bluuebunny/crossref_metadata_2025 huggingface dataset:
Second Curettage for Low-Risk Nonmetastatic Gestational Trophoblastic Neoplasia
Authors: Osborne Raymond J. , Filiaci Virginia L. , Schink Julian C. , Mannel Robert S. , Behbakht Kian , Hoffman James S. , Spirtos Nick M. , Chan John K. , Tidy John A. , Miller David S.
Published: August 2016

OBJECTIVE:

To evaluate the efficacy and safety of second uterine curettage in lieu of chemotherapy for patients with low-risk, nonmetastatic gestational trophoblastic neoplasia (GTN) and to evaluate whether response to second curettage is independent of patient age, World Health Organization (WHO) risk score, registration human chorionic gonadotropin (hCG) level, lesion size, and depth of myometrial invasion measured on ultrasound examination.

METHODS:

This was a cooperative group multicenter prospective phase II study. Prestudy testing included quantitative hCG level, pelvic ultrasonography, and chest radiography. Patients were categorized according to WHO risk scoring criteria (low risk with a score of 0–6).

RESULTS:

Sixty-four women with newly diagnosed low-risk, nonmetastatic GTN were enrolled. Four patients were excluded. Twenty-four patients (40%) (lower 95% confidence limit 27.6%) were cured after second curettage. An additional two patients (3%) achieved a complete response but did not complete follow-up. Overall, 26 of 60 patients were able to avoid chemotherapy. Surgical failure was observed in 34 women (59%) and was more common in women 19 years old or younger or 40 years old or older. One case of grade 1 uterine perforation was successfully managed by observation. Four grade 1 and one grade 3 uterine hemorrhages were reported. New metastatic disease (lung) was identified in one of these women after second curettage. In three patients (surgical failures), the second curettage pathology was placental site trophoblastic tumor, and it was placental nodule in one additional patient.

CONCLUSION:

Second uterine curettage as initial treatment for low-risk, nonmetastatic GTN cures 40% of patients without significant morbidity.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, https://clinicaltrials.gov/, NCT00521118.
Accuracy of Home-Based Ultrasonographic Diagnosis of Obstetric Risk Factors by Primary-Level Health Care Workers in Rural Nepal
Authors: Kozuki Naoko , Mullany Luke C. , Khatry Subarna K. , Ghimire Ram K. , Paudel Sharma , Blakemore Karin , Bird Christine , Tielsch James M. , LeClerq Steven C. , Katz Joanne
Published: August 2016

OBJECTIVE:

To assess the feasibility of ultrasonographic task shifting by estimating the accuracy at which primary-level health care workers can perform community-based third-trimester ultrasound diagnosis for selected obstetric risk factors in rural Nepal.

METHODS:

Three auxiliary nurse–midwives received two 1-week ultrasound trainings at Tribhuvan University Teaching Hospital in Kathmandu. At a study site in rural Nepal, pregnant women who were 32 weeks of gestation or greater were enrolled and received ultrasound examinations from the auxiliary nurse–midwives during home visits. Each auxiliary nurse–midwife screened for noncephalic presentation, multiple gestation, and placenta previa. Deidentified digital ultrasonograms were stored and uploaded onto an online server, where certified sonologists and ultrasonographers reviewed the images and made their own diagnoses for the three conditions. Accuracy of auxiliary nurse–midwife diagnoses was then calculated.

RESULTS:

A total of 804 women contributed to the analysis. Each auxiliary nurse–midwife's κ statistic for diagnosis of noncephalic presentation was above 0.90 compared with the ultrasonogram reviewers. Sensitivity, specificity, and positive and negative predictive values were between 90% and 100% for all auxiliary nurse–midwives. For multiple gestation, the auxiliary nurse–midwives were in perfect agreement with both the ultrasonogram reviewers and maternal postpartum self-report. Two placenta previa cases were detected, and the ultrasonogram reviewers agreed with both.

CONCLUSION:

With limited training, primary-level health care workers in rural Nepal can accurately diagnose selected third-trimester obstetric risk factors using ultrasonography.
Association Between Western and Mediterranean Dietary Patterns and Mammographic Density
Authors: Castelló Adela , Ascunce Nieves , Salas-Trejo Dolores , Vidal Carmen , Sanchez-Contador Carmen , Santamariña Carmen , Pedraz-Pingarrón Carmen , Moreno Maria Pilar , Pérez-Gómez Beatriz , Lope Virginia , Aragonés Nuria , Vioque Jesús , Pollán Marina ,   on behalf of the DDM-Spain Research Group
Published: August 2016

OBJECTIVE:

To examine the association between two dietary patterns (Western and Mediterranean), previously linked to breast cancer risk, and mammographic density.

METHODS:

This cross-sectional study included 3,584 women attending population-based breast cancer screening programs and recruited between October 7, 2007, and July 14, 2008 (participation rate 74.5%). Collected data included anthropometric measurements; demographic, obstetric, and gynecologic characteristics; family and personal health history; and diet in the preceding year. Mammographic density was blindly assessed by a single radiologist and classified into four categories: less than 10%, 10–25%, 25–50%, and greater than 50%. The association between adherence to either a Western or a Mediterranean dietary pattern and mammographic density was explored using multivariable ordinal logistic regression models with random center-specific intercepts. Models were adjusted for age, body mass index, parity, menopause, smoking, family history, hormonal treatment, and calorie and alcohol intake. Differences according to women's characteristics were tested including interaction terms.

RESULTS:

Women with a higher adherence to the Western dietary pattern were more likely to have high mammographic density (n=242 [27%]) than women with low adherence (n=169 [19%]) with a fully adjusted odds ratio (ORQ4vsQ1) of 1.25 (95% confidence interval [CI] 1.03–1.52). This association was confined to overweight–obese women (adjusted ORQ4vsQ1 [95% CI] 1.41 [1.13–1.76]). No association between Mediterranean dietary pattern and mammographic density was observed.

CONCLUSION:

The Western dietary pattern was associated with increased mammographic density among overweight–obese women. Our results might inform specific dietary recommendations for women with high mammographic density.
Risk Factors for Dyspareunia After First Childbirth
Authors: Alligood-Percoco Natasha R. , Kjerulff Kristen H. , Repke John T.
Published: August 2016

OBJECTIVE:

To investigate risk factors for dyspareunia among primiparous women.

METHODS:

This was a planned secondary analysis using data from the 1- and 6-month postpartum interviews of a prospective study of women who delivered their first neonate in Pennsylvania, 2009–2011. Participants who had resumed sexual intercourse by the 6-month interview (N=2,748) constituted the analytic sample. Women reporting a big or medium problem with painful intercourse at 6 months were categorized as having dyspareunia. Multivariable logistic regression was used to evaluate the effect of patient characteristics, obstetric and psychosocial factors, and breastfeeding on dyspareunia.

RESULTS:

There were 583 women (21.2%) who reported dyspareunia at 6 months postpartum. Nearly one third of those breastfeeding at 6 months reported dyspareunia (31.5%) compared with 12.7% of those not breastfeeding (adjusted odds ratio [OR] 2.89, 95% confidence interval [CI] 2.33–3.59, P<.001); 32.5% of those reporting a big or medium problem with perineal pain at 1 month reported dyspareunia at 6 months compared with 15.9% of those who did not (adjusted OR 2.45, 95% CI 1.93–3.10, P<.001); 28.3% of women who reported fatigue all or most of the time at 1 month reported dyspareunia at 6 months compared with 18.0% of those who reported fatigue less often (adjusted OR 1.60, 95% CI 1.30–1.98, P<.001); and 24.1% of those who scored in the upper third on the stress scale at 1 month reported dyspareunia at 6 months postpartum compared with 15.6% of those who scored in the lowest third (adjusted OR 1.55, 95% CI 1.18–2.02, P=.001).

CONCLUSION:

In this prospective cohort study, we identified specific risk factors for dyspareunia in primiparous women that can be discussed at the first postpartum visit, including breastfeeding, perineal pain, fatigue, and stress.
Reverse Vesicouterine Fold Dissection for Laparoscopic Hysterectomy After Prior Cesarean Deliveries
Authors: Nezhat Camran , Grace Lindsey A. , Razavi Gity M. , Mihailide Catalina , Bamford Holden
Published: August 2016

BACKGROUND:

Cesarean delivery adhesions, during laparoscopic hysterectomy, can present surgical challenges, including distortion of anatomy, prolonged operating time, and inadvertent injury to nearby structures.

TECHNIQUE:

At the time of laparoscopic hysterectomy, in patients with significant adhesions from prior cesarean deliveries, we use a reverse inferior to superior vesicouterine fold dissection to mobilize the scarred bladder. We use this as an alternative to the commonly practiced technique of mobilizing the bladder in a superior to inferior fashion at the time of laparoscopic hysterectomy.

EXPERIENCE:

Fifty-two patients with a median age of 42.5 years are presented. Forty-eight patients were discharged within 3–6 hours postoperatively. Sixteen patients were discharged with Foley catheters, because they were unable to void within the protocol for a fast-track discharge. The catheters were removed between postoperative days 1 and 5. There were no gastrointestinal or genitourinary complications. One patient experienced a delayed vaginal cuff abscess and bleeding, which were managed conservatively.

CONCLUSION:

Reverse vesicouterine fold dissection is a useful alternative technique for laparoscopic hysterectomy in women with a history of prior cesarean deliveries.
What Is New in the Prevention of Preeclampsia?
Authors: Norton Mary E.
Published: August 2016

This month we focus on current research in prevention of preeclampsia. Dr. Norton discusses five recent publications, which are 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.
Static Compression Induces ECM Remodeling and Integrin α2β1 Expression and Signaling in a Rat Tail Caudal Intervertebral Disc Degeneration Model
Authors: Yan ZhanJun , Pan YouDong , Wang ShiHui , Cheng MaoHua , Kong HongMei , Sun ChunGuang , Hu Kai , Chen TongLei , Dong QiRong , Chen JianFeng
Published: August 2016

Study Design.

A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD.

Objective.

The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD.

Summary of Background Data.

Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive.

Methods.

Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarov-type apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8–9 was analyzed.

Results.

In three-level IVDD model, significant degeneration of the Co8–9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8–9 disc. Compression loading altered the expression of integrin α2β1 (upregulated) and α10β1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin α1, α2, α11, and β1 were upregulated, whereas α10 was downregulated. Similar activation of integrin signaling was observed.

Conclusion.

Static compression altered collagen and MMP expression, and promoted β1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force.

Level of Evidence: N/A
Hybrid Stabilization of Periprosthetic Distal Femoral Fractures Following Total Knee Replacement: Technique and Results
Authors: Kalyanasundaram Sivaprasad , Pankapilly Biju , Varughese Jacob , Jacob George , Menon Venugopal K.
Published: August 2016

The incidence of periprosthetic distal femoral fractures after total knee replacement has been reported to be in the range of 0.3% to 2.5%. The treatment is technically challenging in fractures with small osteopenic distal fragment that might compromise stable fixation. Proper alignment and stabilization of the fracture is mandatory for early mobilization of the knee. Through the previous midline scar, knee is approached and with minimal soft tissue dissection a 7 or 9 mm supracondylar intramedullary nail is inserted retrograde achieving reduction and temporary stability. To augment the fixation, a distal femoral locking plate is slid submuscular by minimal invasive technique and held with screws. When possible, the nail locking screws are inserted through the plate, achieving stable reduction and adequate fixation to allow early mobilization during the postoperative period. Between 2009 and 2015, 13 patients with 14 type-2 periprosthetic supracondylar fractures were operated with the hybrid fixation technique. All the patients achieved union at 3 months with no loss of alignment or loss of range of motion. In type-2 supracondylar fractures with marked comminution, osteopenia, and small distal fragment, the hybrid fixation technique achieves satisfactory reduction and adequate stabilization that helps in early mobilization and fracture healing without additional periosteal damage to the distal fragment.
Tablet-Based eBooks for Young Children: What Does the Research Say?
Authors: Reich Stephanie M. , Yau Joanna C. , Warschauer Mark
Published: August 2016

Objective:

Young children's use of electronic books (eBooks) is increasing as handheld touch screen devices, such as tablets, become increasingly available. Although older children's reading on tablets has been more broadly investigated, less is known about the impacts of digital reading for infant, toddlers, and preschoolers. This review compares the educational affordances of reading on tablets versus print books for young children's learning.

Method:

A qualitative synthesis of research on tablet-based eReading and young children's learning from screens was conducted.

Results:

When eBooks are designed well, preschool-aged children learn equally well and sometimes more than from print books. However, enhanced eBooks with sounds, animations, and games can distract children and reduce learning. When book-sharing with an adult, conversations during eBook reading are often about the platform while print book conversations are more often about the book content. For young children (0–2 yr), there is a paucity of research, but broader studies on learning from screens suggest limited educational benefits of tablet use for this age group.

Discussion:

The authors recommend that (1) the selection of eBooks (especially enhanced eBooks) be thoughtful as games or animations that are not related to the story content can be distracting for young children, (2) adults share in the reading experience as discussions of the story, text, and characters have been found to enhance comprehension, language development, and print awareness, and (3) tablet eBook use be restricted for infants and toddlers, as they benefit more from face-to-face interaction with caregivers than from interactive screens alone.
Functioning Among Youth with Comorbid Mood Disorder and Chronic Physical Illness in Public Sector Care
Authors: Green Amy E. , Ferrand John , Aarons Gregory A.
Published: August 2016

Objective:

The current study examines parent/caregiver and youth report of psychosocial and health-related functioning among youth served in public systems of care, with mood disorder only, comorbid mood disorder and chronic physical illness, and chronic physical illness only.

Method:

Participants were 539 youths (ages, 11–18; 64% male) with a mood disorder and/or chronic physical illness enrolled in a study of public sector care. Presence of mood disorder was based on youth report on the Diagnostic Interview Schedule for Children-IV. Parents reported whether they had been told by a school or health professional that their child had 1 of 8 categories of chronic physical illnesses. Psychosocial functioning was assessed with the Child Behavior Checklist and Youth Self Report. Parent and child versions of the Child Health Questionnaire assessed health-related functioning. Covariates included demographic variables, substance use, mental health service utilization, disruptive behavior disorders, and anxiety disorders. Multivariate analysis of covariances assessed differences on outcome measures among the 3 groups.

Results:

Parents and youths reported significantly worse psychosocial and health-related functioning for youth with comorbid mood and physical illnesses. Generally, parents reported lower functioning in youth with a physical illness compared with mood disorder, and youth with mood disorders reported lower functioning than those with physical illness.

Conclusion:

Youth with comorbid mood disorder and chronic physical illness experience high levels of impairment. Increased screening of mood disorders in pediatric health settings is warranted. Health systems, clinics, and clinicians should focus on integrating mental and physical health diagnosis and treatment.
Staff Responses When Parents Hit Children in a Hospital Setting
Authors: Font Sarah A. , Gershoff Elizabeth T. , Taylor Catherine A. , Terreros Amy , Nielsen-Parker Monica , Spector Lisa , Foster Rebecca H. , Budzak Garza Ann , Olson-Dorff Denyse
Published: August 2016

Objective:

Physical punishment of children is a prevalent practice that is condemned by most medical professionals given its link with increased risk of child physical abuse and other adverse child outcomes. This study examined the prevalence of parent-to-child hitting in medical settings and the intervention behaviors of staff who witness it.

Method:

Staff at a children's medical center and a general medical center completed a voluntary, anonymous survey. We used descriptive statistics to examine differences in the experiences of physicians, nurses, and other medical staff. We used logistic regression to predict intervention behaviors among staff who witnessed parent-to-child hitting.

Results:

Of the hospital staff who completed the survey (N = 2863), we found that 50% of physicians, 24% of nurses, 27% of other direct care staff, and 17% of nondirect care staff witnessed parent-to-child hitting at their medical center in the past year. A majority of physicians, nurses, and other direct care staff reported intervening sometimes or always. Nondirect care staff rarely intervened. Believing staff have the responsibility to intervene, and having comfortable strategies with which to intervene were strongly predictive of intervention behavior. Staff who did not intervene commonly reported that they did not know how to respond.

Conclusion:

Many medical center staff witness parent-to-child hitting. Although some of the staff reported that they intervened when they witnessed this behavior, the findings indicate that staff may need training to identify when and how they should respond.
FUNDUS AUTOFLUORESCENCE IN A SUBCLINICAL CASE OF BEST DISEASE
Authors: Schönbach Etienne M. , Scholl Hendrik P.
Published: August 2016

Purpose:

To demonstrate the usefulness of fundus autofluorescence for diagnosing a subclinical case of Best disease.

Results:

We describe a 27-year-old white woman without central visual symptoms, visual acuity of 20/12 in both eyes, carrying the previously reported p.Tyr227Cys mutation in the BEST1 gene. Although electrooculography, microperimetry (MP-1), and spectral-domain optical coherence tomography did not reveal unequivocal pathology, fundus autofluorescence imaging allowed to clearly detect a phenotypic correlate of Best disease, namely small areas of significantly increased fundus autofluorescence signals.

Conclusion:

This report suggests that in selected subclinical cases, fundus autofluorescence may be more sensitive than the MP-1 and spectral-domain optical coherence tomography in the detection of subclinical cases of BEST1-associated retinopathy.
RETINAL VEIN OCCLUSION IN A PATIENT WITH MATERNALLY INHERITED DIABETES AND DEAFNESS
Authors: Sanfilippo Christian J. , Prasad Pradeep , Sarraf David
Published: August 2016

Purpose:

To report a case of maternally inherited diabetes and deafness complicated by branch retinal vein occlusion and cystoid macular edema.

Methods:

Retrospective case report. Multimodal imaging including spectral domain optical coherence tomography, en face optical coherence tomography, and fundus autofluorescence was preformed, and the findings are presented.

Findings:

A 58-year-old female with a history of diabetes mellitus, hearing loss, and a previous diagnosis of age-related macular degeneration presented with decreased vision in the right eye. Clinical examination and multimodal imaging demonstrated a right inferior branch retinal vein occlusion complicated by cystoid macular edema and bilateral maculopathy suspicious for maternally inherited diabetes and deafness. Genetic testing confirmed an A3243G mitochondrial mutation.

Conclusion:

Multimodal retinal imaging is a key to guide diagnosis of rare genetic diseases such as maternally inherited diabetes and deafness. We report the unusual presentation of maternally inherited diabetes and deafness complicated by branch retinal vein occlusion and cystoid macular edema.
A probable new syndrome with the storage disease phenotype caused by the VPS33A gene mutation
Authors: Dursun Ali , Yalnizoglu Dilek , Gerdan Omer F. , Yucel-Yilmaz Didem , Sagiroglu Mahmut S. , Yuksel Bayram , Gucer Safak , Sivri Serap , Ozgul Riza K.
Published: August 2016

We present a novel multisystem disease in two siblings with clinical features resembling a lysosomal storage disease. These included coarse face, dysostosis multiplex, respiratory difficulty, proteinuria with glomerular foamy cells, neurological involvement with developmental delays, pyramidal signs, and severe chronic anemia. Detailed enzymatic analysis for lysosomal diseases and whole-exome sequencing studies excluded known lysosomal storage diseases in the proband. Subsequently, genome-wide genotyping and exome sequencing analysis of the family indicated two large homozygous regions on chromosomes 5 and 12, and strongly suggested that a homozygous p. R498W missense mutation in the VPS33A gene might be responsible for this novel disease. Segregation analysis in family members and mutation prediction tools’ results also supported the damaging effect of the missense mutation on the function of the Vps33a protein, which plays a role in the vesicular transport system. Electron microscopic studies of the cornea of the proband showed findings supportive of dysfunction in vesicular transport. The clinical phenotype and genetic studies support the suggestion that the siblings most probably have a novel disease very likely caused by a VPS33A gene defect.
The Prevalence of Celiac Disease in Children With Arterial Ischemic Stroke
Authors: Balci Oya , Sezer Taner
Published: August 2016

Objective:

The association between arterial ischemic stroke (AIS) and celiac disease (CD) has been described in only a few cases in adults and children. We aim to determine the prevalence of CD in children and adolescents with AIS.

Study Design:

We investigated serum levels of tissue transglutaminase antibody immunoglobulin (Ig)A and total IgA from 76 children with AIS and in a healthy control group of 102 children. Study participants who were positive for tissue transglutaminase IgA antibodies underwent a duodenal biopsy.

Results:

A total of 2 patients in the AIS group (2.26%) and 2 in the control group (1.96%) had positive serum tissue transglutaminase antibody (P=0.89; 95% confidence interval, −5.05 to 6.89). Duodenal biopsy confirmed CD in only 1 patient who had AIS.

Conclusions:

In the present study, children with acute arterial stroke did not exhibit a higher prevalence rate of CD compared with healthy controls. Therefore, the screening test for CD is not a necessary part of the management of AIS in children. However, cases of recurrent AIS could be examined for CD.
Hypereosinophilic Syndrome: Hacettepe Experience
Authors: Tavil Betul , Aytaç Selin , Unal Sule , Kuskonmaz Baris , Gumruk Fatma , Cetin Mualla
Published: August 2016

The aim was to evaluate baseline demographic, clinical, and laboratory characteristics, treatment modalities, and outcome of children with idiopathic hypereosinophilic syndrome (HES) followed up in our center. Children who fulfilled the criteria of idiopathic HES followed up at Hacettepe University Faculty of Medicine, Pediatric Hematology Department between June 2004 and October 2013 were included in this study. Medical records of all children with idiopathic HES were reviewed to obtain regarding data. The mean age of 6 children with idiopathic HES was 52.8±44.3 months (13 to 132 mo) at diagnosis. Among 6 children with idiopathic HES; 2 had pulmonary involvement; 1 had cardiac and pulmonary involvement and splenomegaly; 1 had cardiac involvement and hepatosplenomegaly; 1 had cardiac and central nervous system involvement; and 1 had skin involvement. The mean follow-up duration was 36.5±31.4 months. Methyl prednisolone (MP) was used for the first-line therapy. Complete response was achieved with MP in 3 children. All steroid responsive children are alive; whereas 3 children who did not respond to MP had expired. In conclusion, cardiac and pulmonary involvement is the major causes of mortality in HES. Resistance to steroid therapy indicates poor prognosis.
Fibromuscular Dysplasia Complicated With Cerebral Stroke in a Child With Congenital Dyserythropoietic Anemia Type II
Authors: Ozcan Alper , Patiroglu Turkan , Acer Hamit , Gumus Hakan , Senol Serkan , Karakukcu Musa , Ozdemir Mehmet A. , Unal Ekrem
Published: August 2016

Congenital dyserythropoietic anemia type II belongs to a subtype of bone marrow failure syndrome, which is characterized by monolineage involvement and typical morphologic abnormalities in erythroid precursor cells resulting in different degrees of hyporegenerative anemia. Moreover, reticulocytosis, which is not corresponding to the degree of anemia, with jaundice and splenomegaly are major diagnostic criteria. Causative gene is located at SEC23B. Although stroke among children is rare, it can cause significant morbidity and mortality. Herein we present a 3-year-old male with congenital dyserythropoietic anemia type II who presented with stroke-like symptoms, and was diagnosed with fibromuscular dysplasia.
Retropharyngeal Abscess and Mediastinitis in a Well-Appearing Infant With Prolonged Fever
Authors: Vinograd Alexandra M. , Zonfrillo Mark R. , Pawel Barbara
Published: August 2016

Fever is a common presenting chief complaint in the pediatric emergency department. We report the case of a well-appearing 11-month-old female with 2 weeks of daily fevers who was found to have an extensive retropharyngeal abscess with mediastinal and extrapleural extension. We review the literature on retropharyngeal abscesses and mediastinitis in children and note that this patient is unusual as she presented with such extensive disease with minimal symptoms. This case demonstrates the importance of a thorough history and broad differential diagnosis when evaluating children presenting prolonged fevers.
Quantifying cellular and subcellular stretches in embryonic lung epithelia under peristalsis: where to look for mechanosensing
Authors: Bokka Kishore K. , Jesudason Edwin C. , Warburton David , Lubkin Sharon R.
Published: August 2016

Peristalsis begins in the lung as soon as the smooth muscle (SM) forms, and persists until birth. As the prenatal lung is filled with liquid, SM action can, through lumen pressure, deform tissues far from the immediately adjacent tissues. Stretching of embryonic tissues has been shown to have potent morphogenetic effects. We hypothesize that these effects are at work in lung morphogenesis. In order to refine that broad hypothesis in a quantitative framework, we geometrically analyse cell shapes in an epithelial tissue, and individual cell deformations resulting from peristaltic waves that completely occlude the airway. Typical distortions can be very large, with opposite orientations in the stalk and tip regions. Apical distortions are always greater than basal distortions. We give a quantitative estimate of the relationship between length of occluded airway and the resulting tissue stretch in the distal tip. We refine our analysis of cell stresses and strains from peristalsis with a simple mechanical model of deformation of cells within an epithelium, which accounts for basic subcellular geometry and material properties. The model identifies likely stress concentrations near the nucleus and at the apical cell–cell junction. The surprisingly large strains of airway peristalsis may serve to rearrange cells and stimulate other mechanosensitive processes by repeatedly aligning cytoskeletal components and/or breaking and reforming lateral cell–cell adhesions. Stress concentrations between nuclei of adjacent cells may serve as a mechanical control mechanism guiding the alignment of nuclei as an epithelium matures.
A mathematical model of GTPase pattern formation during single-cell wound repair
Authors: Holmes William R. , Golding Adriana E. , Bement William M. , Edelstein-Keshet Leah
Published: August 2016

Rho GTPases are regulatory proteins whose patterns on the surface of a cell affect cell polarization, cell motility and repair of single-cell wounds. The stereotypical patterns formed by two such proteins, Rho and Cdc42, around laser-injured frog oocytes permit experimental analysis of GTPase activation, inactivation, segregation and crosstalk. Here, we review the development and analysis of a spatial model of GTPase dynamics that describe the formation of concentric zones of Rho and Cdc42 activity around wounds, and describe how this model has provided insights into the roles of the GTPase effector molecules protein kinase C (PKCβ and PKCη) and guanosine nucleotide dissociation inhibitor (GDI) in the wound response. We further demonstrate how the use of a ‘sharp switch’ model approximation in combination with bifurcation analysis can aid mapping the model behaviour in parameter space (approximate results confirmed with numerical simulation methods). Using these methods in combination with experimental manipulation of PKC activity (PKC overexpression (OE) and dominant negative conditions), we have shown that: (i) PKCβ most probably acts by enhancing existing positive feedbacks (from Rho to itself via the guanosine nucleotide exchange factor domain of Abr, and from Cdc42 to itself), (ii) PKCη most probably increases basal rates of inactivation (or possibly decreases basal rates of activation) of Rho and Cdc42, and (iii) the graded distribution of PKCη and its effect on initial Rho activity accounts for inversion of zones in a fraction (20%) of PKCη OE cells. Finally, we speculate that GDIs (which sequester GTPases) may have a critical role in defining the spatial domain, where the wound response may occur. This paper provides a more thorough exposition of the methods of analysis used in the investigation, whereas previous work on this topic was addressed to biologists and abbreviated such discussion.
Prediction of traction forces of motile cells
Authors: Roux Clément , Duperray Alain , Laurent Valérie M. , Michel Richard , Peschetola Valentina , Verdier Claude , Étienne Jocelyn
Published: August 2016

When crawling on a flat substrate, living cells exert forces on it via adhesive contacts, enabling them to build up tension within their cytoskeleton and to change shape. The measurement of these forces has been made possible by traction force microscopy (TFM), a technique which has allowed us to obtain time-resolved traction force maps during cell migration. This cell ‘footprint’ is, however, not sufficient to understand the details of the mechanics of migration, that is how cytoskeletal elements (respectively, adhesion complexes) are put under tension and reinforce or deform (respectively, mature and/or unbind) as a result. In a recent paper, we have validated a rheological model of actomyosin linking tension, deformation and myosin activity. Here, we complement this model with tentative models of the mechanics of adhesion and explore how closely these models can predict the traction forces that we recover from experimental measurements during cell migration. The resulting mathematical problem is a PDE set on the experimentally observed domain, which we solve using a finite-element approach. The four parameters of the model can then be adjusted by comparison with experimental results on a single frame of an experiment, and then used to test the predictive power of the model for following frames and other experiments. It is found that the basic pattern of traction forces is robustly predicted by the model and fixed parameters as a function of current geometry only.
Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium
Authors: Bretschneider Till , Othmer Hans G. , Weijer Cornelis J.
Published: August 2016

Movement of cells and tissues is a basic biological process that is used in development, wound repair, the immune response to bacterial invasion, tumour formation and metastasis, and the search for food and mates. While some cell movement is random, directed movement stimulated by extracellular signals is our focus here. This involves a sequence of steps in which cells first detect extracellular chemical and/or mechanical signals via membrane receptors that activate signal transduction cascades and produce intracellular signals. These intracellular signals control the motile machinery of the cell and thereby determine the spatial localization of the sites of force generation needed to produce directed motion. Understanding how force generation within cells and mechanical interactions with their surroundings, including other cells, are controlled in space and time to produce cell-level movement is a major challenge, and involves many issues that are amenable to mathematical modelling.
Viral outbreaks involve destabilized evolutionary networks: evidence from Ebola, Influenza and Zika
Authors: Aris-Brosou Stéphane , Ibeh Neke , Noël Jessica
Published: August 2016

Recent history has provided us with one pandemic (Influenza A/H1N1) and two severe viral outbreaks (Ebola and Zika). In all three cases, post-hoc analyses have given us deep insights into what triggered these outbreaks, their timing, evolutionary dynamics, and phylogeography, but the genomic characteristics of outbreak viruses are still unclear. To address this outstanding question, we searched for a common denominator between these recent outbreaks, positing that the genome of outbreak viruses is in an unstable evolutionary state, while that of non-outbreak viruses is stabilized by a network of correlated substitutions. Here, we show that during regular epidemics, viral genomes are indeed stabilized by a dense network of weakly correlated sites, and that these networks disappear during pandemics and outbreaks when rates of evolution increase transiently. Post-pandemic, these evolutionary networks are progressively re-established. We finally show that destabilization is not caused by substitutions targeting epitopes, but more likely by changes in the environmentsensu lato. Our results prompt for a new interpretation of pandemics as being associated with evolutionary destabilized viruses.
How cognitive genetic factors influence fertility outcomes: A mediational SEM analysis
Authors: Woodley Menie Michael A. , Schwartz Joseph A. , Beaver Kevin M.
Published: August 2016

Utilizing a newly released cognitive Polygenic Score (PGS) from Wave IV of Add Health (n= 1,886), structural equation models (SEMs) examining the relationship between PGS and fertility (which is approximately 50% complete in the present sample), utilizing measures of verbal IQ and educational attainment as potential mediators, were estimated. The results of indirect pathway models revealed that verbal IQ mediates the positive relationship between PGS and educational attainment, and educational attainment in turn mediates the negative relationship between IQ and a latent fertility measure. The direct path from PGS to fertility was non-significant. The model was robust to controlling for age, sex and race, furthermore the results of a multi-group SEM revealed no significant differences in the estimated path coefficients across sex. These results indicate that those predisposed towards higher IQ by virtue of higher PGS values are also predisposed towards trading fertility against time spent in education, which contributes to those with higher PGS values producing fewer offspring.
Tracing co-regulatory network dynamics in noisy, single-cell transcriptome trajectories
Authors: Cordero Pablo , Stuart Joshua M.
Published: August 2016

The availability of gene expression data at the single cell level makes it possible to probe the molecular underpinnings of complex biological processes such as differentiation and oncogenesis. Promising new methods have emerged for reconstructing a progression ‘trajectory’ from static single-cell transcriptome measurements. However, it remains unclear how to adequately model the appreciable level of noise in these data to elucidate gene regulatory network rewiring. Here, we present a framework called Single Cell Inference of MorphIng Trajectories and their Associated Regulation (SCIMITAR) that infers progressions from static single-cell transcriptomes by employing a continuous parametrization of Gaussian mixtures in high-dimensional curves. SCIMITAR yields rich models from the data that highlight genes with expression and co-expression patterns that are associated with the inferred progression. Further, SCIMITAR extracts regulatory states from the implicated trajectory-evolving co-expression networks. We benchmark the method on simulated data to show that it yields accurate cell ordering and gene network inferences. Applied to the interpretation of a single-cell human fetal neuron dataset, SCIMITAR finds progression-associated genes in cornerstone neural differentiation pathways missed by standard differential expression tests. Finally, by leveraging the rewiring of gene-gene co-expression relations across the progression, the method reveals the rise and fall of co-regulatory states and trajectory-dependent gene modules. These analyses implicate new transcription factors in neural differentiation including putative co-factors for the multi-functional NFAT pathway.
Phenome-wide Heritability Analysis of the UK Biobank
Authors: Ge Tian , Chen Chia-Yen , Neale Benjamin M. , Sabuncu Mert R. , Smoller Jordan W.
Published: August 2016

Heritability estimation provides important information about the relative contribution of genetic and environmental factors to phenotypic variation, and provides an upper bound for the utility of genetic risk prediction models. Recent technological and statistical advances have enabled the estimation of additive heritability attributable to common genetic variants (SNP heritability) across a broad phenotypic spectrum. However, assessing the comparative heritability of multiple traits estimated in different cohorts may be misleading due to the population-specific nature of heritability. Here we report the SNP heritability for 551 complex traits derived from the large-scale, population-based UK Biobank, comprising both quantitative phenotypes and disease codes, and examine the moderating effect of three major demographic variables (age, sex and socioeconomic status) on the heritability estimates. Our study represents the first comprehensive phenome-wide heritability analysis in the UK Biobank, and underscores the importance of considering population characteristics in comparing and interpreting heritability.
Single-cell quantitation of histones and histone post-translational modifications across the cell cycle by high-throughput imaging
Authors: Zane Linda , Chapus Fleur , Pegoraro Gianluca , Misteli Tom
Published: August 2016

Post-translational modifications (PTM) of histone proteins are critical determinants of genome function. Analysis of histone PTM levels has traditionally been performed using biochemical bulk methods to measure individual modifications. These approaches are generally unable to detect differences in histone and histone PTM levels during the cell cycle, do not provide information on variability amongst individual cells, and they are not suitable for multiplexing to comprehensively analyze large numbers of histone modifications in single experiments. We have developed HiHiMap (High-throughputHistoneMapping), an automated high-throughput immunofluorescence technique to determine histone and histone PTM levels across the cell cycle at the single-cell level in a highly parallel format. Our approach uses imaging-based quantification of DNA content and cyclin A levels to stage individual cells in the cell cycle combined with determination of the corresponding histone and histone PMT levels in the same cells. We have applied HiHiMap to a set of 22 histone variants and histone modifications. As proof-of-principle for a biological application, we use HiHiMap to the histone and histone PTMs landscape in primary, immortalized and oncogenically transformed cells. We find differences in the behavior of a specific set of histone PTM during the the cell cycle in transformed cells compared to normal and immortalized cells. The method developed here is widely applicable to the systematic study of histone modifications in physiological and pathological settings at the single-cell level.
In vivo dendrite regeneration after injury is different from dendrite development
Authors: Thompson-Peer Katherine L. , DeVault Laura , Li Tun , Jan Lily Yeh , Jan Yuh Nung
Published: August 2016

Neurons receive information along dendrites and send signals along axons to synaptic contacts. The factors that control axon regeneration have been examined in many systems, but dendrite regeneration has been largely unexplored. Here we report that, in intact Drosophila larvae, a discrete injury that removes all dendrites induces robust dendritic growth that recreates many features of uninjured dendrites, including the number of dendrite branches that regenerate and responsiveness to sensory stimuli. However, the growth and patterning of injury-induced dendrites is significantly different from uninjured dendrites. We found that regenerated arbors cover much less territory than uninjured neurons, fail to avoid crossing over other branches from the same neuron, respond less strongly to mechanical stimuli, and are pruned precociously. Finally, silencing the electrical activity of the neurons specifically blocks injury-induced, but not developmental, dendrite growth. By elucidating the essential features of dendrites grown in response to acute injury, our work builds a framework for exploring dendrite regeneration in physiological and pathological conditions.
Accounting doctorates produced in South Africa 2008-2014
Authors: de Jager Phillip , Frick Beatrice Liezel
Published: August 2016

Purpose

This paper aims to investigate the production of accounting doctorates in South Africa during the period from 2008 to 2014. The investigation was prompted by calls to qualify more academics at the doctoral level, bearing in mind that postgraduate supervision forms part of an academic’s core teaching responsibilities.

Design/methodology/approach

This archival study uses data obtained from the institutional repositories of four research-intensive universities in South Africa to construct a profile of the accounting doctoral theses produced.

Findings

Overall, the findings indicate a move towards the international requirement for doctoral-qualified accounting academics, implying an increased research orientation in South African university accounting departments. Some of the detail findings follow: most doctorates were produced at the University of Cape Town and the University of Pretoria. The accounting fields of taxation and financial management produced the most doctorates. Almost 50 per cent of the doctorates went to members of staff. Further, 28 per cent of the doctorates went to students with the CA(SA) professional qualification. The use of the PhD by publication format is growing. The low quantity of PhDs produced can possibly be explained by the low numbers of PhD qualified professorial staff who can act as supervisors. Lastly, the accounting doctorates analysed in this paper were longer and supervised by more people than the typical commerce faculty doctorate.

Research limitations/implications

Not all South African universities were included in the study and therefore some accounting doctorates might have been excluded. In addition, accounting education doctorates, possibly supervised in faculties of education, would also be excluded in view of the approach followed in this paper, which was to identify accounting doctorates via departments and commerce faculties.

Originality/value

This article is the first of its kind to examine the accounting doctorates produced in South Africa since Van der Schyf’s (2008) call for the establishment of a research culture in the accounting departments of South African universities. As such, this paper makes an important contribution towards how such a research culture may be enhanced through cultivating doctoral education in this context.
Re-imagining social enterprise
Authors: Kay Alan , Roy Michael J. , Donaldson Cam
Published: August 2016

Purpose

This intentionally polemical paper will aim to re-examine what is meant by social enterprise and try to assert its role within the current economic system. It is well over a decade since John Pearce’s Social Enterprise in Anytown was first published. Since then the term “social enterprise” has been used in multiple ways by politicians, practitioners and academics – very often for their own ideological ends.

Design/methodology/approach

This paper will outline the context and challenges currently facing social enterprise both from outside and from inside the social enterprise movement.

Findings

This paper re-affirms a paradigm for social enterprises through re-imagining how social enterprise should and could contribute to the creation of a fairer and more just society.

Originality/value

Finally, this paper will conclude with a reflection on what Pearce argued and how the social enterprise movement has to position itself as a viable alternative way of creating goods and services based on socially responsible values.