bluuebunny/crossref_metadata_2025 huggingface dataset:
Concussion in Adolescents Impairs Heart Rate Response to Brief Handgrip Exercise
Authors: Woehrle Emilie , Harriss Alexandra B. , Abbott Kolten C. , Moir Marcy Erin , Balestrini Christopher S. , Fischer Lisa K. , Fraser Douglas D. , Shoemaker Joel Kevin
Published: August 2018

Objective:

Test the hypotheses that (1) concussion in adolescents impairs autonomic neural control of heart rate (HR), and (2) HR reactivity improves with symptom resolution.

Design:

Observational, case–control.

Participants:

Nineteen concussed adolescents (8 female adolescents; age 15 ± 2 years) and 16 healthy controls (6 female adolescents, age 15 ± 2 years).

Intervention:

All participants performed an isometric handgrip (IHG) at 30% maximum voluntary contraction lasting 30 seconds. Heart rate (electrocardiogram) and hemodynamic responses (photoplethysmographic Finometer) were recorded from 30 seconds of baseline and the last 10 seconds of handgrip.

Main Outcome Measures:

The HR response (ΔHR) at the onset of moderate-intensity IHG using a mixed 1-way analysis of variance.

Results:

A group × time interaction (P < 0.005) indicated that handgrip evoked a greater ΔHR among control participants (13 ± 10 beats/min) compared with concussed (6.4 ± 6.3 beats/min; group P = 0.63; time P < 0.001; d = 0.77).

Conclusion:

These preliminary results suggest that a concussion impairs the ability to elevate HR at the exercise onset and, given the nature of the task, this could be interpreted to reflect reduced ability to withdraw cardiovagal control. Therefore, the data support the hypothesis of neural cardiac dysregulation in adolescents diagnosed with concussion.

Clinical Relevance:

The IHG test could aid concussion diagnosis and support return-to-play decisions.
Evolving Trends in Cochlear Implantation: A Critical Look at the Older Population
Authors: Agabigum Bora , Mir Ahsan , Arianpour Khashayar , Svider Peter F. , Walsh Erika M. , Hong Robert S.
Published: August 2018

Objectives/Hypothesis:

Cochlear implantation (CI) is a well-accepted surgical option for the treatment of moderate to profound deafness. The purpose of this study was to evaluate the temporal and geographic trends of this procedure nationwide in the Medicare population in an attempt to explore the impact of evolving technologies and changes in healthcare policy.

Methods:

Medicare Part B national summary procedural datasets from 2007 to 2016 were obtained. Current Procedural Terminology codes for CI as well as auditory osseointegrated implantation were obtained. Centers for Medicare and Medicaid Services (CMS) datasets were evaluated to determine temporal trends. For geographic trends, specific carrier datasets from 2007 and 2016 were used.

Results:

From 2007 through 2016, the number of CI procedures increased annually from 1603 to 3600 (124.6%). Other procedures to treat hearing loss including bone-anchored implantation exhibited comparatively modest increases (23%, 90%). CI procedures increased every year in contrast to bone-anchored implants. Controlling for Medicare population, the greatest number of CI procedures performed per capita in the United States was in the West North Central, with an average 1.05 CIs per 10,000 beneficiaries.

Conclusion:

The number of CI procedures performed in the elderly population has increased markedly over the past 10 years, far outpacing growth in other hearing surgeries. Potential reasons may relate to changes in criteria for CI candidacy over the past decade, although significant regional variability demonstrated suggests a lack of consensus. Further studies would be necessary to ascertain the true reason for geographic disparities.
Novel Computed Tomography Findings Suggestive of Perilymph Gusher
Authors: Varadarajan Varun V. , DeJesus Reordan O. , Antonelli Patrick J.
Published: August 2018

Objectives:

Perilymphatic gusher (PLG) is an uncommon complication of stapedectomy and cochlear implant placement. Computerized tomography (CT) may reveal congenital dysplasia responsible for PLG but may also be (incorrectly) interpreted as normal. The aim of this study was to review CT findings in patients with PLG reported to have normal temporal bones.

Patients:

Patients in which a PLG was encountered and preoperative CT imaging had been interpreted as normal.

Intervention:

Collaborative review of temporal bone computed tomography by neurotologist and neuroradiologist.

Main Outcome Measure:

Identification of undetected inner ear anomalies that may predispose to PLG.

Results:

Unanticipated PLG was encountered during stapes surgery in two patients and cochlear implantation in one. A focal bony dehiscence between the basal turn of the cochlea and internal auditory canal (IAC) was identified on a few oblique reformatted images in all patients.

Conclusions:

High resolution CT with oblique image reformatting is essential to identify focal communication between the IAC and basal turn of the cochlea in ears with PLG.
Prevention of Chlorhexidine Ototoxicity With Poloxamer in Rats
Authors: Dirain Carolyn O. , Vasquez Taylor K. , Antonelli Patrick J.
Published: August 2018

Objective:

Skin preparations, like chlorhexidine, are toxic to the inner ear, preventing their use as a preoperative skin disinfectant in the presence of a nonintact eardrum (e.g., perforation or tube). We aimed to determine if a poloxamer gel applied over perforated eardrums could prevent chlorhexidine ototoxicity.

Study Design:

Controlled, in vivo.

Setting:

Academic research laboratory.

Subjects and Methods:

Bilateral myringotomies were performed on 20 Sprague-Dawley rats. Half had poloxamer placed over both eardrums before treatment. All rats had chlorhexidine instilled in one ear and saline in the other. Auditory brainstem response thresholds were measured before and 2- and 4-weeks posttreatment. Cochlear hair cell damage was assessed using scanning electron microscopy.

Results:

Ears with chlorhexidine without poloxamer had significant hearing loss, 37 to 50 dB worse than the other three ear treatments at 2 and 4 weeks posttreatment, at all tested frequencies (4, 18, 16, and 24 kHz; all p < 0.0001). No significant hearing loss was observed in ears that were treated with poloxamer and chlorhexidine (−2 to 8 dB) and the results were not different from the ears that received saline, with or without poloxamer (−2.5 to 8 dB and 5–17 dB; p > 0.05). Electron microscopy showed far more outer hair cell damage in the no poloxamer + chlorhexidine ears compared with the other three treatments.

Conclusion:

The use of a poloxamer barrier may be an effective approach to prevent ototoxicity before chlorhexidine disinfection of the ear with a nonintact tympanic membrane.
Augmented Reality of the Middle Ear Combining Otoendoscopy and Temporal Bone Computed Tomography
Authors: Marroquin Roberto , Lalande Alain , Hussain Raabid , Guigou Caroline , Grayeli Alexis Bozorg
Published: August 2018

Hypothesis:

Augmented reality (AR) may enhance otologic procedures by providing sub-millimetric accuracy and allowing the unification of information in a single screen.

Background:

Several issues related to otologic procedures can be addressed through an AR system by providing sub-millimetric precision, supplying a global view of the middle ear cleft, and advantageously unifying the information in a single screen. The AR system is obtained by combining otoendoscopy with temporal bone computer tomography (CT).

Methods:

Four human temporal bone specimens were explored by high-resolution CT-scan and dynamic otoendoscopy with video recordings. The initialization of the system consisted of a semi-automatic registration between the otoendoscopic video and the 3D CT-scan reconstruction of the middle ear. Endoscope movements were estimated by several computer vision techniques (feature detectors/descriptors and optical flow) and used to warp the CT-scan to keep the correspondence with the otoendoscopic video.

Results:

The system maintained synchronization between the CT-scan image and the otoendoscopic video in all experiments during slow and rapid (5–10 mm/s) endoscope movements. Among tested algorithms, two feature-based methods, scale-invariant feature transform (SIFT); and speeded up robust features (SURF), provided sub-millimeter mean tracking errors (0.38 ± 0.53 mm and 0.20 ± 0.16 mm, respectively) and an adequate image refresh rate (11 and 17 frames per second, respectively) after 2 minutes of procedure with continuous endoscope movements.

Conclusion:

A precise augmented reality combining video and 3D CT-scan data can be applied to otoendoscopy without the use of conventional neuronavigation tracking thanks to computer vision algorithms.
Complications in Endoscopic Ear Surgery
Authors: Marchioni Daniele , Rubini Alessia , Gazzini Luca , Alicandri-Ciufelli Matteo , Molinari Giulia , Reale Marella , Presutti Livio
Published: August 2018

Objective:

The aim of this study was to examine the premise that endoscopic ear surgery (EES) is associated with a low rate of complications (intraoperative and postoperative).

Study Design:

Retrospective review at two institutions.

Setting:

Tertiary referral center.

Patients:

The study included 825 patients who underwent exclusive EES between 2008 and 2016 at the Otorhinolaryngology-Head and Neck Surgery Department of Modena University Hospital, and between 2014 and 2016 at the Otorhinolaryngology-Head and Neck Surgery Department of Verona University Hospital.

Interventions:

Exclusive endoscopic ear surgery between 2008 and 2016 (tympanoplasties, second look or revision tympanoplasties, myringoplasties, stapedoplasties, canalplasties, ossiculoplasties, and exploratory tympanotomies). All surgical procedures were performed by two experienced surgeons.

Main Outcome Measure:

For each procedure, intraoperative, and early and delayed postoperative complications were evaluated.

Results:

The most common ear pathologies for which patients were sent for EES were cholesteatoma (33.6%), chronic otitis media (36.3%) and otosclerosis (26.8%). There was no case of major intraoperative complications such as injury to the dura or vascular structures. We observed minor intraoperative complications in 4.1% of the cases. Only 1.3% of patients experienced early postoperative complications. Delayed complications affected less than 1% of the cohort.

Conclusions:

Data from this study confirm the safety of the endoscopic technique, with very low complication rates, indicating that EES is a reliable therapeutic option, in particular, for tympanoplasties, myringoplasties, and stapedoplasties, as well as second look procedures. We have reported our experience with EES morbidity so that it can be compared with data from other centers using the same surgical technique.
‘Massive transfusion protocols and the use of tranexamic acid’
Authors: Godbey Elizabeth A. , Schwartz Joseph
Published: August 2018

Purpose of review

We review recent articles pertaining to the use of tranexamic acid (TXA) in populations at risk for massive transfusion. Although there are no recent studies that specifically examine the use of TXA in massive transfusion protocols (MTPs), there are a few studies with subgroups of massive transfusion patients.

Recent findings

In recent years, many publications have discussed outcomes and safety associated with the addition of TXA to treatment plans for bleeding pediatric, trauma, and postpartum hemorrhage patients. In general, TXA appears to decrease mortality and transfusion requirements.

TXA was shown to decrease mortality in several bleeding populations. It is now a common addition to MTPs. There is conflicting evidence regarding the potential of TXA as a risk factor for thrombotic events. Ongoing studies should provide additional evidence regarding the thrombotic risk of TXA in massive transfusion.
Delayed haemolytic and serologic transfusion reactions: pathophysiology, treatment and prevention
Authors: Siddon Alexa J. , Kenney Barton C. , Hendrickson Jeanne E. , Tormey Christopher A.
Published: August 2018

Purpose of review

The aim of this study was to summarize the basic epidemiology, pathophysiology and management of delayed serologic and delayed haemolytic transfusion reactions (DHTRs), as well as recent developments in our understanding of these adverse events.

Recent findings

Several studies have identified risk factors for DHTRs, including high alloantibody evanescence rates among both general patient groups and those with sickle cell disease (SCD). Antibody detection is also hampered by the phenomenon of transfusion record fragmentation. There have also been enhancements in understanding of what may contribute to the more severe, hyperhaemolytic nature of DHTRs in SCD, including data regarding ‘suicidal red blood cell death’ and immune dysregulation amongst transfusion recipients with SCD. With growing recognition and study of hyperhaemolytic DHTRs, there have been improvements in management strategies for this entity, including a multitude of reports on using novel immunosuppressive agents for preventing or treating such reactions.

Delayed serologic and haemolytic reactions remain important and highly relevant transfusion-associated adverse events. Future directions include further unravelling the basic mechanisms, which underlie DHTRs and developing evidence-based approaches for treating these reactions. Implementing practical preventive strategies is also a priority.
Age-related clonal hematopoiesis: implications for hematopoietic stem cell transplantation
Authors: Abelson Sagi , Wang Jean C.Y.
Published: August 2018

Purpose of review

Over the past decade, advances in hematopoietic stem cell transplantation (HSCT) have enabled older individuals to undergo the procedure as well as to serve as donors. Recently, aging has been linked with the development of age-related clonal hematopoiesis (ARCH), defined as the gradual clonal expansion of hematopoietic stem and progenitor cells (HSPC) carrying recurrent disruptive genetic variants in individuals without a diagnosis of hematologic malignancy. Here we will review the implications of ARCH in the context of HSCT.

Recent findings

ARCH is highly prevalent in the general population and commonly involves genes that are recurrently mutated in hematologic malignancies. Nevertheless, the vast majority of individuals with ARCH will not develop overt hematologic disease in their lifetime. The presence of ARCH may increase the risk of therapy-related myeloid neoplasms (t-MN) in individuals undergoing autologous HSCT. In the setting of allogeneic HSCT, ARCH present in the donor may contribute to adverse outcomes such as unexplained cytopenias posttransplant and donor cell leukemia.

A better understanding of the hematopoietic milieu of HSCT recipients and of the importance of ARCH in the context of the replicative pressures imposed on transplanted HSPCs is needed in order to optimize conditioning regimens, donor selection and clinical outcomes post-HSCT.
Preexisting Diabetes Elevates Risk of Local and Systemic Complications in Acute Pancreatitis
Authors: Mikó Alexandra , Farkas Nelli , Garami András , Szabó Imre , Vincze Áron , Veres Gábor , Bajor Judit , Alizadeh Hussain , Rakonczay Zoltán , Vigh Éva , Márta Katalin , Kiss Zoltán , Hegyi Péter , Czakó László
Published: August 2018

The prevalence of diabetes mellitus (DM) and acute pancreatitis (AP) increases continuously, therefore, to understand the effects of preexisting diabetes on AP is crucially needed. Here, we performed a systematic review and meta-analysis in which AP patients including DM and non-DM groups were sorted. Several outcome parameters were analyzed, and the odds ratio (OR) and standardized mean difference with 95% confidence intervals (CIs) were calculated.

We found 1417 articles, of which 9 articles involving 354,880 patients were analyzed. More complications were seen in diabetic patients than in non-DM patients (OR, 1.553 [95% CI, 1.266–1.904]; P < 0.001). Intensive care unit admission (OR, 1.799 [95% CI, 1.442–2.243]; P < 0.001) and renal failure (OR, 1.585 [95% CI, 1.278–1.966]; P < 0.001) were more frequent in DM patients. There was a tendency of higher mortality and local complications (OR, 1.276 [95% CI, 0.991–1.643]; P = 0.059; and OR, 1.267 [95% CI, 0.964–1.659]; P = 0.090, respectively) in preexisting DM. Length of hospitalization was longer in DM patients (standardized mean difference, 0.217 [95% CI, 0.075–0.360]; P = 0.003). Preexisting DM negatively influences the outcome of AP and increases the risk of renal failure, local complications, and mortality.
Physical Activity, the Childhood Cancer Symptom Cluster–Leukemia, and Cognitive Function
Authors: Hooke Mary C. , Rodgers Cheryl , Taylor Olga , Koerner Kari M. , Mitby Pauline , Moore Ida , Scheurer Michael E. , Hockenberry Marilyn J. , Pan Wei
Published: August 2018

Background

Children undergoing leukemia treatment report co-occurring symptoms of fatigue, sleep disturbances, pain, nausea, and depression as a symptom cluster. Physical activity (PA) is essential for development and may influence symptom severity. Children with leukemia are at risk of cognitive impairments from central nervous system therapies. Using a longitudinal parallel-process model, relationships among function and symptom clusters were explored.

Objective

This study examined the longitudinal mediation effects of PA on cognition via a symptom cluster during leukemia treatment.

Methods

Symptoms, PA, and cognitive function of 327 children aged 3 to 18 years were measured over 4 intervals during the first year of leukemia treatment. Children 7 years or older self-reported and parents reported for younger children. Parents completed cognitive function measurements for all children. The influence of the first time point and the subsequent change between all 4 time points of PA on the symptom cluster were explored. Analysis determined whether the symptom cluster mediated the effect of cognition over the treatment period.

Results

Patients with a higher PA at time 1 reduced their symptom cluster severity over the measurements. However, when PA increased over the measurements, symptom cluster severity also increased. When the symptom cluster was more severe at time 1, cognitive function was lower at time 1, and cognitive function decreased over time. When symptoms became more severe over time, cognitive function declined.

Conclusions

The symptom cluster acted as a mediator between PA and cognition.

Implications for Practice

Symptom management during treatment may be an additional strategy for protecting cognitive function.
The Relationships Between Weight Bias, Perceived Weight Stigma, Eating Behavior, and Psychological Distress Among Undergraduate Students in Hong Kong
Authors: Cheng Man Yan , Wang Shu-Mei , Lam Yin Ying , Luk Hiu Tung , Man Yuk Ching , Lin Chung-Ying
Published: August 2018

Weight bias issues are rarely discussed in Asia. Therefore, we examined the relationships between weight bias, perceived weight stigma (PWS), eating behavior, and psychological distress among Hong Kong people. Using cross-sectional design, 400 undergraduate students (175 men) completed questionnaires and were assigned into a self-reported overweight (n = 61) or nonoverweight group (n = 339) using body mass index, and a self-perceived overweight (n = 84) or nonoverweight group (n = 316) based on self-perception. For self-reported and self-perceived overweight groups, more weight bias was related to higher depression (β = −0.403; p = 0.004). Self-perceived group additionally showed that weight bias was related to PWS and inappropriate eating behaviors; PWS related to inappropriate eating behaviors. For self-reported and self-perceived nonoverweight groups, weight bias was related to PWS, inappropriate eating behaviors, anxiety, and depression (β = −0.228 to −0.148; p's < 0.05); PWS was associated with inappropriate eating behaviors, anxiety, and depression. Thus, weight bias issues should not be ignored for both overweight and nonoverweight people.
A Cross-Sectional Study on the Prevalence and Risk Correlates of Mental Disorders: The GRANADΣP Study
Authors: Cervilla Jorge A. , Gutiérrez Blanca , Rodríguez-Barranco Miguel , Ibanez-Casas Inmaculada , Pérez-García Miguel , Valmisa Eulalio , Carmona José , Molina Esther , Moreno-Kustner Berta , Rivera Margarita , Lozano Vanessa , Muñoz-Negro José Eduardo , Ching Ana , Guerrero Margarita , Porras-Segovia Alejandro , Ruiz-Pérez Isabel
Published: August 2018

This is a cross-sectional study of participants from a population census living in the province of Granada (Spain). A total of 1176 persons were contacted, 367 (31%) refused and 54 (6.7%) needed substitution. A final sample of 809 participants (response rate, 69.3%) were screened for mental disorder (MD) using the MINI International Neuropsychiatric Interview, a comprehensive interview validated to generate diagnoses compatible with ICD-10/DSM-4 criteria. Current (1-month) prevalence for any MD was 11.3% (95% confidence interval [CI], 9.7%–13.4%; affective 8.2%, anxiety 9.6%, psychotic 2.1%, addiction 1.8%, personality disorder 3.6%). Lifetime MD prevalence was 24.6% (95% CI, 21.6–27.6; affective 14.9%, anxiety 15.5%, psychotic 3.4%, addiction 4.4%, personality disorder 3.6%). Female sex was associated with MD, but this appeared partially due to higher levels of neuroticism among women. MD also correlated significantly with cannabis use, family history of MD, higher social adversity, higher suicide risk, poorer physical health, poorer cognitive performance, and personality problems.
Improving Time to Antibiotics for Pediatric Oncology Patients With Fever and Suspected Neutropenia by Applying Lean Principles
Authors: Geerlinks Ashley V. , Digout Carol , Bernstein Mark , Chan Andrew , MacPhee Shannon , Pambrun Chantale , Gallant Gloria , Wyatt Lois , Fernandez Conrad V. , Price Victoria E.
Published: August 2018

Background

Fever in the setting of neutropenia is a potentially life-threatening complication of cancer treatment. A time of less than 60 minutes from presentation to antibiotic administration is therefore recommended.

Objective

To use Lean Six Sigma methodology, a quality improvement initiative, to improve time to antibiotics (TTA) for children with chemotherapy-induced febrile neutropenia presenting to the emergency department.

Methods

Lean Six Sigma is a quality improvement method that engages all impacted stakeholders and focuses on streamlining the process by removing process wastes. Stakeholders identified multiple process wastes in an in-depth study of 49 fever episodes in patients attending a tertiary care pediatric hospital, including patients waiting to be registered, waiting for laboratory technicians, delay in accessing central venous access device, waiting for absolute neutrophil count, and delayed antibiotics orders. We implemented multiple solutions: engaging patients in the process through predischarge tours of the emergency department, home application of topical anesthetic, nurse-initiated pathway, early access of central venous access device for all blood work, and planned antibiotic administration no later than 45 minutes after triage. We prospectively determined the impact of these interventions on TTA.

Results

The TTA significantly improved to a median of 59 minutes (interquartile range, 38.5–77.5 minutes) compared with the baseline of 99 minutes (interquartile range, 72.0–132.0 minutes; P < 0.0001).

Conclusions

Lean methodology effectively identifies barriers and provides solutions to remove barriers and improve administration of antibiotics in febrile oncology patients. These can be widely applied, including in smaller institutions with minimal increased utilization of resources.
High-Throughput Screening of Full-Face Clinically Relevant Arterial Variations Using Three-Dimensional Postmortem Computed Tomography
Authors: Zhu Guo-Zhang , Zhao Wei-Rui , Luo Cheng-En , Cai Bing , Kong Xiang-Xue , Zhan Wen-Feng , Sun Zhong-Sheng , Luo Sheng-Kang
Published: August 2018

Background:

Vascular complications resulting from intravascular filler injection and embolism are major safety concerns for facial filler injection. It is essential to systematically screen full-face arterial variations and help design evidence-based safe filler injection protocols.

Methods:

The carotid arteries of 22 cadaveric heads were infused with adequate lead oxide contrast. The facial and superficial temporal arteries of another 12 cadaveric heads were injected with the contrast in a sequential order. A computed tomographic scan was acquired after each contrast injection, and each three-dimensional computed tomographic scan was reconstructed using validated algorithms.

Results:

Three-dimensional computed tomography clearly demonstrated the course, relative depth, and anastomosis of all major arteries in 63 qualified hemifaces. The ophthalmic angiosome consistently deploys two distinctive layers of branch arteries to the forehead. The superficial temporal and superior palpebral arteries run along the preauricular and superior palpebral creases, respectively. The study found that 74.6 percent of the hemifaces had nasolabial trunks coursing along the nasolabial crease, and that 50.8 percent of the hemifaces had infraorbital trunks that ran through the infraorbital region. Fifty percent of the angular arteries were the direct anastomotic channels between the facial and ophthalmic angiosomes, and 29.2 percent of the angular arteries were members of the ophthalmic angiosomes.

Conclusions:

Full-face arterial variations were mapped using postmortem three-dimensional computed tomography. Facial creases were in general correlated with underlying deep arteries. Facial and angular artery variations were identified at high resolution, and reclassified into clinically relevant types to guide medical practice.
Goal-directed platelet transfusions correct platelet dysfunction and may improve survival in patients with severe traumatic brain injury
Authors: Furay Elisa , Daley Mitch , Teixeira Pedro G. , Coopwood Thomas B. , Aydelotte Jayson D. , Malesa Natalia , Tellinghuisen Christian , Ali Sadia , Brown Lawrence H. , Brown Carlos V.R.
Published: August 2018

BACKGROUND

Platelet dysfunction, defined as adenosine diphosphate inhibition greater than 60% on thromboelastogram, is an independent predictor of increased mortality in patients with severe traumatic brain injury (TBI). We changed our practice to transfuse platelets for all patients with severe TBI and platelet dysfunction. We hypothesized that platelet transfusions would correct platelet dysfunction and improve mortality in patients with severe TBI.

METHODS

This retrospective review included adult trauma patients admitted to our Level I trauma center from July 2015 to October 2016 with severe TBI (head Abbreviated Injury Scale score ≥ 3) who presented with platelet dysfunction and subsequently received a platelet transfusion. Serial thromboelastograms were obtained to characterize the impact of platelet transfusion on clot strength. Subsequently, the platelet transfusion group was compared to a group of historical controls with severe TBI patients and platelet dysfunction who did not receive platelet transfusion.

RESULTS

A total of 35 patients with severe TBI presented with platelet dysfunction. Following platelet transfusion clot strength improved as represented by decreased K time, increased α angle, maximum amplitude, and G-value, as well as correction of adenosine diphosphate inhibition. When comparing to 51 historic controls with severe TBI and platelet dysfunction, the 35 study patients who received a platelet transfusion had a lower mortality (9% vs. 35%; p = 0.005). In stepwise logistic regression, platelet transfusion was independently associated with decreased mortality (odds ratio, 0.23; 95% confidence interval, 0.06–0.92; p = 0.038).

CONCLUSION

In patients with severe TBI and platelet dysfunction, platelet transfusions correct platelet inhibition and may be associated with decreased mortality.

LEVEL OF EVIDENCE

Therapeutic, level II.
Safety of Islet Autotransplantation After Pancreatectomy for Adenocarcinoma
Authors: Renaud Florence , Chetboun Mikael , Thevenet Julien , Delalleau Nathalie , Gmyr Valery , Hubert Thomas , Bonner Caroline , Messager Mathieu , Leteurtre Emmanuelle , Mariette Christophe , Kerr-Conte Julie , Piessen Guillaume , Pattou François
Published: August 2018

Background

Total pancreatectomy with intraportal islet autotransplantation (TPIAT) rather than partial pancreatectomy could represent a major shift in the management of patients with resectable pancreatic ductal adenocarcinoma (PDAC) when risks of postoperative pancreatic fistula are well identified. This approach provides a theoretical risk of tumor cell dissemination when islet cells are transplanted into the portal vein. Our objective was to explore the safety of TPIAT in PDAC in a mouse preclinical model of subcutaneous xenotransplantation of human cells isolated from pancreatic specimen during partial pancreatectomy performed for PDAC.

Methods

Patients requiring pancreatectomy for PDAC were prospectively included. Immunocompromised mice were transplanted with pancreatic cells isolated from the nonmalignant part of the surgical specimen (experimental group). Results were compared with pancreatic tumor implants (control group). Pancreatic grafts were explanted at 6 weeks for histological analyses.

Results

Nine patients were included, and 31 mice were transplanted. In the experimental group, explants were microscopically devoid of tumor cell, and no metastasis was observed. In the control group, all explants were composed of tumor.

Conclusions

We report in a preclinical model the absence of local and distant spreading of malignant cells after pancreatic islets xenograft isolated from PDAC patients. These data supports the oncological safety of TPIAT as valuable alternative to partial pancreatectomy for PDAC patients with a high risk of postoperative pancreatic fistula.
Effectiveness of Electroconvulsive Therapy in Patients With Major Depressive Disorder and Comorbid Borderline Personality Disorder
Authors: Lee James H. , Kung Simon , Rasmussen Keith G. , Palmer Brian A.
Published: August 2018

Objective

Previous research suggests that electroconvulsive therapy (ECT)—the criterion standard for the treatment of severe depression—is not as effective when the patient has comorbid borderline personality disorder (BPD). The ECT outcomes of patients with and without BPD were compared in a retrospective chart review to test this claim.

Methods

We enrolled 137 patients with a diagnosis of major depressive disorder who completed the McLean Screening Instrument for Borderline Personality Disorder. Twenty-nine patients had positive screening scores for BPD. The difference in Patient Health Questionnaire (PHQ-9) scores before and after ECT was compared between patients with and without BPD. Follow-up PHQ-9 scores determined after treatment were collected and analyzed.

Results

Electroconvulsive therapy equally improved symptoms of depression as measured by PHQ-9 score in both patients who screened positive and patients who screened negative for BPD. No difference in the increase in PHQ-9 scores between these 2 groups was noted 1 month after treatment (P = 0.19).

Conclusions

These data showed that a positive BPD screen does not necessarily predict a poorer response to ECT, nor does it predict greater symptom recurrence after ECT. This does not suggest that ECT is necessarily an appropriate treatment for major depressive disorder in patients with a comorbid BPD, given the limitations of screening instruments.
Comparison of Site Localization Techniques for Brain Stimulation
Authors: Nikolin Stevan , D'Souza Olav , Vulovic Vedran , Alonzo Angelo , Chand Nicholas , Dong Vanessa , Martin Donel , Loo Colleen
Published: August 2018

Objectives

The dorsolateral prefrontal cortex (DLPFC) is a commonly targeted site using noninvasive brain stimulation techniques. Methods used to localize this site commonly rely on the International 10–20 electroencephalography (EEG) system, including elastic EEG caps, which stretch to accommodate varying head sizes, as well as the Beam F3 algorithm, which uses scalp measurements to calculate the location of the DLPFC. Both methods have been validated against magnetic resonance imaging–based DLPFC localization and are regularly used in research centers and clinics, but an in vivo comparison of reliability has not yet been conducted. This study examines whether Beam F3 and EEG cap methods differ in DLPFC localization, when applied by different practitioners (measurers) on a range of subjects. Further, whether measurer experience or subject head characteristics influence localization.

Methods

Measurers (n = 5) of varying levels of experience identified the location of the left DLFPC on subjects (n = 6) with varying head sizes, using both Beam F3 and EEG cap methods. An independent assessor recorded the measurers' placements along the anterior-posterior and medial-lateral planes. Values were normalized to the subjects' mean nasion-inion and tragus-tragus distances and examined using a mixed effects repeated measures analysis.

Results

The Beam F3 method resulted in significantly more anterior placements (~11.5 mm) compared with the EEG cap. Subjects with smaller head sizes had more anterior placements, compared with medium and large heads, regardless of the method used. There was no significant difference between methods along the medial-lateral plane. Measurer experience did not significantly influence DLPFC localization.

Conclusions

Beam F3 and EEG cap methods resulted in similar DLPFC placements, with a small difference along the anterior-posterior plane. Measurer experience did not affect either method, suggesting that 2 weeks of training is sufficient to achieve competency. Training and reliability of DLPFC placement therefore do not represent substantial barriers to application of either method. Special care should be taken with subjects with small heads as both methods resulted in more anterior DLPFC placements.
Basal ganglia and cortical control of thalamic rebound spikes
Authors: Nejad Mohammadreza Mohagheghi , Rotter Stefan , Schmidt Robert
Published: August 2018

Movement-related decreases in firing rate have been observed in basal ganglia output neurons. They may transmit motor signals to the thalamus, but the effect of these firing rate decreases on downstream neurons in the motor thalamus is not known. One possibility is that they lead to thalamic post-inhibitory rebound spikes. However, it has also been argued that the physiological conditions permitting rebound spiking are pathological, and primarily present in Parkinson’s disease. As in Parkinson’s disease neural activity becomes pathologically correlated, we investigated the impact of correlations in basal ganglia output on the transmission of motor signals using a Hodgkin-Huxley model of thalamocortical neurons. We found that such correlations disrupt the transmission of motor signals via rebound spikes by decreasing the signal-to-noise ratio and increasing the trial-to-trial variability. We further examined the role of sensory responses in basal ganglia output neurons and the effect of cortical excitation of motor thalamus in modulating rebound spiking. Interestingly, both could either promote or suppress the generation of rebound spikes depending on their timing relative to the motor signal. Finally, we determined parameter regimes, such as levels of excitation, under which rebound spiking is feasible in the model, and confirmed that the conditions for rebound spiking are primarily given in pathological regimes. However, we also identified specific conditions in the model that would allow rebound spiking to occur in healthy animals in a small subset of thalamic neurons. Overall, our model provides novel insights into differences between normal and pathological transmission of motor signals.
A Single Adaptive Mutation in Sodium Taurocholate Cotransporting Polypeptide Induced by Hepadnaviruses Determines Virus Species-specificity
Authors: Takeuchi Junko S , Fukano Kento , Iwamoto Masashi , Tsukuda Senko , Suzuki Ryosuke , Aizaki Hideki , Muramatsu Masamichi , Wakita Takaji , Sureau Camille , Watashi Koichi
Published: August 2018

Hepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates from fish to human. Hepadnaviruses and their hosts have a long history of acquiring adaptive mutations. However, there are no reports providing direct molecular evidence for such a coevolutionary “arms race” between hepadnaviruses and their hosts. Here, we present evidence suggesting the adaptive evolution of the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, has been influenced by virus infection. Evolutionary analysis of the NTCP-encoding genes from 20 mammals showed that most NTCP residues are highly conserved among species, exhibiting evolution under negative selection (dN/dS < 1); this observation implies that the evolution of NTCP is restricted by maintaining its original protein function. However, 0.7 % of NTCP amino acid (aa) residues exhibit rapid evolution under positive selection (dN/dS > 1). Notably, a substitution at aa 158, a positively selected residue, converting the human NTCP to a monkey-type sequence abrogated the capacity to support HBV infection; conversely, a substitution at this residue converting the monkey Ntcp to the human sequence was sufficient to confer HBV susceptibility. Together, these observations suggested that positive selection at aa 158 was induced by virus infection. Moreover, the aa 158 sequence determined attachment of the HBV envelope protein to host cell, demonstrating the mechanism whereby HBV infection would create positive selection at this residue in NTCP. In summary, we provide the first evidence in agreement with the function of hepadnavirus as a driver for inducing an adaptive mutation in host receptor.

Importance

Hepatitis B virus (HBV) and its hepadnavirus relatives infect a wide range of vertebrates, with a long infectious history (hundreds of millions of years). Such a long history generally allows adaptive mutations in hosts to escape from infection, while simultaneously allowing adaptive mutations in viruses to overcome host barriers. However, there is no published molecular evidence for such a coevolutionary “arms race” between hepadnaviruses and hosts. In the present study, we performed coevolutionary phylogenetic analysis between hepadnaviruses and the sodium taurocholate cotransporting polypeptide (NTCP), an HBV receptor, combined with virological experimental assays for investigating the biological significance of NTCP sequence variation. Our data provide the first molecular evidences supporting that HBV-related hepadnaviruses drive adaptive evolution in the NTCP sequence, including a mechanistic explanation of how NTCP mutations determine host viral susceptibility. Our novel insights enhance our understanding of how hepadnaviruses evolved with their hosts, permitting the acquisition of strong species-specificity.
Estimating parameters from multiple time series of population dynamics using Bayesian inference
Authors: Rosenbaum Benjamin , Raatz Michael , Weithoff Guntram , Fussmann Gregor F. , Gaedke Ursula
Published: August 2018

Empirical time series of interacting entities, e.g. species abundances, are highly useful to study ecological mechanisms. Mathematical models are valuable tools to further elucidate those mechanisms and underlying processes. However, obtaining an agreement between model predictions and experimental observations remains a demanding task. As models always abstract from reality one parameter often summarizes several properties. Parameter measurements are performed in additional experiments independent of the ones delivering the time series. Transferring these parameter values to different settings may result in incorrect parametrizations. On top of that, the properties of organisms and thus the respective parameter values may vary considerably. These issues limit the use of a priori model parametrizations.

In this study, we present a method suited for a direct estimation of model parameters and their variability from experimental time series data. We combine numerical simulations of a continuous-time dynamical population model with Bayesian inference, using a hierarchical framework that allows for variability of individual parameters. The method is applied to a comprehensive set of time series from a laboratory predator-prey system that features both steady states and cyclic population dynamics.

Our model predictions are able to reproduce both steady states and cyclic dynamics of the data. Additionally to the direct estimates of the parameter values, the Bayesian approach also provides their uncertainties. We found that fitting cyclic population dynamics, which contain more information on the process rates than steady states, yields more precise parameter estimates. We detected significant variability among parameters of different time series and identified the variation in the maximum growth rate of the prey as a source for the transition from steady states to cyclic dynamics.

By lending more flexibility to the model, our approach facilitates parametrizations and shows more easily which patterns in time series can be explained also by simple models. Applying Bayesian inference and dynamical population models in conjunction may help to quantify the profound variability in organismal properties in nature.
A genus definition for Bacteria and Archaea based on genome relatedness and taxonomic affiliation
Authors: Barco R.A. , Garrity G.M. , Scott J.J. , Amend J.P. , Nealson K.H. , Emerson D.
Published: August 2018

Genus assignment is fundamental in the characterization of microbes, yet there is currently no unambiguous way to demarcate genera solely using standard genomic relatedness indices. Here, we propose an approach to demarcate genera that relies on the combined use of the average nucleotide identity, genome alignment fraction, and the distinction between type species and non-type species. More than 750 genomes representing type strains of species from 10 different phyla, and 19 different taxonomic orders/families in Gram-positive/negative, bacterial and archaeal lineages were tested. Overall, all 19 analyzed taxa conserved significant genomic differences between members of a genus and type species of other genera in the same taxonomic family. Bacillus, Flavobacterium, Hydrogenovibrio, Lactococcus, Methanosarcina, Thiomicrorhabdus, Thiomicrospira, Shewanella, and Vibrio are discussed in detail. Less than 1% of the type strains analyzed need reclassification, highlighting that the adoption of the 16S rRNA gene as a taxonomic marker has provided consistency to the classification of microorganisms in recent decades. One exception to this is the genus Bacillus with 61% of type strains needing reclassification, including the human pathogens B. cereus and B. anthracis. The results provide a first line of evidence that the combination of genomic indices provides appropriate resolution to effectively demarcate genera within the current taxonomic framework that is based on the 16S rRNA gene. We also identify the emergence of natural breakpoints at the genome level that can further help in the circumscription of genera. Altogether, these results show that a distinct difference between distant relatives and close relatives at the genome level (i.e., genomic coherence) is an emergent property of genera in Bacteria and Archaea.
Real-time experimental control using network-based parallel processing
Authors: Kim Byounghoon , Kenchappa Shobha , Sunkara Adhira , Chang Ting-Yu , Thompson Lowell , Doudlah Raymond , Rosenberg Ari
Published: August 2018

Modern neuroscience research often requires the coordination of multiple processes such as stimulus generation, real-time experimental control, as well as behavioral and neural measurements. The technical demands required to simultaneously manage these processes with high temporal fidelity limits the number of labs capable of performing such work. Here we present an open-source network-based parallel processing framework that eliminates these barriers. The Real-Time Experimental Control with Graphical User Interface (REC-GUI) framework offers multiple advantages: (i) a modular design agnostic to coding language(s) and operating system(s) that maximizes experimental flexibility and minimizes researcher effort, (ii) simple interfacing to connect measurement and recording devices, (iii) high temporal fidelity by dividing task demands across CPUs, and (iv) real-time control using a fully customizable and intuitive GUI. Testing results demonstrate that the REC-GUI framework facilitates technically demanding, behavior-contingent neuroscience research. Sample code and hardware configurations are downloadable, and future developments will be regularly released.
Carbapenemases on the move: it’s good to be on ICE
Authors: Botelho João , Roberts Adam P. , León-Sampedro Ricardo , Grosso Filipa , Peixe Luísa
Published: August 2018

The evolution and spread of antibiotic resistance is often mediated by mobile geneticelements. Integrative and conjugative elements (ICEs) are the most abundant conjugativeelements among prokaryotes. However, the contribution of ICEs to horizontal gene transferof antibiotic resistance has been largely unexplored. Here we report that ICEs belonging tomating-pair formation (MPF) classes G and T are highly prevalent among the opportunisticpathogen Pseudomonas aeruginosa, contributing to the spread of carbapenemase-encodinggenes (CEGs). Most CEGs of the MPFG class were encoded within class I integrons, which co-harbour genes conferring resistance to other antibiotics. The majority of the integrons werelocated within Tn3-like and composite transposons. A conserved attachment site could bepredicted for the MPFGclass ICEs. MPFTclass ICEs carried the CEGs within compositetransposons which were not associated with integrons. The data presented here provides aglobal snapshot of the different CEG-harbouring ICEs and sheds light on the underappreciatedcontribution of these elements for the evolution and dissemination of antibiotic resistanceon P. aeruginosa.
Intact mast cell content during mild head injury is required for the development of latent pain sensitization - implications for mechanisms underlying post-traumatic headache
Authors: Bree Dara , Levy Dan
Published: August 2018

Posttraumatic headache (PTH) is one of the most common, debilitating and difficult symptoms to manage after a traumatic head injury. While the mechanisms underlying PTH remain elusive, recent studies in rodent models suggest the potential involvement of calcitonin gene-related peptide (CGRP), a mediator of neurogenic inflammation, and the ensuing activation of meningeal mast cells (MCs), pro-algesic resident immune cells that can lead to the activation of the headache pain pathway. Here, we investigated the relative contribution of MCs to the development of PTH-like pain behaviors in a model of mild closed head injury (mCHI) in male rats. We initially tested the relative contribution of peripheral CGRP signaling to the activation of meningeal MCs following mCHI using an anti-CGRP monoclonal antibody. We then employed a prophylactic MC granule depletion approach to address the hypotheses that intact meningeal MC granule content is necessary for the development of PTH-related pain-like behaviors. The data suggest that following mCHI, ongoing activation of meningeal MCs is not mediated by peripheral CGRP signaling, and does not contribute to development of the mCHI-evoked cephalic mechanical pain hypersensitivity. Our data, however, also reveals that the development of latent sensitization, manifested as persistent hypersensitivity upon the recovery from mCHI-evoked acute cranial hyperalgesia to the headache trigger glyceryl trinitrate requires intact MC content during and immediately after mCHI. Collectively, our data implicate the acute activation of meningeal MCs as mediator of chronic pain hypersensitivity following a concussion or mCHI. Targeting MCs may be explored for early prophylactic treatment of PTH.