bluuebunny/crossref_metadata_2025 huggingface dataset:
Left Ventricular Hypertrophy Predicts Cardiovascular Events in Hypertensive Patients With Coronary Artery Calcifications
Authors: Grossman Chagai , Levin Michael , Koren-Morag Nira , Bornstein Gill , Leibowitz Avshalom , Ben-Zvi Ilan , Shemesh Joseph , Grossman Ehud
Published: October 2017

BACKGROUND

Coronary artery calcification (CAC) is associated with increased cardiovascular (CV) risk. Left ventricular hypertrophy (LVH) is an independent risk factor for CV events. Our aim was to estimate the relative CV risk of LVH in the presence of CAC.

METHODS

We included asymptomatic hypertensive patients who were enrolled in the calcification arm of the INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy). Patients had baseline echocardiography and computed tomography to assess CAC. The primary end-point was the first CV event.

RESULTS

Two hundred and fifty-two subjects (mean age 64.7 ± 5.5 years, 54% men) were followed for a mean of 13.3 ± 2.6 years. 72 patients (28.5%) had LVH and 159 patients (63%) had CAC. During follow up, 89 patients had a first CV event. The rate of CV events was higher in those with than in those without CAC (43.4% vs. 21.5%, P < 0.01) and in those with than in those without LVH (44% vs. 31.6%, P < 0.01). However, LVH had no effect on CV events in the absence of CAC, whereas LVH almost doubled the rate of CV events (61.4% vs. 36.5%, P < 0.01) in the presence of CAC. In comparison to patients without CAC and without LVH the hazard ratio for CV event in those with LVH was 1.46 (95% confidence interval [CI], 0.50–4.21) in those without CAC and 4.4 (95% CI, 2.02–9.56) in those with CAC.

CONCLUSIONS

LVH and CAC independently predict CV events in asymptomatic hypertensive patients. However, the risk of LVH is mainly observed in those with CAC.
PyDREAM: high-dimensional parameter inference for biological models in python
Authors: Shockley Erin M , Vrugt Jasper A , Lopez Carlos F
Published: October 2017

Biological models contain many parameters whose values are difficult to measure directly via experimentation and therefore require calibration against experimental data. Markov chain Monte Carlo (MCMC) methods are suitable to estimate multivariate posterior model parameter distributions, but these methods may exhibit slow or premature convergence in high-dimensional search spaces. Here, we present PyDREAM, a Python implementation of the (Multiple-Try) Differential Evolution Adaptive Metropolis [DREAM(ZS)] algorithm developed by Vrugt and ter Braak (2008) and Laloy and Vrugt (2012). PyDREAM achieves excellent performance for complex, parameter-rich models and takes full advantage of distributed computing resources, facilitating parameter inference and uncertainty estimation of CPU-intensive biological models.

Availability and implementation

PyDREAM is freely available under the GNU GPLv3 license from the Lopez lab GitHub repository at http://github.com/LoLab-VU/PyDREAM.

Supplementary information

Supplementary data are available at Bioinformatics online.
BetaSerpentine: a bioinformatics tool for reconstruction of amyloid structures
Authors: Bondarev Stanislav A , Bondareva Olga V , Zhouravleva Galina A , Kajava Andrey V
Published: October 2017

Motivation

Numerous experimental studies have suggested that polypeptide chains of large amyloidogenic regions zig-zag in β-serpentine arrangements. These β-serpentines are stacked axially and form the superpleated β-structure. Despite this progress in the understanding of amyloid folds, the determination of their 3D structure at the atomic level is still a problem due to the polymorphism of these fibrils and incompleteness of experimental structural data. Today, the way to get insight into the atomic structure of amyloids is a combination of experimental studies with bioinformatics.

Results

We developed a computer program BetaSerpentine that reconstructs β-serpentine arrangements from individual β-arches predicted by ArchCandy program and ranks them in order of preference. It was shown that the BetaSerpentine program in combination with the experimental data can be used to gain insight into the detailed 3D structure of amyloids. It opens avenues to the structure-based interpretation and design of the experiments.

Availability and implementation

BetaSerpentine webserver can be accessed through website: http://bioinfo.montp.cnrs.fr/b-serpentine. Source code is available in git.hub repository (github.com/stanislavspbgu/BetaSerpentine).

Supplementary information

Supplementary data are available at Bioinformatics online.
Towards unified quality verification of synthetic count data with countsimQC
Authors: Soneson Charlotte , Robinson Mark D
Published: October 2017

Statistical tools for biological data analysis are often evaluated using synthetic data, designed to mimic the features of a specific type of experimental data. The generalizability of such evaluations depends on how well the synthetic data reproduce the main characteristics of the experimental data, and we argue that an assessment of this similarity should accompany any synthetic dataset used for method evaluation. We describe countsimQC, which provides a straightforward way to generate a stand-alone report that shows the main characteristics of (e.g. RNA-seq) count data and can be provided alongside a publication as verification of the appropriateness of any utilized synthetic data.

Availability and implementation

countsimQC is implemented as an R package (for R versions ≥ 3.4) and is available from https://github.com/csoneson/countsimQC under a GPL (≥2) license.
Reflections on using a community-led research methodology to explore experiences of living with food insecurity
Authors: Greenaway Lesley , McDowell Jacqui
Published: October 2017

This article explores how community-led research in practice relates to the theory and aspirations of a community-led research methodology and how this approach can provide a unique opportunity to increase our understanding about the lived experiences of food insecurity. As an approach, community-led research has growing influence and relevance for communities, organizations, research commissioners, funders and policy makers. This article provides insights and learning for these stakeholders that we discovered in our experience of the ‘Living with food insecurity’ community-led research project. We draw on a range of sources including: community-led research literature, materials developed to support the project, feedback from the research teams, and reflective conversations between the research commissioner and the research specialist who was engaged to support the process. We start by setting out the context for food insecurity in Scotland and identify the research gap that led to the research project. We then discuss some pertinent research challenges in the context of this project, and explore how each of three distinct communities developed different models of community-led research. Learning from this project suggests that community-led research design needs to embrace divergence and facilitate research partnerships that are flexible, open and find ways to ‘live’ out the principles of community-led research in ways that are meaningful to a particular community and its stakeholders.
Investigating the spatiotemporal variation of fish choruses to help identify important foraging habitat for Indo-Pacific humpback dolphins, Sousa chinensis
Authors: Pine Matthew K , Wang Ding , Porter Lindsay , Wang Kexiong
Published: October 2017

Given the common physical overlapping between coastal developments and important marine mammal habitats, there is a need to identify potentially important foraging grounds for dolphins when informing marine spatial planning and management of underwater noise. Hydrophones were deployed at four locations either side of the mainland China–Hong Kong Special Administrative Region border to monitor the presence of soniferous fishes; a key prey item for Indo-Pacific humpback dolphins. Five distinct chorus-types were identified; each showing spatiotemporal variability. Each chorus-type was assumed to represent a separate species. Chorus-type diversity also differed between sites, with SP4 and SP5 types only being detected within Hong Kong waters where bottom trawling is illegal. Chorus-type SP1 was only detected at the recording sites in mainland Chinese waters. Call rates and chorus duration were highest during the spring and summer months. Given these dolphins show a predator-prey relationship, these data provide new information on the local fish communities at a much finer-scale than fish landing records and a baseline of fish activity in an environment that is challenging to explore. Overlaid with acoustic detections of foraging dolphins, these data form a basis for identifying potentially important foraging habitats that should be afforded the highest priority for protection.
Ultrasmall Superparamagnetic Iron Oxide Imaging Identifies Tissue and Nerve Inflammation in Pain Conditions
Authors: Shen Shiqian , Ding Weihua , Ahmed Shihab , Hu Ranliang , Opalacz Arissa , Roth Sarah , You Zerong , Wotjkiewicz Gregory R , Lim Grewo , Chen Lucy , Mao Jianren , Chen John W , Zhang Yi
Published: October 2017

Objective

Correlation between radiologic structural abnormalities and clinical symptoms in low back pain patients is poor. There is an unmet clinical need to image inflammation in pain conditions to aid diagnosis and guide treatment. Ferumoxytol, an ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, is clinically used to treat iron deficiency anemia and showed promise in imaging tissue inflammation in human. We explored whether ferumoxytol can be used to identify tissue and nerve inflammation in pain conditions in animals and humans.

Methods

Complete Freud’s adjuvant (CFA) or saline was injected into mice hind paws to establish an inflammatory pain model. Ferumoxytol (20 mg/kg) was injected intravenously. Magnetic resonance imaging (MRI) was performed prior to injection and 72 hours postinjection. The changes in the transverse relaxation time (T2) before and after ferumoxytol injection were compared between mice that received CFA vs saline injection. In the human study, we administered ferumoxytol (4 mg/kg) to a human subject with clinical symptoms of lumbar radiculopathy and compared the patient with a healthy subject.

Results

Mice that received CFA exhibited tissue inflammation and pain behaviors. The changes in T2 before and after ferumoxytol injection were significantly higher in mice that received CFA vs saline (20.8 ± 3.6 vs 2.2 ± 2.5, P = 0.005). In the human study, ferumoxytol-enhanced MRI identified the nerve root corresponding to the patient’s symptoms, but the nerve root was not impinged by structural abnormalities, suggesting the potential superiority of this approach over conventional structural imaging techniques.

Conclusions

Ferumoxytol-enhanced MRI can identify tissue and nerve inflammation and may provide a promising diagnostic tool in assessing pain conditions in humans.
Distribution and Characterization of Monilinia spp. Causing Apple Fruit Decay in Serbia
Authors: Vasić Miljan , Vico Ivana , Jurick Wayne M. , Duduk Nataša
Published: October 2017

Brown rot, caused by Monilinia spp., is an economically important pre- and postharvest disease of pome and stone fruits worldwide. In Serbia, apple is the most widely grown pome fruit, and the distribution of economically important Monilinia spp. responsible for apple brown rot is unknown. Hence, we conducted a three year survey, from 2010 to 2012, where 349 isolates were obtained from six orchards and four storage facilities from five different apple cultivars with brown rot symptoms. Morphological characterization of the isolates, multiplex PCR, and phylogenetic analysis revealed four species: M. fructigena, M. laxa, M. fructicola, and Monilia polystroma. All species were found in the orchard and in storage, with M. fructigena predominating, followed by M. polystroma. Representative isolates were analyzed in vitro and in vivo where differences in growth rate, sporulation, and virulence on apple fruit were observed. Findings from this investigation demonstrate diversity in the species responsible for pre- and postharvest apple brown rot, which has significant implications for pathogen detection and for developing disease-specific management strategies.
Fluorescein Isothiocyanate Labeling Antigen-Based Immunoassay Strip for Rapid Detection of Acidovorax citrulli
Authors: Zeng Haijuan , Zhai Xuzhao , Xie Manman , Liu Qing
Published: October 2017

A simple and fast immunoassay strip to detect Acidovorax citrulli (Ac) using fluorescein isothiocyanate as a marker was developed. Fluorescein isothiocyanate (FITC) was added to sample culture medium for bacteria incubation, and the bacteria could emit a yellow-green fluorescence under ultraviolet light and become a fluorescent probe. This immunofluorescence strip (IFS) was based on the binding between fluorescent bacteria and the unlabeled monoclonal antibody (McAb) immobilized on the test area in nitrocellulose membrane. The detection limit of the strip was 106 CFU/ml with a result that could be observed within 10 min. The IFS could detect eight strains of Ac and display no cross-reactions with 30 other pathogenic strains. The detection results would not be affected by impurities in plant or unknown microorganisms in natural field samples and were consistent with PCR results, indicating that the IFS has high accuracy. This is the first report of using only one unlabeled McAb to develop a direct-type immunofluorescence strip for the rapid detection of Ac. The IFS reduced detection time and simplified operation procedures compared with the traditional enzyme-linked immunosorbent assay (ELISA) and PCR methods. In addition, this simple and inexpensive method will play a significant role in monitoring plant pathogens on field detection.
Aligning Education With Health Care Transformation: Identifying a Shared Mental Model of “New” Faculty Competencies for Academic Faculty
Authors: Gonzalo Jed D. , Ahluwalia Amarpreet , Hamilton Maria , Wolf Heidi , Wolpaw Daniel R. , Thompson Britta M.
Published: October 2017

Purpose

To develop a potential competency framework for faculty development programs aligned with the needs of faculty in academic health centers (AHCs).

Method

In 2014 and 2015, the authors interviewed 23 health system leaders and analyzed transcripts using constant comparative analysis and thematic analysis. They coded competencies and curricular concepts into subcategories. Lead investigators reviewed drafts of the categorization themes and subthemes related to gaps in faculty knowledge and skills, collapsed and combined competency domains, and resolved disagreements via discussion.

Results

Through analysis, the authors identified four themes. The first was core functional competencies and curricular domains for conceptual learning, including patient-centered care, health care processes, clinical informatics, population and public health, policy and payment, value-based care, and health system improvement. The second was the need for foundational competency domains, including systems thinking, change agency/management, teaming, and leadership. The third theme was paradigm shifts in how academic faculty should approach health care, categorized into four areas: delivery, transformation, provider characteristics and skills, and education. The fourth theme was the need for faculty to be aware of challenges in the culture of AHCs as an influential context for change.

Conclusions

This broad competency framework for faculty development programs expands existing curricula by including a comprehensive scope of health systems science content and skills. AHC leaders can use these results to better align faculty education with the real-time needs of their health systems. Future work should focus on optimal prioritization and methods for teaching.
Leading by Example: Role Modeling Resilience Helps Our Learners and Ourselves
Authors: Abaza Mona M. , Nelson Kathleen G.
Published: October 2017

The issues of burnout and its consequences are some of the most prevalent topics in conversations about the practice of medicine today. Many reports have focused on the contributors that fuel this epidemic, but the time has come to begin to focus on solutions. Prominent national efforts, including a National Academy of Medicine collaborative task force and the 2017 Accreditation Council for Graduate Medical Education common program requirements’ focus on wellness, are presenting opportunities for academic medicine faculty to take the lead in turning this tide. While solutions to the burnout crisis are complex, the foundations of improving this epidemic lie in restoring a sense of purpose and balance in the lives of those who work in academic medicine. The inherent value of academic medicine to improve others’ lives through patient care, the advancement of knowledge, and the education of the next generation is a unique opportunity that many other professions do not share. On the best days, academic medicine faculty must remember to look for that joy and to express it to learners, and, on the worst, they must demonstrate to learners how to practice self-care and how to create personal resilience. By taking on the role of becoming resilient, faculty start to foster a culture of well-being rather than burnout and can begin to find solutions instead of continuing to describe the problem.
A Multi-Institutional Longitudinal Faculty Development Program in Humanism Supports the Professional Development of Faculty Teachers
Authors: Branch William T. , Frankel Richard M. , Hafler Janet P. , Weil Amy B. , Gilligan MaryAnn C. , Litzelman Debra K. , Plews-Ogan Margaret , Rider Elizabeth A. , Osterberg Lars G. , Dunne Dana , May Natalie B. , Derse Arthur R.
Published: October 2017

The authors describe the first 11 academic years (2005–2006 through 2016–2017) of a longitudinal, small-group faculty development program for strengthening humanistic teaching and role modeling at 30 U.S. and Canadian medical schools that continues today. During the yearlong program, small groups of participating faculty met twice monthly with a local facilitator for exercises in humanistic teaching, role modeling, and related topics that combined narrative reflection with skills training using experiential learning techniques. The program focused on the professional development of its participants. Thirty schools participated; 993 faculty, including some residents, completed the program.

In evaluations, participating faculty at 13 of the schools scored significantly more positively as rated by learners on all dimensions of medical humanism than did matched controls. Qualitative analyses from several cohorts suggest many participants had progressed to more advanced stages of professional identity formation after completing the program. Strong engagement and attendance by faculty participants as well as the multimodal evaluation suggest that the program may serve as a model for others. Recently, most schools adopting the program have offered the curriculum annually to two or more groups of faculty participants to create sufficient numbers of trained faculty to positively influence humanistic teaching at the institution.

The authors discuss the program’s learning theory, outline its curriculum, reflect on the program’s accomplishments and plans for the future, and state how faculty trained in such programs could lead institutional initiatives and foster positive change in humanistic professional development at all levels of medical education.
Medical Humanities: The Rx for Uncertainty?
Authors: Ofri Danielle
Published: October 2017

While medical students often fear the avalanche of knowledge they are required to learn during training, it is learning to translate that knowledge into wisdom that is the greatest challenge of becoming a doctor. Part of that challenge is learning to tolerate ambiguity and uncertainty, a difficult feat for doctors who are taught to question anything that is not evidence based or peer reviewed. The medical humanities specialize in this ambiguity and uncertainty, which are hallmarks of actual clinical practice but rarely addressed in medical education. The humanities also force reflection and contemplation—skills that are crucial to thoughtful decision making and to personal wellness. Beyond that, the humanities add a dose of joy and beauty to a training process that is notoriously frugal in these departments. Well integrated, the humanities can be the key to transforming medical knowledge into clinical wisdom.
Right Ventricular Perfusion
Authors: Crystal George J. , Pagel Paul S.
Published: October 2017

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure–flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply–demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic–mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.
A Comparison of Back Pain Functional Scale With Roland Morris Disability Questionnaire, Oswestry Disability Index, and Short Form 36-Health Survey
Authors: Koç Meltem , Bayar Banu , Bayar Kılıçhan
Published: October 2017

Study Design.

A comparison study of Back Pain Functional Scale (BPFS) with Roland Morris Questionnaire (RMQ), Oswestry Disability Index (ODI), and Short Form 36-Health Survey (SF-36).

Objective.

The aim of this study is to investigate the correlation of BPFS with RMQ, ODI, and SF-36.

Summary of Background Data.

The primary goal in the treatment of patients with low back pain is to improve the patients’ levels of activities and participation. Many questionnaires focusing on function have been developed in patients with low back pain. BPFS is one of these questionnaires. No studies have investigated the correlation of BPFS with ODI and SF-36.

Methods.

This study was conducted with 120 patients receiving outpatient and inpatient treatment in physiotherapy and rehabilitation units of a state hospital. BPFS, RMQ, ODI, and SF-36 questionnaires were used to assess the disability in low back pain. Spearman and Pearson Correlation were used to compare the data obtained in the study.

Results.

There was a good correlation among the 5 functional outcome measures (correlation r = −0.693 for BPFS/RMQ, r = −0.794 for BPFS/ODI, r = 0.697 for BPFS/SF-36 Physical function and r = 0.540 for BPFS/SF-36 Pain).

Conclusion.

BPFS demonstrated good correlation with RMQ, ODI, SF-36 physical function, and SF-36 pain.

Level of Evidence: 2
Cartilage Endplate Thickness Variation Measured by Ultrashort Echo-Time MRI Is Associated With Adjacent Disc Degeneration
Authors: Berg-Johansen Britta , Han Misung , Fields Aaron J. , Liebenberg Ellen C. , Lim Brandon J. , Larson Peder EZ , Gunduz-Demir Cigdem , Kazakia Galateia J. , Krug Roland , Lotz Jeffrey C.
Published: October 2017

Study Design.

A magnetic resonance imaging study of human cadaver spines.

Objective.

To investigate associations between cartilage endplate (CEP) thickness and disc degeneration.

Summary of Background Data.

Damage to the CEP is associated with spinal injury and back pain. However, CEP morphology and its association with disc degeneration have not been well characterized.

Methods.

Ten lumbar motion segments with varying degrees of disc degeneration were harvested from six cadaveric spines and scanned with magnetic resonance imaging in the sagittal plane using a T2-weighted two-dimensional (2D) sequence, a three-dimensional (3D) ultrashort echo-time (UTE) imaging sequence, and a 3D T1ρ mapping sequence. CEP thicknesses were calculated from 3D UTE image data using a custom, automated algorithm, and these values were validated against histology measurements. Pfirrmann grades and T1ρ values in the disc were assessed and correlated with CEP thickness.

Results.

The mean CEP thickness calculated from UTE images was 0.74 ± 0.04 mm. Statistical comparisons between histology and UTE-derived measurements of CEP thickness showed significant agreement, with the mean difference not significantly different from zero (P = 0.32). Within-disc variation of T1ρ (standard deviation) was significantly lower for Pfirrmann grade 4 than Pfirrmann grade 3 (P < 0.05). Within-disc variation of T1ρ and adjacent CEP thickness heterogeneity (coefficient of variation) had a significant negative correlation (r = −0.65, P = 0.04). The standard deviation of T1ρand the mean CEP thickness showed a moderate positive correlation (r = 0.40, P = 0.26).

Conclusion.

This study demonstrates that quantitative measurements of CEP thickness measured from UTE magnetic resonance imaging are associated with disc degeneration. Our results suggest that variability in CEP thickness and T1ρ, rather than their mean values, may serve as valuable diagnostic markers for disc degeneration.

Level of Evidence: N/A
PD-1/PD-L1 and VEGF-A/VEGF-C expression in lymph node microenvironment and association with melanoma metastasis and survival
Authors: Alessi Cristina , Scapulatempo Neto Cristovam , Viana Cristiano R. , Vazquez Vinicius de Lima
Published: October 2017

Regional lymph nodes are affected frequently by melanoma metastasis. Its microenvironment may be associated with tumor progression. We investigated sentinel nodes with and without tumor and negative nodes surrounding positive nodes, looking for patterns related to tumor immune interaction and lymphovascular progression. We quantified programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1, vascular endothelial growth factor (VEGF)-A/VEGF-C expressions in lymph nodes of 103 patients who underwent sentinel lymph node biopsy. Two groups were studied: negative sentinel lymph nodes and positive ones. Negative lymph nodes of sequential lymphadenectomy from positive cases were also studied. Markers were assessed by immunohistochemistry. Results were related to clinical/histological outcomes. VEGF-A/VEGF-C analysis showed higher positivity in metastatic nodes and higher positivity in the surrounding negative nodes from positive cases in comparison with nonmetastatic patients. Programmed cell death-ligand 1, studied only in metastasis, presented high positivity, not associated with prognosis. PD-1 expressions were similar in the groups with a 1% cutoff and higher in the metastasis with a 5% cutoff. Higher VEGF-A expression was related to higher pathological stages. PD-1 expression in the lymph node was associated with higher survival. Other clinical and histopatological variables were not associated with marker expression patterns. VEGF-A and VEGF-C expressions in lymph nodes were associated with the presence of lymph node metastasis. PD-1 expression in the lymph node was related to higher survival rates and this should be explored in the context of adjuvant immunotherapy.
Part II: The Effects of Aromatherapy and Guided Imagery for the Symptom Management of Anxiety, Pain, and Insomnia in Critically Ill Patients
Authors: Meghani Naheed , Tracy Mary Fran , Hadidi Niloufar Niakosari , Lindquist Ruth
Published: October 2017

This review is part II of a 2-part series that presents evidence on the effectiveness of aromatherapy and guided imagery for the symptom management of anxiety, pain, and insomnia in adult critically ill patients. Evidence from this review supports the use of aromatherapy for management of pain, insomnia, and anxiety in critically ill patients. Evidence also supports the use of guided imagery for managing these symptoms in critical care; however, the evidence is sparse, mixed, and weak. More studies with larger samples and stronger designs are needed to further establish efficacy of guided imagery for the management of anxiety, pain, and insomnia of critically ill patients; to accomplish this, standardized evidence-based intervention protocols to ensure comparability and to establish optimal effectiveness are needed. Discussion and recommendations related to the use of these therapies in practice and needs for future research in these areas were generated.
Predictive Performance of Vancomycin Trough Concentrations in Patients With Diabetes With Microalbuminuria
Authors: Kimura Hiroshi , Shigematsu Marie , Tanaka Akihiro , Watanabe Shinichi , Takatori Shingo , Tanaka Mamoru , Mizuma Takashi , Araki Hiroaki
Published: October 2017

Background:

The performance of a population pharmacokinetic model in predicting trough concentrations after the initial vancomycin dose was evaluated in patients with albuminuria compared with patients who did not have albuminuria.

Methods:

Data were collected from 52 patients infected with methicillin-resistant Staphylococcus aureus (excluding patients undergoing dialysis and acute kidney injury) and treated with vancomycin. The data included urinary albumin concentration.

Results:

The calculated mean prediction error and mean absolute error for the serum trough concentrations of vancomycin (with 95% confidence intervals) were 4.65 (4.13–5.17) and 6.1 (5.65–6.51), respectively, in microalbuminuria and 0.33 (−0.2 to 0.86) and 4.02 (3.59–4.45), respectively, in those without. There was no significant difference observed in serum creatinine concentration, age, weight, estimation of vancomycin trough concentration in serum, and actual trough concentration of vancomycin in serum between individuals with microalbuminuria and those without albuminuria.

Conclusions:

Microalbuminuria in patients with diabetes is a marker of the difference between predicted vancomycin trough concentrations and actual vancomycin trough concentrations.
ARTERIAL OXYGEN SATURATION IN NEOVASCULARIZATIONS IN PROLIFERATIVE DIABETIC RETINOPATHY
Authors: Bek Toke
Published: October 2017

Purpose:

Retinal neovascularizations in proliferative diabetic retinopathy have been proposed to develop from larger retinal venules. However, angiographic evidence suggests that the new vessels may originate from both arterioles and venules, and the vitreous oxygen tension near retinal neovascularizations is similar to that of retinal arterioles. An assessment of the oxygen saturation in neovascularizations may help characterizing the vascular origin of these vessels in proliferative diabetic retinopathy.

Methods:

Dual wavelength oximetry was used to study the oxygen saturation in arterioles, venules, and retinal neovascularizations in 40 eyes from 40 patients with proliferative diabetic retinopathy.

Results:

The oxygen saturation was significantly lower in retinal venules than in arterioles and neovascularizations (P < 0.0001), and after a correction for the influence of vessel diameter, there was no significant difference between the oxygen saturation in retinal arterioles and neovascularizations (P = 0.71). Age at onset and duration of diabetes mellitus contributed significantly to the variation in oxygen saturation of the venules, whereas none of the clinical background parameters contributed to the variation in oxygen saturation in arterioles and neovascularizations.

Conclusion:

The oxygen saturation in retinal neovascularizations in proliferative diabetic retinopathy is similar to that of the arterioles. Neovascularizations may act as shunts to bypass areas of capillary occlusion.
Genomic Organization of TBK1 Copy Number Variations in Glaucoma Patients
Authors: DeLuca Adam P. , Alward Wallace L.M. , Liebmann Jeffrey , Ritch Robert , Kawase Kazuhide , Kwon Young H. , Robin Alan L. , Stone Edwin M. , Scheetz Todd E. , Fingert John H.
Published: October 2017

Background:

Approximately 1% of normal tension glaucoma (NTG) cases are caused by TANK-binding kinase 1 (TBK1) gene duplications and triplications. However, the precise borders and orientation of these TBK1 gene copy number variations (CNVs) on chromosome 12 are unknown.

Methods:

We determined the exact borders of TBK1 CNVs and the orientation of duplicated or triplicated DNA segments in 5 NTG patients with different TBK1 mutations using whole-genome sequencing.

Results:

Tandemly duplicated chromosome segments spanning the TBK1 gene were detected in 4 NTG patients, each with unique borders. Four of 5 CNVs had borders located within interspersed repetitive DNA sequences (Alu and long interspersed nuclear element-L1 elements), suggesting that mismatched homologous recombinations likely generated these CNVs. A fifth NTG patient had a complex rearrangement including triplication of a chromosome segment spanning the TBK1 gene.

Conclusions:

No specific mutation hotspots for TBK1 CNVs were detected, however, interspersed repetitive sequences (ie, Alu elements) were identified at the borders of TBK1 CNVs, which suggest that mismatch of these elements during meiosis may be the mechanism that generated TBK1 gene dosage mutations.
Acute Angle Closure Secondary to Tubercular Choroidal Granuloma
Authors: Kaushik Sushmita , Singh Ramandeep , Arora Atul , Joshi Gunjan , Sharma Kusum , Tigari Basavraj
Published: October 2017

Acute angle closure is usually thought to be secondary to pupillary block, which is relieved by laser iridotomy. Anterior rotation of the ciliary body at the scleral spur following development of an inflammatory ciliochoroidal detachment may result in a presentation of acute angle closure. It is imperative to recognize this condition correctly, because the management is with cycloplegics and anti-inflammatory drugs, which is diametrically opposite to the treatment of primary angle closure. More importantly, it has been reported as a consequence of serious systemic disease such as HIV infection and Vogt Koyanagi Harada (VKH) syndrome. We report a patient who presented to the medical emergency with headache and vomiting and was subsequently found to have acute angle closure in 1 eye secondary to a tubercular choroidal granuloma. This presentation of ocular tuberculosis has not been reported previously.
Effectiveness and costs of a vocational advice service to improve work outcomes in patients with musculoskeletal pain in primary care: a cluster randomised trial (SWAP trial ISRCTN 52269669)
Authors: Wynne-Jones Gwenllian , Artus Majid , Bishop Annette , Lawton Sarah A. , Lewis Martyn , Jowett Sue , Kigozi Jesse , Main Chris , Sowden Gail , Wathall Simon , Burton A. Kim , van der Windt Danielle A. , Hay Elaine M. , Foster Nadine E. ,   the SWAP Study Team
Published: October 2017

Musculoskeletal pain is a common cause of work absence, and early intervention is advocated to prevent the adverse health and economic consequences of longer-term absence. This cluster randomised controlled trial investigated the effect of introducing a vocational advice service into primary care to provide occupational support. Six general practices were randomised; patients were eligible if they were consulting their general practitioner with musculoskeletal pain and were employed and struggling at work or absent from work <6 months. Practices in the intervention arm could refer patients to a vocational advisor embedded within the practice providing a case-managed stepwise intervention addressing obstacles to working. The primary outcome was number of days off work, over 4 months. Participants in the intervention arm (n = 158) had fewer days work absence compared with the control arm (n = 180) (mean 9.3 [SD 21·7] vs 14·4 [SD 27·7]) days, incidence rate ratio 0·51 (95% confidence interval 0·26, 0·99), P = 0·048). The net societal benefit of the intervention compared with best care was £733: £748 gain (work absence) vs £15 loss (health care costs). The addition of a vocational advice service to best current primary care for patients consulting with musculoskeletal pain led to reduced absence and cost savings for society. If a similar early intervention to the one tested in this trial was implemented widely, it could potentially reduce days absent over 12 months by 16%, equating to an overall societal cost saving of approximately £500 million (US $6 billion) and requiring an investment of only £10 million.
Thirty- Versus Ten-Day Diazepam Treatment for Alcohol Detoxification and a Comparison of Drinking Patterns, Craving, and Anxiety for up to 12 Weeks
Authors: Simioni Nicolas , Labreuche Julien , Behal Hélène , Cottencin Olivier , Rolland Benjamin
Published: October 2017

Purpose

The aim of this study was to evaluate whether a prolonged detoxification treatment could decrease the relapse rate at 3 months after alcohol cessation in alcohol-dependent individuals through decreasing the levels of postdetoxification craving and anxiety.

Methods

Twenty-six adult patients with alcohol dependence (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) who began an outpatient alcohol cessation program with an initial drinking goal of abstinence were enrolled in a 3-month, parallel, randomized (1:1 ratio), controlled, open-label, pilot trial. Participants were randomized to receive a detoxification treatment of diazepam with a duration of 30 (n = 12) or 10 days (n = 14). All participants received BRENDA-based psychotherapy during follow-up.

Results

No significant between-group difference in relapse to any drinking was found at 3 months (P = 0.20). However, relapse to any heavy drinking at 3 months and regular drinking or heavy drinking during follow-up were significantly lower in the 30-day diazepam group (P = 0.009, P = 0.049, and P = 0.004, respectively). These differences were corroborated by significant differences in the alcohol-specific biological marker carbohydrate deficient transferrin at 3 months. Participants in the 30-day diazepam group also displayed significantly lower scores for alcohol craving (P = 0.007), self-reported anxiety (P = 0.024), and clinician-assessed anxiety (P = 0.002) throughout the follow-up. No serious adverse event was reported during the study.

Conclusion

This study provides an evidence-based rationale for a double-blind, randomized, placebo-controlled trial to confirm the efficacy of such a procedure on short-term and mid-/long-term drinking outcomes after alcohol cessation in alcohol-dependent individuals.
Effect of branched-chain amino acid supplements on muscle strength and muscle mass in patients with liver cirrhosis
Authors: Uojima Haruki , Sakurai Seiko , Hidaka Hisashi , Kinbara Takeshi , Sung Ji Hyun , Ichita Chikamasa , Tokoro Shinnosuke , Masuda Sakue , Sasaki Akiko , Koizumi Kazuya , Egashira Hideto , Kako Makoto , Kobayashi Shuzo
Published: October 2017

Objective

The aim of this study was to assess the effect of branched-chain amino acid (BCAA) supplements on muscle strength and muscle mass in patients with liver cirrhosis.

Patients and methods

We carried out a single-center, prospective study of adult cirrhotic patients receiving nutrition therapy at Shonan Kamakura General Hospital. A 28-day pretreatment observation period was followed by a 24-week treatment period. Patients who fulfilled the treatment criteria received one package of oral BCAA supplement powder twice a day and the response was evaluated. A responder to BCAA in muscle strength and muscle mass was defined as a patient with an increased skeletal muscle mass index and hand grip assessed 24 weeks after drug treatment commenced.

Results

Eighty-two patients fulfilled our criteria and completed the treatment. In terms of muscle strength, there were 59 (72.0%) responders to BCAA supplementation with a significant increase in hand grip from before treatment (22.2±6.3 kg) to after treatment (23.9±6.4 kg) (P<0.001). In terms of muscle mass, 36 (43.9%) patients responded to BCAA with a slight decrease in skeletal muscle mass index from before treatment (7.40±1.62) to after treatment (7.30±1.49) (P=0.333).

Conclusion

BCAA supplementation improved low muscle strength in patients with chronic liver disease, but did not increase muscle mass during the treatment period.
Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity
Authors: Cascio Michael J. , Jen Kuang-Yu
Published: October 2017

Purpose of review

Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed.

Recent findings

Although agranulocytosis and cutaneous vasculitis are the major findings in patients who develop cocaine/levamisole-associated autoimmune syndrome (CLAAS), more recent experience indicates that other organ systems can be involved as well. Current studies point to neutrophil activation and neutrophil extracellular trap formation with subsequent antineutrophil cytoplasmic antibody-mediated tissue injury as a possible mechanism of CLAAS.

In the past decade, the detrimental effects of levamisole have reemerged because of its popularity as a cocaine adulterant. Although infrequent, some individuals develop a systemic autoimmune syndrome characterized by immune-mediated agranulocytosis and antineutrophil cytoplasmic antibody-mediated vasculitis. Mechanistically, neutrophil antigens appear to be a major player in inducing CLAAS. Prompt cessation of levamisole exposure is key to treatment, although relapses are frequent because of the addictive effects of cocaine and the high prevalence of levamisole within the cocaine supply.
Sex Determining Region Y Box 9 Induces Chemoresistance in Pancreatic Cancer Cells by Induction of Putative Cancer Stem Cell Characteristics and Its High Expression Predicts Poor Prognosis
Authors: Higashihara Taku , Yoshitomi Hideyuki , Nakata Yasuyuki , Kagawa Shingo , Takano Shigetsugu , Shimizu Hiroaki , Kato Atsushi , Furukawa Katsunori , Ohtsuka Masayuki , Miyazaki Masaru
Published: October 2017

Objectives

Pancreatic cancer is a highly chemoresistant tumor and underlying mechanisms are not well understood. Sex determining region Y box 9 (Sox9) is a transcription factor playing important roles on maintenance of pluripotent cells during pancreatic organogenesis. The purpose of this study is to evaluate the roles of Sox9 in pancreatic cancer.

Methods

The Sox9 expression was evaluated by immunohistochemical analysis. Effects of Sox9 inhibition by siRNA or shRNA on chemosensitivity, sphere formation, stem cell markers expression, and in vivo tumor formation rate were examined using pancreatic cancer cell lines.

Results

High expression of Sox9 in pancreatic cancer tissue is correlated with poor prognosis (P = 0.011). Cells with high Sox9 expression (PANC-1, Capan-1) showed stronger chemoresistance to Gemcitabine than cells with low Sox9 expression (BxPC-3, MIA PaCa-2). The chemosensitivity in PANC-1 was recovered by suppressing Sox9 using siRNA (P < 0.05). Both sphere formation rate and the proportion of CD44highCD24high cells were decreased by Sox9 inhibition. Tumor formation rate of Tet-on inducible Sox9 shRNA-transfected PANC-1 cells in KSN/Slc nude mice was decreased by induction of shRNA with doxycycline feeding (P < 0.05).

Conclusion

Sox9 plays an important role in chemoresistance by the induction of stemness in pancreatic cancer cells.
Feasibility of Prostate PAXgene Fixation for Molecular Research and Diagnostic Surgical Pathology
Authors: Högnäs Gunilla , Kivinummi Kati , Kallio Heini M.L. , Hieta Reija , Ruusuvuori Pekka , Koskenalho Antti , Kesseli Juha , Tammela Teuvo L.J. , Riikonen Jarno , Ilvesaro Joanna , Kares Saara , Hirvikoski Pasi P. , Laurila Marita , Mirtti Tuomas , Nykter Matti , Kujala Paula M. , Visakorpi Tapio , Tolonen Teemu , Bova G. Steven
Published: October 2017

Advances in prostate cancer biology and diagnostics are dependent upon high-fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin-embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied. Our results suggest that it is feasible to use PFPE tissue for routine robot-assisted laparoscopic prostatectomy surgical pathology diagnostics and immunohistochemistry, with the benefit of significantly improvedDNA and RNA quality and RNA picogram yield per nucleus as compared with FFPE tissue. For fresh frozen, FFPE, and PFPE tissues, respectively, the average Genomic Quality Numbers were 7.9, 3.2, and 6.2, average RNA Quality Numbers were 8.7, 2.6, and 6.3, average DNA picogram yields per nucleus were 0.41, 0.69, and 0.78, and average RNA picogram yields per nucleus were 1.40, 0.94, and 2.24. These findings suggest that where DNA and/or RNA analysis of tissue is required, and when tissue size is small, PFPE may provide important advantages over FFPE. The results also suggest several interesting nuances including potential avenues to improve RNA quality in FFPE tissues and confirm recent suggestions that some DNA sequence artifacts associated with FFPE can be avoided.