bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits and Profitability of Fluopyram-Amended Seed Treatments for Suppressing Sudden Death Syndrome and Protecting Soybean Yield: A Meta-Analysis
Authors: Kandel Yuba R. , McCarville Michael T. , Adee Eric A. , Bond Jason P. , Chilvers Martin I. , Conley Shawn P. , Giesler Loren J. , Kelly Heather M. , Malvick Dean K. , Mathew Febina M. , Rupe John C. , Sweets Laura E. , Tenuta Albert U. , Wise Kiersten A. , Mueller Daren S.
Published: November 2017

A meta-analytic approach was used to summarize data on the effects of fluopyram-amended seed treatment on sudden death syndrome (SDS) and yield of soybean (Glycine max L.) in over 200 field trials conducted in 12 U.S. states and Ontario, Canada from 2013 to 2015. In those trials, two treatments—the commercial base (CB), and CB plus fluopyram (CBF)—were tested, and all disease and yield data were combined to conduct a random-effects and mixed-effects meta-analysis (test of moderators) to estimate percent control and yield response relative to CB. Overall, a 35% reduction in foliar disease and 295 kg/ha (7.6%) increase in yield were estimated for CBF relative to CB. Sowing date and geographic region affected both estimates. The variation in yield response was explained partially by disease severity (19%), geographic region (8%), and sowing date (10%) but not by the resistance level of the cultivar. The probability of not offsetting the cost of fluopyram was estimated on a range of grain prices and treatment cost combinations. There was a high probability (>80%) of yield gains when disease level was high in any cost–price combinations tested but very low when the foliar symptoms of the disease were absent.
Candidates’ First-Time Performance on the Certified Nurse Educator Examination
Authors: Ortelli Tracy A.
Published: November 2017

AIM

This quantitative study examined the first-time pass/fail performance of 2,673 academic nurse educators who took the certified nurse educator (CNE) examination between September 28, 2005 and September 30, 2011.

BACKGROUND

This is the first research study designed to analyze candidates' first-time pass/fail performance on the CNE examination.

METHOD

Descriptive statistics, chi-square test of independence, Pearson's r statistic, and binary logistic regression were performed.

RESULTS

The chi-square test of independence revealed the lack of a statistically significant relationship between study participants' eligibility option and first-time pass/fail performance. Binary logistic regression revealed that a one-year increase in full-time experience resulted in a 1.05 times greater likelihood of passing the CNE examination (OR = 1.05; 95 percent CI [1.03, 1.06]; p = .00).

CONCLUSION

This study verifies the need for faculty development and mentoring for nurse educators with less than five years of full-time experience and supports recommendations for doctoral preparation.
Psychosocial Outcomes in Long-Term Cochlear Implant Users
Authors: Castellanos Irina , Kronenberger William G. , Pisoni David B.
Published: November 2017

Objectives:

The objectives of this study were to investigate psychosocial outcomes in a sample of prelingually deaf, early-implanted children, adolescents, and young adults who are long-term cochlear implant (CI) users and to examine the extent to which language and executive functioning predict psychosocial outcomes.

Design:

Psychosocial outcomes were measured using two well-validated, parent-completed checklists: the Behavior Assessment System for Children and the Conduct Hyperactive Attention Problem Oppositional Symptom. Neurocognitive skills were measured using gold standard, performance-based assessments of language and executive functioning.

Results:

CI users were at greater risk for clinically significant deficits in areas related to attention, oppositional behavior, hyperactivity–impulsivity, and social-adaptive skills compared with their normal-hearing peers, although the majority of CI users scored within average ranges relative to Behavior Assessment System for Children norms. Regression analyses revealed that language, visual–spatial working memory, and inhibition–concentration skills predicted psychosocial outcomes.

Conclusions:

Findings suggest that underlying delays and deficits in language and executive functioning may place some CI users at a risk for difficulties in psychosocial adjustment.
Risk of Hip Arthroplasty After Open Reduction Internal Fixation of a Fracture of the Acetabulum: A Matched Cohort Study
Authors: Henry Patrick D. G. , Si-Hyeong Park Sam , Paterson J. Michael , Kreder Hans J. , Jenkinson Richard , Wasserstein David
Published: November 2017

Objectives:

To determine what proportion of operatively treated acetabular fracture patients proceeded to total hip arthroplasty (THA), over what time period, and quantify the influence of patient, provider, and surgical factors on rates of THA.

Design:

Retrospective matched cohort prognostic study using administrative data.

Setting:

This study used the large population database of Ontario (population 13,125,000 in 2010), Canada.

Participants:

Patients who underwent open reduction internal fixation (ORIF) of an acetabulum fracture between 1996 and 2010 in the province of Ontario were identified from administrative health databases.

Method:

Each patient was matched to 4 individuals from the general population according to age, sex, income, and urban/rural residence. The rates of THA at 2, 5, and 10 years were compared using time-to-event analysis. The influence of patient, provider, and surgical factors on the risk of eventual THA was examined using a Cox model.

Intervention:

The primary intervention was ORIF of the acetabulum.

Main Outcome Measurement:

The primary outcome measurement was THA.

Results:

A total of 1725 eligible patients were identified and were matched to 6900 controls. Among cases, there was a 13.9% (N = 240) rate of hip arthroplasty after a median of 6.25 (interquartile range 3.5–10.1) years, compared with 0.6% (N = 38) among matched controls (relative risk = 25.26). The greatest difference in risk of eventually undergoing a THA was in the first 10 years, after which time the risk in the group that had undergone ORIF acetabulum trended down toward that of the control group. Among surgical patients, risk factors for eventual hip arthroplasty included older age [hazard ratio (HR) 1.035 (1.027, 1.044); P < 0.0001]; female sex [HR 1.65 (1.257, 2.165); P = 0.0003]. Higher surgeon volume revealed a 2.6% decreased risk of arthroplasty for each acetabulum ORIF performed above 10 per year [HR 0.974 (0.960, 0.989); P = 0.0007].

Conclusion:

Patients who underwent acetabulum fracture ORIF had a 25 times higher prevalence of hip arthroplasty compared with matched controls. THA rate was greater in women, older patients, and patients whom had ORIF performed by low-volume surgeons.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Patient Mortality in Geriatric Distal Femur Fractures
Authors: Myers Philip , Laboe Patrick , Johnson Kory J. , Fredericks Peter D. , Crichlow Renn J. , Maar Dean C. , Weber Timothy G.
Published: November 2017

Objectives:

To estimate 1-year mortality rates in elderly patients who undergo operative treatment for distal femur fractures and identify potential risk factors for mortality.

Design:

Retrospective chart review.

Setting:

Level 1 and Level 2 trauma centers.

Patients/Participants:

Two hundred eighty-three elderly patients (average age 76.0 years ± 9.8) who sustained distal femur fractures between 2002 and 2012.

Intervention:

Fracture fixation of the distal femur.

Main Outcome Measure:

Survival up to 1 year after surgery.

Results:

The 1-year mortality rate for distal femur fractures in elderly patients was 13.4%. There were no statistically significant differences in overall mortality between native bone and periprosthetic fractures, intramedullary nail or open reduction internal fixation, or across Orthopaedic Trauma Association fracture classifications. Overall patient mortality was significantly higher at 30 days (P = 0.036), 6 months (P = 0.019), and 1 year (P = 0.018), when surgery occurred more than 2 days from the injury. Mean Charlson Comorbidity Index scores were significantly lower in survivors versus nonsurvivors at all time intervals (30 days, P = 0.023; 6 months, P = 0.001 and 1 year P ≤ 0.001). A time to surgery of more than 2 days, regardless of baseline illness, did not result in improved survivability at 1 year.

Conclusions:

Overall mortality for distal femur fractures was 13.4% in the elderly population. A surgical treatment more than 2 days after injury was associated with increased patient mortality.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Should Transfusion Trigger Thresholds Differ for Critical Care Versus Perioperative Patients? A Meta-Analysis of Randomized Trials
Authors: Chong Matthew A. , Krishnan Rohin , Cheng Davy , Martin Janet
Published: November 2017

Objective:

To address the significant uncertainty as to whether transfusion thresholds for critical care versus surgical patients should differ.

Design:

Meta-analysis of randomized controlled trials.

Setting:

Medline, EMBASE, and Cochrane Library searches were performed up to 15 June 2016.

Patients:

Trials had to enroll adult surgical or critically ill patients for inclusion.

Interventions:

Studies had to compare a liberal versus restrictive threshold for the transfusion of allogeneic packed RBCs.

Measurements and Main Results:

The primary outcome was 30-day all-cause mortality, sub-grouped by surgical and critical care patients. Secondary outcomes included myocardial infarction, stroke, renal failure, allogeneic blood exposure, and length of stay. Odds ratios and weighted mean differences were calculated using random effects meta-analysis. To assess whether subgroups were significantly different, tests for subgroup interaction were used. Subgroup analysis by trials enrolling critically ill versus surgical patients was performed. Twenty-seven randomized controlled trials (10,797 patients) were included. In critical care patients, restrictive transfusion resulted in significantly reduced 30-day mortality compared with liberal transfusion (odds ratio, 0.82; 95% CI, 0.70–0.97). In surgical patients, a restrictive transfusion strategy led to the opposite direction of effect for mortality (odds ratio, 1.31; 95% CI, 0.94–1.82). The subgroup interaction test was significant (p = 0.04), suggesting that the effect of restrictive transfusion on mortality is statistically different for critical care (decreased risk) versus surgical patients (potentially increased risk or no difference). Regarding secondary outcomes, for critically ill patients, a restrictive strategy resulted in reduced risk of stroke/transient ischemic attack, packed RBC exposure, transfusion reactions, and hospital length of stay. In surgical patients, restrictive transfusion resulted in reduced packed RBC exposure.

Conclusions:

The safety of restrictive transfusion strategies likely differs for critically ill patients versus perioperative patients. Further trials investigating transfusion strategies in the perioperative setting are necessary.
Liposomal Bupivacaine in Implant-Based Breast Reconstruction
Authors: Motakef Saba , Wong Wendy W. , Ingargiola Michael J. , Nguyen David , Galdyn Izabela A. , Kim Hahns Y. , Gupta Subhas C.
Published: November 2017

Purpose:

This study evaluates the role of liposomal bupivacaine in implant-based breast reconstruction.

Methods:

A prospective, randomized, single-blind trial of liposomal bupivacaine in implant-based breast reconstruction was performed. Patients in the control arm were treated with 20 mL 0.25% bupivacaine with epinephrine 1:200,000 to each breast pocket. Patients in the experimental arm were treated with 10 mL 1.3% liposomal bupivacaine delivered to each breast pocket. Pain scores were recorded over the course of patients’ hospital stay. Consumption of pain medications, benzodiazepines, and anti-emetics was monitored. Length of stay and other direct cost data were collected.

Results:

Twenty-four patients were enrolled, with 12 women randomized to each arm. Average postoperative pain scores were 3.66 for patients in the control arm and 3.68 for patients in the experimental arm. Opioid consumption was 1.43 morphine equivalent dosing/h for patients in the control arm and 0.76 morphine equivalent dosing/h for patients in the experimental arm (P = 0.017). Diazepam consumption was 0.348 mg/h for patients in the control arm and 0.176 mg/h for patients in the experimental arm (P = 0.011). Average length of hospital stay was 46.7 hours for patients in the control arm and 29.8 hours for patients in the experimental arm (P = 0.035). Average hospital charges were $18,632 for patients in the control arm and $10,828 for patients in the experimental arm (P = 0.039).

Conclusions:

Liposomal bupivacaine reduces opioid and benzodiazepine consumption, length of stay, and hospital charges. These data support a role for liposomal bupivacaine in implant-based breast reconstruction.
Use of Indocyanine Green for Sentinel Lymph Node Biopsy: Case Series and Methods Comparison
Authors: McGregor Andrew , Pavri Sabrina N. , Tsay Cynthia , Kim Samuel , Narayan Deepak
Published: November 2017

Introduction:

Sentinel lymph node biopsy is indicated for patients with biopsy-proven thickness melanoma greater than 1.0 mm. Use of lymphoscintigraphy along with vital blue dyes is the gold standard for identifying sentinel lymph nodes intraoperatively. Indocyanine green (ICG) has recently been used as a method of identifying sentinel lymph nodes. We herein describe a case series of patients who have successfully undergone ICG-assisted sentinel lymph node biopsy for melanoma. We compare 2 imaging systems that are used for ICG-assisted sentinel lymph node biopsy.

Methods:

Fourteen patients underwent ICG-assisted sentinel lymph node biopsy for melanoma using the SPY Elite system (Novadaq, Mississigua, Canada) and the Hamamatsu PDE-Neo probe system (Mitaka USA, Park City, Utah). We analyzed costs for 2 systems that utilize ICG for sentinel lymph node biopsies.

Results:

Intraoperative use of ICG for sentinel lymph node biopsies was successful in correctly identifying sentinel lymph nodes. There was no difference between the Hamamatsu PDE-Neo probe and SPY Elite systems in the ability to detect sentinel lymph nodes; however, the former was associated with a lower operating cost and ease of use compared with the latter.

Conclusion:

ICG-assisted sentinel lymph biopsy using the SPY Elite or the Hamamatsu PDE-Neo probe systems for melanoma are comparable in terms of sentinel node detection. The Neo probe system delivers pertinent clinical data with the advantages of lower cost and ease of operation.
Feasibility of Bone Perfusion Evaluation in Cadavers Using Indocyanine Green Fluorescence Angiography
Authors: Yoshimatsu Hidehiko , Steinbacher Johannes , Meng Stefan , Hamscha Ulrike M. , Weninger Wolfgang J. , Tinhofer Ines E. , Yamamoto Takumi , Iida Takuya , Tzou Chieh-Han
Published: November 2017

Bone perfusion evaluation methods in cadaver studies have yet to be established. The aim of this report was to introduce and validate the feasibility of indocyanine green (ICG) fluorescence angiography for evaluation of bone perfusion in the femoral medial condyle in cadavers. In 4 fresh nonembalmed cadavers (2 female), the descending genicular artery was dissected and carefully cannulated bilaterally. A 10 mL solution containing 5 mL ICG solution and 5 mL methylene blue solution was injected into the descending genicular artery. After the injection, the medial femoral condyle was cut with an oscillating saw. A photograph was taken of the cut ends of the bone. The cut ends of the bones were observed using a near-infrared camera. Images corresponding to the previously taken photographs of the cut ends were captured for comparative analysis. After injection of methylene blue and ICG, the blue dye could be seen in the periosteum in all specimens, but not inside the cortex or the cancellous region of the bone. When observed with ICG fluorescence angiography, however, the cancellous region was highlighted through small perforators penetrating the periosteum. Perfusion inside the medial femoral condyle in cadavers was confirmed using ICG fluorescence angiography. Our method can be especially beneficial in confirming the bone perfusion of a new bone flap based on a particular artery, both in cadavers as well as in patients, because ICG can be injected into specific arteries.
History of High Motion Sickness Susceptibility Predicts Vestibular Dysfunction Following Sport/Recreation-Related Concussion
Authors: Sufrinko Alicia M. , Kegel Nathan E. , Mucha Anne , Collins Michael W. , Kontos Anthony P.
Published: November 2017

Objective:

To compare vestibular dysfunction at 1 to 10 and 11 to 20 days following sport/recreation-related concussion (SRC) in athletes with and without history of motion sickness susceptibility. Secondary aims of this study were to investigate differences in neurocognitive performance and affective symptoms in these groups.

Design:

Cross-sectional.

Setting:

Concussion Specialty Clinic.

Participants:

One hundred twenty-four adolescents and adults (82 males, 42 females) aged 14 to 26 (16.36 ± 2.10) years, diagnosed with SRC in the past 10 (4.56 ± 2.54) days; 47 participants composed the sample for quartile analyses.

Independent Variable:

Motion sickness susceptibility questionnaire short form score.

Main Outcome Measures:

Computerized neurocognitive test scores, vestibular/oculomotor screening scores (VOMS), and symptom factor scores from a standardized concussion symptom inventory.

Results:

There was no association between history of motion sickness susceptibility and VOMS scores (above or below clinical cutoff) at 1 to 10 days after injury, although at 11 to 20 days after injury there was an association between high motion sickness susceptibility and symptoms above clinical cutoff on 5 of the 6 VOMS items (Pvalues 0.01-0.04). The high motion sickness group had more affective symptoms on the symptom inventory than the no motion sickness group (P= 0.002) at 1 to 10 days after injury. Groups did not differ on computerized neurocognitive testing (P= 0.11).

Conclusion:

Athletes with a preexisting history of motion sensitivity may exhibit more prolonged vestibular dysfunction following SRC, and may experience more affective symptoms early in recovery.
Different Expression of Aldehyde Dehydrogenases 1A1 and 2 in Oral Leukoplakia With Epithelial Dysplasia and in Oral Squamous Cell Carcinoma
Authors: Herrera Costa Fernanda , Narana Ribeiro El Achkar Vivian , Costa Victor , Paladini Isabela , Kowalski Luiz Paulo , Rodarte Carvalho Yasmin , Kaminagakura Estela
Published: November 2017

Oral potentially malignant disorders (OPMD) may develop malignant characteristics and transform into oral squamous cell carcinoma (OSCC) in a range of 1% to 2% of cases. Chronic alcohol consumption is associated with carcinogenesis, but its mechanism has not yet been fully elucidated. ALDH1A1 and 2, isoenzymes responsible for aldehyde oxidation involved in ethanol metabolism may be associated with the development of malignant head and neck neoplasms. The aim of this study was to analyze the expression of ALDH1A1 and ALDH2 in oral leukoplakia with epithelial dysplasia (OLP) and OSCC. A retrospective study was conducted on 27 cases of OLP and 30 cases of OSCC. Clinical data were obtained from medical records, and all cases were classified as mild, moderate, and severe for OLP, and well-differentiated, moderately differentiated, or poorly differentiated for OSCC cases. The ALDH1A1 and ALDH2 expression in OLP and OSCC was evaluated by the immunohistochemical technique. There was predominance of the male sex, in both OLP and OSCC cases. Oral tongue was the most affected site in both groups. OLP showed positive protein expression of ALDH1A1 in all cases, both basal and suprabasal epithelial layers, whereas ALDH2 showed less protein expression. In OSCC, the immunohistochemical reaction for ALDH1A1 expression was negative in 70%, whereas ALDH2 expression was positive in all cases. This study demonstrated the gradual loss of ALDH1A1 expression in OSCC in comparison with OLP, and the increased ALDH2 expression in OSCC.
Luc's Abscess and Temporomandibular Joint Septic Arthritis
Authors: Tsai Carmelle , Deramo Jennifer , Shen Xiaofan , Vandiver Kathleen , Mittal Vineeta
Published: November 2017

A 5-year-old previously healthy child presented with right-sided otalgia, right facial and temporal swelling, and right jaw pain in the setting of 6 days of low-grade fever. The child had no trauma, vomiting, or prior dental treatments. On physical examination, the patient had facial swelling, erythema, and tenderness over the right temporal region along with trismus, as well as pain on palpation of the right temporomandibular joint (TMJ). A computed tomography scan revealed otitis media, Luc's abscess, and TMJ septic arthritis requiring surgical drainage and intravenous antibiotics. The patient responded well to treatment and recovered without sequelae. Dr. Cardwell Luc first described Luc's abscess in 1913 as a rare complication of middle ear infection leading to an abscess in the infratemporal space. To our knowledge, our case is the first documented case of concurrent Luc's abscess and TMJ septic arthritis in a previously healthy child as complications of acute otitis media. This case highlights 2 rare complications of a common medical condition that pediatric emergency care providers should recognize due to the need for surgical intervention, without which there may be longstanding sequelae.
Pediatric Emergency Research Canada
Authors: Bialy Liza , Plint Amy , Zemek Roger , Johnson David , Klassen Terry , Osmond Martin , Freedman Stephen B.
Published: November 2017

Objective

The objective of the study was to describe the origins, growth, and progress of a national research network in pediatric emergency medicine.

Methods

The success of Pediatric Emergency Research Canada (PERC) is described in terms of advancing the pediatric emergency medicine agenda, grant funding, peer-reviewed publications, mentoring new investigators, and global collaborations.

Results

Since 1995, clinicians and investigators within PERC have grown the network to 15 active tertiary pediatric emergency medicine sites across Canada. Investigators have advanced the research agenda in numerous areas, including gastroenteritis, bronchiolitis, croup, head injury, asthma, and injury management. Since the first PERC Annual Scientific meeting in 2004, the attendance has increased by approximately 400% to 152 attendees, 65 presentations, and 13 project/investigator meetings. More than $33 million in grant funding has been awarded to the network, and has published 76 peer-reviewed articles. In 2011, PERC's success was recognized with a Top Achievement Award in Health Research from Canadian Institutes of Health Research and the Canadian Medical Association Journal.

Conclusions

Moving forward, PERC will continue to focus on the creation of new knowledge, the mentorship of new investigators and fellows in developing research projects, and promoting a pediatric emergency medicine–focused research agenda guided by the pooling of expertise from individuals across the nation. Through collaborations with networks across the globe, PERC will continue to strive for the conduct of high-quality, impactful research that improves outcomes in children with acute illness and injury.
The Power of Academic-Practitioner Collaboration to Enhance Science and Practice Integration: Injury and Violence Prevention Case Studies
Authors: Smith L. Shakiyla , Wilkins Natalie , Marshall Stephen W. , Dellapenna Alan , Pressley Joyce C. , Bauer Michael , South Eugenia C. , Green Keith
Published: November 2017

One of the most substantial challenges facing the field of injury and violence prevention is bridging the gap between scientific knowledge and its real-world application to achieve population-level impact. Much synergy is gained when academic and practice communities collaborate; however, a number of barriers prevent better integration of science and practice. This article presents 3 examples of academic-practitioner collaborations, their approaches to working together to address injury and violence issues, and emerging indications of the impact on integrating research and practice. The examples fall along the spectrum of engagement with nonacademic partners as coinvestigators and knowledge producers. They also highlight the benefits of academic-community partnerships and the engaged scholarship model under which Centers for Disease Control and Prevention–funded Injury Control Research Centers operate to address the research-to-practice and practice-to-research gap.
Interventional Pain Procedures in Physical Medicine and Rehabilitation Residencies
Authors: Agarwal Sanjeev , Cicone Caitlin , Chang Philip
Published: November 2017

Exposure to interventional pain procedures is now a required component of training in physical medicine and rehabilitation residencies as mandated by the Accreditation Council for Graduate Medical Education. Data regarding resident exposure and competency in these procedures remain limited. Objectives were to determine the volume and type of exposure physical medicine and rehabilitation residents have to interventional pain procedures and to obtain faculty-perceived opinions regarding competency of incoming fellows as it pertains to interventional pain management. Online surveys were sent to program directors of physical medicine and rehabilitation residencies and fellowship directors of interventional spine, sports medicine, and pain medicine fellowships. Surveys inquired about educational methods, the volume of procedures in which residents actively participate, and faculty-perceived competency of trainees performing procedures. Thirty-nine residency programs and 27 fellowships responded to the surveys. Of the 39 residencies that responded, there was great variation in the exposure residents receive. Most programs reported that residents have moderate exposure to common procedures such as ultrasound-guided knee injections and lumbar epidural injections. In addition, while most residency program directors report graduates to be “fairly prepared” (33%) to “well prepared” (20.5%) with regard to spine procedures, most fellowship directors (63%) describe incoming fellows to be at the “beginner” level.
Computed Tomographic Artifacts in Maxillofacial Surgery
Authors: Kim Jun Ho , Arita Emiko Saito , Pinheiro Lucas Rodrigues , Yoshimoto Marcelo , Watanabe Plauto Christopher Aranha , Cortes Arthur Rodriguez Gonzalez
Published: November 2017

Objectives:

The present study aimed to present 4 cases and to undertake a systematic review on the current knowledge of the impact of cone beam computed tomographic (CBCT) artifacts on oral and maxillofacial surgical planning and follow-up.

Methods:

The MEDLINE (PubMed) database was searched for the period from February 2004 to February 2017, for studies on the impact of CBCT artifacts on surgical planning of oral and maxillofacial surgeries. The PRISMA statement was followed during data assessment and extraction. As a result, data extraction included information regarding: the use of CBCT to plan or follow-up oral and maxillofacial surgeries, presence and type identification of a CBCT artifact, and details on the impact of artifacts on image quality and/or surgical planning. Four cases were selected to illustrate the topic.

Results:

The search strategy yielded 408 publications in MEDLINE (PubMed). An initial screening of the publications was performed using abstracts and key words. After application of exclusion criteria, a total of 11 studies were finally identified as eligible to be discussed. Studies revealed 3 main types of artifact: beam hardening, streak, and motion artifacts. Most of the studies suggest that artifacts significantly affect oral and maxillofacial surgical planning and follow-up, despite of allowing for identification of metal projectiles in cases of maxillofacial trauma.

Conclusion:

CBCT artifacts have a significant impact on oral and maxillofacial surgical planning and follow-up.
Total Cheek Reconstruction Using the Pre-Expanded Medial Arm Flap With Functional and Aesthetic Donor Site Closure
Authors: Xue Bingjian , Liu Yuanbo , Zhu Shan , Zang Mengqing , Chen Bo , Li Shanshan
Published: November 2017

This clinical study aimed at introducing a reconstructive method for total cheek soft tissue defects using the pre-expanded medial arm flap and to maximally reduce donor site morbidities simultaneously. A retrospective review of data was performed for 3 patients requiring the pre-expanded medial arm flap to reconstruct total cheek defects. The donor site in the medial arm was primarily closed using a pedicle parascapular or thoracodorsal artery perforator flap. All patients had a total unilateral cheek defect after lesion removal. Three pre-expanded medial arm flaps measuring 17 × 11 cm, 22 × 15 cm, and 20 × 15 cm were separately used for cheek defect reconstruction. The donor sites in the medial arm were closed using a pedicle parascapular flap, measuring 22 × 9.5 cm, and 2 pedicle thoracodorsal artery perforator flaps, measuring 22 × 10 cm and 23 × 10 cm. No major complications occurred in any patient. Patients were followed up for 3, 12, and 18 months. Patients (and/or their family members) were satisfied with the final outcomes. Total cheek defect reconstruction using a pre-expanded medial arm flap, with the donor site closed using a pedicle axial back flap, can not only provide sufficient tissue for cheek resurfacing, but also guarantee primary donor site closure and could be an alternative reconstructive option for patients who have a total cheek defect.
Is Osteoplasty With Unilateral Osteotomy Effective in the Correction of the Crooked Nose?
Authors: Koçak Ilker , Gökler Ozan , Şentürk Erol
Published: November 2017

Objective:

The crooked nose is frequently observed, and a significant number of correction methods have previously been described. Nevertheless, the condition remains a challenging problem for rhinoplastic surgeons. Here, the authors present a technique that the authors have used to correct a crooked nose in selected patients.

Methods:

A total of 23 patients underwent surgery for a C-shaped crooked nose, and were followed up for an average of 11.4 months. Pre- and postoperative photographs were taken, and these were analyzed to evaluate the results.

Results:

Osteoplasty and unilateral osteotomy were carried out in all 23 patients and a spreader graft was contralaterally placed. Unilateral osteoplasty was conducted in 17 patients, while bilateral osteoplasty was performed in 6 patients. In 19 patients, a single spreader graft was sufficient, but it was necessary to use a double spreader graft in 4 patients. In summary, 23 C-shaped crooked noses were corrected with osteoplasty plus unilateral osteotomy.

Conclusions:

Osteoplasty plus unilateral osteotomy, combined with a contralateral spreader graft, is an efficient method that can be safely used in the correction of a C-shaped crooked nose.
Human Cytomegalovirus Infection Increases Both Antibody- and Non–Antibody-Dependent Cellular Reactivity by Natural Killer Cells
Authors: Michelo Clive M. , van Cranenbroek Bram , Touw Peran , Claas Frans H. J. , van der Meer Arnold , Joosten Irma
Published: November 2017

Background

Antibody-mediated rejection in solid organ transplantation is an important immunological barrier to successful long-term graft survival. Next to complement activation, natural killer (NK) cells have been implicated in the process. Human cytomegalovirus (CMV), independently associated with decreased graft survival, has a strong imprint on the immune response. Here, we assessed the effect of CMV status on alloreactive NK cell reactivity.

Methods

We compared antibody-mediated NK cell cytolytic activity (CD107a expression) and IFNγ production between healthy CMV-seropositive (n = 8) and CMV-seronegative (n = 11) individuals, in cocultures of NK cells with anti-HLA class I or rituximab (control) antibody-coated Raji cells.

Results

First, we showed that within the NKG2C+ NK cells, it is specifically the NKG2C+/A− subset that is enriched in CMV+ individuals. We then observed that in particular the NK cell antibody-dependent cell mediated cytotoxicity (ADCC), but also non-ADCC alloreactivity toward HLA-positive target cells was increased in CMV+ individuals as compared to CMV− ones. This enhanced ADCC as well as non-ADCC NK cell reactivity in CMV+ individuals was particularly characterized by a significantly higher number of ILT2+ and NKG2C+ NK cells that possessed cytolytic activity and/or produced IFNγ in response to HLA-positive target cells.

Conclusions

With regard to organ transplantation, these data suggest that CMV infection enhances NK cell alloreactivity, which may pose an additional adverse effect on graft survival, especially in the presence of donor specific antibodies.
Factors Related to Different Objects of Awareness in Alzheimer Disease
Authors: Lacerda Isabel B. , Santos Raquel L. , Neto José Pedro Simões , Dourado Marcia C.N.
Published: November 2017

Awareness of deficits is a multidimensional phenomenon described as the ability to acknowledge difficulties and impairments. We investigated whether unawareness affects distinct domains to different degrees and identified the factors related to the awareness impairment in Alzheimer Disease (AD). Using a cross-sectional design, we assessed 89 people with AD (PwAD) and their caregivers. Awareness was evaluated by scoring discrepant responses between PwAD and their caregivers across domains including cognitive functioning and health condition, functional activity impairments, emotional state, social functioning, and interpersonal relationships. The awareness of functional activity impairments domain showed a greater discrepancy compared with the other domains. Multiple regression analysis revealed that lack of awareness of cognitive functioning and health condition was related to PwAD unawareness of functional activity impairments, age, and caregiver burden. The emotional state domain was related to PwAD unawareness of functional activity impairments and depressive symptoms. There was also a relationship between the social functioning and relationships domain and caregiver burden. The functional activity impairments domain was related to deficits in the following domains: cognitive functioning and health condition, emotional state, social and emotional functioning, and PwAD self-reported quality of life. Although we observed that 1 domain can influence another, our results suggest that the factors related to each of the different objects of awareness are varied.
Global orientation in space and the lateralization of brain functions
Authors: Dieterich Marianne , Brandt Thomas
Published: November 2017

Purpose of review

The functional role of the vestibular system for multisensory orientation and sensorimotor control is reviewed with a special focus on hemispherical lateralization and its consequences for neurological disorders of higher cortical function.

Recent findings

The peripheral and central vestibular systems are bilaterally organized with ipsilateral and contralateral ascending pathways and two multisensory cortical networks in the right and left hemisphere. The vestibular cortical system shows a structural and functional lateralization with a dominance of the right hemisphere in right-handers and the left hemisphere in left-handers. Although the vestibular brainstem pathways are evenly distributed at lower pontine level, an increasing lateralization builds up because of an asymmetric number of pontine and mesencephalic crossing fibers from left to right in right-handers. This vestibular lateralization causes more frequent and more severe disorders of higher sensorimotor dysfunction in lesions of the right hemisphere such as in hemispatial neglect and the pusher syndrome.

There is evidence that multisensory higher vestibular functions including large-scale spatial orientation, spatial memory and navigation are dominated by the right temporo-parietal cortex. A beneficial result of lateralization of brain functions in healthy individuals is that it enables the individual to produce a global sensorimotor response even in case of a mismatch of the actual right and left sensory inputs. The consequence for neurology, however, is that lesions in the dominant hemisphere cause more frequently and more severe disorders such as the visuo-spatial hemineglect and the pusher syndrome.
Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype
Authors: Oushy Soliman , Hellwinkel Justin E. , Wang Mary , Nguyen Ger J. , Gunaydin Dicle , Harland Tessa A. , Anchordoquy Thomas J. , Graner Michael W.
Published: November 2017

Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities. We incubated NHAs with GBM EVs and examined the astrocytes for changes in cell migration, cytokine release and tumour cell growth promotion via the conditioned media. We measured alterations in intracellular signalling and transformation capacity (astrocyte growth in soft agar). GBM EV-treated NHAs displayed increased migratory capacity, along with enhanced cytokine production which promoted tumour cell growth. GBM EV-treated NHAs developed tumour-like signalling patterns and exhibited colony formation in soft agar, reminiscent of tumour cells themselves. GBM EVs modify the local environment to benefit the tumour itself, co-opting neighbouring astrocytes to promote tumour growth, and perhaps even driving astrocytes to a tumourigenic phenotype. Such biological activities could have profound impacts in the recurrent GBM setting.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Why the need and how to approach the functional diversity of extracellular vesicles
Authors: Tkach Mercedes , Kowal Joanna , Théry Clotilde
Published: November 2017

In the past decade, cell-to-cell communication mediated by exosomes has attracted growing attention from biomedical scientists and physicians, leading to several recent publications in top-tier journals. Exosomes are generally defined as secreted membrane vesicles, or extracellular vesicles (EVs), corresponding to the intraluminal vesicles of late endosomal compartments, which are secreted upon fusion of multi-vesicular endosomes with the cell's plasma membrane. Cells, however, were shown to release other types of EVs, for instance, by direct budding off their plasma membrane. Some of these EVs share with exosomes major biophysical and biochemical characteristics, such as size, density and membrane orientation, which impose difficulties in their efficient separation. Despite frequent claims in the literature, whether exosomes really display more important patho/physiological functions, or are endowed with higher potential as diagnostic or therapeutic tools than other EVs, is not yet convincingly demonstrated. In this opinion article, we describe reasons for this lack of precision knowledge in the current stage of the EV field, we review recently described approaches to overcome these caveats, and we propose ways to improve our knowledge on the respective functions of distinct EVs, which will be crucial for future development of well-designed EV-based clinical applications.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Functional role of extracellular vesicles and lipoproteins in the tumour microenvironment
Authors: Menard Julien A. , Cerezo-Magaña Myriam , Belting Mattias
Published: November 2017

Cancer can be regarded as an invasive organ that exhibits unique plasticity provided by coordinated, cancer cell-stromal cell communication in the tumour microenvironment. Typical stress factors in the tumour niche, such as hypoxia and acidosis, are major drivers and modulators of these events. Recent findings reveal an important role of extracellular vesicles and lipoproteins in cancer cell adaption to exogenous stress. Adaptive mechanisms include stimulation of angiogenesis and increased metastasis. Here, we will discuss the similarities and distinct features of these endogenous nanoparticles and their roles as signalosomes and nutrient sources in cancer. We will focus on the accumulating evidence for a central role of cell-surface heparan sulphate proteoglycans in the uptake of extracellular vesicles and lipoproteins.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Tumour–adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles
Authors: Robado de Lope Lucía , Alcíbar Olwen Leaman , Amor López Ana , Hergueta-Redondo Marta , Peinado Héctor
Published: November 2017

During metastasis, tumour cells must communicate with their microenvironment by secreted soluble factors and extracellular vesicles. Different stromal cell types (e.g. bone marrow–derived cells, endothelial cells and fibroblasts) influence the growth and progression of tumours. In recent years, interest has extended to other cell types in the tumour microenvironment such as adipocytes and adipose tissue–derived mesenchymal stem cells. Indeed, obesity is becoming pandemic in some developing countries and it is now considered to be a risk factor for cancer progression. However, the true impact of obesity on the metastatic behaviour of tumours is still not yet fully understood. In this ‘Perspective’ article, we will discuss the potential influence of obesity on tumour metastasis, mainly in melanoma, breast and ovarian cancer. We summarize the main mechanisms involved with special attention to the role of extracellular vesicles in this process. We envisage that besides having a direct impact on tumour cells, obesity systemically preconditions the tumour microenvironment for future metastasis by favouring the formation of pro-inflammatory niches.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
MicroRNAs and miRceptors: a new mechanism of action for intercellular communication
Authors: Fabbri Muller
Published: November 2017

MicroRNAs (miRs) are small non-coding RNAs (ncRNAs) that control the expression of target genes by modulating (usually inhibiting) their translation into proteins. This ‘traditional’ mechanism of action of miRs has been recently challenged by new discoveries pointing towards a role of miRs as ‘hormones’, capable of binding to proteic receptors (miRceptors) and triggering their downstream signalling pathways. These findings harbour particular significance within the tumour microenvironment (TME), defined as the variety of non-cancerous cells surrounding cancer cells, but are relevant also for other diseases. In recent years it has become clearer that the TME does not passively assist the growth of cancer cells but contributes to its biology. Some of the mediators of the intercellular communication between cancer cells and TME are miRs shuttled within exosomes, a subtype of cellular released extracellular vesicles. This article will highlight the most recent findings on the biological implications of miR–miRceptor interactions for the biology of the TME and other diseases, and will provide some perspectives on the future development of this fascinating research.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
An apoptosis-driven ‘onco-regenerative niche’: roles of tumour-associated macrophages and extracellular vesicles
Authors: Gregory Christopher D. , Paterson Margaret
Published: November 2017

The cell-death programme, apoptosis, is well established as a tumour suppressor mechanism. Paradoxically, high levels of apoptosis in tumours are closely coupled with poor prognosis. Indeed, where it has been studied, cell loss is a striking feature of high-grade cancers, illustrating the importance of considering malignant disease as an imbalance between cell gain and cell loss that favours cell gain rather than as a unidirectional disorder of cell gain alone. In addition to orchestrating cell loss, apoptosis can signal regenerative responses—for example compensatory proliferation—in neighbouring cells. Accumulating evidence suggests that normal tissue repair and regenerative processes are hijacked in the malignant tissue microenvironment such that cancer may be likened to a ‘wound that fails to stop repairing’. We have proposed that a critical requirement for the successful growth, progression and re-growth of malignant tumours is a complex milieu, conceptually termed the ‘onco-regenerative niche’, which is composed, in addition to transformed neoplastic cells, of a network of normal cells and factors activated as if in tissue repair and regeneration. Our work is based around the hypothesis that tumour cell apoptosis, macrophage activation and endothelial activation are key, interlinked elements of the onco-regenerative niche and that apoptotic tumour cell–derived extracellular vesicles provide critical intercellular communication vehicles of the niche. In aggressive B-cell lymphoma, tumour cell apoptosis promotes both angiogenesis and the accumulation of pro-tumour macrophages in the lymphoma microenvironment. Furthermore, apoptotic lymphoma-derived extracellular vesicles have potent pro-tumour potential. These findings have important implications for the roles of apoptosis in regulation of malignant diseases and for the efficacy of apoptosis-inducing anti-cancer therapies.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.
Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells
Authors: Samuel Priya , Mulcahy Laura Ann , Furlong Fiona , McCarthy Helen O. , Brooks Susan Ann , Fabbri Muller , Pink Ryan Charles , Carter David Raul Francisco
Published: November 2017

Ovarian cancer has a poor overall survival that is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naive cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested. Here we show that treatment of cells with cisplatin led to the release of EVs that could induce invasion and increased resistance when taken up by bystander cells. This coincided with changes in p38 and JNK signalling, suggesting that these pathways may be involved in mediating the effects. We also show that EV uptake inhibitors could prevent this EV-mediated adaptive response and thus sensitize cells
in vitro
to the effects of cisplatin. Our results suggest that preventing pro-tumourigenic EV cross-talk during chemotherapy is a potential therapeutic target for improving outcome in ovarian cancer patients.

This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.