bluuebunny/crossref_metadata_2025 huggingface dataset:
Zika virus and diagnostics
Authors: Gabaglia Claudia Raja
Published: November 2016

Purpose of review

The purpose of this review is to present what is known about the Zika virus (ZIKV) at the time of writing this review. The viral structure and its phylogeny, as well as the limitations of current available techniques used for diagnosis, are discussed.

Recent findings

Crystallography and cryo-electron microscopy of the whole ZIKV, or a few of its proteins, are confirming its overall antigenic relatedness to other flaviviruses. Sequencing has revealed its dynamic genetic variation and has placed the Western cluster of Zika isolates within the Asian phylogenic tree. Genetic codon mutations, although highly prevalent, do not usually translate into modifications at amino acid or proteomic levels, revealing conserved enzymatic functions that could potentially be addressed therapeutically. Clinical characterization of ZIKV infection is complicated because of symptoms similar to dengue and chikungunya. Diagnosis requires specialized laboratories with costly reagents and highly trained personnel. Although commercial labs are now offering ZIKV diagnostic tests, most of them are not fully tested in comparison with standard molecular techniques standardized at CDC and local health departments. We are still in desperate need of simpler diagnostic tests that better discriminate ZIKV from coendemic arboviruses.

The area of better Zika diagnostic assays is a rapidly developing field with the public attention directed to this epidemic. Academic interest in this topic is driving fast disclosure of information in peer-reviewed journals and grey papers via web-based forums. We expect in the near future that new promising strategies for improved Zika diagnostics will translate into preventive and therapeutic tools.
Validation of a Simple Stool Diary Used by Caregivers to Document Diarrhea Among Young Children in a Low‐Income Country
Authors: Grenov Benedikte , Namusoke Hanifa , Nabukeera‐Barungi Nicolette , Lanyero Betty , Ritz Christian , Carlsson Amalie , Vinther Cecilie K. , Michaelsen Kim F. , Holm‐Larsen Tove
Published: November 2016

Objectives:

The aim of the study was the development and validation of a simple stool diary for caretakers collecting data on stool frequency and consistency among young children in a low‐income country.

Methods:

Focus group studies evaluated how diarrhea was understood by caregivers (content validity). The sensitivity, reliability, and correlations between dehydration and diary scores (construct validity) were tested in a clinical trial.

Results:

Caregivers recognized and understood the concept and severity of diarrhea. Stool frequency and liquid consistency decreased in children admitted with diarrhea (P < 0.0001 for both), confirming good sensitivity of the diary. High reliability was obtained after a few days of training. The caregiver intracorrelation coefficients were 0.66 (0.55–0.77) and 0.75 (0.66–0.84) after 2 and 7 days of training, respectively, and subjective staff evaluation of caregiver scores showed that ⩽6% of caregivers had low scoring abilities after 3 days. The degree of dehydration (4‐point score) was correlated with both increasing stool frequency and liquid stool consistency (+0.2 points [0.07–0.3], P = 0.0018 for 6 or more diarrheal stools, compared to 3 or more diarrheal stools per day, and +0.5 points (0.3–0.6), P < 0.0001 for diarrheal episodes with 3 or more watery stools/day compared with episodes with 3 or more “watery + abnormally loose + loose” stools per day).

Conclusions:

The diary showed high validity, good reliability, and high sensitivity. After 3 days of training, caregivers with mainly no or limited education could report stool consistency with good reliability. Stool consistency, which correlated strongly with dehydration, may be considered an important marker of diarrhea severity in future research.
Tumor Necrosis Factor‐Alpha Inhibitor Etanercept Does Not Alter Methotrexate‐Induced Gastrointestinal Mucositis in Rats
Authors: Kuiken Nicoline S.S. , Rings Edmond H.H.M. , Alffenaar Jan‐Willem C. , Havinga Rick , Jurdzinski Angelika , Groen Albert K. , Tissing Wim J.E.
Published: November 2016

Objectives:

Gastrointestinal (GI) mucositis is a severe adverse effect of chemotherapy and radiotherapy. Proinflammatory cytokines are thought to play an important role in the pathophysiology of GI mucositis. We aimed to determine the effect of the tumor necrosis factor‐alpha (TNF‐α) inhibitor etanercept on the severity of mucositis in a previously established methotrexate (MTX)‐induced GI mucositis rat model.

Methods:

Male Wistar rats received 60 mg/kg MTX on day 0 intravenously. Rats were treated daily with either etanercept (TNF‐α inhibitor) 5 mg/kg or NaCl 0.9% subcutaneously from day −3 till day 3. Control rats received NaCl 0.9% intravenously and etanercept subcutaneously. The severity of mucositis was determined by intake, bodyweight, plasma citrulline, and by a function test (absorption of an oral glucose bolus). On day 4 and day 10 rats were terminated. Villus length, crypt length, intestinal myeloperoxidase, and plasma etanercept levels were determined.

Results:

The administration of MTX induced mucositis in all rats. Etanercept did not cause a change in the degree of mucositis. Bodyweight, intake, and glucose levels were not altered by etanercept; villus length was comparable; and there was no difference in myeloperoxidase and citrulline level. Etanercept levels in plasma were significantly increased in the etanercept rats (P < 0.05).

Conclusions:

TNF‐α inhibitor etanercept did not alter the severity of mucositis in the rat, suggesting that targeting only the inflammatory pathway of TNF‐α is not effective for decreasing the severity of GI mucositis induced by high‐dose MTX. Etanercept alone is not useful for the treatment of MTX‐induced GI mucositis.
Serum Vitamins and Minerals at Diagnosis and Follow‐up in Children With Celiac Disease
Authors: Deora Vini , Aylward Nicole , Sokoro AbdulRazaq , El‐Matary Wael
Published: November 2016

Objectives:

Children with celiac disease (CD) may experience deficiencies of several micronutrients. The objectives of the present study were to determine the prevalence of micronutrient deficiencies in children with CD at diagnosis, 6 months, and 18 months after the start of a gluten‐free diet (GFD), and examine any correlation between micronutrient deficiencies, serum tissue transglutaminase (TtG) immunoglobulin A (IgA) antibody titers, and the degree of mucosal damage at diagnosis.

Methods:

Children (<17 years) with CD had their serum vitamins, minerals, and anti‐TtG IgA antibodies measured at diagnosis, 6 and 18 months after starting a GFD. Histopathological changes of duodenal biopsies at diagnosis were documented using modified MARSH classification.

Results:

The medical records of 140 children (mean age at diagnosis 7.8 ± 4.01 years, 87 girls [621%]) with CD were examined. At diagnosis, serum vitamin D was the most commonly deficient vitamin in 70% of children. Serum ferritin was subnormal in 34.5% with zinc in 18.6% children but only 12 (10.9%) children had iron deficiency anemia. There was no correlation between micronutrient deficiencies at diagnosis and serum TtG IgA antibody titers or the degree of villous atrophy. The majority of serum levels of measured micronutrients had normalized after 6 months of starting GFD except for vitamin D, which improved but remained subnormal.

Conclusions:

At diagnosis, most children with CD have vitamin D deficiency. The degree of micronutrient deficiencies does not correlate with the degree of villous atrophy or serum titers of anti‐TtG IgA antibodies.
Effects of Scheduled Waiting for Psychotherapy in Patients With Major Depression
Authors: Ahola Pasi , Joensuu Mikko , Knekt Paul , Lindfors Olavi , Saarinen Pirjo , Tolmunen Tommi , Valkonen-Korhonen Minna , Jääskeläinen Tuija , Virtala Esa , Tiihonen Jari , Lehtonen Johannes
Published: November 2016

The role of nonspecific factors in the outcome of psychotherapy is poorly understood. To study the effects of pretreatment expectancy of scheduled psychotherapy, we examined the effects of an agreed waiting time on the outcome of psychodynamic psychotherapy. Thirty-three treatment-naive outpatients with major depressive disorder were randomly selected to start psychotherapy either directly (DG; n = 17) or after waiting for 6 months (WG; n = 16). In WG, 18% to 60% of the total decline in symptoms took place during the waiting time. After 1 year of active psychotherapy, the anxiety score declined significantly only in WG, and the total length of treatment needed was shorter in WG. No other outcome differences between WG and DG were found. We conclude that scheduled waiting associates with a significant decline in depressive symptoms. Scheduled waiting should be regarded as a preparatory treatment and not as an inert nontreatment control.
Existential Well-Being
Authors: Visser Anja , Garssen Bert , Vingerhoets Ad JJM
Published: November 2016

Measures of spirituality often contain the dimension existential well-being (EWB). However, EWB has been found to overlap with emotional and psychological well-being. Using the Spiritual Attitude and Involvement List (SAIL), we have further investigated the overlap between aspects of spirituality and of well-being among patients with cancer, by determining a) the divergent validity of the subscales of the SAIL compared with a well-being questionnaire and b) the differences in their associations to changes in pain and fatigue, and the occurrence of negative life events. Our findings suggest that a sense of trust that one is able to cope with difficulties of life belongs to the realm of well-being, instead of spirituality. Other aspects, such as a sense of meaning in life, seem more similar to spirituality than to well-being. These results can bring researchers a step further toward constructing “pure” spirituality and well-being measures, which will allow them to investigate the (causal) relationship between these constructs.
Polyphenols in Foods
Authors: Yang Jensine , Dwyer Johanna T. , Peterson Julia J.
Published: November 2016

This brief overview of polyphenols describes what they are, where they are found in foods, and why some may be important to human health. Polyphenols are widely diverse and ubiquitous non-nutrient compounds in plant foods that may have physiological effects on the human body. Sources of polyphenols include fruits and vegetables, whole grains, herbs and spices, coffee, cocoa, and tea. Accumulating research suggests the potential role of polyphenols in promoting health.
Magnetic Resonance Imaging of Parotid Gland Tumors: Dynamic Contrast-Enhanced Sequence Evaluation
Authors: Stefanovic Xavier , Al Tabaa Yassine , Gascou Gregory , Lacombe Sandy , Auge Yves , Delort Philippe , Hagen Paul , Garrel Renaud , Bonafe Alain , Daures Jean-Pierre , Vendrell Jean-François
Published: November 2016

Objective

The aim of the study was to evaluate dynamic contrast-enhanced magnetic resonance (MR) imaging in the characterization of parotid gland tumors.

Methods

Fifty-five parotid lesions in 55 patients were retrospectively included. Two observers interpreted 2 reading protocols derived from all MR imaging in 2 distinct sessions, independently and blinded. Benign versus malignant distinction was carried out for protocol 1 (without contrast administration) and protocol 2 (with dynamic contrast-enhanced sequence). Histopathological results after surgical resection were used as the criterion standard. Diagnostic accuracy was compared between protocols using McNemar test. A P values of less than 0.05 indicated significant difference.

Results

There was no intraobserver statistical discordance between protocols for both observers (P = 0.27 and P = 1). Interobserver reliability showed moderate agreement for protocol 1 (κ = 0.591; 95% confidence interval [CI], 0.376–0.806) and 2 (κ = 0.463, 95% CI, 0.226–0.701). Intraobserver reliability showed moderate agreement for observer 1 (κ = 0.507; 95% CI, 0.279–0.736) and 2 (κ = 0.477; 95% CI, 0.241–0.712).

Conclusions

Magnetic resonance imaging protocol including dynamic sequence for the characterization of parotid gland lesion yielded nonsignificant increases in sensitivity, specificity, or positive predictive values, and negative predictive values over noninjected protocol.
Added Value of Parotid R2* Values for Evaluation of Sjögren Syndrome: A Preliminary Study
Authors: Chu Chen , Zhou Nan , Zhang Huayong , Dou Xin , Li Ming , Liu Song , Wang Jie , Chen Weibo , Chan Queenie , Sun Lingyun , He Jian , Zhou Zhengyang
Published: November 2016

Objective

To explore the application of parotid R2* values for evaluating Sjögren syndrome (SS).

Methods

Twenty-four consecutive SS patients and 24 sex-matched and age-matched healthy volunteers underwent bilateral parotid 3.0 T magnetic resonance (MR) imaging, including blood oxygenation level dependent sequence. Parotid R2* values of SS patients and volunteers were compared. A receiver operating characteristic analysis was used to evaluate the diagnostic performance of parotid R2* value alone and in combination with MR nodular grade.

Results

The left parotid R2* value was significantly lower than the right (P = 0.006) in SS patients. Parotid R2* value in SS patients was significantly lower than that in healthy volunteers (P < 0.001). With a cutoff value of 64.14/s, the sensitivity of the parotid R2* value was 62.5% in the diagnosis of SS. By combining R2* value with MR nodular grade, the sensitivity reached 87.5%.

Conclusions

Parotid R2* value contributed to the diagnosis of Sjögren syndrome combined with MR nodular grade.
Imaging of Hereditary Tumors of the Female Genital System
Authors: Rothan Sarah M. , Menias Christine O. , ElGuindy Yehia M. , Jensen Corey T. , Shaaban Akram M. , Bhosale Priya , Lee Michelle V. , Katabathina Venkata S. , Elsayes Khaled M.
Published: November 2016

Cancers of the female genital system, particularly endometrial and ovarian cancers, can be associated with hereditary cancer syndromes such as hereditary breast and ovarian cancer and Lynch syndrome. Cancers that are found in the setting of a hereditary cancer syndrome are often unique in presentation, clinical features, and pathologic profiles when compared with sporadic tumors. This article reviews the hereditary cancer syndromes associated with gynecological malignancies, as well as the imaging findings and staging system of endometrial and ovarian cancers. These associations are important for proper patient screening, diagnosis, and treatment.
Detection of Bone Marrow Edema Pattern With Dual-Energy Computed Tomography of the Pig Mandible Treated With Radiotherapy and Surgery Compared With Magnetic Resonance Imaging
Authors: Poort Lucas J. , Stadler Annika A.R. , Ludlage Johan H.B. , Hoebers Frank J.P. , Kessler Peter A.W. H. , Postma Alida A.
Published: November 2016

Objective

The aim of the study was to investigate the accuracy of dual-energy computed tomography (DECT) compared with magnetic resonance (MR) imaging for the detection of edema of the mandible.

Materials and methods

Fifteen adult Göttingen mini pigs received irradiation to the mandible with an equivalent dose of 0, 25, 50, or 70 Gy. Six months after irradiation, all animals underwent DECT and MR imaging of the mandible. Magnetic resonance short tau inversion recovery (STIR) was used for the grading of the bone marrow edema (0–3). Dual-energy CT (80 and 140 kVp) was performed, and virtual noncalcium (VNCa) images were calculated.

Results

Increased signal intensity at STIR was found in the higher radiation groups. An increase of signal intensity in MR imaging was accompanied by a significant increase in the Hounsfield unit value of the VNCa images of the bone marrow (STIR: 0, 1, 2, 3; mean Hounsfield unit: −103, −90, −76, −34, respectively; P < 0.05; R
2 = 0.388).

Conclusions

The VNCa images derived from DECT are able to demonstrate bone marrow edema in radiation-induced bone changes in the mandible.
Radiofrequency Ablation of Hepatic Tumor: Subjective Assessment of the Perilesional Vascular Network on Contrast-Enhanced Computed Tomography Before and After Ablation Can Reliably Predict the Risk of Local Recurrence
Authors: Yedururi Sireesha , Terpenning Silanath , Gupta Sanjay , Fox Patricia , Martin Sooyoung Shin , Conrad Claudius , Loyer Evelyne M.
Published: November 2016

Objective

To determine whether simple, subjective analysis of the perilesional vascular network can predict the risk of local recurrence after radiofrequency ablation (RFA) of liver malignancies on contrast-enhanced computed tomography (CECT).

Methods

Contrast-enhanced computed tomography's 103 patients (59 men and 44 women; mean age, 63 years (range, 31–84 years) with 134 lesions who underwent RFA between 2000 and 2010 were retrospectively analyzed. The primary tumors include colorectal carcinoma (58 patients), hepatocellular carcinoma (n = 13), breast carcinoma (n = 8), neuroendocrine tumor (n = 5), and others (n = 19). Three blinded radiologists independently reviewed the CECT (a triple phase liver protocol for hypervascular tumors and a single phase for the hypovascular tumors) before and 6 weeks after RFA and subjectively estimated the width of the ablative margin on a 3-point scale (optimal, 1; suboptimal, 2; and residual tumor, 3). Local recurrence was determined on follow-up CECT.

Results

The consensus score was 1 in 94, 2 in 28, and 3 in 12 lesions. κ among readers was 0.75. Local recurrence occurred in 3 lesions with a score of 1 and 12 lesions with a score of 2. The consensus score was a significant univariate predictor of local recurrence.

Conclusions

Subjective estimation of the width of ablative margin can reliably predict the risk of local recurrence.
The Effect of Psychosocial and Neuropsychiatric Factors on Medication Adherence in a Cohort of Women With Systemic Lupus Erythematosus
Authors: Flower Cindy , Hambleton Ian , Campbell Mike
Published: November 2016

Background

Medication adherence in systemic lupus erythematosus (SLE) reduces disease activity and the risk of flares.

Objectives

We evaluated adherence in women with SLE who exhibit high morbidity and mortality. We evaluated demographic data and 2 conventional adherence predictors: self-efficacy and health literacy, along with 2 potential neuropsychiatric SLE complications: cognitive dysfunction and depression.

Methods

One hundred six women randomly selected from the Barbados National Lupus Registry completed the Self-efficacy for Appropriate Medication Use Scale, Rapid Estimate of Adult Literacy in Medicine–Short Form, Cognitive Symptom Inventory, Beck Depression Inventory II, and Morisky’s Medication Adherence Questionnaire (MAQ). This study explored the effects of psychosocial and neuropsychiatric functioning on adherence using ordinal logistic regression.

Results

Sixty percent reported high MAQ scores. The probability of high MAQ scores was lower among younger patients (P= 0.001) and those with shorter disease duration (P= 0.05). The probability of high MAQ scores fell with lower perceived self-efficacy (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.73–0.89;P< 0.001), worsening cognitive function (OR, 0.90; 95% CI, 0.84–0.97;P= 0.004), and increasing depression (OR, 0.93; 95% CI, 0.88–0.97;P= 0.002). There was no strong relationship between MAQ score and health literacy (OR, 0.37; 95% CI, 0.13–1.03;P= 0.06).

Conclusion

Women with SLE who are younger and those with shorter disease duration should be assessed for medication adherence. Screening at diagnosis followed by routine assessment of cognitive dysfunction and depression along with perceived self-efficacy may further identify the most vulnerable subgroup who should be targeted with personalized intervention strategies.
Comparison of the Detection Rate of Simulated Microcalcifications in Full-Field Digital Mammography, Digital Breast Tomosynthesis, and Synthetically Reconstructed 2-Dimensional Images Performed With 2 Different Digital X-ray Mammography Systems
Authors: Peters Sabine , Hellmich Martin , Stork Alexander , Kemper Jörn , Grinstein Olga , Püsken Michael , Stahlhut Leandra , Kinner Sonja , Maintz David , Krug Kathrin Barbara
Published: November 2016

Objective

The aim of this study was to compare the microcalcification detectability in an anthropomorphic phantom model regarding number, size, and shape in full-field digital mammography (FFDM), synthetically reconstructed 2-dimensional (Synthetic-2D) images, and digital breast tomosynthesis (DBT) performed with 2 different x-ray mammography systems.

Materials and Methods

Simulated microcalcifications of different numbers (0 to >39), sizes (diameter, 100–800 μm), and shapes (round vs heterogeneous) were scattered by random distribution on 50 film phantoms each divided in 4 quadrants. The FFDM and DBT x-rays were taken from each of these 50 films with both x-ray mammography systems (SenoClaire; GE Healthcare, Selenia Dimensions, Hologic) using an anthropomorphic scattering body and automatic exposure control. The resulting exposure factors were similar to a clinical setting. The synthetically reconstructed 2D images were generated automatically on both systems. All FFDM, Synthetic-2D, and DBT images were interpreted in randomized order and independently of each other by 6 radiologists using a structured questionnaire.

Results

The number categories of simulated microcalcifications were correctly evaluated in 55.3% of instances (quadrant by reader) in FFDM, 50.9% in the Synthetic-2D views, and 59.5% in DBT, summarized for 200 quadrants per reader for each Device A and B, respectively. Full-field digital mammography was superior to Synthetic-2D (mean difference, 4%; 95% confidence interval [CI], 2%–7%; P < 0.001), and DBT was superior to both FFDM (mean difference, 4%; 95% CI, 2%–7%; P = 0.002) and Synthetic-2D (mean difference, 9%; 95% CI, 6%–11%; P < 0.001). This trend was consistent in all subgroup analyses. The number of the smallest microcalcifications (100–399 μm) was correctly evaluated in 25.2% of the FFDM, in 14.2% for Synthetic-2D, and in 28.3% of the DBT images. Underestimations of the number of simulated microcalcifications were more common than overestimations. Regarding the size categories of simulated microcalcifications, the rates of correct assessments were in 45.4% of instances in FFDM, 39.9% in the Synthetic-2D views, and 43.6% in DBT, summarized for 200 quadrants per reader and both imaging devices.

Conclusions

In the presented in vitro environment using an anthropomorphic phantom model, standard full-field digital x-ray mammography was superior to synthetically reconstructed 2-dimensional images in the detection of simulated microcalcifications. In view of these results, it is questionable whether Synthetic-2D images can replace FFDM in clinical examinations at the present time. Further investigations are needed to assess the clinical impact of the in vitro results.
Wavelet-Based Angiographic Reconstruction of Computed Tomography Perfusion Data
Authors: Kunz Wolfgang G. , Schuler Felix , Sommer Wieland H. , Fabritius Matthias P. , Havla Lukas , Meinel Felix G. , Reiser Maximilian F. , Ertl-Wagner Birgit , Thierfelder Kolja M.
Published: November 2016

Objective

The aim of this study was to test the diagnostic value of wavelet-based angiographic reconstruction of CT perfusion data (waveletCTA) to detect cerebral venous sinus thrombosis (CVST) in patients who underwent whole-brain CT perfusion imaging (WB-CTP).

Materials and Methods

Datasets were retrospectively selected from an initial cohort of 2863 consecutive patients who had undergone multiparametric CT including WB-CTP. WaveletCTA was reconstructed from WB-CTP: the angiographic signal was generated by voxel-based wavelet transform of time attenuation curves (TACs) from WB-CTP raw data. In a preliminary clinical evaluation, waveletCTA was analyzed by 2 readers with respect to presence and location of CVST. Venous CT and MR angiography (venCTA/venMRA) served as reference standard. Diagnostic confidence for CVST detection and the quality of depiction for venous sections were evaluated on 5-point Likert scales. Thrombus extent was assessed by length measurements. The mean CT attenuation and waveletCTA signal of the thrombus and of flowing blood were quantified.

Results

Sixteen patients were included: 10 patients with venCTA-/venMRA-confirmed CVST and 6 patients with arterial single-phase CT angiography (artCTA)–suspected but follow-up-excluded CVST. The reconstruction of waveletCTA was successful in all patients. Among the patients with confirmed CVST, waveletCTA correctly demonstrated presence, location, and extent of the thrombosis in 10/10 cases. In 6 patients with artCTA-suspected but follow-up–excluded CVST, waveletCTA correctly ruled out CVST in 5 patients. Reading waveletCTA in addition to artCTA significantly increased the diagnostic confidence concerning CVST compared with reading artCTA alone (4.4 vs 3.6, P = 0.044). The mean flowing blood-to-thrombus ratio was highest in waveletCTA, followed by venCTA and artCTA (146.2 vs 5.9 vs 2.6, each with P < 0.001). In waveletCTA, the venous sections were depicted better compared with artCTA (4.2 vs 2.6, P < 0.001), and equally well compared with venCTA/venMRA (4.2 vs 4.1, P = 0.374).

Conclusions

WaveletCTA was technically feasible in CVST patients and reliably identified CVST in a preliminary clinical evaluation. WaveletCTA might serve as an additional reconstruction to rule out or incidentally detect CVST in patients who undergo WB-CTP.
Prenatal Ultrasound Evaluation of the Position of Conus Medullaris for the Diagnosis of Tethered Cord Syndrome
Authors: He Shao-zheng , Lv Guo-rong , Liu Shun-lan , Ruan Jun-xian
Published: November 2016

To determine the conus distance between the end of the conus medullaris and the distal end of the last vertebral body in healthy fetuses with various gestational ages using ultrasonography for its diagnostic value in tethered cord syndrome (TCS). This retrospective study included 540 healthy and 8 autopsy-confirmed TCS fetuses. Ultrasonographic measurement of the conus distance was performed when the fetus was in a prone position within the spine in the near field at 14 to 41 weeks of gestational age. Linear correlation analysis was performed to analyze the relationship between the conus distance and the gestational age, biparietal diameter, femur length, head circumference, and abdominal circumference. The normal results were compared with 8 cases of postnatally confirmed TCS. In 526 (95.9%) of 548 fetuses, the conus distance was successfully measured. The 95% limits of agreement in measurement of conus distance were −2.2 to 2.6 mm for the intraobserver variability and −3.7 to 3.1 mm for the interobserver variability. Significant correlations between the conus distance and the gestational age, biparietal diameter, femur length, head circumference, and abdominal circumference were observed. The most marked association was found to be between conus distance and femur length. The conus distance was significantly less in TCS fetuses than in healthy fetuses. Ultrasonographic measurement of conus distance is an easy and reliable method to evaluate the position of the conus medullaris and, therefore, can be helpful in the prenatal diagnosis of TCS.
Initial Experience of Video Capsule Endoscopy After Intestinal Transplantation
Authors: Varkey Jonas , Oltean Mihai , Pischel Andreas Bernd , Simrén Magnus , Herlenius Gustaf
Published: November 2016

Background

Intestinal transplantation is a procedure which inflicts immunological and infectious complications that affect the transplanted graft, posing both diagnostic and therapeutic challenges. Video capsule endoscopy (VCE) offers easy access to the entire small intestine and presents itself as an interesting option. However, at present, no studies evaluating the usefulness of video capsule endoscopies in this setting have been published. Our aim was to evaluate the usefulness of VCE in detecting complications that arise after intestinal transplantation.

Methods

We included 7 adult patients with either isolated intestine (n = 1) or multivisceral grafts (n = 6). These patients underwent 12 VCE between 2004 and 2015 at the Sahlgrenska University Hospital. The median age was 42 (21-67) years (4 women/3 men). VCE was used in clinical situations where the conventional diagnostic methods failed to provide answers to the clinical question.

Results

Indications for the procedure were: suspicion of rejection (n = 4 examinations), gastrointestinal dysmotility (n = 4 examinations), high stomal output (n = 2 examinations), suspicion of lymphoproliferative disease in the transplanted graft (n = 1 examination), and clinical surveillance (n = 1 examination). The median time after transplantation for performing an examination was 740 (26-3059) days. VCE was useful in 83% of the examinations and the results influenced the planned management. The overall agreement between VCE findings and biopsies was moderate (κ = 0.54, P = 0.05) but increased when comparing the presence of inflammation/rejection (κ = 0.79, P < 0.001).

Conclusions

VCE is a promising diagnostic method after intestinal transplantation. However, larger studies are needed to evaluate its potential risks and gains.
Generation of Repeater F Waves in Healthy Subjects
Authors: Chroni Elisabeth , Veltsista Dimitra , Papapaulou Chris , Trachani Eftychia
Published: November 2016

Purpose:

F waves identical in latency, size, and shape, known as repeater F waves, have been observed occasionally in normal motor conduction recordings. The purpose of this study was to examine the occurrence and characteristics of repeater F waves in healthy subjects under different testing conditions, aiming to selectively excite lower and higher threshold motor fibers.

Methods:

Sessions of 40 traces were recorded from the ulnar nerve in 12 volunteers, applying/using supramaximal, submaximal stimuli (intensity able to elicit 30% and 60% of the maximum compound muscle action potential amplitude), and a collision technique. Repeater F waves were identified and their numbers and relative frequency were estimated. For this purpose, a custom-designed software program was developed, to avoid misjudgments of simple visual inspection.

Results:

Repeater occurrence was significantly higher using 30% submaximal intensity compared with the standard supramaximal stimulation. There was an inverse significant association between repeater index and overall F wave quantity. Repeaters' latency, amplitude, and duration measurements were within the ranges of the nonrepeaters.

Conclusions:

We herein showed that in healthy subjects the presence of repeater F waves might increase, when stimulation conditions other than standard single, supramaximal impulses were used. The frequency of repeaters was dependent on the overall F wave persistence, but there was no evidence to support a relationship with the type of motoneurons that was preferentially stimulated.
Ultrasound-Guided Electrodes for Conduction Studies of the Saphenous Nerve
Authors: Evangelopoulos Maria E. , Humpert Sebastian , Rösler Kai M.
Published: November 2016

Purpose:

Saphenous nerve conduction studies are difficult, because the nerve is hard to localize and evoked responses are small. Ultrasound imaging may assist in the accurate localization and optimal positioning of surface (SE) and needle electrodes (NE).

Methods:

The study population included 39 subjects and was divided into two groups. Group A consisted of 20 healthy subjects, whereas group B of 19 patients with polyneuropathies. Orthodromic conduction was measured by distal supramaximal nerve stimulation. Surface electrode and NE recordings were compared.

Results:

In the control group, SEs recorded responses in 17 of 20 healthy subjects, whereas NEs in 19. In the patients' group, SEs recorded responses in 7 of 19 patients, whereas NEs in 16. In all healthy subjects and patients, sensory nerve action potentials recorded by NEs were significantly larger than those obtained by SEs (healthy subjects: 5.85 ± 3.01 μV vs. 1.98 ± 1.37 μV, P < 0.0001; patients 3.05 ± 2.35 μV vs. 0.71 ± 1.14 μV, t-test P < 0.0001).

Conclusions:

Ultrasound guidance allows precise electrode positioning for saphenous nerve electrophysiological testing. Amplitudes of the recorded sensory nerve action potentials are clearly higher with ultrasound-guided needle than with surface recordings.
Determinants of the VP1/2A junction cleavage by the 3C protease in foot-and-mouth disease virus-infected cells
Authors: Kristensen Thea , Normann Preben , Gullberg Maria , Fahnøe Ulrik , Polacek Charlotta , Rasmussen Thomas Bruun , Belsham Graham J
Published: November 2016

The foot-and-mouth disease virus (FMDV) capsid precursor, P1-2A, is cleaved by FMDV 3C protease to yield VP0, VP3, VP1 and 2A. Cleavage of the VP1/2A junction is the slowest. Serotype O FMDVs with uncleaved VP1-2A (having a K210E substitution in VP1; at position P2 in cleavage site) have been described previously and acquired a second site substitution (VP1 E83K) during virus rescue. Furthermore, introduction of the VP1 E83K substitution alone generated a second site change at the VP1/2A junction (2A L2P, position P2′ in cleavage site). These virus adaptations have now been analysed using next-generation sequencing to determine sub-consensus level changes in the virus; this revealed other variants within the E83K mutant virus population that changed residue VP1 K210. The construction of serotype A viruses with a blocked VP1/2A cleavage site (containing K210E) has now been achieved. A collection of alternative amino acid substitutions was made at this site, and the properties of the mutant viruses were determined. Only the presence of a positively charged residue at position P2 in the cleavage site permitted efficient cleavage of the VP1/2A junction, consistent with analyses of diverse FMDV genome sequences. Interestingly, in contrast to the serotype O virus results, no second site mutations occurred within the VP1 coding region of serotype A viruses with the blocked VP1/2A cleavage site. However, some of these viruses acquired changes in the 2C protein that is involved in enterovirus morphogenesis. These results have implications for the testing of potential antiviral agents targeting the FMDV 3C protease.
Antenatal maternal anxiety modulates the BOLD response in 20-year old adolescents during an endogenous cognitive control task
Authors: Mennes Maarten , Van den Bergh Bea R.H. , Sunaert Stefan , Lagae Lieven , Stiers Peter
Published: November 2016

Evidence is building for an association between the level of anxiety experienced by a mother during pregnancy and the cognitive development of her offspring. The current study uses fMRI to examine whether there is an association between prenatal exposure to maternal anxiety and brain activity in 20 year old adolescents. In line with previous results of this follow-up study, it was found that adolescents of mothers reporting high levels of anxiety during weeks 12–22 of their pregnancy had a different pattern of decision making in a Gambling paradigm requiring endogenous cognitive control compared to adolescents of mothers reporting low to average levels of anxiety during pregnancy. Moreover, the blood oxygenation level dependent (BOLD) response in a number of prefrontal cortical areas was modulated by the level of antenatal maternal anxiety. In particular a number of right lateralized clusters including inferior frontal junction, that were modulated in the adolescents of mothers reporting low to average levels of anxiety during pregnancy by a task manipulation of cognitive control, were not modulated by this manipulation in the adolescents of mothers reporting high levels of anxiety during pregnancy. These results provide a neurobiological underpinning for our previous hypothesis of an association between a deficit in endogenous cognitive control in adolescence and exposure to maternal anxiety in the prenatal life period.
Cell wall remodeling drives engulfment duringBacillus subtilissporulation
Authors: Ojkic Nikola , López-Garrido Javier , Pogliano Kit , Endres Robert G.
Published: November 2016

When starved, the Gram-positive bacteriumBacillus subtilisforms durable spores for survival. Sporulation initiates with an asymmetric cell division, creating a large mother cell and a small forespore. Subsequently, the mother cell membrane engulfs the forespore in a phagocytosis-like process. However, the force generation mechanism for forward membrane movement remains unknown. Here, we show that membrane migration is driven by cell wall remodeling at the leading edge of the engulfing membrane, with peptidoglycan synthesis and degradation mediated by penicillin binding proteins in the forespore and a cell wall degradation protein complex in the mother cell. We propose a simple model for engulfment in which the junction between the septum and the lateral cell wall moves around the forespore by a mechanism resembling the ‘template model’. Hence, we establish a biophysical mechanism for the creation of a force for engulfment based on the coordination between cell wall synthesis and degradation.
Microtubule organization within mitotic spindles revealed by serial block face scanning EM and image analysis
Authors: Nixon Faye M. , Honnor Thomas R. , Starling Georgina P. , Beckett Alison J. , Johansen Adam M. , Brettschneider Julia A. , Prior Ian A. , Royle Stephen J.
Published: November 2016

Serial block face scanning electron microscopy (SBF-SEM) is a powerful method to analyze cells in 3D. Here, working at the resolution limit of the method, we describe a correlative light-SBF-SEM workflow to resolve microtubules of the mitotic spindle in human cells. We present three examples of uses for this workflow which are not practical by light microscopy and/or TEM. First, distinguishing closely associated microtubules within K-fibers; second, resolving bridging fibers in the mitotic spindle; third, visualizing membranes in mitotic cells, relative to the spindle apparatus. Our workflow also includes new computational tools for exploring the spatial arrangement of MTs within the mitotic spindle. We use these tools to show that microtubule order in mitotic spindles is sensitive to the level of TACC3 on the spindle.
A Logical Inquiry of Emotions and Cognition
Authors: Tozzi Arturo , James Colin , Peters James F
Published: November 2016

Experimental procedures in neuroscience rely on the standpoints that the mind is a functional state of the brain and a clear subdivision among different mental faculties does exist in the cortex. According to cognitive neuroscientists, the term "mind" encompasses just the "cognitive" faculties, such as consciousness, perception, thinking, judgement, memory, leaving apart the "emotional" states. Here, taking into account the powerful tools of the first-order predicate logic, we evaluated whether: a) the mind is a function on the physical brain activity; b) different mental faculties can be reduced to a more general one; c) the division of mental faculties in cognition and emotion holds true. We demonstrated that nervous activity is equivalent to mental faculties and that emotions and cognition do not stand for two separated functions of the mind. This means that, counter to our common-sense belief, cognition and emotions are splitted and every faculty of the mind necessarily displays a counterpart in other ones. We point out how it is possible for condensed mind faculties to be unglued in order to become apparently different functions. Therefore, seemingly different mind faculties turn out to be equivalent, because the same logical framework holds for all the types of brain activities, independent of their boundaries and magnitude.
SplitThreader: Exploration and analysis of rearrangements in cancer genomes
Authors: Nattestad Maria , Alford Marley C. , Sedlazeck Fritz J. , Schatz Michael C.
Published: November 2016

Genomic rearrangements and associated copy number changes are important drivers in cancer as they can alter the expression of oncogenes and tumor suppressors, create gene fusions, and misregulate gene expression. Here we present SplitThreader (http://splitthreader.com), an open-source interactive web application for analysis and visualization of genomic rearrangements and copy number variation in cancer genomes. SplitThreader constructs a sequence graph of genomic rearrangements in the sample and uses a priority queue breadth-first search algorithm on the graph to search for novel interactions. This is applied to detect gene fusions and other novel sequences, as well as to evaluate distances in the rearranged genome between any genomic regions of interest, especially the repositioning of regulatory elements and their target genes. SplitThreader also analyzes each variant to categorize it by its relation to other variants and by its copy number concordance. This identifies balanced translocations, identifies simple and complex variants, and suggests likely false positives when copy number is not concordant across a candidate breakpoint. It also provides explanations when multiple variants affect the copy number state and obscure the contribution of a single variant, such as a deletion within a region that is overall amplified. Together, these categories triage the variants into groups and provide a starting point for further systematic analysis and manual curation. To demonstrate its utility, we apply SplitThreader to three cancer cell lines, MCF-7 and A549 with Illumina paired-end sequencing, and SK-BR-3, with long-read PacBio sequencing. Using SplitThreader, we examine the genomic rearrangements responsible for previously observed gene fusions in SK-BR-3 and MCF-7, and discover many of the fusions involved a complex series of multiple genomic rearrangements. We also find notable differences in the types of variants between the three cell lines, in particular a much higher proportion of reciprocal variants in SK-BR-3 and a distinct clustering of interchromosomal variants in SK-BR-3 and MCF-7 that is absent in A549.
miR-106b-responsive gene landscape identifies regulation of Kruppel-like factor family
Authors: Wehrkamp Cody J. , Natarajan Sathish Kumar , Mohr Ashley M. , Phillippi Mary Anne , Mott Justin L.
Published: November 2016

MicroRNA dysregulation is a common feature of cancer and due to the promiscuity of microRNA binding this can result in a wide array of genes whose expression is altered. miR-106b is an oncomiR overexpressed in cholangiocarcinoma and its upregulation in this and other cancers often leads to repression of anti-tumorigenic targets. The goal of this study was to identify the miR-106b-regulated gene landscape in cholangiocarcinoma cells using a genome-wide, unbiased mRNA analysis. Through RNA-Seq we found 112 mRNAs significantly repressed by miR-106b. The majority of these genes contain the specific miR-106b seed-binding site. We have validated 11 genes from this set at the mRNA level and demonstrated regulation by miR-106b of five proteins. Combined analysis of our miR-106b-regulated mRNA data set plus published reports indicate that miR-106b binding is anchored by G:C pairing in and near the seed. Novel targets Kruppel-like factor 2 (KLF2) and KLF6 were verified both at the mRNA and at the protein level. Further investigation showed regulation of four other KLF family members by miR-106b. We have discovered coordinated repression of several members of the KLF family by miR-106b that may play a role in cholangiocarcinoma tumor biology.
Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment
Authors: Vysotskaia Valentina S. , Hogan Gregory J. , Gould Genevieve M. , Wang Xin , Robertson Alex D. , Haas Kevin R. , Theilmann Mark R. , Spurka Lindsay , Grauman Peter V. , Lai Henry H. , Jeon Diana , Haliburton Genevieve , Leggett Matt , Chu Clement S. , Iori Kevin , Maguire Jared R. , Ready Kaylene , Evans Eric A. , Peter Kang H. , Haque Imran S.
Published: November 2016

The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy number variants (CNVs) in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers.
Structural and functional brain changes following four weeks of unimanual motor training: evidence from behaviour, neural stimulation, cortical thickness and functional MRI
Authors: Sale Martin V. , Reid Lee B. , Cocchi Luca , Pagnozzi Alex M. , Rose Stephen E. , Mattingley Jason B.
Published: November 2016

Although different aspects of neuroplasticity can be quantified with behavioural probes, brain stimulation, and brain imaging assessments, no study to date has combined all these approaches into one comprehensive assessment of brain plasticity. Here, 24 healthy right-handed participants practised a sequence of finger-thumb opposition movements for 10 minutes each day with their left hand. After four weeks, performance for the practised sequence improved significantly (p < 0.05 FWE) relative to a matched control sequence, with both the left (mean increase: 53.0% practised, 6.5% control) and right (21.0%; 15.8%) hands. Training also induced significant (cluster p-FWE < 0.001) reductions in functional MRI activation for execution of the learned sequence, relative to the control sequence. These changes were observed as clusters in the premotor and supplementary motor cortices (right hemisphere, 301 voxel cluster; left hemisphere 700 voxel cluster), as well as sensorimotor cortices and superior parietal lobules (right hemisphere 864 voxel cluster; left hemisphere, 1947 voxel cluster). Transcranial magnetic stimulation over the right (‘trained’) primary motor cortex yielded a 58.6% mean increase in a measure of motor evoked potential amplitude, as recorded at the left abductor pollicis brevis muscle. Cortical thickness analyses based on structural MRI suggested changes in the right precentral gyrus, right post central gyrus, right dorsolateral prefrontal cortex and potentially the right supplementary motor area. Such findings are consistent with LTP-like neuroplastic changes in areas that were already responsible for finger sequence execution, rather than improved recruitment of previously non-utilised tissue.