bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic C1-C2 Rotatory Subluxation Reduced by C1 Lateral Mass Screws and C2 Translaminar Screws: A Case Report
Authors: Lavelle William F. , Palomino Kathryn , Badve Siddharth A. , Albanese Stephen A.
Published: June 2016

Background:

C1-C2 rotatory subluxation can result from a variety or etiologies. Pediatric patients are particularly susceptible to C1-C2 rotatory subluxation. If left untreated the condition is termed an atlantoaxial rotatory fixation (AARF) and chronic neck pain and deformity can result. Patients failing conservative treatment or those with recurrent or chronic rotatory subluxation may require halo treatment or surgical intervention. This illustrative case report is about a patient with chronic C1-C2 AARF who was treated with C1 lateral mass screws and C2 translaminar screws, a treatment that has not been addressed by this technique in a pediatric population.

Methods:

This is a retrospective case review.

Results:

After an unsuccessful attempt at reduction, an 11-year-old girl underwent surgery to treat her C1-C2 AARF. Through an all posterior approach, screws were placed bilaterally into the C1 lateral masses followed by the placement of C2 translaminar screws bilaterally. A small amount of distraction was applied through the screw construct to open up the C1-C2 articulation and the AARF was open reduced and fused. A detailed postoperative computed tomographic scan focused on the occiput C1-C2 joint confirmed the anatomical reduction of the joint complex.

Conclusions:

The patient had cosmetically pleasing relief of her torticollis and was doing well at 60 months after surgery.

Level of Evidence:

Level IV.
Age Predicts Disruption of the Articular Surface of the Femoral Condyles in Knee OCD: Can We Reduce Usage of Arthroscopy and MRI?
Authors: Siegall Evan , Faust John R. , Herzog Mackenzie M. , Marshall Kelley W. , Willimon S. Clifton , Busch Michael T.
Published: June 2016

Background:

The purpose of this study was to determine if patient age could accurately identify disrupted articular cartilage overlying an osteochondritis dissecans (OCD) lesion of the femoral condyle in adolescents. This could have important implications for imaging and treatment decisions.

Methods:

All patients from 2001 to 2014 who were arthroscopically treated for a femoral condyle OCD were included in this Institutional Review Board-approved study. Exclusion criteria were trochlear and patellar OCD lesions, idiopathic arthritis, and traumatic osteochondral injuries. Arthroscopy was performed to visualize and probe the articular surface. Arthroscopic and magnetic resonance imaging (MRI) findings were recorded as “intact” or “disrupted” cartilage. Extra-articular drilling was performed when the articular cartilage was intact.

Results:

There were 119 patients (81 male, 68%) with 139 OCD lesions in 136 knees. The mean age at time of surgery was 13.0 years (range, 7.2 to 19.3 y). At arthroscopy, 115 knees had intact cartilage and 24 had disrupted cartilage. There was a significant difference in age between patients with intact versus disrupted cartilage at arthroscopy (12.5 vs. 15.3 y; P<0.0001). Eighty-eight OCD lesions had MRIs preoperatively, showing 69 as intact and 19 (24%) disrupted. MRI reading for cartilage status had 94% sensitivity and 97% specificity. Multivariable regression analysis revealed that age (P<0.01) and MRI status (P<0.0001) were strong predictors of cartilage status. Sixteen years was the critical age in which both sensitivity was maximized and false positive probability was minimized. Over the age of 17 years, 7 of 7 (100%) had disrupted cartilage. Age alone was 100% sensitive for children below the age of 10, and 96% sensitive below the age of 13.

Conclusions:

Age was a good predictor of cartilage status in both younger (<13 y) and older (≥17 y) patients in this study. For patients in the mid-range group (13 through 16 y), age alone is not an adequate predictor of cartilage status, but adding MRI increased accuracy.

Significance:

Age can be used to stratify patients and thereby influence diagnostic and treatment strategies.

Level of Evidence:

Level IV.
The Risk of Cancer With the Use of Recombinant Human Bone Morphogenetic Protein in Spine Fusion
Authors: Dettori Joseph R. , Chapman Jens R. , DeVine John G. , McGuire Robert A. , Norvell Daniel C. , Weiss Noel S.
Published: June 2016

Study Design.

Retrospective cohort study using the Washington State Comprehensive Hospital Abstract Reporting System, the Washington State Cancer Registry, and Washington State death certificates.

Objective.

To study the possible association between recombinant human bone morphogenetic protein (rhBMP) and cancer risk.

Summary of Background Data.

The use of rhBMP in spine fusion surgery remains controversial with respect to its possible role in tumorigenesis.

Methods.

We compared adults who underwent spine fusion for degenerative disease with and without rhBMP between 2002 and 2010. Patients were matched on the basis of age, sex, and year of treatment. We excluded patients with a diagnosis of cancer before or at the index procedure. The primary outcome was the first diagnosis of cancer as identified in the records of the cancer registry.

Results.

We included 16,914 patients who had spine fusion, of whom 4246 received rhBMP. During the study period, 449 patients received a diagnosis of cancer: 117 (2.76% of 4246) in the rhBMP group and 332 (2.62% of 12 668) in the no rhBMP group. The incidence rate was similar between the rhBMP and no rhBMP 9.5 and 9.0 per 1000 person years, respectively (hazard ratio, 1.06; 95% confidence interval, 0.86–1.30). There were no differences in the rate of cancer between the two groups in subgroups defined on the basis of site of fusion or surgical method.

Conclusion.

There was no increase in overall cancer incidence among those receiving rhBMP. An important limitation of this and other studies of rhBMP and cancer that have been conducted to date is their relatively limited duration of follow-up. The examination of cancer incidence following rhBMP administration must continue beyond just the first several years to adequately assess the potential of rhBMP to influence the occurrence of one or more types of malignancy.

Level of Evidence: 3
Building and Participating in a Simulation: Exploring a Continuing Education Intervention Designed to Foster Reflective Practice Among Experienced Clinicians
Authors: Zubairi Mohammad Samad , Lindsay Sally , Parker Kathryn , Kawamura Anne
Published: June 2016

Introduction:

Engaging health professionals in the processes of first building and then participating in simulations has not yet been explored. This qualitative study explored the experience of building and participating in a simulation as an educational intervention with experienced clinicians.

Methods:

Pediatric rehabilitation clinicians, along with a patient facilitator and standardized patients, created simulations and subsequently participated in a live simulation. The educational content of the simulation was culturally sensitive communication. We collected participants' perspectives about the process from individual journal entries and focus groups. A thematic analysis of these data sources was conducted.

Results:

Participants described a process of building and participating in a simulation that provided: 1) a unique opportunity for clinicians to reflect on their current practice; 2) a venue to identify different perspectives through discussion and action in a group; and 3) a safe environment for learning.

Discussion:

The combined process of building and participating in a simulation stimulated reflection about the clinicians' own abilities in culturally sensitive communication through discussion, practice, and feedback. It provided a safe environment for participants to share their multiple perspectives and to develop new ways of communicating. This type of educational intervention may contribute to the continuing education of experienced clinicians in both academic and community settings.
A Prospective Trial Comparing Q-Switched Ruby Laser and a Triple Combination Skin-Lightening Cream in the Treatment of Solar Lentigines
Authors: Imhof Laurence , Dummer Reinhard , Dreier Jil , Kolm Isabel , Barysch Marjam J.
Published: June 2016

BACKGROUND

Quality-switched (QS) laser therapy is a safe and well-established treatment option for removing solar lentigines. Triple combination therapy (TCT) with the active pharmaceutical ingredients hydroquinone 5%, tretinoin 0.03%, and dexamethasone 0.03% is often used for skin-lightening.

OBJECTIVE

This prospective, open-label trial compares the efficacy and safety of a QS Ruby laser (QSRL) and a TCT in the treatment of solar lentigines.

METHODS

In total, 15 patients with symmetrically distributed solar lentigines on the back of both hands were included. The lesions on the back of the right hand were treated in one or 2 sessions with a QSRL, the ones on the back of the left hand with a TCT for 7 weeks accompanied by UV protection. Clinical results were evaluated 4 weeks, 8 weeks, and 20 weeks after baseline.

RESULTS

Treatment with QSRL provided significant lightening (p = .01) compared with TCT. Both procedures were generally well-tolerated. Comparing the side effects, the laser produced significantly more crusting and hyperpigmentation than the TCT.

CONCLUSION

Both QSRL and TCT were capable in reducing solar lentigines in Fitzpatrick skin Type I to IV with an acceptable side effect profile. The QSRL provides faster, superior, and long lasting lightening compared with TCT.
The Impact of Allopurinol on Patients With Acute ST Elevation Myocardial Infarction Undergoing Thrombolytic Therapy
Authors: Separham Ahmad , Ghaffari Samad , Najafi Hossein , Ghaffari Reza , Ziaee Mojtaba , Babaei Hossein
Published: June 2016

Allopurinol may have protective effects over ischemic reperfusion injury and reduce infarct size. In this randomized study, we aimed to evaluate the impact of allopurinol in patients with acute ST elevation myocardial infarction (STEMI) undergoing thrombolytic therapy. Overall, 140 patients with STEMI were randomly assigned to receive 400 mg of allopurinol or placebo before treating with streptokinase. Then, study group received 100 mg of allopurinol daily for 28 days and placebo group received placebo for the same period. ST resolution rate in 90 minutes, in-hospital mortality, and major adverse cardiac events (MACE) were compared. Compared to placebo group, patients receiving allopurinol had significantly higher rate of ST resolution rate ≥50% (68.8% vs. 50%, P = 0.04) and lower levels of peak Creatine kinase (CK) (P = 0.003), Creatine Kinase-MB (CK-MB) (P = 0.005), and Cardiac Troponin I (CTnI) (P < 0.001). Also, patients in allopurinol group had significantly lower rate of in-hospital MACE (P = 0.03), but there was no significant difference between groups regarding in-hospital mortality and cardiac events. In patients admitted with STEMI who are candidates of thrombolytic therapy, allopurinol is associated with better 90-minute ST resolution, lower enzymatically determined infarct size, and in-hospital MACE. More powerful studies are needed to determine the effect on mortality.
Invasive Ocular Surface Squamous Neoplasia Masquerading as Nodular Scleritis
Authors: Sharma Medha , Sundar Dheepak , Vanathi Murugesan , Meel Rachna , Kashyap Seema , Chawla Rohan , Tandon Radhika
Published: June 2016

The authors report a rare case of ocular surface squamous neoplasia with intraocular involvement that had an initial masquerade presentation of recurrent anterior nodular scleritis. A 35-year-old male patient presented with right eye recurrent anterior nodular scleritis for which a lamellar patch graft was done. Two months later, the patient presented with recurrence of symptoms. Histopathology review revealed the presence of well-differentiated squamous cell malignancy. A high index of suspicion for malignancy is required in such cases when they do not respond to conventional therapy.
Pink Papules Around the Mouth
Authors: Jacob Sharon E.
Published: June 2016

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of patient medical information electronically (including history and visual data) obtained in one location to a provider who is in another location (Roman & Jacob, 2015). The construct of the Teledermatology Viewpoint column is such that cases are presented in a standardized teledermatology reader format rpeflective of an actual teledermatology report. This is a case of pink papules around the mouth.
Is patient flow more efficient in Urgent Care Collaborations?
Authors: van Gils-van Rooij Elisabeth S.J. , Meijboom Berthold R. , Broekman Sjoerd M. , Yzermans Christoffel J. , de Bakker Dingenus H.
Published: June 2016

Objective

Emergency Departments and out-of-hours General Practitioner services collaborate increasingly in Urgent Care Collaborations (UCCs) by sharing one combined entrance and joint triage. The aim of this study is to examine the difference between UCCs and providers who operate separately with respect to the efficiency of patient flow.

Methods

This study had a cross-sectional observational design comparing three regions with UCC with three regions with usual care. Outcome measures were efficiency of patient flow, defined as a reducing length of stay (LOS), waiting time (WT) and the mean number of handovers. Data were obtained from electronic medical records.

Results

LOS (median 34:00 vs. 38:52 min) and WT (median 14:00 vs. 18:43 min) were statistically significantly longer in UCCs compared with usual care. This difference is mainly explained by the prolonged LOS and WT for consulting a General Practitioner. The mean number of interunit handovers was larger in UCCs.

Conclusion

The results indicate that, on average, UCCs do not enhance the efficiency of patient flow. The median LOS and WT are longer in UCCs and more handovers occur in UCCs compared with usual care.
Hospital Phenotypes in the Management of Patients Admitted for Acute Myocardial Infarction
Authors: Xu Xiao , Li Shu-Xia , Lin Haiqun , Normand Sharon-Lise T. , Lagu Tara , Desai Nihar , Duan Michael , Kroch Eugene A. , Krumholz Harlan M.
Published: June 2016

Objectives:

To characterize hospital phenotypes by their combined utilization pattern of percutaneous coronary interventions (PCI), coronary artery bypass grafting (CABG) procedures, and intensive care unit (ICU) admissions for patients hospitalized for acute myocardial infarction (AMI).

Research Design:

Using the Premier Analytical Database, we identified 129,138 hospitalizations for AMI from 246 hospitals with the capacity for performing open-heart surgery during 2010–2013. We calculated year-specific, risk-standardized estimates of PCI procedure rates, CABG procedure rates, and ICU admission rates for each hospital, adjusting for patient clinical characteristics and within-hospital correlation of patients. We used a mixture modeling approach to identify groups of hospitals (ie, hospital phenotypes) that exhibit distinct longitudinal patterns of risk-standardized PCI, CABG, and ICU admission rates.

Results:

We identified 3 distinct phenotypes among the 246 hospitals: (1) high PCI—low CABG—high ICU admission (39.2% of the hospitals), (2) high PCI—low CABG—low ICU admission (30.5%), and (3) low PCI—high CABG—moderate ICU admission (30.4%). Hospitals in the high PCI—low CABG—high ICU admission phenotype had significantly higher risk-standardized in-hospital costs and 30-day risk-standardized payment yet similar risk-standardized mortality and readmission rates compared with hospitals in the low PCI—high CABG—moderate ICU admission phenotype. Hospitals in these phenotypes differed by geographic region.

Conclusions:

Hospitals differ in how they manage patients hospitalized for AMI. Their distinctive practice patterns suggest that some hospital phenotypes may be more successful in producing good outcomes at lower cost.
Assessment and consequences of cell senescence in atherosclerosis
Authors: Garrido Abel Martin , Bennett Martin
Published: June 2016

Purpose of review

Cell senescence is a major process regulating tissue mass, architecture and function, and underlies many diseases of ageing. Recent studies have elucidated some of the regulatory pathways leading to cell senescence, and senescence has also been found in the vasculature. However, assessment of cell senescence is problematic, and the effects of vascular cell senescence are in most cases unproven. The present article will review how senescence is assessed, how it is regulated, where senescence has been described, and the role of cell senescence in atherosclerosis.

Recent findings

Senescence results in expression of multiple proteins, both intracellular and secreted. However, to date, none of these are specific for senescence, and multiple markers must be used together for positive identification. Despite these shortfalls, cell senescence is detectable in the vasculature in ageing and in human atherosclerosis, and recent studies in mice have indicated that cell senescence promotes both atherogenesis and multiple features of ‘vulnerable’ lesions in advanced atherosclerotic plaques.

The almost ubiquitous presence of cell senescence in atherosclerosis and the fundamental role of senescence in regulating plaque development and stability suggest that prevention or amelioration of senescence in atherosclerosis is a viable therapeutic target.
New biomaterials versus traditional techniques: advances in cleft palate reconstruction
Authors: Lakhani Raam S.
Published: June 2016

Purpose of review

Cleft lip and palate still remains one of the most common congenital anomalies, and consequently surgical correction of these anomalies is still commonplace. Despite numerous existing surgical techniques having good outcomes, it is still recognized that the morbidity of certain surgical procedures and success rates regarding outcomes can be improved. The purpose of this review is to evaluate new literature and techniques compared with the time tested procedures that are commonly used.

Recent findings

As technology continues to advance, the understanding of details regarding biochemical pathways responsible for the development of cleft defects and also the efficacy of biomaterials that can be used in their correction are being discovered and better understood. Many studies have been conducted in both animal and human study participants that further the understanding of these questions. The efficacy and benefit of newly devised biomaterials seems to indicate that these biomaterials are a viable adjunct and often an alternative in the treatment of cleft palate patients.

In this review of recent literature, the discussion begins with a review of the more traditional and widely accepted iliac crest bone grafting and then evolves into a discussion of several animal and human studies to delineate the progress being made in this field. The literature exploring the details regarding biochemical pathways and cellular mediators that are involved in cleft formation, as well as biomaterials used in surgical repair are evaluated. The findings in the literature suggest that there is a bright future in better understanding the cause of cleft formation on a molecular level and associated attempts that can be made in altering some of these factors along with discovering new biomaterials that can be a useful adjunct to existing techniques.
A Prevalence Study of Psychosocial Distress in Adolescents and Young Adults With Cancer
Authors: Xie Jianfei , Ding Siqing , He Siqi , Duan Yinglong , Yi Kaigui , Zhou Jianda
Published: June 2016

Background:

Psychosocial distress is common among cancer patients. Significant associations between coping and social support with distress and quality of life in adult cancer patients have been identified before, but little is known about the interrelationships between distress, medical coping, and social support in adolescents and young adults (AYAs).

Objective:

The aims of this study are to investigate the prevalence of psychological distress in Chinese AYAs with cancer and examine the associations among distress, anxiety and depression, medical coping, and social support in the same population.

Methods:

A total of 610 AYA patients were recruited for this study; 551 patients completed the Chinese version of the National Comprehensive Cancer Network Distress Thermometer (DT), the Hospital Anxiety and Depression Scale, the Medical Coping Modes Questionnaire, and the Social Support Rating Scale.

Results:

The prevalence of psychological distress was 89.1% in Chinese AYAs with cancer. The DT scores were the highest in the 21- to 25-year-old patients; the DT scores were positively correlated with anxiety and depression (P < .01) but negatively correlated with medical coping and social support (P < .01).

Conclusion:

The prevalence of psychological distress in AYA cancer patients was higher than that in the general cancer population. Medical coping and social support can lower the prevalence of psychological distress in AYA cancer patients.

Implications for Practice:

Findings suggest the need for evidence-based intervention strategies to enhance medical coping and social support in AYA cancer patients. Nurses are crucial to implementing psychological interventions in AYA cancer patients.
The Effectiveness of Remote Facilitation in Simulation-Based Pediatric Resuscitation Training for Medical Students
Authors: Ohta Kunio , Kurosawa Hiroshi , Shiima Yuko , Ikeyama Takanari , Scott James , Hayes Scott , Gould Michael , Buchanan Newton , Nadkarni Vinay , Nishisaki Akira
Published: June 2016

Objectives

To assess the effectiveness of pediatric simulation by remote facilitation. We hypothesized that simulation by remote facilitation is more effective compared to simulation by an on-site facilitator. We defined remote facilitation as a facilitator remotely (1) introduces simulation-based learning and simulation environment, (2) runs scenarios, and (3) performs debriefing with an on-site facilitator.

Methods

A remote simulation program for medical students during pediatric rotation was implemented. Groups were allocated to either remote or on-site facilitation depending on the availability of telemedicine technology. Both groups had identical 1-hour simulation sessions with 2 scenarios and debriefing. Their team performance was assessed with behavioral assessment tool by a trained rater. Perception by students was evaluated with Likert scale (1-7).

Results

Fifteen groups with 89 students participated in a simulation by remote facilitation, and 8 groups with 47 students participated in a simulation by on-site facilitation. Participant demographics and previous simulation experience were similar. Both groups improved their performance from first to second scenario: groups by remote simulation (first [8.5 ± 4.2] vs second [13.2 ± 6.2], P = 0.003), and groups by on-site simulation (first [6.9 ± 4.1] vs second [12.4 ± 6.4], P = 0.056). The performance improvement was not significantly different between the 2 groups (P = 0.94). Faculty evaluation by students was equally high in both groups (7 vs 7; P = 0.65).

Conclusions

A pediatric acute care simulation by remote facilitation significantly improved students' performance. In this pilot study, remote facilitation seems as effective as a traditional, locally facilitated simulation. The remote simulation can be a strong alternative method, especially where experienced facilitators are limited.
Efficiency of Using Pediatrics Emergency Services and Triage Evaluation
Authors: El Desoky Sherif , Mashat Suleiman , Bana Suliman , Alama Mohamed , Dhabab Nawaf , Malibari Ghassan M. , Halwani Manal , Albanna Amr S. , Kari Jameela A.
Published: June 2016

Objective

The aim of the study was to evaluate the pediatric emergency department (PED) in a main teaching hospital.

Methods

Retrospective review of all children presented to PED at King Abdulaziz University Hospital from September to November 2014 was performed. We classified priority into the following 5 stages: 1, need resuscitation; 2, emergent; 3, urgent; 4, less urgent; and 5, nonurgent.

Results

A total of 2567 children (58.9% boys) attended PED for 3 months. Toddler age group was the highest. Respiratory complaints were the commonest (36%), followed by gastrointestinal complaints (20%). The majority were classified as priority 3 (52.3%) and priority 4 (30.7%). The admission rate was 12.3% and the mean (range) length of stay (LOS) was 5.85 (0.2-25) hours. Saudi nationals were less likely to wait for 5 hours or longer, less likely to be admitted, but more likely to leave PED without being evaluated. There was a negative correlation between higher priorities and time from triage to PED. There was a positive correlation between the higher priorities and LOS.

Conclusions

Most children who were seen in PED were priority 3 and therefore needed to be seen. However, a considerable percentage of priority 4 and 5 could have been seen in ambulatory clinics. Most lower priorities were Saudi nationals who were most likely to leave without being seen. Prolonged LOS, overcrowding, and high percentage of admission are the main challenges
Factors Predicting Lung Contusions in Critically Ill Trauma Children
Authors: Chaari Anis , Chelly Hedi , Fourati Hela , Mnif Zeineb , Chtara Kamilia , Baccouche Najeh , Bahloul Mabrouk , Bouaziz Mounir
Published: June 2016

Purpose

The aim of the study was to identify factors predicting lung contusion in trauma children.

Methods

Retrospective study conducted for a period of 8 years (January 01, 2005–December 31, 2012) in a medical surgical intensive care unit. All trauma patients younger than 15 years were included. Two groups were compared: those with lung contusions (C+ group) and those without lung contusions (C− group).

Results

We included 330 patients. The mean (SD) age was 7.6 (4.3) years. Chest injury was diagnosed in 70 patients (21.2%). All our patients needed mechanical ventilation. Lung contusions were diagnosed in 43 patients (13% of all patients and 61.4% of patients with chest trauma). In multivariate analysis, independent factors predicting lung contusion were road traffic accident (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.2–8.6; P = 0.019), increased Pediatric Risk of Mortality (PRISM) score (OR, 1.1; 95% CI, 1.1–1.2; P = 0.017), hepatic contusion (OR, 4.8; 95% CI, 1.3–17.1; P = 0.017), and pelvic ring fracture (OR, 3.5; 95% CI, 1.1–10.5; P = 0.026). Death occurred in 46 patients (13.9%). Intensive care unit mortality was significantly higher in the C+ group (OR, 2.5; 95% CI, 1.2–5.4; P = 0.021). However, mortality was not different between the 2 groups after adjusting for PRISM score (OR, 1.2; 95% CI, 0.5–2.9; P = 0.752) or after adjusting for Injury Severity Score (OR, 0.7; 95% CI, 0.3–2.1; P = 0.565).

Conclusions

Lung contusion is common in critically ill children with chest trauma. The diagnosis should be considered in patients with road traffic accident, increased PRISM score, hepatic contusion, and pelvic ring fracture.
Automated Quantitative Computed Tomography Versus Visual Computed Tomography Scoring in Idiopathic Pulmonary Fibrosis
Authors: Jacob Joseph , Bartholmai Brian J. , Rajagopalan Srinivasan , Kokosi Maria , Nair Arjun , Karwoski Ronald , Raghunath Sushravya M. , Walsh Simon L.F. , Wells Athol U. , Hansell David M.
Published: June 2016

Purpose:

The aim of the study was to determine whether a novel computed tomography (CT) postprocessing software technique (CALIPER) is superior to visual CT scoring as judged by functional correlations in idiopathic pulmonary fibrosis (IPF).

Materials and Methods:

A total of 283 consecutive patients with IPF had CT parenchymal patterns evaluated quantitatively with CALIPER and by visual scoring. These 2 techniques were evaluated against: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), carbon monoxide transfer coefficient (Kco), and a composite physiological index (CPI), with regard to extent of interstitial lung disease (ILD), extent of emphysema, and pulmonary vascular abnormalities.

Results:

CALIPER-derived estimates of ILD extent demonstrated stronger univariate correlations than visual scores for most pulmonary function tests (PFTs): (FEV1: CALIPER R
2=0.29, visual R
2=0.18; FVC: CALIPER R
2=0.41, visual R
2=0.27; DLco: CALIPER R
2=0.31, visual R
2=0.35; CPI: CALIPER R
2=0.48, visual R
2=0.44). Correlations between CT measures of emphysema extent and PFTs were weak and did not differ significantly between CALIPER and visual scoring. Intriguingly, the pulmonary vessel volume provided similar correlations to total ILD extent scored by CALIPER for FVC, DLco, and CPI (FVC: R
2=0.45; DLco: R
2=0.34; CPI: R
2=0.53).

Conclusions:

CALIPER was superior to visual scoring as validated by functional correlations with PFTs. The pulmonary vessel volume, a novel CALIPER CT parameter with no visual scoring equivalent, has the potential to be a CT feature in the assessment of patients with IPF and requires further exploration.
Dyschromatopsia in Multiple Sclerosis Patients: A Marker of Subclinical Involvement?
Authors: Felgueiras Helena , Parra Joana , Cruz Simão , Pereira Pedro , Santos Ana F. , Rua Adriana , Meira Dália , Fonseca Pedro , Pedrosa Catarina , Cardoso João N. , Almeida Cristina , Araújo Maria , Santos Ernestina
Published: June 2016

Background:

In multiple sclerosis (MS), even in the absence of a clinical episode of optic neuritis (ON), the optic nerve and retinal nerve fiber layer (RNFL) may be damaged leading to dyschromatopsia. Subclinical dyschromatopsia has been described in MS associated with lower motor and cognitive performances.

Objectives:

To set the prevalence of dyschromatopsia in eyes of MS patients without a history of ON, to compare its prevalence in patients with and without ON history, and to explore the association between dyschromatopsia and disease duration, average peripapillary RNFL thickness, macular volume, and cognitive and motor performances.

Methods:

An observational cross-sectional study was conducted at multiple medical centers. Data were collected after single neurological and ophthalmological evaluations. Dyschromatopsia was defined by the presence of at least 1 error using Hardy–Rand–Rittler plates.

Results:

In our population of 125 patients, 79 patients (63.2%) never had ON and 35 (28.8%) had unilateral ON. The prevalence of dyschromatopsia in eyes of patients without ON was 25.7%. Patients with dyschromatopsia had a statistically significant lower RNFL thickness (P = 0.004 and P = 0.040, right and left eyes, respectively) and worse performance in symbol digit modalities test (P = 0.012). No differences were found in macular volume or motor function tasks.

Conclusions:

Dyschromatopsia occurs frequently in MS patients. It may be associated with a worse disease status and possibly serve as a marker for the detection of subclinical disease progression since it was detected even in the absence of ON. It correlated with thinner peripapillary RNFL thickness and inferior cognitive performance.
Idiopathic Intracranial Hypertension—A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World
Authors: Rosenblatt Amir , Klein Ainat , Roemer Ségolène , Borruat François-Xavier , Meira Dália , Silva Marta , Gökçay Figen , Çelebisoy Neşe , Kesler Anat
Published: June 2016

Background:

Idiopathic intracranial hypertension (IIH) is a well-characterized syndrome, most commonly affecting obese women of childbearing age. Differences in its prevalence have been reported in various populations. The aim of this article was to determine whether differences in clinical presentation and management exist for patients with IIH between different regions the world.

Methods:

Retrospective database analysis of adult patients with IIH from 4 different neuro-ophthalmology clinics. The data collected included gender, age of onset, body mass index (BMI), lumbar puncture opening pressure, initial visual acuity (VA), initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, final VA, and final VF MD.

Results:

The study population consisted of 244 patients, with significant regional variations of female to male ratio. Overall, there was no significant difference regarding the age of diagnosis or the BMI. Acetazolamide was the first line of treatment in all groups but there was a difference between countries regarding second-line treatment, including the use of surgical interventions. Mean initial VA differed between groups but the final change in VA was the same among all the study groups.

Conclusions:

There are differences in IIH presentation, treatment, and response to therapy among different countries. International prospective studies involving multiple centers are needed to determine the potential influence of environmental and genetic factors on the development of IIH and to improve the management of this potentially blinding disorder.
Electrodiagnosis of Lesions of Median and Ulnar Nerve Hand Sensory Branches: A Case Series
Authors: Zanette Giampietro , Lauriola Matteo F. , Tamburin Stefano
Published: June 2016

Introduction:

The authors have recently tested a new electrodiagnostic technique for palmar proper digital nerves sensory nerve action potentials in normal controls. Here the authors explored whether it may offer additional information in comparison to mixed nerve wrist stimulation in a series of patients.

Methods:

The authors recorded palmar proper digital nerves sensory nerve action potential to selective antidromic webspace stimulation in a group of 19 patients with suspected lesions of median and ulnar nerve hand sensory branches. Coexistent carpal tunnel syndrome was present in 11 patients.

Results:

The webspace stimulation technique offered additional information in 89% patients when compared with mixed nerve wrist stimulation. Webspace stimulation was informative even when carpal tunnel syndrome coexisted with damage to hand sensory branches and biased the interpretation of conventional wrist nerve conduction study.

Conclusions:

Webspace PaPDN stimulation is feasible in patients with lesion of median and ulnar nerve hand sensory branches and offer additional information in comparison with wrist-mixed nerve conduction study, also in patients with coexisting carpal tunnel syndrome.
Comparison of a Novel Dry Electrode Headset to Standard Routine EEG in Veterans
Authors: Halford Jonathan J. , Schalkoff Robert J. , Satterfield Kevin E. , Martz Gabriel U. , Kutluay Ekrem , Waters Chad G. , Dean Brian C.
Published: June 2016

Objective:

This purpose of this study was to evaluate the usefulness of a prototype battery-powered dry electrode system (DES) EEG recording headset in Veteran patients by comparing it with standard EEG.

Methods:

Twenty-one Veterans had both a standard electrode system recording and DES recording in nine different patient states at the same encounter. Setup time, patient comfort, and subject preference were measured. Three experts performed technical quality rating of each EEG recording in a blinded fashion using the web-based EEGnet system. Power spectra were compared between DES and standard electrode system recordings.

Results:

The average time for DES setup was 5.7 minutes versus 21.1 minutes for standard electrode system. Subjects reported that the DES was more comfortable during setup. Most subjects (15 of 21) preferred the DES. On a five-point scale (1—best quality to 5—worst quality), the technical quality of the standard electrode system recordings was significantly better than for the DES recordings, at 1.25 versus 2.41 (P < 0.0001). But experts found that 87% of the DES EEG segments were of sufficient technical quality to be interpretable.

Conclusions:

This DES offers quick and easy setup and is well tolerated by subjects. Although the technical quality of DES recordings was less than standard EEG, most of the DES recordings were rated as interpretable by experts.

Significance:

This DES, if improved, could be useful for a telemedicine approach to outpatient routine EEG recording within the Veterans Administration or other health system.
Diagnostic Accuracy of Single Fiber Electromyography for Myasthenia Gravis in Patients Followed Longitudinally
Authors: Morren John A. , Levin Kerry H. , Shields Robert W.
Published: June 2016

Introduction:

The literature lacks data on accuracy of single fiber electromyography (SFEMG) for myasthenia gravis (MG) patients followed longitudinally.

Methods:

We included patients with a clinical suspicion of MG who received SFEMG and follow-up at our institution between 2003 and 2013. Data collected included demographics, symptom details, clinical deficits, other diagnostic testing results, MG medication regimen, duration on treatment, response to therapy, and ultimate diagnosis after follow-up. When available, information was also extracted from the MG-specific Activities of Daily Living, MG Quality of Life, and European Quality of Life assessments before and after SFEMG.

Results:

Three hundred forty eight SFEMG patients met inclusion criteria. Myasthenia gravis was ultimately diagnosed in 31% (19% ocular, 12% generalized). A sensitivity of 78% was seen for MG regardless of subtype, 73% for ocular MG, and 85% for generalized MG. A specificity of 91% was obtained for MG of either ocular or generalized subtype.

Conclusions:

The diagnostic accuracy of SFEMG using this methodology minimizing incorporation bias is more reliable than that usually described in previous studies. There is utility in increasing diagnostic yield when SFEMG results are combined with clinical data and those from other diagnostic tests, particularly serology.
Distinct combinations of variant ionotropic glutamate 1 receptors mediate thermosensation and hygrosensation inDrosophila
Authors: Knecht Zachary A. , Silbering Ana F. , Ni Lina , Klein Mason , Budelli Gonzalo , Bell Rati , Abuin Liliane , Ferrer Anggie J. , Samuel Aravinthan D.T. , Benton Richard , Garrity Paul A.
Published: June 2016

Ionotropic Receptors (IRs) are a large subfamily of variant ionotropic glutamate receptors present across Protostomia. While these receptors are most extensively studied for their roles in chemosensory detection in insects, recent work has implicated two family members, IR21a and IR25a, in thermosensation inDrosophila. Here we characterize one of the most deeply conserved receptors, IR93a, and show that it is co-expressed and functions with IR21a and IR25a to mediate physiological and behavioral responses to cool temperatures. IR93a is also co-expressed with IR25a and a distinct receptor, IR40a, in a discrete population of sensory neurons in the sacculus, a multi-chambered pocket within the antenna. We demonstrate that this combination of receptors is important for neuronal responses to dry air and behavioral discrimination of humidity differences. Our results identify IR93a as a common component of molecularly and cellularly distinct IR pathways underlying thermosensation and hygrosensation in insects.
Proteobacteria drive significant functional variability in the human gut microbiome
Authors: Bradley Patrick H. , Pollard Katherine S.
Published: June 2016

While human gut microbiomes vary significantly in taxonomic composition, biological pathway abundance is surprisingly invariable across hosts. We hypothesized that healthy microbiomes appear functionally redundant due to factors that obscure differences in gene abundance across hosts. To account for these biases, we developed a powerful test of gene variability, applicable to shotgun metagenomes from any environment. Our analysis of healthy stool metagenomes reveals thousands of genes whose abundance differs signifi-cantly between people consistently across studies, including glycolytic enzymes, lipopolysac-charide biosynthetic genes, and secretion systems. Even housekeeping pathways contain a mix of variable and invariable genes, though most deeply conserved genes are significantly invariable. Variable genes tend to be associated with Proteobacteria, as opposed to taxa used to define enterotypes or the dominant phyla Bacteroidetes and Firmicutes. These re-sults establish limits on functional redundancy and predict specific genes and taxa that may drive physiological differences between gut microbiomes.

Impact Statement

A statistical test for gene variability reveals extensive functional differences between healthy humanmicrobiomes.
The Human Thalamus is an Integrative Hub for Functional Brain Networks
Authors: Hwang Kai , Bertolero Maxwell , Liu William , D’Esposito Mark
Published: June 2016

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that the human thalamus displays network properties capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate heteromodal information and maintain the modular structure of cortical functional networks.
Functional connectivity in neuromuscular system underlying bimanual muscle synergies
Authors: de Vries Ingmar E. J. , Daffertshofer Andreas , Stegeman Dick F. , Boonstra Tjeerd W.
Published: June 2016

Neural synchrony has been suggested as mechanism for integrating distributed sensorimotor systems involved in coordinated movement. To test the role of corticomuscular and intermuscular coherence in the formation of bimanual muscle synergies, we experimentally manipulated the degree of coordination between hand muscles by varying the sensitivity of the visual feedback to differences in bilateral force. In 16 healthy participants, cortical activity was measured using 64-channel electroencephalography (EEG) and muscle activity of the flexor pollicis brevis muscle of both hands using 8×8-channel high-density electromyography (HDsEMG). Using the uncontrolled manifold framework, coordination between bilateral forces was quantified by the synergy indexRVin the time and frequency domain. Functional connectivity was assed using corticomuscular coherence between muscle activity and cortical source activity and intermuscular coherence between bilateral EMG activity. As expected, bimanual synergies were stronger in the high coordination condition.RVwas higher in the high coordination condition in frequencies between 0 and 0.5 Hz, and above 2 Hz. For the 0.5-2 Hz frequency band this pattern was inverted. Corticomuscular coherence in the beta band (16-30 Hz) was maximal in the contralateral motor cortex and was reduced in the high coordination condition. In contrast, intermuscular coherence was observed at 5-12 Hz and increased with bimanual coordination. Within-subject comparisons revealed a negative correlation betweenRVand corticomuscular coherence and a positive correlation betweenRVand intermuscular coherence. Our findings suggest two distinct neural pathways: (1) Corticomuscular coherence reflects direct corticospinal projections involved in controlling individual muscles; (2) intermuscular coherence reflects diverging pathways involved in the coordination of multiple muscles.
PRDM9 forms a multiprotein complex tethering recombination hotspots to the chromosomal axis
Authors: Parvanov Emil D. , Tian Hui , Billings Timothy , Saxl Ruth L. , Spruce Catrina , Aithal Rakesh , Krejci Lumir , Paigen Kenneth , Petkov Petko M.
Published: June 2016

In mammals, meiotic recombination occurs at 1-2 kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We now show that the KRAB domain of PRDM9 forms complexes with additional proteins to allow hotspots to proceed into the next phase of recombination. By a combination of yeast-two hybrid assay,in vitrobinding, and co-immunoprecipitation from mouse spermatocytes, we identified four proteins that directly interact with PRDM9’s KRAB domain, namely CXXC1, EWSR1, EHMT2, and CDYL. These proteins are co-expressed in spermatocytes at the early stages of meiotic prophase I, the limited period when PRDM9 is expressed. We also detected association of PRDM9-bound complexes with the meiotic cohesin REC8 and the synaptonemal complex proteins SYCP3 and SYCP1. Our results suggest a model in which PRDM9-bound hotspot DNA is brought to the chromosomal axis by the action of these proteins, ensuring the proper chromatin and spatial environment for subsequent recombination events.
Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer
Authors: Hiken Jeffrey F. , McDonald James I. , Decker Keith F. , Sanchez Cesar , Hoog Jeremy , VanderKraats Nathan D. , Jung Kyle L. , Akinhanmi Margaret , Ellis Matthew J. , Edwards John R.
Published: June 2016

Approximately 75% of breast cancers express estrogen receptor α (ERα) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit estrogen receptor signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the up-regulation of alternative growth signals. The mechanisms that drive this resistance—especially epigenetic events that alter gene expression—are however not well understood. Genome-wide DNA methylation and expression analysis of cell line models of acquired aromatase inhibitor resistance indicated that prostaglandin E2receptor 4(PTGER4)is up-regulated after demethylation in resistant cells. Knockdown and inhibitor studies demonstrate thatPTGER4is essential for estrogen independent growth. Analysis of downstream signaling indicates thatPTGER4likely promotes AI resistance via ligand independent activation of the ERα-cofactor CARM1. We believe that we have discovered a novel epigenetic mechanism for altering cell signaling and acquiring endocrine therapy resistance. Our findings indicate thatPTGER4is a potential drug target in AI resistant cancers. Additionally, the epigenetic component ofPTGER4regulation suggests that further study ofPTGER4may yield valuable insights into how DNA methylation-targeted diagnoses and treatments can improve AI resistant breast cancer treatment.