitude, responsibility and smoking. Inter-item correlations ranged from 0.24 to 0.61 and corrected item-total correlations from 0.32 to 0.67, across subscales. The Theta coefficient demonstrated good internal consistency. This scale forms a useful starting point in the development of a reliable and valid tool to assess compliance of hypertensive patients, based on several indicators. [ABSTRACT FROM AUTHOR]

A lack of understanding of statistical concepts and procedures is a barrier to conducting research and to using research findings. This article will discuss some basic concepts of statistical hypothesis testing, the interpretation and clinical implications of ensuing results, and their role in health-care research. The distinction between statistical significance and practical importance is stressed. [ABSTRACT FROM AUTHOR]

This article will discuss key features of simple graphical and numerical summaries that are routinely used to describe numerical data. It considers the different types of data and how these influence the choice of appropriate summaries, and helps the consumer to identify information that has been presented in an inappropriate or misleading manner. [ABSTRACT FROM AUTHOR]

AIM: The aim of this study was to compare the safety and effectiveness of anticoagulant nurses and a consultant haematologist in managing anticoagulant patients in a hospital outpatient setting. BACKGROUND: Nurses are increasingly developing roles traditionally undertaken by medical staff. As a result nurse-led practice has expanded in many areas including anticoagulant services. Previous studies have attempted to demonstrate the effectiveness of using other professionals to manage anticoagulant clinics over short periods of time. This research evaluates the safety and effectiveness of a consultant-led and a nurse-led service over two sequential 18-month periods. RESEARCH METHODS: A nonexperimental design was adopted. Data were collected retrospectively, from a random sample of 197 patients, who had been managed by both the consultant-led and nurse-led service. Two main outcome measures were selected: anticoagulant control between professional groups and interval between outpatient clinic appointments. RESULTS: No statistically significant difference in anticoagulant control was found between professional groups (P=0.137). There was evidence that patients attended anticoagulant clinics on significantly fewer occasions with nurse-led management (P < 0.0005). CONCLUSION: At the department within which this research was conducted, anticoagulant nurses were found to be at least as safe and effective as the consultant haematologist in managing outpatient anticoagulant patients over the study period. These findings are of importance in both shaping the future provision of anticoagulant care and also contributing to the wider area in evaluating the impact of nurse-led practice within health care. [ABSTRACT FROM AUTHOR]

This article will describe the context within which statistics are used in health-care research, define 'statistics' in relation to this context and discuss the role of statistics in relation to researchers and consumers of research. Future articles will discuss key aspects of the use of statistics in health-care research. The series will aim to encourage critical interpretation and appropriate use of statistical information. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Though many contaminants are released into the atmosphere, in the US only six air pollutants-ozone, particulate matter, sulfur dioxide, carbon monoxide, nitrogen dioxide, and lead-are closely monitored and carefully assessed for health significance. Other pollutants, even if highly toxic, are neither widely monitored nor routinely assessed at the national level. The goal of this study was to analyze the availability of information needed to characterize the health significance of hazardous air pollutants, focusing on urban areas in California. METHODS: The authors compared different approaches to identifying which contaminants should be considered hazardous air pollutants of potential health concern; reviewed the availability of toxicity values for these pollutants; and analyzed the usefulness of air monitoring data from California agencies for determining populations risks, by comparing method detection limits with health benchmarks. RESULTS: Approaches to identifying air contaminants of possible health concern differ. Toxicity values are not available for many hazardous air pollutants, including those identified in the Clean Air Act. In California, monitoring data are available for many, though not all, pollutants of concern. Monitoring methods for several pollutants do not have adequate sensitivity to detect all relevant concentrations. CONCLUSION: The information necessary to fully assess the health significance of hazardous air pollutants is not currently available. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether the Arthritis Self-Management Programme (ASMP) is effective in promoting perceived control and self-management ability when delivered in an adult education setting. The study was a pre-test-post-test design based on a sample of 89 people attending an ASMP. Data were collected by self-administered questionnaires prior to the intervention and after the intervention, 4 months from baseline. The sample comprised 80% women, with a mean age of 57 years and a mean disease duration of 13 years. Most participants had either osteoarthritis or rheumatoid arthritis. After 4 months, participants demonstrated significant increases in arthritis self-efficacy (P < 0.0005), cognitive symptom management (P < 0.0005), communication with doctors (P = 0.018), exercise (P = 0.003) and relaxation (P < 0.00005). In addition, significant decreases were found in terms of pain (P = 0.034) and visits to other health professionals (P = 0.004). The first evaluation of the ASMP, delivered within the context of adult education, suggests that this form of community health education programme can offer substantial benefits for participants, particularly in terms of perceived ability to control various aspects of arthritis and in greater utilization of cognitive-behavioral techniques. [ABSTRACT FROM AUTHOR]

Objective.A previous UK evaluation of the Arthritis Self-Management Programme (ASMP) demonstrated 4 month improvements in physical and psychological well-being including increased arthritis self-efficacy and increased use of self-management behaviours such as cognitive symptom management, and reductions in pain, fatigue and anxiety. The purpose of this study was to determine whether these effects were maintained at 12 month follow-up. [ABSTRACT FROM PUBLISHER]

Despite the wide availability of disease-related leaflets, their impact on patients' knowledge and well-being has rarely been evaluated. A randomized controlled study of a 'Rheumatoid Arthritis' leaflet revealed increased knowledge among the intervention group after 3 weeks. In addition, the leaflet was viewed as a source of reassurance. The purpose of the follow-up study was to determine whether the increase in knowledge was maintained in the longer term and to examine psychological well-being. Eighty-four patients (42 intervention and 42 control) completed the 6 month follow-up. There were no significant changes (P > 0.01) in mean outcome measures over the period 3 weeks-6 months for either the intervention or control groups. Patients in the intervention group retained the increase in knowledge observed at 3 weeks. Moreover, there was no evidence of adverse reactions to the leaflet in terms of psychological distress. Leaflets can be effective in promoting longer term increases in knowledge. [ABSTRACT FROM PUBLISHER]

Objective.With the advent of community-based arthritis education programmes, it is important to determine the accuracy of participants' self-reported diagnoses. The purpose of this study was to determine the level of agreement between general practitioner (GP)-recorded and self-reported diagnoses of participants attending an Arthritis Self-Management Programme (ASMP). [ABSTRACT FROM PUBLISHER]

Background: This retrospective comparative cohort study aimed to evaluate the effects of COVID-19 on professionalism within the perioperative environment of a tertiary cancer center across three periods: pre-pandemic, pandemic, and an interventional endemic phase., Methods: A retrospective observational review of a prospectively maintained safety event report (SER) database at MD Anderson Cancer Center, with an intervention during the COVID-19 endemic phase, was conducted. This was performed to compare the incidence of professionalism-related events (PRE), which are included in the SER database, during the COVID-19 pandemic period (March 2020 to May 2022), with a pre-pandemic period (September 2011 to February 2020) and a postintervention endemic phase (June 2022 to March 2023). Study interventions included the application of the Vanderbilt Professionalism Escalation Model with broad staff and surgical team education., Results: During the study period, 17,425 SERs were reviewed. Of these, 11,731 (mean 115.0 SERs/month) were reported in the pre-pandemic period, 4,004 SERs (mean 148.3 SERs/month) in the pandemic period, and 1,690 SERs (mean 169.0 SERs/month) in the endemic phase (p = 0.001). There was a statistically significant increase in the incidence of PRE during the pandemic compared to the pre-pandemic and endemic periods. Specifically, 264 PRE (1.5%) were identified during the study period: 114 PRE (mean 1.1 PRE/month) in the pre-pandemic period, 121 PRE (mean 4.5 PRE/month) in the pandemic period, and 29 PRE (mean 2.9 PRE/month) in the endemic phase (p = 0.001). The increase in PRE during the pandemic period corresponded to a concomitant increase in staff turnover rates (15.5%) compared to the pre-pandemic period (8.3%). However, a time shift of four months into the postintervention endemic phase demonstrated a successful reduction to less than pre-pandemic levels of staff turnover (6.7%, p = 0.001)., Conclusion: The COVID-19 pandemic was associated with a significant increase in SERs describing professionalism lapses among health care providers in the perioperative environment. Hospital organizations must recognize the impact of professionalism on morale and turnover and seek to mitigate its effects. Education, promoting individual accountability, confidential reporting, addressing wellness concerns, and providing modes of resilience can enhance workplace culture and potentially cultivate better employee retention rates., (Copyright © 2024 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

The challenges facing the health care industry in the post-coronavirus disease 2019 (COVID-19) pandemic world are numerous, jeopardizing wellness, and performance. Maintaining engagement and fulfillment of anesthesiologists in their work is now a critical issue in various practice settings: academic, private practice, and corporate medicine. In this article, we offer insights on how mentorship, sponsorship, and allyship are important in the advancement of the anesthesiology workforce including women and underrepresented minorities inclusive of race, gender, and disability. Mentorship, sponsorship, and allyship require a framework that intentionally addresses the programmatic structures needed to optimize the environment for increasing women, underrepresented minorities, and other diverse groups. These 3 distinct yet interrelated concepts are defined with a discussion on the value of implementation. In addition, the concept of "belonging" and its importance in enhancing the culture in anesthesiology is explored. We believe that part of the solution to wellness, recruitment and retention and improved job satisfaction of clinicians is having an environment where mentorship, sponsorship, and allyship are foundational., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Objective: To evaluate variability among hospitals in susceptibility of common uropathogens to antimicrobial agents frequently used in transurethral procedures in order to examine whether state-based guidelines might be more appropriate than national prophylactic guidelines., Methods: Hospital-level antibiograms were requested from all hospitals throughout the state of Missouri. We studied Escherichia coli, Klebsiella, and Proteus sensitivities to evaluate common guideline recommended antimicrobials including trimethoprim sulfamethoxazole (TMP-SMX), third-generation cephalosporins, cefazolin, penicillin combinations, gentamicin, and fluoroquinolones. We evaluated variability and association between hospital characteristics and antimicrobial sensitivities., Results: Data was requested from 81 hospitals across the state and 38 provided the requested data (47% response rate). Susceptibility was highest for third-generation cephalosporins for E. coli (mean of 94%), Proteus (96%), and Klebsiella (96%). Gentamicin also had high susceptibility for the bacteria studied; 94% for E. coli and 96% for Klebsiella. Current first line recommended agents showed more modest coverage for E. coli (cefazolin 84%, TMP-SMX 78%), Proteus (cefazolin 82%, TMP-SMX 71%), and Klebsiella (cefazolin 90%, TMP-SMX 89%)., Conclusion: Post transurethral procedure infections are common. Rates can be limited with appropriate prophylaxis. Deciding on empirical coverage must take into account local resistance patterns. There is substantial variability among and within states in antimicrobial susceptibility for common uropathogens. When selecting antimicrobial prophylaxis, urologists should consider local- rather than state- or nation-level antibiograms, given the considerable variability. Future studies should consider the merits of very-broad spectrum prophylaxis and the potential role of molecular urinary pathogen (and pathogen-resistance) testing when selecting an optimal regimen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mycobacterium tuberculosis is a highly specialized human pathogen. The success of M. tuberculosis is due to its ability to replicate within host macrophages, resist host immune responses, and ultimately enter a persistent state during a latent tuberculosis infection. Understanding how M. tuberculosis adapts to and replicates in the intracellular environment of the host is crucial for the development of novel, targeted therapeutics. We report the characterization of an M. tuberculosis mutant lacking Rv3249c, a TetR transcriptional regulator. We show that Rv3249c directly represses the adjacent alkB-rubA-rubB operon encoding an alkane hydroxylase/rubredoxin system. For consistency with related systems, we have named the rv3249c gene alkX . The alkX mutant survived better than wild-type M. tuberculosis inside macrophages. This could be phenocopied by overexpression of the alkB-rubA-rubB locus. We hypothesized that the improved intracellular survival phenotype is a result of increased fitness of the mutant; however, we found that the alkX mutant had a defect when grown on some host-associated carbon sources in vitro . We also found that the alkX mutant had a defect in biofilm formation, also linked to the overexpression of the alkB-rubAB genes. Combined, these results define the primary role of AlkX as a transcriptional repressor of the alkB-rubAB operon and suggest the operon contributes to intracellular survival of the pathogen. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is the leading cause of death worldwide due to a single infectious agent. It is important to understand how M. tuberculosis adapts to and replicates in the intracellular environment of the host. In this study, we characterized the TetR transcriptional regulator Rv3249c and show that it regulates a highly conserved alkane hydroxylase/rubredoxin system. Our data demonstrate that the AlkBRubAB system contributes to the success of the bacterium in host macrophages.

The role of boron in terrestrial plant physiology is diverse and increasingly well understood, but its role in marine aquatic eukaryotes is less clear. Our research reveals a distinctive and large offset in boron isotopes from seawater, irrespective of seaweed type or season. We show that the offset is consistent with the incorporation of borate from seawater. Boron is a known micronutrient in plants but very few studies have used boron isotopes to investigate boron's role in plant physiology. Seaweed, as the most primitive multicellular plant, has an important role in investigating wider plant adaptations that use boron to meet functional needs. Furthermore, seaweed and other plants are a key base nutrient provider in food webs, supplying boron to consumers and playing a critical role in boron environmental cycling.

Objectives: To eliminate catheter-associated urinary tract infections in a pediatric cardiac ICU., Design: Quality improvement methodology., Setting: Twenty-five bed cardiac ICU in a quaternary freestanding children's hospital., Patients: All patients with an indwelling urinary catheter admitted to the cardiac ICU., Interventions: Catheter-associated urinary tract infection was defined according to National Healthcare Safety Network criteria. Failure modes and effects analysis and Pareto charts were used to determine etiology of process failures. We implemented a team-based multi-interventional approach in 2012 using the Model for Improvement, which included as follows: 1) establish indications for inserting and/or maintaining bladder catheterization, 2) standardization of maintenance care for the indwelling urinary catheters, 3) protocol for management of the leaking urinary catheters, 4) incorporation of urinary catheter days and prompts for removal in daily rounds, and 5) review of all cases of prolonged indwelling urinary catheter use (> 3 d). Process control charts were used to evaluate change., Measurements and Main Results: From 2011 to 2018, we showed an early and sustained improvement in catheter-associated urinary tract infection prevention standards compliance from 44% to 96% (52% improvement). These interventions showed a reduction and then elimination of catheter-associated urinary tract infections from January 2012 to the present day, despite fluctuations in total indwelling urinary catheter days., Conclusions: Utilization of quality improvement methodology allowed us to identify components of care that contributed to catheter-associated urinary tract infections. After addressing these issues, we noted a substantial reduction and then elimination of catheter-associated urinary tract infections in our pediatric cardiac ICU. Widely disseminating these interventions across multiple pediatric hospitals to determine the ability to achieve similar results are important next steps.

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.

Obstetrical chain placement requires location of specific landmarks and a certain dexterity that must be practiced. Use of low-fidelity models may not always provide students with a realistic experience. In this study we developed an anatomically correct high-fidelity calf leg model that would serve as a better teaching model for pre-clinical veterinary students than a pre-existing low-fidelity polyvinyl chloride (PVC) model. One hundred and twenty pre-clinical veterinary students were instructed how to use obstetrical chains with a low-fidelity PVC model and the anatomically correct high-fidelity calf leg model. After a 45-minute lab, students were surveyed on their experience with both models. Overall students felt the anatomically correct high-fidelity calf leg model increased accuracy in chain placement and provided more accurate landmarks, a more realistic model, and more real-life scenario training.

The mycobacterial cell wall is crucial to the host-pathogen interface, because it provides a barrier against antibiotics and the host immune response. In addition, cell wall lipids are mycobacterial virulence factors. The m ycobacterial m embrane p rotein l arge (MmpL) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and Mycobacterium tuberculosis pathogenesis. MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria, a feature consistent with an important role in the basic physiology of the bacterium. MmpL3 is essential and transports trehalose monomycolate to the mycobacterial surface. In this report, we characterize the role of MmpL11 in M. tuberculosis. M. tuberculosis mmpL11 mutants have altered biofilms associated with lower levels of mycolic acid wax ester and long-chain triacylglycerols than those for wild-type bacteria. While the growth rate of the mmpL11 mutant is similar to that of wild-type M. tuberculosis in macrophages, the mutant exhibits impaired survival in an in vitro granuloma model. Finally, we show that the survival or recovery of the mmpL11 mutant is impaired when it is incubated under conditions of nutrient and oxygen starvation. Our results suggest that MmpL11 and its cell wall lipid substrates are important for survival in the context of adaptive immune pressure and for nonreplicating persistence, both of which are critically important aspects of M. tuberculosis pathogenicity., (Copyright © 2017 American Society for Microbiology.)

Background and Objectives: Reflection after patient encounters is an important aspect of clinical learning. After our medical school instituted a reflection paper assignment for all clerkships, we wanted to learn about the types of encounters that students found meaningful on a family medicine clerkship and how they impacted students' learning., Methods: Family and Community Medicine Clerkship students completed a reflection paper after the clerkship, based on guidelines that were used for all clerkship reflection papers at our medical school. Two reviewers independently organized student responses into themes and then jointly prioritized common themes and negotiated any initial differences into other themes., Results: A total of 272 reflection papers describing an actual learning moment in patient care were submitted during the study period of January 2011--December 2012. In describing actions performed, students most frequently wrote about aspects of patient-centered care such as listening to the patient, carefully assessing the patient's condition, or giving a detailed explanation to the patient. In describing effects of those actions, students wrote about what they learned about the patient-physician interaction, the trust that patients demonstrated in them, the approval they gained from their preceptors, and the benefits they saw from their actions., Conclusions: An important contribution of a family medicine clerkship is the opportunity for students to further their skills in patient-centered care and realize the outcomes of providing that type of care.

Mycobacterium tuberculosis is a pathogenic bacterial species, which is neither Gram positive nor Gram negative. It has a unique cell wall, making it difficult to kill and conferring resistance to antibiotics that disrupt cell wall biosynthesis. Thus, the mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the mycobacterial membrane protein large (MmpL) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complicated regulatory network system. Here we report crystallographic structures of two forms of the TetR-family transcriptional regulator Rv0302, which participates in regulating the expression of MmpL proteins. The structures reveal a dimeric, two-domain molecule with architecture consistent with the TetR family of regulators. Comparison of the two Rv0302 crystal structures suggests that the conformational changes leading to derepression may be due to a rigid body rotational motion within the dimer interface of the regulator. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by this protein. In addition, our isothermal titration calorimetry and electrophoretic mobility shift experiments indicate that fatty acids may be the natural ligand of this regulator. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters., (© 2015 The Protein Society.)

The mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the MmpL (mycobacterial membrane protein large) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complex regulatory network, including the TetR family transcriptional regulators Rv3249c and Rv1816. Here we report the crystal structures of these two regulators, revealing dimeric, two-domain molecules with architecture consistent with the TetR family of regulators. Buried extensively within the C-terminal regulatory domains of Rv3249c and Rv1816, we found fortuitous bound ligands, which were identified as palmitic acid (a fatty acid) and isopropyl laurate (a fatty acid ester), respectively. Our results suggest that fatty acids may be the natural ligands of these regulatory proteins. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by these proteins. Binding of palmitic acid renders these regulators incapable of interacting with their respective operator DNAs, which will result in derepression of the corresponding mmpL genes. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

As demonstrated by the 2011 publication of the National Heart, Lung, and Blood Institute Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, the information available regarding the treatment of pediatric lipid disorders has greatly expanded. HMG-CoA reductase inhibitor, or statin, therapy is now considered a first-line pharmacologic intervention for pediatric patients with severe dyslipidemias failing treatment with diet and exercise alone. Despite their ability to effectively reduce cholesterol levels, bile acid sequestrants continue to pose challenges for pediatric patients because of their unpalatability and are typically used as adjunctive therapy or for patients not able to tolerate statins. Fibric acid derivatives, as a class of medications, not only lack a Food and Drug Administration (FDA)-approved agent, but also continue to lack significant pediatric safety and efficacy data. Niacin, a potential adjunct therapy, lacks FDA approval for pediatric patients and is plagued by significant adverse effects making it an unlikely therapy option for pediatric patients. Ezetimibe provides clinicians with an alternative adjunct therapy option when synergistically paired with an HMG-CoA reductase inhibitor or it can be used as monotherapy for patients intolerant to statins and bile acid sequestrants. Finally, despite several marketed formulations, omega-3 fish oils currently lack FDA approval in pediatric patients and have failed to demonstrate statistically significant lipid lowering in pediatric and adolescent patients. Although recent years have witnessed a dramatic increase in data available for the use of lipid-lowering medications for pediatric patients, long-term study data are still generally lacking and continues to present an active focus of research., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Following reactivation from latency, there are two distinct steps in the spread of herpes simplex virus (HSV) from infected neurons to epithelial cells: (i) anterograde axonal transport of virus particles from neuron bodies to axon tips and (ii) exocytosis and spread of extracellular virions across cell junctions into adjacent epithelial cells. The HSV heterodimeric glycoprotein gE/gI is important for anterograde axonal transport, and gE/gI cytoplasmic domains play important roles in sorting of virus particles into axons. However, the roles of the large (∼400-residue) gE/gI extracellular (ET) domains in both axonal transport and neuron-to-epithelial cell spread have not been characterized. Two gE mutants, gE-277 and gE-348, contain small insertions in the gE ET domain, fold normally, form gE/gI heterodimers, and are incorporated into virions. Both gE-277 and gE-348 did not function in anterograde axonal transport; there were markedly reduced numbers of viral capsids and glycoproteins compared with wild-type HSV. The defects in axonal transport were manifest in neuronal cell bodies, involving missorting of HSV capsids before entry into proximal axons. Although there were diminished numbers of mutant gE-348 capsids and glycoproteins in distal axons, there was efficient spread to adjacent epithelial cells, similar to wild-type HSV. In contrast, virus particles produced by HSV gE-277 spread poorly to epithelial cells, despite numbers of virus particles similar to those for HSV gE-348. These results genetically separate the two steps in HSV spread from neurons to epithelial cells and demonstrate that the gE/gI ET domains function in both processes., Importance: An essential phase of the life cycle of herpes simplex virus (HSV) and other alphaherpesviruses is the capacity to reactivate from latency and then spread from infected neurons to epithelial tissues. This spread involves at least two steps: (i) anterograde transport to axon tips followed by (ii) exocytosis and extracellular spread from axons to epithelial cells. HSV gE/gI is a glycoprotein that facilitates this virus spread, although by poorly understood mechanisms. Here, we show that the extracellular (ET) domains of gE/gI promote the sorting of viral structural proteins into proximal axons to begin axonal transport. However, the gE/gI ET domains also participate in the extracellular spread from axon tips across cell junctions to epithelial cells. Understanding the molecular mechanisms involved in gE/gI-mediated sorting of virus particles into axons and extracellular spread to adjacent cells is fundamentally important for identifying novel targets to reduce alphaherpesvirus disease., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Objective: To assess the inter-rater reliability (IRR) of two novel observation tools for measuring surgical safety checklist performance and teamwork., Summary Background: Data surgical safety checklists can promote adherence to standards of care and improve teamwork in the operating room. Their use has been associated with reductions in mortality and other postoperative complications. However, checklist effectiveness depends on how well they are performed., Methods: Authors from the Safe Surgery 2015 initiative developed a pair of novel observation tools through literature review, expert consultation and end-user testing. In one South Carolina hospital participating in the initiative, two observers jointly attended 50 surgical cases and independently rated surgical teams using both tools. We used descriptive statistics to measure checklist performance and teamwork at the hospital. We assessed IRR by measuring percent agreement, Cohen's κ, and weighted κ scores., Results: The overall percent agreement and κ between the two observers was 93% and 0.74 (95% CI 0.66 to 0.79), respectively, for the Checklist Coaching Tool and 86% and 0.84 (95% CI 0.77 to 0.90) for the Surgical Teamwork Tool. Percent agreement for individual sections of both tools was 79% or higher. Additionally, κ scores for six of eight sections on the Checklist Coaching Tool and for two of five domains on the Surgical Teamwork Tool achieved the desired 0.7 threshold. However, teamwork scores were high and variation was limited. There were no significant changes in the percent agreement or κ scores between the first 10 and last 10 cases observed., Conclusions: Both tools demonstrated substantial IRR and required limited training to use. These instruments may be used to observe checklist performance and teamwork in the operating room. However, further refinement and calibration of observer expectations, particularly in rating teamwork, could improve the utility of the tools., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Use of fecal indicator bacteria (FIB) for monitoring beach water quality is based on their co-occurrence with human pathogens, a relationship that can be dramatically altered by fate and transport processes after leaving the human intestine. We conducted a prospective cohort study at Avalon Beach, California (USA), where the indicator relationship is potentially affected by the discharge of sewage-contaminated groundwater and by solar radiation levels at this shallow, relatively quiescent beach. The goals of this study were to determine: 1) if swimmers exposed to marine water were at higher risk of illness than non-swimmers; 2) if FIB measured in marine water were associated with swimmer illness, and; 3) if the associations between FIB and swimmer health were modified by either submarine groundwater discharge or solar radiation levels. There were 7317 individuals recruited during the summers of 2007-08, 6165 (84%) of whom completed follow-up within two weeks of the beach visit. A total of 703 water quality samples were collected across multiple sites and time periods during recruitment days and analyzed for FIB using both culture-based and molecular methods. Adjusted odds ratios (AOR) indicated that swimmers who swallowed water were more likely to experience Gastrointestinal Illness (GI Illness) within three days of their beach visit than non-swimmers, and that this risk was significantly elevated when either submarine groundwater discharge was high (AOR [95% CI]:2.18 [1.22-3.89]) or solar radiation was low (2.45 [1.25-4.79]). The risk of GI Illness was not significantly elevated for swimmers who swallowed water when groundwater discharge was low or solar radiation was high. Associations between GI Illness incidence and FIB levels (Enterococcus EPA Method 1600) among swimmers who swallowed water were not significant when we did not account for groundwater discharge, but were strongly associated when groundwater discharge was high (1.85 [1.06, 3.23]) compared to when it was low (0.77 [0.42, 1.42]; test of interaction: P = 0.03). These results demonstrate the need to account for local environmental conditions when monitoring for, and making decisions about, public health at recreational beaches. The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Recent work demonstrates that the MmpL (mycobacterial membrane protein large) transporters are dedicated to the export of mycobacterial lipids for cell wall biosynthesis. An MmpL transporter frequently works with an accessory protein, belonging to the MmpS (mycobacterial membrane protein small) family, to transport these key virulence factors. One such efflux system in Mycobacterium tuberculosis is the MmpS5-MmpL5 transporter. The expression of MmpS5-MmpL5 is controlled by the MarR-like transcriptional regulator Rv0678, whose open reading frame is located downstream of the mmpS5-mmpL5 operon. To elucidate the structural basis of Rv0678 regulation, we have determined the crystal structure of this regulator, to 1.64 Å resolution, revealing a dimeric two-domain molecule with an architecture similar to members of the MarR family of transcriptional regulators. Rv0678 is distinct from other MarR regulators in that its DNA-binding and dimerization domains are clustered together. These two domains seemingly cooperate to bind an inducing ligand that we identified as 2-stearoylglycerol, which is a fatty acid glycerol ester. The structure also suggests that the conformational change leading to substrate-mediated derepression is primarily caused by a rigid body rotational motion of the entire DNA-binding domain of the regulator toward the dimerization domain. This movement results in a conformational state that is incompatible with DNA binding. We demonstrate using electrophoretic mobility shift assays that Rv0678 binds to the mmpS5-mmpL5, mmpS4-mmpL4, and the mmpS2-mmpL2 promoters. Binding by Rv0678 was reversed upon the addition of the ligand. These findings provide new insight into the mechanisms of gene regulation in the MarR family of regulators., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objective: To investigate whether feedback inducing an external focus (EF) of attention (about movement effects) was more effective for retraining reach-to-grasp after stroke compared with feedback inducing an internal focus (IF) of attention (about body movement). It was predicted that inducing an EF of attention would be more beneficial to motor performance., Design: Crossover trial where participants were assigned at random to two feedback order groups: IF followed by EF or EF followed by IF., Setting: Research laboratory., Participants: Forty-two people with upper limb impairment after stroke., Intervention: Participants performed three reaching tasks: (A) reaching to grasp a jar; (B) placing a jar forwards on to a table; and (C) placing a jar on to a shelf. Ninety-six reaches were performed in total over one training session., Main Outcome Measures: Kinematic measures were collected using motion analysis. Primary outcome measures were movement duration, peak velocity of the wrist, size of peak aperture and peak elbow extension., Results: Feedback inducing an EF of attention produced shorter movement durations {first feedback order group: IF mean 2.53 seconds [standard deviation (SD) 1.85]; EF mean 2.12 seconds (SD 1.63), mean difference 0.41 seconds; 95% confidence interval -0.68 to 1.5; P=0.008}, an increased percentage time to peak deceleration (P=0.01) when performing Task B, and an increased percentage time to peak velocity (P=0.039) when performing Task A compared with feedback inducing an IF of attention. However, an order effect was present whereby performance was improved if an EF of attention was preceded by an IF of attention., Conclusions: Feedback inducing an EF of attention may be of some benefit for improving motor performance of reaching in people with stroke in the short term; however, these results should be interpreted with caution. Further research using a randomised design is recommended to enable effects on motor learning to be assessed., (Copyright © 2013 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)