bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Albumin in Combination With Mannitol on Whole-blood Coagulation In Vitro Assessed by Thromboelastometry
Authors: Lillemäe Kadri , Laine Antti T. , Schramko Alexey , Niemi Tomi T.
Published: May 2017

Background:

Albumin and mannitol may interfere with hemostasis, but their coinfluence is unclear. We aimed to determine the effects of albumin alone and in combination with mannitol or Ringer acetate (RAC) on hemostasis in crossover in vitro study.

Materials and Methods:

From citrated fresh whole blood withdrawn from 10 volunteers, we prepared 2.5, 5, 10, 15, and 20 vol% dilutions of 4% albumin (Alb group). Each sample was thereafter diluted by 15% mannitol (Alb/Man group) or RAC (Alb/RAC group) at a ratio of 9:1. Using thromboelastometry, FibTEM (fibrinogen ROTEM) and ExTEM (extrinsic ROTEM) tests were performed.

Results:

A 20 vol%, but not 2.5 to 15 vol% dilution of albumin caused a prolonged clot formation time, α-angle decrease, and maximum clot firmness (MCF) weakening compared with undiluted sample (P<0.05). Clot formation time prolonged more in Alb5/Man than in Alb5 and Alb5/RAC dilution (P<0.05). In Alb2.5/Man, Alb10/Man, and Alb15/Man, dilution α-angle was lower than in corresponding Alb/RAC and Alb-group dilutions (P<0.05). In ExTEM, MCF decreased similarly in every dilution of Alb/Man and Alb/RAC compared with Alb group (P<0.05). In FibTEM, MCF decreased more in Alb10/Man than in Alb10/RAC dilution (P<0.05).

Conclusions:

In up to 15 vol% dilutions, albumin alone did not impair hemostasis in vitro, but in combination with mannitol or RAC coagulation was disturbed similarly at most concentrations. There was some significant additional effect with mannitol at certain concentrations. Our results indicate that coadministration of mannitol and albumin needs further study in vivo.
Intracervical Foley Catheter With and Without Oxytocin for Labor Induction
Authors: Schoen Corina N. , Grant Gwendolyn , Berghella Vincenzo , Hoffman Matthew K. , Sciscione Anthony
Published: May 2017

OBJECTIVE:

To evaluate whether adding oxytocin to preinduction cervical ripening with a Foley catheter increases the rate of delivery within 24 hours.

METHODS:

This was a randomized, multicenter, parallel trial of women with a singleton pregnancy at 24 weeks of gestation or greater undergoing labor induction. Women were randomly allocated to an intracervical Foley catheter followed by oxytocin or Foley with concurrent oxytocin infusion. Nulliparous and multiparous women were randomized and analyzed separately based on parallel design. The primary outcome was Foley placement to delivery at 24 hours or less. A sample size of 100 nulliparous women and 75 multiparous women per group would be required to detect a 20% increase in baseline 24-hour delivery rate with 80% power for each parity group.

RESULTS:

From January 2015 through July 2016, 323 patients were enrolled: 184 nulliparous women and 139 multiparous women. Nulliparous women who received concurrent Foley and oxytocin delivered more frequently within 24 hours of Foley placement than did the Foley followed by oxytocin group (64% compared with 43%, P=.003, relative risk 1.51, 95% confidence interval [CI] 1.14–2.00). Multiparous women who received concurrent Foley and oxytocin delivered more frequently within 24 hours than the Foley followed by oxytocin group (87% compared with 72%, relative risk 1.22, 95% CI 1.02–1.45). Median time to delivery was shorter in both nulliparous women (20.9 compared with 26.1 hours, P<.001) and in multiparous women, (14.9 compared with 18.6 hours, P=.01) who received concurrent Foley and oxytocin compared with Foley followed by oxytocin. There were no significant differences in the rates of cesarean delivery, postpartum hemorrhage, chorioamnionitis, or neonatal intensive care unit admission between the randomization groups.

CONCLUSION:

Induction with concurrent oxytocin infusion added to Foley significantly increases the rate of delivery within 24 hours in both nulliparous and multiparous compared with Foley followed by oxytocin.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02273115.
What Is New in Hysterectomy?
Authors: Whiteside James L.
Published: May 2017

This month, we focus on current research in hysterectomy. Dr. Whiteside discusses four recent publications, and each is concluded with a “bottom line” that is the take-home message. The complete reference for each can be found in Box 1 on this page, along with direct links to the abstracts.
Transitioning to an Intramedullary Lengthening and Compression Nail
Authors: Fragomen Austin T.
Published: May 2017

The magnetic intramedullary lengthening nail is an innovative technology that allows for creative ways to treat difficult problems. The lengthening option has revolutionized femur fracture management with bone loss and malunion therapy. The compression version of this nail has provided a gradual method to compress nonunions and difficult fractures that may obviate the need for many current uses of external fixation. Three cases are presented in this manuscript demonstrating a new paradigm in the management of bone loss/shortening of the tibia and femur, and recalcitrant nonunions.
Controlled Compression Nailing for At Risk Humeral Shaft Fractures
Authors: Watson J. Tracy , Sanders Roy W.
Published: May 2017

Compression techniques seem to be the primary factor in determining the success of both plating and nailing techniques for the management of acute fractures and for delayed and nonunion management of these fractures. An intramedullary nail that can provide continual compression (like a plate) and mechanical manipulation of the callous throughout the course of treatment is an ideal device that provides all the advantages of plating and nailing and avoids the noted limitations of both. The UNYTE compression humeral nail is based on the PRECICE intramedullary limb lengthening system. This nail provides the ability to intraoperatively compress a humeral fracture immediately and continue compression in the outpatient setting with the external remote controller. This compression nail allows the surgeon to continually modulate stability through controlled compression and the ability to relengthen if necessary. The capacity to achieve constant compression at the fracture site has demonstrated rapid healing of the “at risk” humerus fracture in this series. We review the current indications for use of this device after its early introduction. In most cases, this was the failure of conservative brace management that presented with a progressive distraction gap and minimal callous formation or those fractures that could not be adequately controlled in the brace with malalignment greater than 20 degrees. The protocol for intraoperative compression using the external remote controller is detailed, as is the outpatient protocol for follow-up. The compression algorithm for progression to full fracture healing is also reviewed.
MGMT methylation correlates with melphalan pelvic perfusion survival in stage III melanoma patients: a pilot study
Authors: Guadagni Stefano , Fiorentini Giammaria , Clementi Marco , Palumbo Giancarlo , Masedu Francesco , Deraco Marcello , De Manzoni Giovanni , Chiominto Alessandro , Valenti Marco , Pellegrini Cristina
Published: May 2017

Approximately 25% of melanoma patients with locoregional metastases are nonresponsive to new molecular target therapy and immunotherapy. When metastases are located in the pelvis, melphalan hypoxic perfusion can be an optional treatment. Because methylation of MGMT promoter increases the efficacy of alkylating agents, studies on melanoma outcome of patients treated with melphalan regional chemotherapy should consider this epigenetic change. This study aims to evaluate whether the survival of stage III melanoma patients treated with melphalan regional chemotherapy may be correlated with MGMT methylation status. The metastatic tissues of 27 stage III melanoma patients with locoregional metastases located in the pelvis subjected to melphalan hypoxic pelvic perfusion were examined. The methylation status of the MGMT promoter was investigated by MS-MLPA probes analysis and the presence of the BRAF V600E mutation was analyzed by CAST-PCR. The median survival times were estimated using the Kaplan–Meier curves and were stratified according to the clinicopathological characteristics of patients and lesions. The overall median survival time was 17 months. The 1-year, 3-year, and 5-year survival rates were 66.7, 18.5, and 7.4%, respectively. Disease stage, burden, and percentage of MGMT methylation significantly affected survival. We estimated an MGMT promoter methylation cut-off of at least 14%, which was significantly associated with a longer survival after melphalan regional chemotherapy. Our data suggest that MGMT promoter methylation could be an important factor in determining which melanoma patients should receive melphalan regional chemotherapy, but its prognostic significance in the routine clinical setting needs to be clarified in a larger study.
Inappropriate oophorectomy at time of benign premenopausal hysterectomy∗
Authors: Mahal Amandeep S. , Rhoads Kim F. , Elliott Christopher S. , Sokol Eric R.
Published: May 2017

Objective:

We assessed rates of oophorectomy during benign hysterectomy around the release of the American College of Obstetricians and Gynecologists 2008 practice bulletin on prophylactic oophorectomy, and evaluated predictors of inappropriate premenopausal oophorectomy.

Methods:

A cross-sectional administrative database analysis was performed utilizing the California Office of Statewide Health Planning Development Patient Discharge Database for years 2005 to 2011. After identifying all premenopausal women undergoing hysterectomy for benign conditions, International Classification of Diseases (ICD)-9 diagnosis codes were reviewed to create a master list of indications for oophorectomy. We defined appropriate oophorectomy as cases with concomitant coding for ovarian cyst, breast cancer susceptibility gene carrier status, and other diagnoses. Using patient demographics and hospital characteristics to predict inappropriate oophorectomy, a logistic regression model was created.

Results:

We identified 57,776 benign premenopausal hysterectomies with oophorectomies during the period studied. Of the premenopausal oophorectomies, 37.7% (21,783) were deemed “inappropriate” with no documented reason for removal. The total number of premenopausal inpatient hysterectomies with oophorectomy decreased yearly (12,227/y in 2005 to 5,930/y in 2011). However, the percentage of inappropriate oophorectomies remained stable. In multivariate analysis, Hispanic and African American ethnicity/race associated with increased odds of inappropriate oophorectomy (P < 0.001). Urban and at low Medi-Cal utilization hospitals showed increased odds of inappropriate oophorectomy.

Conclusions:

In premenopausal women undergoing benign hysterectomy, over one-third undergo oophorectomy without an appropriate indication documented. The rate of inappropriate oophorectomy in California has not changed since the 2008 American College of Obstetricians and Gynecologists guidelines. Whereas the absolute number of inpatient hysterectomies for benign indications has decreased, our work suggests persistent utilization of oophorectomy in premenopausal women, despite well-documented long-term adverse health implications.
Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus
Authors: Alió del Barrio Jorge L. , El Zarif Mona , de Miguel María P. , Azaar Albert , Makdissy Norman , Harb Walid , El Achkar Ibrahim , Arnalich-Montiel Francisco , Alió Jorge L.
Published: May 2017

Purpose:

The aim of this phase 1 study was to preliminarily evaluate the safety and efficacy of autologous adipose-derived adult stem cell (ADASC) implantation within the corneal stroma of patients with advanced keratoconus.

Methods:

Five consecutive patients were selected. Autologous ADASCs were obtained by elective liposuction. ADASCs (3 × 106) contained in 1 mL saline were injected into the corneal stroma through a femtosecond-assisted 9.5-mm diameter lamellar pocket under topical anesthesia. Patients were reviewed at 1 day, 1 week, 1, 3, and 6 months postoperatively. Visual function, manifest refraction, slit-lamp biomicroscopy, intraocular pressure, endothelial cell density, corneal topography, corneal optical coherence tomography, and corneal confocal biomicroscopy were recorded.

Results:

No intraoperative or postoperative complications were recorded, with full corneal transparency recovery within 24 hours. Four patients completed the full follow-up. All patients improved their visual function (mean: 1 line of unaided and spectacle-corrected distance vision and 2 lines of rigid contact lens distance vision). Manifest refraction and topographic keratometry remained stable. Corneal optical coherence tomography showed a mean improvement of 16.5 μm in the central corneal thickness, and new collagen production was observed as patchy hyperreflective areas at the level of the stromal pocket. Confocal biomicroscopy confirmed the survival of the implanted stem cells at the surgical plane. Intraocular pressure and endothelial cell density remained stable.

Conclusions:

Cellular therapy of the human corneal stroma in vivo with autologous ADASCs appears to be safe. Stem cells survive in vivo with intrastromal new collagen production. Future studies with larger samples are required to confirm these preliminary results.
Varicella Zoster Virus–Associated Necrotizing Retinitis After Chickenpox in a 10-Year-Old Female
Authors: Shin Yong Un , Kim Jihong , Hong Eun Hee , Kim Jieun , Sohn Joo Hyun , Cho Heeyoon
Published: May 2017

A necrotizing retinitis in children is a rare but vision-threatening ocular complication of chickenpox. We report a 10-year-old girl who developed chickenpox 1 month before presenting with panuveitis and necrotizing retinitis. After prompt antiviral treatment, her inflammatory signs were resolved. Early detection and treatment of varicella zoster–associated necrotizing retinitis after chickenpox can achieve good visual outcome.
Toll-like receptor 7 is overexpressed in the bladder of Hunner-type interstitial cystitis, and its activation in the mouse bladder can induce cystitis and bladder pain
Authors: Ichihara Koji , Aizawa Naoki , Akiyama Yoshiyuki , Kamei Jun , Masumori Naoya , Andersson Karl-Erik , Homma Yukio , Igawa Yasuhiko
Published: May 2017

Toll-like receptor 7 (TLR7) is associated with the pathophysiology of systemic lupus erythematosus and Sjögren syndrome, well-known diseases accompanying interstitial cystitis (IC). We studied TLR7 expression in the bladder of patients with Hunner-type IC (HIC) and its functional roles in bladder inflammation and nociception using mice. Bladder biopsy specimens were obtained from patients with HIC. Specimens from the noncancerous portion of the bladder of patients with bladder cancer served as controls. The specimens were examined by immunohistochemistry and real-time polymerase chain reaction of TLR7. Loxoribine (LX), a TLR7 agonist, was instilled in the bladder of C57BL/6N female mice, and TLR7-mRNA expression and histological changes of the bladder, bladder pain–like licking behavior, voiding behavior, cystometry, and bladder afferent nerve activities were investigated. The effects of hydroxychloroquine, a TLR7 antagonist, on the LX-induced changes on cystometry and voiding behavior were studied. The number of TLR7 immuno-reactive cells and the mRNA expression of TLR7 were significantly increased in HIC specimens. Intravesical instillation of LX induced edema, congestion, inflammation, and significantly increased TLR7-mRNA expression in the mouse bladder. Loxoribine-instillation also significantly increased licking behavior, voiding frequency, and afferent nerve activities associated with decreased single-voided volume and intercontraction interval of micturitions. Hydroxychloroquine reversed the LX-induced cystometric and voiding behavioral changes. Toll-like receptor 7 was up-regulated in the bladder mucosa of patients with HIC, and activation of TLR7 in the mouse bladder induced cystitis with sensory hyperactivity of the bladder. Blocking the TLR7 pathway may be an innovative treatment target of HIC.
Learned expectations and uncertainty facilitate pain during classical conditioning
Authors: Taylor Veronique A. , Chang Luke , Rainville Pierre , Roy Mathieu
Published: May 2017

Pain spontaneously activates adaptive and dynamic learning processes affecting the anticipation of, and the responses to, future pain. Computational models of associative learning effectively capture the production and ongoing changes in conditioned anticipatory responses (eg, skin conductance response), but the impact of this dynamic process on unconditional pain responses remains poorly understood. Here, we investigated the dynamic modulation of pain and the nociceptive flexion reflex by fear learning in healthy human adult participants undergoing a classical conditioning procedure involving an acquisition, reversal and extinction phase. Conditioned visual stimuli (CS+) coterminated with a noxious transcutaneous stimulation applied to the sural nerve on 50% of trials (unconditioned stimuli). Expected pain probabilities and cue associability were estimated using computational modeling by fitting a hybrid learning model to skin conductance response elicited by the CS+. Multilevel linear regression analyses confirmed that trial-by-trial changes in expected pain and associability positively predict ongoing fluctuations in pain outcomes. Mediation analysis further demonstrated that both expected probability and associability affect pain perception through a direct effect and an indirect effect mediated by descending modulatory mechanisms affecting spinal nociceptive activity. Moderation analyses further showed that hyperalgesic effects of associability were larger in individuals reporting more harm vigilance and less emotional detachment. Higher harm vigilance was also associated with a stronger mediation of hyperalgesic effects by spinal processes. These results demonstrate how dynamic changes in pain can be explained by associative learning theory and that resilient attitudes towards fear/pain can attenuate the adverse impact of adaptive aversive learning processes on pain.
Asking a Better Question: Development and Evaluation of the Need For Trauma Intervention (NFTI) Metric as a Novel Indicator of Major Trauma
Authors: Roden-Foreman Jacob W. , Rapier Nakia R. , Yelverton Luanna , Foreman Michael L.
Published: May 2017

Many existing metrics, such as Injury Severity Score (ISS), cannot fully describe many trauma patients because of comorbidities. This study developed and evaluated the Need For Trauma Intervention (NFTI) metric as a novel indicator of major trauma. The NFTI metric was developed from an analysis of 2,396 trauma patients at a Level I trauma center. Six commonly recorded registry variables were found to be indicative of major trauma and comprised the NFTI criteria: receiving packed red blood cells within 4 hr; discharge from the emergency department (ED) to the operating room within 90 min; discharge from the ED to interventional radiology; discharge from the ED to the intensive care unit (ICU) with an ICU length of stay (LOS) of 3 or more days; mechanical ventilation outside of procedural anesthesia within 3 days; or death within 60 hr. Patients meeting any NFTI criteria are classified as having major traumas and, therefore, needing trauma activations (NFTI+). Need For Trauma Intervention was tested in an overlapping sample of 9,737 patients. Being NFTI+ was associated with higher trauma activation levels, older age, higher ISS, worse ED vitals, longer hospital LOS, and mortality. Only 13 of 561 deaths were not NFTI+ and all were in patients with do not resuscitate (DNR) orders; using ISS greater than 15 missed 73 mortalities, 46 with DNR orders. Results suggest that NFTI provides a comprehensive view of both anatomy and physiology in a manner that self-adjusts for age, frailty, and comorbidities as long as care teams adjust their treatments. Need For Trauma Intervention appears to be a unique, simple, and effective tool to retrospectively identify major trauma, regardless of ISS.
A Preliminary Analysis of Compassion Satisfaction and Compassion Fatigue With Considerations for Nursing Unit Specialization and Demographic Factors
Authors: Mooney Claire , Fetter Katrina , Gross Brian W. , Rinehart Cole , Lynch Caitlin , Rogers Frederick B.
Published: May 2017

Compassion fatigue (CF), or vicarious traumatization, is a state of physical/emotional distress that results from caring for those experiencing pain. We sought to characterize levels of CF in intensive care unit (ICU) and oncology nursing populations with subanalyses comparing specific personal/professional demographic factors. The Professional Quality of Life (ProQOL) scale, a validated tool for assessing CF, burnout (BO), and compassion satisfaction (CS), was distributed to the ICU and oncology divisions of a community hospital. Demographic data and ProQOL scale scores were collected and compared within specialty and gender subgroups. Two-sample t tests and regression analyses were used to compare groups. Statistical significance was defined as p < .05. A total of 86 nurses submitted completed surveys able to be analyzed. Levels of CS were significantly lower (p = .023) and levels of BO were significantly higher (p = .029) in ICU nurses than in oncology nurses. Male nurses exhibited significantly higher CS (p = .001) and significantly lower BO (p = .021) and CF (p = .014) than female nurses. Intensive care unit nurses and female nurses from both ICU and oncology specialties may be at increased risk for developing a poorer overall ProQOL and CF.
Portal Vein Thrombosis in Cirrhosis
Authors: Loudin Michael , Ahn Joseph
Published: May 2017

Portal vein thrombosis (PVT) in the cirrhotic population is a challenging clinical phenomenon requiring a nuanced management approach. Uncertainty exists regarding the clinical significance of PVT in the cirrhotic population because the data for PVT are based mainly on retrospective, small cohort studies. Therefore, strong recommendations regarding the optimal timing, modality, and duration of therapy for PVT in the cirrhotic population cannot be made. However, this review aims to summarize the current literature and provide stepwise guidance in diagnosing and managing PVT in patients with cirrhosis.
Retrospective Comparison of Fluticasone Propionate and Oral Viscous Budesonide in Children With Eosinophilic Esophagitis
Authors: Fable Jacqueline M. , Fernandez Marina , Goodine Susan , Lerer Trudy , Sayej Wael N.
Published: May 2017

Background:

Eosinophilic esophagitis (EoE) is treated with dietary modification and/or pharmacologic management with swallowed topical steroids. Swallowed fluticasone propionate (FP) and oral viscous budesonide (OVB) have proven to be effective in resolving symptoms and reversing histologic changes in children and adults with EoE. There are minimal comparative studies between the 2 agents.

Objective:

The aim of the study was to retrospectively compare endoscopic and histologic outcomes after FP versus OVB therapy in children with EoE in our center.

Methods:

We performed a retrospective chart review of subjects diagnosed with EoE at a tertiary care center between 2010 and 2015. Inclusion criteria were FP or OVB therapy for ≥8 weeks along with pre‐ and post‐treatment endoscopic evaluation. Demographic and clinical features and endoscopic and histologic assessment were recorded for comparative analysis. Histologic response was defined as <15 eos/hpf and remission as <5 eos/hpf.

Results:

The study included 68 EoE patients (20 FP and 48 OVB) with a mean age of 10.6 ± 5.2 years (range 1–20 years); 81% were boys and 68% were Caucasian. No significant demographic or clinical differences were noted between the 2 study groups. Overall histologic response to topical steroids was seen in 44 of 68 (65%) patients. A significantly greater number of patients achieved histologic response with OVB (36/48, 75%) than with FP (8/20, 40%) (P = 0.0059). Mean pretreatment peak eos/hpf was 46 ± 19 in the FP group versus 45 ± 23 in the OVB group. Mean post‐treatment peak eos/hpf was 20 ± 29 in the FP group versus 12 ± 16 in the OVB group (P = 0.002). There was also a significantly greater difference in the change of absolute eos/hpf from pre‐ to post‐treatment in the OVB group (−33) versus FP (18) (P = 0.047). A greater number of OVB‐treated patients without asthma had a histologic response compared to those with asthma (P = 0.031). The response to OVB was not affected by the delivery vehicle, namely sucralose (Splenda) versus Neocate Duocal.

Conclusions:

Our data suggest that treatment with OVB leads to better endoscopic and histologic outcomes than FP. Adherence to treatment and history of asthma are major determining factors in the response to treatments. Using Neocate Duocal as the OVB delivery vehicle is just as effective as sucralose.
Starved Guts
Authors: Attia Suzanna , Feenstra Marjon , Swain Nathan , Cuesta Melina , Bandsma Robert H.J.
Published: May 2017

Malnutrition contributes significantly to death and illness worldwide and especially to the deaths of children younger than 5 years. The relation between intestinal changes in malnutrition and morbidity and mortality has not been well characterized; however, recent research indicates that the functional and morphologic changes of the intestine secondary to malnutrition itself contribute significantly to these negative clinical outcomes and may be potent targets of intervention. The aim of this review was to summarize current knowledge of experimental and clinically observed changes in the intestine from malnutrition preclinical models and human studies. Limited clinical studies have shown villous blunting, intestinal inflammation, and changes in the intestinal microbiome of malnourished children. In addition to these findings, experimental data using various animal models of malnutrition have found evidence of increased intestinal permeability, upregulated intestinal inflammation, and loss of goblet cells. More mechanistic studies are urgently needed to improve our understanding of malnutrition‐related intestinal dysfunction and to identify potential novel targets for intervention.
Gunshot Wound in an 18-Year-Old Woman, Inflicted With a Hunting Weapon Through an Obstacle (Mobile Phone)
Authors: Smędra Anna , Sidelnik Przemysław , Goryca Wojciech , Berent Jarosław
Published: May 2017

The article presents a case of an 18-year-old woman wounded by a shot fired from a distance with a hunting weapon. Because the location of the entrance and exit wounds initially seemed inconsistent with the reports (both wounds were described as “large and irregular in shape”) and no photographs documenting the inflicted injuries were taken, the case was referred for an opinion to the Department of Forensic Medicine in Lodz. After a review of the medical records, radiology, the victim's clothing, and performance of an experiment using the gun and ammunition, it was established that the entrance wound was located on the abdomen, and the exit wound was located on the buttock. The initial problems with recognizing the entrance and exit wounds encountered by the surgical team were caused by bullet deformation. Before hitting the body, the projectile pierced a mobile phone that was in the pocket of the woman's jacket, subsequently causing a large atypical secondary entrance wound. The experiment confirmed that, when the projectile passed through an obstacle with consequent deformation, it caused more extensive gunshot wounds, both at the entrance and at the exit, as well as more severe damage to the bones.
Synovial Sarcoma of Peripheral Nerves
Authors: Chrisinger John S.A. , Salem Usama I. , Kindblom Lars-Gunnar , Amini Behrang , Hansson Magnus , Meis Jeanne M.
Published: May 2017

Synovial sarcoma of peripheral nerve (SSPN) is rare with only 26 cases reported in English. SSPN is often mistaken for a benign or malignant peripheral nerve sheath tumor (PNST) by clinicians and pathologists. Fifteen cases of SSPN were retrieved from the pathology files of 3 institutions. All tumors arose in a nerve based on imaging and/or operative findings and the diagnoses were histologically confirmed. Neuropathic symptoms predominated in 11 women and 4 men, 19- to 62-year-old (median, 39 years) with tumors involving the ulnar (5), median (3), peroneal (3) or sciatic (2) nerve, or the L4 or T1 nerve root (2). Tumor sizes ranged from 2 to 13 cm (median, 3.8 cm). The leading clinical diagnosis was PNST (9). Treatment was surgical (14) supplemented with radiation therapy (8) and chemotherapy (6). Fourteen tumors were monophasic and 1 was biphasic; 4 had poorly differentiated (PD) foci (1 rhabdoid). Diagnoses in 12 cases were verified by fluorescence in situ hybridization, reverse transcription polymerase chain reaction or both methods. Follow-up in 14 patients (median, 32 mo) revealed that 2/4 patients with PD tumors died with pulmonary metastases; another was alive with no current evidence of disease (NED) following 2 local recurrences, while the fourth had NED. In contrast, 9/10 patients without PD tumors were alive (7 NED) and 1 died at 12 months with pulmonary infiltrates. SSPN is under-recognized clinically and histologically as it mimics benign and malignant PNST. Molecular analysis is recommended to confirm the diagnosis. PD foci, including rhabdoid areas, may portend a worse outcome, similar to non-neural–based tumors.
An Adolescent Presenting With Seizures as a Symptom of Gliomatosis Cerebri
Authors: Blanco-Iglesias Elena , Cabeza Beatriz , Esparza Elena Garcia , de Prada Inmaculada , Lassaletta Alvaro , Budke Marcelo , Serrano Ana
Published: May 2017

Gliomatosis cerebri is a diffuse infiltrating glioma of neuroepithelial origin that affects more than 2 cerebral lobes. This is rarely seen in pediatric patients. The clinical presentation and imaging are very unspecific, and a biopsy is typically needed for the diagnosis. Given the widespread nature of the disease, surgical treatment is not possible and has a poor overall prognosis. A pediatric patient presented with elevated intracranial pressure. All initial studies were negative, and the imaging showed a symmetrical affection involving the supratentorial and infratentorial regions. A biopsy ultimately confirmed gliomatosis cerebri. This case describes a unique clinical presentation of gliomatosis cerebri in a pediatric patient.
Influence of Visceral Interoceptive Experience on the Brain's Response to Food Images in Anorexia Nervosa
Authors: Kerr Kara L. , Moseman Scott E. , Avery Jason A. , Bodurka Jerzy , Simmons W. Kyle
Published: May 2017

Objective

The aim of the study was to determine how visceral sensations affect responses to food stimuli in anorexia nervosa (AN).

Methods

Twenty weight-restored, unmedicated adolescent and young adult women with AN and twenty healthy control participants completed an interoceptive attention task during which they focused on sensations from the heart, stomach, and bladder and made ratings of these sensations. They then underwent functional magnetic resonance imaging scanning while viewing pictures of food and nonfood objects. Between-groupsttests were employed to investigate group differences in the relationship between interoceptive sensation ratings and brain hemodynamic response to food pictures and, specifically, to highly palatable foods.

Results

In response to food pictures, AN participants exhibited a positive relationship between stomach sensation ratings and posterior insula activation (peakt= 4.30). AN participants displayed negative relationships between stomach sensation ratings and amygdala activation (peakt= −4.05) and heart sensation ratings and ventromedial prefrontal cortex activation (peakt= −3.52). In response to highly palatable foods, AN was associated with positive relationships between stomach sensation ratings and activity in the subgenual anterior cingulate (peakt= 3.88) and amygdala (peakt= 4.83), and negative relationships in the ventral pallidum (peakt= −3.99) and ventral tegmental area (peakt= −4.03). AN participants also exhibited negative relationships between cardiac sensations and activation in response to highly palatable foods in the putamen (peakt= −3.41) and ventromedial prefrontal cortex (peakt= −3.61). Healthy participants exhibited the opposite pattern in all of these regions.

Conclusions

Hedonic and interoceptive inferences made by individuals with AN at the sight of food may be influenced by atypical visceral interoceptive experience, which could contribute to restrictive eating.
Improving Retention in Care Among Pregnant Women and Mothers Living With HIV: Lessons From INSPIRE and Implications for Future WHO Guidance and Monitoring
Authors: Rollins Nigel C. , Essajee Shaffiq M. , Bellare Nita , Doherty Meg , Hirnschall Gottfried O.
Published: May 2017

Identifying women living with HIV, initiating them on lifelong antiretroviral treatment (ART), and retaining them in care are among the important challenges facing this generation of health care managers and public health researchers. Implementation research attempts to solve a wide range of implementation problems by trying to understand and work within real-world conditions to find solutions that have a measureable impact on the outcomes of interest. Implementation research is distinct from clinical research in many ways yet demands similar standards of conceptual thinking and discipline to generate robust evidence that can be, to some extent, generalized to inform policy and service delivery. In 2011, the World Health Organization (WHO), with funding from Global Affairs Canada, began support to 6 implementation research projects in Malawi, Nigeria, and Zimbabwe. All focused on evaluating approaches for improving rates of retention in care among pregnant women and mothers living with HIV and ensuring their continuation of ART. This reflected the priority given by ministries of health, program implementers, and researchers in each country to the importance of women living with HIV returning to health facilities for routine care, adherence to ART, and improved health outcomes. Five of the studies were cluster randomized controlled trials, and 1 adopted a matched cohort design. Here, we summarize some of the main findings and key lessons learned. We also consider some of the broader implications, remaining knowledge gaps, and how implementation research is integral to, and essential for, global guideline development and to inform HIV/AIDS strategies.
Tolerance to herbivory and the resource availability hypothesis
Authors: Gianoli Ernesto , Salgado-Luarte Cristian
Published: May 2017

The resource availability hypothesis (RAH), the most successful theory explaining plant defence patterns, predicts that defence investment is related to the relative growth rate (RGR) of plant species, which is associated with habitat quality. Thus, fast-growing species should show lower resistance than slow-growing species, which would lead fast growers to sustain higher herbivory rates, but the fitness consequences of herbivory would be greater for slow growers. The latter is often assumed but rarely tested. In a temperate rainforest, we tested the expected pattern of tolerance to herbivory derived from the RAH: that fast-growing species should be more tolerant than slow-growing species. We also evaluated whether other plant features covary with RGR (leaf lifespan, shade tolerance and leaf toughness) and thus could also contribute to the patterns of tolerance to herbivory. As expected, seedlings from tree species with higher RGR showed greater tolerance to herbivory. Among the three plant features included, only leaf lifespan showed a significant association with RGR, but RGR was the best predictor of tolerance. We argue that plant tolerance to herbivory must be evaluated to properly verify the assumptions of the RAH.
Meta analysis of microbiome studies identifies shared and disease-specific patterns
Authors: Duvallet Claire , Gibbons Sean , Gurry Thomas , Irizarry Rafael , Alm Eric
Published: May 2017

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Hundreds of clinical studies have been published that demonstrate associations between the human microbiome and a variety of diseases. Yet, fundamental questions remain on how we can generalize this knowledge. For example, if diseases are mainly characterized by a small number of pathogenic species, then new targeted antimicrobial therapies may be called for. Alternatively, if diseases are characterized by a lack of healthy commensal bacteria, then new probiotic therapies might be a better option. Results from individual studies, however, can be inconsistent or in conflict, and comparing published data is further complicated by the lack of standard processing and analysis methods.

Here, we introduce the MicrobiomeHD database, which includes 29 published case-control gut microbiome studies spanning ten different diseases. Using standardized data processing and analyses, we perform a comprehensive crossdisease meta-analysis of these studies. We find consistent and specific patterns of disease-associated microbiome changes. A few diseases are associated with many individual bacterial associations, while most show only around 20 genus-level changes. Some diseases are marked by the presence of pathogenic microbes whereas others are characterized by a depletion of health-associated bacteria. Furthermore, over 60% of microbes associated with individual diseases fall into a set of “core” health and disease-associated microbes, which are associated with multiple disease states. This suggests a universal microbial response to disease.
The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals its Role in Community Composition
Authors: Verster Adrian J. , Ross Benjamin D. , Radey Matthew C. , Bao Yiqiao , Goodman Andrew L. , Mougous Joseph D. , Borenstein Elhanan
Published: May 2017

While the composition of the human gut microbiome has been well defined, the forces governing its assembly are poorly understood. Recently, prominent members of this community from the orderBacteroidaleswere shown to possess the type VI secretion system (T6SS), which mediates contact-dependent antagonism between Gram-negative bacteria. However, the distribution of the T6SS in human gut microbiomes and its role have not yet been characterized. To address this challenge, we construct an extensive catalog of T6SS effector/immunity (E-I) genes from three genetic architectures (GA1-3) found inBacteroidalesgenomes. We then use metagenomic analysis to assess the abundances of these genes across a large set of gut microbiome samples. We find that despite E–I diversity across reference strains, each individual microbiome harbors a limited set of E-I genes representing a single E–I genotype. Importantly, for GA1-2, these genotypes are not associated with a specific species, suggesting selection for compatibility. GA3, in contrast, is restricted toB. fragilis, and its low diversity reflects a singleB. fragilisstrain per sample. We further show that in infant microbiomes GA3 is enriched andB. fragilisstrains are replaced over time, suggesting competition for dominance in developing microbiomes. Finally, we find a strong association between the presence of GA3 and increased abundance ofBacteroides,indicating that this system confers a selective advantagein vivoinBacteroidesrich ecosystems. Combined, our findings provide the first comprehensive characterization of the T6SS landscape in the human microbiome, implicating it in both intra- and inter-species interactions.
Copb2is essential for embryogenesis and hypomorphic mutations cause human microcephaly
Authors: DiStasio Andrew , Driver Ashley , Sund Kristen , Donlin Milene , Muraleedharan Ranjith M. , Pooya Shabnam , Kline-Fath Beth , Kaufman Kenneth M. , Prows Cynthia A. , Schorry Elizabeth , DasGupta Biplab , Stottmann Rolf W.
Published: May 2017

Primary microcephaly is a congenital brain malformation characterized by a head circumference less than three standard deviations below the mean for age and sex and results in moderate to severe mental deficiencies and decreased lifespan. We recently studied two children with primary microcephaly in an otherwise unaffected family. Exome sequencing identified an autosomal recessive mutation leading to an amino acid substitution in a WD40 domain of the highly conservedCoatomer Protein Complex, Subunit Beta 2 (COPB2). To study the role ofCopb2in neural development, we utilized genome editing technology to generate an allelic series in the mouse. Two independent null alleles revealed thatCopb2is essential for early stages of embryogenesis. Mice homozygous for the patient variant (Copb2R254C/R254C) appear to have a grossly normal phenotype, likely due to differences in corticogenesis between the two species. Strikingly, mice heterozygous for the patient mutation and a null allele (Copb2R254C/Znf) show a severe perinatal phenotype including low neonatal weight, significantly increased apoptosis in the brain, and death within the first week of life. Immunostaining of theCopb2R254C/Znfbrain revealed a reduction in layer V (CTIP2+) neurons, while the overall cell density of the cortex is unchanged. Moreover, disruption ofCopb2in mouse neurospheres resulted in reduced proliferation. These results identify a general requirement forCOPB2in embryogenesis and a specific role in corticogenesis. We further demonstrate the utility of CRISPR-Cas9 generated mouse models in the study of potential pathogenicity of variants of potential clinical interest.
Basal Ganglia Control of Reflexive Saccades: A Computational Model Integrating Physiology Anatomy and Behaviour
Authors: Cope Alex J. , Chambers Jonathan M. , Prescott Tony J. , Gurney Kevin N.
Published: May 2017

It is hypothesised that the basal ganglia play a key role in solving the problem of action selection. Here we investigate this hypothesis through computational modelling of the primate saccadic oculomotor system. This system is an excellent target for computational modelling because it is supported by a reasonably well understood functional anatomy, has limited degrees of freedom, and there is a wealth of behavioural and electrophysiological data for model comparison. Here, we describe a computational model of the reflexive saccadic oculomotor system incorporating the basal ganglia, key structures in motor control and competition between possible actions. To restrict the likelihood of overfitting the model it is structured and parameterised by the known anatomy and neurophysiology along with data from a single experimental behavioural paradigm, then validated by testing against several additional behavioural experimental data without modification of the parameters. With this model we reproduce a range of fundamental reflexive saccadic results both qualitatively and quantitatively, comprising: the distribution of saccadic latencies; the effect of eccentricity, luminance and fixation-target interactions on saccadic latencies; and the effect of competing targets on saccadic endpoint. By investigating the model dynamics we are able to provide mechanistic explanations for the sources of these behaviours. Further, because of its accesibility, the oculomotor system has also been used to study general principle of sensorimotor control. We interpret the ability of the basal ganglia to successfully control saccade selection in our model as further evidence for the action selection hypothesis.
Inverse Modeling for MEG/EEG Data
Authors: Sorrentino Alberto , Piana Michele
Published: May 2017

We provide an overview of the state-of-the-art for mathematical methods that are used to reconstruct brain activity from neurophysiological data. After a brief introduction on the mathematics of the forward problem, we discuss standard and recently proposed regularization methods, as well as Monte Carlo techniques for Bayesian inference. We classify the inverse methods based on the underlying source model, and discuss advantages and disadvantages. Finally we describe an application to the pre–surgical evaluation of epileptic patients.
Kinship governs fertility with pre-and post-zygotic mechanisms mediated by match of methylation patterns
Authors: Herbert M.
Published: May 2017

It has been shown that kinship normally determines fertility in humans and animals. At smaller populations the curve of fertility against kinship rises steeply as kinship rises until inbreeding is reached. In large and progressively larger populations, fertility slowly falls. At an equilibrium point fertility matches replacement. Away from that, fertility changes by one of four published time courses. Earlier we demonstrated damped oscillation in a population of captive fruit flies. I hypothesized that since fertility changes so rapidly, DNA base mutations could not be the cause. The mechanism must be epigenetic, the control of genes, and gave varying doses of a methylating cocktail to the same flies. The fly population changed in a complex way, which only happens when there are pre-zygotic and post-zygotic processes in effect together.

One Sentence Summary

There is evidence for an epigenetic effect – with both pre-zygotic and post-zygotic components – of kinship on fertility of flies (Drosophila melanogaster)induced by a methylating cocktail.
Dynamic Current Clamp Experiments Define the Functional Roles of IK1 and Ito,f in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Marrus Scott B. , Springer Steven , Johnson Eric , Martinez Rita J. , Dranoff Edward J. , Mellor Rebecca , Yamada Kathryn
Published: May 2017

The transient outward potassium current (Ito) plays a key, albeit incompletely defined, role in cardiomyocyte physiology and pathophysiology. In light of the technical challenges of studying adult human cardiomyocytes, this study examines the use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a system which potentially preserves the native cellular milieu of human cardiomyocytes. ISPC-CMs express a robust Ito with slow recovery kinetics and fail to express the rapidly recovering Ito,f which is implicated in human disease. Overexpression of the accessory subunit KChIP2 (which is not expressed in iPSC-CMs) resulted in restoration of a rapid component of recovery. To define the functional role of Ito, dynamic current clamp was used to introduce computationally modeled currents into iPSC-CMs while recording action potentials. However, iPSC-CMs exhibit action potentials with multiple immature physiological properties, including slow upstroke velocity, heterogeneous action potential waveforms, and the absence of a phase 1 notch, thus potentially limiting the utility of these cells as a model of adult cardiomyocytes. Importantly, the introduction of modeled inwardly rectified current (IK1) ameliorated these immature properties by restoring a hyperpolarized resting membrane potential. In this context of normalized action potential morphologies, dynamic current clamp experiments introducing Ito,f demonstrated that there is significant cell-to-cell heterogeneity and that the functional effect of Ito,f is highly sensitive to the action potential plateau voltage in each cell.