bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal model for calcium alternans due to SR release refractoriness
Authors: Cantalapiedra Inma R. , Alvarez-Lacalle Enrique , Peñaranda Angelina , Echebarria Blas
Published: September 2017

In the heart, rapid pacing rates may induce alternations in the strength of cardiac contraction, termed pulsus alternans. Often, this is due to an instability in the dynamics of the intracellular calcium concentration, whose transients become larger and smaller at consecutive beats. This alternation has been linked experimentally and theoretically to two different mechanisms: an instability due to (1) a strong dependence of calcium release on sarcoplasmic reticulum (SR) load, together with a slow calcium reuptake into the SR or (2) to SR release refractoriness, due to a slow recovery of the ryanodine receptors (RyR2) from inactivation. The relationship between calcium alternans and refractoriness of the RyR2 has been more elusive than the corresponding SR Ca load mechanism. To study the former, we reduce a general calcium model, which mimics the deterministic evolution of a calcium release unit, to its most basic elements. We show that calcium alternans can be understood using a simple nonlinear equation for calcium concentration at the dyadic space, coupled to a relaxation equation for the number of recovered RyR2s. Depending on the number of RyR2s that are recovered at the beginning of a stimulation, the increase in calcium concentration may pass, or not, over an excitability threshold that limits the occurrence of a large calcium transient. When the recovery of the RyR2 is slow, this produces naturally a period doubling bifurcation, resulting in calcium alternans. We then study the effects of inactivation, calcium diffusion, and release conductance for the onset of alternans. We find that the development of alternans requires a well-defined value of diffusion while it is less sensitive to the values of inactivation or release conductance.
Assessment of burn severity in Middle Povozhje with Landsat multitemporal data
Authors: Kurbanov Eldar , Vorobyev Oleg , Leznin Sergey , Polevshikova Yulia , Demisheva Ekaterina
Published: September 2017

Forests of Middle Povolzhje in the Russian Federation were seriously affected by severe wildfires in 2010. The importance of accurate estimation of burn severity levels is because fire-affected areas may have important societal, ecological and economic consequences to the region. The aim of the study was to explore the performance of the differenced Normalized Burn Ratio (dNBR) and Composite Burn Index (CBI) to evaluate the burnt forest areas of the 2010 wildfires in the Republics of Mari El and Chuvashia of the Russian Federation with the use of Landsat-5 Thematic Mapper (TM) time series images. In total, 625 forest sites were sampled for ground-based burn severity data following the CBI protocol. Both datasets for Mari El and Chuvashia were statistically similar with correlation coefficients of 0.87, which confirms pooling them into a single dataset for the forests of Middle Povozhje. A non-linear third-degree polynomial model form of third order best represented the relationship (R2=0.79) between the dNBR and CBI data. Our model estimates that the total forest burnt area on the study area was 113000ha in 2010, mostly in coniferous stands. Almost half (45.9% or 51900ha) of the burnt forest areas were classified in the high-severity category. The accuracy assessment shows that severity classification results were accurate for estimating burn severity levels, with both producer’s and user’s accuracies higher than 80% for the unburned, low and high classes. Lower user and producer accuracies were noticed for the moderate class of burn severity.
Development of electro-co-deposited Ni–Fe(Ti,W)C nanocomposite coatings
Authors: Khorsand S. , Karbasi M. , Sayyedan F.S. , Eshaghian M. , Razavi M.
Published: September 2017

The parameters for the electroplating process of Ni-Fe(Ti,W)C nanocomposite on the steel substrate were developed and optimised. for this purpose, the coating process was performed under a direct current using a nickel bath. The coating was fully characterised employing the X-ray diffraction, scanning electron microscopy, energy-dispersive spectroscopy and microhardness tester. The results indicated that the Ni-Fe(Ti,W)C nanocomposite can be coated on the steel with an appropriate structure using the current density and the concentration of 40 mA cm−2 and 6 g L−1, respectively.
Yeast silencing factor Sir4 and a subset of nucleoporins form a complex distinct from nuclear pore complexes
Authors: Lapetina Diego L. , Ptak Christopher , Roesner Ulyss K. , Wozniak Richard W.
Published: September 2017

Interactions occurring at the nuclear envelope (NE)–chromatin interface influence both NE structure and chromatin organization. Insights into the functions of NE–chromatin interactions have come from the study of yeast subtelomeric chromatin and its association with the NE, including the identification of various proteins necessary for tethering subtelomeric chromatin to the NE and the silencing of resident genes. Here we show that four of these proteins—the silencing factor Sir4, NE-associated Esc1, the SUMO E3 ligase Siz2, and the nuclear pore complex (NPC) protein Nup170—physically and functionally interact with one another and a subset of NPC components (nucleoporins or Nups). Importantly, this group of Nups is largely restricted to members of the inner and outer NPC rings, but it lacks numerous others including cytoplasmically and nucleoplasmically positioned Nups. We propose that this Sir4-associated Nup complex is distinct from holo-NPCs and that it plays a role in subtelomeric chromatin organization and NE tethering.
Adhesion to the host cell surface is sufficient to mediateListeria monocytogenesentry into epithelial cells
Authors: Ortega Fabian E. , Rengarajan Michelle , Chavez Natalie , Radhakrishnan Prathima , Gloerich Martijn , Bianchini Julie , Siemers Kathleen , Luckett William S. , Lauer Peter , Nelson W. James , Theriot Julie A.
Published: September 2017

The intestinal epithelium is the first physiological barrier breached by the Gram-positive facultative pathogen Listeria monocytogenes during an in vivo infection. Listeria monocytogenes binds to the epithelial host cell receptor E-cadherin, which mediates a physical link between the bacterium and filamentous actin (F-actin). However, the importance of anchoring the bacterium to F-actin through E-cadherin for bacterial invasion has not been tested directly in epithelial cells. Here we demonstrate that depleting αE-catenin, which indirectly links E-cadherin to F-actin, did not decrease L. monocytogenes invasion of epithelial cells in tissue culture. Instead, invasion increased due to increased bacterial adhesion to epithelial monolayers with compromised cell–cell junctions. Furthermore, expression of a mutant E-cadherin lacking the intracellular domain was sufficient for efficient L. monocytogenes invasion of epithelial cells. Importantly, direct biotin-mediated binding of bacteria to surface lipids in the plasma membrane of host epithelial cells was sufficient for uptake. Our results indicate that the only requirement for L. monocytogenes invasion of epithelial cells is adhesion to the host cell surface, and that E-cadherin–mediated coupling of the bacterium to F-actin is not required.
α5β1-Integrin promotes tension-dependent mammary epithelial cell invasion by engaging the fibronectin synergy site
Authors: Miroshnikova Y. A. , Rozenberg G. I. , Cassereau L. , Pickup M. , Mouw J. K. , Ou G. , Templeman K. L. , Hannachi E.-I. , Gooch K. J. , Sarang-Sieminski A. L. , García A. J. , Weaver V. M.
Published: September 2017

Tumors are fibrotic and characterized by abundant, remodeled, and cross-linked collagen that stiffens the extracellular matrix stroma. The stiffened collagenous stroma fosters malignant transformation of the tissue by increasing tumor cell tension to promote focal adhesion formation and potentiate growth factor receptor signaling through kinase. Importantly, collagen cross-linking requires fibronectin (FN). Fibrotic tumors contain abundant FN, and tumor cells frequently up-regulate the FN receptor α5β1 integrin. Using transgenic and xenograft models and tunable two- and three-dimensional substrates, we show that FN-bound α5β1 integrin promotes tension-dependent malignant transformation through engagement of the synergy site that enhances integrin adhesion force. We determined that ligation of the synergy site of FN permits tumor cells to engage a zyxin-stabilized, vinculin-linked scaffold that facilitates nucleation of phosphatidylinositol (3,4,5)-triphosphate at the plasma membrane to enhance phosphoinositide 3-kinase (PI3K)-dependent tumor cell invasion. The data explain why rigid collagen fibrils potentiate PI3K activation to promote malignancy and offer a perspective regarding the consistent up-regulation of α5β1 integrin and FN in many tumors and their correlation with cancer aggression.
Use of Smoking Cessation Methods Among Patients Receiving Office-based Buprenorphine Maintenance Treatment
Authors: Shah Pooja A. , Cunningham Chinazo O. , Brisbane Mia T. , DeLuca Joseph P. , Nahvi Shadi
Published: September 2017

Objectives:

Provision of smoking-cessation treatment is limited in office-based buprenorphine maintenance treatment (BMT) settings. This study describes smoking and smoking-cessation behaviors among patients receiving office-based BMT.

Methods:

Cross-sectional study of patients receiving office-based BMT at a community health center in the Bronx, NY. We interviewed patients assessing sociodemographic, and substance use and tobacco use characteristics, including methods used for smoking cessation. We reported simple frequencies and explored associations of BMT characteristics with smoking behaviors.

Results:

Of 68 patients, 87.7% were current cigarette smokers, 7.9% were former smokers, and 4.4% had never smoked. Of lifetime smokers, 83.1% reported at least 1 prior quit attempt, and 78.5% had used medication (75.4% used nicotine replacement therapy, 29.2% varenicline, and 9.2% bupropion). Ten patients (15.4%) reported using electronic cigarettes to try to quit smoking. Stopping “cold turkey” (40.0%) and gradually decreasing the number of cigarettes smoked (32.3%) were nonpharmacological methods of quitting tried most often. Use of behavioral support, including stop-smoking programs and counseling, was low. Higher dose and longer duration of BMT was associated with greater smoking frequency.

Conclusions:

Patients receiving BMT have a high prevalence of cigarette smoking, though most have tried to quit, and have prior experience with pharmacotherapy for smoking cessation. Efforts to optimize smoking-cessation treatments among BMT patients are needed.
Be Sweet to Babies During Painful Procedures
Authors: Harrison Denise , Larocque Catherine , Reszel Jessica , Harrold JoAnn , Aubertin Cheryl
Published: September 2017

Background:

Breastfeeding (BF), skin-to-skin care (SSC), and sucrose effectively reduce babies' pain during newborn blood work, but these strategies are infrequently used. Our team developed a parent-targeted video intervention showing the effectiveness of the 3 pain management strategies.

Purpose:

To evaluate neonatal intensive care unit (NICU) parents' (1) baseline knowledge and previous use of BF, SSC, and sucrose for procedural pain management; (2) intention to advocate/use BF, SSC, or sucrose for their infants' future blood work after viewing the video; (3) intention to recommend the video to other parents; and (4) perceptions of the video and identify areas for improvement.

Methods:

Cross-sectional survey of parents in an NICU.

Results:

Fifty parents were enrolled: 33 mothers and 17 fathers. More than two-thirds (68%) of parents had prior knowledge of analgesic effects of sucrose; knowledge of SSC and BF as pain-reduction strategies was lower: 44% and 34%, respectively. Eighty-six percent of parents felt the video was the right length; 7 (14%) felt the video was too long. After viewing the video, 96% of parents intended to advocate for BF, SSC, or sucrose for pain management and 88% parents would recommend the video to other parents.

Implications for practice:

The video is acceptable to parents, is feasible to deliver to parents in an NICU, and has potential to increase parents' intent to advocate for pain management strategies for their infants.

Implications for research:

Future studies are required to evaluate the effectiveness of this parent-targeted intervention on increasing actual use of pain management in clinical practice.
Change in Human Papillomavirus Prevalence Among U.S. Women Aged 18–59 Years, 2009–2014
Authors: Berenson Abbey B. , Hirth Jacqueline M. , Chang Mihyun
Published: September 2017

OBJECTIVE:

To examine changes in prevalence of vaginal human papillomavirus (HPV) between 2009–2010 and 2013–2014 among both vaccinated and unvaccinated U.S. women.

METHODS:

We evaluated HPV prevalence among women 18–59 years old using cross-sectional survey data from three different cycles of the National Health and Nutrition Examination Survey. Data were stratified into four age groups (18–26, 27–34, 35–44, and 45–49 years) to examine trends over time among women of different ages in the postvaccine era. Multivariable analyses, which controlled for descriptive variables, were used to examine the prevalence of quadrivalent vaccine-type HPV by vaccination status.

RESULTS:

We observed a significant decrease in the prevalence of vaccine-type HPV among women 18–59 years of age from 2009–2010 to 2013–2014. This decline was only significant in those 18–26 years old when the sample was stratified into the four age groups. Among vaccinated 18–26 year olds, HPV prevalence remained low from 2009–2010 (3.9%) to 2013–2014 (2.0%; prevalence ratio 0.51, 95% CI 0.18–1.46). Unvaccinated women 18–26 years old also demonstrated a significant decrease over time from 19.5% in 2009–2010 to 9.7% in 2013–2014 (prevalence ratio 0.44, 95% CI 0.22–0.91). Prevalence did not significantly change among unvaccinated women 26 years old or older.

CONCLUSIONS:

The decline in HPV infections among unvaccinated 18- to 26-year-old women suggests that young women in the United States are beginning to benefit from herd immunity resulting from the introduction of the HPV vaccine.
Improvement in Outcomes of Major Obstetric Hemorrhage Through Systematic Change
Authors: Skupski Daniel W. , Brady David , Lowenwirt Isaac P. , Sample Jason , Lin Stephanie N. , Lohana Rahul , Eglinton Gary S.
Published: September 2017

OBJECTIVE:

To report the outcomes over 14 years of sustained systematic institutional focus on the care of women with major obstetric hemorrhage, defined as estimated blood loss greater than 1,500 mL.

METHODS:

A retrospective cohort study of women with major obstetric hemorrhage at our hospital from 2000 to 2014 compares baseline conditions (age, multiparity, prior cesarean delivery, morbidly adherent placenta), morbidity (lowest mean temperature, lowest mean pH, coagulopathy, hysterectomy), and mortality among three time periods (period 1=January 2000 to December 2001, period 2=January 2002 to August 2005, period 3=September 2005 to December 2014). We also describe the systematic changes that helped to sustain our improved outcomes.

RESULTS:

During the three time periods, there were 5,811, 12,912, and 38,971 births; the rate of major obstetric hemorrhage increased over these periods: 2.1, 3.8 and 5.3 cases per 1,000 births, respectively. Two deaths from hemorrhage occurred in period 1 and none thereafter. Among women who experienced massive hemorrhage, morbidity significantly improved in each successive period: median lowest pH increased from 7.23 to 7.34 to 7.35 (periods 2 and 3 significantly higher than period 1), median lowest maternal temperature (°C) improved, 35.2 to 36.1 to 36.4 (all difference significant), and the rate of coagulopathy decreased, 58.3% to 28.6% to 13.2% (period 3 significantly lower than periods 1 and 2) (all P values <.001). Peripartum hysterectomies were more frequent and more frequently planned over time rather than urgent in each successive period: 0 of 6 to 6 of 18 (33%) to 31 of 64 (48.4%) (P=.044). During period 3, we reorganized the obstetric rapid response team, instituted a massive transfusion protocol and use of uterine balloon tamponade, and promoted a culture of safety in two ways—through more intensive education regarding hemorrhage and escalation (encouraging all staff to contact senior leaders).

CONCLUSION:

A sustained level of patient safety is achievable when treating major obstetric hemorrhage, as shown by a progressive decrease in morbidity despite increasing rates of hemorrhage.
Early Second-Trimester Fetal Growth Restriction and Adverse Perinatal Outcomes
Authors: Temming Lorene A. , Dicke Jeffrey M. , Stout Molly J. , Rampersad Roxane M. , Macones George A. , Tuuli Methodius G. , Cahill Alison G.
Published: September 2017

OBJECTIVE:

To estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation.

METHODS:

This was a retrospective cohort study of all singleton, nonanomalous pregnancies undergoing ultrasonography to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infectious etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight less than the 10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birth weight less than the 10th percentile. Secondary outcomes included preterm delivery at less than 37 and less than 28 weeks of gestation, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis.

RESULTS:

Of 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with a more than fivefold increase in risk of SGA at birth (36.9% compared with 9.1%, adjusted odds ratio [OR] 5.5, 95% CI 4.3–7.0), stillbirth (2.5% compared with 0.4%, OR 6.2, 95% CI 2.7–12.8), and neonatal death (1.4% compared with 0.3%, OR 5.2, 95% CI 1.6–13.5). Rates of indicated preterm birth at less than 37 weeks of gestation (7.3% compared with 3.3%, OR 2.3, 95% CI 1.5–3.5) and less than 28 weeks of gestation (2.5% compared with 0.2%, OR 10.8, 95% CI 4.5–23.4), neonatal need for respiratory support (16.9% compared with 7.8%, adjusted OR 1.6, 95% CI 1.1–2.2), and necrotizing enterocolitis (1.4% compared with 0.2%, OR 7.7, 95% CI 2.3–20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different.

CONCLUSION:

Although fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.
Reducing Pain During Intrauterine Device Insertion
Authors: Akers Aletha Y. , Steinway Caren , Sonalkar Sarita , Perriera Lisa K. , Schreiber Courtney , Harding Jennifer , Garcia-Espana J. Felipe
Published: September 2017

OBJECTIVE:

To estimate the effect of a 1% lidocaine paracervical nerve block on pain during intrauterine device (IUD) insertion compared with a sham block in adolescents and young women.

METHODS:

We conducted a multisite, single-blind, sham-controlled randomized trial in adolescents and young women having a 13.5-mg levonorgestrel IUD inserted. Enrollment occurred at three family planning clinics in Philadelphia, Pennsylvania. Eligible adolescents and young women were aged 14–22 years, nulliparous, not currently or recently pregnant, and English-speaking. Participants were randomized using computer-generated allocation in block sizes of four to receive a 10-mL 1% lidocaine paracervical block or a sham block (1 cm depression of the vaginal epithelium at paracervical block sites with a wooden cotton-tipped applicator). Only patients were blinded. The primary outcome was pain after IUD insertion measured with a 100-mm visual analog scale. Using a two-sided t test and assuming a 20-mm difference in visual analog scale scores, a SD of 28 mm, an α of 0.05, and 90% power, a sample of 43 participants per group was estimated.

RESULTS:

Between March 2015 and July 2016, 95 participants enrolled (47 lidocaine block group; 48 sham block group). All were included in the analysis. Forty-four percent were white, 36% black, 65% privately insured, and 79% previously used contraception. The median visual analog scale score after IUD insertion was 30.0 (95% CI 20.0–58.0) in the lidocaine block group and 71.5 (95% CI 66.0–82.0) in the sham block (P<.001).

CONCLUSION:

A 10-mL 1% lidocaine paracervical nerve block reduces pain during IUD insertion in adolescents and young women compared with a sham block with pressure on the vaginal epithelium.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02352714.
Internal Validation of the Sepsis in Obstetrics Score to Identify Risk of Morbidity From Sepsis in Pregnancy
Authors: Albright Catherine M. , Has Phinnara , Rouse Dwight J. , Hughes Brenna L.
Published: September 2017

OBJECTIVE:

To prospectively validate the Sepsis in Obstetrics Score, a pregnancy-specific sepsis scoring system, to identify risk for intensive care unit (ICU) admission for sepsis in pregnancy.

METHODS:

This is a prospective validation study of the Sepsis in Obstetrics Score. The primary outcome was admission to the ICU for sepsis. Secondary outcomes included admission to a telemetry unit and time to administration of antibiotic therapy. We evaluated test characteristics of a predetermined score of 6 or greater.

RESULTS:

Between March 2012 and May 2015, 1,250 pregnant or postpartum women presented to the emergency department and met systemic inflammatory response syndrome criteria. Of those, 425 (34%) had a clinical suspicion or diagnosis of an infection, 14 of whom (3.3%) were admitted to the ICU. The Sepsis in Obstetrics Score had an area under the curve of 0.85 (95% CI 0.76–0.95) for prediction of ICU admission for sepsis. This is within the prespecified 15% margin of the area under the curve of 0.97 found in the derivation cohort. A score of 6 or greater had a sensitivity of 64%, specificity of 88%, positive predictive value of 15%, and negative predictive value of 98.6%. Women with a score 6 or greater were more likely to be admitted to the ICU (15% compared with 1.4%, P<.01), admitted to a telemetry unit (37.3% compared with 7.2%, P<.01), and have antibiotic therapy initiated (90% compared with 72.9%, P<.01), initiated more quickly (3.2 compared with 3.7 hours, P=.03), although not within 1 hour (5.6 compared with 3.4%, P=.44).

CONCLUSION:

The Sepsis in Obstetrics Score is a validated pregnancy-specific score to identify risk of ICU admission for sepsis with the threshold score of 6 having a negative predictive value of 98.6%. Adherence to antibiotic administration guidelines is poor.
Accuracy of Endometrial Sampling in Endometrial Carcinoma
Authors: Visser Nicole C. M. , Reijnen Casper , Massuger Leon F. A. G. , Nagtegaal Iris D. , Bulten Johan , Pijnenborg Johanna M. A.
Published: September 2017

OBJECTIVE:

To assess the agreement between preoperative endometrial sampling and final diagnosis for tumor grade and subtype in patients with endometrial carcinoma.

DATA SOURCES:

MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane library were searched from inception to January 1, 2017, for studies that compared tumor grade and histologic subtype in preoperative endometrial samples and hysterectomy specimens.

METHODS OF STUDY SELECTION:

In eligible studies, the index test included office endometrial biopsy, hysteroscopic biopsy, or dilatation and curettage; the reference standard was hysterectomy. Outcome measures included tumor grade, histologic subtype, or both.

TABULATION, INTEGRATION, AND RESULTS:

Two independent reviewers assessed the eligibility of the studies. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies). A total of 45 studies (12,459 patients) met the inclusion criteria. The pooled agreement rate on tumor grade was 0.67 (95% CI 0.60–0.75) and Cohen's κ was 0.45 (95% CI 0.34–0.55). Agreement between hysteroscopic biopsy and final diagnosis was higher (0.89, 95% CI 0.80–0.98) than for dilatation and curettage (0.70, 95% CI 0.60–0.79; P=.02); however, it was not significantly higher than for office endometrial biopsy (0.73, 95% CI 0.60–0.86; P=.08). The lowest agreement rate was found for grade 2 carcinomas (0.61, 95% CI 0.53–0.69). Downgrading was found in 25% and upgrading was found in 21% of the endometrial samples. Agreement on histologic subtypes was 0.95 (95% CI 0.94–0.97) and 0.81 (95% CI 0.69–0.92) for preoperative endometrioid and nonendometrioid carcinomas, respectively.

CONCLUSION:

Overall there is only moderate agreement on tumor grade between preoperative endometrial sampling and final diagnosis with the lowest agreement for grade 2 carcinomas.
Distressing Sexual Function at Midlife
Authors: Simon James A. , Lukas Vanessa A.
Published: September 2017

Female sexual dysfunction (FSD) is characterized as chronic sexual symptoms that manifest with personal distress in the domains of desire, arousal, orgasm, and pain. Extensive epidemiologic evidence estimates that almost 50% of perimenopausal and postmenopausal women experience FSD. Screening for FSD is not readily conducted and patient–physician discussion of sexuality is limited by the lack of physician training on the topic and by the patient-held belief that sexual issues are not medical in nature. The purpose of this commentary is to provide clinicians with a framework to approach the discussion of FSD, to clinically identify FSD through patient symptoms and physical signs, and to manage FSD in perimenopausal and postmenopausal patients with the available U.S. Food and Drug Administration–approved and off-label treatments. Particular attention will be paid to FSD with common midlife onset including vulvovaginal atrophy, vulvodynia, and hypoactive sexual desire disorder. Although evaluating FSD can be a challenge, triaging symptoms by addressing pain before desire and arousal will improve patient outcomes and greatly simplify FSD management.
How Common Is the Ponticulus Posticus?
Authors: Saleh Ahmed , Gruber Jilian , Bakhsh Wajeeh , Rubery Paul T. , Mesfin Addisu
Published: September 2017

Study Design.

A computed tomography (CT) study of the morphology of the C1 vertebra.

Objective.

Is to determine the prevalence of ponticulus posticus (PP) by analyzing CT scans performed on a large, diverse population in the northeast United States. This study also proposes a CT-based classification system both to aid in unifying the description of PP, and to aid in future research.

Summary of Background Data.

The prevalence of PP varies from 5% to 68% in published studies. There may be geographic variation in the prevalence of PP. Our objective was to establish the prevalence of PP in the general population, and to develop a comprehensive classification system to describe PP.

Methods.

We evaluated cervical spine CT scans performed on patients in the emergency room of a level I trauma center over a 1-year period (January 1, 2014–December 31, 2014). The CT images were evaluated for the presence of a PP, and if present the following demographic data were collected: age, sex, race/ethnicity, and body mass index (BMI). We propose a novel classification system to standardize the description of PP identified on CT scan.

Results.

Two thousand, nine hundred and seventeen cervical spine CT scans were reviewed in this study. The prevalence of PP was 22.5%. Men had a higher prevalence of PP than women (53.5% male vs. 46.5% female P ≤ 0.01). When compared with the overall population, African–Americans were more likely to have a PP (P ≤ 0.01), while Caucasian patients were less likely (P ≤ 0.01). The novel classification consisted of a two letter designation for each patient, with the first letter denoting the right sided arch and the second letter the left sided arch. Each side of the arch described as an A, B, or C type. The A type had no presence of a PP, B type had in incomplete PP, and C type had a complete PP. The most common type of a PP was CC encompassing 25% of the patients. The presence of a PP was more common in the left sided arch than the right side (B and C type Left 89.2% vs. B and C type Right 84.7%, P = 0.02).

Conclusion.

We found a 22.5% prevalence of PP in 2917 patients undergoing a cervical spine CT. This is the largest study to evaluating the prevalence of PP.

Level of Evidence: 4
Advances in immunotherapy in multiple myeloma
Authors: Boussi Leora , Niesvizky Ruben
Published: September 2017

Purpose of review

Here, we explore the significant progress made in the treatment of multiple myeloma, focusing on immunotherapy and the promise it has offered to patients suffering from advanced disease.

Recent findings

Multiple myeloma, a B-cell malignancy, is characterized by unregulated plasma cell growth in the bone marrow as well as strong immunosuppression in the tumor microenvironment. mAbs targeting tumor antigens overcome this, increasing T-cell activation, multiple myeloma cell death, and depth of response. Similarly, adoptive T-cell therapy aims to engineer or isolate tumor-specific T cells for a targeted approach. Finally, peptide and dendritic cell/tumor fusion vaccines reeducate the immune system, expanding the immune response and generating long-term memory to prevent relapse of disease. Many of these approaches have been combined with existing therapies to enhance antitumor immunity.

Immunotherapeutic approaches have remarkably changed the treatment paradigm for multiple myeloma, and encouraging patient responses have warranted further investigation into mAbs, adoptive T-cell therapy, vaccines, and combination therapy.
Clinical Pearls in Venovenous Extracorporeal Life Support for Adult Respiratory Failure
Authors: Tay Chee Kiang , Sung Kiick , Cho Yang Hyun
Published: September 2017

Extracorporeal life support (ECLS) has been widely utilized to treat neonatal respiratory failure for two decades. However, its uptake in the case of adult respiratory failure has been slow because of a paucity of quality evidence and a sluggish tempo of ECLS-related technological advances. In recent years, interest in ECLS has been piqued after encouraging results were reported from its use during the 2009 H1N1 influenza pandemic. In a world constantly under threat from another influenza epidemic or deadly novel respiratory infection, e.g., the severe acute respiratory syndrome (SARS) virus, the Middle East respiratory syndrome coronavirus (MERS-CoV), the role of venovenous (VV) ECLS as a treatment modality for acute respiratory distress syndrome (ARDS) cannot be overemphasized. In hopes of standardizing practice, the Extracorporeal Life Support Organization (ELSO) has published books and guidelines on ECLS. However, high-level evidence to guide clinical decisions is still expediently needed in this field. Relying on the available literature and our experience in the recent South Korean MERS-CoV outbreak, we hope to highlight key physiologic and clinical points in VV ECLS for adult respiratory failure in this review.
Successful Esophageal Dilation of Eosinophilic Esophagitis (EoE) Patients With a Previous Postdilation Complication
Authors: Lipka Seth , Kumar Ambuj , Richter Joel E.
Published: September 2017

Introduction:

Esophageal dilation is an effective and safe treatment option for fibrostenotic eosinophilic esophagitis (EoE). Despite the safety, adverse events occur, yet there is scarce literature on the best treatment postcomplications.

Methods:

Patients with diagnosis of EoE (≥15 eosinophils per high-power field) from 2011 to 2015 treated at our center were included. Thirty patients with fibrostenotic disease had records available regarding serial dilation therapy. Eight patients previously experienced complications by outside providers. Groups were created based on history of complication before our dilation versus a group without. Mean difference and odds ratio with 95% confidence interval (CI) were calculated.

Results:

There were 8 complications, 7 occurred during dilation and 1 during passage of the endoscope. Esophageal diameter at initial dilation was lower in patients with prior complications 9.0±1.51 versus 11.73±2.98 mm (95% CI: −4.44, −1.02; P=0.003). However, end-esophageal diameter was similar across both groups 15.8±1.8 versus 16.1±2.0 mm. Total number of dilation sessions: 4.0±1.8 versus 2.32±1.0 (95% CI: 0.17, 3.19; P=0.03), as well as sessions to reach 17 mm diameter 3.8±1.0 versus 2.3±1.0 (95% CI: −0.08, 2.89; P=0.04), were higher in the patients with complications. The length of time in months to reach an esophageal diameter of 17 mm was longer in patients with complications, but the difference was not statistically significant 3.50±0.6 versus 2.3±2.3 months (P=0.09).

Conclusions:

Esophageal dilation is a safe and effective modality to treat severe fibrostenotic EoE in patients with prior history of complications. The keys to success are: (1) start with lower diameter bougies and (2) dilate slowly over a longer time course to reach targeted diameter and symptom resolution.
Impact of a Nurse Residency Program on Transition to Specialty Practice
Authors: Boyer Susan A. , Valdez-Delgado Krystal K. , Huss Jody L. , Barker Amber J. , Mann-Salinas Elizabeth A.
Published: September 2017

A nurse residency program can support transition for new-to-specialty nurses but requires commitment of time and resources. This implementation project used a specialty residency program shown to be effective in a Burn Center, and translated it into the Emergency Department and Maternal Child Health area located within the same medical treatment facility. Preceptor survey responses and leadership assessment of program suitability provided data related to intervention impact. The evidence pertaining to developing specialty knowledge, skills, competency, and clinical reasoning validated program efficacy. Project outcomes justify investment in building a standardized transitional support system.
Epigenetic Alterations in Bone and Soft Tissue Tumors
Authors: Wojcik John , Cooper Kumarasen
Published: September 2017

Human malignancies are driven by heritable alterations that lead to unchecked cellular proliferation, invasive growth and distant spread. Heritable changes can arise from changes in DNA sequence, or, alternatively, through altered gene expression rooted in epigenetic mechanisms. In recent years, high-throughput sequencing of tumor genomes has revealed a central role for mutations in epigenetic regulatory complexes in oncogenic processes. Through interactions with or direct modifications of chromatin, these proteins help control the accessibility of genes, and thus the transcriptional profile of a cell. Dysfunction in these proteins can lead to activation of oncogenic pathways or silencing of tumor suppressors. Although epigenetic regulators are altered across a broad spectrum of human malignancies, they play a particularly central role in tumors of mesenchymal and neuroectodermal origin. This review will focus on recent advances in the understanding of the molecular pathogenesis of a subset of tumors in which alterations in the polycomb family of chromatin modifying complexes, the SWI/SNF family of nucleosome remodelers, and histones play a central role in disease pathogenesis. Although this review will focus predominantly on the molecular mechanisms underlying these tumors, each section will also highlight areas in which an understanding of the molecular pathogenesis of these diseases has led to the adoption of novel immunohistochemical and molecular markers.
If it is Not a Glioblastoma, Then What is it? A Differential Diagnostic Review
Authors: Gokden Murat
Published: September 2017

As its historical name glioblastoma multiforme implies, glioblastoma is a histologically diverse, World Health Organization grade IV astrocytic neoplasm. In spite of its simple definition of presence of vascular proliferation and/or necrosis in a diffuse astrocytoma, the wide variety of cytohistomorphologic appearances overlap with many other neoplastic or non-neoplastic lesions. Here, after a brief review of glioblastoma is provided, the differential diagnostic possibilities with an emphasis on mimics and pitfalls are discussed. To provide an approach applicable to diagnostic practice, these discussions are grouped arbitrarily according to general malignant appearance such as pleomorphic xanthoastrocytoma and ganglioglioma, especially their anaplastic versions, and cellular features such as small cell and epithelioid glioblastoma. Some non-neoplastic lesions that can potentially be mistaken for glioblastoma under certain circumstances are also briefly mentioned. Additional studies, including immunohistochemistry and molecular markers, are included where applicable. Otherwise, exhaustive review of these individual entities, including their epidemiology and molecular biology, is outside the scope of this discussion.
Getting the Word Out: New Approaches for Disseminating Public Health Science
Authors: Brownson Ross C. , Eyler Amy A. , Harris Jenine K. , Moore Justin B. , Tabak Rachel G.
Published: September 2017

The gap between discovery of public health knowledge and application in practice settings and policy development is due in part to ineffective dissemination. This article describes (1) lessons related to dissemination from related disciplines (eg, communication, agriculture, social marketing, political science), (2) current practices among researchers, (3) key audience characteristics, (4) available tools for dissemination, and (5) measures of impact. Dissemination efforts need to take into account the message, source, audience, and channel. Practitioners and policy makers can be more effectively reached via news media, social media, issue or policy briefs, one-on-one meetings, and workshops and seminars. Numerous “upstream” and “midstream” indicators of impact include changes in public perception or awareness, greater use of evidence-based interventions, and changes in policy. By employing ideas outlined in this article, scientific discoveries are more likely to be applied in public health agencies and policy-making bodies.
Is Orbital Floor Reconstruction With Titanium Mesh Safe?
Authors: Al-Khdhairi Omar Bakr Hazm , Abdulrazaq Saif Saadedeen
Published: September 2017

To reconstruct the orbital floor defects there are a lot of reconstruction materials, the surgeon must choose one of them. The authors share their experience with 10 patients suffering from orbital trauma causing orbital floor fracture; those fractures were reconstructed using titanium mesh. No complications were encountered postoperatively apart from 1 patient with ectropion. Titanium mesh is a perfect material for the reconstruction of the orbital fractures, eliminating the need for autogenous bone graft.
Evidence for Persistent Immune Suppression in Patients Who Develop Chronic Critical Illness After Sepsis
Authors: Stortz Julie A. , Murphy Tyler J. , Raymond Steven L. , Mira Juan C. , Ungaro Ricardo , Dirain Marvin L. , Nacionales Dina C. , Loftus Tyler J. , Wang Zhongkai , Ozrazgat-Baslanti Tezcan , Ghita Gabriela L. , Brumback Babette A. , Mohr Alicia M. , Bihorac Azra , Efron Philip A. , Moldawer Lyle L. , Moore Frederick A. , Brakenridge Scott C.
Published: September 2017

Background:

Many sepsis survivors develop chronic critical illness (CCI) and are assumed to be immunosuppressed, but there is limited clinical evidence to support this. We sought to determine whether the incidence of secondary infections and immunosuppressive biomarker profiles of patients with CCI differ from those with rapid recovery (RAP) after sepsis.

Methods:

This prospective observational study evaluated 88 critically ill patients with sepsis and 20 healthy controls. Cohorts were defined based on clinical trajectory (early death, RAP, or CCI), whereas immunosuppression was clinically determined by the presence of a postsepsis secondary infection. Serial blood samples were collected for absolute lymphocyte counts (ALCs), monocytic human leukocyte antigen-DR (mHLA-DR) expression, and plasma-soluble programmed death-ligand 1 (sPD-L1) concentrations.

Results:

Of the 88 patients with sepsis, 3 (3%) died within 14 days of sepsis onset, 50 (57%) experienced RAP, and 35 (40%) developed CCI. Compared with RAP patients, CCI patients exhibited a higher incidence and overall number of infections adjusted for hospital length of stay. ALC and mHLA-DR levels were dramatically reduced at the time of sepsis diagnosis when compared with healthy controls, whereas sPD-L1 concentrations were significantly elevated. There were no differences between RAP and CCI patients in ALC, sPD-L1, or mHLA-DR at the time of diagnosis or within 24 h after sepsis diagnosis. However, in contrast to the RAP group, CCI patients failed to exhibit any trend toward restoration of normal values of ALC, HLA-DR, and sPD-L1.

Conclusions:

Septic patients demonstrate clinical and biological evidence to suggest they are immunosuppressed at the time of sepsis diagnosis. Those who develop CCI have a greater incidence of secondary infections and persistently aberrant markers of impaired host immunity, although measurements at the time of sepsis onset did not distinguish between subjects with RAP and CCI.
Modeling Surgical Technical Skill Using Expert Assessment for Automated Computer Rating
Authors: Azari David P. , Frasier Lane L. , Quamme Sudha R. Pavuluri , Greenberg Caprice C. , Pugh Carla M. , Greenberg Jacob A. , Radwin Robert G.
Published: September 2017

Objective:

Computer vision was used to predict expert performance ratings from surgeon hand motions for tying and suturing tasks.

Summary Background Data:

Existing methods, including the objective structured assessment of technical skills (OSATS), have proven reliable, but do not readily discriminate at the task level. Computer vision may be used for evaluating distinct task performance throughout an operation.

Methods:

Open surgeries was videoed and surgeon hands were tracked without using sensors or markers. An expert panel of 3 attending surgeons rated tying and suturing video clips on continuous scales from 0 to 10 along 3 task measures adapted from the broader OSATS: motion economy, fluidity of motion, and tissue handling. Empirical models were developed to predict the expert consensus ratings based on the hand kinematic data records.

Results:

The predicted versus panel ratings for suturing had slopes from 0.73 to 1, and intercepts from 0.36 to 1.54 (Average R
2 = 0.81). Predicted versus panel ratings for tying had slopes from 0.39 to 0.88, and intercepts from 0.79 to 4.36 (Average R
2 = 0.57). The mean square error among predicted and expert ratings was consistently less than the mean squared difference among individual expert ratings and the eventual consensus ratings.

Conclusions:

The computer algorithm consistently predicted the panel ratings of individual tasks, and were more objective and reliable than individual assessment by surgical experts.
The hominoid-specific gene DSCR4 is involved in regulation of human leukocyte migration
Authors: Saber Morteza Mahmoudi , Karimiavargani Marziyeh , Hettiarachchi Nilmini , Hamada Michiaki , Uzawa Takanori , Ito Yoshihiro , Saitou Naruya
Published: September 2017

DSCR4 (Down syndrome critical region 4) is an orphan retrotransposon-derived de-novo originated protein coding gene present only in hominoids (humans and great apes). Despite being located on the medically critical genomic region and abundance of evidences indicating its functionality, the role of this gene in human cells was utterly unknown. Due to absence of any prior knowledge regarding the function of DSCR4, for the first time here we used a gene-overexpression approach to discover biological importance and cellular roles of this gene. Our analysis strongly indicates DSCR4 to be mainly involved in regulation of the interconnected biological pathways related to cell migration, coagulation and immune system. We also showed that the predicted biological functions are consistent with tissue-specific expression of DSCR4 in migratory immune system leukocyte cells and neural crest cells that shape facial morphology of human embryo. Immune system and neural crest cells are also shown to be affected in Down syndrome patients who suffer from the same type of DSCR4 misregulation as in our study which further support our findings. Providing evidence for the critical roles of DSCR4 in human cells, our findings establish the basis for further investigations on the roles of DSCR4 in etiology of Down syndrome and unique characteristics of hominoids.
Synthesis of a eukaryotic chromosome reveals a role for N6-methyladenine in nucleosome organization
Authors: Beh Leslie Y. , Debelouchina Galia T. , Lindblad Kelsi A. , Kulej Katarzyna , Hutton Elizabeth R. , Bracht John R. , Sebra Robert P. , Garcia Benjamin A. , Muir Tom W. , Landweber Laura F.
Published: September 2017

Biochemical studies of chromatin have typically used either artificial DNA templates with unnaturally high affinity for histones, or small genomic DNA fragments deprived of their cognate physical environment. It has thus been difficult to dissect chromatin structure and function within fully native DNA substrates. Here, we circumvent these limitations by exploiting the minimalist genome of the eukaryoteOxytricha trifallax, whose notably small ~3kb chromosomes mainly encode single genes. Guided by high-resolution epigenomic maps of nucleosome organization, transcription, and DNA N6-methyladenine (m6dA) locations, we reconstruct full-lengthOxytrichachromosomesin vitroand use these synthetic facsimiles to dissect the influence of m6dA and histone post-translational modifications on nucleosome organization. We show that m6dA directly disfavors nucleosomes in a quantitative manner, leading to local decreases in nucleosome occupancy that are synergistic with histone acetylation. The effect of m6dA can be partially reversed by the action of an ATP-dependent chromatin remodeler. Furthermore, erasing m6dA marks fromOxytrichachromosomes leads to proportional increases in nucleosome occupancy across the genome. This work showcasesOxytrichachromosomes as powerful yet practical models for studying eukaryotic chromatin and transcription in the context of biologically relevant DNA substrates.

Highlights

De novosynthesis of complete, epigenetically definedOxytrichachromosomes

Epigenomic profiles of chromatin organization inOxytricha’sminiature chromosomes

m6dA directly disfavors nucleosome occupancy in natural and synthetic chromosomes

Histone acetylation and chromatin remodelers temper the impact of m6dA on chromatin