bluuebunny/crossref_metadata_2025 huggingface dataset:
Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a Glycoprotein D Receptor-Retargeted Herpes Simplex Virus
Authors: Okubo Yu , Uchida Hiroaki , Wakata Aika , Suzuki Takuma , Shibata Tomoko , Ikeda Hitomi , Yamaguchi Miki , Cohen Justus B. , Glorioso Joseph C. , Tagaya Mitsuo , Hamada Hirofumi , Tahara Hideaki
Published: October 2016

Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains. To address this question, we took advantage of mutant viruses whose viral entry into cells relies on the uniquely specific interaction of an engineered gD with epidermal growth factor receptor (EGFR). We introduced selected syncytial mutations into gB and/or gK of the EGFR-retargeted HSV and found that these mutations, especially when combined, enabled formation of extensive syncytia by human cancer cell lines that express the target receptor; these syncytia were substantially larger than the plaques formed by the parental retargeted HSV strain. We assessed the EGFR dependence of entry and spread separately by using direct entry and infectious center assays, respectively, and we found that the syncytial mutations did not override the receptor specificity of the retargeted viruses at either stage. We discuss the implications of these results for the development of more effective targeted oncolytic HSV vectors.

IMPORTANCE
Herpes simplex virus (HSV) is investigated not only as a human pathogen but also as a promising agent for oncolytic virotherapy. We previously showed that both the initial entry and subsequent lateral spread of HSV can be retargeted to cells expressing tumor-associated antigens by single-chain antibodies fused to a receptor-binding-deficient envelope glycoprotein D (gD). Here we introduced syncytial mutations into the gB and/or gK gene of gD-retargeted HSVs to determine whether viral tropism remained dependent on the interaction of gD with the target receptor. Entry and spread profiles of the recombinant viruses indicated that gD retargeting does not abolish the hyperfusogenic activity of syncytial mutations and that these mutations do not eliminate the dependence of HSV entry and spread on a specific gD-receptor interaction. These observations suggest that syncytial mutations may be valuable for increasing the tumor-specific spreading of retargeted oncolytic HSV vectors.
DNA from Dust: Comparative Genomics of Large DNA Viruses in Field Surveillance Samples
Authors: Pandey Utsav , Bell Andrew S. , Renner Daniel W. , Kennedy David A. , Shreve Jacob T. , Cairns Chris L. , Jones Matthew J. , Dunn Patricia A. , Read Andrew F. , Szpara Moriah L.
Published: October 2016

Despite both clinical and laboratory data that show increased virulence in field isolates of MDV-1 over the last half century, we do not yet understand the genetic basis of its pathogenicity. Our knowledge of genome-wide variation between strains of this virus comes exclusively from isolates that have been cultured in the laboratory. MDV-1 isolates tend to lose virulence during repeated cycles of replication in the laboratory, raising concerns about the ability of cultured isolates to accurately reflect virus in the field. The ability to directly sequence and compare field isolates of this virus is critical to understanding the genetic basis of rising virulence in the wild. Our approaches remove the prior requirement for cell culture and allow direct measurement of viral genomic variation within and between hosts, over time, and during adaptation to changing conditions.
Versatility of Biofilm Matrix Molecules in Staphylococcus epidermidis Clinical Isolates and Importance of Polysaccharide Intercellular Adhesin Expression during High Shear Stress
Authors: Schaeffer Carolyn R. , Hoang Tra-My N. , Sudbeck Craig M. , Alawi Malik , Tolo Isaiah E. , Robinson D. Ashley , Horswill Alexander R. , Rohde Holger , Fey Paul D.
Published: October 2016

Staphylococcus epidermidis
is a leading cause of infections related to biomaterials, mostly due to their ability to form biofilm. Biofilm accumulation mechanisms vary, including those that are dependent on specific proteins, environmental DNA (eDNA), or polysaccharide intercellular adhesin (PIA). We found that those isolates obtained from high-shear environments, such as the lumen of a catheter, are more likely to produce PIA-mediated biofilms than those isolates obtained from a low-shear biomaterial-related infection. This suggests that PIA functions as a mechanism that is protective against shear flow. Finally, we performed selection experiments documenting the heterogeneity of biofilm accumulation molecules that function in the absence of PIA, further documenting the biofilm-forming potential of
S. epidermidis
.
Duplication cyst of ileum presenting as acute intestinal obstruction in an adult
Authors: Gupta Ashish , Chakaravarthi Karikal , Pattnaik Bramhadatta , Kaman Lileswar
Published: October 2016

Duplication cysts occur because of congenital aberration during gut development. They are commonly diagnosed during infancy and rarely during adulthood. We present an adult male who presented to surgical emergency with acute intestinal obstruction. Intraoperatively, this patient was found to have a non-communicating duplication cyst of ileum causing proximal obstruction. The involved segment of the small bowel was resected and a divided loop ileostomy was created.
Severe human monocytic ehrlichiosis presenting with altered mental status and seizures
Authors: Geier Christian , Davis Jessica , Siegel Marc
Published: October 2016

A previously healthy 66-year-old woman living in the Mid-Atlantic USA presented to the hospital with lethargy, ataxia and slurred speech. 2 weeks prior she had removed a tick from her right groin. She reported malaise, fevers, diarrhoea, cough and a rash. Physical examination revealed a maculopapular rash on her chest, and lung auscultation revealed bi-basilar rales. Laboratory tests were remarkable for hyponatraemia, leucopenia and thrombocytopenia. Chest X-ray demonstrated bilateral pleural effusions with pulmonary oedema. She was treated with ceftriaxone and azithromycin for possible community-acquired pneumonia but declining mental status necessitated intensive care unit transfer. Vancomycin and doxycycline were added. Her course was complicated by seizures requiring antiepileptic therapy. Peripheral blood smear demonstrated morulae in monocytes. SerumEhrlichia chaffeensisDNA was positive confirming the diagnosis of human monocytic ehrlichiosis. She recovered without residual neurological deficits after 10 days of doxycycline therapy.
Physical activity and exercise for erectile dysfunction: systematic review and meta-analysis
Authors: Silva André B , Sousa Nelson , Azevedo Luís F , Martins Carlos
Published: October 2016

Background

A growing body of evidence suggests that physical activity and exercise may improve erectile function.

Objective

To conduct a systematic review and meta-analysis evaluating the effects of physical activity modalities and exercise on erectile function in erectile dysfunction trials.

Methods

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. We searched 6 electronic databases between January 1990 and July 2016 and hand-searched reference lists for randomised controlled trials. Only patients with a diagnosis of erectile dysfunction were included. The mean differences between intervention and control groups were calculated for meta-analysis.

Results

7 studies were eligible, including 478 participants allocated to aerobic, pelvic or combined exercise interventions. Follow-up ranged from 8 weeks to 2 years. The risk of bias in the trials was deemed moderate to high mainly due to impossible blinding of patients and personnel, as well as questionable blinding of outcome assessors. Random-effects meta-analyses were performed. Pooled data showed a statistically significant improvement in erectile function score (mean difference 3.85, 95% CI 2.33 to 5.37). A benefit was still demonstrable after a sensitivity analysis because the mean difference in International Index of Erectile Function (IIEF) score ranged from 3.39 (95% CI 1.92 to 4.87) to 4.28 (95% CI 2.54 to 6.02). A benefit was also detected in short-term and long-term interventions as well as in trials evaluating physical activity and exercise alone or in addition to usual care.

Conclusions

The present study suggests that physical activity and exercise interventions improve patient-reported erectile dysfunction, particularly aerobic exercise with moderate-to-vigorous intensity.
Controlling cardiovascular diseases in low and middle income countries by placing proof in pragmatism
Authors: Owolabi Mayowa , Miranda Jaime J , Yaria Joseph , Ovbiagele Bruce
Published: October 2016

Low and middle income countries (LMICs) bear a huge, disproportionate and growing burden of cardiovascular disease (CVD) which constitutes a threat to development. Efforts to tackle the global burden of CVD must therefore emphasise effective control in LMICs by addressing the challenge of scarce resources and lack of pragmatic guidelines for CVD prevention, treatment and rehabilitation. To address these gaps, in this analysis article, we present animplementation cyclefor developing, contextualising, communicating and evaluating CVD recommendations for LMICs. This includes atranslatability scaleto rank the potential ease of implementing recommendations, prescriptions for engaging stakeholders in implementing the recommendations (stakeholders such as providers and physicians, patients and the populace, policymakers and payers) and strategies for enhancing feedback. This approach can help LMICs combat CVD despite limited resources, and can stimulate new implementation science hypotheses, research, evidence and impact.
Toxoplasma gondiiseroprevalence in the Portuguese population: comparison of three cross-sectional studies spanning three decades
Authors: Gargaté Maria João , Ferreira Idalina , Vilares Anabela , Martins Susana , Cardoso Carlos , Silva Susana , Nunes Baltazar , Gomes João Paulo
Published: October 2016

Background

Toxoplasma gondiiis an obligate intracellular protozoan infecting up to one-third of the world's population, constituting a life threat if transmitted from mother to child during pregnancy. In Portugal, there is a lack of knowledge of the current epidemiological situation, as the unique toxoplasmosis National Serological Survey was performed in 1979/1980.

Methods

We studied the seroprevalence trends in the Portuguese general population over the past 3 decades, by assessing chronological spread cross-sectional studies, with special focus on women of childbearing age, by age group, region and gender.

Results

TheT. gondiioverall seroprevalence decreased from 47% in 1979/1980 to 22% (95% CI 20% to 24%) in 2013. Generally, we observed that the prevalence ofT. gondiiIgG increased significantly with age and it decreased over time, both in the general population and in the childbearing women (18% prevalence in 2013).

Conclusions

The scenario observed for the latter indicates that more than 80% of childbearing women are susceptible to primary infection yielding a risk of congenital toxoplasmosis and respective sequelae. Since there is no vaccine to prevent human toxoplasmosis, the improvement of primary prevention constitutes a major tool to avoid infection in such susceptible groups.
IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial
Authors: Shantsila Eduard , Haynes Ronnie , Calvert Melanie , Fisher James , Kirchhof Paulus , Gill Paramjit S , Lip Gregory Y H
Published: October 2016

Introduction

Patients with atrial fibrillation frequently suffer from heart failure with preserved ejection fraction. At present there is no proven therapy to improve physical capacity and quality of life in participants with permanent atrial fibrillation with preserved left ventricular contractility.

Objective

The single-centre IMproved exercise tolerance In heart failure With PReserved Ejection fraction by Spironolactone On myocardial fibrosiS In Atrial Fibrillation (IMPRESS-AF) trial aims to establish whether treatment with spironolactone as compared with placebo improves exercise tolerance (cardiopulmonary exercise testing), quality of life and diastolic function in patients with permanent atrial fibrillation.

Methods and analysis

A total of 250 patients have been randomised in this double-blinded trial for 2-year treatment with 25 mg daily dose of spironolactone or matched placebo. Included participants are 50 years old or older, have permanent atrial fibrillation and ejection fraction >55%. Exclusion criteria include contraindications to spironolactone, poorly controlled hypertension and presence of severe comorbidities with life expectancy <2 years. The primary outcome is improvement in exercise tolerance at 2 years and key secondary outcomes include quality of life (assessed using the EuroQol EQ-5D-5L (EQ-5D) and Minnesota Living with Heart Failure (MLWHF) questionnaires), diastolic function and all-cause hospitalisation.

Ethics and dissemination

The study has been approved by the National Research and Ethics Committee West Midlands—Coventry and Warwickshire (REC reference number 14/WM/1211). The results of the trial will be published in an international peer-reviewed journal.

Trial registration numbers

EudraCT2014-003702-33;NCT02673463; Pre-results.
Readmissions and mortality in delirious versus non-delirious octogenarian patients after aortic valve therapy: a prospective cohort study
Authors: Eide Leslie S P , Ranhoff Anette H , Fridlund Bengt , Haaverstad Rune , Hufthammer Karl Ove , Kuiper Karel K J , Nordrehaug Jan Erik , Norekvål Tone M
Published: October 2016

Objectives

To determine whether postoperative delirium predicts first-time readmissions and mortality in octogenarian patients within 180 days after aortic valve therapy with surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI), and to determine the most common diagnoses at readmission.

Design

Prospective cohort study of patients undergoing elective SAVR or TAVI.

Setting

Tertiary university hospital that performs all SAVRs and TAVIs in Western Norway.

Participants

Patients 80+ years scheduled for SAVR or TAVI and willing to participate in the study were eligible. Those unable to speak Norwegian were excluded. Overall, 143 patients were included, and data from 136 are presented.

Primary and secondary outcome measures

The primary outcome was a composite variable of time from discharge to first all-cause readmission or death. Secondary outcomes were all-cause first readmission alone and mortality within 180 days after discharge, and the primary diagnosis at discharge from first-time readmission. Delirium was assessed with the confusion assessment method. First-time readmissions, diagnoses and mortality were identified in hospital information registries.

Results

Delirium was identified in 56% of patients. The effect of delirium on readmissions and mortality was greatest during the first 2 months after discharge (adjusted HR 2.9 (95% CI 1.5 to 5.7)). Of 30 first-time readmissions occurring within 30 days, 24 (80%) were patients who experienced delirium. 1 patient (non-delirium group) died within 30 days after therapy. Delirious patients comprised 35 (64%) of 55 first-time readmissions occurring within 180 days. Circulatory system diseases and injuries were common causes of first-time readmissions within 180 days in delirious patients. 8 patients died 180 days after the procedure; 6 (75%) of them experienced delirium.

Conclusions

Delirium in octogenarians after aortic valve therapy might be a serious risk factor for postoperative morbidity and mortality. Cardiovascular disorders and injuries were associated with first-time readmissions in these patients.
Integration of palliative and supportive care in the management of advanced liver disease: development and evaluation of a prognostic screening tool and supportive care intervention
Authors: Hudson Benjamin E , Ameneshoa Kelly , Gopfert Anya , Goddard Rachael , Forbes Karen , Verne Julia , Collins Peter , Gordon Fiona , Portal Andrew J , Reid Colette , McCune C Anne
Published: October 2016

Background and objectives

Patients with decompensated cirrhosis rarely receive palliative and supportive care interventions, which are routine in other life-limiting diseases. We aimed to design and evaluate a prognostic screening tool to routinely identify inpatients with decompensated cirrhosis at high risk of dying over the coming year, alongside the development of a supportive care intervention.

Design

Clinical notes from consecutive patients admitted as an emergency to University Hospitals Bristol with a diagnosis of cirrhosis over two distinct 90-day periods were scrutinised retrospectively for the presence or absence of five evidence-based factors associated with poor prognosis. These were analysed against their ability to predict mortality at 1 year. ‘Plan-Do-Study-Act’ (PDSA) methodology was used to incorporate poor-prognosis screening into the routine assessment of patients admitted with cirrhosis, and develop a supportive care intervention.

Results

73 admissions were scrutinised (79.5% male, 63% alcohol-related liver disease, median age 54). The presence of three or more poor-prognosis criteria at admission predicted 1-year mortality with sensitivity, specificity and positive predictive value of 72.2%, 83.8% and 81.3%, respectively, and was used as a trigger for implementing the supportive care intervention. Following modification from six PDSA cycles, prognostic screening was integrated into the assessment of all patients admitted with decompensated cirrhosis, with the supportive care intervention (developed simultaneously) instigated for appropriate patients.

Conclusions

We describe a model of care which identifies inpatients with cirrhosis at significant risk of dying over the coming year, and describe development of a supportive care intervention, which can be offered to suitable patients in parallel to ongoing active management.
Diagnosing migraine
Authors: MacGregor E Anne
Published: October 2016

Migraine is a common headache disorder, particularly in women. It usually starts during the teens and twenties, a time when many women are seeking contraception advice. Migraine without aura is the most prevalent type of migraine, affecting up to 70% of people with migraine, while the remainder experience attacks with and/or without aura. Aura is a phase of focal neurological symptoms, typically visual. An increasing body of evidence identifies aura as a marker of increased risk of ischaemic stroke and its presence is a contraindication to the use of combined hormonal contraception (CHC). However, aura is often confused with more generalised premonitory visual symptoms of migraine that may precede attacks of migraine with and without aura, which are not associated with stroke risk. Diagnostic confidence is needed so that CHC is not withheld unnecessarily.
Dual contraceptive method use in HIV-serodiscordant Kenyan couples
Authors: Roxby Alison C , Ben-Youssef Leïla , Marx Grace , Kinoti Freda , Bosire Rose , Guthrie Brandon , Mackelprang Romel , Kiarie James , John-Stewart Grace , Farquhar Carey
Published: October 2016

Background

World Health Organization (WHO) guidelines recommend dual contraceptive method use with condoms and another contraceptive to reduce both incidence of HIV/sexually transmitted infection transmission and unintended pregnancies. This qualitative study assessed the barriers to and motivations for dual contraceptive use in Kenyan HIV-serodiscordant couples.

Methods

HIV-serodiscordant couples in Nairobi, Kenya, were recruited from two longitudinal cohorts. Qualitative semistructured interviews were conducted using a semistructured questionnaire. Twelve male and 12 female members of serodiscordant couples and 10 women with incident pregnancies during the cohort studies were included.

Results

Few couples reported using dual contraceptive methods, with men reporting more condom use than women. No HIV-seropositive men or HIV-seronegative women reported using non-condom contraception. Men and women agreed that men play a dominant role in decisions to use both condoms and contraception in HIV-serodiscordant couples. Participants reported that perceptions of side effects, male partner preference, and reproductive desire were critical factors in contraceptive decisions. Both men and women saw dual contraceptive method use as redundant and a sign of possible unfaithfulness. Many participants actively desired pregnancy, but few were able to accurately define monthly fertility windows.

Conclusions

Dual contraceptive method use was low in these HIV-serodiscordant couples, with some couples finding it unnecessary while using condoms, and others being more focused on conceiving a child. Biomedical HIV prevention, including male circumcision, pre-exposure prophylaxis or antiretroviral therapy to reduce HIV transmission, may be more acceptable strategies to promote safer sexual relations among HIV-serodiscordant couples and safer conception when desired.
A randomised trial comparing pain and ease of use of two different stabilising forceps for insertion of intrauterine contraception
Authors: Speedie Joanna M M , Mansour Diana , Landy Rebecca , Clement Kathryn M
Published: October 2016

Background

Pain at intrauterine contraception (IUC) fitting may be a deterrent for women and any reduction in discomfort would be likely to be beneficial to both women and clinicians.

Aim

This study investigated the associated pain and the ease of use of two different stabilising forceps at the time of IUC placement.

Design

Single-blinded randomised controlled trial. One hundred parous women aged 18–50 years who had undergone at least one vaginal delivery were recruited.

Setting

An integrated sexual health service in the North of England.

Methods

Women were randomised to the use of either a Littlewoods forceps or a single-toothed tenaculum forceps to stabilise the cervix at the time of IUC placement. Pain levels were measured at forceps application, IUC insertion, and 5 and 10 minutes post-procedure using a visual analogue scale (VAS). A clinician graded ease of use of the forceps and any associated bleeding. Wilcoxon rank-sum tests were used to compare pain levels between the two forceps groups. Linear regression was used when adjusting for potential confounders.

Results

Mean VAS scores were similar at forceps application (p=0.52), IUC fitting (p=0.10) and at 5 minutes (p=0.32). There was a statistical difference in the degree of pain experienced at 10 minutes in the tenaculum group (p=0.01). Physicians found both forceps easy to use and there was no difference in bleeding (p=0.49).

Conclusions

Parous women who have had a vaginal delivery can be reassured that IUC fitting is well tolerated. Pain scores were not affected by the type of forceps used to stabilise the cervix at IUC placement. Both forceps investigated were easy to use.
Is it objectionable to create a child as a carer for a disabled parent?
Authors: Pojer Benjamin
Published: October 2016

In his recent paper, Adam Cureton presents a compelling case in support of the right of parents with disabilities to conceive and raise children. Cureton argues that (a) caring for a parent with a disability may be beneficial for a child and (b) the creation of a child with the intention of him/her being a carer for his/her disabled parent is objectionable. This response to Cureton's paper will focus on the creation of children with the purpose of them being carers for their disabled parents. I will respond to Cureton on three counts. First, I propose that claims (a) and (b) are incompatible. Second, I will argue that even from a Kantian perspective it is not clear that creating a child as a carer is objectionable. Third, I will argue more broadly that the intentions with which parents bring children into the world are not predictive of the concern parents should show their children once they come into existence.
Lingual mast cell tumour in a cat
Authors: Sommer Breann C , Flesner Brian K , Dehghanpir Shannon , Evans Dawn , Gaunt Stephen D
Published: October 2016

A 12‐year‐old male neutered domestic shorthair cat was presented for staging and treatment recommendations of a lingual mast cell tumour (MCT). Cytology after fine‐needle aspiration of the mandibular lymph nodes revealed regional metastasis. There are limited reports of the biological behaviour, response to treatment and overall prognosis of feline oral MCT. The clinical presentation, cytological and histological features, and response to treatment of a feline lingual MCT are discussed.
Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obesefa/faZucker rats
Authors: Devassy Jessay G. , Wojcik Jennifer L. , Ibrahim Naser H.M. , Zahradka Peter , Taylor Carla G. , Aukema Harold M.
Published: October 2016

Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.
A molecular phylogenetic and DNA barcode assessment of the tribe Pterosiphonieae (Ceramiales, Rhodophyta) emphasizing the Northeast Pacific
Authors: Savoie Amanda M. , Saunders Gary W.
Published: October 2016

Sequence data (COI-5P and rbcL) for North American members of the tribe Pterosiphonieae were compared with collections from around the world. Phylogenetic analyses resolved Pterosiphonia as polyphyletic and many species required transfer to other genera. In our analyses Pterosiphonia sensu stricto included only the type species P. cloiophylla (C. Agardh) Falkenberg and P. complanata (Clemente) Falkenberg, as well as the South African species P. stegengae sp. nov. A new genus, Xiphosiphonia gen. nov., was described for X. ardreana (Maggs & Hommersand) comb. nov., X. pennata (C. Agardh) comb. nov., and X. pinnulata (Kützing) comb. nov. Some Asian, European and North American species previously attributed to Pterosiphonia were transferred to Symphyocladia including S. baileyi (Harvey) comb. nov., S. dendroidea (Montagne) comb. nov., S. plumosa nom. nov. (for P. gracilis Kylin), and S. tanakae (S. Uwai & M. Masuda) comb. nov. We also described two new North American species, Symphyocladia brevicaulis sp. nov. and S. rosea sp. nov. Other species formed a well-supported clade for which the genus name Polyostea Ruprecht was resurrected. Included in Polyostea were P. arctica (J. Agardh) comb. nov., P. bipinnata (Postels & Ruprecht) Ruprecht, P. hamata (E.S. Sinova) comb. nov., and P. robusta (N.L. Gardner) comb. nov.
Seismic velocity model of the crust in the northern Canadian Cordillera from Rayleigh wave dispersion data
Authors: Ma Shutian , Audet Pascal
Published: October 2016

Models of the seismic velocity structure of the crust in the seismically active northern Canadian Cordillera remain poorly constrained, despite their importance in the accurate location and characterization of regional earthquakes. On 29 August 2014, a moderate earthquake with magnitude 5.0, which generated high-quality Rayleigh wave data, occurred in the Northwest Territories, Canada, ∼100 km to the east of the Cordilleran Deformation Front. We carefully selected 23 seismic stations that recorded the Rayleigh waves and divided them into 13 groups according to the azimuth angle between the earthquake and the stations; these groups mostly sample the Cordillera. In each group, we measured Rayleigh wave group velocity dispersion, which we inverted for one-dimensional shear-wave velocity models of the crust. We thus obtained 13 models that consistently show low seismic velocities with respect to reference models, with a slow upper and lower crust surrounding a relatively fast mid crustal layer. The average of the 13 models is consistent with receiver function data in the central portion of the Cordillera. Finally, we compared earthquake locations determined by the Geological Survey of Canada using a simple homogenous crust over a mantle half space with those estimated using the new crustal velocity model, and show that estimates can differ by as much as 10 km.
Some Comments on the Current State of Econometrics
Authors: Judge George
Published: October 2016

Regarding the current econometric scene, in this review I argue that (a) traditional econometric modeling approaches do not provide a reliable basis for making inferences about the causal effect of a supposed treatment of data in observational and quasi-experimental settings; and (b) the focus on conventional reductionist models and information recovery methods has led to irrelevant economic theories and questionable inferences and has failed in terms of prediction and the extraction of information relative to the nature of underlying economic behavior systems. Looking ahead, a nontraditional econometric approach is outlined. This method recognizes that our knowledge regarding the underlying behavioral system and observed data process is complex, partial, and incomplete. It then suggests a self-organized, agent-based, algorithmic-representation system that involves networks, machine learning, and an information theoretic basis for estimation, inference, model evaluation, and prediction.
Solute transport and oxygen consumption along the nephrons: effects of Na+transport inhibitors
Authors: Layton Anita T. , Laghmani Kamel , Vallon Volker , Edwards Aurélie
Published: October 2016

Sodium and its associated anions are the major determinant of extracellular fluid volume, and the reabsorption of Na+by the kidney plays a crucial role in long-term blood pressure control. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+transport (TNa) along the nephron alter urinary solute excretion and TNaefficiency and how those effects may vary along different nephron segments. To accomplish that goal, we used the multinephron model developed in the companion study (28). That model represents detailed transcellular and paracellular transport processes along the nephrons of a rat kidney. We simulated the inhibition of the Na+/H+exchanger (NHE3), the bumetanide-sensitive Na+-K+-2Cl−transporter (NKCC2), the Na+-Cl−cotransporter (NCC), and the amiloride-sensitive Na+channel (ENaC). Under baseline conditions, NHE3, NKCC2, NCC, and ENaC reabsorb 36, 22, 4, and 7%, respectively, of filtered Na+. The model predicted that inhibition of NHE3 substantially reduced proximal tubule TNaand oxygen consumption (QO2). Whole-kidney TNaefficiency, as reflected by the number of moles of Na+reabsorbed per moles of O2consumed (denoted by the ratio TNa/QO2), decreased by ∼20% with 80% inhibition of NHE3. NKCC2 inhibition simulations predicted a substantial reduction in thick ascending limb TNaand QO2; however, the effect on whole-kidney TNa/QO2was minor. Tubular K+transport was also substantially impaired, resulting in elevated urinary K+excretion. The most notable effect of NCC inhibition was to increase the excretion of Na+, K+, and Cl−; its impact on whole-kidney TNaand its efficiency was minor. Inhibition of ENaC was predicted to have opposite effects on the excretion of Na+(increased) and K+(decreased) and to have only a minor impact on whole-kidney TNaand TNa/QO2. Overall, model predictions agree well with measured changes in Na+and K+excretion in response to diuretics and Na+transporter mutations.
Collecting duct-specific knockout of nitric oxide synthase 3 impairs water excretion in a sex-dependent manner
Authors: Gao Yang , Stuart Deborah , Pollock Jennifer S. , Takahishi Takamune , Kohan Donald E.
Published: October 2016

Nitric oxide (NO) inhibits collecting duct (CD) Na+and water reabsorption. Mice with CD-specific knockout (KO) of NO synthase 1 (NOS1) have salt-sensitive hypertension. In contrast, the role of NOS3 in CD salt and water reabsorption is unknown. Mice with CD NOS3 KO were generated with loxP-flanked exons 9–12 (encodes the calmodulin binding site) of the NOS3 gene and the aquaporin-2 promoter-Cre transgene. There were no differences between control and CD NOS3 KO mice, irrespective of sex, in food intake, water intake, urine volume, urinary Na+or K+excretion, plasma renin concentration, blood pressure, or pulse during 7 days of normal (0.3%), high (3.17%), or low (0.03%) Na+intake. Blood pressure was similar between genotypes during DOCA-high salt. CD NOS3 KO did not alter urine volume or urine osmolality after water deprivation. In contrast, CD NOS3 KO male, but not female, mice had lower urine volume and higher urine osmolality over the course of 7 days of water loading compared with control mice. Male, but not female, CD NOS3 KO mice had reduced urinary nitrite+nitrate excretion compared with controls after 7 days of water loading. Urine AVP and AVP-stimulated cAMP accumulation in isolated inner medullary CD were similar between genotypes. Western analysis did not reveal a significant effect of CD NOS3 KO on renal aquaporin expression. In summary, these data suggest that CD NOS3 may be involved in the diuretic response to a water load in a sex-specific manner; the mechanism of this effect remains to be determined.
Secondary generalization of focal-onset seizures: examining the relationship between seizure propagation and epilepsy surgery outcome
Authors: Tomlinson Samuel B. , Venkataraman Arun
Published: October 2016

Surgical intervention often fails to achieve seizure-free results in patients with intractable epilepsy. Identifying features of the epileptic brain that dispose certain patients to unfavorable outcomes is critical for improving surgical candidacy assessments. Recent research by Martinet, Ahmad, Lepage, Cash, and Kramer ( J Neurosci 35: 9477–9490, 2015) suggests that pathways of secondary seizure generalization distinguish patients with favorable (i.e., seizure free) vs. unfavorable (i.e., seizure persistent) surgical outcomes, lending insights into the network mechanisms of epilepsy surgery failure.
Cephalopod Susceptibility to Asphyxiation via Ocean Incalescence, Deoxygenation, and Acidification
Authors: Seibel Brad A.
Published: October 2016

Squids are powerful swimmers with high metabolic rates despite constrained oxygen uptake and transport. They have evolved novel physiological strategies for survival in extreme environments that provide insight into their susceptibility to asphyxiation under anthropogenic ocean incalescence (warming), deoxygenation, and acidification. Plasticity of ecological and physiological traits, in conjunction with vertical and latitudinal mobility, may explain their evolutionary persistence and ensure their future survival.
Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma
Authors: Bochatay Laurent , Majno Pietro , Giostra Emiliano , Frossard Jean Louis
Published: October 2016

IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy.
Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with Hemoglobin E-β-Thalassemia in Northeast Thailand
Authors: Yamsri Supawadee , Pakdee Naruwat , Fucharoen Goonnapa , Sanchaisuriya Kanokwan , Fucharoen Supan
Published: October 2016

Non-transfusion-dependent thalassemia (NTDT) is associated with various forms of thalassemia and genetic modifiers. We report the molecular basis of NTDT in hemoglobin (Hb) E-β-thalassemia disease. This study was done in 73 adult patients encountered at the prenatal diagnosis center of Khon Kaen University, Northeast Thailand. Hematological parameters and Hb patterns were collected, and α- and β-globin gene mutations were determined. Multiple single-nucleotide polymorphisms (SNPs) including the rs7482144/Gγ-XmnI polymorphism, rs2297339, rs2838513, rs4895441, and rs9399137 in the HBS1L-MYB gene, rs4671393 and rs11886868 in the BCL11A gene, and G176AfsX179 in the KLF1 gene were examined. Five β0-thalassemia mutations and a severe β+-thalassemia mutation in trans to the βE gene were identified. No significant difference in hematological parameters was observed among β-thalassemia genotypes. Coinheritance of α-thalassemia was observed in 31 of the 73 subjects (42.5%). Four SNPs including Gγ-XmnI, rs2297339, rs4895441, and rs9399137 of HBS1L-MYB were found to be associated with high Hb F levels in 39 (53.4%) subjects. The molecular basis of NTDT in the remaining 3 (4.1%) cases could not be defined. These results indicate multiple genetic factors in NTDT patients and underline the importance of complete genotyping to provide proper management, make clinical predictions, and improve genetic counseling.
Karyotype and Mapping of Repetitive DNAs in the African Butterfly Fish Pantodon buchholzi, the Sole Species of the Family Pantodontidae
Authors: Ráb Petr , Yano Cassia F. , Lavoué Sébastien , Jegede Oladele I. , Bertollo Luiz A.C. , Ezaz Tariq , Majtánová Zuzana , de Oliveira Ezequiel A. , Cioffi Marcelo B.
Published: October 2016

The monophyletic order Osteoglossiformes represents one of the most ancestral groups of teleosts and has at least 1 representative in all continents of the southern hemisphere, with the exception of Antarctica. However, despite its phylogenetic and biogeographical importance, cytogenetic data in Osteoglossiformes are scarce. Here, karyotype and chromosomal characteristics of the lower Niger River population of the African butterfly fish Pantodon buchholzi, the sole species of the family Pantodontidae (Osteoglossiformes), were examined using conventional and molecular cytogenetic approaches. All specimens examined had 2n = 46 chromosomes, with a karyotype composed of 5 pairs of metacentric, 5 pairs of submetacentric, and 13 pairs of acrocentric chromosomes in both sexes. No morphologically differentiated sex chromosomes were identified. C-bands were located in the centromeric/pericentromeric region of all chromosomes and were associated with the single AgNOR site. FISH with ribosomal DNA probes revealed that both 5S and 18S rDNA were present in only 1 pair of chromosomes each, but did not colocalize. CMA3+ bands were observed near the telomeres in several chromosome pairs and also at the 18S rDNA sites. The mapping of di- and trinucleotide repeat motifs, Rex6 transposable element, and U2 snRNA showed a scattered distribution over most of the chromosomes, but for some microsatellites and the U2 snRNA also a preferential accumulation at telomeric regions. This study presents the first detailed cytogenetic analysis in the African butterfly fish by both conventional and molecular cytogenetic protocols. This is the first of a series of further cytogenetic and cytogenomic studies on osteoglossiforms, aiming to comprehensively examine the chromosomal evolution in this phylogenetically important fish order.
The Impact of Integrating Oral Health Education into a Medical Curriculum
Authors: Park Sang E. , Donoff R. Bruce , Saldana Fidencio
Published: October 2016

Objective: The purpose of this study was to evaluate our pilot program incorporating oral health education into the medical curriculum by evaluating students' perspectives on the oral health curriculum. Subjects and Methods: Two hundred second-year students were asked to fill in a presession survey online regarding their familiarity with basic oral health concepts and their comfort level with performing oral examinations, and a postsession survey on paper that repeated the presession questions and added questions on the effectiveness of the session. Results: Of the 200 students, 164 (82%) participated in the surveys. The pre- and postsurvey results showed that the session helped students become more comfortable with performing oral examinations and recognizing risks for periodontal disease, with an increase from 40 (27%) to 119 (82%) and 51 (35%) to 124 (86%), respectively. Conclusion: In this study, the oral health education session contributed to an increase in student awareness and understanding of oral health. Considering the reported effectiveness of the interactive session on student comfort with performing a basic clinical examination, this model shows promise for further use in other institutions.
Cash Loans to Ottoman Timariots during Military Campaigns (Sixteenth-Seventeenth Centuries)
Authors: Tekgul Nil
Published: October 2016

Scholarship has argued that the Ottomantimarsystem was an efficient way to provide military forces in a non-monetized economy. As the state granted its sources of revenue totimariots in return for military service, it was financially relieved of the need to pay the expenses of the cavalry. Several documents so far neglected by scholars and evidencing the practice of cash loans to timariots during military campaigns prove otherwise. This paper analyzes the process of the generation of timariots’ disposable income in the framework of actor-network theory. It is argued that the granting of loans demonstrated an attempt to regulate the cash flow of the timariot’s income during campaigns, which was necessitated by problems of transforming tax revenues into disposable form. In the light of documents evidencing cash loans, it is further argued that cash loans reflect the vulnerability of the Ottoman timar system.
Postmodern Epistemophilia
Authors: Javangwe Tasiyana D.
Published: October 2016

The postmodern promises to transcend all conventional or traditional ways of knowing and understanding both the self’s experience and the world that the self inhabits. Postmodern existence is characterized by a desire to reformulate how, as persons, individuals have come to know themselves and to relate to those who are in their lives and to the ‘knowledges’ that used to define their being prior to psychological sojourns into the postmodern world. This essay seeks to interrogate the ways in which the character(s) in Chinodya’s Chairman of Fools (2005), particularly the main character, desire and drift towards an epistemic knowing and naming of a postmodern self in an environment that tends to insist on traditional ways of social behaviour and family relations. The essay argues that characters in this novel are caught up in the conflict between a postmodern desire to know and name personal experience differently and the maintenance of relationship structures as defined in a set-up of African traditions. The act of writing, which is what Farai, the main character, is engaged in, is expressive of that desire to explore new modes of knowing and naming both self experience and relations that govern both personal and communal relations in Zimbabwe’s Shona culture.
Creating a Bildungsroman from a Collage
Authors: Okolo Ifeyinwa Genevieve
Published: October 2016

The essay re-reads all of the stories in Shimmer Chinodya’s collection Can We Talk and Other Stories as one entity—a collage—that establishes the framework of a bildungsroman. Here, the exploration of the bildungsroman is limited to the tracing of levels/stages of growth and is extended to the protagonist’s adult life, against the traditional early years of life. From the opening story, of a three-year-old protagonist looking at the adult world through the stories of different protagonists who grapple with different stages of life, to the last story, of an embittered husband in a dysfunctional marriage, the collection strongly suggests a conscious arrangement conveying a sense of a coming of age, both individual and national. In essence, at the end of reading the collection, there is a strong indication that the different situations of the lives of the different protagonists of the eleven stories in the collection build up to yield a unified sense of growth.