bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic and Pharmacodynamic Properties of Metronidazole in Pediatric Patients With Acute Appendicitis: A Prospective Study
Authors: Child Jason , Chen Xinhui , Mistry Rakesh D , Somme Stig , MacBrayne Christine , Anderson Peter L , Jones Ronald N , Parker Sarah K
Published: April 2018

Background

Metronidazole is traditionally dosed every 6–8 hours even though in adults it has a long half-life, concentration-dependent killing, and 3-hour postantibiotic effect. Based on this logic, some pediatric hospitals adopted once-daily dosing for appendicitis, despite limited pharmacokinetics-pharmacodynamics (PK/PD) in children. We studied pediatric patients with appendicitis given metronidazole once daily to determine whether this dosing would meet target area under the curve (AUC)/minimum inhibitory concentration (MIC) ratio of ≥70 for Bacteroides fragilis.

Methods

One hundred pediatric patients aged 4–17 years had an average of 3 blood draws per patient during the first 24 hours after a 30 mg/kg per dose of intravenous metronidazole. Concentrations of drug were determined using validated liquid chromatography and tandem mass spectrometry. A NONMEM model was constructed for determining PK, followed by Monte Carlo simulations to generate a population of plasma concentration-time AUC of metronidazole and hydroxy-metronidazole.

Results

Simulated AUC values met target attainment (AUC/MIC ratio of ≥70 to B fragilis MICs) for 96%–100% of all patients for an MIC of 2 mcg/mL. For MICs of 4 and 8 mcg/mL, target attainment ranged from 61% to 97% and 9% to 71%, respectively. Areas under the curve were similar to that of adults receiving 1000 mg and 1500 mg q24, or 500 mg q8 hours.

Conclusions

Metronidazole, 30 mg/kg per dose, once daily achieved AUC target attainment for B fragilis with an MIC of 2 mcg/mL or less in pediatric appendicitis patients. Based on this and studies in adults, there does not seem to be any PK/PD advantage of more frequent dosing in this population.
Calcium signals in the plant nucleus: origin and function
Authors: Charpentier Myriam
Published: April 2018

The universality of calcium as an intracellular messenger depends on the dynamics of its spatial and temporal release from calcium stores. Accumulating evidence over the past two decades supports an essential role for nuclear calcium signalling in the transduction of specific stimuli into cellular responses. This review focuses on mechanisms underpinning changes in nuclear calcium concentrations and discusses what is known so far about the origin of the nuclear calcium signals identified, primarily in the context of microbial symbioses and abiotic stresses.
Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease
Authors: Wilkinson Thomas J , Gould Douglas W , Nixon Daniel G D , Watson Emma L , Smith Alice C
Published: April 2018

Background

Chronic kidney disease (CKD) is characterized by adverse changes in body composition, which are associated with poor clinical outcome and physical functioning. Whilst size is the key for muscle functioning, changes in muscle quality specifically increase in intramuscular fat infiltration (myosteatosis) and fibrosis (myofibrosis) may be important. We investigated the role of muscle quality and size on physical performance in non-dialysis CKD patients.

Methods

Ultrasound (US) images of the rectus femoris (RF) were obtained. Muscle quality was assessed using echo intensity (EI), and qualitatively using Heckmatt’s visual rating scale. Muscle size was obtained from RF cross-sectional area (RF-CSA). Physical function was measured by the sit-to-stand-60s (STS-60) test, incremental (ISWT) and endurance shuttle walk tests, lower limb and handgrip strength, exercise capacity (VO2peak) and gait speed.

Results

A total of 61 patients (58.5 ± 14.9 years, 46% female, estimated glomerular filtration rate 31.1 ± 20.2 mL/min/1.73 m2) were recruited. Lower EI (i.e. higher muscle quality) was significantly associated with better physical performance [STS-60 (r = 0.363) and ISWT (r = 0.320)], and greater VO2peak (r = 0.439). The qualitative rating was closely associated with EI values, and significant differences in function were seen between the ratings. RF-CSA was a better predictor of performance than muscle quality.

Conclusions

In CKD, increased US-derived EI was negatively correlated with physical performance; however, muscle size remains the largest predictor of physical function. Therefore, in addition to the loss of muscle size, muscle quality should be considered an important factor that may contribute to deficits in mobility and function in CKD. Interventions such as exercise could improve both of these factors.
Does Mindfulness Training Enhance the Professional Development of Residents? A Qualitative Study
Authors: Verweij Hanne , van Ravesteijn Hiske , van Hooff Madelon L.M. , Lagro-Janssen Antoine L.M. , Speckens Anne E.M.
Published: April 2018

Purpose

In addition to developing diagnostic and clinical skills, postgraduate medical education should stimulate residents’ professional development. Teaching medical professionalism is challenging and is often left largely to the informal and hidden curricula. An intervention that might be beneficial for medical residents is mindfulness-based stress reduction (MBSR). The authors implemented MBSR as an optional course for residents and qualitatively explored how it influenced residents professionally.

Method

Between 2014 and 2016, the authors conducted 19 in-depth, face-to-face interviews with residents who had participated in an MBSR course at Radboud university medical center, The Netherlands. Medical and surgical residents, across a range of disciplines, participated. The authors used the constant comparison method to analyze the data.

Results

The analysis of the data resulted in five themes: awareness of thoughts, emotions, bodily sensations, and behavior; increased self-reflection; acceptance and nonjudgment; increased resilience; and relating to others. Residents indicated that the MBSR training increased their awareness and self-reflection at work, and they were more accepting toward themselves and toward their limitations. Furthermore, they mentioned being more resilient and better at setting priorities and limits. They improved their self-care and work–life balance. In addition, residents indicated that the training made them more aware of how they communicated. They asked for help more often and seemed to be more open toward feedback. Lastly, they indicated an increased sense of compassion for others.

Conclusions

This study indicated that mindfulness training can serve as a tool to cultivate important professional competencies for residents.
Postinterview Communications: Two Surveys of Internal Medicine Residency Program Directors Before and After Guideline Implementation
Authors: Chacko Karen M. , Reddy Shalini , Kisielewski Michael , Call Stephanie , Willett Lisa L. , Chaudhry Saima
Published: April 2018

Purpose

Guidelines surrounding postinterview communication (PIC) after residency interviews were issued by the National Resident Matching Program and Association of Program Directors in Internal Medicine. How they have influenced PIC and program directors’ (PDs’) reasons for PIC is unknown.

Method

Annual surveys of 365 U.S. internal medicine residency PDs in 2013 and 368 in 2015 were used. Questions about frequency, intent, and usefulness of PIC and knowledge of guidelines before and after new PIC guidelines were included. Chi-square tests were used to compare data sets, and multivariate logistic regression was performed for 2015 data to identify factors predicting engagement in PIC, using program characteristics, PD characteristics, and beliefs about the benefits of PIC as independent variables.

Results

There were 265 (73%) respondents in 2013 and 227 (62%) in 2015. While the number of programs with a PIC policy increased 43%, the level of contact increased 7%. Few PDs indicated PIC was helpful to them; however, PDs who felt PIC helps target applicants were more likely to engage in PIC (OR 4.21, SE 1.88, P = .001). The main reason for continuing PIC (50% of PDs) was that PIC, part of their program’s culture, was considered “good manners.”

Conclusions

New guidelines increased the number of programs with a PIC policy, but the overall rate of applicant contact did not change despite few PDs feeling PIC was helpful to recruitment. The culture surrounding PIC may be difficult to overcome via guidelines alone, and more definitive rules are necessary to implement change.
The dilemma of aneuploidy screening on low responders
Authors: Morin Scott J. , Kaser Daniel J. , Franasiak Jason M.
Published: April 2018

Purpose of review

Preimplantation genetic testing for aneuploidy (PGT-A) has been demonstrated to improve implantation and pregnancy rates and decrease miscarriage rates over standard morphology-based embryo selection. However, there are limited data on its efficacy in patients with diminished ovarian reserve or a poor response to stimulation who may have fewer embryos to select amongst.

Recent findings

Early findings demonstrate that PGT-A reduces the miscarriage rate and decreases the time to delivery in poor responders. These studies highlight the importance of designing trials that compare outcomes over multiple cycles as the benefit of PGT-A in this patient population lies in eliminating the time lost to futile transfers of aneuploid embryos. Furthermore, recent studies have demonstrated that a catch-all category of ‘poor responder’ may need to be reevaluated as different subpopulations of patients with low response exhibit different clinical characteristics.

More information is needed on characterizing the physiology of ovarian aging across multiple phenotypes of diminished ovarian reserve and establishing the predictive value of aneuploid results across multiple PGT-A platforms. However, initial data suggests benefit of PGT-A in poor responders.
Development of a New Patient-reported Outcome Instrument to Evaluate Treatments for Scars: The SCAR-Q
Authors: Klassen Anne F. , Ziolkowski Natalia , Mundy Lily R. , Miller H. Catherine , McIlvride Alison , DiLaura Allison , Fish Joel , Pusic Andrea L.
Published: April 2018

Background:

Every year millions of individuals acquire scars. A literature review of patient-reported outcome (PRO) instruments identified content limitations in existing scar-specific measures. The aim of this study was to develop a new PRO instrument called SCAR-Q for children and adults with surgical, traumatic, and burn scars.

Methods:

We performed a secondary analysis of the qualitative datasets used in the development of PRO instruments for plastic and reconstructive surgery, that is, BREAST-Q, FACE-Q, BODY-Q, and CLEFT-Q. The keyword “scar*” was used to extract scar-specific text. Data were analyzed to identify concepts of interest and to form a comprehensive item pool. Scales were developed and refined through multiple rounds of cognitive interviews with patients and with input from international clinical experts between July 2015 and December 2016.

Results:

A total of 52 children and 192 adults from the qualitative datasets provided between 1 and 34 scar-specific codes (n = 1,227). The analysis led to the identification of 3 key domains for which scales were developed: scar appearance (eg, size, color, contour), scar symptoms (eg, painful, tight, itchy), and psychosocial impact (eg, feeling self-conscious, bothered by scar). Cognitive interviews with 25 adults and 20 pediatric participants with scars, plus feedback from 27 clinical experts, led to rewording and removal of items, and new items added. These steps ensured content validity for SCAR-Q in a broad range of scars.

Conclusions:

The SCAR-Q is now being field-tested. Once completed, we anticipate SCAR-Q will be used in clinical practice and in clinical trials to test different scar therapies.
Progression of Exercise Training in Early Outpatient Cardiac Rehabilitation
Authors: Squires Ray W. , Kaminsky Leonard A. , Porcari John P. , Ruff Jeanne E. , Savage Patrick D. , Williams Mark A.
Published: April 2018

Aerobic and resistance exercise training is a cornerstone of early outpatient cardiac rehabilitation (CR) and provides impressive benefits for patients. The components of the exercise prescription for patients with cardiovascular diseases are provided in guideline documents from several professional organizations and include frequency (how many sessions per week); intensity (how hard to exercise); time (duration of the exercise training session); type (modalities of exercise training); volume (the total amount or dose of exercise); and progression (the rate of increasing the dose of exercise). The least discussed, least appreciated, and most challenging component of the exercise prescription for CR health care professionals is the rate of progression of the dose of exercise. One reason for this observation is the heterogeneity of patients who participate in CR. All components of the exercise prescription should be developed specifically for each individual patient. This statement provides an overview of the principles of exercise prescription for patients in CR with special emphasis on the rate of progression. General recommendations for progression are given and patient case examples are provided to illustrate the principles of progression in exercise training.
OPTIMAL MANAGEMENT OF PIGMENT EPITHELIAL DETACHMENTS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Khanani Arshad M. , Eichenbaum David , Schlottmann Patricio G. , Tuomi Lisa , Sarraf David
Published: April 2018

Purpose:

This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on review of available evidence in the literature.

Methods:

A comprehensive literature review evaluates previous retrospective and prospective studies that assessed the treatment of PEDs in nAMD.

Results:

Studies illustrated that anti–vascular endothelial growth factor (VEGF) therapy can be effective in eyes with PED secondary to nAMD. Similar visual outcomes are associated with different anti-VEGF treatments. Higher anti-VEGF doses may improve anatomical response, without correlation with vision improvement. Fibrovascular PEDs may be difficult to treat, but even these eyes can gain vision with anti-VEGF therapy. A retinal pigment epithelial tear may develop in 15% to 20% of eyes with PEDs after anti-VEGF therapy, especially in PEDs greater than 500 µm to 600 µm in height; however, vision may stabilize with continued therapy. Atrophy may complicate eyes with PED and nAMD after anti-VEGF therapy, especially in association with complete PED resolution.

Conclusion:

Available literature suggests that anti-VEGF therapy is safe and efficacious for PED and nAMD. Treatment should focus on vision gains rather than PED resolution because there is no apparent correlation between anatomical and functional improvement in most eyes with PED and nAMD.
DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES
Authors: Iglicki Matias , Busch Catharina , Zur Dinah , Okada Mali , Mariussi Miriana , Chhablani Jay Kumar , Cebeci Zafer , Fraser-Bell Samantha , Chaikitmongkol Voraporn , Couturier Aude , Giancipoli Ermete , Lupidi Marco , Rodríguez-Valdés Patricio J. , Rehak Matus , Fung Adrian Tien-chin , Goldstein Michaella , Loewenstein Anat
Published: April 2018

Purpose:

To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment.

Methods:

This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded.

Results:

A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19–9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 μm, P = 0.10).

Conclusion:

Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.
Acanthamoeba: An Overview of the Challenges to the Development of a Consensus Methodology of Disinfection Efficacy Testing for Contact Lens Care Products
Authors: Brocious Jeffrey , Tarver Michelle E. , Hampton Denise , Eydelman Malvina
Published: April 2018

With the increasing incidence of more pathogens that can cause microbial keratitis (MK), it is necessary to periodically reassess disinfection multipurpose solutions testing requirements to ensure that relevant organisms to challenge them are being used. Current testing protocols have included common pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, Serratia marcescens, Candida albicans, and Fusarium solani but have omitted less common pathogens such as Acanthamoeba. Specifically, Acanthamoeba sp. has recently been identified as a prevalent cause of MK in certain countries. Developing an appropriate protocol for this unique organism presents a challenge, given its two distinct life stages, methods to grow the organism, encystment techniques, and many other parameters that can affect testing outcomes. Therefore, the appropriate combination of these parameters is crucial to developing a protocol that ensures consistent, accurate results. The FDA has recognized the importance of establishing a standardized testing protocol for this pathogen and embarked on research efforts to provide a recommended testing protocol for testing contact lens care products.
A Systematic Review of Early Warning Systems’ Effects on Nurses’ Clinical Performance and Adverse Events Among Deteriorating Ward Patients
Authors: Lee Ju-Ry , Kim Eun-Mi , Kim Sun-Aee , Oh Eui Geum
Published: April 2018

Objective

Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses’ clinical performance and patients’ adverse events. This review aimed to determine the ability of EWSs to improve nurses’ clinical performance and prevent adverse events among deteriorating ward patients.

Method

The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses’ clinical performance (vital sign monitoring and rapid response team notification) and patients’ adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission).

Results

The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses’ clinical performance, based on their frequency of documenting vital signs that were related to the patient’s clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death.

Conclusions

It seems that EWSs can improve nurses’ clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.
HIV Self-Testing Increases HIV Testing Frequency in High-Risk Men Who Have Sex With Men: A Randomized Controlled Trial
Authors: Katz David A. , Golden Matthew R. , Hughes James P. , Farquhar Carey , Stekler Joanne D.
Published: April 2018

Background:

Self-testing may increase HIV testing and decrease the time people with HIV are unaware of their status, but there is concern that absence of counseling may result in increased HIV risk.

Setting:

Seattle, Washington.

Methods:

We randomly assigned 230 high-risk HIV-negative men who have sex with men to have access to oral fluid HIV self-tests at no cost versus testing as usual for 15 months. The primary outcome was self-reported number of HIV tests during follow-up. To evaluate self-testing's impact on sexual behavior, we compared the following between arms: non–HIV-concordant condomless anal intercourse and number of male condomless anal intercourse partners in the last 3 months (measured at 9 and 15 months) and diagnosis with a bacterial sexually transmitted infection (STI: early syphilis, gonorrhea, and chlamydial infection) at the final study visit (15 months). A post hoc analysis compared the number of STI tests reported during follow-up.

Results:

Men randomized to self-testing reported significantly more HIV tests during follow-up (mean = 5.3, 95% confidence interval = 4.7 to 6.0) than those randomized to testing as usual (3.6, 3.2 to 4.0; P < 0.0001), representing an average increase of 1.7 tests per participant over 15 months. Men randomized to self-testing reported using an average of 3.9 self-tests. Self-testing was noninferior with respect to all markers of HIV risk. Men in the self-testing arm reported significantly fewer STI tests during follow-up (mean = 2.3, 95% confidence interval = 1.9 to 2.7) than men in the control arm (3.2, 2.8 to 3.6; P = 0.0038).

Conclusions:

Access to free HIV self-testing increased testing frequency among high-risk men who have sex with men and did not impact sexual behavior or STI acquisition.
Performance of an Automated Versus a Manual Whole-Body Magnetic Resonance Imaging Workflow
Authors: Stocker Daniel , Finkenstaedt Tim , Kuehn Bernd , Nanz Daniel , Klarhoefer Markus , Guggenberger Roman , Andreisek Gustav , Kiefer Berthold , Reiner Caecilia S.
Published: April 2018

Objectives

The aim of this study was to evaluate the performance of an automated workflow for whole-body magnetic resonance imaging (WB-MRI), which reduces user interaction compared with the manual WB-MRI workflow.

Materials and Methods

This prospective study was approved by the local ethics committee. Twenty patients underwent WB-MRI for myopathy evaluation on a 3 T MRI scanner. Ten patients (7 women; age, 52 ± 13 years; body weight, 69.9 ± 13.3 kg; height, 173 ± 9.3 cm; body mass index, 23.2 ± 3.0) were examined with a prototypical automated WB-MRI workflow, which automatically segments the whole body, and 10 patients (6 women; age, 35.9 ± 12.4 years; body weight, 72 ± 21 kg; height, 169.2 ± 10.4 cm; body mass index, 24.9 ± 5.6) with a manual scan. Overall image quality (IQ; 5-point scale: 5, excellent; 1, poor) and coverage of the study volume were assessed by 2 readers for each sequence (coronal T2-weighted turbo inversion recovery magnitude [TIRM] and axial contrast-enhanced T1-weighted [ce-T1w] gradient dual-echo sequence). Interreader agreement was evaluated with intraclass correlation coefficients. Examination time, number of user interactions, and MR technicians' acceptance rating (1, highest; 10, lowest) was compared between both groups.

Results

Total examination time was significantly shorter for automated WB-MRI workflow versus manual WB-MRI workflow (30.0 ± 4.2 vs 41.5 ± 3.4 minutes, P < 0.0001) with significantly shorter planning time (2.5 ± 0.8 vs 14.0 ± 7.0 minutes, P < 0.0001). Planning took 8% of the total examination time with automated versus 34% with manual WB-MRI workflow (P < 0.0001). The number of user interactions with automated WB-MRI workflow was significantly lower compared with manual WB-MRI workflow (10.2 ± 4.4 vs 48.2 ± 17.2, P < 0.0001). Planning efforts were rated significantly lower by the MR technicians for the automated WB-MRI workflow than for the manual WB-MRI workflow (2.20 ± 0.92 vs 4.80 ± 2.39, respectively; P = 0.005). Overall IQ was similar between automated and manual WB-MRI workflow (TIRM: 4.00 ± 0.94 vs 3.45 ± 1.19, P = 0.264; ce-T1w: 4.20 ± 0.88 vs 4.55 ± .55, P = 0.423). Interreader agreement for overall IQ was excellent for TIRM and ce-T1w with an intraclass correlation coefficient of 0.95 (95% confidence interval, 0.86–0.98) and 0.88 (95% confidence interval, 0.70–0.95). Incomplete coverage of the thoracic compartment in the ce-T1w sequence occurred more often in the automated WB-MRI workflow (P = 0.008) for reader 2. No other significant differences in the study volume coverage were found.

Conclusions

In conclusion, the automated WB-MRI scanner workflow showed a significant reduction of the examination time and the user interaction compared with the manual WB-MRI workflow. Image quality and the coverage of the study volume were comparable in both groups.
Combining Intraoral Scans, Cone Beam Computed Tomography and Face Scans: The Virtual Patient
Authors: Mangano Carlo , Luongo Fabrizia , Migliario Mario , Mortellaro Carmen , Mangano Francesco Guido
Published: April 2018

Purpose:

The aim of this literature review was to provide an update on the current scientific knowledge in the field of 3D virtual patient science and to identify a possible easy, smart, and affordable method to combine different file formats obtained from different digital devices.

Methods:

Electronic searches of the Medline database was performed, up to May 2017, for articles dealing with the construction of a 3D virtual patient; the matching of data acquired with different digital devices (cone beam computed tomography, CBCT; face scanner, FS; intraoral scanner, IOS; and desktop scanner, DS) was considered. The inclusion of studies was based on the superimposition of at least 2 different digital sources.

Results:

Twenty-five studies were selected for subsequent examination. Only 3 studies analyzed the feasibility of superimposition of 3 different types of 3D data (CBCT + FS + IOS/DS). The most frequently used matching procedure was between CBCT and FS and CBCT and IOS/DS.

Conclusion:

The procedure of superimposition of data from CBCT, IOS, and FS is currently feasible and it is now possible to create a 3D “virtual patient” to better diagnose, plan the treatment, and communicate with patients.
Retrospective, Multicenter Comparison of the Clinical Presentation of Patients Presenting With Diplopia From Giant Cell Arteritis vs Other Causes
Authors: Ross Ahmara G. , Jivraj Imran , Rodriguez Geoffrey , Pistilli Maxwell , Chen John J. , Sergott Robert C. , Moster Mark , Sheldon Claire A. , Liu Grant T. , Foroozan Rod , Ko Melissa W. , Francis Courtney E. , Williams Zoë R. , Lee Andrew G. , McClelland Collin M. , Shindler Kenneth S. , Yalamanchili Sushma , Osborne Benjamin , Hedges Thomas R. , Van Stavern Gregory P. , Puckett Ernest , Rigi Mohammed , García-Basterra Ignacia , Tamhankar Madhura A.
Published: April 2018

Background:

Although giant cell arteritis (GCA) is a well-known cause of transient and permanent vision loss, diplopia as a presenting symptom of this condition is uncommon. We compared symptoms and signs of patients presenting with diplopia from GCA to those from other causes.

Methods:

This was a multicenter, retrospective study comparing the clinical characteristics of patients presenting with diplopia from GCA with age-matched controls. Demographic information, review of symptoms, ophthalmic examination, and laboratory data of biopsy-proven patients with GCA were compared with those of age-matched controls presenting with diplopia.

Results:

A total of 27 patients presented with diplopia from GCA, 19 with constant diplopia, and 8 with transient diplopia. All patients with constant diplopia from GCA were matched with 67 control subjects who had diplopia from other etiologies. Patients with GCA were more likely to describe other accompanying visual symptoms (58% vs 25%, P = 0.008), a greater number of systemic GCA symptoms (3.5, GCA vs 0.6, controls, P < 0.001) such as headache (94% [17/18] vs 39% [23/67]; P < 0.001), jaw claudication (80% [12/15] vs 0% [0/36]; P < 0.001), and scalp tenderness (44% [7/16] vs 7% [3/43]; P < 0.001). Ocular ischemic lesions (26% vs 1%, P < 0.001) were also common in patients with diplopia from GCA. Inflammatory markers were elevated significantly in patients with GCA vs controls (erythrocyte sedimentation rate: 91% [10/11] vs 12% [3/25], P < 0.001; C-reactive protein: 89% [8/9] vs 11% [2/19], P < 0.001).

Conclusions:

GCA is a rare but serious cause of diplopia among older adults and must be differentiated from other more common benign etiologies. Our study suggests that most patients with diplopia from GCA have concerning systemic symptoms and/or elevated inflammatory markers that should trigger further work-up. Moreover, careful ophthalmoscopic examination should be performed to look for presence of ocular ischemic lesions in older patients presenting with acute diplopia.
Bacterial transmembrane signalling systems and their engineering for biosensing
Authors: Jung Kirsten , Fabiani Florian , Hoyer Elisabeth , Lassak Jürgen
Published: April 2018

Every living cell possesses numerous transmembrane signalling systems that receive chemical and physical stimuli from the environment and transduce this information into an intracellular signal that triggers some form of cellular response. As unicellular organisms, bacteria require these systems for survival in rapidly changing environments. The receptors themselves act as ‘sensory organs’, while subsequent signalling circuits can be regarded as forming a ‘neural network’ that is involved in decision making, adaptation and ultimately in ensuring survival. Bacteria serve as useful biosensors in industry and clinical diagnostics, in addition to producing drugs for therapeutic purposes. Therefore, there is a great demand for engineered bacterial strains that contain transmembrane signalling systems with high molecular specificity, sensitivity and dose dependency. In this review, we address the complexity of transmembrane signalling systems and discuss principles to rewire receptors and their signalling outputs.
Reducing language to rhythm: Amazonian Bora drummed language exploits speech rhythm for long-distance communication
Authors: Seifart Frank , Meyer Julien , Grawunder Sven , Dentel Laure
Published: April 2018

Many drum communication systems around the world transmit information by emulating tonal and rhythmic patterns of spoken languages in sequences of drumbeats. Their rhythmic characteristics, in particular, have not been systematically studied so far, although understanding them represents a rare occasion for providing an original insight into the basic units of speech rhythm as selected by natural speech practices directly based on beats. Here, we analyse a corpus of Bora drum communication from the northwest Amazon, which is nowadays endangered with extinction. We show that four rhythmic units are encoded in the length of pauses between beats. We argue that these units correspond to vowel-to-vowel intervals with different numbers of consonants and vowel lengths. By contrast, aligning beats with syllables, mora or only vowel length yields inconsistent results. Moreover, we also show that Bora drummed messages conventionally select rhythmically distinct markers to further distinguish words. The two phonological tones represented in drummed speech encode only few lexical contrasts. Rhythm thus appears to crucially contribute to the intelligibility of drummed Bora. Our study provides novel evidence for the role of rhythmic structures composed of vowel-to-vowel intervals in the complex puzzle concerning the redundancy and distinctiveness of acoustic features embedded in speech.
In situ
investigations of the phase change behaviour of tungsten oxide nanostructures
Authors: Thummavichai Kunyapat , Wang Nannan , Xu Fang , Rance Graham , Xia Yongda , Zhu Yanqiu
Published: April 2018

This study uses two
in situ
techniques to investigate the geometry and phase change behaviour of bundled ultrathin W
18
O
49
nanowires and WO
3
nanoparticles. The
in situ
X-ray diffraction (XRD) results have shown that the phase transition of WO
3
nanoparticles occurs in sequence from monoclinic (room temperature) → orthorhombic (350°C) → tetragonal (800°C), akin to bulk WO
3
; however, W
18
O
49
nanowires remain stable as the monoclinic phase up to 500°C, after which a complete oxidation to WO
3
and transformation to the orthorhombic β-phase at 550°C is observed. The
in situ
Raman spectroscopy investigations have revealed the Raman peak downshifts as the temperature increases, and have identified the 187.6 cm
−1
as the fingerprint band for the phase transition from γ- to β-phase of the WO
3
nanoparticle. Furthermore, WO
3
nanoparticles exhibit the γ- to β-phase conversion at 275°C, which is about 75°C lower than the relaxation temperature of 350°C for the monoclinic γ-W
18
O
49
nanowires. These new fundamental understandings on the phase transition behaviour offer important guidance for the design and development of tungsten oxide-based nanodevices by defining their allowed operating conditions.
Leishmania naiffiandLeishmania guyanensisreference genomes highlight genome structure and gene evolution in theVianniasubgenus
Authors: Coughlan Simone , Taylor Ali Shirley , Feane Eoghan , Sanders Mandy , Schonian Gabriele , Cotton James A. , Downing Tim
Published: April 2018

The unicellular protozoan parasiteLeishmaniacauses the neglected tropical disease leishmaniasis, affecting 12 million people in 98 countries. In South America, where theVianniasubgenus predominates, so far onlyL.(Viannia)braziliensisandL.(V.)panamensishave been sequenced, assembled and annotated as reference genomes. Addressing this deficit in molecular information can inform species typing, epidemiological monitoring and clinical treatment. Here,L.(V.)naiffiandL.(V.)guyanensisgenomic DNA was sequenced to assemble these two genomes as draft references from short sequence reads. The methods used were tested using short sequence reads forL. braziliensisM2904 against its published reference as a comparison. This assembly and annotation pipeline identified 70 additional genes not annotated on the original M2904 reference. Phylogenetic and evolutionary comparisons ofL. guyanensisandL. naiffiwith 10 otherVianniagenomes revealed four traits common to allViannia: aneuploidy, 22 orthologous groups of genes absent in otherLeishmaniasubgenera, elevated TATE transposon copies and a high NADH-dependent fumarate reductase gene copy number. Within theViannia, there were limited structural changes in genome architecture specific to individual species: a 45 Kb amplification on chromosome 34 was present in all barL. lainsoni,L. naiffihad a higher copy number of the virulence factor leishmanolysin, and laboratory isolateL. shawiM8408 had a possible minichromosome derived from the 3’ end of chromosome 34.This combination of genome assembly, phylogenetics and comparative analysis across an extended panel of diverseVianniahas uncovered new insights into the origin and evolution of this subgenus and can help improve diagnostics for leishmaniasis surveillance.
Inverse design of an isotropic suspended Kirchhoff rod: theoretical and numerical results on the uniqueness of the natural shape
Authors: Bertails-Descoubes Florence , Derouet-Jourdan Alexandre , Romero Victor , Lazarus Arnaud
Published: April 2018

Solving the equations for Kirchhoff elastic rods has been widely explored for decades in mathematics, physics and computer science, with significant applications in the modelling of thin flexible structures such as DNA, hair or climbing plants. As demonstrated in previous experimental and theoretical studies, the natural curvature plays an important role in the equilibrium shape of a Kirchhoff rod, even in the simple case where the rod is isotropic and suspended under gravity. In this paper, we investigate the reverse problem: can we characterize the natural curvature of a suspended isotropic rod, given an equilibrium curve? We prove that although there exists an infinite number of natural curvatures that are compatible with the prescribed equilibrium, they are all equivalent in the sense that they correspond to a unique natural shape for the rod. This natural shape can be computed efficiently by solving in sequence three linear initial value problems, starting from any framing of the input curve. We provide several numerical experiments to illustrate this uniqueness result, and finally discuss its potential impact on non-invasive parameter estimation and inverse design of thin elastic rods.
Sterols and stanols as novel tracers of waterbird population dynamics in freshwater ponds
Authors: Hargan Kathryn E. , Stewart Emily M. , Michelutti Neal , Grooms Christopher , Kimpe Linda E. , Mallory Mark L. , Smol John P. , Blais Jules M.
Published: April 2018

With the expansion of urban centres in the mid-twentieth century and the post-1970 decrease in pesticides, populations of double-crested cormorants (Phalacrocorax auritus) and ring-billed gulls (Larus delawarensis) around Lake Ontario (Canada and USA) have rapidly rebounded, possibly to unprecedented numbers. Along with the use of traditional palaeolimnological methods (e.g. stable isotopes, biological proxies), we now have the capacity to develop specific markers for directly tracking the presence of waterbirds on nesting islands. Here, we apply the use of lipophilic sterols and stanols from both plant and animal-faecal origins as a reliable technique, independent of traditional isotopic methods, for pinpointing waterbird arrival and population growth over decadal timescales. Sterol and stanol concentrations measured in the guano samples of waterbird species were highly variable within a species and between the three species of waterbirds examined. However, cholesterol was the dominant sterol in guano, and phytosterols were also high in ring-billed gull guano. This variability highlights a specialist piscivorous diet for cormorants compared to a generalist, omnivorous diet for gulls, which may now often include grain and invertebrates from agricultural fields. A ratio that includes cholesterol and sitosterol plus their aerobically reduced products (cholestanol, stigmastanol) best explained the present range of bird abundance across the islands and was significantly correlated to sedimentary δ15N. Overall, we demonstrate the use of sterols and stanols as a direct means for tracking the spatial and temporal presence of waterbirds on islands across Lake Ontario, and probably elsewhere.
Ndr/Lats kinases bind specific Mob-family coactivators through a conserved and modular interface
Authors: Parker Benjamin W. , Gógl Gergő , Bálint Mónika , Hetenyi Csaba , Remenyi Attila , Weiss Eric L.
Published: April 2018

Ndr/Lats kinases bind Mob coactivator proteins to form complexes that are essential and deeply conserved components of “Hippo” signaling pathways, which control cell proliferation and morphogenesis in eukaryotes. All Ndr/Lats kinases have a characteristic N-terminal region (NTR) that binds a specific Mob co-factor: Lats kinases associate with Mob1 proteins, and Ndr kinases associate with Mob2 proteins. To better understand the functional significance of Mob protein association with Ndr/Lats kinases and selective binding of Ndr and Lats to distinct Mob co-factors, we solved crystal structures of Saccharomyces cerevisiae Cbk1(NTR)-Mob2 and Dbf2(NTR)-Mob1 and experimentally assessed determinants of Mob cofactor binding and specificity. This significantly refines the previously determined structure of Cbk1 kinase bound to Mob2, presently the only crystallographic model of a full length Ndr/Lats kinase complexed with a Mob cofactor. Our analysis indicates that the Ndr/Lats NTR-Mob interface provides a distinctive kinase regulation mechanism, in which Mob co-factor organizes the Ndr/Lats NTR to interact with the AGC kinase C-terminal hydrophobic motif (HM) activation segment. The Mob-organized NTR appears to mediate HM association with an allosteric site on the kinase N-lobe. We also found that Cbk1 and Dbf2 associated highly specifically with Mob2 and Mob1, respectively. Alteration of specific positions in the Cbk1 NTR allows association of non-cognate Mob co-factor, indicating that cofactor specificity is restricted by discrete sites rather than broadly distributed. Overall, our analysis provides a new picture of the functional role of Mob association and indicates that the Ndr/Lats(NTR)-Mob interface overall is largely a common structural platform that mediates kinase-cofactor binding.
GOcats: A tool for categorizing Gene Ontology into subgraphs of user-defined concepts
Authors: Hinderer Eugene W. , Moseley Hunter N.B.
Published: April 2018

Gene Ontology is used extensively in scientific knowledgebases and repositories to organize the wealth of available biological information. However, interpreting annotations derived from differential gene lists is difficult without manually sorting into higher-order categories. To address these issues, we present GOcats, a novel tool that organizes the Gene Ontology (GO) into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. We tested GOcats performance using subcellular location categories to mine annotations from GO-utilizing knowledgebases and evaluating their accuracy against immunohistochemistry datasets in the Human Protein Atlas (HPA).

In comparison to mappings generated from UniProt’s controlled vocabulary and from GO slims via OWLTools’ Map2Slim, GOcats outperforms these methods without reliance on a human-curated set of GO terms. By identifying and properly defining relations with respect to semantic scope, GOcats can use traditionally problematic relations without encountering erroneous term mapping. We applied GOcats in the comparison of HPA-sourced knowledgebase annotations to experimentally-derived annotations provided by HPA directly. During the comparison, GOcats improved correspondence between the annotation sources by adjusting semantic granularity. Utilized in this way, GOcats can perform an accurate knowledgebase-level evaluation of curated HPA-based annotations.
The genome ofEctocarpus subulatus– a highly stress-tolerant brown alga
Authors: Dittami Simon M. , Corre Erwan , Brillet-Guéguen Loraine , Lipinska Agnieszka P. , Pontoizeau Noé , Aite Meziane , Avia Komlan , Caron Christophe , Cho Chung Hyun , Collén Jonas , Cormier Alexandre , Delage Ludovic , Doubleau Sylvie , Frioux Clémence , Gobet Angélique , González-Navarrete Irene , Groisillier Agnès , Hervé Cécile , Jollivet Didier , KleinJan Hetty , Leblanc Catherine , Liu Xi , Marie Dominique , Markov Gabriel V. , Minoche André E. , Monsoor Misharl , Pericard Pierre , Perrineau Marie-Mathilde , Peters Akira F. , Siegel Anne , Siméon Amandine , Trottier Camille , Yoon Hwan Su , Himmelbauer Heinz , Boyen Catherine , Tonon Thierry
Published: April 2018

Brown algae are multicellular photosynthetic stramenopiles that colonize marine rocky shores worldwide.Ectocarpussp. Ec32 has been established as a genomic model for brown algae. Here we present the genome and metabolic network of the closely related species,Ectocarpus subulatusKützing, which is characterized by high abiotic stress tolerance. Since their separation, both strains show new traces of viral sequences and the activity of large retrotransposons, which may also be related to the expansion of a family of chlorophyll-binding proteins. Further features suspected to contribute to stress tolerance include an expanded family of heat shock proteins, the reduction of genes involved in the production of halogenated defence compounds, and the presence of fewer cell wall polysaccharide-modifying enzymes. Overall,E. subulatushas mainly lost members of gene families down-regulated in low salinities, and conserved those that were up-regulated in the same condition. However, 96% of genes that differed between the two examinedEctocarpusspecies, as well as all genes under positive selection, were found to encode proteins of unknown function. This underlines the uniqueness of brown algal stress tolerance mechanisms as well as the significance of establishingE. subulatusas a comparative model for future functional studies.
Quantitative photoacoustic imaging study of tumours in vivo: baseline variations in quantitative measurements
Authors: Costa Márcia Martinho , Shah Anant , Rivens Ian , Box Carol , O’Shea Tuathan , Papaevangelou Efthymia , Bamber Jeffrey , ter Haar Gail
Published: April 2018

Photoacoustic imaging (PAI) provides information on haemoglobin levels and blood oxygenation (sO2). To facilitate assessment of the variability in sO2 and haemoglobin in tumours, for example in response to therapies, the baseline variability of these parameters was evaluated in subcutaneous head and neck tumours in mice, using a PAI system (MSOT-inVision-256TF). Tumours of anaesthetized animals (midazolam-fentanyl-medetomidine) were imaged for 75 minutes; in varying positions; and repeatedly over 6 days. An increasing linear trend for average tumoural haemoglobin and blood sO2 was observed, when imaging over 75 minutes. There were no significant differences in these temporal trends, when re-positioning tumours. A negative correlation was found between the percent decrease in blood sO2 over 6 days and tumour growth rate. This paper shows the potential of PAI to provide baseline data for assessing the significance of intra- and inter-tumoural variations that may eventually have value for predicting and/or monitoring cancer treatment response.
BioVR: a platform for virtual reality assisted biological data integration and visualization
Authors: Zhang Jimmy F , Paciorkowski Alex R , Craig Paul A , Cui Feng
Published: April 2018

Background: The effective visualization and presentation of biological data is of critical importance to research scientists. The increasing rate at which experiments generate data has exacerbated the visualization problem. While biological datasets continue to increase in size and complexity, the shift to adopt new user interface (UI) paradigms has historically lagged. Consequently, a major bottleneck for analysis of next-generation sequencing data is the continued use of the UIs primarily inspired from single-type and small-scale data in 1990's. Results: We have developed BioVR, an easy-to-use interactive, virtual reality (VR)-assisted platform for visualizing DNA/RNA sequences and protein structures using Unity3D and the C# programming language. It utilizes the cutting-edge Oculus Rift, and Leap Motion hand detection, resulting in intuitive navigation and exploration of various types of biological data. Using Gria2 and its associated gene product as an example, we present this proof-of-concept software to integrate protein sequence and structure information. For any residue of interest in the Gria2 sequence, it can be quickly visualized in its protein structure within VR. Conclusions: Using innovative 3D techniques, we provide a VR-based platform for visualization of DNA/RNA sequences and protein structures in aggregate, which can be extended to view omics data.