bluuebunny/crossref_metadata_2025 huggingface dataset:
CE: Original Research: Pain in Nonverbal Children with Medical Complexity: A Two-Year Retrospective Study
Authors: Quinn Brenna L. , Solodiuk Jean C. , Morrill Dominick , Mauskar Sangeeta
Published: July 2018

Purpose: Children with medical complexity experience frequent pain. But it can be challenging to recognize unexpected behaviors as pain related, especially in the absence of self-report. Often these children undergo extensive workups aimed at diagnosing the sources of pain. This study had three objectives: to describe the signs and symptoms parents of nonverbal children with medical complexity found worrisome, to describe the sources of pain in these children, and to describe nursing pain assessment practices in this population.

Design and methods: Retrospective chart review was used to identify the initial presenting symptoms, sources of pain, and nursing documentation for 46 children with medical complexity who were admitted with a chief concern of pain to a 395-bed pediatric teaching hospital in the northeastern United States.

Results: Irritability, pain, feeding intolerance, and “not acting like herself [or himself]” were common parent-reported symptoms that prompted further evaluation. On average, five diagnostic studies were taken to identify a source of pain, and four specialty services were consulted during the admission. Nursing assessments of pain were documented approximately every three hours; the mean pain intensity score documented was 1.1 out of 10. The discharge diagnoses included infection (including urinary tract infection), seizures, constipation, chronic pain, failure to thrive, dehydration, and subdural hematoma.

Conclusions: The discharge diagnoses covered a wide range. A systematic approach to pain evaluation could help to ensure that the diagnostic process is both thorough and efficient. Common childhood ailments such as constipation or urinary tract infection, as well as other causes, must be considered when diagnosing pain in this population. Practice implications include consulting parents regarding changes in a child's behavior.
The Effect of Fluid Loading and Hypertonic Saline Solution on Cortical Cerebral Microcirculation and Glycocalyx Integrity
Authors: Dostalova Vlasta , Astapenko David , Dostalova Vlasta , Kraus Jaroslav , Cerny Vladimir , Ticha Alena , Hyspler Radomir , Radochova Vera , Paral Jiri , Dostal Pavel
Published: July 2018

Background:

Fluid loading and hyperosmolar solutions can modify the cortical brain microcirculation and the endothelial glycocalyx (EG). This study compared the short-term effects of liberal fluid loading with a restrictive fluid intake followed by osmotherapy with hypertonic saline (HTS) on cerebral cortical microcirculation and EG integrity in a rabbit craniotomy model.

Methods:

The experimental rabbits were allocated randomly to receive either <2 mL/kg/h (group R, n=14) or 30 mL/kg/h (group L, n=14) of balanced isotonic fluids for 1 hour. Then, the animals were randomized to receive 5 mL/kg intravenous infusion of either 3.2% saline (group HTS, n=14) or 0.9% saline (group normal saline, n=13) in a 20-minute infusion. Microcirculation in the cerebral cortex based on sidestream dark-field imaging, a morphologic index of glycocalyx damage to sublingual and cortical brain microcirculation (the perfused boundary region), and serum syndecan-1 levels were evaluated.

Results:

Lower cortical brain perfused small vessel density (P=0.0178), perfused vessel density (P=0.0286), and total vessel density (P=0.0447) were observed in group L, compared with group R. No differences were observed between the HTS and normal saline groups after osmotherapy. Cerebral perfused boundary region values (P=0.0692) and hematocrit-corrected serum syndecan-1 levels (P=0.0324) tended to be higher in group L than in group R animals.

Conclusions:

Liberal fluid loading was associated with altered cortical cerebral microcirculation and EG integrity parameters. The 3.2% saline treatment did not affect cortical cerebral microcirculation or EG integrity markers.
Solitary Plasmacytoma of Bone of the Spine
Authors: Wang Yufu , Li Hui , Liu Chao , Chen Chao , Yan Jinglong
Published: July 2018

Study Design.

Retrospective analysis.

Objective.

To determine the prognostic indicators in patients with solitary plasmacytoma of bone (SPB) of the spine.

Summary of Background Data.

Population-level estimates for prognosis among patients with SPB of the spine are still lacking. Sociodemographic and clinical predictors of outcome have not been well characterized.

Methods.

The Surveillance, Epidemiology, and End Results Registry was used to identify all patients with SPB of the spine from 1995 through 2014. Associated population data were used to determine annual incidence and limited-duration prevalence. Overall survival (OS) estimates were obtained using the Kaplan–Meier method and compared across groups using log-rank test. A Cox regression model was used for multivariate analysis of survival. Logistic regression was performed to identify predictors of the progression to multiple myeloma (MM).

Results.

The incidence and prevalence of the disease increased during the study period. Spinal SPB most commonly affected older people (>50) with a male preponderance. The median OS were 74.0 months. The 5 and 10-year survival rates for these patients were 56.1% and 36.7%, respectively. On multivariable analyses, older age, and surgery without radiotherapy were correlated with poor survival of patients with spinal SPB. The 3-year probability of progression to MM was 10.1%. Patients aged >70 years were associated with progression to MM. There was no significant association between the methods of surgical resection (radical or local/partial) and OS or progression to MM.

Conclusion.

The findings of this study provide population-based estimates of the incidence, prevalence and prognosis for patients with SPB of the spine. This analysis indicated that the only identifiable prognostic indicators were older age and surgery without radiotherapy. Moreover, the methods of surgical resection did not influence the OS or progression to MM.

Level of Evidence: 4
Development of a Modified Cervical Deformity Frailty Index
Authors: Passias Peter G. , Bortz Cole A. , Segreto Frank A. , Horn Samantha R. , Lafage Renaud , Lafage Virginie , Smith Justin S. , Line Breton , Kim Han Jo , Eastlack Robert , Hamilton David Kojo , Protopsaltis Themistocles , Hostin Richard A. , Klineberg Eric O. , Burton Douglas C. , Hart Robert A. , Schwab Frank J. , Bess Shay , Shaffrey Christopher I. , Ames Christopher P.
Published: July 2018

Study Design.

Retrospective review.

Objective.

Develop a simplified frailty index for cervical deformity (CD) patients.

Summary of Background Data.

To improve preoperative risk stratification for surgical CD patients, a CD frailty index (CD-FI) incorporating 40 health deficits was developed. While novel, the CD-FI is clinically impractical due to the large number of factors needed for its calculation. To increase clinical utility, a simpler, modified CD-FI (mCD-FI) is necessary.

Methods.

CD patients (C2-C7 Cobb>10°, CL>10°, cSVA>4 cm, or CBVA>25°) >18 year with preoperative CD-FI component factors. Pearson bivariate correlation assessed relationships between component deficits of the CD-FI and overall CD-FI score. Top deficits contributing to CD-FI score were included in multiple stepwise regression models. Deficits from model with largest R2 were dichotomized, and the mean score of all deficits calculated, resulting in mCD-FI score from 0 to 1. Patients were stratified by mCD-FI: Not Frail (NF, <0.3), Frail (0.3–0.5), Severely Frail (SF, >0.5). Means comparison tests established correlations between frailty category and clinical outcomes.

Results.

Included: 121 CD patients (61 ± 11 yr, 60%F). Multiple stepwise regression models identified 15 deficits as responsible for 86% of the variation in CD-FI; these factors were used to construct the mCD-FI. Overall, mean mCD-FI was 0.31 ± 0.14. Breakdown of patients by mCD-FI category: NF: 47.9%, Frail: 46.3%, SF: 5.8%. Compared with NF and Frail, SF patients had the longest inpatient hospital stays (P = 0.042), as well as greater baseline neck pain (P = 0.033), inferior Neck Disability Index scores (P<0.001) and inferior EQ-5D scores (P < 0.001). Frail patients had higher odds of superficial infection (OR:1.1[1.0–1.2]), and SF patients had increased odds of mortality (OR:8.3[1.3–53.9]).

Conclusion.

Increased frailty, assessed by mCD-FI, correlated with increased length of stay, neck pain, and decreased health-related quality of life. Frail patients were at greater risk for infection, and severely frail patients had greater odds of mortality. This relationship between frailty and clinical outcomes suggests that mCD-FI offers clinical utility as a preoperative risk stratification tool.

Level of Evidence: 3
The Natural Course of Compensatory Lumbar Curves in Nonoperated Patients With Thoracic Adolescent Idiopathic Scoliosis
Authors: Ohashi Masayuki , Watanabe Kei , Hirano Toru , Hasegawa Kazuhiro , Katsumi Keiichi , Shoji Hirokazu , Mizouchi Tatsuki , Takahashi Ikuko , Endo Naoto
Published: July 2018

Study Design.

A retrospective, long-term follow-up study.

Objective.

We investigated the natural course of compensatory lumbar curves in patients with primary thoracic adolescent idiopathic scoliosis (AIS).

Summary of Background Data.

The natural course of compensatory lumbar curves in primary thoracic AIS remains unknown.

Methods.

Inclusion criteria were right-sided primary thoracic AIS ≥30° with a Lenke lumbar modifier of A or B at skeletal maturity and ≥30 years of age at the time of the survey. Fifty-one patients (mean age, 40.2 yr) returned for a follow-up evaluation (follow-up rate, 34.2%). Patients were classified into three groups based on the lumbar modifier (A or B) and direction of L4 tilt [right (R) or left (L)] (AR, n.11; AL, n.18; and B, n.22). At the time of the survey, 42 patients underwent radiological examinations and 37 underwent lumbar magnetic resonance imaging. Quality of life questionnaires were completed in all patients and in a 1:1 matched control group (no history of scoliosis).

Results.

The thoracic curves had significantly progressed in all patient groups, while the compensatory lumbar curve progressed only in the B group. The C7 translation and L4 tilt shifted to the right in the AR and AL groups, but did not change in the B group. As a result, the L4 tilt (median, 11°) and C7 translation (18.6 mm) tended to be the greatest in the AR group. The incidences of Modic changes at L4/5 discs and ≥3 cm on the visual analogue scale for low back pain were significantly higher in the AR group (77.8% and 54.5%, respectively) compared with that in the other groups.

Conclusion.

The natural course of compensatory lumbar curves is dependent on the lumbar modifier and direction of L4 tilt. Adolescent patients with right-sided primary thoracic AIS (≥30°) with L4 tilted to the right should be considered for periodic follow-ups into adulthood.

Level of Evidence: 4
Evaluating the Cross-Cultural Adaptation, Reliability, and Validity of the Persian Versions of the Copenhagen Neck Function Disability Scale and Neck Bournemouth Questionnaire
Authors: Ghasemi Fateme , Kordi Yoosefinejad Amin , Pirouzi Soraya , Ghaem Haleh
Published: July 2018

Study Design.

A cross-sectional study.

Objective.

To evaluate cross-cultural adaptation and psychometric properties of the Copenhagen Neck Function Disability Scale (CNFDS) and Neck Bournemouth Questionnaire (NBQ) in patients with chronic nonspecific neck pain.

Summary of Background Data.

CNFDS and NBQ are among the most popular scales to investigate aspects of life in patients with chronic neck pain. To date, the Persian versions of these scales have not been validated.

Methods.

Following the translation process, the questionnaires were given to 106 patients with chronic nonspecific neck pain. To evaluate reliability, Cronbach alpha and test–retest reliability were evaluated. To investigate construct validity, the Neck Disability Index (NDI) and Neck Pain Disability Scale (NPDS) were used. Internal consistency of the scales was evaluated with exploratory factor analysis.

Results.

No missing data were observed for the NBQ, and missing data affected 0% to 3% of the CNFDS items. There were no floor or ceiling effects. Cronbach alpha was 0.92 for the CNFDS and 0.95 for the NBQ. Test–retest reliability was estimated as 0.86 for the CNFDS and 0.91 for the NBQ. The CNFDS correlated very well with the NDI pain subscale, and the NPDS. The NBQ correlated very well with the NPDS and NDI, and correlated well with the CNFDS and its subscales. Exploratory factor analysis detected three dimensions for the CNFDS and confirmed unidimensionality of the NBQ.

Conclusion.

The Persian versions of the CNFDS and NBQ have acceptable validity and reliability for use with Persian-speaking patients with chronic nonspecific neck pain.

Level of Evidence: 2
Revised Cardiac Risk Index as a Predictor for Myocardial Infarction and Cardiac Arrest Following Posterior Lumbar Decompression
Authors: Bronheim Rachel S. , Oermann Eric K. , Bronheim David S. , Caridi John M.
Published: July 2018

Study Design.

A retrospective analysis of prospectively collected data.

Objective.

The aim of this study was to determine the ability of Revised Cardiac Risk Index (RCRI) to predict adverse cardiac events following posterior lumbar decompression (PLD).

Summary of Background Data.

PLD is an increasingly common procedure used to treat a variety of degenerative spinal conditions. The RCRI is used to predict risk for cardiac events following noncardiac surgery. There is a paucity of literature that directly addresses the relationship between RCRI and outcomes following PLD, specifically, the discriminative ability of the RCRI to predict adverse postoperative cardiac events.

Methods.

ACS-NSQIP was utilized to identify patients undergoing PLD from 2006 to 2014. Fifty-two thousand sixty-six patients met inclusion criteria. Multivariate and ROC analysis was utilized to identify associations between RCRI and postoperative complications.

Results.

Membership in the RCRI=1 cohort was a predictor for myocardial infarction (MI) [odds ratio (OR) = 3.3, P = 0.002] and cardiac arrest requiring cardiopulmonary resuscitation (CPR) (OR = 3.4, P = 0.013). Membership in the RCRI = 2 cohort was a predictor for MI (OR = 5.9, P = 0.001) and cardiac arrest requiring CPR (OR = 12.5), Membership in the RCRI = 3 cohort was a predictor for MI (OR = 24.9) and cardiac arrest requiring CPR (OR = 26.9, P = 0.006). RCRI had a good discriminative ability to predict both MI [area under the curve (AUC) = 0.876] and cardiac arrest requiring CPR (AUC = 0.855). The RCRI had a better discriminative ability to predict these outcomes that did ASA status, which had discriminative abilities of “fair” (AUC = 0.799) and “poor” (AUC = 0.674), respectively. P < 0.001 unless otherwise specified.

Conclusion.

RCRI was predictive of cardiac events following PLD, and RCRI had a better discriminative ability to predict MI and cardiac arrest requiring CPR than did ASA status. Consideration of the RCRI as a component of preoperative surgical risk stratification can minimize patient morbidity and mortality. Studies such as this can allow for implementation of guidelines that better estimate the preoperative risk profile of surgical patients.

Level of Evidence: 3
Dose Reduction Protocol for Full Spine X-ray Examination Using Copper Filters in Patients With Adolescent Idiopathic Scoliosis
Authors: Minehiro Kaori , Demura Satoru , Ichikawa Katsuhiro , Sasagawa Takeshi , Takahashi Naoki , Minami Syuhei , Murakami Hideki , Tsuchiya Hiroyuki
Published: July 2018

Study Design.

A prospective case series.

Objective.

The aim of this study was to assess a new protocol for full spine X-ray using copper (Cu) filters to reduce radiation exposure in patients with adolescent idiopathic scoliosis (AIS).

Summary of Background Data.

Radiation exposure is associated with an increased risk of cancer development in children. To reduce the radiation exposure without compromising the image quality using existing radiographic equipment, a new computed radiography protocol was optimized using a variety of heavy metal filters.

Methods.

Study 1: Whole spine radiographs were obtained using a human body phantom, and radiation doses without and with 0.1, 0.2, and 0.3 mm thick Cu filters were compared. Study 2: Patients with AIS who underwent posterior fusion were radiographically evaluated at follow-ups; the X-ray protocols with or without the use of 0.2-mm Cu filters were alternated between consecutive follow-ups. The image quality was independently evaluated using six points in the anterior–posterior (AP) view and seven in the lateral [left–right (LR)] view by three spine surgeons using a three-point grading system.

Results.

Study 1: The surface doses while obtaining nonfiltered X-rays in AP and LR views were 0.31 and 0.93 mGy, respectively, whereas those with 0.1-, 0.2-, and 0.3-mm Cu filters were 0.16 and 0.52, 0.11 and 0.36, and 0.08 and 0.27 mGy, respectively.

Study 2: In patients with AIS, the percentage of grade 3 scores (both endplates were identifiable) on AP-view images was 85% with nonfiltered X-rays and 75% with the filtered X-rays. However, there were no significant differences between the two protocols. On LR images, the frequency of grade 3 scores was significantly lower at Th2 and Th12 on filtered images than on nonfiltered ones.

Conclusion.

Whole spine radiographs using 0.2-mm Cu filters in patients with AIS could reduce radiation exposure more than 60% while preserving the image quality.

Level of Evidence: 4
Subjective Versus Objective Measures of Medication Adherence in Adolescents/Young Adults with Attention-Deficit Hyperactivity Disorder
Authors: Schaefer Megan R. , Wagoner Scott T. , Young Margaret E. , Rawlinson Alana Resmini , Kavookjian Jan , Shapiro Steven K. , Gray Wendy N.
Published: July 2018

Objective:

To examine the frequency of medication nonadherence using both objective and subjective data and to compare the differences between these measures in adolescents and young adults (AYAs) with attention-deficit hyperactivity disorder (ADHD).

Method:

Fifty-four participants enrolled. Frequency (mean percent of prescribed doses not taken) of nonadherence was measured using subjective (visual analog scale) and objective (pill count and electronic monitoring) methods. Differences between measures were compared using t tests and analysis of variances.

Results:

Objective measures showed that participants missed 40% to 43% of their prescribed doses. Contrastingly, subjective measures indicated that participants missed 25% of their prescribed doses. Frequency of nonadherence was significantly higher when relying on objective measures rather than on subjective measures (t[46] = −4.51, p < 0.01 for pill counts, and t[47] = −4.81, p < 0.01 for electronic monitoring).

Conclusion:

Nonadherence is high in AYAs with ADHD. These individuals tend to overestimate their adherence when self-reporting. Physicians should exercise caution when prescribing based on patient report of adherence and use objective measures when possible.
Early Phacoemulsification After Acute Angle Closure in Patients With Coexisting Cataract
Authors: Römkens Hellen C.S. , Beckers Henny J.M. , Schouten Jan S.A.G. , Nuijts Rudy M.M.A. , Berendschot Tos T.J.M. , Breusegem Christophe M. , Webers Carroll A.B.
Published: July 2018

Purpose:

The purpose of this study is to evaluate the effect of early phacoemulsification on the management of acute angle closure glaucoma in patients with coexisting cataract after initial treatment with medical therapy and laser peripheral iridotomy.

Patients and Methods:

This study involved a retrospective analysis of patients presenting to the Maastricht University Medical Center+ with acute angle closure and coexisting cataract between 2005 and 2015. Patients were included after initial treatment with a standard protocol comprising topical and systemic medical therapy and laser peripheral iridotomy. Patients underwent small-incision phacoemulsification with intraocular lens implantation into the capsular bag by experienced surgeons within 3 months of the acute angle closure episode. The effect on intraocular pressure, number of glaucoma medications, visual acuity, and complications was assessed.

Results:

A total 35 patients were included in the study (mean age, 71±10 y; 20% male; mean refractive error, +1.6±1.8 diopters). The mean duration between acute angle closure episode and phacoemulsification was 37±22 days. There were no complications. Intraocular pressure decreased in all patients from 17.0±8.2 mm Hg to 13.2±3.9 mm Hg after 3 months (P=0.008), whereas the mean number of glaucoma medications decreased from 2.9±1.1 to 0.7±0.9 (P<0.001), with 56% of patients discontinuing all medications. Visual acuity improved from 0.9±0.9 logMAR to 0.2±0.3 logMAR (P<0.001).

Conclusions:

Early phacoemulsification with intraocular lens implantation results in a reduced intraocular pressure and number of glaucoma medications after an acute angle closure glaucoma crisis in patients with coexisting cataract. Although surgery may be challenging, the results are promising, with significant improvement in visual acuity in most patients.
Neuropathic pain clinical trials: factors associated with decreases in estimated drug efficacy
Authors: Finnerup Nanna B. , Haroutounian Simon , Baron Ralf , Dworkin Robert H. , Gilron Ian , Haanpaa Maija , Jensen Troels S. , Kamerman Peter R. , McNicol Ewan , Moore Andrew , Raja Srinivasa N. , Andersen Niels T. , Sena Emily S. , Smith Blair H. , Rice Andrew S.C. , Attal Nadine
Published: July 2018

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. This study is a secondary analysis of data from a previous published NeuPSIG systematic review and meta-analysis, updated to include studies published up till March 2017. We included double-blind, randomized, placebo-controlled trials examining the effect of drugs for which we had made strong or weak recommendations for use in neuropathic pain in the previously published review. As the primary outcome, we used an aggregated number needed to treat for 50% pain reduction (alternatively 30% pain reduction or moderate pain relief). Analyses involved 128 trials. Number needed to treat values increased from around 2 to 4 in trials published between 1982 and 1999 to much higher (less effective) values in studies published from 2010 onwards. Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses.
Isolated nociceptors reveal multiple specializations for generating irregular ongoing activity associated with ongoing pain
Authors: Odem Max A. , Bavencoffe Alexis G. , Cassidy Ryan M. , Lopez Elia R. , Tian Jinbin , Dessauer Carmen W. , Walters Edgar T.
Published: July 2018

Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors, but rodent models of pain-related OA have concentrated on allodynia rather than ongoing pain, and on OA generated in non-nociceptive Aβ fibers rather than C-fiber nociceptors. Little is known about how ongoing pain or nociceptor OA is generated. To define neurophysiological alterations underlying nociceptor OA, we have used isolated dorsal root ganglion neurons that continue to generate OA after removal from animals displaying ongoing pain. We subclassify OA as either spontaneous activity generated solely by alterations intrinsic to the active neuron or as extrinsically driven OA. Both types of OA were implicated previously in nociceptors in vivo and after isolation following spinal cord injury, which produces chronic ongoing pain. Using novel automated algorithms to analyze irregular changes in membrane potential, we have found, in a distinctive, nonaccommodating type of probable nociceptor, induction by spinal cord injury of 3 alterations that promote OA: (1) prolonged depolarization of resting membrane potential, (2) a hyperpolarizing shift in the voltage threshold for action potential generation, and (3) an increase in the incidence of large depolarizing spontaneous fluctuations (DSFs). Can DSFs also be enhanced acutely to promote OA in neurons from uninjured animals? A low dose of serotonin failed to change resting membrane potential but lowered action potential threshold. When combined with artificial depolarization to model inflammation, serotonin also strongly potentiated DSFs and OA. These findings reveal nociceptor specializations for generating OA that may promote ongoing pain in chronic and acute conditions.
Inflammation induces Epac-protein kinase C alpha and epsilon signaling in TRPV1-mediated hyperalgesia
Authors: Gu Yanping , Li Guangwen , Huang Li-Yen Mae
Published: July 2018

The exchange proteins activated by cAMP (Epacs) have been shown to play important roles in producing inflammation-induced nociception. Transient receptor potential vanilloid type 1 (TRPV1) is a major receptor processing thermal and chemosensitive nociceptive information. The role of Epacs in modulating the activity of TRPV1 has yet to be determined. Studying the effect of complete Freund adjuvant (CFA)-induced inflammation on capsaicin-activated TRPV1 nociceptive responses in dorsal root ganglia (DRG), we found that CFA produced a large increase in capsaicin-induced responses. The increase was inhibited by Epac1 and Epac2 antagonists. Thus, activation of Epacs is critical in producing enhancement in TRPV1-mediated responses under inflammatory conditions. In addition, the inflammation-induced enhancement of TRPV1 responses was blocked by PKCα and PKCε inhibitors, suggesting the essential roles of these PKCs in enhancing TRPV1 responses. To determine the mechanism underlying the Epac actions on TRPV1, we studied the effects of the Epac activator, 8-(4-chlorophenylthio)-2-O-methyl-cAMP (CPT), on capsaicin-induced nociceptive behavioral responses, capsaicin-activated currents, expression and membrane trafficking of PKC and TRPV1 in DRG. CPT was found to enhance capsaicin-induced nociception and ionic currents. The enhancement was inhibited by PKCα and PKCε inhibitors. In addition, CPT increased the expression of phosphorylated PKCα (pPKCα) and membrane TRPV1 expression in DRG. Studying the colocalization of TRPV1 and pPKCα or pPKCε in DRG slices prepared from CFA-treated rats, we found that pPKCα or pPKCε expressed with TRPV1 in different-sized neurons to exert differential influences on TRPV1 activity. Thus, Epac–PKC signaling is critically important in producing inflammation-induced potentiation of TRPV1 functions.
Exclusive enteral nutrition in pediatric inflammatory bowel disease
Authors: Miller Talya , Suskind David L.
Published: July 2018

Purpose of review

Nutritional interventions play a central role in the treatment and management of inflammatory bowel disease (IBD) in children. Although malnutrition is a common presenting sign of IBD, nutritional interventions have focused not only on correction of the malnourished state but also on treatment of the primary disease.

Recent findings

Exclusive enteral nutrition (EEN) has been the primary therapy utilized in pediatric IBD specifically, Crohn's disease. This intervention provides total calories from formula meeting complete macronutrient and micronutrient needs for a patient. EEN has been shown to improve growth and correct micronutrient deficiencies as well as improve comorbid conditions like osteopenia and anemia. EEN has also been shown to be equally as efficacious as steroids in inducing remission with better mucosal healing.

EEN is a primary therapy in IBD. Both the North American and European Societies of Pediatric Gastroenterology, Hepatology and Nutrition consider EEN as first line therapy for inducing remission in Crohn's disease.
Feeding tubes in children
Authors: Volpe Andrea , Malakounides Georgina
Published: July 2018

Purpose of review

A practical guide to different feeding tubes available for nutritional support in children, focused on indications, placement methods and complications.

Recent findings

Enteral nutritional support refers to the delivery of nutrition into the gastrointestinal tract distal to the oesophagus. Different feeding tubes are available for exclusive or supplemental nutritional support in children who are unable to independently sustain their own growth, nutritional and hydration status. Gastric feeding is the first choice; however, jejunal feeding provides a good alternative route in the presence of contraindications or intolerance. Feeding tubes can be short or long term: nasogastric and nasojejunal tubes provide short-term nutrition support, gastrostomy and jejunostomy tubes, long-term enteral feeding. The latter are established surgically through the formation of a stoma, an artificial connection between gastric or jejunal lumen and the abdominal wall, performed either endoscopically (percutaneous endoscopic gastrostomy, percutaneous endoscopic gastrojejunostomy) or surgically (gastrostomy, direct jejunostomy). Awareness of different available options, technical considerations and potential risks will inform the decision-making process for an individual patient to ensure the correct balance between adequate enteral nutritional and unnecessary morbidity.

Successful administration of nutrition support requires knowledge of the correct indication, route and specific functional details of the appropriate feeding tube.
Initial Assessment of a Prototype 3D Cone-Beam Computed Tomography System for Imaging of the Lumbar Spine, Evaluating Human Cadaveric Specimens in the Upright Position
Authors: Benz Robyn Melanie , Harder Dorothee , Amsler Felix , Voigt Johannes , Fieselmann Andreas , Falkowski Anna Lucja , Stieltjes Bram , Hirschmann Anna
Published: July 2018

Objectives

The aims of this study were to assess feasibility, image quality, and radiation dose and to estimate the optimal dose protocol for the lumbar spine of cadaveric specimens with different body mass indices (BMIs) in the upright position using a prototype 3-dimensional cone-beam computed tomography (CT) software implemented on a robotic x-ray system and compare with CT.

Materials and Methods

The lumbar spine of 5 formalin-fixed human cadaveric specimens (BMI, 22–35 kg/m2) was prospectively assessed in the upright position using prototype software for 3-dimensional tomography implemented on a robotic x-ray system. Specimens were scanned with varying kilovolt values (70, 81, 90, 100, 109, 121 kV) and thereafter with 80 kV (BMI ≤30 kg/m2) and 121 kV (BMI >30 kg/m2) and varying dose levels (DLs; 0.278, 0.435, 0.548, 0.696, 0.87, 1.09). Computed tomography data were acquired with a standard clinical protocol. Two independent readers rated visibility of the cortex, endplates, facet joints, trabeculae, neuroforamina, posterior alignment, and spinal canal as well as nerve roots. Radiation dose was measured with a cylindrical CTDI phantom. Descriptive statistics and analysis of variance were used (P < 0.05).

Results

Average intraclass correlation was excellent (0.94). The lowest technically possible kilovolt and the highest technically possible DL yielded the best image quality. In specimens with a BMI of 30 kg/m2 or less, depiction of all structures was good and comparable to CT, except for nerve roots. For specimens with a BMI greater than 30 kg/m2, image quality was limited.

Conclusions

Three-dimensional cone-beam CT of the lumbar spine in cadaveric specimens in the upright position is feasible. An optimal dose protocol was estimated. Depiction of osseous structures is comparable to CT in specimens with BMI of 30 kg/m2 or less. Image quality is limited for soft tissue structures and specimens with BMI greater than 30 kg/m2.
Psychological support for patients with cancer: evidence review and suggestions for future directions
Authors: Hulbert-Williams Nicholas J. , Beatty Lisa , Dhillon Haryana M.
Published: July 2018

Purpose of review

Psychological distress and mental health comorbidity are common in cancer. Various therapeutic frameworks have been used for interventions to improve psychological wellbeing and quality of life in cancer patients with mixed results. This article reviews contributions to that literature published since January 2017.

Recent findings

The majority of new psychological intervention research in cancer has used cognitive behavioural therapy (CBT) or mindfulness-based interventions. CBT has been considered a gold-standard intervention and recent evidence justifies continuation of this. Recent reviews call into question the validity of evidence for mindfulness-based interventions. A smaller number of trials using acceptance and commitment therapy, meta-cognitive therapy, dignity therapy and coaching have emerged, and whereas findings are promising, additional fully powered trials are required. Weaker evidence exists for counselling, support-based and narrative therapy interventions.

Efficacious, timely and acceptable psychological interventions are a necessary component of comprehensive cancer care. There is some way to go before the evidence conclusively points towards which interventions work for which cancer groups and for which specific outcomes. Methodological limitations must be addressed in future trials; at the forefront remains the need for fully powered, head-to-head comparison trials.
Reduced repertoire of cortical microstates and neuronal ensembles in medically-induced loss of consciousness
Authors: Wenzel Michael , Han Shuting , Smith Elliot H. , Hoel Erik , Greger Bradley , House Paul A. , Yuste Rafael
Published: July 2018

Medically-induced loss of consciousness (mLOC) has been linked to a macroscale break-down of brain connectivity, yet the neural microcircuit correlates of mLOC remain unknown. We applied non-linear t-stochastic neighbor embedding (t-SNE) and Lempel-Ziv-Welch complexity analysis to two-photon calcium imaging and local field potential (LFP) measurements of cortical microcircuit activity across anesthetic depth in mice, and to micro-electrode array recordings in human subjects. We find that mLOC disrupts population activity patterns by i) a reduction of discriminable network microstates and ii) a reduction of independent neuronal ensembles. These alterations are not explained by a simple reduction of neuronal activity and reveal abnormal functional microcircuits. Thus, normal neuronal ensemble dynamics could contribute to the emergence of conscious states.
Motion and physiological noise effects on amygdala real-time fMRI neurofeedback learning
Authors: Hellrung Lydia , Borchardt Viola , Götting Florian N. , Stadler Jörg , Tempelmann Claus , Tobler Philippe N. , Walter Martin , van der Meer Johan N.
Published: July 2018

Real-time fMRI neurofeedback allows to learn control over activity in a localized brain region. However, with fMRI, physiological factors such as the cardiac cycle and respiration interfere with the measurement of brain activation. In conventional fMRI studies this is usually mitigated by inclusion of motion parameters and/or physiological parameters as nuisance regressors at the analysis stage, allowing to correct for and filter out such confounders. In real-time fMRI, however, such an approach is not routinely feasible due to the necessity to process all signals during the runtime of an experiment. The absence of on-line correction can therefore compromise real-time fMRI study outcomes reporting volitional self-regulation capability as BOLD signal changes. This is especially true for BOLD signal changes in subcortical regions situated close to blood vessels or air cavities, such as the amygdala. We therefore aimed to establish the effects of motion, heart rate, heart rate variability, and respiratory volume on learning effects, which means here an increase in BOLD signal change over NF training, in an amygdala neurofeedback experiment. Specifically, we investigate motion parameters from two emotion regulation studies - performed at 3T and 7T scanners - and additionally acquired physiological variance for the latter one. Our results revealed differences in these parameters between groups and especially between regulation and resting periods within each participant. However, strictly considering these parameters as nuisance regressors in data analysis revealed that the learning of volitional self-regulation of the amygdala is not driven by motion and physiological changes. As validation of our real-time findings, we compare them to the gold standard of assessment of motion and physiology from the Human Connectome Project. Based on this, we recommend to carefully report neurofeedback study results including physiological nuisance regression. To our knowledge, this is the first study investigating the effects of motion and physiological noise correction on neurofeedback BOLD effects.
Motor cortex can modulate somatosensory processing via cortico-thalamo-cortical pathway
Authors: Lohse Michael , Cooper Matthew , Sader Elie , Langfelder Antonia , Kahn Martin , Baxter Luke , Bartram Julian , Phillips James W. , Upton A. Louise , Mann Edward O.
Published: July 2018

The somatosensory and motor systems are intricately linked, providing several routes for the sensorimotor interactions necessary for haptic processing. Here, we used electrical and optogenetic stimulation to study the circuits that enable primary motor cortex (M1) to exert top-down modulation of whisker-evoked responses, at the levels of brain stem, thalamus and somatosensory cortex (S1). We find that activation of M1 drives somatosensory responsive cells at all levels, and that this excitation is followed by a period of tactile suppression, which gradually increases in strength along the ascending somatosensory pathway. Using optogenetic stimulation in the layer-specific Cre driver lines, we find that activation of layer VI cortico-thalamic neurons is sufficient to drive spiking in higher order thalamus, and that this is reliably followed by excitation of S1, suggesting a cross-modal cortico-thalamo-cortical pathway. Cortico-thalamic excitation predicts the degree of subsequent tactile suppression, consistent with a strong role for thalamic circuits in the expression of inhibitory sensorimotor interactions. These results provide evidence of a role for M1 in dynamic modulation of S1, largely under cortico-thalamic control.
The effect of spatial variation for predicting aphid epidemics
Authors: Damgaard Christian , Bruus Marianne , Axelsen Jørgen Aagaard
Published: July 2018

In order to improve forecasting of aphid epidemics, it is important to know the spatial scale at which specific forecasts are reliable. To investigate the spatial scale of aphid epidemics, we have developed a spatio-temporal stochastic aphid population growth model, and fitted the model to empirical spatial time-series aphid population data using a Bayesian hierarchical fitting procedure. Furthermore, detailed spatial data of the initial phases of epidemic development was investigated in a semivariogram. Our results suggest that there is limited spatial variation in the initial occurrence probability at a spatial scale of 10 km. Consequently, the results support the hypothesis that initial aphid population sizes and epidemics may be predicted in fields within a 10 km radius. For farmers, this may imply that they can rely their decision of whether to spray against aphids on observations made by other nearby farmers or by the consultancy service.
MTrack: Automated Detection, Tracking, and Analysis of Dynamic Microtubules
Authors: Kapoor Varun , Hirst William G. , Hentschel Christoph , Preibisch Stephan , Reber Simone
Published: July 2018

Microtubules are polar, dynamic filaments fundamental to many cellular processes. In vitro reconstitution approaches with purified tubulin are essential to elucidate different aspects of microtubule behavior. To date, deriving data from fluorescence microscopy images by manually creating and analyzing kymographs is still commonplace. Here, we present MTrack, implemented as a plug-in for the open-source platform Fiji, which automatically identifies and tracks dynamic microtubules with sub-pixel resolution using advanced objection recognition. MTrack provides automatic data interpretation yielding relevant parameters of microtubule dynamic instability together with population statistics. The application of our software produces unbiased and comparable quantitative datasets in a fully automated fashion. This helps the experimentalist to achieve higher reproducibility at higher throughput on a user-friendly platform. We use simulated data and real data to benchmark our algorithm and show that it reliably detects, tracks, and analyzes dynamic microtubules and achieves sub-pixel precision even at low signal-to-noise ratios.
Whole genome sequencing identifies high-impact variants in well-known pharmacogenomic genes
Authors: Choi Jihoon , Tantisira Kelan G. , Duan Qing Ling
Published: July 2018

More than 1,100 genetic loci have been correlated with drug response outcomes but disproportionately few have been translated into clinical practice. One explanation for the low rate of clinical implementation is that the majority of associated variants may be in linkage disequilibrium (LD) with the causal variants, which are often elusive. This study aims to identify and characterize likely causal variants within well-established pharmacogenomic genes using next-generation sequencing data from the 1000 Genomes Project. We identified 69,319 genetic variations within 160 pharmacogenomic genes, of which 8,207 variants are in strong LD (r2 > 0.8) with known pharmacogenomic variants. Of the latter, 8 are coding or structural variants predicted to have high-impact, with 19 additional missense variants that are predicted to have moderate-impact. In conclusion, we identified putatively functional variants within known pharmacogenomics loci that could account for the association signals and represent the missing causative variants underlying drug response phenotypes.
A systems and treatment perspective of models of influenza virus-induced host responses
Authors: Mochan Ericka , Ackerman Emily , Shoemaker Jason E.
Published: July 2018

Severe influenza infections are often characterized as having unique host responses (e.g. early, severe hypercytokinemia). Neuraminidase inhibitors can be effective in controlling the severe symptoms of influenza but are often not administered until late in the infection. Several studies suggest that immune modulation may offer protection to high risk groups. Here, we review the current state of mathematical models of influenza-induced host responses. Selecting three models with conserved immune response components, we determine if the immune system components which most affect virus replication when perturbed are conserved across the models. We also test each model’s response to a pre-induction of interferon before the virus is administered. We find that each model emphasizes the importance of controlling the infected cell population to control viral replication. Moreover, our work shows that the structure of current models does not allow for significant responses to increased interferon concentrations. These results suggest that the current library of available published models of influenza infection does not adequately represent the complex interactions of the virus, interferon, and other aspects of the immune response. Specifically, the method used to model virus-resistant cells may need to be adapted in future work to more realistically represent the immune response to viral infection.
Parameterization of Proximal Humerus Locking Plate Impingement with In Vitro, In Silico, and In Vivo Techniques
Authors: Bachner Emily M. , Schmidt Elaine C , Chin Matthew , Namdari Surena , Baxter Josh R. , Hast Michael W.
Published: July 2018

Background

Locked plating of displaced proximal humerus fractures is common, but rates of subacromial impingement remain high. Computational predictions of implant impingement have yet to be sufficiently explored in proximal humerus fixation. The goal of this study was to utilize a multidisciplinary approach to elucidate the relationships between common surgical parameters, anatomical variability, and the likelihood of plate impingement.

Methods

The experiment was completed in three phases. First, a controlled in vitro experiment was conducted to simulate impingement. Second, a dynamic in silico musculoskeletal model was developed to simulate changes to implant geometry, surgical techniques, and acromial anatomy, where a collision detection algorithm was used to simulate contact between the plate and acromion. Finally, in vivo shoulder kinematics were recorded for nine activities of daily living and motions that created a high likelihood of impingement were identified.

Results

Impingement was measured at 73.3±14.5° abduction in the cadaveric model and 92.0°±34.0° with computational simulations. Impingement events were limited to ranges of motion between 10–40° of cross-body adduction. Activities of daily living, such as combing one’s hair, lifting and object overhead, and reaching behind one’s head are likely to cause impingement.

Discussion and Conclusion

This multidisciplinary experiment quantified key preoperative factors to assist with implantation decisions. Results demonstrated that proximal implant placement, superior translation of the humeral center of rotation, increases in plate thickness, and increases in acromial tilt all increase the likelihood of impingement. Careful preoperative planning that includes these factors could help guide operative decision making and improve clinical outcomes.

Level of Evidence: V
Effects of thermal stress on amount, composition, and antibacterial properties of coral mucus
Authors: Wright Rachel M. , Strader Marie E. , Genuise Heather M. , Matz Mikhail V.
Published: July 2018

The surface mucus layer of reef-building corals supports several essential functions including feeding, sediment clearing, and protection from pathogenic invaders. For the reef ecosystem, coral mucus provides energy to support heterotrophic benthic communities. Mucus production represents a substantial metabolic investment on behalf of the coral: as much as half of the fixed carbon supplied by the corals’ algal symbionts is incorporated into expelled mucus. In this study, we examined if bleaching (disruption of the coral–algal symbiosis) has the potential to indirectly disturb reef ecosystem function by impacting the nutritional composition of coral mucus. In a controlled laboratory thermal stress challenge, visibly paled corals produced mucus with higher protein and lipid content and increased antibacterial activity relative to healthy corals. These results are likely explained by the expelled symbionts in the mucus of bleached individuals. This study illuminates how the immediate effects of coral bleaching could impact the reef-ecosystem indirectly through modulation of available nutrients within the ecosystem.