bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Uncivil Nursing Students Become Uncivil Nurses? A National Survey of Faculty
Authors: Luparell Susan , Frisbee Kristi
Published: May 2019

BACKGROUND

Faculty frequently express anecdotal concerns that poorly behaving nursing students will go on to behave poorly as licensed nurses. Unfortunately, no empirical evidence exists to support or refute these concerns.

AIM

The purpose of this study was to determine what knowledge faculty have of poorly behaving nursing students who also behaved poorly in subsequent practice.

METHOD

A cross-sectional, descriptive design using online survey methods was used to gather data from a national sample of nurse educators.

RESULTS

Approximately 37 percent of respondents reported having personal knowledge of a former poorly behaving student who went on to display poor behavior as a licensed provider; 71 percent reported that at least one student had graduated in the previous year whom they thought should not have graduated based on unprofessional behaviors.

CONCLUSION

Study findings provide troubling evidence that at least some poorly behaving students continue to demonstrate unprofessional behavior as licensed nurses.
Developing Authentic Leadership Voice: Novice Faculty Experience
Authors: Patterson Barbara J. , Dzurec Laura , Sherwood Gwen , Forrester D. Anthony
Published: May 2019

AIM

The aim of this study was to determine the perceptions of 14 novice nurse faculty of a 20-month experiential leadership academy on the leadership development.

BACKGROUND

Managing the complexities of nursing faculty roles requires significant leadership skills that often are hard won. Evidence suggests that leadership preparation to prepare nursing faculty through guided mentoring can enhance faculty recruitment, satisfaction, and retention.

METHOD

Participants completed open-ended questions about their experiences in Sigma Theta Tau International’s Nurse Faculty Leadership Academy.

RESULTS

Data analysis revealed a meta-theme of “Finding Authentic Leadership Voice.” Four subthemes emerged to shape the meta-theme: Identifying Inner Strengths and Areas for Improvement, Increasing Self-Confidence and Self-Awareness, Increasing Focus on Others, and Clarifying Aspirations for a Leadership Future.

CONCLUSION

Reflecting on their experiences, participants recognized changes in their leadership roles as they found an authentic voice that helped them persist and thrive amid the complexities of their faculty roles.
Beliefs and Experiences of Nurse Educators Regarding Changing Answers on Examinations
Authors: Blakeman John R. , Laskowski Pamela S.
Published: May 2019

AIM

The purpose of this study was to explore nurse educators’ beliefs and experiences regarding students changing answers on multiple-choice examinations.

BACKGROUND

Studies suggest that answer-changing behavior does not negatively affect academic performance and may actually have a positive impact, but published studies reporting nurse educators’ beliefs and experiences on this topic are limited.

METHOD

A mixed-methods approach, QUAN + Qual, was employed. A survey with closed- and open-ended questions was emailed to nurse educators in Illinois.

RESULTS

Of the 125 nurse educators who completed the survey, a majority held negative views of answer-changing behavior; many noted that their experiences with students had shaped their views.

CONCLUSION

Nurse educators in this sample held an overall negative view of this behavior, contrary to the overall body of evidence suggesting there is possible benefit in changing answers. Several reasons exist to explain the inconsistency observed.
Prior Learning Assessment in Nursing: An Accelerated Pathway to Degree Completion
Authors: Lee Shirleatha , Dapremont Jill
Published: May 2019

The purpose of this study was to identify RN-BSN students’ perceived satisfaction with the use of prior learning assessments (PLAs) and to examine graduation rates for students who utilized PLA in comparison to non-PLA users. Students were surveyed to examine satisfaction with PLA use; retrospective data were examined to determine graduation status by PLA option. A high percentage of students perceived PLA as flexible and affordable, and users had significantly higher graduation rates. The PLA option is highly associated with degree completion.
Intraoperative bone tunnel laceration affects integrity of arthroscopic transosseous rotator cuff repair with a tunneling device
Authors: Hirakawa Yoshihiro , Manaka Tomoya , Ito Yoichi , Ichikawa Koichi , Matsuda Yoshinobu , Shimizu Hayato , Nakamura Hiroaki
Published: May 2019

Background:

We aimed to evaluate the functional outcomes, incidence of bone tunnel laceration, and bone tunnel morphology of transosseous arthroscopic rotator cuff repair (ARCR) with the Arthro-TunnelerTM.

Methods:

Between May 2012 and April 2013, patients with full-thickness tears who underwent transosseous ARCR with the Arthro-TunnelerTM and could be followed for a minimum of 2 yr were included in this retrospective study. Functional outcomes, cuff repair integrity, intraoperative bone tunnel laceration, and postoperative bone tunnel morphology were analyzed.

Results:

We retrospectively evaluated 42 consecutive patients (average age: 67.6 yr) who underwent transosseous ARCR. The mean active forward elevation, mean active abduction, mean Constant-Murley score, mean American Shoulder and Elbow Surgeon Score (ASES), and pain Visual Analogue Scale (VAS) improved from preoperative values of 127 degrees, 118 degrees, 50.3 points, 53.2 points, and 4.5 to 159 degrees, 160 degrees, 83.3 points, 78.5 points, and 1.7, respectively, at the final follow-up (P<0.001, P<0.01, P<0.001, P<0.001, P<0.001, respectively). The re-tear rate was 16.7%. The intraoperative bone tunnel laceration occurrence was 67.8% (61 tunnels). Bone tunnel laceration and re-tear were significantly correlated. We evaluated the morphology of 81 bone tunnels with MRI of 90 bone tunnels. Eight, 37, and 36 tunnels were L-shaped, curve-shaped, and straight-shaped, respectively.

Conclusions:

The clinical results of transosseous ARCR with the Arthro-TunnelerTM were significantly improved at a minimum of 2 yr of follow-up. However, patients older than 65 yr were at a high risk of developing bone tunnel laceration, which was associated with rotator cuff re-tear.
Incidence and Clinical Impact of Anti-TNFα Treatment of Severe Immune Checkpoint Inhibitor-induced Colitis in Advanced Melanoma: The Mecolit Survey
Authors: Lesage Candice , Longvert Christine , Prey Sorilla , Maanaoui Sarah , Dréno Brigitte , Machet Laurent , Zehou Ouidad , Kramkimel Nora , Jeudy Géraldine , Skowron François , Aubin François , Visseaux Laetitia , Mansard Sandrine , Dereure Olivier , Lesage François-Xavier , Guillot Bernard
Published: May 2019

Immune checkpoint inhibitors (ICI) significantly improve overall survival (OS) in patients with advanced melanoma, but immune-related colitis may occur and warrant anti-tumor necrosis factor α (TNFα) treatment in severe forms. A nationwide, multicenter retrospective survey was conducted to assess both, the real-life incidence of grade 3/4 ICI-induced colitis treated with anti-TNFα, in patients with advanced melanoma, and the consequence of this therapeutic strategy on disease outcome. All patients with advanced melanoma treated with anti-TNFα agents for severe ICI-related colitis in the participating centers were included. Relative incidence was calculated according to the total number of patients treated with ICI in network centers during the period of inclusion. The possible impact of anti-TNFα treatment on disease outcome was evaluated through comparison of objective response rate, progression-free survival, and OS with pivotal literature data. Twenty-seven patients from 13 tertiary referral centers were included. Overall, severe ICI-related colitis treated with anti-TNFα occurred in 1% of patients with advanced melanoma, mostly with ipilimumab. Infliximab was successfully used in all patients but 1, mostly after 1 infusion. OS and progression-free survival of 12 and 3 months, respectively, were observed in these patients, along with an objective response rate of 41% at 12 months. This survey shows a low real-life incidence of severe colitis requiring anti-TNFα. Response rates to immunotherapy and survival data do not appear to significantly differ from those observed in pivotal studies. Severe ICI-induced colitis requiring anti-TNFα treatment appears to be a rare event in advanced melanoma, and infliximab does not seem to adversely affect disease outcome.
Clinical Consequences of Antibody Formation, Serum Concentrations, and HLA-Cw6 Status in Psoriasis Patients on Ustekinumab
Authors: De Keyser Eline , Busard Celine I. , Lanssens Sven , Meuleman Lieve , Hutten Barbara A. , Costanzo Antonio , van den Reek Juul M. , Zweegers Jeffrey , Lambert Jo , Spuls Phyllis I.
Published: May 2019

Background:

Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine.

Methods:

To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for ≥16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or ≥64 of ustekinumab treatment.

Results:

A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02–3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6–positive and HLA-Cw6–negative patients (P = 0.164).

Conclusions:

The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged.
Safety of Long-Term Storage and Shipping of Prestripped, Prestained, and Preloaded Descemet Membrane Endothelial Keratoplasty Tissue
Authors: Hooton Jason , Kim Kyeong Hwan , Lentz Stephen I. , Hicks Nicholas , Jones Kayla , McCoy Kristen , Mian Shahzad I.
Published: May 2019

Purpose:

The purpose of this study was to determine the safety of long-term storage and shipping of prestripped, prestained, and preloaded Descemet membrane endothelial keratoplasty (p3DMEK) grafts.

Methods:

A total of 33 cadaveric corneas were prestripped, prestained, and preloaded using modified Jones tube injectors as p3DMEK. The corneas were masked to groups that were prepared <9 hours (control), 48 hours, and 72 hours before unloading and analysis. The 48- and 72-hour tissues were shipped by airfreight on each day before arrival to simulate domestic and international shipping. The corneas were then stained using Calcein AM vital dye (Molecular Probes, Eugene, OR) and imaged using an inverted confocal microscope. Primary outcome measures were endothelial cell loss (ECL, %) and sustainability of staining. MetaMorph software (Molecular Devices, Downingtown, PA) was used to quantify ECL, and staining was evaluated subjectively using all-or-none rating.

Results:

There was no difference in the mean ECL for the control, 48-hour, and 72-hour groups, which were 25.1% ± 8.8%, 26.4% ± 17.5%, and 19.2% ± 11.5%, respectively (P = 0.45; Kruskal–Wallis test). In all tissues of each group, no loss of staining was identified at each time point of analysis.

Conclusions:

ECL in p3DMEK tissue prepared 48 and 72 hours in advance and shipped using standard methods is similar to that in p3DMEK tissue prepared on the same day. These findings support the safety of domestic and international shipping of p3DMEK grafts.
Comparison of Endobronchial Ultrasound–guided Transbronchial Needle Aspiration With Stylet Retracted Partially Versus Completely for Molecular Testing
Authors: Fernandez-Bussy Sebastian , Biswas Abhishek , Labarca Gonzalo , Jantz Michael A. , Mehta Hiren J.
Published: May 2019

Background:

Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) is considered to be the initial diagnostic modality for most patients with lung cancer. However, the optimal technique for maximizing yield continues to vary in the real-world setting.

Objectives:

To evaluate the diagnostic yield of EBUS-TBNA with capillary sampling compared with complete stylet removal for molecular testing.

Methods:

Retrospective study, data from patients between January to May 2017 with indication of EBUS-TBNA whom ancillary testing, that is, next-generation sequencing, anaplastic lymphoma kinase (ALK), and programed death ligand-1 (PD-L1) expression was reviewed. The yield of 2 techniques, stylet retracted halfway (group 1) versus complete retraction (group 2), was compared.

Results:

A total of 24/27 (88.88%) samples were adequate for next-generation sequencing analysis in group 1 and 21/23 (91.30%) in group 2. For other molecular analyses, 24/27 (88.88%) samples in group 1 and 20/23 (86.95%) samples in group 2 were adequate for ALK analysis. 23/27 (85.18%) samples for group 1 and 20/23 (86.95%) samples for group 2 were adequate for PD-L1 analysis. Positive expression of PD-L1>50% was achieved in 9/23 (39.13%) of group 1 and 5/20 (25%) of group 2. There was no statistical difference in the yield between the 2 groups.

Conclusion:

EBUS-TBNA using either capillary sampling or complete stylet removal are effective and has a high proportion of satisfactory results for ancillary testing.
Effects of Changes in ICU Bed Supply on ICU Utilization
Authors: Barbash Ian J. , Wallace David J. , Kahn Jeremy M.
Published: May 2019

Background:

The availability of intensive care unit (ICU) beds may influence the demand for critical care. Although small studies support a model of supply-induced demand in the ICU, there is a paucity of system-wide data.

Objective:

The objective of this study was to determine the relationship between ICU bed supply and ICU admission in United States hospitals.

Research Design:

Retrospective cohort study using all-payer inpatient records from Florida, Massachusetts, New Jersey, New York, and Washington from 2010 to 2012, linked to hospital data from Medicare’s Healthcare Cost Reporting Information System.

Subjects:

Three patient groups with a low likelihood of benefiting from ICU admission—low severity patients with acute myocardial infarction and pulmonary embolism; and high severity patients with metastatic cancer at the end of life.

Measures:

We compared the risk-adjusted probability of ICU admission at hospitals that increased their ICU bed supply over time to matched hospitals that did not, using a difference-in-differences approach.

Results:

For patients with acute myocardial infarction, ICU supply increases were associated with an increase in the probability of ICU admission that diminished over time. For patients with pulmonary embolism, there was a trend toward an association between change in ICU supply and ICU admission that did not meet statistical significance. For patients with metastatic cancer, admission to hospitals with an increasing ICU supply was not associated with changes in the probability of ICU admission.

Conclusions:

Increases in ICU bed supply were associated with inconsistent changes in the probability of ICU admission that varied across patient subgroups.
Hirschsprung Disease
Authors: Harrington Amanda W. , Gasior Alessandra C. , Einarsdottir Hulda , Rothstein David H. , Rollins Michael D. , Ozgediz Doruk E.
Published: May 2019

Hirschsprung disease, like most surgically correctable congenital anomalies, is now survivable well into adulthood. Patients are, therefore, presenting later in life with problems that were previously infrequently encountered by colorectal surgeons or gastroenterologists. The goals of our review are to describe the current state of care transition for this patient population, identify the specific needs for these patients, and propose guidelines which could inform a future model of transition from the pediatric to adult setting. This is a review of the current state of care transition and long‐term outcomes for patients with Hirschsprung disease. Although these patients report a generally good quality of life, the majority suffer from some degree of lifelong gastrointestinal complication, regardless of the type of operative repair. A more formalized transition of care will provide a guide for pediatric surgeons and patients, alleviate colorectal surgeon and gastroenterologist concerns, and provide better long‐term care for these patients.
Making Patients Fit for Surgery
Authors: van Rooijen Stefanus J. , Molenaar Charlotte J.L. , Schep Goof , van Lieshout Rianne H.M.A. , Beijer Sandra , Dubbers Rosalie , Rademakers Nicky , Papen-Botterhuis Nicole E. , van Kempen Suzanne , Carli Francesco , Roumen Rudi M.H. , Slooter Gerrit D.
Published: May 2019

Background

Considering the relation between preoperative functional capacity and postoperative complications, enhancing patients’ functional capacity before surgery with a prehabilitation program may facilitate faster recovery and improve quality of life. However, time before surgery is short, mandating a multimodal and high-intensity training approach. This study investigated feasibility and safety of a prehabilitation program for colorectal cancer.

Methods

Multimodal prehabilitation was offered to patients eligible for participation and they were assigned to an intervention or control group by program availability. The prehabilitation program consisted of the following four interventions: in-hospital high-intensity endurance and strength training, high-protein nutrition and supplements, smoking cessation, and psychological support. Program attendance, patient satisfaction, adverse events, and functional capacity were determined.

Results

Fifty patients participated in this study (prehabilitation 20, control 30). Program evaluation revealed a high (90%) attendance rate and high level of patient satisfaction. No adverse events occurred. Endurance and/or strength were improved. Eighty-six percent of patients with prehabilitation recovered to their baseline functional capacity 4 weeks postoperatively, 40% in the control group (P < 0.01).

Conclusions

Multimodal prehabilitation including high-intensity training for colorectal cancer patients is feasible, safe, and effective. A randomized controlled trial (NTR5947) was initiated to determine whether prehabilitation may lower morbidity and mortality rates in colorectal surgery.
Brief Report: Impact of ART Classes on the Increasing Risk of Cerebral Small-Vessel Disease in Middle-Aged, Well-Controlled, cART-Treated, HIV-Infected Individuals
Authors: Januel Edouard , Godin Ophelia , Moulignier Antoine , Lescure François-Xavier , Savatovsky Julien , Lamirel Cédric , Valin Nadia , Tubiana Roland , Canestri Ana , Roux Pascal , Sadik Jean-Claude , Salomon Laurence , Katlama Christine , Yazdanpanah Yazdan , Pialoux Gilles , Girard Pierre-Marie , Costagliola Dominique , Assoumou Lambert ,   for the Microvascular Brain Retina And Kidney (MicroBREAK) Study Group
Published: May 2019

Background:

Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD.

Methods:

The MicroBREAK-2 case–control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group.

Results:

Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class.

Conclusion:

No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.
Impact of the Affordable Care Act on trauma and emergency general surgery: An Eastern Association for the Surgery of Trauma systematic review and meta-analysis
Authors: Zerhouni Yasmin A. , Scott John W. , Ta Christina , Hsu Paul Chiu-Hsieh , Crandall Marie , Gale Stephen C. , Schoenfeld Andrew J. , Bottiggi Anthony J. , Cornwell Edward E. , Eastman Alexander , Davis Jennifer Knight , Joseph Bellal , Robinson Bryce R. H. , Shafi Shahid , White Cassandra Q. , Williams Brian H. , Haut Elliott R. , Haider Adil H.
Published: May 2019

BACKGROUND

Trauma and emergency general surgery (EGS) patients who are uninsured have worse outcomes as compared with insured patients. Partially modeled after the 2006 Massachusetts Healthcare Reform (MHR), the Patient Protection and Affordable Care Act was passed in 2010 with the goal of expanding health insurance coverage, primarily through state-based Medicaid expansion (ME). We evaluated the impact of ME and MHR on outcomes for trauma patients, EGS patients, and trauma systems.

METHODS

This study was approved by the Eastern Association for the Surgery of Trauma Guidelines Committee. Using Grading of Recommendations Assessment, Development and Evaluation methodology, we defined three populations of interest (trauma patients, EGS patients, and trauma systems) and identified the critical outcomes (mortality, access to care, change in insurance status, reimbursement, funding). We performed a systematic review of the literature. Random effect meta-analyses and meta-regression analyses were calculated for outcomes with sufficient data.

RESULTS

From 4,593 citations, we found 18 studies addressing all seven predefined outcomes of interest for trauma patients, three studies addressing six of seven outcomes for EGS patients, and three studies addressing three of eight outcomes for trauma systems. On meta-analysis, trauma patients were less likely to be uninsured after ME or MHR (odds ratio, 0.49; 95% confidence interval, 0.37–0.66). These coverage expansion policies were not associated with a change in the odds of inpatient mortality for trauma (odds ratio, 0.96; 95% confidence interval, 0.88–1.05). Emergency general surgery patients also experienced a significant insurance coverage gains and no change in inpatient mortality. Insurance expansion was often associated with increased access to postacute care at discharge. The evidence for trauma systems was heterogeneous.

CONCLUSION

Given the evidence quality, we conditionally recommend ME/MHR to improve insurance coverage and access to postacute care for trauma and EGS patients. We have no specific recommendation with respect to the impact of ME/MHR on trauma systems. Additional research into these questions is needed.

LEVEL OF EVIDENCE

Review, Economic/Decision, level III
Long-Term Stability of Neuroaxonal Structure in Alemtuzumab-Treated Relapsing–Remitting Multiple Sclerosis Patients
Authors: Chan Jillian K. , Hernandez Martínez de Lapiscina Elena , Taylor Carolyn , Nguyen Ai-Lan , Alba-Arbalat Salut , Devonshire Virginia , Sayao Ana-Luiza , Carruthers Robert , Costello Fiona , Traboulsee Anthony
Published: May 2019

Background:

Patients with multiple sclerosis (MS) experience progressive thinning in optical coherence tomography (OCT) measures of neuroaxonal structure regardless of optic neuritis history. Few prospective studies have investigated the effects of disease-modifying therapies on neuroaxonal degeneration in the retina. Alemtuzumab is a monoclonal antibody shown to be superior to interferon β-1a in treating relapsing–remitting MS (RRMS). The purpose of this study was to assess the effects of alemtuzumab and first-line injectable treatments on OCT measures of neuroaxonal structure including peripapillary retinal nerve fiber layer (RNFL) thickness and combined ganglion cell–inner plexiform (GCIP) layer volume in RRMS patients followed up over 5 years.

Methods:

In this retrospective pilot study with prospectively collected double cohort data, spectral domain OCT measures of RNFL thickness and GCIP volume were compared between alemtuzumab-treated RRMS patients (N = 24) and RRMS patients treated with either interferon-β or glatiramer acetate (N = 21).

Results:

Over a median of 60 months (range 42–60 months), the alemtuzumab cohort demonstrated a change in the mean RNFL thickness (thinning from baseline) of −0.88 μm (95% confidence interval [CI] −2.63 to 0.86;P= 0.32) and mean GCIP volume of +0.013 mm3(95% CI −0.006 to 0.032;P= 0.18). Over the same time period, the first-line therapy–treated cohort demonstrated greater degrees of RNFL thinning (mean change in RNFL thickness was −3.65 μm [95% CI −5.40 to −1.89;P= 0.0001]). There was also more prominent GCIP volume loss relative to baseline in the first-line therapy group (−0.052 mm3[95% CI −0.070 to −0.034;P< 0.0001]).

Conclusions:

Alemtuzumab-treated patients with RRMS demonstrated relative stability of OCT-measured neuroaxonal structure compared with RRMS patients treated with either interferon-β or glatiramer acetate over a 5-year period. These findings, along with previous demonstration of improved brain atrophy rates, suggest that alemtuzumab may offer long-term preservation of neuroaxonal structure in patients with RRMS.
Somatodendritic HCN channels in hippocampal OLM cells revealed by a convergence of computational models and experiments
Authors: Sekulić Vladislav , Yi Feng , Garrett Tavita , Guet-McCreight Alexandre , Lopez Yvette Y. , Solis-Wheeler Mychael , Wang Rui , Liu Xiaobo , Lawrence J.Josh , Skinner Frances K.
Published: May 2019

Determining details of spatially extended neurons is a challenge that needs to be overcome. The oriens-lacunosum/moleculare (OLM) interneuron has been implicated as a critical controller of hippocampal memory making it essential to understand how its biophysical properties contribute to function. We previously used computational models to show that OLM cells exhibit theta spiking resonance frequencies that depend on their dendrites having hyperpolarization-activated cation channels (h-channels). However, whether OLM cells have dendritic h-channels is unknown. We performed a set of whole-cell recordings of OLM cells from mouse hippocampus and constructed multi-compartment models using morphological and electrophysiological parameters extracted from the same cell. The models matched experiments only when dendritic h-channels were present. Immunohistochemical localization of the HCN2 subunit confirmed dendritic expression. These models can be used to obtain insight into hippocampal function. Our work shows that a tight integration of model and experiment tackles the challenge of characterizing spatially extended neurons.
Fetal whole-heart 4D flow cine MRI using multiple non-coplanar balanced SSFP stacks
Authors: Roberts Thomas A. , van Amerom Joshua FP , Uus Alena , Lloyd David FA , Price Anthony N. , Tournier Jacques-Donald , Jackson Laurence H. , Malik Shaihan J , van Poppel Milou PM , Pushparajah Kuberan , Rutherford Mary A , Rezavi Reza , Deprez Maria , Hajnal Joseph V.
Published: May 2019

Purpose

To develop an MRI framework for reconstruction of 4D velocity vector blood flow volumes for visualisation and quantification of circulation in the fetal heart and major vessels.

Methods

A novel method of velocity-encoding using multiple non-coplanar stacks of bSSFP phase images was combined with a previous framework for reconstruction of motion-corrected 4D magnitude cine volumes to generate spatiotemporally-paired 4D flow cine volumes of the fetal circulatory system. The multiple stack velocity-encoding scheme was validated in a simulated flow phantom and compared with a gold-standard method for velocity-encoding in a physical flow phantom. The 4D flow cine framework was evaluated in seven fetal subjects. Reconstructed 4D flow volumes were evaluated by an expert fetal cardiologist and preliminary flow measurements were taken in various major vessels of the heart.

Results

Phantom experiments showed that the multiple non-coplanar stack velocity-encoding scheme was accurate. The 4D flow cine reconstruction framework was robust in fetal subjects and generated multi-dimensional velocity vector maps of blood flow through the cardiac cycle. Directionality of blood flow was consistent with expected fetal circulatory hemodynamics. Relative blood flow rates in the major vessels were in line with previous observations, although absolute values were underestimated by a factor of approximately two due to limitations of spatial and temporal resolution.

Conclusion

4D flow cine volumes can be reconstructed from multiple non-coplanar stacks of slices. The proposed framework was used to visualise and quantify flow through the whole fetal heart and great vessels, but is applicable to any imaging scenario where motion is a major challenge.
Predator recognition and anti-predatory behaviour in a recent aquatic invader, the killer shrimp (Dikerogammarus villosus)
Authors: Rolla Matteo , Consuegra Sonia , de Leaniz Carlos Garcia
Published: May 2019

The killer shrimp (Dikerogammarus villosus) is one of the most recent, but also most damaging, aquatic invasive species in Europe, but information on how the species responds to novel predation pressures in recently invaded areas is very limited. We employed an open test arena to examine predator recognition and anti-predatory behaviour in killer shrimp exposed to either blank water or water conditioned with fish kairomones to simulate a predator threat. Within five years after their introduction, killer shrimp spent much more time hiding in the presence of fish kairomones than when they were exposed to blank water. However, no significant difference was found in aggregation behaviour, and killer shrimp were strongly attracted to the scent of conspecifics regardless of predator threat. Given the strong selective pressures that fish predators can exert on native and invasive gammarids, our findings highlight the need to consider prey-predator interactions to better predict the dispersal and likely impact of killer shrimp into invaded ecosystems.
TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
Authors: Castellanos Aida , Pujol-Coma Anna , Andres-Bilbe Alba , Negm Ahmed , Callejo Gerard , Soto David , Noël Jacques , Comes Nuria , Gasull Xavier
Published: May 2019

Changes in TRESK K+ channel expression/function enhance sensory neurons excitability, but its role in somatosensory perception and nociception is poorly understood. We show that TRESK regulates the sensitivity to mechanical and cold stimuli but not the perception of heat. TRESK knockout mice nociceptive neurons present an enhanced excitability; skin nociceptive C-fibers show an increased activation by lower intensity cold or mechanical stimulation and mice lacking TRESK present mechanical and cold hypersensitivity. TRESK is also involved in osmotic pain and in early phases of formalin-induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that it regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing, acting as a brake to prevent activation by low-intensity stimuli.
Spatial Distribution of Cholesterol in Lipid Bilayers
Authors: Aghaaminiha M. , Sharma S.
Published: May 2019

1.

We have performed molecular simulations to study spatial distribution and orientation of cholesterol molecules within three symmetric lipid bilayer systems: two binary lipid mixtures, namely, DOPC/CHOL (1, 2-dioleoyl-sn-glycero-3-phosphocholine/cholesterol) and SM/CHOL (d20:1/20:0 sphingomyelin /Cholesterol), and a tertiary mixture of DOPC/SM/CHOL. We have studied the behavior of these bilayers at temperatures varying from 400 K to 210 K and cholesterol molar concentration from 0% to 60%.We observe that the spatial distribution of cholesterol is strongly correlated with the phase of the bilayer. In the disordered phase, cholesterol molecules are predominantly present near the center of the bilayer. In the ordered phase, cholesterol molecules are mainly present in the leaflets. At the order - disorder transition temperature, the fraction of cholesterol molecules is equal in the two leaflets and the center. In the leaflets, cholesterol molecules are oriented parallel to the bilayer normal, while near the center, cholesterol molecules are randomly oriented. In agreement with previous experimental studies, we find that increasing the cholesterol concentration favors ordered phase of the bilayers. The preference of cholesterol molecules to be present in the leaflets in the ordered phase is attributed to their favorable hydrophobic interactions with the lipid tails.

2.

Statement of Significance

Cholesterol has an important role in governing the physical properties of lipid bilayers, including their structural integrity, phase behavior and permeability. The spatial distribution of cholesterol in lipid bilayers is not well-understood because of the challenges associated with performing experiments for such a measurement. We show, via molecular simulations, that the spatial distribution of cholesterol molecules is strongly correlated with the phase behavior of the lipid bilayers. In the ordered phase, cholesterol molecules are predominantly present in the leaflets, whereas in the disordered phase, cholesterol molecules are in the center region of the bilayer. These results are important for understanding the relationship between lipid bilayer composition and their biological function and response.
Rapid adaptation to Elevated Extracellular Potassium in the Pyloric Circuit of the Crab, Cancer borealis
Authors: He Lily S. , Rue Mara C.P. , Morozova Ekaterina O. , Powell Daniel J. , James Eric J. , Kar Manaswini , Marder Eve
Published: May 2019

Elevated [K+] is often used to alter excitability in neurons and networks by shifting the potassium equilibrium potential (EK) and, consequently, the resting membrane potential. We studied the effects of increased extracellular [K+] on the well-described pyloric circuit of the crab, Cancer borealis. A 2.5-fold increase in extracellular [K+] (2.5x[K+]) depolarized Pyloric Dilator (PD) neurons and resulted in short-term loss of their normal bursting activity. This period of silence was followed within 5-10 minutes by the recovery of spiking and/or bursting activity during continued superfusion of 2.5x[K+] saline. In contrast, when PD neurons were pharmacologically isolated from pyloric presynaptic inputs, they exhibited no transient loss of spiking activity in 2.5x[K+], suggesting the presence of an acute inhibitory effect mediated by circuit interactions. Action potential threshold in PD neurons hyperpolarized during an hour-long exposure to 2.5x[K+] concurrent with the recovery of spiking and/or bursting activity. Thus, the initial loss of activity appears to be mediated by synaptic interactions within the network, but the secondary adaptation depends on changes in the intrinsic excitability of the pacemaker neurons. The complex sequence of events in the responses of pyloric neurons to elevated [K+] demonstrates that electrophysiological recordings are necessary to determine both the transient and longer-term effects of even modest alterations of K+ concentrations on neuronal activity.

Significance Statement

Solutions with elevated extracellular potassium are commonly used as a depolarizing stimulus. Moreover, hyperkalemia is associated with a number of disease states, including epileptic seizures and brain traumas. We studied the effects of high [K+] saline on the well-described pyloric circuit of the crab stomatogastric ganglion. A 2.5-fold increase in extracellular [K+] led to a transient loss of activity in pyloric neurons that was not due to depolarization block. This was followed by a rapid increase in excitability and concurrent recovery of spiking and rhythmic bursting activity within minutes. These results suggest that effects of high [K+] on neuronal circuits can be complex and non-stationary.
Human Demographic Outcomes of a Restored Agro-Ecological Balance
Authors: Wyckhuys K.A.G. , Burra D.D. , Pretty J. , Neuenschwander P.
Published: May 2019

As prominent features of the Anthropocene, biodiversity loss and invasive species are exacting serious negative economic, environmental and societal impacts. While the monetary aspects of species invasion are reasonably well assessed, their human and social livelihood outcomes often remain obscure. Here, we empirically demonstrate the (long-term) human demographic consequences of the 1970s invasion of a debilitating pest affecting cassava -a carbohydrate-rich food staple-across sub-Saharan Africa. Successive pest attack in 18 African nations inflicted an 18 ± 29% drop in crop yield, with cascading effects on birth rate (−6%), adult mortality (+4%) and decelerating population growth. The 1981 deliberate release of the parasitic waspAnagyrus lopezipermanently restored food security and enabled parallel recovery of multiple demographic indices. This analysis draws attention to the societal repercussions of ecological disruptions in subsistence farming systems, providing lessons for efforts to meet rising human dietary needs while safeguarding agro-ecological functionality and resilience during times of global environmental change.
When tension is exciting: an EEG exploration of excitement in music
Authors: Turrell Amelia , Halpern Andrea R , Javadi Amir-Homayoun
Published: May 2019

Music powerfully affects people’s emotions. In particular, moments of tension and deviation in musical features, including frequency, pitch, and rhythm (known as a Drop), are associated with positive emotions. However, the neuro-correlates of Drops emotive effects have never been explored. Thirty-six participants listened to music pieces containing a Drop, while undergoing continuous EEG, and rated felt excitement. Source reconstruction of EEG data showed significantly different activity in five brain regions before and after Drops: pre- and post-central gyri (PreCG and PostCG), and precuneus (PCUN) were more active before Drops and the inferior frontal gyrus (IFG), and middle frontal gyrus (MFG) were more active after Drops. Importantly, activity in the IFG and MFG showed a strong correlation with subjective excitement ratings during Drop apprehension. These results suggest expectancy is important to the induction of musical emotions, in agreement with the ITPRA theory. Specifically, when Drops are expected but do not occur immediately, moderate tension is induced. Strong positive emotions then ensue when expected deviations finally occur, due to contrastive valence. This is reflected in significant brain activity for regions associated with high arousing, pleasurable emotions, such as excitement.
Stereomotion processing in the non-human primate brain
Authors: Héjja-Brichard Yseult , Rima Samy , Rapha Emilie , Durand Jean-Baptiste , Cottereau Benoit R.
Published: May 2019

The cortical areas that process disparity-defined motion-in-depth (i.e. cyclopean stereomotion) were characterised with functional magnetic resonance imaging in two awake, behaving macaques. The experimental protocol was similar to previous human neuroimaging studies. We contrasted the responses to dynamic random-dot patterns that continuously changed their binocular disparity over time with those to a control condition that shared the same properties, except that the temporal frames were shuffled. A whole-brain voxel-wise analysis revealed that in all four cortical hemispheres, three areas showed consistent sensitivity to cyclopean stereomotion. Two of them were localised respectively in the lower bank of the superior temporal sulcus (CSMSTS) and on the neighbouring infero-temporal gyrus (CSMITG). The third area was situated in the posterior parietal cortex (CSMPPC). Additional ROIs-based analyses within retinotopic areas defined in both animals indicated weaker but significant responses to cyclopean stereomotion within the MT cluster (most notably in areas MSTv and FST). Altogether, our results are in agreement with previous findings in both human and macaque and suggest that the cortical networks that process cyclopean stereomotion is relatively well preserved between the two primate species.
Active Poroelastic Two-Phase Model for the Motion of Physarum Microplasmodia
Authors: Kulawiak Dirk Alexander , Löber Jakob , Bär Markus , Engel Harald
Published: May 2019

The onset of self-organized motion is studied in a poroelastic two-phase model with free boundaries for Physarum microplasmodia (MP). In the model, an active gel phase is assumed to be interpenetrated by a passive fluid phase on small length scales. A feedback loop between calcium kinetics, mechanical deformations, and induced fluid flow gives rise to pattern formation and the establishment of an axis of polarity. Altogether, we find that the calcium kinetics that breaks the conservation of the total calcium concentration in the model and a nonlinear friction between MP and substrate are both necessary ingredients to obtain an oscillatory movement with net motion of the MP. By numerical simulations in one spatial dimension, we find two different types of oscillations with net motion as well as modes with time-periodic or irregular switching of the axis of polarity. The more frequent type of net motion is characterized by mechano-chemical waves traveling from the front towards the rear. The second type is characterized by mechano-chemical waves that appear alternating from the front and the back. While both types exhibit oscillatory forward and backward movement with net motion in each cycle, the trajectory and gel flow pattern of the second type are also similar to recent experimental measurements of peristaltic MP motion. We found moving MPs in extended regions of experimentally accessible parameters, such as length, period and substrate friction strength. Simulations of the model show that the net speed increases with the length, provided that MPs are longer than a critical length of ≈ 120 µm. Both predictions are in line with recent experimental observations.
Analyzing the weak dimerization of a cellulose binding module by sedimentation velocity experiments
Authors: Fedorov Dmitrii , Batys Piotr , Sammalkorpi Maria , Linder Markus B.
Published: May 2019

Cellulose binding modules (CBMs) are found widely in different proteins that act on cellulose. Because they allow a very easy way of binding recombinant proteins to cellulose, they have become widespread in many biotechnological applications involving cellulose. One commonly used variant is the CBMCipAfromClostridium thermocellum. Here we studied the dimerization of CBMCipA, because we were interested if its solution behavior could have an impact on its use in biotechnical applications. As the principal approach, we used sedimentation velocity analytical ultracentrifugation. To enhance our understanding of the possible interactions, we used molecular dynamics simulations. By analysis of the sedimentation velocity data using a discrete model genetic algorithm we found that the CBMCipAshows a weak dimerization interaction with a dissociation constantKDof about 87 μM. As theKDof CBMCipAbinding to cellulose is about 0.6 μM, we conclude that the dimerization is unlikely to affect cellulose binding. However, at the high concentrations used in some applications of the CMBCipA, its dimerization is likely to have an effect on its solution behavior. The work shows that analytical ultracentrifugation is a very efficient tool to analyze this type of weak interactions. Moreover, we provide here a protocol for data analysis in the program Ultrascan for determining dissociation constants by sedimentation velocity experiments.
Addiction of mesenchymal phenotypes on the FGF/FGFR axis in oral squamous cell carcinoma cells
Authors: Osada Asami Hotta , Endo Kaori , Kimura Yujiro , Sakamoto Kei , Nakamura Ryosuke , Sakamoto Kaname , Ueki Koichiro , Yoshizawa Kunio , Miyazawa Keiji , Saitoh Masao
Published: May 2019

The epithelial–mesenchymal transition (EMT) is a crucial morphological event that occurs during epithelial tumor progression. ZEB1/2 are EMT transcription factors that are positively correlated with EMT phenotypes and breast cancer aggressiveness. ZEB1/2 regulate the alternative splicing and hence isoform switching of fibroblast growth factor receptors (FGFRs) by repressing the epithelial splicing regulatory proteins, ESRP1 and ESRP2. Here, we show that the mesenchymal-like phenotypes of oral squamous cell carcinoma (OSCC) cells are dependent on autocrine FGF–FGFR signaling. Mesenchymal-like OSCC cells express low levels of ESRP1/2 and high levels of ZEB1/2, resulting in constitutive expression of the IIIc-isoform of FGFR, FGFR(IIIc). By contrast, epithelial-like OSCC cells showed opposite expression profiles for these proteins and constitutive expression of the IIIb-isoform of FGFR2, FGFR2(IIIb). Importantly, ERK was constitutively phosphorylated through FGFR1(IIIc), which was activated by factors secreted autonomously by mesenchymal-like OSCC cells and involved in sustained high-level expression of ZEB1. Antagonizing FGFR1 with either an inhibitor or siRNAs considerably repressed ZEB1 expression and restored epithelial-like traits. Therefore, autocrine FGF–FGFR(IIIc) signaling appears to be responsible for sustaining ZEB1/2 at high levels and the EMT phenotype in OSCC cells.