bluuebunny/crossref_metadata_2025 huggingface dataset:
Method of App Selection for Healthcare Providers Based on Consumer Needs
Authors: Lee Jisan , Kim Jeongeun
Published: October 2017

Mobile device applications can be used to manage health. However, healthcare providers hesitate to use them because selection methods that consider the needs of health consumers and identify the most appropriate application are rare. This study aimed to create an effective method of identifying applications that address user needs. Women experiencing dysmenorrhea and premenstrual syndrome were the targeted users. First, we searched for related applications from two major sources of mobile applications. Brainstorming, mind mapping, and persona and scenario techniques were used to create a checklist of relevant criteria, which was used to rate the applications. Of the 2784 applications found, 369 were analyzed quantitatively. Of those, five of the top candidates were evaluated by three groups: application experts, clinical experts, and potential users. All three groups ranked one application the highest; however, the remaining rankings differed. The results of this study suggest that the method created is useful because it considers not only the needs of various users but also the knowledge of application and clinical experts. This study proposes a method for finding and using the best among existing applications and highlights the need for nurses who can understand and combine opinions of users and application and clinical experts.
DosOpt: A Tool for Personalized Bayesian Dose Adjustment of Vancomycin in Neonates
Authors: Tasa Tõnis , Metsvaht Tuuli , Kalamees Riste , Vilo Jaak , Lutsar Irja
Published: October 2017

Background:

Our main aim has been to design a framework to improve vancomycin dosing in neonates. This required the development and verification of a computerized dose adjustment application, DosOpt, to guide the selection.

Methods:

Model fitting in DosOpt uses Bayesian methods for deriving individual pharmacokinetic (PK) estimates from population priors and patient therapeutic drug monitoring measurements. These are used to simulate concentration–time curves and target-constrained dose optimization. DosOpt was verified by assessing bias and precision through several error metrics and normalized prediction distribution errors on samples simulated from the Anderson et al PK model. The performance of DosOpt was also evaluated using retrospective clinical data. Achieved probabilities of target concentration attainment were benchmarked against corresponding attainments in our clinical retrospective data set.

Results:

Simulations showed no systemic forecast biases. Normalized prediction distribution error values of the base model were distributed by standardized Gaussian (P= 0.1), showing good model suitability. A retrospective test data set included 149 treatment episodes with 1–10 vancomycin concentration measurements per patient (median 2). Individual concentrations in PK estimation improved probability of target attainment and decreased the variance of the estimation. Including 3 individual concentrations in the kinetics estimation increased the probability of Ctroughattainment within 10–15 mg/L from 16% obtained with no individual data (95% confidence interval, 11%–24%) to 43% (21%–47%).

Conclusions:

DosOpt uses individual concentration data to estimate kinetics and find optimal doses that increase the probability of achieving desired trough concentrations. Its performance started to exceed target levels attained in retrospective clinical data sets with the inclusion of a single individual input concentration. This tool is freely available at http://www.biit.cs.ut.ee/DosOpt.
Companion and Complementary Diagnostics–Focus on PD-L1 Expression Assays for PD-1/PD-L1 Checkpoint Inhibitors in Non–Small Cell Lung Cancer
Authors: Hersom Maria , Jørgensen Jan T.
Published: October 2017

Over the last couple of decades, molecular diagnostics have played an increasing role in drug development. Especially within oncology, more and more drugs are being developed together with a predictive biomarker assay using the drug-diagnostic codevelopment model. Not only do these assays support the development process but also the use of the drugs after regulatory approval as an important treatment decision tool. When these predictive biomarker assays are linked to a specific drug, they are called companion diagnostics. Furthermore, these assays are also considered an important element in the realization of precision medicine. Today, 21 different drugs have obtained US FDA approval together with a companion diagnostic assay, and the requirement for testing is part of their regulatory labeling. More than half of these drugs are for treatment of non–small cell lung cancer (NSCLC). With the approval of the different programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors, for the treatment of advanced stage NSCLC, a new class of predictive biomarker assays—complementary diagnostics—has emerged. Until now, 3 immune checkpoint inhibitors have obtained regulatory approval for treatment of NSCLC, and they all have a biomarker assay linked to their use. However, only for pembrolizumab, the PD-L1 immunohistochemical (IHC) 22C3 pharmDx assay has status as a companion diagnostic. For nivolumab and atezolizumab, the assays PD-L1 IHC 22C3 pharmDx and Ventana PD-L1 (SP142) have status as complementary diagnostics, which means that there are no requirements for testing included in the labeling for these drugs. Here, the authors discuss the clinical performance of the different IHC PD-L1 expression assays including the selection of the clinical cutoff values.
Efficacy of Telerehabilitation for Adults With Traumatic Brain Injury: A Systematic Review
Authors: Ownsworth Tamara , Arnautovska Urska , Beadle Elizabeth , Shum David H. K. , Moyle Wendy
Published: October 2017

Objective:

To identify and appraise studies evaluating the efficacy of telerehabilitation for adults with traumatic brain injury (TBI).

Methods:

A systematic search of Cochrane Library, MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and PsycINFO databases was conducted from January 1980 to April 23, 2017, for studies evaluating the efficacy of telerehabilitation for adults with TBI. Two reviewers independently assessed articles for eligibility and rated methodological quality using 16 criteria related to internal validity, descriptive, and statistical characteristics.

Results:

The review yielded 13 eligible studies, including 10 randomized controlled trials and 3 pre-/postgroup studies (n ≥ 10). These evaluated the feasibility and/or efficacy of telephone-based (10 studies) and Internet-based (3 studies) interventions. Overall, the evidence of efficacy was somewhat mixed. The most common study design evaluated the efficacy of telephone-based interventions relative to usual care, for which 4 of 5 randomized controlled trials reported positive effects at postintervention (d = 0.28-0.51). For these studies, improvements in global functioning, posttraumatic symptoms and sleep quality, and depressive symptoms were reported. The feasibility of Internet-based interventions was generally supported; however, the efficacy could not be determined because of insufficient studies.

Conclusions:

Structured telephone interventions were found to be effective for improving particular outcomes following TBI. Controlled studies of Internet-based therapy and comparisons of the clinical and cost-effectiveness of in-person and telerehabilitation formats are recommended for future research.
Window to Hope: A Randomized Controlled Trial of a Psychological Intervention for the Treatment of Hopelessness Among Veterans With Moderate to Severe Traumatic Brain Injury
Authors: Brenner Lisa A. , Forster Jeri E. , Hoffberg Adam S. , Matarazzo Bridget B. , Hostetter Trisha A. , Signoracci Gina , Simpson Grahame K.
Published: October 2017

Objective:

To evaluate the efficacy of a psychological intervention to reduce moderate to severe hopelessness among Veterans with moderate to severe traumatic brain injury (TBI).

Design:

Two-arm parallel group, controlled, randomized crossover trial, with 3-month follow-up for those initially allocated to treatment. Participants were randomly allocated in blocks of 4 on a 1:1 ratio to treatment (n = 15) or waitlist (n = 20) groups.

Setting:

A Veterans Affairs Medical Center.

Participants:

Veterans between the ages of 26 and 65 years, with a history of moderate to severe TBI, and moderate to severe hopelessness.

Interventions:

A 20-hour manualized small group cognitive-behavioral intervention.

Main Outcome Measures:

Beck Hopelessness Scale (primary), Beck Depression Inventory, and Beck Scale for Suicide Ideation.

Results:

A significant difference between groups was found for postintervention scores on the Beck Hopelessness Scale (P = .03). Significant decreases were maintained at follow-up. For those initially allocated to the waitlist group who completed the intervention, treatment gains were noted in decreased hopelessness (P = .01) and depression (P = .003).

Conclusions:

Findings from this trial provide additional support for the efficacy of this method of psychological treatment of hopelessness among individuals with moderate to severe TBI.
Postconcussion Symptom Reporting After Mild Traumatic Brain Injury in Female Service Members: Impact of Gender, Posttraumatic Stress Disorder, Severity of Injury, and Associated Bodily Injuries
Authors: Lippa Sara M. , Brickell Tracey A. , Bailie Jason M. , French Louis M. , Kennedy Jan E. , Lange Rael T.
Published: October 2017

Objective:

Examine effects of diagnostically relevant posttraumatic stress disorder (PTSD) symptoms, mild traumatic brain injury (TBI) severity, and associated bodily injury severity on postconcussion symptom reporting in female service members (SM) compared with a matched sample of male SM.

Setting:

Six US military medical treatment facilities.

Participants:

A total of 158 SM (79 females, 79 males) evaluated within 30 months after mild TBI. Men and women were matched by age, days postinjury, PTSD symptom status, mild TBI severity, and bodily injury severity. All passed a measure of symptom validity.

Design:

Compare reported postconcussion symptoms for men and women stratified by PTSD diagnostic symptoms (present/absent), mild TBI severity (alteration of consciousness/loss of consciousness), and bodily injury severity (mild/moderate-severe).

Main Measures:

Neurobehavioral Symptom Inventory, PTSD Checklist, Abbreviated Injury Scale.

Results:

Overall postconcussion symptom reporting increased with PTSD but did not significantly differ based on severity of mild TBI or associated bodily injury. Females reported more somatosensory and/or vestibular symptoms than males under some circumstances. Females in the PTSD-Present group, Alteration of Consciousness Only group, and Moderate-Severe Bodily Injury group reported more somatosensory symptoms than males in those groups. Females in the Alteration of Consciousness Only group and Minor Bodily Injury group reported more vestibular symptoms than males in those groups.

Conclusion:

Diagnostically relevant PTSD symptoms, mild TBI severity, and bodily injury severity differentially impact somatosensory and vestibular postconcussion symptom reporting for male and female SM after mild TBI. Controlling for PTSD and symptom validity resulted in fewer gender-based differences in postconcussive symptoms than previously demonstrated in the literature.
Intracranial Pathology (CT+) in Emergency Department Patients With High GCS and High Standard Assessment of Concussion (SAC) Scores
Authors: Curley Kenneth C. , O'Neil Brian J. , Naunheim Rosanne , Wright David W.
Published: October 2017

Objective:

To demonstrate that a subpopulation of patients with mild/moderate traumatic brain injury (TBI) had intracranial pathology despite having a Glasgow Coma Scale (GCS) score of 15 and a Standardized Assessment of Concussion (SAC) score of 25 or higher.

Setting:

A network of 11 US emergency departments (ED) enrolling patients in a multisite study of TBI.

Participants:

Men and women between the ages of 18 and 85 years admitted to a participating ED having sustained a closed head injury within the prior 72 hours and a GCS score of 13 to 15 at the time of enrollment.

Design:

Prospective observational study.

Main Measures:

GCS, SAC, computed tomography (CT) positive or negative for intracranial pathology, Marshall scoring of CT scans.

Results:

Of 191 patients with intracranial pathology (CT+) and having a SAC score recorded, 24% (46/191) had a SAC score in the normal range (≥25) as well as a GCS score of 15. All causes of CT+ brain injury were present in both SAC groups.

Conclusion:

A normal GCS score and a SAC score do not exclude the possibility of significant intracranial injury.
Postrehabilitation Mental Health Treatment Utilization in Veterans With Traumatic Brain Injury: A VA TBI Model Systems Study
Authors: Finn Jacob A. , Lamberty Greg J. , Tang Xinyu , Saylors Marie E. , Stevens Lillian Flores , Kretzmer Tracy
Published: October 2017

Objective:

To identify preinjury variables related to mental health treatment utilization at 2 years post-traumatic brain injury (TBI).

Setting:

Veterans Affairs (VA) TBI Model Systems includes 5 VA Polytrauma Rehabilitation Centers.

Participants:

Veterans and service members enrolled in TBI Model Systems who completed the year 2 follow-up assessment and provided mental health information. Sample was largely male (97%) and White (72%), with median age of 30 years.

Design:

Participants with elevated mental health symptoms were identified by measures of depression, anxiety, and posttraumatic distress; suicide attempt in the past year; or problematic substance use in the past year. Forty-seven percent of participants had elevated mental health symptoms at 2 years postinjury. Among those with elevated symptoms, comparisons were made between those who sought mental health treatment in past year and those who did not.

Main Measures:

Demographic, historic, environmental, psychological/mental health, and injury/rehabilitation variables.

Results:

Within the sample, 23% denied utilizing mental health services. Nonutilizers were more likely to deny a preinjury mental health treatment history, to report problematic substance use at year 2, and to report lower levels of internalizing symptoms than the treatment utilizers.

Conclusion:

Veterans and service members with elevated mental health symptoms may require tailored tactics to promote treatment utilization post-TBI.
Is burning mouth syndrome a neuropathic pain condition?
Authors: Jääskeläinen Satu K.
Published: October 2017

Primary burning mouth syndrome (BMS) is defined as an “intraoral burning or dysaesthetic sensation, recurring daily… more than 3 months, without clinically evident causative lesions” (IHS 2013). In addition to pain, taste alterations are frequent (dysgeusia, xerostomia). Although lacking clinical signs of neuropathy, more accurate diagnostic methods have shown neuropathic involvement at various levels of the neuraxis in BMS: peripheral small fiber damage (thermal quantitative sensory testing, electrogustatometry, epithelial nerve fiber density), trigeminal system lesions in the periphery or the brainstem (brainstem reflex recordings, trigeminal neurography, evoked potentials), or signs of decreased inhibition within the central nervous system (deficient brainstem reflex habituation, positive signs in quantitative sensory testing, neurotransmitter–positron emission tomography findings indicative of deficient striatal dopamine function). Abnormalities in electrogustatometry indicate the involvement of the small Aδ taste afferents, in addition to somatosensory small fibers. According to these findings, the clinical entity of BMS can be divided into 2 main subtypes compatible with either peripheral or central neuropathic pain, which may overlap in individual patients. The central type does not respond to local treatments and associates often with psychiatric comorbidity (depression or anxiety), whereas the peripheral type responds to peripheral lidocaine blocks and topical clonazepam. Burning mouth syndrome is most prevalent in postmenopausal women, having led to a hypothesis that BMS is triggered as a consequence of nervous system damage caused by neurotoxic factors affecting especially vulnerable small fibers and basal ganglia in a setting of decrease in neuroprotective gonadal hormones and increase in stress hormone levels, typical for menopause.
The Accuracy and Validity of Modus Trex Activity Monitor in Determining Functional Level in Veterans with Transtibial Amputations
Authors: Godfrey Bradeigh , Berdan Jeffery , Kirk Melissa Nuntapreda , Chou Teri Rosenbaum
Published: October 2017

Introduction

The objective of this study was to investigate the accuracy and reliability of Modus Trex–derived K-level to differentiate between Medicare Functional Classification levels (K-levels) in individuals with lower-limb amputation.

Methods

This study was a prospective study monitoring walking behavior. Subjects were recruited from an outpatient clinic for persons with amputation at a Veterans Affairs medical center. Subjects were blinded to results of the Global Positioning System and activity data. Physicians were blinded to Modus Trex–derived K-level, 6-minute walk test (6MWT), and Amputee Mobility Predictor with Prosthesis (AMPPRO) results.

The study enrolled 29 subjects with transtibial amputation. Twenty-seven subjects were included in the data analysis. Two subjects were excluded due to incomplete or unreliable data. Patients were eligible if they were at least 1 year postamputation surgery and could walk with a well-fitting and functioning prosthesis. Patients were excluded if they had other musculoskeletal injuries that impacted their ambulation ability.

A clinical K-level, 6MWT, and AMPPRO were obtained. An activity monitor and Global Positioning System device were attached to the prosthesis to record activity for 2 weeks. Study physicians used number of steps in community, steps per day, peak cadence, and environmental barriers traversed in the subjects' first 6 to 10 days, as well as clinical judgement, to determine a Modified Clinical K-level (MCK-level) for each subject. The MCK-level was the criterion to which all other measures were compared.

Results

The Modus Trex–derived K-level correlated most strongly with the MCK-levels (r = 0.96, P < 0.001) with 85% accuracy/sensitivity. Repeat (week 1 to week 2) was excellent (interclass correlation coefficient = 0.92). Other outcome measures also correlated to MCK-levels: AMPPRO (r = 0.93), 6MWT (r = 0.89), peak cadence (r = 0.89), and daily steps (r = 0.76).

Conclusions

The Modus Trex–derived K-level was reliable and accurate at estimating MCK-levels and can be useful as a component in K-level evaluation.
Exploring Gaps in Concussion Knowledge and Knowledge Translation Among Coaches of Youth Female Hockey
Authors: Guo David , Verweel Lee , Reed Nick
Published: October 2017

Objective:

To better understand the level of concussion knowledge of youth female hockey coaches and to identify preferred methods of knowledge translation for this population.

Design:

Cross-sectional survey.

Setting:

Participants independently completed written surveys before in-person concussion information sessions or online surveys through link provided in emails.

Participants:

Convenience sampling yielded 130 coaches of youth female hockey from Canada.

Main Outcome Measures:

Knowledge level on concussion, resources from which coaches obtained information on concussion, opinions on the current level of concussion knowledge, and knowledge translation.

Results:

Coaches demonstrated adequate knowledge on concussion, achieving 84% correct on true–false questions and 92% correct on symptom identification accuracy. However, coaches showed limited awareness of concussion specific to mechanisms for injury (identification) and postconcussion symptoms. Internet resources were rated as the most used resources for concussion yet were not rated very helpful. Nonetheless, coaches indicated online courses and web sites as the most preferred method for concussion knowledge translation.

Conclusions:

Youth female hockey coaches have overall adequate knowledge of concussion; however, gaps in knowledge do exist. Future efforts to raise the concussion knowledge among coaches of female youth hockey should include information specific to the mechanism of injury, along with sign and symptom identification, with particular attention paid to emotional symptoms. Given the reported preferences and the widespread availability of the Internet, further exploration and research validation of online courses and web sites tailored to the youth female hockey community is encouraged.
Using Clinical Notes and Natural Language Processing for Automated HIV Risk Assessment
Authors: Feller Daniel J. , Zucker Jason , Yin Michael T. , Gordon Peter , Elhadad Noémie
Published: October 2017

Objective:

Universal HIV screening programs are costly, labor intensive, and often fail to identify high-risk individuals. Automated risk assessment methods that leverage longitudinal electronic health records (EHRs) could catalyze targeted screening programs. Although social and behavioral determinants of health are typically captured in narrative documentation, previous analyses have considered only structured EHR fields. We examined whether natural language processing (NLP) would improve predictive models of HIV diagnosis.

Methods:

One hundred eighty-one HIV+ individuals received care at New York Presbyterian Hospital before a confirmatory HIV diagnosis and 543 HIV negative controls were selected using propensity score matching and included in the study cohort. EHR data including demographics, laboratory tests, diagnosis codes, and unstructured notes before HIV diagnosis were extracted for modeling. Three predictive algorithms were developed using machine-learning algorithms: (1) a baseline model with only structured EHR data, (2) baseline plus NLP topics, and (3) baseline plus NLP clinical keywords.

Results:

Predictive models demonstrated a range of performance with F measures of 0.59 for the baseline model, 0.63 for the baseline + NLP topic model, and 0.74 for the baseline + NLP keyword model. The baseline + NLP keyword model yielded the highest precision by including keywords including “msm,” “unprotected,” “hiv,” and “methamphetamine,” and structured EHR data indicative of additional HIV risk factors.

Conclusions:

NLP improved the predictive performance of automated HIV risk assessment by extracting terms in clinical text indicative of high-risk behavior. Future studies should explore more advanced techniques for extracting social and behavioral determinants from clinical text.
Ring-Like Enhancement of Hepatocellular Carcinoma in Gadoxetic Acid–Enhanced Multiphasic Hepatic Arterial Phase Imaging With Differential Subsampling With Cartesian Ordering
Authors: Ichikawa Shintaro , Motosugi Utaroh , Oishi Naoki , Shimizu Tatsuya , Wakayama Tetsuya , Enomoto Nobuyuki , Matsuda Masanori , Onishi Hiroshi
Published: October 2017

Objective

The aim of this study was to evaluate the efficacy of multiphasic hepatic arterial phase (HAP) imaging using DISCO (differential subsampling with Cartesian ordering) in increasing the confidence of diagnosis of hepatocellular carcinoma (HCC).

Materials and Methods

This retrospective study was approved by the institutional review board, and the requirement for informed patient consent was waived. Consecutive patients (from 2 study periods) with malignant liver nodules were examined by gadoxetic acid–enhanced magnetic resonance imaging using either multiphasic (6 phases; n = 135) or single (n = 230) HAP imaging, which revealed 519 liver nodules other than benign ones (HCC, 497; cholangiocarcinoma, 11; metastases, 10; and malignant lymphoma, 1). All nodules were scored in accordance with the Liver Imaging Reporting and Data System (LI-RADS v2014), with or without consideration of ring-like enhancement in multiphasic HAP images as a major feature.

Results

In the multiphasic HAP group, 178 of 191 HCCs were scored as LR-3 to LR-5 (3 [1.69%], 85 [47.8%], and 90 [50.6%], respectively). Upon considering ring-like enhancement in multiphasic HAP images as a major feature, 5 more HCCs were scored as LR-5 (95 [53.4%]), which was a significantly more confident diagnosis than that with single HAP images (295 of 306 HCCs scored as LR-3 to LR-5: 13 [4.41%], 147 [49.8%], and 135 [45.8%], respectively; P = 0.0296). There was no significant difference in false-positive or false-negative diagnoses between the multiphasic and single HAP groups (P = 0.8400 and 0.1043, respectively).

Conclusions

Multiphasic HAP imaging can improve the confidence of diagnosis of HCCs in gadoxetic acid–enhanced magnetic resonance imaging.
Pediatric Facial Fractures: An Assessment of Airway Management
Authors: Viviano Stephen L. , Hoppe Ian C. , Halsey Jordan N. , Chen Jeffrey S. , Russo Gerardo J. , Lee Edward S. , Granick Mark S.
Published: October 2017

Pediatric facial fractures present unique and challenging management considerations, especially with regards to airway management. Anatomical differences in children increase both airway resistance and the difficulty of intubation. A surgical airway may be required if intubation is unable to be performed. The purpose of this study was to examine a single center's experience with pediatric facial fractures to determine the frequency of advanced airway use, as well as the risk factors that may predispose a patient to requiring an advanced airway. A retrospective review of all facial fractures at a level 1 trauma center was performed from 2000 to 2012. Patients age 18 years and younger were included. Patient demographics were collected, as well as location of fractures, concomitant injuries, services consulted, and surgical management strategies. Information was collected regarding the need for an advanced airway, including intubation and the need for a surgical airway. A total of 285 patients met inclusion criteria. Of these, 57 patients (20%) required emergency intubation and 5 (1.8%) required a surgical airway. Intubation was significantly related to fractures of the midface, frontal sinuses, spine, skull, and pelvis, as well as depressed Glasgow coma scores and traumatic brain injury. The need for a surgical airway is extremely uncommon (1.8%), and tracheostomy was only needed in the setting of penetrating head trauma. Both emergent intubation and tracheostomy are associated with complications, but these complications must be weighed against the potentially life-saving measure of securing an airway.
Comparison of Postoperative Outcomes Between Monitored Anesthesia Care and General Anesthesia in Closed Reduction of Nasal Fracture
Authors: Kyung Hyunwoo , Choi Jae-Ik , Song Seung-Han , Oh Sang-Ha , Kang Nakheon
Published: October 2017

Fracture of nasal bone is among the most common facial bone fractures. Reduction of nasal bone fracture is able to be performed under local or general anesthesia. The aim of this study is to compare monitored anesthetic care (MAC) and general anesthesia (GA) based on intraoperative vital signs, and the adverse effects after closed reduction of nasal bone fractures.

The authors performed a retrospective study of 45 patients who underwent a closed reduction of nasal bone fracture between January 1, 2016 and December 31, 2016. Patients are divided into an MAC group (n = 17) or GA group (n = 28). A sore throat, postoperative pain scores, nausea, vomiting, hospital stay, operation time, and the result of surgery are compared between the groups. All the patients have interviewed their satisfaction of aesthetic and functional outcome.

The operation time and hospital stay were lower in the MAC group. There is no difference in a sore throat, postoperative pain score, and the result of surgery significantly. In the MAC and GA groups, there was no statistically significant difference in the postoperative cosmetic and functional satisfaction scores.

Closed reduction of nasal bone fracture using MAC is as safe and efficient as GA. However, MAC anesthesia may not be feasible if airway discomfort due to bleeding is expected, or fracture is severe and multiple manipulations are required. Therefore, MAC is considered to be a good alternative when patients undergoing short-term or small operations do not prefer general anesthesia.
The Effect of Unilateral Concha Bullosa on Olfactory Bulb Volume: an Assessment by Magnetic Resonance Imaging
Authors: Özkiriş Mahmut , Gencer Zeliha Kapusuz , Saydam Levent
Published: October 2017

Background:

In this study, the authors compared the right and left olfactory bulb volumes by magnetic resonance image findings of patients with unilateral concha bullosa (CB).

Methods:

The cranial magnetic resonance imaging studies of 24 patients having unilateral CB were reviewed. There were 10 males and 14 females ranging in age from 29 to 51 years (mean age, 29 ± 15.2 years). The volumes of both olfactory bulbs (contralateral and ipsilateral to the concha bullosa side) were calculated by using the computer program.

Results:

The average values for olfactory bulb volumes were 46.57 ± 8.03 mm3 in the CB side of the nasal cavity and 54.80 ± 10.031 mm3 in the normal side of the nasal cavity. We found a statistically significant difference in olfactory bulb volume between the contralateral and ipsilateral to the concha bullosa side of the patients (t = −3.08 and P < 0.01 for CB side, t = −3.47 and P < 0.01 for left normal side).

Conclusion:

Our results may point out a possible relationship between CB and ipsilateral decreased olfactory bulb volume, yet the exact mechanism still remains unclear. Decreased nasal air flow on the CB side may be attributed to the pathophysiologic mechanism of this finding. Also, the significant reduction in olfactory bulb volumes ipsilateral to CB compared with the contralateral olfactory bulb volumes seems to support our hypothesis.
Effect of Irrigation Time of Antiseptic Solutions on Bone Cell Viability and Growth Factor Release
Authors: Sawada Kosaku , Nakahara Ken , Haga-Tsujimura Maiko , Fujioka-Kobayashi Masako , Iizuka Tateyuki , Miron Richard J.
Published: October 2017

Antiseptic solutions are commonly utilized to treat local infection in the oral and maxillofacial region. However, surrounding vital bone is also exposed to antiseptic agents during irrigation and may have a potential negative impact on bone survival. The aim of the present study was therefore to investigate the effect of rinsing time with various antiseptic solutions on bone cell viability, as well as their subsequent release of growth factors important for bone regeneration. The bone samples collected from porcine mandible were rinsed in the following commonly utilized antiseptic solutions; povidone-iodine (0.5%), chlorhexidine digluconate (CHX, 0.2%), hydrogen peroxide (1%), and sodium hypochlorite (0.25%) for 1, 5, 10, 20, 30, or 60 minutes and assessed for cell viability and release of growth factors including vascular endothelial growth factor, transforming growth factor beta 1, bone morphogenetic protein 2, receptor activator of nuclear factor kappa-B ligand, and interleukin-1 beta by enzyme-linked immunosorbent assay. It was found in all the tested groups that the long exposure of any of the tested antiseptic solutions drastically promoted higher cell death. Sodium hypochlorite demonstrated the significantly highest cell death and at all time points. Interestingly, bone cell viability was highest in the CHX group post short-term rinsing of 1, 5, or 10 minutes when compared with the other 4 tested groups. A similar trend was also observed in subsequent growth factor release. The present study demonstrated that of the 4 tested antiseptic solutions, short-term CHX rinsing (ideally within 1 minute) favored bone cell viability and growth factor release. Clinical protocols should be adapted accordingly.
A Review of Randomized Controlled Trials in Cleft and Craniofacial Surgery
Authors: Bekisz Jonathan M. , Fryml Elise , Flores Roberto L.
Published: October 2017

This study presents a systematic review of randomized controlled trials (RCTs) in cleft and craniofacial surgery. All studies reporting on RCTs in cleft and craniofacial surgery were identified on PubMed using the search terms “cleft,” “velopharyngeal insufficiency,” “velopharyngeal dysfunction,” “nasoalveolar molding,” “gingivoperiosteoplasty,” “Pierre Robin sequence,” “craniofacial,” “craniosynostosis,” “craniofacial microsomia,” “hemifacial microsomia,” “hypertelorism,” “Le Fort,” “monobloc,” “distraction osteogenesis,” “Treacher Collins,” and “Goldenhar.” Studies were excluded if they were not randomized, did not focus primarily on topics related to cleft or craniofacial surgery, included repeat publications of data, or were unavailable in English. Studies were evaluated on demographic and bibliometric data, study size, specific area of focus, and findings reported. Four hundred forty-seven unique studies were identified. One hundred eighty-three papers met inclusion criteria (115 cleft lip and palate, 65 craniofacial, and 3 spanning both disciplines). Sixty-six (36%) were dedicated to topics related to surgical techniques. There were no studies comparing current cleft lip or soft palate repair techniques and no studies on cleft rhinoplasty. The most frequently reported surgical topic was cleft palate. There were several studies on orthognathic techniques which compared distraction osteogenesis to traditional advancement. Most craniofacial operations, such as cranial vault remodeling and frontofacial advancement/distraction, were not represented. Several standard operations in cleft and craniofacial surgery are not supported by Level I evidence from randomized controlled trials. Our community should consider methods by which more RCTs can be performed, or redefine the acceptable standards of evidence to guide our clinical decisions.
De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates
Authors: Skuk Daniel , Tremblay Jacques P.
Published: October 2017

Background

Transplantation of myogenic cells has potential applications in the treatment of muscle pathologies. Excluding purely autologous cell transplantation, graft viability depends on an adequate control of acute rejection (AR). To contribute in understanding AR in this context, we analyzed whether de novo circulating antibodies against donor’s cells are detected during induced AR of graft-derived myofibers in nonhuman primates.

Methods

We allotransplanted satellite cell-derived myoblasts in macaques immunosuppressed with tacrolimus. To induce AR of graft-derived myofibers, we administered tacrolimus for 4 weeks to allow complete myofiber formation, and then we stopped tacrolimus administration. Cell-grafted sites were biopsied at tacrolimus withdrawal and then every 2 weeks and analyzed by histology until AR completion. Blood samples were taken before immunosuppression, at tacrolimus withdrawal and then every 2 weeks to detect antibodies against the donor’s cells by flow cytometry.

Results

There was an increase of antibodies against the donor’s cells related to AR in all monkeys. This increase was variable in intensity, and preceded, coincided or followed the histological evidence of AR (focal accumulations of lymphocytes) and/or the loss of myofibers of donor origin, and remained until the end of the follow-up (up to 8 weeks after tacrolimus withdrawal).

Conclusions

Flow cytometry detection of de novo circulating antibodies against the donor’s cells was consistently associated with AR. A clear increase in this antibody detection indicated current or recent AR. Smaller increases in comparison to the preimmunosuppression values were not associated with AR.
Rituximab and Monitoring Strategies for Late Antibody-Mediated Rejection After Kidney Transplantation
Authors: Parajuli Sandesh , Mandelbrot Didier A. , Muth Brenda , Mohamed Maha , Garg Neetika , Aziz Fahad , Redfield Robert R. , Zhong Weixiong , Astor Brad C. , Djamali Arjang
Published: October 2017

Background

There is limited information on treatment strategies and monitoring strategies for late antibody-mediated rejection (ABMR) after kidney transplantation.

Methods

In this observational and nonrandomized study, we compared 78 patients diagnosed with late ABMR (>3 months after transplant) who were treated with standard of care steroids/IVIG (n = 38) ± rituximab (n = 40) at our center between March 1, 2013 and December 31, 2016. All patients had follow-up biopsy and donor-specific antibodies (DSA) monitoring within 3 to 12 weeks.

Results

Patients had biopsy 7.3 ± 7 years after transplant and were followed for 15.9 ± 9.6 months after ABMR was diagnosed. Both treatment strategies were associated with a significant decline in DSA, microvascular inflammation (peritubular capillaritis + glomerulitis), and C4d Banff scores. In univariate regression analyses, rituximab, estimated glomerular filtration rate (eGFR), Banff i, t, v, chronicity (interstitial fibrosis + tubular atrophy + fibrous intimal thickening + allograft glomerulopathy) scores on the first biopsy, and eGFR and Banff v score on follow-up biopsy were associated with graft loss. Multivariate analyses retained only rituximab (hazard ratio, 0.23; 95% confidence interval, 0.06-0.84; P = 0.03) and eGFR at follow-up biopsy (0.84; 95% confidence interval, 0.76-0.92; P < 0.001) as significant predictors of graft loss. Kaplan-Meier analyses demonstrated that the benefit associated with rituximab was apparent after 1 year (15% vs 32% graft loss, P = 0.02).

Conclusion

Treatment of late ABMR with steroids/IVIG ± rituximab was effective in reducing DSA and microcirculation inflammation. The addition of rituximab was associated with better graft survival. Follow-up biopsies could be considered in the management of acute rejection to monitor the effect of therapy. Randomized studies on the best therapeutic options for ABMR are needed.
Sequence Transfer Learning for Neural Decoding
Authors: Elango Venkatesh , Patel Aashish N , Miller Kai J , Gilja Vikash
Published: October 2017

A fundamental challenge in designing brain-computer interfaces (BCIs) is decoding behavior from time-varying neural oscillations. in typical applications, decoders are constructed for individual subjects and with limited data leading to restrictions on the types of models that can be utilized. currently, the best performing decoders are typically linear models capable of utilizing rigid timing constraints with limited training data. Here we demonstrate the use of Long Short-Term Memory (LSTM) networks to take advantage of the temporal information present in sequential neural data collected from subjects implanted with electrocorticographic (ECoG) electrode arrays performing a finger flexion task. our constructed models are capable of achieving accuracies that are comparable to existing techniques while also being robust to variation in sample data size. Moreover, we utilize the LSTM networks and an affine transformation layer to construct a novel architecture for transfer learning. We demonstrate that in scenarios where only the affine transform is learned for a new subject, it is possible to achieve results comparable to existing state-of-the-art techniques. The notable advantage is the increased stability of the model during training on novel subjects. Relaxing the constraint of only training the affine transformation, we establish our model as capable of exceeding performance of current models across all training data sizes. Overall, this work demonstrates that LSTMS are a versatile model that can accurately capture temporal patterns in neural data and can provide a foundation for transfer learning in neural decoding.
Development of migrating entheses involves replacement of progenitor populations
Authors: Felsenthal Neta , Rubin Sarah , Stern Tomer , Krief Sharon , Pal Deepanwita , Pryce Brian A. , Schweitzer Ronen , Zelzer Elazar
Published: October 2017

Attachment sites of tendons to bones, called entheses, are essential for proper musculoskeletal function. They are formed embryonically bySox9+ progenitors and undergo a developmental process that continues into the postnatal period and involvesGli1lineage cells. During bone elongation, some entheses maintain their relative positions by actively migrating along the bone shaft, while others, located at the bone’s extremities, remain stationary. Despite their importance, we lack information on the developmental transition from embryonic to mature enthesis and on the relation betweenSox9+ progenitors andGli1lineage cells. Here, by performing a series of lineage tracing experiments, we identify the onset ofGli1lineage contribution to different entheses during embryogenesis. We show thatGli1expression is regulated by SHH signaling during embryonic development, whereas postnatally it is maintained by IHH signaling. Interestingly, we found that unlike in stationary entheses, whereSox9+ cells differentiate into theGli1lineage, in migrating entheses theSox9lineage is replaced byGli1lineage and do not contribute to the mature enthesis. Moreover, we show that theseGli1+progenitors are pre-specified embryonically to form the different cellular domains of the mature enthesis.

Overall, these findings demonstrate a developmental strategy whereby one progenitor population establishes a simple, embryonic tissue, whereas another population is responsible for its maturation into a complex structure during its migration. Moreover, they suggest that different cell populations may be considered for cell-based therapy of enthesis injuries.
A microbial perspective on the life-history evolution of marine invertebrate larvae: if, where, and when to feed
Authors: Carrier Tyler J. , Macrander Jason , Reitzel Adam M.
Published: October 2017

The feeding environment for planktotrophic larvae has a major impact on development and progression towards competency for metamorphosis. High phytoplankton environments that promote growth often have a greater microbial load and incidence of pathogenic microbes, while areas with lower food availability have a lower number of potential pathogens. Trade-offs between metabolic processes associated with growth and immune functionality have been described throughout the animal kingdom and may influence the life-history evolution of marine invertebrate planktotrophic larvae in these environments. Namely, to avoid potential incidences of microbial-mediated mortality and/or dysbiosis, larvae should regulate time spent between these two feeding environments. We describe here transcriptomic and microbiome data that supports this trade-off in larvae, where larvae in a well-fed environment upregulate genes associated with metabolism and may regularly enter a state of dysbiosis, resulting in mortality. To address the hypothesis that the environmental microbiota is a selective force on if, where, and when planktotrophic larvae should feed, we present a strategy for determining the specific interactions of larvae and microbes at a scale representative of their larger pelagic environment.
Microglial elimination of dopamine D1 receptors defines sex-specific changes in nucleus accumbens development and social play behavior during adolescence
Authors: Kopec Ashley M. , Smith Caroline J. , Ayre Nathan R. , Sweat Sean C. , Bilbo Staci D.
Published: October 2017

Adolescence is a developmental period in which the mesolimbic dopaminergic ‘reward’ circuitry of the brain, including the nucleus accumbens (NAc), undergoes significant developmental plasticity and neural circuit maturation. Dopamine D1 receptors (D1rs) in the NAc have recently been demonstrated to be critical modulators of social behavior, but how these receptors are regulated in adolescence to mediate social behavior is not well understood. In this report, we used multi-plexed immunohistochemistry with volumetric reconstructions, co-immunoprecipitation,ex vivo, andin vivostereotaxic, microglial manipulation, and social behavior assessment to demonstrate that microglia and complement-mediated phagocytic activity shapes sex-specific NAc development. Moreover, we report for the first time that microglia-mediated phagocytosis is required for natural developmental changes in behavior, specifically, adolescent male social play behavior. These data have broad implications for understanding how experience interacts with the developing reward circuity, sex-specific responses to stimuli in adolescence, and how neuropsychiatric disorders may arise in a sexually dimorphic manner.
Pteridine glycosyltransferase from Chlorobium tepidum: crystallization and X-ray analysis
Authors: Killivalavan Asaithambi , Park Young Shik , Lee Kon Ho
Published: October 2017

The pteridine glycosyltransferase (PGT) found in Chlorobium tepidum (CtPGT) catalyzes the conversion of L-threo-tetrahydrobiopterin to 1-O-(L-threo-biopterin-2′-yl)-β-N-acetylglucosamine using UDP-N-acetylglucosamine. The gene for CtPGT was cloned, and selenomethionine-derivatized protein was overexpressed and purified using various chromatographic techniques. The protein was crystallized by the hanging-drop vapour-diffusion method using 0.24 M triammonium citrate pH 7.0, 14%(w/v) PEG 3350 as a reservoir solution. Multiple-wavelength anomalous diffraction data were collected to 2.15 Å resolution from a single CtPGT crystal. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 189.61, b = 79.98, c = 105.92 Å, β = 120.5°.
Biochemical and structural studies of mutants indicate concerted movement of the dimer interface and ligand-binding region ofMycobacterium tuberculosispantothenate kinase
Authors: Paul A. , Kumar P. , Surolia A. , Vijayan M.
Published: October 2017

Two point mutants and the corresponding double mutant ofMycobacterium tuberculosispantothenate kinase have been prepared and biochemically and structurally characterized. The mutants were designed to weaken the affinity of the enzyme for the feedback inhibitor CoA. The mutants exhibit reduced activity, which can be explained in terms of their structures. The crystals of the mutants are not isomorphous to any of the previously analysed crystals of the wild-type enzyme or its complexes. The mycobacterial enzyme and its homologousEscherichia colienzyme exhibit structural differences in their nucleotide complexes in the dimer interface and the ligand-binding region. In three of the four crystallographically independent mutant molecules the structure is similar to that in theE. colienzyme. Although the mutants involve changes in the CoA-binding region, the dimer interface and the ligand-binding region move in a concerted manner, an observation which might be important in enzyme action. This work demonstrates that the structure of the mycobacterial enzyme can be transformed into a structure similar to that of theE. colienzyme through minor perturbations without external influences such as those involving ligand binding.
Four highly pseudosymmetric and/or twinned structures of d(CGCGCG)2extend the repertoire of crystal structures of Z-DNA
Authors: Luo Zhipu , Dauter Zbigniew , Gilski Miroslaw
Published: October 2017

DNA oligomer duplexes containing alternating cytosines and guanines in their sequences tend to form left-handed helices of the Z-DNA type, with the sugar and phosphate backbone in a zigzag conformation and a helical repeat of two successive nucleotides. Z-DNA duplexes usually crystallize as hexagonally arranged parallel helical tubes, with various relative orientations and translation of neighboring duplexes. Four novel high-resolution crystal structures of d(CGCGCG)2duplexes are described here. They are characterized by a high degree of pseudosymmetry and/or twinning, with three or four independent duplexes differently oriented in a monoclinicP21lattice of hexagonal metric. The various twinning criteria give somewhat conflicting indications in these complicated cases of crystal pathology. The details of molecular packing in these crystal structures are compared with other known crystal forms of Z-DNA.