bluuebunny/crossref_metadata_2025 huggingface dataset:
Editorial: Ingenious designs and causal inference in child psychology and psychiatry
Authors: Green Jonathan
Published: April 2016

The embryology of behaviour – This title of a book by the great developmental psychologist Arnold Gesell (Gesell, ) continues nicely to encapsulate for me a core endeavour in child psychology and psychiatry; in the use of scientific method to tease out causes and processes within developmental science and psychopathology. This edition of JCPP includes some tremendous examples of the increasing rigour and sophistication with which such questions are being addressed. Particularly encouraging for me, as primarily an interventionist, is the use of well‐designed randomized controlled trials (RCTs) for that end.
Searching for the physiological role of glucose‐dependent insulinotropic polypeptide
Authors: Holst Jens Juul , Windeløv Johanne Agerlin , Boer Geke Aline , Pedersen Jens , Svendsen Berit , Christensen Mikkel , Torekov Signe , Asmar Meena , Hartmann Bolette , Nissen Anne
Published: April 2016

Glucose‐dependent insulinotropic polypeptide (GIP) was established as a gut hormone more than 40 years ago, and there is good experimental support for its role as an incretin hormone although deletion of the GIP receptor or the GIP cells or GIP receptor mutations have only minor effects on glucose metabolism. Unlike the related hormone, GLP‐1, GIP stimulates the secretion of glucagon, which in healthy individuals may help to stabilize glucose levels, but in people with type 2 diabetes may contribute to glucose intolerance. A role in lipid metabolism is supported by numerous indirect observations and by resistance to diet‐induced obesity after deletion of the GIP receptor. However, a clear effect on lipid clearance could not be identified in humans, raising doubt about its importance. The GIP receptor is widely expressed in the body and also appears to be expressed on bone cells, and experimental studies in rodent point to effects on bone metabolism. Recent studies revealed pronounced inhibitory effects of GIP on bone resorption markers in humans and suggest that GIP may be (one of the) gastrointestinal regulators of bone turn‐over. In support of this, a loss‐of‐function GIP receptor mutation in humans is associated with a marked increase in fracture risk. The lack of a reliable GIP receptor antagonist contributes to the uncertainty regarding the physiological role of GIP.
Cellular models for Parkinson's disease
Authors: Falkenburger Björn H. , Saridaki Theodora , Dinter Elisabeth
Published: April 2016

Developing new therapeutic strategies for Parkinson's disease requires cellular models. Current models reproduce the two most salient changes found in the brains of patients with Parkinson's disease: The degeneration of dopaminergic neurons and the existence of protein aggregates consisting mainly of α‐synuclein. Cultured cells offer many advantages over studying Parkinson's disease directly in patients or in animal models. At the same time, the choice of a specific cellular model entails the requirement to focus on one aspect of the disease while ignoring others. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types the aspects of Parkinson's disease they model along with technical advantages and disadvantages. It might also be helpful for researchers from other fields consulting literature on cellular models of Parkinson's disease. Important models for the study of dopaminergic neuron degeneration include Lund human mesencephalic cells and primary neurons, and a case is made for the use of non‐dopaminergic cells to model pathogenesis of non‐motor symptoms of Parkinson's disease. With regard to α‐synuclein aggregates, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques.

image

Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α‐synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques.

This article is part of a special issue on Parkinson disease.
Short‐Term Outcomes of Patent Ductus Arteriosus Closure With New Occlutech® Duct Occluder: A Multicenter Study
Authors: Dedeoglu Reyhan , Bilici Meki , Demir Fikri , Demir Fadli , Acar Onur Çağlar , Hallioglu Olgu , Pac Ayşenur , Kiziltas Alev , Karabel Duran , Kula Serdar , Cimen Derya , Baspinar Osman , Atik Sezen Ugan , Saltik Irfan Levent
Published: April 2016

Aim

Over the past 2 decades, transcatheter occlusion of patent ductus arteriosus (PDA) with coils and the duct occluders evolved to be the procedure of choice. A new device, the Occlutech PDA® occluder (ODO) device has been designed. Herein, we aimed to evaluate the characteristics and short‐term results of patients who underwent transcatheter closure of PDA using the ODO.

Methods

We reviewed the clinical records of 60 patients from different centers in Turkey between December 2013 and January 2016. The medical records were reviewed for demographic characteristics and echocardiographic findings. Device size was selected on the narrowest diameter of PDA.

Results

The median patient age was 2.5 years (6 months–35 years), and median PDA diameter was 2.5 mm (1.2–11 mm). Fifty‐eight of 60 patients (96.6%) had successful ODO implantation. The occlusion rates were 37/58 (63.7%) at the end of the procedure, 51/58 (87.9%) at 24–48 hours post‐procedure, and 57/58 (98.2%) on echocardiography at a median follow‐up of 7.6 months.

Conclusion

Our results indicate that transcatheter closure of PDA using the ODO is effective. Larger studies and longer follow‐up are required to assess whether its shape and longer length make it superior to other duct occluders in large, tubular, or window‐type ducts. (J Interven Cardiol 2016;29:325–331)
Melatonin improves reprogramming efficiency and proliferation of bovine‐induced pluripotent stem cells
Authors: Bai Chunyu , Li Xiangchen , Gao Yuhua , Yuan Ziao , Hu Pengfei , Wang Hui , Liu Changqing , Guan Weijun , Ma Yuehui
Published: April 2016

Melatonin can modulate neural stem cell (NSC) functions such as proliferation and differentiation into NSC‐derived pluripotent stem cells (N‐iPS) in brain tissue, but the effect and mechanism underlying this are unclear. Thus, we studied how primary cultured bovine NSCs isolated from the retinal neural layer could transform into N‐iPS cell. NSCs were exposed to 0.01, 0.1, 1, 10, or 100 μm melatonin, and cell viability studies indicated that 10 μm melatonin can significantly increase cell viability and promote cell proliferation in NSCs in vitro. Thus, 10 μm melatonin was used to study miR‐302/367‐mediated cell reprogramming of NSCs. We noted that this concentration of melatonin increased reprogramming efficiency of N‐iPS cell generation from primary cultured bovine NSCs and that this was mediated by downregulation of apoptosis‐related genes p53 and p21. Then, N‐iPS cells were treated with 1, 10, 100, or 500 μm melatonin, and N‐iPS (M‐N‐iPS) cell proliferation was measured. We noted that 100 μm melatonin increased proliferation of N‐iPS cells via increased phosphorylation of intracellular ERK1/2 via activation of its pathway in M‐N‐iPS via melatonin receptors 1 (MT1). Finally, we verified that N‐iPS cells and M‐N‐iPS cells are similar to typical embryonic stem cells including the expression of pluripotency markers (Oct4 and Nanog), the ability to form teratomas in vivo, and the capacity to differentiate into all three embryonic germ layers.
‘The character rests heavily within me’: drama students as standardized patients in mental health nursing education
Authors: Jacobs A. C. , van Jaarsveldt D. E.
Published: April 2016

Accessible summary

What is known on the subject?

Standardized patient (SP) simulation is an internationally recognized learning strategy that has proven effective in enhancing nursing students’ competencies necessary for mental health practice.

What does this paper add to existing knowledge?

A deeper exploration of the process from the perspective of SPs and more particularly drama students, revealed the complexity they need to navigate and the personal vulnerability they are exposed to when creating an authentic learning opportunity for nursing students.

What are the implications for practice?

Their vulnerability justifies deeper consideration of support, as well as research on the ethical implications of SP simulation.

Nursing students need to be well grounded in therapeutic communication before engaging with mental health users. This should include opportunities to question personal frames of reference that could hinder therapeutic engagement with diverse others.

In future, the drama students can be involved in scenario development to enhance the authenticity of simulations.

Introduction

The effectiveness of Standardized patient (SP) simulation in enhancing students’ mental health nursing competencies is well published. Nevertheless, the believable and accurate portrayal of a patient with a mental health issue during SP simulation is complex. Though vital to the creation of safe authentic learning experiences, the perspectives of SPs and particularly of drama students involved in SP simulation are unknown.

Aim

The aim of this paper is therefore to explore and describe the experiences of 11 drama students engaged in mental health simulations for nursing students.

Method

A qualitative approach was taken and data were gathered using various techniques.

Findings

The content analysis revealed that these SPs negotiated three roles during this interdisciplinary learning experience, namely of a facilitator of learning, a drama student and the person within.

Discussion

The study provided valuable insight into the world of an SP, including the complexities they navigate and the vulnerability they experience.

Implications for Practice

Nurse educators are alerted to SP's need for support and the necessity of establishing good interpersonal skills before nursing students enter the practice setting. Involvement of SPs in scenario development could enhance the authenticity of future simulations. The ethical implications of SP simulation requires further exploration.
Reproducing Disability and Degeneration in the Victorian Fin de Siècle
Authors: Andree Courtney J.
Published: April 2016

Understandings of disability were in flux in the Victorian fin de siècle as eugenic thought and degeneration theory gained in popularity. Increasingly imagined as a marker of national and familial decline in the scientific and popular literature of the day, people with disabilities were refigured as domestic threats in the late‐19th century, and increasingly immersed in a culture of shame and secret keeping. While fin de siècle works from Conrad, Haggard, and Wells banished disability to the ends of empire and projected it into the distant future, New Woman novelists like Emma Frances Brooke and Sarah Grand sought to “contain” and ultimately eradicate disability from the British home by rationalizing women's role in marriage and reproduction. Brooke'sA Superfluous Woman(1894) synthesizes late‐19th century outlooks on degeneration and heredity as it locates disability and deviance in the upper class home. By engaging with recent histories of disability and literary studies of degeneration and eugenics, this article identifies the dearth of literary scholarship on disability in the fin de siècle and points to future opportunities for inquiry.
An autopsy case of cortical superficial siderosis with persistent abnormal behavior
Authors: Torii Youta , Iritani Shuji , Fujishiro Hiroshige , Sekiguchi Hirotaka , Habuchi Chikako , Umeda Kentaro , Matsunaga Shinji , Mimuro Maya , Ozaki Norio , Yoshida Mari , Fujita Kiyoshi
Published: April 2016

In recent years, MRI has revealed cortical superficial siderosis (cSS), which exhibits hemosiderin deposition in only the cortical surface. However, the associations between the histological findings and clinical symptoms of cSS remain unclear. We herein report an autopsy case of a 75‐year‐old Japanese man with cSS with persistent abnormal behavior according to cognitive impairment, hallucination and delusion. At 73 years of age, the patient presented with unusual behavior that indicated auditory hallucination and delusion. One year later, he was admitted to the hospital for malignant lymphoma. On admission, cognitive impairment was detected by a screening test. Soon after hospitalization, he presented with active delirium including visual hallucination and delusion. The patient's excited behavior was improved by the administration of a major tranquilizer. However, the abnormal behavior and cognitive impairment persisted. At 75 years of age, he died of heart failure. A neuropathological investigation revealed hemosiderin depositions in the superficial layer of the cortex in the medial and lateral frontal lobe, the lateral temporal lobe, the parietal lobe, and the medial and lateral occipital lobe. Neuritic plaques and diffuse plaques were extensively observed, which corresponded to Braak stage C and CERAD B, although NFTs were observed that corresponded to Braak stage II. Cortical amyloid angiopathy was not observed in any regions. Ischemic change of brain was also mild. Our report suggests that localized deposition of hemosiderin in the cortex might affect the manifestation of cognitive impairments and hallucination. Further clinicopathological studies are needed to clarify the clinical manifestations of patients with cSS.
Asthma, hay fever, and food allergy are associated with caregiver‐reported speech disorders in US children
Authors: Strom Mark A. , Silverberg Jonathan I.
Published: April 2016

Background

Children with asthma, hay fever, and food allergy may have several factors that increase their risk of speech disorder, including allergic inflammation, ADD/ADHD, and sleep disturbance. However, few studies have examined a relationship between asthma, allergic disease, and speech disorder. We sought to determine whether asthma, hay fever, and food allergy are associated with speech disorder in children and whether disease severity, sleep disturbance, or ADD/ADHD modified such associations.

Methods

We analyzed cross‐sectional data on 337,285 children aged 2–17 years from 19 US population‐based studies, including the 1997–2013 National Health Interview Survey and the 2003/4 and 2007/8 National Survey of Children's Health.

Results

In multivariate models, controlling for age, demographic factors, healthcare utilization, and history of eczema, lifetime history of asthma (odds ratio [95% confidence interval]: 1.18 [1.04–1.34], p = 0.01), and one‐year history of hay fever (1.44 [1.28–1.62], p < 0.0001) and food allergy (1.35 [1.13–1.62], p = 0.001) were associated with increased odds of speech disorder. Children with current (1.37 [1.15–1.59] p = 0.0003) but not past (p = 0.06) asthma had increased risk of speech disorder. In one study that assessed caregiver‐reported asthma severity, mild (1.58 [1.20–2.08], p = 0.001) and moderate (2.99 [1.54–3.41], p < 0.0001) asthma were associated with increased odds of speech disorder; however, severe asthma was associated with the highest odds of speech disorder (5.70 [2.36–13.78], p = 0.0001).

Conclusion

Childhood asthma, hay fever, and food allergy are associated with increased risk of speech disorder. Future prospective studies are needed to characterize the associations.
Incidence and risk factors for postoperative vomiting following atrial septal defect repair in children
Authors: Lee Joshua , Faraoni David , Lee Sandra , Brown Morgan , Odegard Kirsten , Randolph Adrienne , DiNardo James A. , Yuki Koichi
Published: April 2016

Background

The incidence and risk factors for postoperative vomiting (POV) after pediatric cardiac surgery has not been studied.

Aims

This study sought to assess the incidence and risk factors for POV in children undergoing surgical repair of an atrial septal defect (ASD).

Methods

We retrospectively collected perioperative data from 160 patients who underwent surgical repair of an ASD and met early extubation criteria. Demographic and clinical data that could potentially influence the incidence of POV were collected. Univariate analysis was performed using Student t‐test or Wilcoxon rank test to identify factors associated with POV. Continuous variables were dichotomized based on the cutoff values derived from the receiver operating characteristic (ROC) curve analysis and the Youden‐J index. We used multivariate logistic regression analysis using backward selection to determine the independent predictors using a univariate cutoff of P < 0.10 for inclusion and P > 0.05 for removal to determine factors independently associated with POV. The accuracy of our multivariate model was assessed by the area under the ROC curve (AUC).

Results

Overall the incidence of POV was 37.5% in all the children who underwent surgical ASD repair. POV did not significantly differ between patients who received and did not receive antiemetics intraoperatively. Age of ≥4 years and cardiopulmonary bypass (CPB) time ≥51 min were identified as independent risk predictors for POV and the AUC of logistic regression model was 0.650 (95% confidence interval; 0.565–0.735).

Conclusions

The incidence of POV in children undergoing surgical ASD repair was 37.5%. Age ≥4 years and CPB time ≥51 min were identified as independent predictors.
Volatile compounds emitted by diverse phytopathogenic microorganisms promote plant growth and flowering through cytokinin action
Authors: Sánchez‐López Ángela María , Baslam Marouane , De Diego Nuria , Muñoz Francisco José , Bahaji Abdellatif , Almagro Goizeder , Ricarte‐Bermejo Adriana , García‐Gómez Pablo , Li Jun , Humplík Jan F. , Novák Ondřej , Spíchal Lukáš , Doležal Karel , Baroja‐Fernández Edurne , Pozueta‐Romero Javier
Published: April 2016

It is known that volatile emissions from some beneficial rhizosphere microorganisms promote plant growth. Here we show that volatile compounds (VCs) emitted by phylogenetically diverse rhizosphere and non‐rhizhosphere bacteria and fungi (including plant pathogens and microbes that do not normally interact mutualistically with plants) promote growth and flowering of various plant species, including crops. In Arabidopsis plants exposed to VCs emitted by the phytopathogen Alternaria alternata, changes included enhancement of photosynthesis and accumulation of high levels of cytokinins (CKs) and sugars. Evidence obtained using transgenic Arabidopsis plants with altered CK status show that CKs play essential roles in this phenomenon, because growth and flowering responses to the VCs were reduced in mutants with CK‐deficiency (35S:AtCKX1) or low receptor sensitivity (ahk2/3). Further, we demonstrate that the plant responses to fungal VCs are light‐dependent. Transcriptomic analyses of Arabidopsis leaves exposed to A. alternata VCs revealed changes in the expression of light‐ and CK‐responsive genes involved in photosynthesis, growth and flowering. Notably, many genes differentially expressed in plants treated with fungal VCs were also differentially expressed in plants exposed to VCs emitted by the plant growth promoting rhizobacterium Bacillus subtilis GB03, suggesting that plants react to microbial VCs through highly conserved regulatory mechanisms.
Beyond Being on Call: Time, Contingency, and Unpredictability Among Family Caregivers for the Elderly
Authors: Altomonte Guillermina
Published: April 2016

This article explores contingency as a central yet underappreciated feature of care work. It does so by focusing on family elder care and the complex temporal interactions between caregiver, care receiver, and healthcare institutions in the U.S. context. Drawing on in‐depth interviews with 19 family caregivers for an elderly relative, I show that their experience of time is, paradoxically, systematically unpredictable. It is shaped by three dimensions: uncertain futures (not knowing how long, or how much, they will have to care), conflicting rhythms (mediating between the temporalities of institutions and that of the elderly relative), and flooded time (ongoing expectations of interruption). Focusing on caregivers’ experiences of unpredictability highlights their exclusion from broader social temporalities and the obstruction of their possibilities to craft their own futures. I therefore suggest that the experience and management of contingency may constitute its own form of inequality and is a fruitful site for exploring the temporal relations between paid and unpaid labor. Also, sociological theories of time and labor may benefit from foregrounding care work to advance understandings of the complex and hierarchical interactions between multiple temporal orders in post‐Fordist economies.
A review of antiviral drugs and other compounds with activity against feline herpesvirus type 1
Authors: Thomasy Sara M. , Maggs David J.
Published: April 2016

Feline herpesvirus type 1 (FHV‐1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected withFHV‐1. Translational use of drugs in this manner ideally requires methodical investigation of theirin vitroefficacy againstFHV‐1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo‐controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client‐owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity againstFHV‐1, as well as a discussion of their safety in cats.
Freestanding Flexible Si Nanoparticles–Multiwalled Carbon Nanotubes Composite Anodes for Li-Ion Batteries and Their Prelithiation by Stabilized Li Metal Powder
Authors: Yao K. , Liang R. , Zheng J. P.
Published: April 2016

Freestanding flexible Si nanoparticles–multiwalled carbon nanotubes (SiNPs–MWNTs) composite paper anodes for Li-ion batteries (LIBs) have been prepared using a combination of ultrasonication and pressure filtration. No conductive additive, binder, or metal current collector is used. The SiNPs–MWNTs composite electrode material achieves first cycle specific discharge and charge capacities of 2298 and 1492 mAh/g, respectively. To address the first cycle irreversibility, stabilized Li metal powder (SLMP) has been utilized to prelithiate the composite anodes. As a result, the first cycle irreversible capacity loss is reduced from 806 to 28 mAh/g and the first cycle coulombic efficiency is increased from 65% to 98%. The relationship between different SLMP loadings and cell performance has been established to understand the prelithiation process of SLMP and to optimize the construction of Si-based cells. A cell containing the prelithiated anode is able to deliver charge capacity over 800 mAh/g without undergoing the initial discharge process, which enables the exploration of novel cathode materials.
Assessing Cogeneration Activity in Extraction–Condensing Steam Turbines: Dissolving the Issues by Applied Thermodynamics
Authors: Verbruggen Aviel , Klemeš Jiří Jaromír , Rosen Marc A.
Published: April 2016

Extraction–condensing steam turbines mix cold-condensing and cogeneration activities making the respective power and fuel flows not directly observable. A flawed assessment of the flows is causing confusion and bias. A steam expansion path on a Mollier diagram reveals the design characteristics of a thermal power plant and of its embedded combined heat and power (CHP) activities. State variable data on a unit mass of steam, entering the turboset as life steam and leaving it at one of the heat extraction exhausts, provide the roster of the power-heat production possibility set of the plant. The actual production possibilities are drawn from the roster by applying capacity data and constraints on the heat extraction points. Design power-to-heat ratios of CHP activities are univocally identified, allowing accurate assessments of cogenerated power. This information is needed for proper incentive regulation of CHP activities, pursuing maximization of CHP quality and quantity. Quality is gauged by the power-to-heat ratio, principally a design (investment) decision. Quantity is gauged by the operational amounts of recovered heat exhausts. Optimal regulatory specificity is attained through setting generic frameworks by technology, accommodating investment and operational decisions by plant owners. Our novel method is explained and applied with numerical data, also revealing the flaws in present regulations.
A Single-Loop Kriging Surrogate Modeling for Time-Dependent Reliability Analysis
Authors: Hu Zhen , Mahadevan Sankaran
Published: April 2016

Current surrogate modeling methods for time-dependent reliability analysis implement a double-loop procedure, with the computation of extreme value response in the outer loop and optimization in the inner loop. The computational effort of the double-loop procedure is quite high even though improvements have been made to improve the efficiency of the inner loop. This paper proposes a single-loop Kriging (SILK) surrogate modeling method for time-dependent reliability analysis. The optimization loop used in current methods is completely removed in the proposed method. A single surrogate model is built for the purpose of time-dependent reliability assessment. Training points of random variables and over time are generated at the same level instead of at two separate levels. The surrogate model is refined adaptively based on a learning function modified from time-independent reliability analysis and a newly developed convergence criterion. Strategies for building the surrogate model are investigated for problems with and without stochastic processes. Results of three numerical examples show that the proposed single-loop procedure significantly increases the efficiency of time-dependent reliability analysis without sacrificing the accuracy.
FOXF1 maintains endothelial barrier function and prevents edema after lung injury
Authors: Cai Yuqi , Bolte Craig , Le Tien , Goda Chinmayee , Xu Yan , Kalin Tanya V. , Kalinichenko Vladimir V.
Published: April 2016

The transcription factor FOXF1 activates a signaling pathway in endothelial cells that promotes recovery from lung injury.
Frequency and Distribution of Tuberculosis Resistance-Associated Mutations between Mumbai, Moldova, and Eastern Cape
Authors: Georghiou S. B. , Seifert M. , Catanzaro D. , Garfein R. S. , Valafar F. , Crudu V. , Rodrigues C. , Victor T. C. , Catanzaro A. , Rodwell T. C.
Published: April 2016

Molecular diagnostic assays, with their ability to rapidly detect resistance-associated mutations in bacterial genes, are promising technologies to control the spread of drug-resistant tuberculosis (DR-TB). Sequencing assays provide detailed information for specific gene regions and can help diagnostic assay developers prioritize mutations for inclusion in their assays. We performed pyrosequencing of sevenMycobacterium tuberculosisgene regions (katG,inhA,ahpC,rpoB,gyrA,rrs, andeis) for 1,128 clinical specimens from India, Moldova, and South Africa. We determined the frequencies of each mutation among drug-resistant and -susceptible specimens based on phenotypic drug susceptibility testing results and examined mutation distributions by country. The most common mutation among isoniazid-resistant (INHr) specimens was thekatG315ACC mutation (87%). However, in the Eastern Cape, INHrspecimens had a lower frequency ofkatGmutations (44%) and higher frequencies ofinhA(47%) andahpC(10%) promoter mutations. The most common mutation among rifampin-resistant (RIFr) specimens was therpoB531TTG mutation (80%). The mutation was common in RIFrspecimens in Mumbai (83%) and Moldova (84%) but not the Eastern Cape (17%), where the 516GTC mutation appeared more frequently (57%). The most common mutation among fluoroquinolone-resistant specimens was thegyrA94GGC mutation (44%). Therrs1401G mutation was found in 84%, 84%, and 50% of amikacin-resistant, capreomycin-resistant, and kanamycin (KAN)-resistant (KANr) specimens, respectively. Theeispromoter mutation −12T was found in 26% of KANrand 4% of KAN-susceptible (KANs) specimens. Inclusion of theahpCandeispromoter gene regions was critical for optimal test sensitivity for the detection of INH resistance in the Eastern Cape and KAN resistance in Moldova. (This study has been registered atClinicalTrials.govunder registration number NCT02170441.)
Daptomycin in Combination with Ceftolozane-Tazobactam or Cefazolin against Daptomycin-Susceptible and -Nonsusceptible Staphylococcus aureus in an
In Vitro
, Hollow-Fiber Model
Authors: Smith Jordan R. , Arya Anu , Yim Juwon , Barber Katie E. , Hallesy Jessica , Singh Nivedita B. , Rybak Michael J.
Published: April 2016

Ceftolozane-tazobactam (TOL-TAZ) is a novel cephalosporin/beta-lactamase inhibitor with activity against several Gram-negative pathogens. Daptomycin (DAP) has demonstrated synergistic activity with beta-lactams against methicillin-resistant
Staphylococcus aureus
(MRSA) isolates with reduced lipopeptide and glycopeptide susceptibilities. Our objective was to determine if DAP and TOL-TAZ possess synergy in hollow-fiber pharmacokinetic/pharmacodynamic (PK/PD) models. One isogenic pair of daptomycin-susceptible and daptomycin-nonsusceptible MRSA strains was evaluated. DAP, TOL-TAZ, and cefazolin (CFZ) MIC determinations were performed. DAP MIC determinations were also performed in the presence of subinhibitory concentrations of TOL-TAZ and CFZ. Ninety-six-hour
in vitro
models were run, simulating DAP at 10 mg/kg of body weight/day; TOL-TAZ at 1,500 mg every 8 h; TOL at 1,000 mg every 8 h; and DAP combined with TOL-TAZ (DAP+TOL-TAZ), DAP+TOL, DAP+TAZ, and DAP+CFZ at 2,000 mg every 8 h. DAP MICs were 0.5 and 4 μg/ml for strains R8845 and R8846, respectively. In the presence of CFZ, R8845 and R8846 DAP MICs were reduced 8-fold and 16-fold, respectively. TOL and TAZ had no effect on DAP MICs. PK/PD models demonstrated bactericidal activity with DAP+CFZ against both strains. The combination of DAP+TOL-TAZ was bactericidal against R8845 but was not bactericidal against daptomycin-nonsusceptible strain R8846. DAP+TOL and DAP+TAZ were not bactericidal. No other regimens were bactericidal. DAP+TOL-TAZ did not demonstrate synergistic activity against daptomycin-nonsusceptible
S. aureus
but prevented daptomycin-nonsusceptible MRSA emergence. Because DAP+TOL or TAZ alone did not prevent daptomycin-nonsusceptible MRSA emergence, the combination TOL-TAZ may be necessary for synergy with DAP. DAP+CFZ demonstrated enhancement against both strains. The combination of DAP+CFZ warrants further clinical study.
Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice
Authors: Deshpande Abhishek , Hurless Kelly , Cadnum Jennifer L. , Chesnel Laurent , Gao Lihong , Chan Luisa , Kundrapu Sirisha , Polinkovsky Alexander , Donskey Curtis J.
Published: April 2016

The use of oral vancomycin or metronidazole for treatment of
Clostridium difficile
infection (CDI) may promote colonization by health care-associated pathogens due to disruption of the intestinal microbiota. Because the macrocyclic antibiotic fidaxomicin causes less alteration of the intestinal microbiota than vancomycin, we hypothesized that it would not lead to a loss of colonization resistance to vancomycin-resistant enterococci (VRE) and extended-spectrum-β-lactamase-producing
Klebsiella pneumoniae
(ESBL-Kp). Mice (8 per group) received orogastric saline, vancomycin, or fidaxomicin daily for 5 days at doses resulting in stool concentrations in mice similar to those measured in humans. The mice were challenged with 10
5
CFU of orogastric VRE or ESBL-Kp on day 2 of treatment and concentrations of the pathogens in stool were monitored. The impact of drug exposure on the microbiome was measured by cultures, real-time PCR for selected anaerobic bacteria, and deep sequencing. In comparison to saline controls, oral vancomycin promoted establishment of high-density colonization by VRE and ESBL-Kp in stool (8 to 10 log
10
CFU/g;
P
< 0.001), whereas fidaxomicin did not (<4 log
10
CFU;
P
> 0.5). Vancomycin treatment resulted in significant reductions in enterococci,
Bacteroides
spp., and
Clostridium leptum
, whereas the population of aerobic and facultative Gram-negative bacilli increased; deep-sequencing analysis demonstrated suppression of
Firmicutes
and expansion of
Proteobacteria
during vancomycin treatment. Fidaxomicin did not cause significant alteration of the microbiota. In summary, in contrast to vancomycin, fidaxomicin treatment caused minimal disruption of the intestinal microbiota and did not render the microbiota susceptible to VRE and ESBL-Kp colonization.
The Periodontal Pathogen Porphyromonas gingivalis Preferentially Interacts with Oral Epithelial Cells in S Phase of the Cell Cycle
Authors: Al-Taweel Firas B. , Douglas C. W. Ian , Whawell Simon A.
Published: April 2016

Porphyromonas gingivalis
, a key periodontal pathogen, is capable of invading a variety of cells, including oral keratinocytes, by exploiting host cell receptors, including alpha-5 beta-1 (α5β1) integrin. Previous studies have shown that
P. gingivalis
accelerates the cell cycle and prevents apoptosis of host cells, but it is not known whether the cell cycle phases influence bacterium-cell interactions. The cell cycle distribution of oral keratinocytes was characterized by flow cytometry and BrdU (5-bromo-2-deoxyuridine) staining following synchronization of cultures by serum starvation. The effect of cell cycle phases on
P. gingivalis
invasion was measured by using antibiotic protection assays and flow cytometry, and these results were correlated with gene and surface expression levels of α5 integrin and urokinase plasminogen activator receptor (uPAR). There was a positive correlation (
R
= 0.98) between the number of cells in S phase and
P. gingivalis
invasion, the organism was more highly associated with cells in S phase than with cells in G
2
and G
1
phases, and S-phase cells contained 10 times more bacteria than did cells that were not in S phase. Our findings also show that α5 integrin, but not uPAR, was positively correlated with cells in S phase, which is consistent with previous reports indicating that
P. gingivalis
invasion of cells is mediated by α5 integrin. This study shows for the first time that
P. gingivalis
preferentially associates with and invades cells in the S phase of the cell cycle. The mechanism of targeting stable dividing cells may have implications for the treatment of periodontal diseases and may partly explain the persistence of this organism at subgingival sites.
Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma
Authors: Bedi Brahmchetna , Yuan Zhihong , Joo Myungsoo , Zughaier Susu M. , Goldberg Joanna B. , Arbiser Jack L. , Hart C. Michael , Sadikot Ruxana T.
Published: April 2016

The pathogenic profile of
Pseudomonas aeruginosa
is related to its ability to secrete a variety of virulence factors. Quorum sensing (QS) is a mechanism wherein small diffusible molecules, specifically acyl-homoserine lactones, are produced by
P. aeruginosa
to promote virulence. We show here that macrophage clearance of
P. aeruginosa
(PAO1) is enhanced by activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ). Macrophages treated with a PPARγ agonist (pioglitazone) showed enhanced phagocytosis and bacterial killing of PAO1. It is known that PAO1 QS molecules are inactivated by PON-2. QS molecules are also known to inhibit activation of PPARγ by competitively binding PPARγ receptors. In accord with this observation, we found that infection of macrophages with PAO1 inhibited expression of PPARγ and PON-2. Mechanistically, we show that PPARγ induces macrophage paraoxonase 2 (PON-2), an enzyme that degrades QS molecules produced by
P. aeruginosa
. Gene silencing studies confirmed that enhanced clearance of PAO1 in macrophages by PPARγ is PON-2 dependent. Further, we show that PPARγ agonists also enhance clearance of
P. aeruginosa
from lungs of mice infected with PAO1. Together, these data demonstrate that
P. aeruginosa
impairs the ability of host cells to mount an immune response by inhibiting PPARγ through secretion of QS molecules. These studies define a novel mechanism by which PPARγ contributes to the host immunoprotective effects during bacterial infection and suggest a role for PPARγ immunotherapy for
P. aeruginosa
infections.
Adverse drug reactions of systemic antihistamines in children in the Netherlands
Authors: de Vries Tjalling W , van Hunsel Florence
Published: April 2016

Background

Antihistamines are used for the treatment of allergic rhinitis, allergic conjunctivitis, chronic spontaneous urticaria and atopic eczema.

Objective

To study the reports of adverse drug reactions (ADRs) in children using antihistamines to provide prescribers with an overview of the possible toxicity.

Design

We studied ADRs in children reported to the Netherlands Pharmacovigilance Centre Lareb in the years 1991–2014, assessed the Naranjo score and, when possible, computed the reporting OR.

Results

Serious ADRs included one death (malignant neuroleptic syndrome), cardiac arrhythmia (one case) and convulsions (three cases). Skin eruptions, headache and somnolence were the most frequently reported ADRs. Aggression and agitation were also reported.

Conclusions

Toxicity can occur with second-generation antihistamines. The main toxicity relates to skin eruptions and central nervous system problems.
Tuberculous suprasternal notch abscess in a child
Authors: Vijay Vipul , Vaishya Raju
Published: April 2016

Tuberculosis has been declared a ‘Global Emergency’ by the WHO. Owing to the magnitude of the problem, knowledge of unusual presentations at rare sites can help identify the disease early and achieve good to fair results. We present one such rare case of a child with an anterior midline swelling. An anterior midline swelling in a child raises multiple diagnostic possibilities. Although cervical lymphadenitis is a common cause of neck swelling, tuberculous suprasternal notch abscess, secondary to lymphadenitis, has rarely been described. Radiological investigations revealed necrotic tissue in the base of the suprasternal notch. The diagnosis was made using needle aspiration and cytology, which was suggestive of tuberculous lymphadenitis for the neck swelling. Antituberculous therapy gave good results, with complete healing of the ulcer and resolution of the abscess.
Initial presentation of CNS-restricted acute lymphoblastic B cell leukaemia as peripheral polyneuropathy
Authors: Piovezani Ramos Guilherme , Villasboas Bisneto Jose C , Chen Dong , Pardanani Animesh
Published: April 2016

We report a case of a 58-year-old woman who presented with a 1-month course of progressive lower and upper extremity weakness in addition to binocular diplopia. Diagnostic lumbar puncture revealed atypical lymphoid cells with 28% blasts. Immunophenotype was consistent with B cell acute lymphoblastic leukaemia (B-ALL). Further work up showed no systemic involvement but extensive thoracolumbar-sacral leptomeningeal disease. The patient was treated with several courses of intrathecal and systemic chemotherapy followed by craniospinal irradiation for consolidation. There was initial steady improvement in neurological symptoms and leptomeningeal disease, the latter being ascertained through radiological studies and cerebrospinal fluid examination. After 10 months of response, the patient relapsed with central nervous system (CNS) and systemic disease. B-ALL is a rare precursor lymphoid neoplasm that generally presents with systemic disease. While CNS involvement is not uncommon, isolated involvement of this compartment without systemic disease is exceedingly rare.
Chilblain-like leukaemia cutis
Authors: Tran Chi , McEwen Gary , Fraga Garth Robert
Published: April 2016

Chilblain, also known as pernio, is an abnormal inflammatory response to cold, moist environmental conditions. Persistent or atypical lesions should prompt investigation to exclude underlying systemic illness. We describe a case of acute myeloid leukaemia that presented with chilblain-like leukaemia cutis.
Diagnosis of a rare fetal haemoglobinopathy in the age of next-generation sequencing
Authors: Hooven Thomas A , Hooper Ellen M , Wontakal Sandeep N , Francis Richard O , Sahni Rakesh , Lee Margaret T
Published: April 2016

Neonatal cyanosis resulting from a fetal methaemoglobin variant is rare. Most such variants are only described in a few published case reports. We present the case of a newborn with unexplained persistent cyanosis, ultimately determined to have a γ-chain mutation causing Hb FM-Fort Ripley. This neonatal haemoglobinopathy can be challenging to diagnose, as significant oxygen desaturation may result from barely detectable levels of the mutant haemoglobin and co-oximetry studies may show a falsely normal methaemoglobin level. Our analysis of the infant's haemoglobin included high-performance liquid chromatography, cellulose acetate electrophoresis and citrate agar electrophoresis, which showed trace amounts of a suspected variant. Ultimately, the diagnosis was made through a novel application of next-generation sequencing (NGS). NGS-based diagnostic approaches are becoming increasingly available to clinicians, and our case provides a framework and evidence for the utilisation of such testing paradigms in the diagnosis of a rare cause of neonatal cyanosis.
Data for development in health: a case study and monitoring framework from Kazakhstan
Authors: Obermann Konrad , Chanturidze Tata , Richardson Erica , Tanirbergenov Serik , Shoranov Marat , Nurgozhaev Ali
Published: April 2016

Healthcare reforms are often not coupled with a relevant and appropriate monitoring framework, leaving policymakers and the public without evidence about the implications of such reforms.

Kazakhstan has embarked on a large-scale reform of its healthcare system in order to achieve Universal Health Coverage. The health-related 2020 Strategic Development Goals reflect this political ambition. In a case-study approach and on the basis of published and unpublished evidence as well as personal involvement and experience (A) the indicators in the 2020 Strategic Development Goals were assessed and (B) a ‘data-mapping’ exercise was conducted, where the WHO health system framework was used to describe the data available at present in Kazakhstan and comment on the different indicators regarding their usefulness for monitoring the current health-related 2020 Strategic Development Goals in Kazakhstan.

It was concluded that the country’s current monitoring framework needs further development to track the progress and outcomes of policy implementation. The application of a modified WHO/World Bank/Global Fund health system monitoring framework was suggested to examine the implications of recent health sector reforms. Lessons drawn from the Kazakhstan experience on tailoring the suggested framework, collecting the data, and using the generated intelligence in policy development and decision-making can serve as a useful example for other middle-income countries, potentially enabling them to fast-track developments in the health sector.
Support of public–private partnerships in health promotion and conflicts of interest
Authors: Hernandez-Aguado Ildefonso , Zaragoza G A
Published: April 2016

Objectives

Public–private partnerships (PPPs) are considered key elements in the development of effective health promotion. However, there is little research to back the enthusiasm for these partnerships. Our objective was to describe the diversity of visions on PPPs and to assess the links between the authors and corporations engaged in such ventures.

Methods

We reviewed the scientific literature through PubMed in order to select all articles that expressed a position or recommendation on governments and industries engaging in PPPs for health promotion. We included any opinion paper that considered agreements between governments and corporations to develop health promotion. Papers that dealt with healthcare provision or clinical preventive services and those related to tobacco industries were excluded. We classified the articles according to the authors' position regarding PPPs: strongly agree, agree, neutral, disagree and strongly disagree. We related the type of recommendation to authors' features such as institution and conflicts of interest. We also recorded whether the recommendations were based on previous assessments.

Results

Of 46 papers analysed, 21 articles (45.6%) stated that PPPs are helpful in promoting health, 1 was neutral and 24 (52.1%) were against such collaborations. 26 papers (57%) set out conditions to assure positive outcomes of the partnerships. Evidence for or against PPPs was mentioned in 11 papers that were critical or neutral (44%) but not in any of those that advocated collaboration. Where conflicts were declared (26 papers), absence of conflicts was more frequent in critics than in supporters (86% vs 17%).

Conclusions

Although there is a lack of evidence to support PPPs for health promotion, many authors endorse this approach. The prevalence of ideas encouraging PPPs can affect the intellectual environment and influence policy decisions. Public health researchers and professionals must make a contribution in properly framing the PPP issue.
Disaster anxiety and self-assistance behaviours among persons with cervical cord injury in Japan: a qualitative study
Authors: Takahashi Kyo , Kitamura Yayoi
Published: April 2016

Objectives

Persons with disabilities, especially those with a severe disability, have a vague anxiety about future disasters; however, the measures of self-assistance for disaster preparedness have not been standardised. The present study aimed to describe disaster-related anxiety and behaviours related to disaster preparedness among persons who have cervical cord injury in Japan.

Design

Qualitative study.

Setting

Tokyo Metropolitan area, Japan.

Participants

16 persons with cervical cord injury participated. Inclusion criteria were being 20 years old and older, being diagnosed with cervical cord injury, being able to communicate verbally, having an interest in disaster preparedness, and belonging to a self-help group of persons with cervical cord injury in the Tokyo Metropolitan area.

Results

Participants usually had ‘anxiety about health management’ and it became more serious once they thought about a disaster. We identified three themes in relation to their anxiety: ‘storing needed items,’ ‘staying in a safe place’ and ‘having reliable caregivers.’ We also identified three other themes that were the reasons behind these themes: ‘travel experiences,’ ‘experiences of failure’ and ‘information from peers.’

Conclusions

To buffer the anxiety about health management in a disaster, it would be important for persons with cervical cord injury to store needed items, stay in a safe place and have reliable caregivers. Various daily experiences, including experiences of failure, would encourage such behaviours.